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1. The role of socio-economic disparities in the relative success and persistence of SARS-CoV-2 variants in New York City in early 2021.

Author

Vasylyeva, Tetyana, Havens, Jennifer, Wang, Jade, Luoma, Elizabeth, Hassler, Gabriel, Amin, Helly, Di Lonardo, Steve, Taki, Faten, Omoregie, Enoma, Hughes, Scott, and Wertheim, Joel

Subjects
Humans, New York City, SARS-CoV-2, COVID-19, Seroepidemiologic Studies, Socioeconomic Factors, Male, Female, Adult, Middle Aged, Mutation
Abstract

Socio-economic disparities were associated with disproportionate viral incidence between neighborhoods of New York City (NYC) during the first wave of SARS-CoV-2. We investigated how these disparities affected the co-circulation of SARS-CoV-2 variants during the second wave in NYC. We tested for correlation between the prevalence, in late 2020/early 2021, of Alpha, Iota, Iota with E484K mutation (Iota-E484K), and B.1-like genomes and pre-existing immunity (seropositivity) in NYC neighborhoods. In the context of varying seroprevalence we described socio-economic profiles of neighborhoods and performed migration and lineage persistence analyses using a Bayesian phylogeographical framework. Seropositivity was greater in areas with high poverty and a larger proportion of Black and Hispanic or Latino residents. Seropositivity was positively correlated with the proportion of Iota-E484K and Iota genomes, and negatively correlated with the proportion of Alpha and B.1-like genomes. The proportion of persisting Alpha lineages declined over time in locations with high seroprevalence, whereas the proportion of persisting Iota-E484K lineages remained the same in high seroprevalence areas. During the second wave, the geographic variation of standing immunity, due to disproportionate disease burden during the first wave of SARS-CoV-2 in NYC, allowed for the immune evasive Iota-E484K variant, but not the more transmissible Alpha variant, to circulate in locations with high pre-existing immunity.

Published
2024

2. A global synthesis reveals biodiversity-mediated benefits for crop production.

Author

Dainese, Matteo, Martin, Emily A, Aizen, Marcelo A, Albrecht, Matthias, Bartomeus, Ignasi, Bommarco, Riccardo, Carvalheiro, Luisa G, Chaplin-Kramer, Rebecca, Gagic, Vesna, Garibaldi, Lucas A, Ghazoul, Jaboury, Grab, Heather, Jonsson, Mattias, Karp, Daniel S, Kennedy, Christina M, Kleijn, David, Kremen, Claire, Landis, Douglas A, Letourneau, Deborah K, Marini, Lorenzo, Poveda, Katja, Rader, Romina, Smith, Henrik G, Tscharntke, Teja, Andersson, Georg KS, Badenhausser, Isabelle, Baensch, Svenja, Bezerra, Antonio Diego M, Bianchi, Felix JJA, Boreux, Virginie, Bretagnolle, Vincent, Caballero-Lopez, Berta, Cavigliasso, Pablo, Ćetković, Aleksandar, Chacoff, Natacha P, Classen, Alice, Cusser, Sarah, da Silva E Silva, Felipe D, de Groot, G Arjen, Dudenhöffer, Jan H, Ekroos, Johan, Fijen, Thijs, Franck, Pierre, Freitas, Breno M, Garratt, Michael PD, Gratton, Claudio, Hipólito, Juliana, Holzschuh, Andrea, Hunt, Lauren, Iverson, Aaron L, Jha, Shalene, Keasar, Tamar, Kim, Tania N, Kishinevsky, Miriam, Klatt, Björn K, Klein, Alexandra-Maria, Krewenka, Kristin M, Krishnan, Smitha, Larsen, Ashley E, Lavigne, Claire, Liere, Heidi, Maas, Bea, Mallinger, Rachel E, Martinez Pachon, Eliana, Martínez-Salinas, Alejandra, Meehan, Timothy D, Mitchell, Matthew GE, Molina, Gonzalo AR, Nesper, Maike, Nilsson, Lovisa, O'Rourke, Megan E, Peters, Marcell K, Plećaš, Milan, Potts, Simon G, Ramos, Davi de L, Rosenheim, Jay A, Rundlöf, Maj, Rusch, Adrien, Sáez, Agustín, Scheper, Jeroen, Schleuning, Matthias, Schmack, Julia M, Sciligo, Amber R, Seymour, Colleen, Stanley, Dara A, Stewart, Rebecca, Stout, Jane C, Sutter, Louis, Takada, Mayura B, Taki, Hisatomo, Tamburini, Giovanni, Tschumi, Matthias, Viana, Blandina F, Westphal, Catrin, Willcox, Bryony K, Wratten, Stephen D, Yoshioka, Akira, Zaragoza-Trello, Carlos, Zhang, Wei, and Zou, Yi

Subjects
Humans, Crops, Agricultural, Ecosystem, Biodiversity, Pest Control, Biological, Agriculture, Pollination, Crop Production, Crops, Agricultural, Pest Control, Biological
Abstract

Human land use threatens global biodiversity and compromises multiple ecosystem functions critical to food production. Whether crop yield-related ecosystem services can be maintained by a few dominant species or rely on high richness remains unclear. Using a global database from 89 studies (with 1475 locations), we partition the relative importance of species richness, abundance, and dominance for pollination; biological pest control; and final yields in the context of ongoing land-use change. Pollinator and enemy richness directly supported ecosystem services in addition to and independent of abundance and dominance. Up to 50% of the negative effects of landscape simplification on ecosystem services was due to richness losses of service-providing organisms, with negative consequences for crop yields. Maintaining the biodiversity of ecosystem service providers is therefore vital to sustain the flow of key agroecosystem benefits to society.

Published
2019

3. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Author

Collaborators, GBD 2016 Neurology, Feigin, Valery L, Nichols, Emma, Alam, Tahiya, Bannick, Marlena S, Beghi, Ettore, Blake, Natacha, Culpepper, William J, Dorsey, E Ray, Elbaz, Alexis, Ellenbogen, Richard G, Fisher, James L, Fitzmaurice, Christina, Giussani, Giorgia, Glennie, Linda, James, Spencer L, Johnson, Catherine Owens, Kassebaum, Nicholas J, Logroscino, Giancarlo, Marin, Benoît, Mountjoy-Venning, W Cliff, Nguyen, Minh, Ofori-Asenso, Richard, Patel, Anoop P, Piccininni, Marco, Roth, Gregory A, Steiner, Timothy J, Stovner, Lars Jacob, Szoeke, Cassandra EI, Theadom, Alice, Vollset, Stein Emil, Wallin, Mitchell Taylor, Wright, Claire, Zunt, Joseph Raymond, Abbasi, Nooshin, Abd-Allah, Foad, Abdelalim, Ahmed, Abdollahpour, Ibrahim, Aboyans, Victor, Abraha, Haftom Niguse, Acharya, Dilaram, Adamu, Abdu A, Adebayo, Oladimeji M, Adeoye, Abiodun Moshood, Adsuar, Jose C, Afarideh, Mohsen, Agrawal, Sutapa, Ahmadi, Alireza, Ahmed, Muktar Beshir, Aichour, Amani Nidhal, Aichour, Ibtihel, Aichour, Miloud Taki Eddine, Akinyemi, Rufus Olusola, Akseer, Nadia, Al-Eyadhy, Ayman, Salman, Rustam Al-Shahi, Alahdab, Fares, Alene, Kefyalew Addis, Aljunid, Syed Mohamed, Altirkawi, Khalid, Alvis-Guzman, Nelson, Anber, Nahla Hamed, Antonio, Carl Abelardo T, Arabloo, Jalal, Aremu, Olatunde, Ärnlöv, Johan, Asayesh, Hamid, Asghar, Rana Jawad, Atalay, Hagos Tasew, Awasthi, Ashish, Quintanilla, Beatriz Paulina Ayala, Ayuk, Tambe B, Badawi, Alaa, Banach, Maciej, Banoub, Joseph Adel Mattar, Barboza, Miguel A, Barker-Collo, Suzanne Lyn, Bärnighausen, Till Winfried, Baune, Bernhard T, Bedi, Neeraj, Behzadifar, Masoud, Behzadifar, Meysam, Béjot, Yannick, Bekele, Bayu Begashaw, Belachew, Abate Bekele, Bennett, Derrick A, Bensenor, Isabela M, Berhane, Adugnaw, Beuran, Mircea, Bhattacharyya, Krittika, Bhutta, Zulfiqar A, Biadgo, Belete, Bijani, Ali, Bililign, Nigus, Bin Sayeed, Muhammad Shahdaat, Blazes, Christopher Kynrint, Brayne, Carol, Butt, Zahid A, Campos-Nonato, Ismael R, and Cantu-Brito, Carlos

Subjects
Neurosciences, Headaches, Pain Research, Aging, Brain Disorders, Prevention, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Neurological, Good Health and Well Being, Adult, Age Factors, Aged, Aged, 80 and over, Cause of Death, Dementia, Disability Evaluation, Female, Global Burden of Disease, Humans, Incidence, Male, Middle Aged, Nervous System Diseases, Prevalence, Quality-Adjusted Life Years, Risk Factors, Sex Factors, Socioeconomic Factors, GBD 2016 Neurology Collaborators, Clinical Sciences, Neurology & Neurosurgery
Abstract

BackgroundNeurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.MethodsWe estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.FindingsGlobally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247-308]) and second leading cause of deaths (9·0 million [8·8-9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34-44] and DALYs by 15% [9-21]) whereas their age-standardised rates decreased (deaths by 28% [26-30] and DALYs by 27% [24-31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6-46·1]), migraine (16·3% [11·7-20·8]), Alzheimer's and other dementias (10·4% [9·0-12·1]), and meningitis (7·9% [6·6-10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05-1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5-90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8-35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8-17·5] of DALYs are risk attributable).InterpretationGlobally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.FundingBill & Melinda Gates Foundation.

Published
2019

4. Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Author

Murray, Christopher JL, Callender, Charlton SKH, Kulikoff, Xie Rachel, Srinivasan, Vinay, Abate, Degu, Abate, Kalkidan Hassen, Abay, Solomon M, Abbasi, Nooshin, Abbastabar, Hedayat, Abdela, Jemal, Abdelalim, Ahmed, Abdel-Rahman, Omar, Abdi, Alireza, Abdoli, Nasrin, Abdollahpour, Ibrahim, Abdulkader, Rizwan Suliankatchi, Abebe, Haftom Temesgen, Abebe, Molla, Abebe, Zegeye, Abebo, Teshome Abuka, Abejie, Ayenew Negesse, Aboyans, Victor, Abraha, Haftom Niguse, Abreu, Daisy Maria Xavier, Abrham, Aklilu Roba, Abu-Raddad, Laith Jamal, Abu-Rmeileh, Niveen ME, Accrombessi, Manfred Mario Kokou, Acharya, Pawan, Adamu, Abdu A, Adebayo, Oladimeji M, Adedeji, Isaac Akinkunmi, Adekanmbi, Victor, Adetokunboh, Olatunji O, Adhena, Beyene Meressa, Adhikari, Tara Ballav, Adib, Mina G, Adou, Arsène Kouablan, Adsuar, Jose C, Afarideh, Mohsen, Afshin, Ashkan, Agarwal, Gina, Agesa, Kareha M, Aghayan, Sargis Aghasi, Agrawal, Sutapa, Ahmadi, Alireza, Ahmadi, Mehdi, Ahmed, Muktar Beshir, Ahmed, Sayem, Aichour, Amani Nidhal, Aichour, Ibtihel, Aichour, Miloud Taki Eddine, Akanda, Ali S, Akbari, Mohammad Esmaeil, Akibu, Mohammed, Akinyemi, Rufus Olusola, Akinyemiju, Tomi, Akseer, Nadia, Alahdab, Fares, Al-Aly, Ziyad, Alam, Khurshid, Alebel, Animut, Aleman, Alicia V, Alene, Kefyalew Addis, Al-Eyadhy, Ayman, Ali, Raghib, Alijanzadeh, Mehran, Alizadeh-Navaei, Reza, Aljunid, Syed Mohamed, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Almasi, Ali, Alonso, Jordi, Al-Raddadi, Rajaa M, Alsharif, Ubai, Altirkawi, Khalid, Alvis-Guzman, Nelson, Amare, Azmeraw T, Ammar, Walid, Anber, Nahla Hamed, Andrei, Catalina Liliana, Androudi, Sofia, Animut, Megbaru Debalkie, Ansari, Hossein, Ansha, Mustafa Geleto, Antonio, Carl Abelardo T, Appiah, Seth Christopher Yaw, Aremu, Olatunde, Areri, Habtamu Abera, Arian, Nicholas, Ärnlöv, Johan, Artaman, Al, Aryal, Krishna K, Asayesh, Hamid, Asfaw, Ephrem Tsegay, Asgedom, Solomon Weldegebreal, Assadi, Reza, Atey, Tesfay Mehari Mehari, and Atique, Suleman

Subjects
Health Sciences, Behavioral and Social Science, Contraception/Reproduction, Basic Behavioral and Social Science, Aging, Aetiology, 2.4 Surveillance and distribution, Reproductive health and childbirth, Good Health and Well Being, Adolescent, Adult, Aged, Birth Rate, Child, Child, Preschool, Female, Global Burden of Disease, Global Health, Humans, Infant, Infant, Newborn, Male, Maternal Age, Middle Aged, Mortality, Population Density, Population Growth, Young Adult, GBD 2017 Population and Fertility Collaborators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundPopulation estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods.MethodsWe estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10-54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10-14 years and 50-54 years was estimated from data on fertility in women aged 15-19 years and 45-49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories.FindingsFrom 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4-52·0). The TFR decreased from 4·7 livebirths (4·5-4·9) to 2·4 livebirths (2·2-2·5), and the ASFR of mothers aged 10-19 years decreased from 37 livebirths (34-40) to 22 livebirths (19-24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3-200·8) since 1950, from 2·6 billion (2·5-2·6) to 7·6 billion (7·4-7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15-64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9-1·2) in Cyprus to a high of 7·1 livebirths (6·8-7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07-0·09) in South Korea to 2·4 livebirths (2·2-2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3-0·4) in Puerto Rico to a high of 3·1 livebirths (3·0-3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger.InterpretationPopulation trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress.FundingBill & Melinda Gates Foundation.

Published
2018

5. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017

Author

Collaborators, GBD 2017 Causes of Death, Roth, Gregory A, Abate, Degu, Abate, Kalkidan Hassen, Abay, Solomon M, Abbafati, Cristiana, Abbasi, Nooshin, Abbastabar, Hedayat, Abd-Allah, Foad, Abdela, Jemal, Abdelalim, Ahmed, Abdollahpour, Ibrahim, Abdulkader, Rizwan Suliankatchi, Abebe, Haftom Temesgen, Abebe, Molla, Abebe, Zegeye, Abejie, Ayenew Negesse, Abera, Semaw F, Abil, Olifan Zewdie, Abraha, Haftom Niguse, Abrham, Aklilu Roba, Abu-Raddad, Laith Jamal, Accrombessi, Manfred Mario Kokou, Acharya, Dilaram, Adamu, Abdu A, Adebayo, Oladimeji M, Adedoyin, Rufus Adesoji, Adekanmbi, Victor, Adetokunboh, Olatunji O, Adhena, Beyene Meressa, Adib, Mina G, Admasie, Amha, Afshin, Ashkan, Agarwal, Gina, Agesa, Kareha M, Agrawal, Anurag, Agrawal, Sutapa, Ahmadi, Alireza, Ahmadi, Mehdi, Ahmed, Muktar Beshir, Ahmed, Sayem, Aichour, Amani Nidhal, Aichour, Ibtihel, Aichour, Miloud Taki Eddine, Akbari, Mohammad Esmaeil, Akinyemi, Rufus Olusola, Akseer, Nadia, Al-Aly, Ziyad, Al-Eyadhy, Ayman, Al-Raddadi, Rajaa M, Alahdab, Fares, Alam, Khurshid, Alam, Tahiya, Alebel, Animut, Alene, Kefyalew Addis, Alijanzadeh, Mehran, Alizadeh-Navaei, Reza, Aljunid, Syed Mohamed, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Alonso, Jordi, Altirkawi, Khalid, Alvis-Guzman, Nelson, Amare, Azmeraw T, Aminde, Leopold N, Amini, Erfan, Ammar, Walid, Amoako, Yaw Ampem, Anber, Nahla Hamed, Andrei, Catalina Liliana, Androudi, Sofia, Animut, Megbaru Debalkie, Anjomshoa, Mina, Ansari, Hossein, Ansha, Mustafa Geleto, Antonio, Carl Abelardo T, Anwari, Palwasha, Aremu, Olatunde, Ärnlöv, Johan, Arora, Amit, Arora, Monika, Artaman, Al, Aryal, Krishna K, Asayesh, Hamid, Asfaw, Ephrem Tsegay, Ataro, Zerihun, Atique, Suleman, Atre, Sachin R, Ausloos, Marcel, Avokpaho, Euripide FGA, Awasthi, Ashish, Quintanilla, Beatriz Paulina Ayala, Ayele, Yohanes, Ayer, Rakesh, Azzopardi, Peter S, Babazadeh, Arefeh, Bacha, Umar, Badali, Hamid, and Badawi, Alaa

Subjects
Brain Disorders, Pediatric, Prevention, Aetiology, 2.4 Surveillance and distribution, Infection, Good Health and Well Being, Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Cause of Death, Child, Child, Preschool, Female, Global Burden of Disease, Global Health, Humans, Infant, Infant, Newborn, Life Expectancy, Male, Middle Aged, Sex Distribution, Socioeconomic Factors, Young Adult, GBD 2017 Causes of Death Collaborators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundGlobal development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017.MethodsThe causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries-Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised.FindingsAt the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5-74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 18·6% (17·9-19·6), and injuries 8·0% (7·7-8·2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22·7% (21·5-23·9), representing an additional 7·61 million (7·20-8·01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7·9% (7·0-8·8). The number of deaths for CMNN causes decreased by 22·2% (20·0-24·0) and the death rate by 31·8% (30·1-33·3). Total deaths from injuries increased by 2·3% (0·5-4·0) between 2007 and 2017, and the death rate from injuries decreased by 13·7% (12·2-15·1) to 57·9 deaths (55·9-59·2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000-289 000) globally in 2007 to 352 000 (334 000-363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118·0% (88·8-148·6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36·4% (32·2-40·6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33·6% (31·2-36·1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respiratory infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990-neonatal disorders, lower respiratory infections, and diarrhoeal diseases-were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases.InterpretationImprovements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade.FundingBill & Melinda Gates Foundation.

Published
2018

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

Author

James, Spencer L, Abate, Degu, Abate, Kalkidan Hassen, Abay, Solomon M, Abbafati, Cristiana, Abbasi, Nooshin, Abbastabar, Hedayat, Abd-Allah, Foad, Abdela, Jemal, Abdelalim, Ahmed, Abdollahpour, Ibrahim, Abdulkader, Rizwan Suliankatchi, Abebe, Zegeye, Abera, Semaw F, Abil, Olifan Zewdie, Abraha, Haftom Niguse, Abu-Raddad, Laith Jamal, Abu-Rmeileh, Niveen ME, Accrombessi, Manfred Mario Kokou, Acharya, Dilaram, Acharya, Pawan, Ackerman, Ilana N, Adamu, Abdu A, Adebayo, Oladimeji M, Adekanmbi, Victor, Adetokunboh, Olatunji O, Adib, Mina G, Adsuar, Jose C, Afanvi, Kossivi Agbelenko, Afarideh, Mohsen, Afshin, Ashkan, Agarwal, Gina, Agesa, Kareha M, Aggarwal, Rakesh, Aghayan, Sargis Aghasi, Agrawal, Sutapa, Ahmadi, Alireza, Ahmadi, Mehdi, Ahmadieh, Hamid, Ahmed, Muktar Beshir, Aichour, Amani Nidhal, Aichour, Ibtihel, Aichour, Miloud Taki Eddine, Akinyemiju, Tomi, Akseer, Nadia, Al-Aly, Ziyad, Al-Eyadhy, Ayman, Al-Mekhlafi, Hesham M, Al-Raddadi, Rajaa M, Alahdab, Fares, Alam, Khurshid, Alam, Tahiya, Alashi, Alaa, Alavian, Seyed Moayed, Alene, Kefyalew Addis, Alijanzadeh, Mehran, Alizadeh-Navaei, Reza, Aljunid, Syed Mohamed, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Alouani, Mohamed ML, Altirkawi, Khalid, Alvis-Guzman, Nelson, Amare, Azmeraw T, Aminde, Leopold N, Ammar, Walid, Amoako, Yaw Ampem, Anber, Nahla Hamed, Andrei, Catalina Liliana, Androudi, Sofia, Animut, Megbaru Debalkie, Anjomshoa, Mina, Ansha, Mustafa Geleto, Antonio, Carl Abelardo T, Anwari, Palwasha, Arabloo, Jalal, Arauz, Antonio, Aremu, Olatunde, Ariani, Filippo, Armoon, Bahroom, Ärnlöv, Johan, Arora, Amit, Artaman, Al, Aryal, Krishna K, Asayesh, Hamid, Asghar, Rana Jawad, Ataro, Zerihun, Atre, Sachin R, Ausloos, Marcel, Avila-Burgos, Leticia, Avokpaho, Euripide FGA, Awasthi, Ashish, Ayala Quintanilla, Beatriz Paulina, Ayer, Rakesh, Azzopardi, Peter S, Babazadeh, Arefeh, Badali, Hamid, Badawi, Alaa, and Bali, Ayele Geleto

Subjects
Prevention, 2.4 Surveillance and distribution, Aetiology, Good Health and Well Being, Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Child, Child, Preschool, Disabled Persons, Female, Global Burden of Disease, Global Health, Humans, Incidence, Infant, Infant, Newborn, Life Expectancy, Male, Middle Aged, Morbidity, Prevalence, Sex Distribution, Socioeconomic Factors, Wounds and Injuries, Young Adult, GBD 2017 Disease and Injury Incidence and Prevalence Collaborators, Medical and Health Sciences, General & Internal Medicine
Abstract

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

Published
2018

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

Author

Collaborators, GBD 2017 Risk Factor, Stanaway, Jeffrey D, Afshin, Ashkan, Gakidou, Emmanuela, Lim, Stephen S, Abate, Degu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbasi, Nooshin, Abbastabar, Hedayat, Abd-Allah, Foad, Abdela, Jemal, Abdelalim, Ahmed, Abdollahpour, Ibrahim, Abdulkader, Rizwan Suliankatchi, Abebe, Molla, Abebe, Zegeye, Abera, Semaw F, Abil, Olifan Zewdie, Abraha, Haftom Niguse, Abrham, Aklilu Roba, Abu-Raddad, Laith Jamal, Abu-Rmeileh, Niveen ME, Accrombessi, Manfred Mario Kokou, Acharya, Dilaram, Acharya, Pawan, Adamu, Abdu A, Adane, Akilew Awoke, Adebayo, Oladimeji M, Adedoyin, Rufus Adesoji, Adekanmbi, Victor, Ademi, Zanfina, Adetokunboh, Olatunji O, Adib, Mina G, Admasie, Amha, Adsuar, Jose C, Afanvi, Kossivi Agbelenko, Afarideh, Mohsen, Agarwal, Gina, Aggarwal, Anju, Aghayan, Sargis Aghasi, Agrawal, Anurag, Agrawal, Sutapa, Ahmadi, Alireza, Ahmadi, Mehdi, Ahmadieh, Hamid, Ahmed, Muktar Beshir, Aichour, Amani Nidhal, Aichour, Ibtihel, Aichour, Miloud Taki Eddine, Akbari, Mohammad Esmaeil, Akinyemiju, Tomi, Akseer, Nadia, Al-Aly, Ziyad, Al-Eyadhy, Ayman, Al-Mekhlafi, Hesham M, Alahdab, Fares, Alam, Khurshid, Alam, Samiah, Alam, Tahiya, Alashi, Alaa, Alavian, Seyed Moayed, Alene, Kefyalew Addis, Ali, Komal, Ali, Syed Mustafa, Alijanzadeh, Mehran, Alizadeh-Navaei, Reza, Aljunid, Syed Mohamed, Alkerwi, Ala'a, Alla, François, Alsharif, Ubai, Altirkawi, Khalid, Alvis-Guzman, Nelson, Amare, Azmeraw T, Ammar, Walid, Anber, Nahla Hamed, Anderson, Jason A, Andrei, Catalina Liliana, Androudi, Sofia, Animut, Megbaru Debalkie, Anjomshoa, Mina, Ansha, Mustafa Geleto, Antó, Josep M, Antonio, Carl Abelardo T, Anwari, Palwasha, Appiah, Lambert Tetteh, Appiah, Seth Christopher Yaw, Arabloo, Jalal, Aremu, Olatunde, Ärnlöv, Johan, Artaman, Al, Aryal, Krishna K, Asayesh, Hamid, Ataro, Zerihun, Ausloos, Marcel, Avokpaho, Euripide FGA, Awasthi, Ashish, Quintanilla, Beatriz Paulina Ayala, Ayer, Rakesh, and Ayuk, Tambe B

Subjects
Prevention, Aetiology, 2.2 Factors relating to the physical environment, Good Health and Well Being, Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Child, Child, Preschool, Disabled Persons, Environmental Exposure, Female, Global Burden of Disease, Global Health, Health Risk Behaviors, Humans, Infant, Infant, Newborn, Life Expectancy, Male, Metabolic Diseases, Middle Aged, Occupational Diseases, Occupational Exposure, Quality-Adjusted Life Years, Risk Assessment, Sex Distribution, Socioeconomic Factors, Young Adult, GBD 2017 Risk Factor Collaborators, Medical and Health Sciences, General & Internal Medicine
Abstract

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

Published
2018

8. Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Author

Collaborators, GBD 2017 Mortality, Dicker, Daniel, Nguyen, Grant, Abate, Degu, Abate, Kalkidan Hassen, Abay, Solomon M, Abbafati, Cristiana, Abbasi, Nooshin, Abbastabar, Hedayat, Abd-Allah, Foad, Abdela, Jemal, Abdelalim, Ahmed, Abdel-Rahman, Omar, Abdi, Alireza, Abdollahpour, Ibrahim, Abdulkader, Rizwan Suliankatchi, Abdurahman, Ahmed Abdulahi, Abebe, Haftom Temesgen, Abebe, Molla, Abebe, Zegeye, Abebo, Teshome Abuka, Aboyans, Victor, Abraha, Haftom Niguse, Abrham, Aklilu Roba, Abu-Raddad, Laith Jamal, Abu-Rmeileh, Niveen ME, Accrombessi, Manfred Mario Kokou, Acharya, Pawan, Adebayo, Oladimeji M, Adedeji, Isaac Akinkunmi, Adedoyin, Rufus Adesoji, Adekanmbi, Victor, Adetokunboh, Olatunji O, Adhena, Beyene Meressa, Adhikari, Tara Ballav, Adib, Mina G, Adou, Arsène Kouablan, Adsuar, Jose C, Afarideh, Mohsen, Afshin, Ashkan, Agarwal, Gina, Aggarwal, Rakesh, Aghayan, Sargis Aghasi, Agrawal, Sutapa, Agrawal, Anurag, Ahmadi, Mehdi, Ahmadi, Alireza, Ahmadieh, Hamid, Ahmed, Mohamed Lemine Cheikh brahim, Ahmed, Sayem, Ahmed, Muktar Beshir, Aichour, Amani Nidhal, Aichour, Ibtihel, Aichour, Miloud Taki Eddine, Akanda, Ali S, Akbari, Mohammad Esmaeil, Akibu, Mohammed, Akinyemi, Rufus Olusola, Akinyemiju, Tomi, Akseer, Nadia, Alahdab, Fares, Al-Aly, Ziyad, Alam, Khurshid, Alebel, Animut, Aleman, Alicia V, Alene, Kefyalew Addis, Al-Eyadhy, Ayman, Ali, Raghib, Alijanzadeh, Mehran, Alizadeh-Navaei, Reza, Aljunid, Syed Mohamed, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Allen, Christine A, Alonso, Jordi, Al-Raddadi, Rajaa M, Alsharif, Ubai, Altirkawi, Khalid, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amini, Erfan, Ammar, Walid, Amoako, Yaw Ampem, Anber, Nahla Hamed, Andrei, Catalina Liliana, Androudi, Sofia, Animut, Megbaru Debalkie, Anjomshoa, Mina, Anlay, Degefaye Zelalem, Ansari, Hossein, Ansariadi, Ansariadi, Ansha, Mustafa Geleto, Antonio, Carl Abelardo T, Appiah, Seth Christopher Yaw, Aremu, Olatunde, Areri, Habtamu Abera, Ärnlöv, Johan, Arora, Megha, and Artaman, Al

Subjects
Behavioral and Social Science, Pediatric, Prevention, Basic Behavioral and Social Science, 2.4 Surveillance and distribution, Aetiology, Good Health and Well Being, Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Global Burden of Disease, Global Health, Humans, Infant, Infant, Newborn, Life Expectancy, Male, Middle Aged, Mortality, Sex Distribution, Socioeconomic Factors, Young Adult, GBD 2017 Mortality Collaborators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundAssessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally.MethodsThe GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950.FindingsGlobally, 18·7% (95% uncertainty interval 18·4-19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2-59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5-49·6) to 70·5 years (70·1-70·8) for men and from 52·9 years (51·7-54·0) to 75·6 years (75·3-75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5-51·7) for men in the Central African Republic to 87·6 years (86·9-88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3-238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6-42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2-5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development.InterpretationThis analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing.FundingBill & Melinda Gates Foundation.

Published
2018

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

Author

Kyu, Hmwe Hmwe, Abate, Degu, Abate, Kalkidan Hassen, Abay, Solomon M, Abbafati, Cristiana, Abbasi, Nooshin, Abbastabar, Hedayat, Abd-Allah, Foad, Abdela, Jemal, Abdelalim, Ahmed, Abdollahpour, Ibrahim, Abdulkader, Rizwan Suliankatchi, Abebe, Molla, Abebe, Zegeye, Abil, Olifan Zewdie, Aboyans, Victor, Abrham, Aklilu Roba, Abu-Raddad, Laith Jamal, Abu-Rmeileh, Niveen ME, Accrombessi, Manfred Mario Kokou, Acharya, Dilaram, Acharya, Pawan, Ackerman, Ilana N, Adamu, Abdu A, Adebayo, Oladimeji M, Adekanmbi, Victor, Ademi, Zanfina, Adetokunboh, Olatunji O, Adib, Mina G, Adsuar, Jose C, Afanvi, Kossivi Agbelenko, Afarideh, Mohsen, Afshin, Ashkan, Agarwal, Gina, Agesa, Kareha M, Aggarwal, Rakesh, Aghayan, Sargis Aghasi, Agrawal, Anurag, Ahmadi, Alireza, Ahmadi, Mehdi, Ahmadieh, Hamid, Ahmed, Muktar Beshir, Ahmed, Sayem, Aichour, Amani Nidhal, Aichour, Ibtihel, Aichour, Miloud Taki Eddine, Akinyemiju, Tomi, Akseer, Nadia, Al-Aly, Ziyad, Al-Eyadhy, Ayman, Al-Mekhlafi, Hesham M, Al-Raddadi, Rajaa M, Alahdab, Fares, Alam, Khurshid, Alam, Tahiya, Alashi, Alaa, Alavian, Seyed Moayed, Alene, Kefyalew Addis, Alijanzadeh, Mehran, Alizadeh-Navaei, Reza, Aljunid, Syed Mohamed, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Alonso, Jordi, Alsharif, Ubai, Altirkawi, Khalid, Alvis-Guzman, Nelson, Aminde, Leopold N, Amini, Erfan, Amiresmaili, Mohammadreza, Ammar, Walid, Amoako, Yaw Ampem, Anber, Nahla Hamed, Andrei, Catalina Liliana, Androudi, Sofia, Animut, Megbaru Debalkie, Anjomshoa, Mina, Ansha, Mustafa Geleto, Antonio, Carl Abelardo T, Anwari, Palwasha, Arabloo, Jalal, Aremu, Olatunde, Ärnlöv, Johan, Arora, Amit, Arora, Megha, Artaman, Al, Aryal, Krishna K, Asayesh, Hamid, Ataro, Zerihun, Ausloos, Marcel, Avila-Burgos, Leticia, Avokpaho, Euripide FGA, Awasthi, Ashish, Ayala Quintanilla, Beatriz Paulina, Ayer, Rakesh, Azzopardi, Peter S, Babazadeh, Arefeh, Badali, Hamid, and Balakrishnan, Kalpana

Subjects
Prevention, Aging, Good Health and Well Being, Aged, Communicable Diseases, Disabled Persons, Female, Global Burden of Disease, Health Status, Healthy Lifestyle, Humans, Life Expectancy, Male, Mortality, Mortality, Premature, Prevalence, Quality-Adjusted Life Years, Risk Factors, Socioeconomic Factors, Wounds and Injuries, GBD 2017 DALYs and HALE Collaborators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundHow long one lives, how many years of life are spent in good and poor health, and how the population's state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life-years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years.MethodsWe used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Socio-demographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males.FindingsGlobally, from 1990 to 2017, life expectancy at birth increased by 7·4 years (95% uncertainty interval 7·1-7·8), from 65·6 years (65·3-65·8) in 1990 to 73·0 years (72·7-73·3) in 2017. The increase in years of life varied from 5·1 years (5·0-5·3) in high SDI countries to 12·0 years (11·3-12·8) in low SDI countries. Of the additional years of life expected at birth, 26·3% (20·1-33·1) were expected to be spent in poor health in high SDI countries compared with 11·7% (8·8-15·1) in low-middle SDI countries. HALE at birth increased by 6·3 years (5·9-6·7), from 57·0 years (54·6-59·1) in 1990 to 63·3 years (60·5-65·7) in 2017. The increase varied from 3·8 years (3·4-4·1) in high SDI countries to 10·5 years (9·8-11·2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1·0 year (0·4-1·7) in Saint Vincent and the Grenadines (62·4 years [59·9-64·7] in 1990 to 63·5 years [60·9-65·8] in 2017) to 23·7 years (21·9-25·6) in Eritrea (30·7 years [28·9-32·2] in 1990 to 54·4 years [51·5-57·1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1·4 years (0·6-2·3) in Algeria to 11·9 years (10·9-12·9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75·8 years [72·4-78·7]) and males (72·6 years [69·8-75·0]) and the lowest estimates were in Central African Republic (47·0 years [43·7-50·2] for females and 42·8 years [40·1-45·6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischaemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardised DALY rates decreased by 41·3% (38·8-43·5) for communicable diseases and by 49·8% (47·9-51·6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40·1% (36·8-43·0), although age-standardised DALY rates decreased by 18·1% (16·0-20·2).InterpretationWith increasing life expectancy in most countries, the question of whether the additional years of life gained are spent in good health or poor health has been increasingly relevant because of the potential policy implications, such as health-care provisions and extending retirement ages. In some locations, a large proportion of those additional years are spent in poor health. Large inequalities in HALE and disease burden exist across countries in different SDI quintiles and between sexes. The burden of disabling conditions has serious implications for health system planning and health-related expenditures. Despite the progress made in reducing the burden of communicable diseases and neonatal disorders in low SDI countries, the speed of this progress could be increased by scaling up proven interventions. The global trends among non-communicable diseases indicate that more effort is needed to maximise HALE, such as risk prevention and attention to upstream determinants of health.FundingBill & Melinda Gates Foundation.

Published
2018

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

Author

Collaborators, GBD 2016 Healthcare Access and Quality, Fullman, Nancy, Yearwood, Jamal, Abay, Solomon M, Abbafati, Cristiana, Abd-Allah, Foad, Abdela, Jemal, Abdelalim, Ahmed, Abebe, Zegeye, Abebo, Teshome Abuka, Aboyans, Victor, Abraha, Haftom Niguse, Abreu, Daisy MX, Abu-Raddad, Laith J, Adane, Akilew Awoke, Adedoyin, Rufus Adesoji, Adetokunboh, Olatunji, Adhikari, Tara Ballav, Afarideh, Mohsen, Afshin, Ashkan, Agarwal, Gina, Agius, Dominic, Agrawal, Anurag, Agrawal, Sutapa, Kiadaliri, Aliasghar Ahmad, Aichour, Miloud Taki Eddine, Akibu, Mohammed, Akinyemi, Rufus Olusola, Akinyemiju, Tomi F, Akseer, Nadia, Lami, Faris Hasan Al, Alahdab, Fares, Al-Aly, Ziyad, Alam, Khurshid, Alam, Tahiya, Alasfoor, Deena, Albittar, Mohammed I, Alene, Kefyalew Addis, Al-Eyadhy, Ayman, Ali, Syed Danish, Alijanzadeh, Mehran, Aljunid, Syed M, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Allen, Christine, Alomari, Mahmoud A, Al-Raddadi, Rajaa, Alsharif, Ubai, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amenu, Kebede, Ammar, Walid, Amoako, Yaw Ampem, Anber, Nahla, Andrei, Catalina Liliana, Androudi, Sofia, Antonio, Carl Abelardo T, Araújo, Valdelaine EM, Aremu, Olatunde, Ärnlöv, Johan, Artaman, Al, Aryal, Krishna Kumar, Asayesh, Hamid, Asfaw, Ephrem Tsegay, Asgedom, Solomon Weldegebreal, Asghar, Rana Jawad, Ashebir, Mengistu Mitiku, Asseffa, Netsanet Abera, Atey, Tesfay Mehari, Atre, Sachin R, Atteraya, Madhu S, Avila-Burgos, Leticia, Avokpaho, Euripide Frinel G Arthur, Awasthi, Ashish, Quintanilla, Beatriz Paulina Ayala, Ayalew, Animut Alebel, Ayele, Henok Tadesse, Ayer, Rakesh, Ayuk, Tambe Betrand, Azzopardi, Peter, Azzopardi-Muscat, Natasha, Babalola, Tesleem Kayode, Badali, Hamid, Badawi, Alaa, Banach, Maciej, Banerjee, Amitava, Banstola, Amrit, Barber, Ryan M, Barboza, Miguel A, Barker-Collo, Suzanne L, Bärnighausen, Till, Barquera, Simon, Barrero, Lope H, Bassat, Quique, Basu, Sanjay, Baune, Bernhard T, Bazargan-Hejazi, Shahrzad, and Bedi, Neeraj

Subjects
Health Services and Systems, Public Health, Health Sciences, Clinical Research, Biodefense, Prevention, Vaccine Related, Good Health and Well Being, Communicable Diseases, Global Burden of Disease, Health Services Accessibility, Humans, Noncommunicable Diseases, Quality of Health Care, Wounds and Injuries, GBD 2016 Healthcare Access and Quality Collaborators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

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

Published
2018

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

Author

Collaborators, GBD 2016 Risk Factors, Gakidou, Emmanuela, Afshin, Ashkan, Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M, Abd-Allah, Foad, Abdulle, Abdishakur M, Abera, Semaw Ferede, Aboyans, Victor, Abu-Raddad, Laith J, Abu-Rmeileh, Niveen ME, Abyu, Gebre Yitayih, Adedeji, Isaac Akinkunmi, Adetokunboh, Olatunji, Afarideh, Mohsen, Agrawal, Anurag, Agrawal, Sutapa, Ahmadieh, Hamid, Ahmed, Muktar Beshir, Aichour, Miloud Taki Eddine, Aichour, Amani Nidhal, Aichour, Ibtihel, Akinyemi, Rufus Olusola, Akseer, Nadia, Alahdab, Fares, Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore, Alam, Tahiya, Alasfoor, Deena, Alene, Kefyalew Addis, Ali, Komal, Alizadeh-Navaei, Reza, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Al-Raddadi, Rajaa, Alsharif, Ubai, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amini, Erfan, Ammar, Walid, Amoako, Yaw Ampem, Ansari, Hossein, Antó, Josep M, Antonio, Carl Abelardo T, Anwari, Palwasha, Arian, Nicholas, Ärnlöv, Johan, Artaman, Al, Aryal, Krishna Kumar, Asayesh, Hamid, Asgedom, Solomon Weldegebreal, Atey, Tesfay Mehari, Avila-Burgos, Leticia, Avokpaho, Euripide Frinel G Arthur, Awasthi, Ashish, Azzopardi, Peter, Bacha, Umar, Badawi, Alaa, Balakrishnan, Kalpana, Ballew, Shoshana H, Barac, Aleksandra, Barber, Ryan M, Barker-Collo, Suzanne L, Bärnighausen, Till, Barquera, Simon, Barregard, Lars, Barrero, Lope H, Batis, Carolina, Battle, Katherine E, Baumgarner, Blair R, Baune, Bernhard T, Beardsley, Justin, Bedi, Neeraj, Beghi, Ettore, Bell, Michelle L, Bennett, Derrick A, Bennett, James R, Bensenor, Isabela M, Berhane, Adugnaw, Berhe, Derbew Fikadu, Bernabé, Eduardo, Betsu, Balem Demtsu, Beuran, Mircea, Beyene, Addisu Shunu, Bhansali, Anil, Bhutta, Zulfiqar A, Bicer, Burcu Kucuk, Bikbov, Boris, Birungi, Charles, Biryukov, Stan, Blosser, Christopher D, Boneya, Dube Jara, Bou-Orm, Ibrahim R, Brauer, Michael, and Breitborde, Nicholas JK

Subjects
Epidemiology, Health Sciences, Prevention, Aetiology, 2.2 Factors relating to the physical environment, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Air Pollution, Body Mass Index, Cause of Death, Child, Child, Preschool, Communicable Diseases, Disabled Persons, Environmental Health, Female, Global Burden of Disease, Humans, Infant, Infant, Newborn, Life Expectancy, Male, Metabolic Diseases, Middle Aged, Noncommunicable Diseases, Occupational Diseases, Quality-Adjusted Life Years, Risk Assessment, Sex Distribution, Smoking, Water Supply, Young Adult, GBD 2016 Risk Factors Collaborators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundThe Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context.MethodsWe used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined.FindingsSince 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124·1 million DALYs [95% UI 111·2 million to 137·0 million]), high systolic blood pressure (122·2 million DALYs [110·3 million to 133·3 million], and low birthweight and short gestation (83·0 million DALYs [78·3 million to 87·7 million]), and for women, were high systolic blood pressure (89·9 million DALYs [80·9 million to 98·2 million]), high body-mass index (64·8 million DALYs [44·4 million to 87·6 million]), and high fasting plasma glucose (63·8 million DALYs [53·2 million to 76·3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9·3% (6·9-11·6) decline in deaths and a 10·8% (8·3-13·1) decrease in DALYs at the global level, while population ageing accounts for 14·9% (12·7-17·5) of deaths and 6·2% (3·9-8·7) of DALYs, and population growth for 12·4% (10·1-14·9) of deaths and 12·4% (10·1-14·9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27·3% (24·9-29·7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks.InterpretationIncreasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade.FundingThe Bill & Melinda Gates Foundation, Bloomberg Philanthropies.

Published
2017

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

Author

Collaborators, GBD 2016 DALYs and HALE, Hay, Simon I, Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M, Abd-Allah, Foad, Abdulkader, Rizwan Suliankatchi, Abdulle, Abdishakur M, Abebo, Teshome Abuka, Abera, Semaw Ferede, Aboyans, Victor, Abu-Raddad, Laith J, Ackerman, Ilana N, Adedeji, Isaac A, Adetokunboh, Olatunji, Afshin, Ashkan, Aggarwal, Rakesh, Agrawal, Sutapa, Agrawal, Anurag, Ahmed, Muktar Beshir, Aichour, Miloud Taki Eddine, Aichour, Amani Nidhal, Aichour, Ibtihel, Aiyar, Sneha, Akinyemiju, Tomi F, Akseer, Nadia, Al Lami, Faris Hasan, Alahdab, Fares, Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore, Alam, Tahiya, Alasfoor, Deena, Alene, Kefyalew Addis, Ali, Raghib, Alizadeh-Navaei, Reza, Alkaabi, Juma M, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Allen, Christine, Al-Maskari, Fatma, AlMazroa, Mohammad AbdulAziz, Al-Raddadi, Rajaa, Alsharif, Ubai, Alsowaidi, Shirina, Althouse, Benjamin M, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amini, Erfan, Ammar, Walid, Amoako, Yaw Ampem, Ansha, Mustafa Geleto, Antonio, Carl Abelardo T, Anwari, Palwasha, Ärnlöv, Johan, Arora, Megha, Artaman, Al, Aryal, Krishna Kumar, Asgedom, Solomon W, Atey, Tesfay Mehari, Atnafu, Niguse Tadele, Avila-Burgos, Leticia, Avokpaho, Euripide Frinel G Arthur, Awasthi, Ashish, Awasthi, Shally, Azarpazhooh, Mahmoud Reza, Azzopardi, Peter, Babalola, Tesleem Kayode, Bacha, Umar, Badawi, Alaa, Balakrishnan, Kalpana, Bannick, Marlena S, Barac, Aleksandra, Barker-Collo, Suzanne L, Bärnighausen, Till, Barquera, Simon, Barrero, Lope H, Basu, Sanjay, Battista, Robert, Battle, Katherine E, Baune, Bernhard T, Bazargan-Hejazi, Shahrzad, Beardsley, Justin, Bedi, Neeraj, Béjot, Yannick, Bekele, Bayu Begashaw, Bell, Michelle L, Bennett, Derrick A, Bennett, James R, Bensenor, Isabela M, Benson, Jennifer, Berhane, Adugnaw, Berhe, Derbew Fikadu, Bernabé, Eduardo, Betsu, Balem Demtsu, Beuran, Mircea, and Beyene, Addisu Shunu

Subjects
Epidemiology, Public Health, Health Sciences, Clinical Research, Prevention, Behavioral and Social Science, Burden of Illness, Social Determinants of Health, 2.4 Surveillance and distribution, Good Health and Well Being, Adult, Age Distribution, Aged, Aged, 80 and over, Cause of Death, Communicable Diseases, Disabled Persons, Female, Global Burden of Disease, Global Health, Humans, Life Expectancy, Male, Middle Aged, Noncommunicable Diseases, Quality-Adjusted Life Years, Residence Characteristics, Sex Distribution, Wounds and Injuries, GBD 2016 DALYs and HALE Collaborators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundMeasurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI).MethodsWe used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate.FindingsThe highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally.InterpretationAt a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support.FundingBill & Melinda Gates Foundation.

Published
2017

13. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016

Author

Collaborators, GBD 2016 Causes of Death, Naghavi, Mohsen, Abajobir, Amanuel Alemu, Abbafati, Cristiana, Abbas, Kaja M, Abd-Allah, Foad, Abera, Semaw Ferede, Aboyans, Victor, Adetokunboh, Olatunji, Afshin, Ashkan, Agrawal, Anurag, Ahmadi, Alireza, Ahmed, Muktar Beshir, Aichour, Amani Nidhal, Aichour, Miloud Taki Eddine, Aichour, Ibtihel, Aiyar, Sneha, Alahdab, Fares, Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore, Alam, Tahiya, Alene, Kefyalew Addis, Al-Eyadhy, Ayman, Ali, Syed Danish, Alizadeh-Navaei, Reza, Alkaabi, Juma M, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Allen, Christine, Al-Raddadi, Rajaa, Alsharif, Ubai, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amini, Erfan, Ammar, Walid, Amoako, Yaw Ampem, Anber, Nahla, Andersen, Hjalte H, Andrei, Catalina Liliana, Androudi, Sofia, Ansari, Hossein, Antonio, Carl Abelardo T, Anwari, Palwasha, Ärnlöv, Johan, Arora, Megha, Artaman, Al, Aryal, Krishna Kumar, Asayesh, Hamid, Asgedom, Solomon W, Atey, Tesfay Mehari, Avila-Burgos, Leticia, Avokpaho, Euripide Frinel G, Awasthi, Ashish, Babalola, Tesleem Kayode, Bacha, Umar, Balakrishnan, Kalpana, Barac, Aleksandra, Barboza, Miguel A, Barker-Collo, Suzanne L, Barquera, Simon, Barregard, Lars, Barrero, Lope H, Baune, Bernhard T, Bedi, Neeraj, Beghi, Ettore, Béjot, Yannick, Bekele, Bayu Begashaw, Bell, Michelle L, Bennett, James R, Bensenor, Isabela M, Berhane, Adugnaw, Bernabé, Eduardo, Betsu, Balem Demtsu, Beuran, Mircea, Bhatt, Samir, Biadgilign, Sibhatu, Bienhoff, Kelly, Bikbov, Boris, Bisanzio, Donal, Bourne, Rupert RA, Breitborde, Nicholas JK, Bulto, Lemma Negesa Bulto, Bumgarner, Blair R, Butt, Zahid A, Cahuana-Hurtado, Lucero, Cameron, Ewan, Campuzano, Julio Cesar, Car, Josip, Cárdenas, Rosario, Carrero, Juan Jesus, Carter, Austin, Casey, Daniel C, Castañeda-Orjuela, Carlos A, Catalá-López, Ferrán, Charlson, Fiona J, Chibueze, Chioma Ezinne, and Chimed-Ochir, Odgerel

Subjects
Pediatric, Clinical Research, Infant Mortality, Infectious Diseases, 2.4 Surveillance and distribution, Aetiology, Infection, Cardiovascular, Good Health and Well Being, Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Cause of Death, Child, Child, Preschool, Communicable Diseases, Disasters, Female, Global Burden of Disease, Global Health, Humans, Infant, Infant, Newborn, Male, Middle Aged, Noncommunicable Diseases, Nutrition Disorders, Pregnancy, Pregnancy Complications, Socioeconomic Factors, Wounds and Injuries, Young Adult, GBD 2016 Causes of Death Collaborators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundMonitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends.MethodsWe estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016.FindingsThe quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72·3% (95% uncertainty interval [UI] 71·2-73·2) of deaths in 2016 with 19·3% (18·5-20·4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8·43% (8·00-8·67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006-16-age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1·80 million deaths (95% UI 1·59 million to 1·89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176-181) increase in deaths in ages 90-94 years and a 210% (208-212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2·89%); the median annualised rate of change for all other causes was lower (a decrease of 1·59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe.InterpretationThe past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems.FundingBill & Melinda Gates Foundation.

Published
2017

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

Author

Collaborators, GBD 2016 SDG, Fullman, Nancy, Barber, Ryan M, Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M, Abd-Allah, Foad, Abdulkader, Rizwan Suliankatchi, Abdulle, Abdishakur M, Abera, Semaw Ferede, Aboyans, Victor, Abu-Raddad, Laith J, Abu-Rmeileh, Niveen ME, Adedeji, Isaac Akinkunmi, Adetokunboh, Olatunji, Afshin, Ashkan, Agrawal, Anurag, Agrawal, Sutapa, Kiadaliri, Aliasghar Ahmad, Ahmadieh, Hamid, Ahmed, Muktar Beshir, Aichour, Miloud Taki Eddine, Aichour, Amani Nidhal, Aichour, Ibtihel, Aiyar, Sneha, Akinyemi, Rufus Olusola, Akseer, Nadia, Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore, Alasfoor, Deena, Alene, Kefyalew Addis, Alizadeh-Navaei, Reza, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Allen, Christine, Al-Raddadi, Rajaa, Alsharif, Ubai, Altirkawi, Khalid A, Alvis-Guzman, Nelson, Amare, Azmeraw T, Amini, Erfan, Ammar, Walid, Ansari, Hossein, Antonio, Carl Abelardo T, Anwari, Palwasha, Arora, Megha, Artaman, Al, Aryal, Krishna Kumar, Asayesh, Hamid, Asgedom, Solomon Weldegebreal, Assadi, Reza, Atey, Tesfay Mehari, Atre, Sachin R, Avila-Burgos, Leticia, Avokpaho, Euripide Frinel G Arthur, Awasthi, Ashish, Azzopardi, Peter, Bacha, Umar, Badawi, Alaa, Balakrishnan, Kalpana, Bannick, Marlena S, Barac, Aleksandra, Barker-Collo, Suzanne L, Bärnighausen, Till, Barrero, Lope H, Basu, Sanjay, Battle, Katherine E, Baune, Bernhard T, Beardsley, Justin, Bedi, Neeraj, Beghi, Ettore, Béjot, Yannick, Bell, Michelle L, Bennett, Derrick A, Bennett, James R, Bensenor, Isabela M, Berhane, Adugnaw, Berhe, Derbew Fikadu, Bernabé, Eduardo, Betsu, Balem Demtsu, Beuran, Mircea, Beyene, Addisu Shunu, Bhala, Neeraj, Bhansali, Anil, Bhatt, Samir, Bhutta, Zulfiqar A, Bicer, Burcu Kucuk, Bidgoli, Hassan Haghparast, Bikbov, Boris, Bilal, Arebu I, Birungi, Charles, Biryukov, Stan, Bizuayehu, Habtamu Mellie, Blosser, Christopher D, Boneya, Dube Jara, Bose, Dipan, and Bou-Orm, Ibrahim R

Subjects
Infectious Diseases, Pediatric, Prevention, Rare Diseases, Good Health and Well Being, Adolescent, Adult, Child, Child Abuse, Sexual, Child, Preschool, Conservation of Natural Resources, Female, Global Burden of Disease, Global Health, Health Status, Health Status Indicators, Humans, Infant, Infant Mortality, Infant, Newborn, Male, Middle Aged, Noncommunicable Diseases, Quality-Adjusted Life Years, Sex Offenses, Young Adult, GBD 2016 SDG Collaborators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundThe UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of "leaving no one behind". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030.MethodsWe used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2·5th percentile estimated between 1990 and 2030, and 100 as the 97·5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment.FindingsGlobally, the median health-related SDG index was 56·7 (IQR 31·9-66·8) in 2016 and country-level performance markedly varied, with Singapore (86·8, 95% uncertainty interval 84·6-88·9), Iceland (86·0, 84·1-87·6), and Sweden (85·6, 81·8-87·8) having the highest levels in 2016 and Afghanistan (10·9, 9·6-11·9), the Central African Republic (11·0, 8·8-13·8), and Somalia (11·3, 9·5-13·1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past.InterpretationGBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations.FundingBill & Melinda Gates Foundation.

Published
2017

15. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Author

Collaborators, GBD 2016 Disease and Injury Incidence and Prevalence, Vos, Theo, Abajobir, Amanuel Alemu, Abate, Kalkidan Hassen, Abbafati, Cristiana, Abbas, Kaja M, Abd-Allah, Foad, Abdulkader, Rizwan Suliankatchi, Abdulle, Abdishakur M, Abebo, Teshome Abuka, Abera, Semaw Ferede, Aboyans, Victor, Abu-Raddad, Laith J, Ackerman, Ilana N, Adamu, Abdu Abdullahi, Adetokunboh, Olatunji, Afarideh, Mohsen, Afshin, Ashkan, Agarwal, Sanjay Kumar, Aggarwal, Rakesh, Agrawal, Anurag, Agrawal, Sutapa, Ahmadieh, Hamid, Ahmed, Muktar Beshir, Aichour, Miloud Taki Eddine, Aichour, Amani Nidhal, Aichour, Ibtihel, Aiyar, Sneha, Akinyemi, Rufus Olusola, Akseer, Nadia, Al Lami, Faris Hasan, Alahdab, Fares, Al-Aly, Ziyad, Alam, Khurshid, Alam, Noore, Alam, Tahiya, Alasfoor, Deena, Alene, Kefyalew Addis, Ali, Raghib, Alizadeh-Navaei, Reza, Alkerwi, Ala'a, Alla, François, Allebeck, Peter, Allen, Christine, Al-Maskari, Fatma, Al-Raddadi, Rajaa, Alsharif, Ubai, Alsowaidi, Shirina, Altirkawi, Khalid A, Amare, Azmeraw T, Amini, Erfan, Ammar, Walid, Amoako, Yaw Ampem, Andersen, Hjalte H, Antonio, Carl Abelardo T, Anwari, Palwasha, Ärnlöv, Johan, Artaman, Al, Aryal, Krishna Kumar, Asayesh, Hamid, Asgedom, Solomon W, Assadi, Reza, Atey, Tesfay Mehari, Atnafu, Niguse Tadele, Atre, Sachin R, Avila-Burgos, Leticia, Avokphako, Euripide Frinel G Arthur, Awasthi, Ashish, Bacha, Umar, Badawi, Alaa, Balakrishnan, Kalpana, Banerjee, Amitava, Bannick, Marlena S, Barac, Aleksandra, Barber, Ryan M, Barker-Collo, Suzanne L, Bärnighausen, Till, Barquera, Simon, Barregard, Lars, Barrero, Lope H, Basu, Sanjay, Battista, Bob, Battle, Katherine E, Baune, Bernhard T, Bazargan-Hejazi, Shahrzad, Beardsley, Justin, Bedi, Neeraj, Beghi, Ettore, Béjot, Yannick, Bekele, Bayu Begashaw, Bell, Michelle L, Bennett, Derrick A, Bensenor, Isabela M, Benson, Jennifer, Berhane, Adugnaw, Berhe, Derbew Fikadu, Bernabé, Eduardo, Betsu, Balem Demtsu, Beuran, Mircea, and Beyene, Addisu Shunu

Subjects
Biomedical and Clinical Sciences, Epidemiology, Public Health, Clinical Sciences, Health Sciences, Brain Disorders, Mental Health, Behavioral and Social Science, Burden of Illness, Neurosciences, Women's Health, Aging, 2.4 Surveillance and distribution, Good Health and Well Being, Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Cause of Death, Child, Child, Preschool, Communicable Diseases, Disabled Persons, Female, Global Burden of Disease, Global Health, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Noncommunicable Diseases, Prevalence, Sex Distribution, Wounds and Injuries, Young Adult, GBD 2016 Disease and Injury Incidence and Prevalence Collaborators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundAs mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.MethodsWe estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FindingsGlobally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8-75·9 million [7·2%, 6·0-8·3]), 45·1 million (29·0-62·8 million [5·6%, 4·0-7·2]), 36·3 million (25·3-50·9 million [4·5%, 3·8-5·3]), 34·7 million (23·0-49·6 million [4·3%, 3·5-5·2]), and 34·1 million (23·5-46·0 million [4·2%, 3·2-5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3-3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0-11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228).InterpretationThe decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response.FundingBill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

Published
2017

16. Global mortality associated with 33 bacterial pathogens in 2019

Author

Kevin S Ikuta, Lucien R Swetschinski, Gisela Robles Aguilar, Fablina Sharara, Tomislav Mestrovic, Authia P Gray, Nicole Davis Weaver, Eve E Wool, Chieh Han, Anna Gershberg Hayoon, Amirali Aali, Semagn Mekonnen Abate, Mohsen Abbasi-Kangevari, Zeinab Abbasi-Kangevari, Sherief Abd-Elsalam, Getachew Abebe, Aidin Abedi, Amir Parsa Abhari, Hassan Abidi, Richard Gyan Aboagye, Abdorrahim Absalan, Hiwa Abubaker Ali, Juan Manuel Acuna, Tigist Demssew Adane, Isaac Yeboah Addo, Oyelola A Adegboye, Mohammad Adnan, Qorinah Estiningtyas Sakilah Adnani, Muhammad Sohail Afzal, Saira Afzal, Zahra Babaei Aghdam, Bright Opoku Ahinkorah, Aqeel Ahmad, Araz Ramazan Ahmad, Rizwan Ahmad, Sajjad Ahmad, Sohail Ahmad, Sepideh Ahmadi, Ali Ahmed, Haroon Ahmed, Jivan Qasim Ahmed, Tarik Ahmed Rashid, Marjan Ajami, Budi Aji, Mostafa Akbarzadeh-Khiavi, Chisom Joyqueenet Akunna, Hanadi Al Hamad, Fares Alahdab, Ziyad Al-Aly, Mamoon A Aldeyab, Alicia V Aleman, Fadwa Alhalaiqa Naji Alhalaiqa, Robert Kaba Alhassan, Beriwan Abdulqadir Ali, Liaqat Ali, Syed Shujait Ali, Yousef Alimohamadi, Vahid Alipour, Atiyeh Alizadeh, Syed Mohamed Aljunid, Kasim Allel, Sami Almustanyir, Edward Kwabena Ameyaw, Arianna Maever L Amit, Nivedita Anandavelane, Robert Ancuceanu, Catalina Liliana Andrei, Tudorel Andrei, Dewi Anggraini, Adnan Ansar, Anayochukwu Edward Anyasodor, Jalal Arabloo, Aleksandr Y Aravkin, Demelash Areda, Timur Aripov, Anton A Artamonov, Judie Arulappan, Raphael Taiwo Aruleba, Muhammad Asaduzzaman, Tahira Ashraf, Seyyed Shamsadin Athari, Daniel Atlaw, Sameh Attia, Marcel Ausloos, Tewachew Awoke, Beatriz Paulina Ayala Quintanilla, Tegegn Mulatu Ayana, Sina Azadnajafabad, Amirhossein Azari Jafari, Darshan B B, Muhammad Badar, Ashish D Badiye, Nayereh Baghcheghi, Sara Bagherieh, Atif Amin Baig, Indrajit Banerjee, Aleksandra Barac, Mainak Bardhan, Francesco Barone-Adesi, Hiba Jawdat Barqawi, Amadou Barrow, Pritish Baskaran, Saurav Basu, Abdul-Monim Mohammad Batiha, Neeraj Bedi, Melaku Ashagrie Belete, Uzma Iqbal Belgaumi, Rose G Bender, Bharti Bhandari, Dinesh Bhandari, Pankaj Bhardwaj, Sonu Bhaskar, Krittika Bhattacharyya, Suraj Bhattarai, Saeid Bitaraf, Danilo Buonsenso, Zahid A Butt, Florentino Luciano Caetano dos Santos, Jiao Cai, Daniela Calina, Paulo Camargos, Luis Alberto Cámera, Rosario Cárdenas, Muge Cevik, Joshua Chadwick, Jaykaran Charan, Akhilanand Chaurasia, Patrick R Ching, Sonali Gajanan Choudhari, Enayet Karim Chowdhury, Fazle Rabbi Chowdhury, Dinh-Toi Chu, Isaac Sunday Chukwu, Omid Dadras, Fentaw Teshome Dagnaw, Xiaochen Dai, Saswati Das, Anna Dastiridou, Sisay Abebe Debela, Fitsum Wolde Demisse, Solomon Demissie, Diriba Dereje, Msganaw Derese, Hardik Dineshbhai Desai, Fikadu Nugusu Dessalegn, Samuel Abebe A Dessalegni, Belay Desye, Kartik Dhaduk, Meghnath Dhimal, Sameer Dhingra, Nancy Diao, Daniel Diaz, Shirin Djalalinia, Milad Dodangeh, Deepa Dongarwar, Bezabih Terefe Dora, Fariba Dorostkar, Haneil Larson Dsouza, Eleonora Dubljanin, Susanna J Dunachie, Oyewole Christopher Durojaiye, Hisham Atan Edinur, Habtamu Bekele Ejigu, Michael Ekholuenetale, Temitope Cyrus Ekundayo, Hassan El-Abid, Muhammed Elhadi, Mohamed A Elmonem, Amir Emami, Luchuo Engelbert Bain, Daniel Berhanie Enyew, Ryenchindorj Erkhembayar, Babak Eshrati, Farshid Etaee, Adeniyi Francis Fagbamigbe, Shahab Falahi, Aida Fallahzadeh, Emerito Jose A Faraon, Ali Fatehizadeh, Ginenus Fekadu, João C Fernandes, Allegra Ferrari, Getahun Fetensa, Irina Filip, Florian Fischer, Masoud Foroutan, Peter Andras Gaal, Muktar A Gadanya, Abhay Motiramji Gaidhane, Balasankar Ganesan, Mesfin Gebrehiwot, Reza Ghanbari, Mohammad Ghasemi Nour, Ahmad Ghashghaee, Ali Gholamrezanezhad, Abdolmajid Gholizadeh, Mahaveer Golechha, Pouya Goleij, Davide Golinelli, Amador Goodridge, Damitha Asanga Gunawardane, Yuming Guo, Rajat Das Gupta, Sapna Gupta, Veer Bala Gupta, Vivek Kumar Gupta, Alemu Guta, Parham Habibzadeh, Atlas Haddadi Avval, Rabih Halwani, Asif Hanif, Md. Abdul Hannan, Harapan Harapan, Shoaib Hassan, Hadi Hassankhani, Khezar Hayat, Behzad Heibati, Golnaz Heidari, Mohammad Heidari, Reza Heidari-Soureshjani, Claudiu Herteliu, Demisu Zenbaba Heyi, Kamal Hezam, Praveen Hoogar, Nobuyuki Horita, Md Mahbub Hossain, Mehdi Hosseinzadeh, Mihaela Hostiuc, Sorin Hostiuc, Soodabeh Hoveidamanesh, Junjie Huang, Salman Hussain, Nawfal R Hussein, Segun Emmanuel Ibitoye, Olayinka Stephen Ilesanmi, Irena M Ilic, Milena D Ilic, Mohammad Tarique Imam, Mustapha Immurana, Leeberk Raja Inbaraj, Arnaud Iradukunda, Nahlah Elkudssiah Ismail, Chidozie C D Iwu, Chinwe Juliana Iwu, Linda Merin J, Mihajlo Jakovljevic, Elham Jamshidi, Tahereh Javaheri, Fatemeh Javanmardi, Javad Javidnia, Sathish Kumar Jayapal, Umesh Jayarajah, Rime Jebai, Ravi Prakash Jha, Tamas Joo, Nitin Joseph, Farahnaz Joukar, Jacek Jerzy Jozwiak, Salah Eddine Oussama Kacimi, Vidya Kadashetti, Laleh R Kalankesh, Rohollah Kalhor, Vineet Kumar Kamal, Himal Kandel, Neeti Kapoor, Samad Karkhah, Bekalu Getnet Kassa, Nicholas J Kassebaum, Patrick DMC Katoto, Mohammad Keykhaei, Himanshu Khajuria, Abbas Khan, Imteyaz A Khan, Maseer Khan, Md Nuruzzaman Khan, Moien AB Khan, Moawiah Mohammad Khatatbeh, Mona M Khater, Hamid Reza Khayat Kashani, Jagdish Khubchandani, Hanna Kim, Min Seo Kim, Ruth W Kimokoti, Niranjan Kissoon, Sonali Kochhar, Farzad Kompani, Soewarta Kosen, Parvaiz A Koul, Sindhura Lakshmi Koulmane Laxminarayana, Fiorella Krapp Lopez, Kewal Krishan, Vijay Krishnamoorthy, Vishnutheertha Kulkarni, Naveen Kumar, Om P Kurmi, Ambily Kuttikkattu, Hmwe Hmwe Kyu, Dharmesh Kumar Lal, Judit Lám, Iván Landires, Savita Lasrado, Sang-woong Lee, Jacopo Lenzi, Sonia Lewycka, Shanshan Li, Stephen S Lim, Wei Liu, Rakesh Lodha, Michael J Loftus, Ayush Lohiya, László Lorenzovici, Mojgan Lotfi, Ata Mahmoodpoor, Mansour Adam Mahmoud, Razzagh Mahmoudi, Azeem Majeed, Jamal Majidpoor, Alaa Makki, Galana Ayana Mamo, Yosef Manla, Miquel Martorell, Clara N Matei, Barney McManigal, Entezar Mehrabi Nasab, Ravi Mehrotra, Addisu Melese, Oliver Mendoza-Cano, Ritesh G Menezes, Alexios-Fotios A Mentis, Georgia Micha, Irmina Maria Michalek, Ana Carolina Micheletti Gomide Nogueira de Sá, Neda Milevska Kostova, Shabir Ahmad Mir, Mojgan Mirghafourvand, Seyyedmohammadsadeq Mirmoeeni, Erkin M Mirrakhimov, Mohammad Mirza-Aghazadeh-Attari, Abay Sisay Misganaw, Awoke Misganaw, Sanjeev Misra, Esmaeil Mohammadi, Mokhtar Mohammadi, Abdollah Mohammadian-Hafshejani, Shafiu Mohammed, Syam Mohan, Mohammad Mohseni, Ali H Mokdad, Sara Momtazmanesh, Lorenzo Monasta, Catrin E Moore, Maryam Moradi, Mostafa Moradi Sarabi, Shane Douglas Morrison, Majid Motaghinejad, Haleh Mousavi Isfahani, Amin Mousavi Khaneghah, Seyed Ali Mousavi-Aghdas, Sumaira Mubarik, Francesk Mulita, Getaneh Baye B Mulu, Sandra B Munro, Saravanan Muthupandian, Tapas Sadasivan Nair, Atta Abbas Naqvi, Himanshi Narang, Zuhair S Natto, Muhammad Naveed, Biswa Prakash Nayak, Shumaila Naz, Ionut Negoi, Seyed Aria Nejadghaderi, Sandhya Neupane Kandel, Che Henry Ngwa, Robina Khan Niazi, Antonio Tolentino Nogueira de Sá, Nafise Noroozi, Hasti Nouraei, Ali Nowroozi, Virginia Nuñez-Samudio, Jerry John Nutor, Chimezie Igwegbe Nzoputam, Ogochukwu Janet Nzoputam, Bogdan Oancea, Rahman Md Obaidur, Vivek Anand Ojha, Akinkunmi Paul Okekunle, Osaretin Christabel Okonji, Andrew T Olagunju, Bolajoko Olubukunola Olusanya, Ahmed Omar Bali, Emad Omer, Nikita Otstavnov, Bilcha Oumer, Mahesh P A, Jagadish Rao Padubidri, Keyvan Pakshir, Tamás Palicz, Adrian Pana, Shahina Pardhan, Jose L Paredes, Utsav Parekh, Eun-Cheol Park, Seoyeon Park, Ashish Pathak, Rajan Paudel, Uttam Paudel, Shrikant Pawar, Hamidreza Pazoki Toroudi, Minjin Peng, Umberto Pensato, Veincent Christian Filipino Pepito, Marcos Pereira, Mario F P Peres, Norberto Perico, Ionela-Roxana Petcu, Zahra Zahid Piracha, Indrashis Podder, Nayanum Pokhrel, Ramesh Poluru, Maarten J Postma, Naeimeh Pourtaheri, Akila Prashant, Ibrahim Qattea, Mohammad Rabiee, Navid Rabiee, Amir Radfar, Saber 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Shakhmardanov, Mequannent Melaku Sharew, Athena Sharifi-Razavi, Purva Sharma, Rahim Ali Sheikhi, Ali Sheikhy, Pavanchand H Shetty, Mika Shigematsu, Jae Il Shin, Hesamaddin Shirzad-Aski, K M Shivakumar, Parnian Shobeiri, Seyed Afshin Shorofi, Sunil Shrestha, Migbar Mekonnen Sibhat, Negussie Boti Sidemo, Mustafa Kamal Sikder, Luís Manuel Lopes Rodrigues Silva, Jasvinder A Singh, Paramdeep Singh, Surjit Singh, Md Shahjahan Siraj, Samarjeet Singh Siwal, Valentin Yurievich Skryabin, Anna Aleksandrovna Skryabina, Bogdan Socea, Damtew Damtew Solomon, Yimeng Song, Chandrashekhar T Sreeramareddy, Muhammad Suleman, Rizwan Suliankatchi Abdulkader, Saima Sultana, Miklós Szócska, Seyed-Amir Tabatabaeizadeh, Mohammad Tabish, Majid Taheri, Elahe Taki, Ker-Kan Tan, Sarmila Tandukar, Nathan Y Tat, Vivian Y Tat, Belay Negash Tefera, Yibekal Manaye Tefera, Gebremaryam Temesgen, Mohamad-Hani Temsah, Samar Tharwat, Arulmani Thiyagarajan, Imad I Tleyjeh, Christopher E Troeger, Krishna Kishore Umapathi, Era 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Abdul, Harapan, Harapan, Hassan, Shoaib, Hassankhani, Hadi, Hayat, Khezar, Heibati, Behzad, Heidari, Golnaz, Heidari, Mohammad, Heidari-Soureshjani, Reza, Herteliu, Claudiu, Heyi, Demisu Zenbaba, Hezam, Kamal, Hoogar, Praveen, Horita, Nobuyuki, Hossain, Md Mahbub, Hosseinzadeh, Mehdi, Hostiuc, Mihaela, Hostiuc, Sorin, Hoveidamanesh, Soodabeh, Huang, Junjie, Hussain, Salman, Hussein, Nawfal R, Ibitoye, Segun Emmanuel, Ilesanmi, Olayinka Stephen, Ilic, Irena M, Ilic, Milena D, Imam, Mohammad Tarique, Immurana, Mustapha, Inbaraj, Leeberk Raja, Iradukunda, Arnaud, Ismail, Nahlah Elkudssiah, Iwu, Chidozie C D, Iwu, Chinwe Juliana, J, Linda Merin, Jakovljevic, Mihajlo, Jamshidi, Elham, Javaheri, Tahereh, Javanmardi, Fatemeh, Javidnia, Javad, Jayapal, Sathish Kumar, Jayarajah, Umesh, Jebai, Rime, Jha, Ravi Prakash, Joo, Tama, Joseph, Nitin, Joukar, Farahnaz, Jozwiak, Jacek Jerzy, Kacimi, Salah Eddine Oussama, Kadashetti, Vidya, Kalankesh, Laleh R, Kalhor, Rohollah, Kamal, Vineet Kumar, Kandel, Himal, Kapoor, Neeti, Karkhah, Samad, Kassa, Bekalu Getnet, Kassebaum, Nicholas J, Katoto, Patrick DMC, Keykhaei, Mohammad, Khajuria, Himanshu, Khan, Abba, Khan, Imteyaz A, Khan, Maseer, Khan, Md Nuruzzaman, Khan, Moien AB, Khatatbeh, Moawiah Mohammad, Khater, Mona M, Khayat Kashani, Hamid Reza, Khubchandani, Jagdish, Kim, Hanna, Kim, Min Seo, Kimokoti, Ruth W, Kissoon, Niranjan, Kochhar, Sonali, Kompani, Farzad, Kosen, Soewarta, Koul, Parvaiz A, Koulmane Laxminarayana, Sindhura Lakshmi, Krapp Lopez, Fiorella, Krishan, Kewal, Krishnamoorthy, Vijay, Kulkarni, Vishnutheertha, Kumar, Naveen, Kurmi, Om P, Kuttikkattu, Ambily, Kyu, Hmwe Hmwe, Lal, Dharmesh Kumar, Lám, Judit, Landires, Iván, Lasrado, Savita, Lee, Sang-woong, Lenzi, Jacopo, Lewycka, Sonia, Li, Shanshan, Lim, Stephen S, Liu, Wei, Lodha, Rakesh, Loftus, Michael J, Lohiya, Ayush, Lorenzovici, László, Lotfi, Mojgan, Mahmoodpoor, Ata, Mahmoud, Mansour Adam, Mahmoudi, Razzagh, Majeed, Azeem, Majidpoor, Jamal, Makki, Alaa, Mamo, Galana Ayana, Manla, Yosef, Martorell, Miquel, Matei, Clara N, McManigal, Barney, Mehrabi Nasab, Entezar, Mehrotra, Ravi, Melese, Addisu, Mendoza-Cano, Oliver, Menezes, Ritesh G, Mentis, Alexios-Fotios A, Micha, Georgia, Michalek, Irmina Maria, Micheletti Gomide Nogueira de Sá, Ana Carolina, Milevska Kostova, Neda, Mir, Shabir Ahmad, Mirghafourvand, Mojgan, Mirmoeeni, Seyyedmohammadsadeq, Mirrakhimov, Erkin M, Mirza-Aghazadeh-Attari, Mohammad, Misganaw, Abay Sisay, Misganaw, Awoke, Misra, Sanjeev, Mohammadi, Esmaeil, Mohammadi, Mokhtar, Mohammadian-Hafshejani, Abdollah, Mohammed, Shafiu, Mohan, Syam, Mohseni, Mohammad, Mokdad, Ali H, Momtazmanesh, Sara, Monasta, Lorenzo, Moore, Catrin E, Moradi, Maryam, Moradi Sarabi, Mostafa, Morrison, Shane Dougla, Motaghinejad, Majid, Mousavi Isfahani, Haleh, Mousavi Khaneghah, Amin, Mousavi-Aghdas, Seyed Ali, Mubarik, Sumaira, Mulita, Francesk, Mulu, Getaneh Baye B, Munro, Sandra B, Muthupandian, Saravanan, Nair, Tapas Sadasivan, Naqvi, Atta Abba, Narang, Himanshi, Natto, Zuhair S, Naveed, Muhammad, Nayak, Biswa Prakash, Naz, Shumaila, Negoi, Ionut, Nejadghaderi, Seyed Aria, Neupane Kandel, Sandhya, Ngwa, Che Henry, Niazi, Robina Khan, Nogueira de Sá, Antonio Tolentino, Noroozi, Nafise, Nouraei, Hasti, Nowroozi, Ali, Nuñez-Samudio, Virginia, Nutor, Jerry John, Nzoputam, Chimezie Igwegbe, Nzoputam, Ogochukwu Janet, Oancea, Bogdan, Obaidur, Rahman Md, Ojha, Vivek Anand, Okekunle, Akinkunmi Paul, Okonji, Osaretin Christabel, Olagunju, Andrew T, Olusanya, Bolajoko Olubukunola, Omar Bali, Ahmed, Omer, Emad, Otstavnov, Nikita, Oumer, Bilcha, P A, Mahesh, Padubidri, Jagadish Rao, Pakshir, Keyvan, Palicz, Tamá, Pana, Adrian, Pardhan, Shahina, Paredes, Jose L, Parekh, Utsav, Park, Eun-Cheol, Park, Seoyeon, Pathak, Ashish, Paudel, Rajan, Paudel, Uttam, Pawar, Shrikant, Pazoki Toroudi, Hamidreza, Peng, Minjin, Pensato, Umberto, Pepito, Veincent Christian Filipino, Pereira, Marco, Peres, Mario F P, Perico, Norberto, Petcu, Ionela-Roxana, Piracha, Zahra Zahid, Podder, Indrashi, Pokhrel, Nayanum, Poluru, Ramesh, Postma, Maarten J, Pourtaheri, Naeimeh, Prashant, Akila, Qattea, Ibrahim, Rabiee, Mohammad, Rabiee, Navid, Radfar, Amir, Raeghi, Saber, Rafiei, Sima, Raghav, Pankaja Raghav, Rahbarnia, Leila, Rahimi-Movaghar, Vafa, Rahman, Mosiur, Rahman, Muhammad Aziz, Rahmani, Amir Masoud, Rahmanian, Vahid, Ram, Pradhum, Ranjha, Muhammad Modassar Ali Nawaz, Rao, Sowmya J, Rashidi, Mohammad-Mahdi, Rasul, Azad, Ratan, Zubair Ahmed, Rawaf, Salman, Rawassizadeh, Reza, Razeghinia, Mohammad Sadegh, Redwan, Elrashdy Moustafa Mohamed, Regasa, Misganu Teshoma, Remuzzi, Giuseppe, Reta, Melese Abate, Rezaei, Nazila, Rezapour, Aziz, Riad, Abanoub, Ripon, Rezaul Karim, Rudd, Kristina E, Saddik, Basema, Sadeghian, Saeid, Saeed, Umar, Safaei, Mohsen, Safary, Azam, Safi, Sher Zaman, Sahebazzamani, Maryam, Sahebkar, Amirhossein, Sahoo, Harihar, Salahi, Saina, Salahi, Sarvenaz, Salari, Hedayat, Salehi, Sana, Samadi Kafil, Hossein, Samy, Abdallah M, Sanadgol, Nima, Sankararaman, Senthilkumar, Sanmarchi, Francesco, Sathian, Brijesh, Sawhney, Monika, Saya, Ganesh Kumar, Senthilkumaran, Subramanian, Seylani, Allen, Shah, Pritik A, Shaikh, Masood Ali, Shaker, Elaheh, Shakhmardanov, Murad Ziyaudinovich, Sharew, Mequannent Melaku, Sharifi-Razavi, Athena, Sharma, Purva, Sheikhi, Rahim Ali, Sheikhy, Ali, Shetty, Pavanchand H, Shigematsu, Mika, Shin, Jae Il, Shirzad-Aski, Hesamaddin, Shivakumar, K M, Shobeiri, Parnian, Shorofi, Seyed Afshin, Shrestha, Sunil, Sibhat, Migbar Mekonnen, Sidemo, Negussie Boti, Sikder, Mustafa Kamal, Silva, Luís Manuel Lopes Rodrigue, Singh, Jasvinder A, Singh, Paramdeep, Singh, Surjit, Siraj, Md Shahjahan, Siwal, Samarjeet Singh, Skryabin, Valentin Yurievich, Skryabina, Anna Aleksandrovna, Socea, Bogdan, Solomon, Damtew Damtew, Song, Yimeng, Sreeramareddy, Chandrashekhar T, Suleman, Muhammad, Suliankatchi Abdulkader, Rizwan, Sultana, Saima, Szócska, Mikló, Tabatabaeizadeh, Seyed-Amir, Tabish, Mohammad, Taheri, Majid, Taki, Elahe, Tan, Ker-Kan, Tandukar, Sarmila, Tat, Nathan Y, Tat, Vivian Y, Tefera, Belay Negash, Tefera, Yibekal Manaye, Temesgen, Gebremaryam, Temsah, Mohamad-Hani, Tharwat, Samar, Thiyagarajan, Arulmani, Tleyjeh, Imad I, Troeger, Christopher E, Umapathi, Krishna Kishore, Upadhyay, Era, Valadan Tahbaz, Sahel, Valdez, Pascual R, Van den Eynde, Jef, van Doorn, H. Rogier, Vaziri, Siavash, Verras, Georgios-Ioanni, Viswanathan, Harimadhav, Vo, Bay, Waris, Abdul, Wassie, Gizachew Tadesse, Wickramasinghe, Nuwan Darshana, Yaghoubi, Sajad, Yahya, Gahin Abdulraheem Tayib Yahya, Yahyazadeh Jabbari, Seyed Hossein, Yigit, Arzu, Yiğit, Vahit, Yon, Dong Keon, Yonemoto, Naohiro, Zahir, Mazyar, Zaman, Burhan Abdullah, Zaman, Sojib Bin, Zangiabadian, Moein, Zare, Iman, Zastrozhin, Mikhail Sergeevich, Zhang, Zhi-Jiang, Zheng, Peng, Zhong, Chenwen, Zoladl, Mohammad, Zumla, Alimuddin, Hay, Simon I, Dolecek, Christiane, Sartorius, Benn, Murray, Christopher J L, and Naghavi, Mohsen

Subjects
Male, Bacteria, Syndrome, Bacterial Infections, General Medicine, Global Health, Global Burden of Disease, Risk Factors, Sepsis, Humans, Female, Mortality, Child, Africa South of the Sahara
Abstract

Background: Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods: We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. Findings: From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation: The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund.

Published
2022

17. Infective endocarditis caused by Salmonella enteritidis in a dialysis patient: a case report and literature review

Author

Tsugawa, Yusuke, Futatsuyama, Miyuki, Furukawa, Keiichi, Taki, Fumika, Nishizaki, Yuji, Tamagaki, Keiichi, Kaneshiro, Yuki, and Komatsu, Yasuhiro

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Digestive Diseases, Prevention, Cardiovascular, Foodborne Illness, Rare Diseases, Heart Disease, Orphan Drug, Emerging Infectious Diseases, Hematology, Renal and urogenital, Aged, Anti-Bacterial Agents, Ceftriaxone, Ciprofloxacin, Endocarditis, Bacterial, Female, Humans, Renal Dialysis, Salmonella Infections, Salmonella enteritidis, Microbiology, Clinical sciences, Medical microbiology, Public health
Abstract

BackgroundInfective endocarditis is significantly more common in haemodialysis patients as compared with the general population, the causative pathogen is generally Staphylococcus aureus; there have been no previously reported cases of infective endocarditis caused by a Salmonella species in haemodialysis patients.Case presentationWe report the case of a 68 year-old woman on haemodialysis who developed infective endocarditis as a result of Salmonella enteritidis. Although we treated the patient with ceftriaxone combined with ciprofloxacin, infective endocarditis was not detected early enough and unfortunately developed into cerebral septic emboli, which ultimately resulted in death.ConclusionAlthough there are several reports that Salmonella endocarditis without cardiac failure can be successfully treated with antibiotics alone, early surgical intervention is essential for some cases to prevent life-threatening complications. Transesophageal echocardiography should be performed in any patient with high clinical suspicion of infective endocarditis. To the best of our knowledge, this is the first case-report of Salmonella endocarditis in a haemodialysis patient.

Published
2009

18. The impact of tertiary lymphoid structures on clinicopathological, genetic and gene expression characteristics in lung adenocarcinoma

Author

Yutaro, Tamiya, Tokiko, Nakai, Ayako, Suzuki, Sachiyo, Mimaki, Katsuya, Tsuchihara, Kei, Sato, Kiyotaka, Yoh, Shingo, Matsumoto, Yoshitaka, Zenke, Kaname, Nosaki, Hiroki, Izumi, Yuji, Shibata, Tetsuya, Sakai, Tetsuro, Taki, Saori, Miyazaki, Reiko, Watanabe, Naoya, Sakamoto, Shingo, Sakashita, Motohiro, Kojima, Naozumi, Hashimoto, Masahiro, Tsuboi, Koichi, Goto, and Genichiro, Ishii

Subjects
Pulmonary and Respiratory Medicine, History, Cancer Research, Lung Neoplasms, Polymers and Plastics, Gene Expression, Adenocarcinoma of Lung, Prognosis, B7-H1 Antigen, Industrial and Manufacturing Engineering, Tertiary Lymphoid Structures, Oncology, Biomarkers, Tumor, Humans, Business and International Management
Abstract

Tertiary lymphoid structures (TLS) are observed in several cancers and are associated with favorable prognosis. This study aimed to examine the clinicopathological, genetic, and gene expression profiles of lung adenocarcinoma patients with TLS.A total of 112 patients with pathological stage IB lung adenocarcinoma who underwent complete resection between 2011 and 2015 were enrolled in this study. We investigated whether TLS correlated with prognosis and programmed death-ligand 1 (PD-L1) expression. Furthermore, the correlation of TLS with tumor mutation burden (TMB) and genetic mutations was evaluated in patients for whom whole-exon sequencing data were available. In addition, using the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) dataset, gene expression analysis according to the TLS status was performed.Among the 112 patients, 49 were TLS-positive (TLS+). TLS+ correlated with longer recurrence-free survival (RFS) than TLS-negative cases (TLS-) (hazard ratio [HR], 0.47; 95 % confidence interval [CI]: 0.23-0.88, p = 0.02). In the multivariate analysis, TLS was a better independent prognostic factor for RFS (HR 0.37, 95 %CI 0.18-0.72, p 0.01). PD-L1 expression was not significantly different between TLS+ and TLS- patients (p = 0.54). TMB in TLS+ was similar to that in TLS- patients (p = 0.39); however, it tended to be lower than that in TLS- especially among smokers (p = 0.07). In gene expression analysis, RNA expression of chemokines related to lymph node formation, such as CXCL13, CCL19 and CCL21, was significantly higher, and biological processes such as positive regulation of humoral immune response and regulation of antigen receptor-mediated signaling pathway were enhanced in TLS+.TLS was a favorable prognostic factor and was not associated with PD-L1 expression in patients with lung adenocarcainoma. Moreover, gene expression analysis indicated that TLS is a site for the generation and regulation of antitumor immune responses.

Published
2022
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19. New Conversion Formula Between B-Type Natriuretic Peptide and N-Terminal-Pro-B-Type Natriuretic Peptide ― Analysis From a Multicenter Study ―

Author

Satomi, Ishihara, Shinya, Hiramitsu, Koshiro, Kanaoka, Mizuri, Taki, Hitoshi, Nakagawa, Tomoya, Ueda, Ayako, Seno, Taku, Nishida, Kenji, Onoue, Tsunenari, Soeda, Tomohito, Ohtani, Makoto, Watanabe, Rika, Kawakami, Yasushi, Sakata, Kazuomi, Kario, and Yoshihiko, Saito

Subjects
Cohort Studies, Heart Failure, Natriuretic Peptide, Brain, Humans, General Medicine, Cardiology and Cardiovascular Medicine, Peptide Fragments, Biomarkers
Abstract

Although B-type natriuretic peptide (BNP) and N-terminal (NT)-proBNP are commonly used markers of heart failure, a simple conversion formula between these peptides has not yet been developed for clinical use.Methods and Results: A total of 9,394 samples were obtained from Nara Medical University, Jichi Medical University, and Osaka University. We randomly selected 70% for a derivation set to investigate a conversion formula from BNP to NT-proBNP using estimated glomerular filtration rate (eGFR) and body mass index (BMI); the remaining 30% was used as the internal validation set and we used a cohort study from Nara Medical University as an external validation set. Multivariate linear regression analysis revealed a new conversion formula: log NT-proBNP = 1.21 + 1.03 × log BNP - 0.009 × BMI - 0.007 × eGFR (rThis new and simple conversion formula of BNP and NT-proBNP with eGFR and BMI is potentially useful in clinical practice.

Published
2022
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20. Features and Outcomes of Histologically Proven Myocarditis With Fulminant Presentation

Author

Koshiro Kanaoka, Kenji Onoue, Satoshi Terasaki, Tomoya Nakano, Michikazu Nakai, Yoko Sumita, Kinta Hatakeyama, Fumio Terasaki, Rika Kawakami, Yoshitaka Iwanaga, Yoshihiro Miyamoto, Yoshihiko Saito, Satoshi Yuda, Masaya Tanno, Toru Takahashi, Hisashi Yokoshiki, Masahiro Toba, Toshihisa Anzai, Toshiyuki Nagai, Takuma Sato, Takashi Takenaka, Seiji Yamazaki, Yuki Katagiri, Toshiharu Takeuchi, Kazuya Sugitatsu, Shigeo Kakinoki, Tomoaki Matsumoto, Kazushi Urasawa, Michinao Tan, Ichizo Tsujino, Mitsunori Kamigaki, Hirofumi Tomita, Kenji Hanada, Motoi Kushibiki, Akihiro Nakamura, Yoshihiro Morino, Takahito Nasu, Satoshi Yasuda, Hideaki Suzuki, Kaoru Iwabuchi, Kanako Tsuji, Shigeto Namiuchi, Tatsuya Komaru, Masahiro Yagi, Shoko Uematsu, Toshiaki Takahashi, Satoru Takeda, Toru Nakanishi, Masafumi Watanabe, Masahiro Wanezaki, Motoyuki Matsui, Shigeo Sugawara, Yasuchika Takeishi, Masayoshi Oikawa, Nobuo Komatsu, Satoshi Suzuki, Hiroshi Okamoto, Noriyuki Takeyasu, Daiki Akiyama, Yutaka Eki, Tsunekazu Kakuta, Tomoyo Sugiyama, Tomomi Koizumi, Koji Ueno, Kazuomi Kario, Mizuri Taki, Yuri Matsumoto, Takanori Yasu, Osamu Nishioka, Shigeto Naito, Makoto Murata, Shoichi Tange, Katsumi Kaneko, Makoto Muto, Hiroshi Inagaki, Shuichi Hasegawa, Eizo Tachibana, Wataru Atsumi, Masahiro Suzuki, Toshihiro Muramatsu, Yoshihiro Yamada, Isao Taguchi, Yoshiaki Fukuda, Akihiro Matsui, Junji Kanda, Koji Hozawa, Akihiko Matsumura, Wataru Shimizu, Takeshi Yamamoto, Issei Komuro, Masaru Hatano, Takanori Ikeda, Shunsuke Kiuchi, Taishiro Chikamori, Yasuyoshi Takei, Kyoko Soejima, Toshinori Minamishima, Hiroyuki Tanaka, Shigeo Shimizu, Masashi Kasao, Tadayuki Kadohira, Tohru Minamino, Kazunori Shimada, Hiroshi Iwata, Yukihiko Momiyama, Takashi Ashikaga, Toshihiro Nozato, Yasumasa Fujiwara, Kenji Inoue, Tetsuo Sasano, Junji Matsuda, Yasuhiro Ishii, Yuichi Ono, Kengo Tanabe, Yu Horiuchi, Toshiro Shinke, Yusuke Kodama, Masao Moroi, Yoshiyuki Yazaki, Taisuke Mizumura, Hiroshi Ohta, Yoshihiro Akashi, Nozomi Kotoku, Yuji Ikari, Mitsunori Maruyama, Yasuhiro Sato, Koichi Tamura, Masaaki Konishi, Hiroshi Suzuki, Mio Ebato, Kazuki Fukui, Kazuhiko Yumoto, Takamasa Iwasawa, Takeshi Kashimura, Kazuyoshi Takahashi, Yoshinobu Okada, Bunji Kaku, Kazuo Usuda, Michiro Maruyama, Tomoki Kameyama, Toshinori Higashikata, Akihiko Hodatsu, Kazuo Osato, Yoji Nagata, Koji Maeno, Kazuo Satake, Takao Sawanobori, Noboru Watanabe, Koichiro Kuwahara, Hirohiko Motoki, Hiroshi Kitabayashi, Kyuhachi Otagiri, Tsunesuke Kono, Daisuke Yamagishi, Yoshikazu Yazaki, Toshiyuki Noda, Itsuro Morishima, Naoki Watanabe, Shinichiro Tanaka, Tomoya Onodera, Ryuzo Nawada, Akinori Watanabe, Masaki Matsunaga, Satoru Suwa, Hiroshi Sakamoto, Hiroki Sakamoto, Takeshi Aoyama, Norio Kanamori, Masahiro Muto, Yuichiro Maekawa, Hayato Ohtani, Yukio Ozaki, Kenshin Naruse, Kenji Takemoto, Haruo Kamiya, Takeshi Suzuki, Yasushi Tomita, Susumu Suzuki, Ryosuke Kametani, Hidekazu Aoyama, Hiroyuki Osanai, Ken Harada, Kenji Kada, Tomoaki Saeki, Koichi Kobayashi, Yasuhiro Ogawa, Akihiro Terasawa, Masanori Shinoda, Mitsutoshi Oguri, Kiyokazu Shimizu, Akinori Sawamura, Atsushi Sugiura, Kosuke Hattori, Shinji Mokuno, Kazuhisa Kondo, Kaoru Dohi, Keishi Moriwaki, Atsunobu Kasai, Tetsuya Nakakuki, Kazuaki Kaitani, Toshikazu Jinnai, Takashi Yamamoto, Hiroyuki Kurata, Atsuyuki Wada, Masaharu Akao, Yasuhiro Hamatani, Kazuya Ishibashi, Yoshiki Akakabe, Yasuhide Asaumi, Hideo Matama, Yasushi Sakata, Hidetaka Kioka, Hiroshi Takaishi, Toru Takase, Mitsuo Matsuda, Fumi Sato, Shinji Hasegawa, Kenichi Ishigami, Minoru Ichikawa, Takashi Takagi, Moriaki Inoko, Masaaki Hoshiga, Shuichi Fujita, Yoshihiro Takeda, Takahiko Kawarabayashi, Hideyuki Takaoka, Kenji Nakajima, Tadashi Yuguchi, Tatsuya Kawasaki, Yukinori Shinoda, Yukihito Sato, Masaharu Ishihara, Yuki Matsumoto, Hiroya Kawai, Tomofumi Takaya, Kouki Matsuo, Toshiaki Mano, Kenichi Hirata, Eriko Hisamatsu, Nobutaka Inoue, Koichi Tamita, Naoki Mukohara, Hisashi Shimoyama, Toru Miyajima, Toshihiro Tamura, Yodo Tamaki, Megumi Suzuki, Ryoji Yokota, Manabu Horii, Kazuo Yamanaka, Hiroyuki Kawata, Yukihiro Hashimoto, Yasuki Nakada, Hitoshi Nakagawa, Tomoya Ueda, Taku Nishida, Ayako Seno, Makoto Watanabe, Takashi Akasaka, Takashi Tanimoto, Mamoru Toyofuku, Kazuhiro Yamamoto, Yoshiharu Kinugasa, Masayuki Hirai, Hiroshi Nasu, Kinya Shirota, Tsuyoshi Oda, Takefumi Oka, Kazushige Kadota, Masanobu Ohya, Hiroshi Ito, Kazufumi Nakamura, Soichiro Ogura, Soichiro Fuke, Shiro Uemura, Hiromi Matsubara, Atsuyuki Watanabe, Nobuyuki Morishima, Yasuki Kihara, Takayuki Hidaka, Hironori Ueda, Yujiro Ono, Yuji Muraoka, Miyo Hatanari, Yoshinori Miyamoto, Keigo Dote, Masaya Kato, Masafumi Yano, Mamoru Mochizuki, Yasuhiro Ikeda, Hiroyuki Fujinaga, Shinobu Hosokawa, Masataka Sata, Koji Yamaguchi, Naoko Aki, Tetsuo Minamino, Yuichi Miyake, Yuichiro Takagi, Masayuki Doi, Yoshio Taketani, Hideki Okayama, Tatsuya Shigematsu, Akinori Higaki, Osamu Yamaguchi, Shinji Inaba, Shuntaro Ikeda, Kazuya Kawai, Hiroaki Kitaoka, Toru Kubo, Kenji Ando, Kaoru Inui, Yoshihiro Fukumoto, Kensuke Hori, Takehiro Homma, Tomohiro Kawasaki, Masahiro Mohri, Masaki Fujiwara, Hiroyuki Tsutsui, Tomomi Ide, Shin-Ichiro Miura, Takashi Kuwano, Hideki Shimomura, Toshiaki Kadokami, Masanao Taba, Katsuhiro Kondou, Toru Kubota, Daisuke Nagatomo, Yasushi Mukai, Ryuichi Matsukawa, Hideki Tashiro, Mitsuhiro Shimomura, Koji Maemura, Hiroaki Kawano, Koji Oku, Toshihiko Yamasa, Yoshihisa Kizaki, Tomohiro Sakamoto, Yudai Tamura, Teruhiko Ito, Kazuteru Fujimoto, Kenichi Tsujita, Seiji Takashio, Hirofumi Kurokawa, Naohiko Takahashi, Shotaro Saito, Masaya Arikawa, Yoshisato Shibata, Kensaku Nishihira, Toshihiro Tsuruda, Masahiro Sonoda, Nobuhiko Atsuchi, Mitsuru Ohishi, Koji Higuchi, Masaaki Miyata, Naoya Oketani, Yoshinori Akimoto, Tomohiro Asahi, and Minoru Wake

Subjects
Male, Myocarditis, Physiology (medical), Humans, Heart Transplantation, Female, Arrhythmias, Cardiac, Middle Aged, Prognosis, Cardiology and Cardiovascular Medicine, Retrospective Studies
Abstract

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Published
2022
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21. An analysis of the outbreak situation and background risk factors for drug-resistant urinary tract infection in nursing homes

Author

Jun, Matsuura, Mitsuhiro, Shirakawa, Natsuko, Takahashi, Yukari, Taki, Megumi, Miyata, and Takashi, Nabata

Subjects
Risk Factors, Urinary Tract Infections, Escherichia coli, Humans, Geriatrics and Gerontology, Aged, Nursing Homes
Abstract

The present study clarified the outbreak situation and background risk factors for drug-resistant bacteria infection in nursing homes.Subjects were 48 elderly individuals with urinary tract infections in 3 nursing homes during the 12-month period from January to December 2020. We analyzed the drug resistance of cultured bacteria using medical records.Escherichia coli was the most frequently cultured bacteria (37.1%), and extended-spectrum β-lactamase (ESBL) -producing E. coli accounted for 26.1% of specimens. E. coli susceptibility to levofloxacin (LVFX) was seen in 47.8%, resistance in 47.8%, and intermediate response in 4.4%. E. coli susceptibility to ceftriaxone (CTRX) was seen in 73.9%, and resistance in 26.1%. E. coli susceptibility to sulfamethoxazole trimethoprim (ST) mixture was seen 81.8%, while resistance was seen in 18.2%. In addition, among ESBL-producing E. coli, susceptibility to LVFX was seen in 0% and resistance in 83.3%, and an intermediate response was seen in 16.7%, while susceptibility to ST mixture was seen in 83.3% and resistance in 16.7%. No marked differences in background risk factors were seen between the groups with LVFX-resistant and LVFX-susceptible E. coli. However, the body mass index was significantly lower (p=0.0389), and significantly more patients were treated with antimicrobial agents during the 1-year period preceding the sample acquisition and analysis (p=0.0418) in the group with CTRX-resistant E. coli than in the group with CTRX-susceptible E. coli.In the nursing homes examined, LVFX-resistant E. coli were highly prevalent, and ESBL-producing bacteria were also common. When we treat urinary tract infections, refraining from the use of LVFX is desirable, and antimicrobials should be chosen with care.

Published
2022
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22. Risk Factors for Candidiasis as an Intra-Abdominal Infection after Gastrectomy in Patients with Gastric Cancer

Author

Kyota Tatsuta, Yusuke Taki, Eiji Nakatani, Kazuya Higashizono, Erina Nagai, Masato Nishida, Shinsuke Sato, Ko Ohata, Masaya Watanabe, Hideyuki Kanemoto, and Noriyuki Oba

Subjects
Microbiology (medical), Infectious Diseases, Gastrectomy, Risk Factors, Stomach Neoplasms, Candidiasis, Humans, Intraabdominal Infections, General Medicine, Retrospective Studies
Abstract

Intra-abdominal infections (IAIs) develop in 2.4%-26.6% of patients who underwent gastrectomy for gastric cancer and are occasionally serious. However, there are few reports on the causative organisms of IAI following upper gastrointestinal tract surgery and subsequent risk factors for Candida infections. This study aimed to identify the microorganisms that cause IAIs after gastrectomy and risk factors for Candida-related IAI. The records of patients who underwent gastrectomy for gastric cancer between January 2009 and December 2019 at Shizuoka General Hospital were retrospectively collected. Patients with IAIs of grade II or higher, as measured by the Clavien-Dindo classification, were included in the analysis. The selected patients were divided into the Candida and non-Candida groups according to the presence or absence of Candida as the causative organism. Of 1,379 patients, 56 (4.1%) were diagnosed with IAIs after gastrectomy. Fifty-two patients were included in the study based on culture analyses. A total of 111 strains and 28 bacterial species were isolated during the initial culture test. Candida constituted 7.2% of all identified pathogens. Regarding the risk factors for Candida-related IAI, a history of antimicrobial use and ≥ 4 postoperative days of IAI development were independent risk factors for Candida-related IAI.

Published
2022
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23. Impact of constipation on progression of Alzheimer's disease: A retrospective study

Author

Taizen Nakase, Yasuko Tatewaki, Benjamin Thyreau, Tatsushi Mutoh, Naoki Tomita, Shuzo Yamamoto, Yumi Takano, Michiho Muranaka, and Yasuyuki Taki

Subjects
Pharmacology, Psychiatry and Mental health, Alzheimer Disease, Physiology (medical), Disease Progression, Humans, Cognitive Dysfunction, Pharmacology (medical), Neuropsychological Tests, Magnetic Resonance Imaging, Constipation, Retrospective Studies
Abstract

In terms of the gut-brain axis, constipation has been considered to be an important factor of neurodegenerative diseases, although the exact mechanism is still controversial. Herein, we aimed to investigate the contribution of constipation to the progression of dementia in a retrospective study.Patients of Alzheimer's disease(AD) and amnestic mild cognitive impairment were consecutively screened between January 2015 and December 2020, and those of whom brain MRI and neuropsychological tests were performed twice were enrolled in this study. Participants were classified into with constipation (Cons[+], n = 20) and without constipation (Cons[-], n = 64) groups. Laboratory data at the first visit were used. Regression analysis was performed in MMSE, ADAS-Cog, and the volumes of hippocampus on MRI-MPRAGE images and deep white matter lesions (DWMLs) on MRI-FLAIR images obtained at two different time points.The main finding was that the Cons[+] group showed 2.7 times faster decline in cognitive impairment compared with the Cons[-] group, that is, the liner coefficients of ADAS-Cog were 2.3544 points/year in the Cons[+] and 0.8592 points/year in the Cons[-] groups. Ancillary, changes of DWMLs showed significant correlation with the time span (p 0.01), and the liner coefficients of DWMLs were 24.48 ml/year in the Cons[+] and 14.83 ml/year in the Cons[-] group, although annual rate of hippocampal atrophy was not different between the two groups. Moreover, serum homocysteine level at baseline was significantly higher in the Cons[+] group than Cons[-] group (14.6 ± 6.4 and 11.5 ± 4.2 nmol/ml, respectively: p = 0.03).There is a significant correlation between constipation and faster progression of AD symptoms along with expansion of DWMLs.

Published
2022
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24. RELN rs7341475 Associates with Brain Structure in Japanese Healthy Females

Author

Ryo Yamaguchi, Izumi Matsudaira, Hikaru Takeuchi, Tadashi Imanishi, Ryosuke Kimura, Hiroaki Tomita, Ryuta Kawashima, and Yasuyuki Taki

Subjects
Adult, Male, Reelin Protein, Japan, General Neuroscience, Brain, Humans, Female
Abstract

Although temperament has been regarded as an innate aspect of human personality, its association with proteins involved in embryonic development is unclear. Reelin, encoded by RELN, plays an important role in brain development. Herein, we investigated the association between the RELN rs7341475 (G/A) single nucleotide polymorphism, detected as a female-specific risk factor for schizophrenia, brain structure, and temperament to elucidate the role of RELN in the development of human personality. In this study, 1580 healthy young Japanese adults were genotyped for RELN rs7341475 and completed the Temperament and Character Inventory. Whole-brain analysis of covariance was conducted to investigate differences between genotypes in regional gray matter volume (rGMV) and cortical morphology. Additionally, multiple regression analysis was performed to examine the association of four temperaments with rGMV. Those statistical analyses were performed separately for males and females. Individuals with G/G homozygosity showed significantly greater rGMV in several areas of the brain, particularly the bilateral cingulate and temporal gyrus, as well as a larger value of fractal dimension in the left lateral occipital cortex. Furthermore, of the four temperaments, the novelty seeking was significantly and positively associated with rGMV in the right superior temporal gyrus, partially overlapping with areas where differences between the rs7341475 genotypes were detected. The above findings were detected only in females, but not in males. This is the first study to demonstrate the contribution of RELN rs7341475 to differences in brain structure in Japanese females, which may indicate vulnerability to schizophrenia and variations in human personality.

Published
2022
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25. Cabotegravir/Rilpivirine: the last FDA-approved drug to treat HIV

Author

Elahe, Taki, Faezeh, Soleimani, Arezoo, Asadi, Hossein, Ghahramanpour, Ali, Namvar, and Mohsen, Heidary

Subjects
Microbiology (medical), Drug Combinations, Infectious Diseases, Anti-Retroviral Agents, Pharmaceutical Preparations, Anti-HIV Agents, Pyridones, Virology, Rilpivirine, Humans, HIV Infections, Diketopiperazines, Microbiology
Abstract

The development of long-acting (LA) drugs has changed the management of common medical conditions for human replication immunodeficiency virus (HIV). Cabenuva (cabotegravir/Rilpivirine) is the first LA antiretroviral injectable drug composed of nano-formulation of cabotegravir (CAB) and rilpivirine (RPV).In this review article, we aim to have a brief overview of results of major clinical trials that administrated Cabotegravir/Rilpivirine for patients considering the efficacy and safety profiles. Moreover, we discuss about CAB and RPV chemical structure, mechanism of action, ‎activity against drug-sensitive and -resistant HIV, and pharmacodynamics/pharmacokinetics properties.Based on the results of the ATLAS and FLAIR trials, Cabotegravir/Rilpivirine regimen once-monthly has shown equal effectivity to oral combination antiretroviral therapy (cART) in maintaining HIV-1 suppression in patients. Furthermore, ATLAS-2 M study revealed the non-inferiority of Cabotegravir/Rilpivirine regimen every 8 weeks compared to every 4 weeks. The injectable LA ART reduces the number of treatment intake as well as increases adherence, especially in patients with HIV-related stigma. Administration of extended-release agents probably minimize the risk of treatment-related toxicity and resistance related to sub-optimal adherence to oral ART, so Cabotegravir/Rilpivirine can be suggested as a suitable alternative for HIV infection control in current era.

Published
2022
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26. <scp>Higher‐resolution</scp> quantification of white matter hypointensities by large‐scale transfer learning from <scp>2D</scp> images on the <scp>JPSC‐AD</scp> cohort

Author

Benjamin, Thyreau, Yasuko, Tatewaki, Liying, Chen, Yuji, Takano, Naoki, Hirabayashi, Yoshihiko, Furuta, Jun, Hata, Shigeyuki, Nakaji, Tetsuya, Maeda, Moeko, Noguchi-Shinohara, Masaru, Mimura, Kenji, Nakashima, Takaaki, Mori, Minoru, Takebayashi, Toshiharu, Ninomiya, and Yasuyuki, Taki

Subjects
Machine Learning, Japan, Neurology, Radiological and Ultrasound Technology, Brain, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Neurology (clinical), Anatomy, Magnetic Resonance Imaging, White Matter, Aged
Abstract

White matter lesions (WML) commonly occur in older brains and are quantifiable on MRI, often used as a biomarker in Aging research. Although algorithms are regularly proposed that identify these lesions from T2-fluid-attenuated inversion recovery (FLAIR) sequences, none so far can estimate lesions directly from T1-weighted images with acceptable accuracy. Since 3D T1 is a polyvalent and higher-resolution sequence, it could be beneficial to obtain the distribution of WML directly from it. However a serious difficulty, both for algorithms and human, can be found in the ambiguities of brain signal intensity in T1 images. This manuscript shows that a cross-domain ConvNet (Convolutional Neural Network) approach can help solve this problem. Still, this is non-trivial, as it would appear to require a large and varied dataset (for robustness) labelled at the same high resolution (for spatial accuracy). Instead, our model was taught from two-dimensional FLAIR images with a loss function designed to handle the super-resolution need. And crucially, we leveraged a very large training set for this task, the recently assembled, multi-sites Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) cohort. We describe the two-step procedure that we followed to handle such a large number of imperfectly labeled samples. A large-scale accuracy evaluation conducted against FreeSurfer 7, and a further visual expert rating revealed that WML segmentation from our ConvNet was consistently better. Finally, we made a directly usable software program based on that trained ConvNet model, available at https://github.com/bthyreau/deep-T1-WMH.

Published
2022
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27. Altruistic Social Activity, Depressive Symptoms, and Brain Regional Gray Matter Volume: Voxel-Based Morphometry Analysis From 8,695 Old Adults

Author

Yingxu, Liu, Ye, Zhang, Benjamin, Thyreau, Yasuko, Tatewaki, Izumi, Matsudaira, Yuji, Takano, Naoki, Hirabayashi, Yoshihikto, Furuta, Jun, Hata, Toshiharu, Ninomiya, Yasuyuki, Taki, and Michiaki, Kubo Yutaka Kiyohara

Subjects
Aging, Cross-Sectional Studies, Depression, Brain, Humans, Dementia, Prospective Studies, Gray Matter, Geriatrics and Gerontology, Magnetic Resonance Imaging, Aged
Abstract

Altruistic social activity, such as giving support to others, has shown protective benefits on dementia risk and cognitive decline. However, the pathological mechanism is unclear. In the present study, we investigated the association between altruistic social activity and brain regional gray matter. Furthermore, to explore the psychological interplay in altruistic social activity, we tested mediating effect of depressive symptoms on brain regional gray matter. We performed a cross-sectional voxel-based morphology (VBM) analysis including 8 695 old adults (72.9 ± 6.1 years) from Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) Cohort. We measured altruistic social activities by self-report questionnaires, depressive symptoms by Geriatric Depression Scale (GDS)-short version. We employed the whole-brain VBM method to detect relevant structural properties related to altruistic social activity. We then performed multiple regression models to detect the mediating effect of depressive symptoms on particular brain regional gray matter volume while adjusting possible physical and social lifestyle covariables. We found that altruistic social activity is associated with larger gray matter volume in posterior insula, middle cingulate gyrus, hippocampus, thalamus, superior temporal gyrus, anterior orbital gyrus, and middle occipital gyrus. Depressive symptoms mediated over 10% on altruistic social activity and hippocampus volume, over 20% on altruistic social activity and cingulate gyrus volume. Our results indicated that altruistic social activity might preserve brain regional gray matter which are sensitive to aging and cognitive decline. Meanwhile, this association may be explained by indirect effect on depressive symptoms, suggesting that altruistic social activity may mitigate the neuropathology of dementia.

Published
2022
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28. Darier disease successfully treated with a topical agent containing vitamin A (retinyl palmitate), vitamin E, and urea

Author

Akira Miyazaki, Tomoki Taki, Takuya Takeichi, Michihiro Kono, Hiroaki Yagi, and Masashi Akiyama

Subjects
Retinoids, Retinyl Esters, Adolescent, Humans, Urea, Vitamin E, Female, Dermatology, General Medicine, Diterpenes, Vitamin A, Darier Disease
Abstract

Darier disease (DD), also called keratosis follicularis, is an autosomal dominant hereditary keratinization disorder that manifests as keratotic papules with plaques in seborrheic areas. There are no validated curative treatments for DD, with the majority of cases treated symptomatically. We report the efficacy of a topical over-the-counter agent which contains retinyl palmitate, vitamin E, and urea for a patient with DD. A 13-year-old girl had brown papules on her scalp, neck, shoulders, and axillae since entering elementary school. A skin biopsy revealed hyperkeratosis, suprabasal acantholysis, and dyskeratosis manifested as corps ronds and grains in the epidermis. Sanger sequencing found the previously reported heterozygous mutation c.1484CT in ATP2A2. The application of an over-the-counter topical agent containing retinyl palmitate 2750 μg/g (5000 IU/g), tocopheryl acetate 20 mg/g, urea 200 mg/g, and monoammonium glycyrrhizinate 5 mg/g twice daily for 2 months improved the papules without serious adverse events. Oral or topical aromatic vitamin A analogs (retinoids) are often used to treat DD. However, several adverse events are associated with retinoid treatment, and many patients only undergo their intermittent use or discontinue the treatments. Retinyl palmitate is more stable and has a lower irritative profile than other retinoic acids. When applied topically, however, retinyl palmitate cannot penetrate the skin as well as retinol can. Some reports have noted that vitamin E increases the biological availability of vitamin A and that urea helps mechanical percutaneous drug delivery. Our case suggests that retinyl palmitate has a sufficient therapeutic effect when combined with vitamin E and urea. In conclusion, we propose that topical agents containing retinyl palmitate, vitamin E, and urea might have a satisfactory effect on the skin lesions of DD patients, without the serious risks of adverse events.

Published
2022
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29. Impact of medium-chain triglycerides on gait performance and brain metabolic network in healthy older adults: a double-blind, randomized controlled study

Author

Tatsushi Mutoh, Keiko Kunitoki, Yasuko Tatewaki, Shuzo Yamamoto, Benjamin Thyreau, Izumi Matsudaira, Ryuta Kawashima, and Yasuyuki Taki

Subjects
Male, Aging, Glucose, Brain, Humans, Female, Original Article, Geriatrics and Gerontology, Gait, Metabolic Networks and Pathways, Triglycerides, Aged
Abstract

Nutritional supplementation with medium-chain triglycerides (MCTs) has the potential to increase memory function in elderly patients with frailty and dementia. Our aim was to investigate the effects of MCT on cognitive and gait functions and their relationships with focal brain metabolism and functional connectivity even in healthy older adults. Participants were blindly randomized and allocated to two groups: 18 g/day of MCT oil and matching placebo formula (control) administered as a jelly stick (6 g/pack, ingested three times a day). Gait analysis during the 6-m walk test, cognition, brain focal glucose metabolism quantified by (18)F-fluorodeocyglucose positron emission tomography, and magnetic resonance imaging-based functional connectivity were assessed before and after a 3-month intervention. Sixty-three healthy, normal adults (females and males) were included. Compared with the control group, the MCT group showed better balance ability, as represented by the lower Lissajous index (23.1 ± 14.4 vs. 31.3 ± 18.9; P

Published
2022
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30. Immunosuppressive tumor microenvironment in uterine serous carcinoma via CCL7 signal with myeloid-derived suppressor cells

Author

Yuka Mise, Junzo Hamanishi, Takiko Daikoku, Shiro Takamatsu, Taito Miyamoto, Mana Taki, Koji Yamanoi, Ken Yamaguchi, Masayo Ukita, Naoki Horikawa, Kaoru Abiko, Ryusuke Murakami, Yoko Furutake, Yuko Hosoe, Jumpei Terakawa, Masahiro Kagabu, Tamotsu Sugai, Mitsumasa Osakabe, Hiroshi Fujiwara, Noriomi Matsumura, Masaki Mandai, and Tsukasa Baba

Subjects
Mice, Inbred C57BL, Mice, Cancer Research, Cell Line, Tumor, Myeloid-Derived Suppressor Cells, Tumor Microenvironment, Animals, Humans, Female, General Medicine, Chemokine CCL7, Cystadenocarcinoma, Serous, Endometrial Neoplasms
Abstract

Serous carcinoma of the uterus (USC) is a pathological subtype of high-grade endometrial cancers, with no effective treatment for advanced cases. Since such refractory tumors frequently harbor antitumor immune tolerance, many immunotherapies have been investigated for various malignant tumors using immuno-competent animal models mimicking their local immunities. In this study, we established an orthotopic mouse model of high-grade endometrial cancer and evaluated the local tumor immunity to explore the efficacy of immunotherapies against USC. A multivariate analysis of 62 human USC cases revealed that the tumor-infiltrating cell status, few CD8+ cells and abundant myeloid-derived suppressor cells (MDSCs), was an independent prognostic factor (P < 0.005). A murine endometrial cancer cell (mECC) was obtained from C57BL/6 mice via endometrium-specific deletion of Pten and Tp53, and another high-grade cell (HPmECC) was established by further overexpressing Myc in mECCs. HPmECCs exhibited higher capacities of migration and anchorage-independent proliferation than mECCs (P < 0.01, P < 0.0001), and when both types of cells were inoculated into the uterus of C57BL/6 mice, the prognosis of mice bearing HPmECC-derived tumors was significantly poorer (P < 0.001). Histopathological analysis of HPmECC orthotopic tumors showed serous carcinoma-like features with prominent tumor infiltration of MDSCs (P < 0.05), and anti-Gr-1 antibody treatment significantly prolonged the prognosis of HPmECC-derived tumor-bearing mice (P < 0.05). High CCL7 expression was observed in human USC and HPmECC, and MDSCs migration was promoted in a CCL7 concentration-dependent manner. These results indicate that antitumor immunity is suppressed in USC due to increased number of tumor-infiltrating MDSCs via CCL signal.

Published
2022
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31. Switching from aflibercept to brolucizumab for the treatment of refractory neovascular age-related macular degeneration

Author

Hikaru Ota, Jun Takeuchi, Yuyako Nakano, Etsuyo Horiguchi, Yosuke Taki, Yasuki Ito, Hiroko Terasaki, Koji M. Nishiguchi, and Keiko Kataoka

Subjects
Recombinant Fusion Proteins, Visual Acuity, Angiogenesis Inhibitors, General Medicine, Antibodies, Monoclonal, Humanized, Uveitis, Macular Degeneration, Ophthalmology, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, Intravitreal Injections, Wet Macular Degeneration, Humans, Tomography, Optical Coherence
Abstract

To examine the 16-week outcomes of switching to brolucizumab in eyes with neovascular age-related macular degeneration (nAMD) refractory to aflibercept.Retrospective observational study.Data of eyes with nAMD who switched to brolucizumab because of resistance to aflibercept were collected. The best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status on optical coherence tomography were analyzed.A total of 48 eyes of 48 patients were reviewed. At 4 to 7 weeks after switching, BCVA changed from 0.26 ± 0.19 to 0.25 ± 0.21 (not significant; P = 0.95), but CRT significantly decreased from 298.9 ± 108.4 µm to 241.9 ± 92.5 µm (P 0.001) and CCT from 182.6 ± 89.3 µm to 169.7 ± 82.6 µm (P 0.001). Of the 23 eyes refractory to monthly aflibercept injections, 12 (52.2%) achieved a dry macula, and 8 (34.8%) reduced exudative changes at 1 month. At 16 weeks, 31 eyes (64.6%) achieved the treatment interval ≥ 8 weeks. Two patients (4.2%) dropped out, 7 eyes (14.6%) developed intraocular inflammation (IOI), and 8 eyes (16.7%) switched back to aflibercept because of the failure to extend the treatment interval ≥ 8 weeks.Switching to brolucizumab in eyes refractory to aflibercept conferred favorable outcomes in controlling exudative changes. However, IOI and the regulation of the treatment interval to at least 8 weeks during the maintenance phase disrupted the continuation of brolucizumab treatment.

Published
2022
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32. Prognostic impact of count of extratumoral lymphatic permeation in lung adenocarcinoma and its relation to the immune microenvironment

Author

Takahiro Niimi, Tokiko Nakai, Keiju Aokage, Kenta Tane, Tomohiro Miyoshi, Joji Samejima, Saori Miyazaki, Tetsuro Taki, Naoya Sakamoto, Shingo Sakashita, Reiko Watanabe, Motohiro Kojima, Kenji Suzuki, Masahiro Tsuboi, and Genichiro Ishii

Subjects
Cancer Research, Lung Neoplasms, Lymphocytes, Tumor-Infiltrating, Oncology, Tumor Microenvironment, Humans, Adenocarcinoma of Lung, Forkhead Transcription Factors, General Medicine, Prognosis
Abstract

Extratumoral lymphatic permeation (ly-ext) has been reported as an independent poor prognostic factor for lung adenocarcinoma, but whether or not the number of ly-ext foci is associated with prognosis and its relationship to the immune microenvironment is unclear. We counted the number of ly-ext foci on pathological slides from patients with completely resected lung adenocarcinoma with ly-ext, and divided them into two groups: a group with a high number of ly-ext foci (ly-ext high) and one with a low number of ly-ext foci (ly-ext low). Among the patients with ly-ext, only a high number of ly-ext foci was an independent poor prognostic factor. The 3-year recurrence-free survival (RFS) rate of the ly-ext high group was significantly lower than that of the ly-ext low group (14.7% vs. 50.0%, P 0.01). Then, we analyzed the immune microenvironment of pT1 lung adenocarcinoma with ly-ext (13 cases of ly-ext high and 11 cases of ly-ext low tumor) by immunohistochemistry using antibodies for stem cell markers (aldehyde dehydrogenase 1 A1 and CD44), tumor-promoting mucin (MUC1), tumor-infiltrating lymphocytes (CD4, CD8, FOXP3, and CD79a), and tumor-associated macrophages (CD204). The number of CD8+ TILs within the primary lesion was significantly lower and the number of FOXP3+ TILs within the primary lesion was significantly higher in the ly-ext high group (P 0.05 and P 0.01, respectively). Our results indicated that a high number of ly-ext foci was an independent poor prognostic factor. Moreover, tumors with high numbers of ly-ext foci had a more immunosuppressive microenvironment.

Published
2022
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33. 18F‐fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma

Author

Kotaro Nomura, Tokiko Nakai, Yukino Nishina, Naoya Sakamoto, Tomohiro Miyoshi, Kenta Tane, Joji Samejima, Keiju Aokage, Motohiro Kojima, Shingo Sakashita, Tetsuro Taki, Saori Miyazaki, Reiko Watanabe, Kenji Suzuki, Masahiro Tsuboi, and Genichiro Ishii

Subjects
Cancer Research, Lung Neoplasms, Adenocarcinoma of Lung, General Medicine, Prognosis, Oncology, Fluorodeoxyglucose F18, Lymphatic Metastasis, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Tumor Microenvironment, Humans, Lymph Nodes, Retrospective Studies
Abstract

Positron emission tomography is a useful technique for diagnosing lymph node (LN) metastasis. This study aimed to elucidate the association between fluorodeoxyglucose accumulation and the microenvironment in metastatic LNs in lung adenocarcinoma. We retrospectively analyzed 62 patients with surgically resected pathological N2 lung adenocarcinoma who underwent preoperative PET. The maximum standardized uptake value (SUV

Published
2022
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34. Shame proneness is associated with individual differences in temporal pole white matter structure

Author

Carlos Makoto Miyauchi, Hikaru Takeuchi, Yasuyuki Taki, Seishu Nakagawa, Sugiko Hanawa, Atsushi Sekiguchi, Rui Nouchi, Yuko Sassa, and Ryuta Kawashima

Subjects
Adult, Male, Adolescent, Social Psychology, Emotions, Individuality, Shame, Development, White Matter, Young Adult, Behavioral Neuroscience, Guilt, Humans, Female
Abstract

Shame and guilt are distinct negative moral emotions, although they are usually regarded as overlapping affective experiences. Of these two emotions, shame is more closely related to concerns about other people's judgment, whereas guilt is more related to concerns about one's own judgment. Although some studies have tried to identify the psychological process underlying shame as opposed to guilt, there is no clear evidence of brain regions that are specifically relevant to the experience of shame rather than guilt and, more generally, self-blame. We therefore investigated associations between individual differences in shame- and guilt-proneness and the gray and white matter structures of the brain using magnetic resonance imaging and voxel-based morphometry while controlling for associations with guilt- or shame-proneness. To accomplish this goal, we enrolled 590 healthy, right-handed individuals (338 men and 252 women; age, 20.6 ± 1.8 years). We administered a questionnaire to assess shame proneness and guilt proneness. Based on our hypothesis, we found that high shame proneness was associated with decreased regional white matter density only in the right inferior temporal pole, whereas no significant region was associated with guilt. The function of this area may be important for the underlying processes differentiating shame from guilt.

Published
2022
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35. Age–sex differences in the global burden of lower respiratory infections and risk factors, 1990–2019: results from the Global Burden of Disease Study 2019

Author

Hmwe Hmwe Kyu, Avina Vongpradith, Sarah Brooke Sirota, Amanda Novotney, Christopher E Troeger, Matthew C Doxey, Rose G Bender, Jorge R Ledesma, Molly H Biehl, Samuel B Albertson, Joseph Jon Frostad, Katrin Burkart, Fiona B Bennitt, Jeff T Zhao, William M Gardner, Hailey Hagins, Dana Bryazka, Regina-Mae Villanueva Dominguez, Semagn Mekonnen Abate, Michael Abdelmasseh, Amir Abdoli, Gholamreza Abdoli, Aidin Abedi, Vida Abedi, Tadesse M Abegaz, Hassan Abidi, Richard Gyan Aboagye, Hassan Abolhassani, Yonas Derso Abtew, Hiwa Abubaker Ali, Eman Abu-Gharbieh, Ahmed Abu-Zaid, Kidist Adamu, Isaac Yeboah Addo, Oyelola A Adegboye, Mohammad Adnan, Qorinah Estiningtyas Sakilah Adnani, Muhammad Sohail Afzal, Saira Afzal, Bright Opoku Ahinkorah, Aqeel Ahmad, Araz Ramazan Ahmad, Sajjad Ahmad, Ali Ahmadi, Sepideh Ahmadi, Haroon Ahmed, Jivan Qasim Ahmed, Tarik Ahmed Rashid, Mostafa Akbarzadeh-Khiavi, Hanadi Al Hamad, Luciana Albano, Mamoon A Aldeyab, Bezatu Mengistie Alemu, Kefyalew Addis Alene, Abdelazeem M Algammal, Fadwa Alhalaiqa Naji Alhalaiqa, Robert Kaba Alhassan, Beriwan Abdulqadir Ali, Liaqat Ali, Musa Mohammed Ali, Syed Shujait Ali, Yousef Alimohamadi, Vahid Alipour, Adel Al-Jumaily, Syed Mohamed Aljunid, Sami Almustanyir, Rajaa M Al-Raddadi, Rami H Hani Al-Rifai, Saif Aldeen S AlRyalat, Nelson Alvis-Guzman, Nelson J Alvis-Zakzuk, Edward Kwabena Ameyaw, Javad Javad Aminian Dehkordi, John H Amuasi, Dickson A Amugsi, Etsay Woldu Anbesu, Adnan Ansar, Anayochukwu Edward Anyasodor, Jalal Arabloo, Demelash Areda, Ayele Mamo Argaw, Zeleke Gebru Argaw, Judie Arulappan, Raphael Taiwo Aruleba, Mulusew A Asemahagn, Seyyed Shamsadin Athari, Daniel Atlaw, Engi F Attia, Sameh Attia, Avinash Aujayeb, Tewachew Awoke, Tegegn Mulatu Ayana, Martin Amogre Ayanore, Sina Azadnajafabad, Mohammadreza Azangou-Khyavy, Samad Azari, Amirhossein Azari Jafari, Muhammad Badar, Ashish D Badiye, Nayereh Baghcheghi, Sara Bagherieh, Atif Amin Baig, Maciej Banach, Indrajit Banerjee, Mainak Bardhan, Francesco Barone-Adesi, Hiba Jawdat Barqawi, Amadou Barrow, Azadeh Bashiri, Quique Bassat, Abdul-Monim Mohammad Batiha, Abate Bekele Belachew, Melaku Ashagrie Belete, Uzma Iqbal Belgaumi, Akshaya Srikanth Bhagavathula, Nikha Bhardwaj, Pankaj Bhardwaj, Parth Bhatt, Vijayalakshmi S Bhojaraja, Zulfiqar A Bhutta, Soumitra S Bhuyan, Ali Bijani, Saeid Bitaraf, Belay Boda Abule Bodicha, Nikolay Ivanovich Briko, Danilo Buonsenso, Muhammad Hammad Butt, Jiao Cai, Paulo Camargos, Luis Alberto Cámera, Promit Ananyo Chakraborty, Muluken Genetu Chanie, Jaykaran Charan, Vijay Kumar Chattu, Patrick R Ching, Sungchul Choi, Yuen Yu Chong, Sonali Gajanan Choudhari, Enayet Karim Chowdhury, Devasahayam J Christopher, Dinh-Toi Chu, Natalie L Cobb, Aaron J Cohen, Natália Cruz-Martins, Omid Dadras, Fentaw Teshome Dagnaw, Xiaochen Dai, Lalit Dandona, Rakhi Dandona, An Thi Minh Dao, Sisay Abebe Debela, Biniyam Demisse, Fitsum Wolde Demisse, Solomon Demissie, Diriba Dereje, Hardik Dineshbhai Desai, Abebaw Alemayehu Desta, Belay Desye, Sameer Dhingra, Nancy Diao, Daniel Diaz, Lankamo Ena Digesa, Linh Phuong Doan, Milad Dodangeh, Deepa Dongarwar, Fariba Dorostkar, Wendel Mombaque dos Santos, Haneil Larson Dsouza, Eleonora Dubljanin, Oyewole Christopher Durojaiye, Hisham Atan Edinur, Elham Ehsani-Chimeh, Ebrahim Eini, Michael Ekholuenetale, Temitope Cyrus Ekundayo, Eman D El Desouky, Iman El Sayed, Maysaa El Sayed Zaki, Muhammed Elhadi, Ahmed Mahmoud Rabie Elkhapery, Amir Emami, Luchuo Engelbert Bain, Ryenchindorj Erkhembayar, Farshid Etaee, Mohamad Ezati Asar, Adeniyi Francis Fagbamigbe, Shahab Falahi, Aida Fallahzadeh, Anwar Faraj, Emerito Jose A Faraon, Ali Fatehizadeh, Pietro Ferrara, Allegra Allegra Ferrari, Getahun Fetensa, Florian Fischer, Joanne Flavel, Masoud Foroutan, Peter Andras Gaal, Abhay Motiramji Gaidhane, Santosh Gaihre, Nasrin Galehdar, Alberto L Garcia-Basteiro, Tushar Garg, Mesfin Damtew Gebrehiwot, Mathewos Alemu Gebremichael, Yibeltal Yismaw Gela, Belete Negese Belete Gemeda, Bradford D Gessner, Melaku Getachew, Asmare Getie, Seyyed-Hadi Ghamari, Mohammad Ghasemi Nour, Ahmad Ghashghaee, Ali Gholamrezanezhad, Abdolmajid Gholizadeh, Rakesh Ghosh, Sherief Ghozy, Pouya Goleij, Mohamad Golitaleb, Giuseppe Gorini, Alessandra C Goulart, Girma Garedew Goyomsa, Habtamu Alganeh Guadie, Zewdie Gudisa, Rashid Abdi Guled, Sapna Gupta, Veer Bala Gupta, Vivek Kumar Gupta, Alemu Guta, Parham Habibzadeh, Arvin Haj-Mirzaian, Rabih Halwani, Samer Hamidi, Md Abdul Hannan, Mehdi Harorani, Ahmed I Hasaballah, Hamidreza Hasani, Abbas M Hassan, Shokoufeh Hassani, Hossein Hassanian-Moghaddam, Hadi Hassankhani, Khezar Hayat, Behzad Heibati, Mohammad Heidari, Demisu Zenbaba Heyi, Kamal Hezam, Ramesh Holla, Sung Hwi Hong, Nobuyuki Horita, Mohammad-Salar Hosseini, Mehdi Hosseinzadeh, Mihaela Hostiuc, Mowafa Househ, Soodabeh Hoveidamanesh, Junjie Huang, Nawfal R Hussein, Ivo Iavicoli, Segun Emmanuel Ibitoye, Kevin S Ikuta, Olayinka Stephen Ilesanmi, Irena M Ilic, Milena D Ilic, 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S., Zeng, W., Zhang, M., Zhang, Z. -J., Zhong, C., Zoladl, M., Zumla, A., Lim, S. S., Vos, T., Naghavi, M., Brauer, M., Hay, S. I., Murray, C. J. L., University of St Andrews. School of Medicine, University of St Andrews. 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D, Anbesu, E, Ansar, A, Anyasodor, A, Arabloo, J, Areda, D, Argaw, A, Argaw, Z, Arulappan, J, Aruleba, R, Asemahagn, M, Athari, S, Atlaw, D, Attia, E, Attia, S, Aujayeb, A, Awoke, T, Ayana, T, Ayanore, M, Azadnajafabad, S, Azangou-Khyavy, M, Azari, S, Azari Jafari, A, Badar, M, Badiye, A, Baghcheghi, N, Bagherieh, S, Baig, A, Banach, M, Banerjee, I, Bardhan, M, Barone-Adesi, F, Barqawi, H, Barrow, A, Bashiri, A, Bassat, Q, Batiha, A, Belachew, A, Belete, M, Belgaumi, U, Bhagavathula, A, Bhardwaj, N, Bhardwaj, P, Bhatt, P, Bhojaraja, V, Bhutta, Z, Bhuyan, S, Bijani, A, Bitaraf, S, Bodicha, B, Briko, N, Buonsenso, D, Butt, M, Cai, J, Camargos, P, Camera, L, Chakraborty, P, Chanie, M, Charan, J, Chattu, V, Ching, P, Choi, S, Chong, Y, Choudhari, S, Chowdhury, E, Christopher, D, Chu, D, Cobb, N, Cohen, A, Cruz-Martins, N, Dadras, O, Dagnaw, F, Dai, X, Dandona, L, Dandona, R, Dao, A, Debela, S, Demisse, B, Demisse, F, Demissie, S, Dereje, D, Desai, H, Desta, A, Desye, B, Dhingra, S, Diao, N, Diaz, D, Digesa, L, Doan, L, Dodangeh, M, Dongarwar, D, Dorostkar, F, dos Santos, W, Dsouza, H, Dubljanin, E, Durojaiye, O, Edinur, H, Ehsani-Chimeh, E, Eini, E, Ekholuenetale, M, Ekundayo, T, El Desouky, E, El Sayed, I, El Sayed Zaki, M, Elhadi, M, Elkhapery, A, Emami, A, Engelbert Bain, L, Erkhembayar, R, Etaee, F, Ezati Asar, M, Fagbamigbe, A, Falahi, S, Fallahzadeh, A, Faraj, A, Faraon, E, Fatehizadeh, A, Ferrara, P, Ferrari, A, Fetensa, G, Fischer, F, Flavel, J, Foroutan, M, Gaal, P, Gaidhane, A, Gaihre, S, Galehdar, N, Garcia-Basteiro, A, Garg, T, Gebrehiwot, M, Gebremichael, M, Gela, Y, Gemeda, B, Gessner, B, Getachew, M, Getie, A, Ghamari, S, Ghasemi Nour, M, Ghashghaee, A, Gholamrezanezhad, A, Gholizadeh, A, Ghosh, R, Ghozy, S, Goleij, P, Golitaleb, M, Gorini, G, Goulart, A, Goyomsa, G, Guadie, H, Gudisa, Z, Guled, R, Gupta, S, Gupta, V, Guta, A, Habibzadeh, P, Haj-Mirzaian, A, Halwani, R, Hamidi, S, Hannan, M, Harorani, M, Hasaballah, A, Hasani, H, Hassan, A, Hassani, S, Hassanian-Moghaddam, H, Hassankhani, H, Hayat, K, Heibati, B, Heidari, M, Heyi, D, Hezam, K, Holla, R, Hong, S, Horita, N, Hosseini, M, Hosseinzadeh, M, Hostiuc, M, Househ, M, Hoveidamanesh, S, Huang, J, Hussein, N, Iavicoli, I, Ibitoye, S, Ikuta, K, Ilesanmi, O, Ilic, I, Ilic, M, Immurana, M, Ismail, N, Iwagami, M, Jaafari, J, Jamshidi, E, Jang, S, Javadi Mamaghani, A, Javaheri, T, Javanmardi, F, Javidnia, J, Jayapal, S, Jayarajah, U, Jayaram, S, Jema, A, Jeong, W, Jonas, J, Joseph, N, Joukar, F, Jozwiak, J, K, V, Kabir, Z, Kacimi, S, Kadashetti, V, Kalankesh, L, Kalhor, R, Kamath, A, Kamble, B, Kandel, H, Kanko, T, Karaye, I, Karch, A, Karkhah, S, Kassa, B, Katoto, P, Kaur, H, Kaur, R, Keikavoosi-Arani, L, Keykhaei, M, Khader, Y, Khajuria, H, Khan, E, Khan, G, Khan, I, Khan, M, Khan, Y, Khatatbeh, M, Khosravifar, M, Khubchandani, J, Kim, M, Kimokoti, R, Kisa, A, Kisa, S, Kissoon, N, Knibbs, L, Kochhar, S, Kompani, F, Koohestani, H, Korshunov, V, Kosen, S, Koul, P, Koyanagi, A, Krishan, K, Kuate Defo, B, Kumar, G, Kurmi, O, Kuttikkattu, A, Lal, D, Lam, J, Landires, I, Ledda, C, Lee, S, Levi, M, Lewycka, S, Liu, G, Liu, W, Lodha, R, Lorenzovici, L, Lotfi, M, Loureiro, J, Madadizadeh, F, Mahmoodpoor, A, Mahmoudi, R, Mahmoudimanesh, M, Majidpoor, J, Makki, A, Malakan Rad, E, Malik, A, Mallhi, T, Manla, Y, Matei, C, Mathioudakis, A, Maude, R, Mehrabi Nasab, E, Melese, A, Memish, Z, Mendoza-Cano, O, Mentis, A, Meretoja, T, Merid, M, Mestrovic, T, Micheletti Gomide Nogueira de Sa, A, Mijena, G, Minh, L, Mir, S, Mirfakhraie, R, Mirmoeeni, S, Mirza, A, Mirza, M, Mirza-Aghazadeh-Attari, M, Misganaw, A, Mohammadi, E, Mohammadi, M, Mohammed, A, Mohammed, S, Mohan, S, Mohseni, M, Moka, N, Mokdad, A, Momtazmanesh, S, Monasta, L, Moniruzzaman, M, Montazeri, F, Moore, C, Moradi, A, Morawska, L, Mosser, J, Mostafavi, E, Motaghinejad, M, Mousavi Isfahani, H, Mousavi-Aghdas, S, Mubarik, S, Murillo-Zamora, E, Mustafa, G, Nair, S, Nair, T, Najafi, H, Naqvi, A, Narasimha Swamy, S, Natto, Z, Nayak, B, Nejadghaderi, S, Nguyen, H, Niazi, R, Nogueira de Sa, A, Nouraei, H, Nowroozi, A, Nunez-Samudio, V, Nzoputam, C, Nzoputam, O, Oancea, B, Ochir, C, Odukoya, O, Okati-Aliabad, H, Okekunle, A, Okonji, O, Olagunju, A, Olufadewa, I, Omar Bali, A, Omer, E, Oren, E, Ota, E, Otstavnov, N, Oulhaj, A, P A, M, Padubidri, J, Pakshir, K, Pakzad, R, Palicz, T, Pandey, A, Pant, S, Pardhan, S, Park, E, Pashazadeh Kan, F, Paudel, R, Pawar, S, Peng, M, Pereira, G, Perna, S, Perumalsamy, N, Petcu, I, Pigott, D, Piracha, Z, Podder, V, Polibin, R, Postma, M, Pourasghari, H, Pourtaheri, N, Qadir, M, Raad, M, Rabiee, M, Rabiee, N, Raeghi, S, Rafiei, A, Rahim, F, Rahimi, M, Rahimi-Movaghar, V, Rahman, A, Rahman, M, Rahmani, A, Rahmanian, V, Ram, P, Ramezanzadeh, K, Rana, J, Ranasinghe, P, Rani, U, Rao, S, Rashedi, S, Rashidi, M, Rasul, A, Ratan, Z, Rawaf, D, Rawaf, S, Rawassizadeh, R, Razeghinia, M, Redwan, E, Reitsma, M, Renzaho, A, Rezaeian, M, Riad, A, Rikhtegar, R, Rodriguez, J, Rogowski, E, Ronfani, L, Rudd, K, Saddik, B, Sadeghi, E, Saeed, U, Safary, A, Safi, S, Sahebazzamani, M, Sahebkar, A, Sakhamuri, S, Salehi, S, Salman, M, Samadi Kafil, H, Samy, A, Santric-Milicevic, M, Sao Jose, B, Sarkhosh, M, Sathian, B, Sawhney, M, Saya, G, Seidu, A, Seylani, A, Shaheen, A, Shaikh, M, Shaker, E, Shamshad, H, Sharew, M, Sharhani, A, Sharifi, A, Sharma, P, Sheidaei, A, Shenoy, S, Shetty, J, Shiferaw, D, Shigematsu, M, Shin, J, Shirzad-Aski, H, Shivakumar, K, Shivalli, S, Shobeiri, P, Simegn, W, Simpson, C, Singh, H, Singh, J, Singh, P, Siwal, S, Skryabin, V, Skryabina, A, Soltani-Zangbar, M, Song, S, Song, Y, Sood, P, Sreeramareddy, C, Steiropoulos, P, Suleman, M, Tabatabaeizadeh, S, Tahamtan, A, Taheri, M, Taheri Soodejani, M, Taki, E, Talaat, I, Tampa, M, Tandukar, S, Tat, N, Tat, V, Tefera, Y, Temesgen, G, Temsah, M, Tesfaye, A, Tesfaye, D, Tessema, B, Thapar, R, Ticoalu, J, Tiyuri, A, Tleyjeh, I, Togtmol, M, Tovani-Palone, M, Tufa, D, Ullah, I, Upadhyay, E, Valadan Tahbaz, S, Valdez, P, Valizadeh, R, Vardavas, C, Vasankari, T, Vo, B, Vu, L, Wagaye, B, Waheed, Y, Wang, Y, Waris, A, West, T, Wickramasinghe, N, Xu, X, Yaghoubi, S, Yahya, G, Yahyazadeh Jabbari, S, Yon, D, Yonemoto, N, Zaman, B, Zandifar, A, Zangiabadian, M, Zar, H, Zare, I, Zareshahrabadi, Z, Zarrintan, A, Zastrozhin, M, Zeng, W, Zhang, M, Zhang, Z, Zhong, C, Zoladl, M, Zumla, A, Lim, S, Vos, T, Naghavi, M, Brauer, M, Hay, S, Murray, C, HUS Comprehensive Cancer Center, and Department of Oncology

Subjects
Adult, Male, Global Health, Time, Global Burden of Disease, SDG 3 - Good Health and Well-being, Risk Factors, RA0421, RA0421 Public health. Hygiene. Preventive Medicine, Humans, Ambient air-quality, Child, Respiratory Tract Infections, Aged, Aged, 80 and over, MCC, Sex Characteristics, Malnutrition, Pyridinolcarbamate, Bayes Theorem, 3rd-DAS, 3142 Public health care science, environmental and occupational health, Infectious Diseases, 3121 General medicine, internal medicine and other clinical medicine, Child, Preschool, Female, Particulate Matter, Quality-Adjusted Life Years, Covid-19, LRI
Abstract

Funding: Bill & Melinda Gates Foundation. Background: The global burden of lower respiratory infections (LRIs) and corresponding risk factors in children older than 5 years and adults has not been studied as comprehensively as it has been in children younger than 5 years. We assessed the burden and trends of LRIs and risk factors across all age groups by sex, for 204 countries and territories. Methods: In this analysis of data for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we used clinician-diagnosed pneumonia or bronchiolitis as our case definition for LRIs. We included International Classification of Diseases 9th edition codes 079.6, 466–469, 470.0, 480–482.8, 483.0–483.9, 484.1–484.2, 484.6–484.7, and 487–489 and International Classification of Diseases 10th edition codes A48.1, A70, B97.4–B97.6, J09–J15.8, J16–J16.9, J20–J21.9, J91.0, P23.0–P23.4, and U04–U04.9. We used the Cause of Death Ensemble modelling strategy to analyse 23 109 site-years of vital registration data, 825 site-years of sample vital registration data, 1766 site-years of verbal autopsy data, and 681 site-years of mortality surveillance data. We used DisMod-MR 2.1, a Bayesian meta-regression tool, to analyse age–sex-specific incidence and prevalence data identified via systematic reviews of the literature, population-based survey data, and claims and inpatient data. Additionally, we estimated age–sex-specific LRI mortality that is attributable to the independent effects of 14 risk factors. Findings: Globally, in 2019, we estimated that there were 257 million (95% uncertainty interval [UI] 240–275) LRI incident episodes in males and 232 million (217–248) in females. In the same year, LRIs accounted for 1·30 million (95% UI 1·18–1·42) male deaths and 1·20 million (1·07–1·33) female deaths. Age-standardised incidence and mortality rates were 1·17 times (95% UI 1·16–1·18) and 1·31 times (95% UI 1·23–1·41) greater in males than in females in 2019. Between 1990 and 2019, LRI incidence and mortality rates declined at different rates across age groups and an increase in LRI episodes and deaths was estimated among all adult age groups, with males aged 70 years and older having the highest increase in LRI episodes (126·0% [95% UI 121·4–131·1]) and deaths (100·0% [83·4–115·9]). During the same period, LRI episodes and deaths in children younger than 15 years were estimated to have decreased, and the greatest decline was observed for LRI deaths in males younger than 5 years (–70·7% [–77·2 to –61·8]). The leading risk factors for LRI mortality varied across age groups and sex. More than half of global LRI deaths in children younger than 5 years were attributable to child wasting (population attributable fraction [PAF] 53·0% [95% UI 37·7–61·8] in males and 56·4% [40·7–65·1] in females), and more than a quarter of LRI deaths among those aged 5–14 years were attributable to household air pollution (PAF 26·0% [95% UI 16·6–35·5] for males and PAF 25·8% [16·3–35·4] for females). PAFs of male LRI deaths attributed to smoking were 20·4% (95% UI 15·4–25·2) in those aged 15–49 years, 30·5% (24·1–36·9) in those aged 50–69 years, and 21·9% (16·8–27·3) in those aged 70 years and older. PAFs of female LRI deaths attributed to household air pollution were 21·1% (95% UI 14·5–27·9) in those aged 15–49 years and 18·2% (12·5–24·5) in those aged 50–69 years. For females aged 70 years and older, the leading risk factor, ambient particulate matter, was responsible for 11·7% (95% UI 8·2–15·8) of LRI deaths. Interpretation: The patterns and progress in reducing the burden of LRIs and key risk factors for mortality varied across age groups and sexes. The progress seen in children younger than 5 years was clearly a result of targeted interventions, such as vaccination and reduction of exposure to risk factors. Similar interventions for other age groups could contribute to the achievement of multiple Sustainable Development Goals targets, including promoting wellbeing at all ages and reducing health inequalities. Interventions, including addressing risk factors such as child wasting, smoking, ambient particulate matter pollution, and household air pollution, would prevent deaths and reduce health disparities. Publisher PDF

Published
2022

36. Development of Radiohalogenated Osimertinib Derivatives as Imaging Probes for Companion Diagnostics of Osimertinib

Author

Kenji Mishiro, Ryuichi Nishii, Izumi Sawazaki, Tomoki Sofuku, Takeshi Fuchigami, Hitomi Sudo, Nurmaya Effendi, Akira Makino, Yasushi Kiyono, Kazuhiro Shiba, Junichi Taki, Seigo Kinuya, and Kazuma Ogawa

Subjects
Male, Acrylamides, Mice, Inbred BALB C, Aniline Compounds, Halogenation, Mice, Nude, ErbB Receptors, Iodine Radioisotopes, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Mutation, Drug Discovery, Animals, Humans, Molecular Medicine, Tissue Distribution, Bromine Radioisotopes, Radiopharmaceuticals
Abstract

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for treating non-small-cell lung cancer (NSCLC) with EGFR mutations. Genetic testing is required to detect the mutation for selecting patients who can use osimertinib. Here, we report an attempt to develop nuclear imaging probes that detect the EGFR mutations. We designed and synthesized I-osimertinib and Br-osimertinib with a radioactive or nonradioactive halogen atom at an indole ring in osimertinib and evaluated them.

Published
2022
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37. B7-H3 Suppresses Antitumor Immunity via the CCL2–CCR2–M2 Macrophage Axis and Contributes to Ovarian Cancer Progression

Author

Yuko Hosoe, Nathan Mise, Shiro Takamatsu, Naoki Horikawa, Masayo Ukita, Taito Miyamoto, Koji Yamanoi, Ken Yamaguchi, Noriomi Matsumura, Yuka Mise, Tsukasa Baba, Junzo Hamanishi, Mana Taki, Ryusuke Murakami, Masaki Mandai, Kenji Tanigaki, and Kaoru Abiko

Subjects
Cancer Research, B7 Antigens, Stromal cell, Receptors, CCR2, Immunology, Mice, Nude, CD8-Positive T-Lymphocytes, Biology, CCL2, Mice, Lymphocytes, Tumor-Infiltrating, Cell Line, Tumor, Immune Tolerance, Tumor Microenvironment, medicine, Animals, Humans, Macrophage, Chemokine CCL2, Ovarian Neoplasms, Tumor microenvironment, Macrophages, M2 Macrophage, medicine.disease, Xenograft Model Antitumor Assays, Mice, Inbred C57BL, Tumor progression, Cancer research, Female, Ovarian cancer, CD8, Transcription Factors
Abstract

New approaches beyond PD-1/PD-L1 inhibition are required to target the immunologically diverse tumor microenvironment (TME) in high-grade serous ovarian cancer (HGSOC). In this study, we explored the immunosuppressive effect of B7-H3 (CD276) via the CCL2–CCR2–M2 macrophage axis and its potential as a therapeutic target. Transcriptome analysis revealed that B7-H3 is highly expressed in PD-L1–low, nonimmunoreactive HGSOC tumors, and its expression negatively correlated with an IFNγ signature, which reflects the tumor immune reactivity. In syngeneic mouse models, B7-H3 (Cd276) knockout (KO) in tumor cells, but not in stromal cells, suppressed tumor progression, with a reduced number of M2 macrophages and an increased number of IFNγ+CD8+ T cells. CCL2 expression was downregulated in the B7-H3 KO tumor cell lines. Inhibition of the CCL2–CCR2 axis partly negated the effects of B7-H3 suppression on M2 macrophage migration and differentiation, and tumor progression. In patients with HGSOC, B7-H3 expression positively correlated with CCL2 expression and M2 macrophage abundance, and patients with B7-H3–high tumors had fewer tumoral IFNγ+CD8+ T cells and poorer prognosis than patients with B7-H3–low tumors. Thus, B7-H3 expression in tumor cells contributes to CCL2–CCR2–M2 macrophage axis–mediated immunosuppression and tumor progression. These findings provide new insights into the immunologic TME and could aid the development of new therapeutic approaches against the unfavorable HGSOC phenotype.

Published
2022

38. CGM Metrics Predict Imminent Progression to Type 1 Diabetes: Autoimmunity Screening for Kids (ASK) Study

Author

Andrea K, Steck, Fran, Dong, Cristy, Geno Rasmussen, Kimberly, Bautista, Flor, Sepulveda, Judith, Baxter, Liping, Yu, Brigitte I, Frohnert, Marian J, Rewers, Marian, Rewers, Aaron, Barbour, Daniel, Felipe-Morales, Paul, Dormond-Brooks, Kimberly, Driscoll, Brigitte, Frohnert, Cristy Geno, Rasmussen, Patricia, Gesualdo, Michelle, Hoffman, Rachel, Karban, Hanan, Shorrosh, Kimberly, Simmons, Andrea, Steck, Iman, Taki, Kathleen, Waugh, Edwin, Liu, Marisa, Gallant, R Brett, McQueen, and Jill M, Norris

Subjects
Blood Glucose, Glycated Hemoglobin, Male, Advanced and Specialized Nursing, Blood Glucose Self-Monitoring, Endocrinology, Diabetes and Metabolism, Infant, Newborn, Infant, Autoimmunity, Benchmarking, Diabetes Mellitus, Type 1, Child, Preschool, Internal Medicine, Humans, Female, Child
Abstract

OBJECTIVE Children identified with stage 1 type 1 diabetes are at high risk for progressing to stage 3 (clinical) diabetes and require accurate monitoring. Our aim was to establish continuous glucose monitoring (CGM) metrics that could predict imminent progression to diabetes. RESEARCH DESIGN AND METHODS In the Autoimmunity Screening for Kids study, 91 children who were persistently islet autoantibody positive (median age 11.5 years; 48% non-Hispanic White; 57% female) with a baseline CGM were followed for development of diabetes for a median of 6 (range 0.2–34) months. Of these, 16 (18%) progressed to clinical diabetes in a median of 4.5 (range 0.4–29) months. RESULTS Compared with children who did not progress to clinical diabetes (nonprogressors), those who did (progressors) had significantly higher average sensor glucose levels (119 vs. 105 mg/dL, P < 0.001) and increased glycemic variability (SD 27 vs. 16, coefficient of variation, 21 vs. 15, mean of daily differences 24 vs. 16, and mean amplitude of glycemic excursions 43 vs. 26, all P < 0.001). For progressors, 21% of the time was spent with glucose levels >140 mg/dL (TA140) and 8% of time >160 mg/dL, compared with 3% and 1%, respectively, for nonprogressors. In survival analyses, the risk of progression to diabetes in 1 year was 80% in those with TA140 >10%; in contrast, it was only 5% in the other participants. Performance of prediction by receiver operating curve analyses showed area under the curve of ≥0.89 for both individual and combined CGM metric models. CONCLUSIONS TA140 >10% is associated with a high risk of progression to clinical diabetes within the next year in autoantibody-positive children. CGM should be included in the ongoing monitoring of high-risk children and could be used as potential entry criterion for prevention trials.

Published
2021
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39. Clinical outcomes of intervention for carbapenems and anti-methicillin-resistant Staphylococcus aureus antibiotics by an antimicrobial stewardship team

Author

Yoh Takekuma, Yusuke Niinuma, Tatsuya Fukumoto, Junichi Sugita, Nobuhisa Ishiguro, Takehiro Yamada, Mutsumi Nishida, Mitsuru Sugawara, Keisuke Kagami, Sumio Iwasaki, Keisuke Taki, Takanori Teshima, and Kasumi Hayasaka

Subjects
Methicillin-Resistant Staphylococcus aureus, medicine.medical_specialty, Carbapenem, Epidemiology, medicine.drug_class, Antibiotics, MRSA, medicine.disease_cause, Meropenem, Antimicrobial Stewardship, ASP, Interquartile range, Internal medicine, medicine, Antimicrobial stewardship, Humans, AST, Retrospective Studies, Outcome, business.industry, Health Policy, Public Health, Environmental and Occupational Health, Retrospective cohort study, Methicillin-resistant Staphylococcus aureus, Discontinuation, Anti-Bacterial Agents, Infectious Diseases, Carbapenems, Antibiotic use, business, medicine.drug
Abstract

Background: There are no reports on the effects of interventions, such as discontinuation and change and/or deescalation of carbapenems and anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics by an antimicrobial stewardship team focusing on detailed patient outcomes. This study aimed to evaluate these effects. Methods: This retrospective cohort study was conducted at a tertiary care hospital from December 2018 to November 2019. Results: Favorable clinical responses were obtained in 165 of 184 cases (89.7%) in the intervention-accepted group, higher than those in the not accepted group (14/19 cases, 73.7%; P = .056). All-cause 30 day mortality was lower in the accepted group than in the not accepted group (1.1% and 10.5%, respectively; P = .045). The microbiological outcomes were similar between the two groups. Duration of carbapenem and anti-MRSA antibiotic use in the accepted group was significantly lower than that in the not accepted group (median [interquartile range]: 8 days [5-13] versus 14 days [8-15], respectively, P = .026 for carbapenem; 10 days [5.3-15] vs 15.5 days [13.8-45.3], respectively, P = .014 for anti-MRSA antibiotic). Conclusions: This is the first study to investigate the effects of interventions such as discontinuation and change and/ or de-escalation of antibiotics on detailed outcomes. Our intervention could reduce the duration of carbapenem and anti-MRSA antibiotic use without worsening clinical and microbiological outcomes. (c) 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Published
2021

40. Direct and indirect contributions of molecular genetics to farm animal welfare: a review

Author

Umit Bilginer, Taki Karsli, Murat Soner Balcıoğlu, and Eymen Demir

Subjects
medicine.medical_specialty, Farms, business.industry, media_common.quotation_subject, Biology, Animal Welfare, Veterinarians, Biotechnology, Genome editing, Animals, Domestic, Animal welfare, Molecular genetics, Well-being, medicine, Trait, Animals, Humans, Animal Science and Zoology, Prosperity, Domestication, business, Molecular Biology, Welfare, media_common
Abstract

Since domestication, farm animals have played a key role to increase the prosperity of humankind, while animal welfare (AW) is debated even today. This paper aims to comprehensively review the contributions of developing molecular genetics to farm animal welfare (FAW) and to raise awareness among both scientists and farmers about AW. Welfare is a complex trait affected by genetic structure and environmental factors. Therefore, the best welfare status can be achieved not only to enhance environmental factors such as management and feeding practices, but also the genetic structure of animals must be improved. In this regard, advances in molecular genetics have made great contributions to improve the genetic structure of farm animals, which has increased AW. Today, by sequencing and/or molecular markers, genetic diseases may be detected and eliminated in local herds. Additionally, genes related to diseases or adaptations are investigated by molecular techniques, and the frequencies of desired genotypes are increased in farm animals to keep welfare at an optimized level. Furthermore, stress on animals can be reduced with DNA extraction from stool and feather samples which reduces physical contact between animals and veterinarians. Together with molecular genetics, advances in genome editing tools and biotechnology are promising to improve FAW in the future.

Published
2021
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41. A case of systemic sarcoidosis with mesangial proliferative glomerulonephritis showing predominant deposition of IgG in the mesangial region

Author

Masaaki Nakayama, Koyu Suzuki, Kimio Watanabe, Kasumi Konishi, Yugo Ito, Takuya Fujimaru, Sho Fukui, Fumika Taki, and Masahiko Nagahama

Subjects
Adult, Male, Nephrology, medicine.medical_specialty, Pathology, Necrosis, Sarcoidosis, Interstitial nephritis, Case Report, Nephropathy, chemistry.chemical_compound, Glomerulonephritis, Internal medicine, Biopsy, medicine, Humans, Hematuria, Creatinine, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, Glomerular Mesangium, chemistry, Immunoglobulin G, Mesangial proliferative glomerulonephritis, Female, Renal biopsy, medicine.symptom, business
Abstract

A 37-year-old African–British man was referred to our hospital for detailed examination because of persistent fever, swelling and pain in both ankle joints, and blurred vision for two months. Inguinal lymph node biopsy showed a large number of epithelioid granulomas without necrosis. Granulomatous anterior uveitis, nephropathy, high serum angiotensin-converting enzyme activity, and high serum-soluble interleukin-2 receptor were observed, and the diagnosis of systemic sarcoidosis was made. His serum creatinine was 1.4 mg/dL and hematuria, leukocyturia, and urine protein were also seen. The renal biopsy finding was mesangial proliferative glomerulonephritis, with no findings of granuloma formation or tubular interstitial nephritis. Immunofluorescence staining showed deposition of IgG, C3, and C1q in the mesangial region. IgG3 was dominant in subclass staining. There was no monoclonality on kappa and lambda staining. Electron microscopy showed predominant deposition in the mesangial region with some subepithelial and endothelial deposition. His hematuria and leukocyturia disappeared with steroid therapy, suggesting sarcoidosis-related nephropathy. A case of systemic sarcoidosis with mesangial proliferative glomerulonephritis showing predominant deposition of IgG in the mesangial region is presented. No cases of such histological findings have been reported so far, and it is necessary to analyze further cases to clarify the pathogenic significance of the renal biopsy findings observed in this case.

Published
2021
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42. HER2 targeting near‐infrared photoimmunotherapy for a CDDP‐resistant small‐cell lung cancer

Author

Kazuomi Takahashi, Shunichi Taki, Chiaki Koike, Yoshitaka Isobe, Toshinori Matsui, Yuko Nishinaga, Kazuhide Sato, Misae Shimizu, and Hirotoshi Yasui

Subjects
Cancer Research, Lung Neoplasms, near‐infrared photoimmunotherapy, Receptor, ErbB-2, medicine.medical_treatment, Mice, Nude, cisplatin, Receptor tyrosine kinase, Targeted therapy, Mice, chemotherapy‐resistant, Trastuzumab, In vivo, Cell Line, Tumor, HER2, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, skin and connective tissue diseases, neoplasms, Research Articles, RC254-282, Cisplatin, biology, business.industry, Clinical Cancer Research, small‐cell lung cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Photoimmunotherapy, Phototherapy, Small Cell Lung Carcinoma, Xenograft Model Antitumor Assays, Oncology, Cell culture, Cancer cell, biology.protein, Cancer research, Female, Immunotherapy, business, Research Article, medicine.drug
Abstract

Background Human epidermal growth factor receptor 2 (HER2) is tyrosine kinase receptor that belongs to the ErbB family and is overexpressed on the membrane surface of various cancer cells, including small cell lung cancer (SCLC); however, no HER2 targeted therapy for SCLC have yet been established. Near‐infrared photoimmunotherapy (NIR‐PIT) is a novel cancer therapy based on photo‐absorber, IRDye‐700DX (IR700), ‐antibody conjugates, and near‐infrared (NIR) light. Methods We used HER2‐positive SCLC parental cell lines (SBC‐3) and its chemoresistant cell lines, and examined therapeutic efficacy of HER2 targeting NIR‐PIT using anti HER2 antibody trastuzumab. Results We found that HER2 expression was upregulated on chemoresistant cell lines, especially cisplatin‐resistance (SBC‐3/CDDP). In vitro, the rate of cell death increased with the amount of NIR‐light irradiation, and it was significantly higher in SBC‐3/CDDP than in SBC‐3. In vivo, tumor growth was more suppressed in SBC‐3/CDDP group than in SBC‐3 group, and survival period tended to be prolonged. Conclusion In this study, we demonstrated that HER2 targeting NIR‐PIT using trastuzumab is promising therapy for HER2‐positive SCLC, and is more effective when HER2 expression is upregulated due to CDDP resistance, suggesting that the HER2 expression level positively corelated with the efficacy of NIR‐PIT., We found that human epidermal growth factor receptor 2 (HER2) was expressed in small‐cell lung cancer (SCLC) parental cell lines (SBC‐3) and its chemoresistant cell lines, and HER2 was upregulated in chemoresistant SCLC cells, especially CDDP‐resistant cells (SBC‐3/CDDP). The HER2‐targeting near‐infrared photoimmunotherapy (NIR‐PIT) using an anti‐HER2 antibody, trastuzumab, induced HER2‐expressing SCLC cells death, and efficacy of this therapy was significantly higher in SBC‐3/CDDP than in SBC‐3 in vitro and in vivo. These findings suggest a positive correlation between the cancer antigen expression level and the NIR‐PIT effect. Implications of all the available evidence. Our finding suggests that NIR‐PIT targeting HER2 using trastuzumab is a novel therapeutic approach for HER2‐positive SCLC when SCLC acquired CDDP‐based chemotherapy resistance and HER2 expression was upregulated.

Published
2021
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43. Estimation and feasibility of correction modelling for mother-reported child height and weight at 2 years using data from the Australian CHAT trial

Author

Yan Cheng, Huilan Xu, Chris Rissel, Philayrath Phongsavan, Limin Buchanan, Sarah Taki, Alison Hayes, Louise A. Baur, and Li Ming Wen

Subjects
Adult, Multidisciplinary, Adolescent, Child, Preschool, Body Weight, Australia, Humans, Mothers, Reproducibility of Results, Female, Overweight, Body Height, Body Mass Index
Abstract

Correction modelling using reported BMI values has been employed in adolescent and adult populations to improve the accuracy of self-reporting. This study aimed to evaluate the feasibility of establishing correction modelling for mother-reported child height and weight at 2 years using data from an Australian trial in 2019. Correction modelling for BMI was conducted using mother-reported and objectively measured height and weight of 2-year-olds. Mother-reported height, weight and BMI values of 2-year-old children were adjusted based on objectively measured anthropometric data using linear regression models. ‘Direct’ and ‘indirect’ corrections were applied to the correction of BMI values. We defined the direct collection as using corrected BMI values that were predicted directly by the model and indirect correction as using corrected weight and height values to calculate corrected BMI values. Corrected BMI values via the indirect correction showed higher sensitivity or similar specificity in predicting overweight status, compared to the direct correction, and also showed higher agreement with measured values compared to the mother-reported measures. Corrected self-reported measures via an indirect correction had a better accuracy and agreement with the objectively measured data in the BMI values and classification of overweight, compared to the mother-reported values.

Published
2022
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44. No association between habitat, autogeny and genetics in Moroccan Culex pipiens populations

Author

Soukaina Arich, Yuki Haba, Najlaa Assaid, Megan L. Fritz, Carolyn S. McBride, Mylène Weill, Hassan Taki, M’hammed Sarih, Pierrick Labbé, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), University Hassan II [Casablanca], Institut Pasteur du Maroc, Réseau International des Instituts Pasteur (RIIP), Princeton University, University of Maryland [Baltimore], Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)

Subjects
[SDV]Life Sciences [q-bio], Mosquito Vectors, Culex, Morocco, Infectious Diseases, Autogeny, Humans, Animals, Female, Parasitology, Vector, Ecosystem, Retrospective Studies, Microsatellite Repeats
Abstract

Background Mosquitoes of the Culex pipiens complex are found across the globe and are the focus of many research studies. Among the temperate species C. pipiens sensu stricto (s.s.), two forms are usually described: molestus and pipiens. These two forms are indistinguishable in terms of morphology but show behavioral and physiological differences that may have consequences for their associated epidemiology. The two forms are well defined in the northern part of the species distribution, where autogeny is strictly associated with the molestus form. However, whether the two remain distinct and show the characteristic differences in behavior is less clear in North Africa, at the southern edge of their range. Methods The association between autogeny, as determined by ovarian dissection, and molecular forms, based on the CQ11 microsatellite marker, was studied in six Moroccan populations of C. pipiens. Results An overall low prevalence of autogeny was found at three of the Moroccan regions studied, although it reached 17.5% in the Agadir population. The prevalence of form-specific CQ11 alleles was quite similar across all populations, with the molestus allele being rarer (approx. 15%), except in the Agadir population where it reached 43.3%. We found significant deficits in heterozygotes at the diagnostic CQ11 locus in three populations, but the three other populations showed no significant departure from panmixia, which is in line with the results of a retrospective analysis of the published data. More importantly, we found no association between the autogeny status and CQ11 genotypes, despite the many females analyzed. Conclusions There was limited evidence for two discrete forms in Morocco, where individuals carrying pipiens and molestus alleles breed and mate in the same sites and are equally likely to be capable of autogeny. These observations are discussed in the epidemiological context of Morocco, where C. pipiens is the main vector of several arboviruses. Graphical Abstract

Published
2022
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45. Brain charts for the human lifespan

Author

Armin Raznahan, Eric Courchesne, Andrea Parolin Jackowski, Kamen A. Tsvetanov, Cameron T. Ellis, R.C. Gur, Bin Bae J, Park Mtm, Pedro A. Valdes-Sosa, Simon N. Vandekar, Jacob W. Vogel, Juan Zhou, Machteld Marcelis, Kiho Im, Patricia Ellen Grant, Minhui Ouyang, Blesa Cabez M, Michael V. Lombardo, Sarah E. Morgan, James P. Boardman, Adamson C, Calhoun Vd, Delarue M, James H. Cole, Pichet Binette A, Roberto Toro, David H. Rowitch, Nynke A. Groenewold, Kevin M. Anderson, David T.W. Jones, Michael Schöll, Wang Ys, Aiden Corvin, R.E. Gur, Damien A. Fair, Gareth Ball, Herma Lina Schaare, Andrew Zalesky, Evdokia Anagnostou, Michael J. Meaney, Taki Y, Gareth J. Sullivan, Warrier, Petra E. Vértes, Chixiang Chen, Lisa T. Eyler, Wei Liao, Tomáš Paus, Jeremy A. Elman, Phillip McGuire, Hisham Ziauddeen, William S. Kremen, Etienne Vachon-Presseau, E.T. Bullmore, Christophe Tzourio, White, Hammill Cf, Mothersill D, Richard N. Henson, Jiang Qiu, Duncan E. Astle, Fabrice Crivello, Paul C. Fletcher, Chertavian C, Kim K, Jennifer Crosbie, Russell Schachar, Gabriel A. Devenyi, Manfred G. Kitzbichler, Tianye Jia, Trey Hedden, Sang Jae Lee, Ross D. Markello, Silke Kern, Ian M. Goodyer, Keith A. Johnson, Frauke Beyer, Bernard Mazoyer, A. Heinz, Sylvane Desrivières, Rosenberg, Gary Donohoe, Ong Mq, Alexander D. Edwards, Dan J. Stein, Nenad Medic, Zuo Xn, Travis T. Mallard, Peter Fonagy, Lindsay W. Victoria, Ingmar Skoog, Avram J. Holmes, Jason P. Lerch, Jed T. Elison, Jianfu Li, John H. Gilmore, Rosemary Holt, Caitlin K. Rollins, Carol E. Franz, Pedro Mario Pan, Saashi A Bedford, Yang N, Jonathan C Ipser, Richard A. I. Bethlehem, Tuulari Jj, Stolicyn A, Hua Huang, Bratislav Misic, Conor Liston, Ayub M, Lisa Ronan, Yeo Bt, Sophie Adler, Charles J. Lynch, Faith M. Gunning, Konrad Wagstyl, M. Mallar Chakravarty, John Suckling, Theodore D. Satterthwaite, Bharath Holla, Yap Seng Chong, Jinglei Lv, Jakob Seidlitz, Niall J Bourke, Xinlei Qian, Simon Baron-Cohen, Cynthia M. Ortinau, Deirel Paz Linares, Thyreau B, René S. Kahn, Aaron P. Schultz, Vanessa Cropley, Eric Westman, Mitchell Valdés-Sosa, Rik Ossenkoppele, André Zugman, Hasse Karlsson, Sylvia Villeneuve, Katja Heuer, Di Biase Ma, Margaret L. Westwater, Sofie L. Valk, David J. Sharp, Brigitte Landeau, Matthew Borzage, Kirsten A. Donald, Timothy Rittman, Richard Beare, Giovanni Abrahão Salum, Gunter Schumann, Ryuta Kawashima, Romero-Garcia R, John Blangero, Yun Hj, Russel T. Shinohara, Nicolas Crossley, Simon K. Warfield, Karen Pierce, George S. Alexopoulos, Katharine Dunlop, David C. Glahn, Francois Lalonde, Anqi Qiu, Lana Vasung, Gaël Chételat, Lídice Galán-García, Clifford R. Jack, Reisa A. Sperling, Anna Zettergren, Elizabeth Kelley, Arno Villringer, Andrea Mechelli, Benegal, Aaron Alexander-Bloch, Nicholas B. Turk-Browne, van Amelsvoort T, John D. Lewis, Heather C. Whalley, A. V. Witte, Zdenka Pausova, Joel T. Nigg, Heather J. Zar, Raymond J. Dolan, Christopher D. Smyser, Jay N. Giedd, Lena Palaniyappan, Ali Gholipour, Areces-Gonzalez A, Peter B. Jones, Jacqueline Hoare, Oskar Hansson, Linnea Karlsson, C Pantelis, Paly L, Bonnie Auyeung, Jorge Bosch-Bayard, Bethlehem, Richard [0000-0002-0714-0685], White, Simon [0000-0001-8642-7037], Astle, Duncan [0000-0002-7042-5392], Baron-Cohen, Simon [0000-0001-9217-2544], Henson, Rik [0000-0002-0712-2639], Jones, Peter [0000-0002-0387-880X], Kitzbichler, Manfred [0000-0002-4494-0753], Rittman, Timothy [0000-0003-1063-6937], Rowitch, David [0000-0002-0079-0060], Tsvetanov, Kamen A. [0000-0002-3178-6363], Westwater-Wozniak, Margaret [0000-0002-2918-0979], Ziauddeen, Hisham [0000-0003-4044-1719], Apollo - University of Cambridge Repository, British Academy, Autism Research Trust, National Institute of Mental Health (US), UK Research and Innovation, Medical Research Council (UK), National Institute for Health and Care Research (US), Wellcome Trust, University of Cambridge, Cambridge Biomedical Research Centre, University of Cambridge [UK] (CAM), University of Pennsylvania, Yale University [New Haven], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Child and Adolescent Psychiatry Department [AP- HP Hôpital Robert Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Neuroscience - Department of Neuroscience, Centre de Recherche Interdisciplinaire / Center for Research and Interdisciplinarity [Paris, France] (CRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Med Staf Spec Psychiatrie (9), Neurology, Amsterdam Neuroscience - Neurodegeneration, 3R-BRAIN, AIBL, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s Disease Repository Without Borders Investigators, CALM Team, Cam-CAN, CCNP, COBRE, cVEDA, ENIGMA Developmental Brain Age Working Group, Developing Human Connectome Project, FinnBrain, Harvard Aging Brain Study, IMAGEN, KNE96, The Mayo Clinic Study of Aging, NSPN, POND, The PREVENT-AD Research Group, VETSA, [Bethlehem, R. A. I.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Auyeung, B.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Baron-Cohen, S.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Bedford, S. A.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Holt, R.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Lombardo, M. V.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Bethlehem, R. A. I.] Univ Cambridge, Dept Psychiat, Brain Mapping Unit, Cambridge, England, [Kitzbichler, M. G.] Univ Cambridge, Dept Psychiat, Brain Mapping Unit, Cambridge, England, [Seidlitz, J.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Vogel, J. W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Gur, R. E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Gur, R. C.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Jackowski, A. P.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Satterthwaite, T. D.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Alexander-Bloch, A. F.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Seidlitz, J.] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat & Behav Sci, Philadelphia, PA 19104 USA, [Alexander-Bloch, A. F.] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat & Behav Sci, Philadelphia, PA 19104 USA, [Seidlitz, J.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Chertavian, C.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Gur, R. E.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Gur, R. C.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Alexander-Bloch, A. F.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [White, S. R.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Goodyer, I. M.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Henson, R. N.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Jones, P. B.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Kitzbichler, M. G.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Medic, N.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Morgan, S. E.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Romero-Garcia, R.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Ronan, L.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Suckling, J.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Vertes, P. E.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Warrier, V.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Westwater, M. L.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Ziauddeen, H.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Bullmore, E. T.] Univ Cambridge, Dept Psychiat, Cambridge, England, [White, S. R.] Univ Cambridge, MRC Biostat Unit, Cambridge, England, [Vogel, J. W.] Univ Penn, Lifespan Informat & Neuroimaging Ctr, Philadelphia, PA 19104 USA, [Satterthwaite, T. D.] Univ Penn, Lifespan Informat & Neuroimaging Ctr, Philadelphia, PA 19104 USA, [Anderson, K. M.] Yale Univ, Dept Psychol, New Haven, CT USA, [Ellis, C. T.] Yale Univ, Dept Psychol, New Haven, CT USA, [Turk-Browne, N. B.] Yale Univ, Dept Psychol, New Haven, CT USA, [Adamson, C.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Ball, G.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Beare, R.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Jackowski, A. P.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Adamson, C.] Monash Univ, Dept Med, Melbourne, Vic, Australia, [Beare, R.] Monash Univ, Dept Med, Melbourne, Vic, Australia, [Adler, S.] UCL Great Ormond St Inst Child Hlth, London, England, [Alexopoulos, G. S.] Weill Cornell Med, Dept Psychiat, Weill Cornell Inst Geriatr Psychiat, New York, NY USA, [Anagnostou, E.] Univ Toronto, Dept Pediat, Toronto, ON, Canada, [Anagnostou, E.] Holland Bloorview Kids Rehabil Hosp, Toronto, ON, Canada, [Pierce, K.] Holland Bloorview Kids Rehabil Hosp, Toronto, ON, Canada, [Areces-Gonzalez, A.] Univ Elect Sci & Technol China, MOE Key Lab NeuroInformat, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Paz-Linares, D.] Univ Elect Sci & Technol China, MOE Key Lab NeuroInformat, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Areces-Gonzalez, A.] Univ Pinar del Rio Hermanos Saiz Montes de Oca, Pinar Del Rio, Cuba, [Astle, D. E.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Henson, R. N.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Whalley, H. C.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Auyeung, B.] Univ Edinburgh, Sch Philosophy Psychol & Language Sci, Dept Psychol, Edinburgh, Midlothian, Scotland, [Pausova, Z.] Univ Edinburgh, Sch Philosophy Psychol & Language Sci, Dept Psychol, Edinburgh, Midlothian, Scotland, [Ayub, M.] Queens Univ, Dept Psychiat, Ctr Neurosci Studies, Kingston, ON, Canada, [Ayub, M.] UCL, Mental Hlth Neurosci Res Dept, Div Psychiat, London, England, [Bae, J.] Seoul Natl Univ, Bundang Hosp, Dept Neuropsychiat, Seongnam, South Korea, [Ball, G.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia, [Baron-Cohen, S.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge Lifetime Asperger Syndrome Serv CLASS, Cambridge, England, [Benegal, V.] Natl Inst Mental Hlth & Neurosci NIMHANS, Ctr Addict Med, Bengaluru, India, [Beyer, F.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Villringer, A.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Witte, A. V.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Blangero, J.] Univ Texas Rio Grande Valley, South Texas Diabet & Obes Inst, Dept Human Genet, Edinburg, TX USA, [Blesa Cabez, M.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Boardman, J. P.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Sullivan, G.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Borzage, M.] Univ Southern Calif, Childrens Hosp Los Angeles, Keck Sch Med, Fetal & Neonatal Inst,Div Neonatol,Dept Pediat, Los Angeles, CA 90007 USA, [Bosch-Bayard, J. F.] Montreal Neurol Inst, Ludmer Ctr Neuroinformat & Mental Hlth, McGill Ctr Integrat Neurosci, Montreal, PQ, Canada, [Bosch-Bayard, J. F.] McGill Univ, Montreal, PQ, Canada, [Chakravarty, M. M.] McGill Univ, Montreal, PQ, Canada, [Bourke, N.] Imperial Coll London, Dept Brain Sci, London, England, [Sharp, D.] Imperial Coll London, Dept Brain Sci, London, England, [Alexander-Bloch, A. F.] Imperial Coll London, Dept Brain Sci, London, England, [Bourke, N.] Dementia Res Inst, Care Res & Technol Ctr, London, England, [Calhoun, V. D.] Georgia State Univ, Triinst Ctr Translat Res Neuroimaging & Data Sci, Georgia Inst Technol, Atlanta, GA 30303 USA, [Calhoun, V. D.] Emory Univ, Atlanta, GA 30322 USA, [Chakravarty, M. M.] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Comp Brain Anat CoBrA Lab, Montreal, PQ, Canada, [Chen, C.] Univ Penn, Penn Stat Imaging & Visualizat Ctr, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA 19104 USA, [Shinohara, R. T.] Univ Penn, Penn Stat Imaging & Visualizat Ctr, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA 19104 USA, [Chetelat, G.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Delarue, M.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Landeau, B.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Paly, L.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Chong, Y. S.] Agcy Sci Technol & Res, Singapore Inst Clin Sci, Singapore, Singapore, [Chong, Y. S.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Obstet & Gynaecol, Singapore, Singapore, [Cole, J. H.] UCL, Ctr Med Image Comp CMIC, London, England, [Cole, J. H.] UCL, Dementia Res Ctr DRC, London, England, [Corvin, A.] Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland, [Costantino, M.] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Verdun, PQ, Canada, [Costantino, M.] McGill Univ, Undergrad Program Neurosci, Montreal, PQ, Canada, [Courchesne, E.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA, [Courchesne, E.] Univ Calif San Diego, Autism Ctr Excellence, San Diego, CA 92103 USA, [Crivello, F.] Univ Bordeaux, Inst Neurodegenerat Disorders, CNRS UMR5293, CEA, Bordeaux, France, [Mazoyer, B.] Univ Bordeaux, Inst Neurodegenerat Disorders, CNRS UMR5293, CEA, Bordeaux, France, [Cropley, V. L.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Di Biase, M. A.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Lv, J.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Zalesky, A.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Hammill, C. F.] Hosp Sick Children, Toronto, ON, Canada, [Schachar, R. J.] Hosp Sick Children, Toronto, ON, Canada, [Crossley, N.] Pontificia Univ Catolica Chile, Sch Med, Dept Psychiat, Santiago, Chile, [Crossley, N.] Kings Coll London, Dept Psychosis Studies, Inst Psychiat Psychol & Neurosci, London, England, [McGuire, P.] Kings Coll London, Dept Psychosis Studies, Inst Psychiat Psychol & Neurosci, London, England, [Crossley, N.] Inst Milenio Intelligent Healthcare Engn, Santiago, Chile, [Delorme, R.] Robert Debre Univ Hosp, AP HP, Child & Adolescent Psychiat Dept, Paris, France, [Delorme, R.] Inst Pasteur, Human Genet & Cognit Funct, Paris, France, [Desrivieres, S.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England, [Devenyi, G. A.] Douglas Mental Hlth Univ Inst, McGill Dept Psychiat, Cerebral Imaging Ctr, Montreal, PQ, Canada, [Devenyi, G. A.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada, [Di Biase, M. A.] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA, [Dolan, R.] UCL, Max Planck UCL Ctr Computat Psychiat & Ageing Res, London, England, [Dolan, R.] Wellcome Ctr Human Neuroimaging, London, England, [Wagstyl, K.] Wellcome Ctr Human Neuroimaging, London, England, [Donald, K. A.] Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, Div Dev Paediat, Cape Town, South Africa, [Donald, K. A.] Univ Cape Town, Neurosci Inst, Cape Town, South Africa, [Groenewold, N. A.] Univ Cape Town, Neurosci Inst, Cape Town, South Africa, [Donohoe, G.] Natl Univ Ireland Galway, Sch Psychol, Ctr Neuroimaging Cognit & Genom NICOG, Galway, Ireland, [Dunlop, K.] Weill Cornell Med, Dept Psychiat, Weil Family Brain & Mind Res Inst, New York, NY USA, [Lynch, C.] Weill Cornell Med, Dept Psychiat, Weil Family Brain & Mind Res Inst, New York, NY USA, [Edwards, A. D.] Kings Coll London, Ctr Dev Brain, London, England, [Edwards, A. 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S.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Yang, N.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Yeo, B.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Zuo, X. N.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Wang, Y. S.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Yang, N.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Zuo, X. N.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Wang, Y. S.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Yang, N.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Zuo, X. N.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Wang, Y. 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H.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Translat Magnet Resonance Res, Singapore, Singapore, [Ziauddeen, H.] Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Cambridge, England, [Zugman, A.] NIMH, NIH, Bethesda, MD 20892 USA, [Zugman, A.] Escola Paulista Med, Dept Psychiat, Sao Paulo, Brazil, [Zuo, X. N.] Nanning Normal Univ, Sch Educ Sci, Key Lab Brain & Educ, Nanning, Peoples R China, British Academy Postdoctoral fellowship, NIMH, UKRI Medical Research Council, NIHR Cambridge Biomedical Research Centre, NIHR Senior Investigator award, MRC research infrastructure award, Commonwealth Scientific and Industrial Research Organisation (CSIRO), and Ontario Brain Institute

Subjects
631/378/2649, OpenPain Project, KNE96, Growth, Psychiatric-disorders, DISEASE, 3R-BRAIN, Brain charts, MRI Brain, OASIS-3, Disease, CCNP, 631/378/2571, UMN BCP, Multidisciplinary, medicine.diagnostic_test, PSYCHIATRIC-DISORDERS, article, Brain, Human brain, ASSOCIATION, Magnetic Resonance Imaging, Harvard Aging Brain Study, The Mayo Clinic Study of Aging, NSPN, medicine.anatomical_structure, GROWTH, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ddc:500, BURDEN, WHITE-MATTER, FinnBrain, Harvard Aging Brain Study, Organization, Mri, MRI, medicine.medical_specialty, Concurrent validity, MODELS, Cam-CAN, Longevity, CALM Team, POND, Neuroimaging, Burden, ORGANIZATION, AIBL, The PREVENT-AD Research Group, VETSA, Cortical thickness, Association, Physical medicine and rehabilitation, FinnBrain, IMAGEN, KNE96, White-matter, medicine, Humans, ASRB, 631/378/1689, COBRE, business.industry, 631/378/2611, Brain morphometry, Neurosciences, Alzheimer’s Disease Repository Without Borders Investigators, Magnetic resonance imaging, Alzheimer’s Disease Neuroimaging Initiative, Anthropometry, Body Height, Brain growth, Birth, 59/57, Normative, IMAGEN, ENIGMA Developmental Brain Age working group, NSPN, business, CCNP, 3R-BRAIN, CORTICAL THICKNESS, Developing Human Connectome Project, ENIGMA Developmental Brain Age working group, The PREVENT-AD Research Group, VETSA, Bullmore, E.T
Abstract

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes., R.A.I.B. was supported by a British Academy Postdoctoral fellowship and by the Autism Research Trust. J. Seidlitz was supported by NIMH T32MH019112-29 and K08MH120564. S.R.W. was funded by UKRI Medical Research Council MC_UU_00002/2 and was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). E.T.B. was supported by an NIHR Senior Investigator award and the Wellcome Trust collaborative award for the Neuroscience in Psychiatry Network. A.F.A.-B. was supported by NIMH K08MH120564. Data were curated and analysed using a computational facility funded by an MRC research infrastructure award (MR/M009041/1) to the School of Clinical Medicine, University of Cambridge and supported by the mental health theme of the NIHR Cambridge Biomedical Research Centre.

Published
2022
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46. Visualization of Dynamic Expression of Myocardial Sigma-1 Receptor After Myocardial Ischemia and Reperfusion Using Radioiodine-Labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) Imaging

Author

Takashi Kozaka, Junichi Taki, Norihito Akatani, Hiroshi Wakabayashi, Hiroshi Mori, Kazuhiro Shiba, Anri Inaki, Tomo Hiromasa, Kazuma Ogawa, and Seigo Kinuya

Subjects
Technetium Tc 99m Sestamibi, medicine.medical_specialty, Myocardial Ischemia, Sigma-1 receptor, Myocardial Reperfusion, Coronary Artery Disease, Cyclopentanes, Memory imaging, Iodine Radioisotopes, chemistry.chemical_compound, Left coronary artery, OI5V, Cyclopentanol, In vivo, Internal medicine, medicine.artery, Animals, Humans, Receptors, sigma, Medicine, Distribution (pharmacology), Receptor, business.industry, Myocardium, General Medicine, Rats, Intensity (physics), chemistry, Reperfusion, Cardiology, Radiopharmaceuticals, Cardiology and Cardiovascular Medicine, business, Perfusion
Abstract

金沢大学疾患モデル総合研究センター, Background: This study chronologically evaluated the expression of the intensity and distribution of the sigma-1 receptor (σ1R) demonstrated by radiolabeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) in a rat model of myocardial ischemia and reperfusion. Methods and Results: The left coronary artery was occluded for 30 min, followed by reperfusion. Dual-tracer autoradiography with 125I-OI5V and 99 mTc-MIBI was performed to assess the spatiotemporal changes in 125I-OI5V uptake (n=5-6). Significant and peaked 125I-OI5V uptake in the ischemic area was observed at 3 days after reperfusion, and the 125I-OI5V uptake ratio of ischemic area to normally perfused left ventricular area decreased gradually from 3 to 28 days (mean value ± SD; 0.90±0.12 at 1 day, 1.89±0.19 at 3 days, 1.52±0.17 at 7 days, 1.34±0.13 at 14 days, and 1.16±0.14 at 28 days, respectively). Triple-tracer autoradiography with 125I-OI5V, 99 mTc-MIBI, and 201TlCl was performed to evaluate 125I-OI5V uptake in the ischemic area in relation to the residual perfusion at 7 days (n=4). The 125I-OI5V uptake ratio of the non-salvaged area was higher compared to that of the salvaged area in the ischemic area. 123I-OI5V and 99 mTc-MIBI SPECT/CT was performed 3 days after reperfusion (n=3), and the in vivo images showed clear uptake of 123I-OI5V in the perfusion defect area. Conclusions: The present study confirmed the spatiotemporal expression pattern of σ1R expression. Non-invasive σ1R imaging with 123I or 125I-OI5V was feasible to monitor the expression of σ1R after myocardial ischemia and reperfusion. © 2021 Japanese Circulation Society. All rights reserved.

Published
2021
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47. Polygenic risk score for bipolar disorder associates with divergent thinking and brain structures in the prefrontal cortex

Author

Zhiqian Yu, Yasuyuki Taki, Rui Nouchi, Yuka Kotozaki, Yoshie Kikuchi, Kunio Iizuka, Ryosuke Kimura, Susumu Yokota, Shigeyuki Ikeda, Daniele Magistro, Tadashi Imanishi, Hiroaki Tomita, Ryoichi Yokoyama, Atsushi Sekiguchi, Carlos Makoto Miyauchi, Kelssy Hitomi dos Santos Kawata, Kohei Sakaki, Izumi Matsudaira, Hikaru Takeuchi, Sugiko Hanawa, Tsuyoshi Araki, Seishu Nakagawa, Takayuki Nozawa, Ryuta Kawashima, and Chiaki Ono

Subjects
Adult, Male, Risk, Multifactorial Inheritance, Adolescent, Creativity, Young Adult, Fluency, Neuroimaging, medicine, Humans, Genetic Predisposition to Disease, voxel‐based morphometry, Radiology, Nuclear Medicine and imaging, Bipolar disorder, Prefrontal cortex, Research Articles, bipolar disorder, prefrontal cortex, Radiological and Ultrasound Technology, Confounding, Voxel-based morphometry, medicine.disease, Magnetic Resonance Imaging, Mood, Neurology, polygenic risk score, Female, Neurology (clinical), Anatomy, Psychology, Divergent thinking, Research Article, Clinical psychology
Abstract

It has been hypothesized that a higher genetic risk of bipolar disorder (BD) is associated with greater creativity. Given the clinical importance of bipolar disorder and the importance of creativity to human society and cultural development, it is essential to reveal their associations and the neural basis of the genetic risk of bipolar disorder to gain insight into its etiology. However, despite the previous demonstration of the associations of polygenic risk score (PRS) of BD and creative jobs, the associations of BD‐PRS and creativity measured by the divergent thinking (CMDT) and regional gray matter volume (rGMV) as well as regional white matter volume (rWMV) have not been investigated. Using psychological analyses and whole‐brain voxel‐by‐voxel analyses, we examined these potential associations in 1558 young, typically developing adult students. After adjusting for confounding variables and multiple comparisons, a greater BD‐PRS was associated with a greater total CMDT fluency score, and a significant relationship was found in fluency subscores. A greater BD‐PRS was also associated with lower total mood disturbance. Neuroimaging analyses revealed that the BD‐PRS was associated with greater rGMV in the right inferior frontal gyrus, which is a consistently affected area in BD, as well as a greater rWMV in the left middle frontal gyrus, which has been suggested to play a central role in the increased creativity associated with the risk of BD with creativity. These findings suggest a relationship between the genetic risk of BD and CMDT and prefrontal cortical structures among young educated individuals., We used brain structural imaging, genome‐wide gene polymorphism data, and creativity data as measured by divergent thinking. And we showed that a higher genetic risk of bipolar disorder is associated with higher creativity and prefrontal cortical gray matter/white matter volume in young adults.

Published
2021
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48. Pro‐tumoral behavior of omental adipocyte‐derived fibroblasts in tumor microenvironment at the metastatic site of ovarian cancer

Author

Shohei Iyoshi, Kazuhisa Kitami, Keiji Kajiwara, Kae Nakamura, Shigehiro Yamaguchi, Yoshihiro Koya, Hiroaki Kajiyama, Masato Yoshihara, Sho Tano, Mai Sugiyama, Kazumasa Mogi, Hiroyuki Tomita, Kaname Uno, Masayasu Taki, and Akihiro Nawa

Subjects
Cancer Research, Biology, Imides, Mice, chemistry.chemical_compound, Cancer-Associated Fibroblasts, Cell Movement, In vivo, 3T3-L1 Cells, Wnt3A Protein, Adipocyte, Adipocytes, Tumor Microenvironment, medicine, Animals, Humans, Myofibroblasts, Fibroblast, Wnt Signaling Pathway, Peritoneal Neoplasms, Cell Proliferation, Ovarian Neoplasms, Tumor microenvironment, Mesenchymal stem cell, Wnt signaling pathway, Ascites, Mesenchymal Stem Cells, Cell Dedifferentiation, medicine.disease, Actins, medicine.anatomical_structure, Oncology, chemistry, Cell culture, Quinolines, Cancer research, Female, Ovarian cancer, Omentum
Abstract

Adipocyte-rich omentum offers "good soil" for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro co-culturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon co-culturing with O-ADF. Additionally, exogenous transforming growth factor-β1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/β-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks. This article is protected by copyright. All rights reserved.

Published
2021
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49. Efficacy of renin-angiotensin-aldosterone system blockades for acute phase hypertensive emergencies in patient complicating severe acute kidney injury

Author

Yugo Ito, Masahiko Nagahama, Kimio Watanabe, Fumika Taki, Takayuki Hamada, Keiki Shimada, Takuya Fujimaru, and Masaaki Nakayama

Subjects
Adult, Male, Losartan Potassium, Nephrology, medicine.medical_specialty, Case Report, Angiotensin-Converting Enzyme Inhibitors, Spironolactone, Renin-Angiotensin System, Angiotensin Receptor Antagonists, chemistry.chemical_compound, Internal medicine, Renin–angiotensin system, medicine, Humans, Hypertensive emergency, business.industry, Acute kidney injury, Posterior reversible encephalopathy syndrome, General Medicine, Acute Kidney Injury, medicine.disease, Blood pressure, chemistry, Cardiology, Female, Posterior Leukoencephalopathy Syndrome, Emergencies, business
Abstract

Renin-angiotensin-aldosterone system (RAAS) is primarily involved with pathological mechanism of developing hypertensive emergencies. However, none of clinical practice guidelines mention RAAS blockers for the treatment of hypertensive emergencies. A 44 year-old woman presented with severe hypertension, brain stem posterior reversible encephalopathy syndrome and severe acute kidney injury (AKI). We started anti-hypertensive therapy with continuous intravenous nitroglycerin and oral calcium channel blocker (CCB) and spironolactone. Since severe AKI persisted despite this therapy, we administered losartan potassium, which resulted in improvement in her blood pressure and creatinine. Clinical course of our patient suggests that timely initiation of ARB and spironolactone for hypertensive emergencies could be beneficial in terms of blood pressure control and for protection of target organs from this condition.

Published
2021
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50. Bone responsiveness to parathyroid hormone is negatively associated with parathyroid hormone-lowering drug use in patients undergoing hemodialysis: a cross-sectional study

Author

Hirofumi Sumi, Yugo Shibagaki, Masayuki Yamanouchi, Naoto Tominaga, Tomoki Yonaha, Yasuhiro Taki, Kazuhiro Shiizaki, and Shozo Yano

Subjects
Male, medicine.medical_specialty, Calcitriol, medicine.medical_treatment, Calcium-sensing receptor agonists, Parathyroid hormone, Osteoclasts, Bone resorption, Bone remodeling, Tartrate-resistant acid phosphatase-5b, Japan, Renal Dialysis, Internal medicine, medicine, Humans, Bone Resorption, Dialysis, Etelcalcetide, business.industry, Tartrate-Resistant Acid Phosphatase, Research, Middle Aged, Diseases of the genitourinary system. Urology, Endocrinology, Cross-Sectional Studies, Nephrology, Hemodialysis, Vitamin D receptor activators, Kidney Failure, Chronic, Receptors, Calcitriol, Female, Bone Remodeling, RC870-923, business, Body mass index, Peritoneal Dialysis, Receptors, Calcium-Sensing, medicine.drug
Abstract

Background Parathyroid hormone (PTH) acts on bone to indirectly increase the number and activity of osteoclasts. Thus, PTH has a stimulatory effect on bone resorption and upregulates bone turnover. However, the responsiveness of bone to PTH varies widely among patients receiving dialysis. In fact, relative to the serum PTH level, the level of serum tartrate-resistant acid phosphatase-5b (TRACP-5b), a bone resorption marker derived from osteoclasts, varies as well. This study aimed to examine factors related to bone responsiveness to PTH in patients undergoing chronic hemodialysis (HD). Methods This study included patients receiving chronic HD in Kawasaki Municipal Tama Hospital (Kanagawa, Japan) and Yonaha Medical Clinic (Okinawa, Japan) and excluded patients who received HD for less than 6 months, those who received a combination of HD and peritoneal dialysis, and those who had cancer bone metastases or myeloma. The TRACP-5b/intact PTH (iPTH) ratio was created as an index of bone responsiveness to PTH, categorized into tertiles (low, medium, and high), and a cross-sectional study was conducted. P Results One hundred and six patients were analyzed. Age (P = 0.010), body mass index (BMI) (P = 0.003), use of calcium-sensing receptor (CaSR) agonists (P = 0.008), use of vitamin D receptor activators (VDRAs) (P = 0.012), plasma iPTH level (P 2D level (P = 0.003), and serum TRACP-5b level (P P = 0.016), corrected serum calcium level (P = 0.007), and ln [1,25(OH)2D] (P = 0.044) showed a significant positive correlation with ln [TRACP-5b/iPTH], whereas BMI (P = 0.026), use of CaSR agonists (P = 0.001), use of VDRAs (P = 0.009), and serum phosphorus level (P = 0.018) showed a significant negative correlation. Upon conducting multiple linear regression analysis incorporating significant variables in the single linear regression analysis, a significant negative correlation was observed between the TRACP-5b/iPTH ratio and intravenous administration of a CaSR agonist (etelcalcetide) and/or a VDRA (calcitriol or maxacalcitol) in all the adjusted models. Conclusions Bone responsiveness to PTH is negatively correlated with the intravenous administration of a CaSR agonist and/or a VDRA in patients undergoing chronic HD.

Published
2021

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