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1. Site-specific acetylation of polynucleotide kinase 3′-phosphatase regulates its distinct role in DNA repair pathways

Author

Islam, Azharul, Chakraborty, Anirban, Sarker, Altaf H, Aryal, Uma K, Pan, Lang, Sharma, Gulshan, Boldogh, Istvan, and Hazra, Tapas

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, Rare Diseases, Neurosciences, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Humans, Mice, Acetylation, DNA Damage, DNA Repair, DNA Repair Enzymes, Mammals, Phosphotransferases (Alcohol Group Acceptor), Polynucleotide 5'-Hydroxyl-Kinase, Environmental Sciences, Information and Computing Sciences, Developmental Biology, Biological sciences, Chemical sciences, Environmental sciences
Abstract

Mammalian polynucleotide kinase 3'-phosphatase (PNKP), a DNA end-processing enzyme with 3'-phosphatase and 5'-kinase activities, is involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes. Here we report that PNKP is acetylated at K142 (AcK142) by p300 constitutively but at K226 (AcK226) by CBP, only after DSB induction. Co-immunoprecipitation analysis using AcK142 or AcK226 PNKP-specific antibodies showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP with DSBR proteins. Despite the modest effect of acetylation on PNKP's enzymatic activity in vitro, cells expressing non-acetylable PNKP (K142R or K226R) accumulated DNA damage in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington's Disease (HD)-based mouse model, K142, but not K226, was acetylated. This is consistent with the reported degradation of CBP, but not p300, in HD cells. Moreover, transcribed genomes of HD cells progressively accumulated DSBs. Chromatin-immunoprecipitation analysis demonstrated the association of Ac-PNKP with the transcribed genes, consistent with PNKP's role in transcription-coupled repair. Thus, our findings demonstrate that acetylation at two lysine residues, located in different domains of PNKP, regulates its distinct role in BER/SSBR versus DSBR.

Published
2024

2. Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimers disease.

Author

Agra Almeida Quadros, Ana, Li, Zhaozhi, Wang, Xue, Ndayambaje, I, Aryal, Sandeep, Ramesh, Nandini, Nolan, Matthew, Jayakumar, Rojashree, Han, Yi, Stillman, Hannah, Aguilar, Corey, Wheeler, Hayden, Connors, Theresa, Lopez-Erauskin, Jone, Baughn, Michael, Melamed, Zeev, Beccari, Melinda, Olmedo Martínez, Laura, Canori, Michael, Lee, Chao-Zong, Moran, Laura, Draper, Isabelle, Kopin, Alan, Oakley, Derek, Dickson, Dennis, Cleveland, Don, Hyman, Bradley, Das, Sudeshna, Ertekin-Taner, Nilüfer, and Lagier-Tourenne, Clotilde

Subjects
Alzheimer’s disease, Cryptic exons, SCG-10, Stathmin-2, TARDBP, TDP-43, UNC13A, Humans, Alzheimer Disease, Amyotrophic Lateral Sclerosis, DNA-Binding Proteins, Frontotemporal Dementia, Pick Disease of the Brain, RNA Splicing, RNA, Messenger, Stathmin
Abstract

Nuclear clearance and cytoplasmic accumulations of the RNA-binding protein TDP-43 are pathological hallmarks in almost all patients with amyotrophic lateral sclerosis (ALS) and up to 50% of patients with frontotemporal dementia (FTD) and Alzheimers disease. In Alzheimers disease, TDP-43 pathology is predominantly observed in the limbic system and correlates with cognitive decline and reduced hippocampal volume. Disruption of nuclear TDP-43 function leads to abnormal RNA splicing and incorporation of erroneous cryptic exons in numerous transcripts including Stathmin-2 (STMN2, also known as SCG10) and UNC13A, recently reported in tissues from patients with ALS and FTD. Here, we identify both STMN2 and UNC13A cryptic exons in Alzheimers disease patients, that correlate with TDP-43 pathology burden, but not with amyloid-β or tau deposits. We also demonstrate that processing of the STMN2 pre-mRNA is more sensitive to TDP-43 loss of function than UNC13A. In addition, full-length RNAs encoding STMN2 and UNC13A are suppressed in large RNA-seq datasets generated from Alzheimers disease post-mortem brain tissue. Collectively, these results open exciting new avenues to use STMN2 and UNC13A as potential therapeutic targets in a broad range of neurodegenerative conditions with TDP-43 proteinopathy including Alzheimers disease.

Published
2024

3. Health system quality and COVID-19 vaccination: a cross-sectional analysis in 14 countries

Author

Arsenault, Catherine, Lewis, Todd P, Kapoor, Neena R, Okiro, Emelda A, Leslie, Hannah H, Armeni, Patrizio, Jarhyan, Prashant, Doubova, Svetlana V, Wright, Katherine D, Aryal, Amit, Kounnavong, Sengchanh, Mohan, Sailesh, Odipo, Emily, Lee, Hwa-Young, Shin, Jeonghyun, Ayele, Wondimu, Medina-Ranilla, Jesús, Espinoza-Pajuelo, Laura, Mebratie, Anagaw Derseh, Elorrio, Ezequiel García, Mazzoni, Agustina, Oh, Juhwan, SteelFisher, Gillian K, Tarricone, Rosanna, and Kruk, Margaret E

Subjects
Health Services and Systems, Public Health, Health Sciences, Emerging Infectious Diseases, Clinical Research, Health Services, Prevention, Immunization, Vaccine Related, Behavioral and Social Science, 3.4 Vaccines, Prevention of disease and conditions, and promotion of well-being, Generic health relevance, Good Health and Well Being, Humans, Cross-Sectional Studies, COVID-19 Vaccines, COVID-19, Vaccination, Vaccines, Microbiology, Public Health and Health Services, Epidemiology, Health services and systems, Public health
Abstract

The social and behavioural determinants of COVID-19 vaccination have been described previously. However, little is known about how vaccinated people use and rate their health system. We used surveys conducted in 14 countries to study the health system correlates of COVID-19 vaccination. Country-specific logistic regression models were adjusted for respondent age, education, income, chronic illness, history of COVID-19, urban residence, and minority ethnic, racial, or linguistic group. Estimates were summarised across countries using random effects meta-analysis. Vaccination coverage with at least two or three doses ranged from 29% in India to 85% in Peru. Greater health-care use, having a regular and high-quality provider, and receiving other preventive health services were positively associated with vaccination. Confidence in the health system and government also increased the odds of vaccination. By contrast, having unmet health-care needs or experiencing discrimination or a medical mistake decreased the odds of vaccination. Associations between health system predictors and vaccination tended to be stronger in high-income countries and in countries with the most COVID-19-related deaths. Access to quality health systems might affect vaccine decisions. Building strong primary care systems and ensuring a baseline level of quality that is affordable for all should be central to pandemic preparedness strategies.

Published
2024

4. Evolving academic and research partnerships in global health: a capacity-building partnership to assess primary healthcare in the Philippines

Author

Aryal, Anu, Garcia, Fernando B, Scheitler, AJ, Faraon, Emerito Jose A, Moncatar, TJ Robinson T, Saniel, Ofelia P, Lorenzo, Fely Marilyn E, Rosadia, Roberto Antonio F, Shimkhada, Riti, Macinko, James, and Ponce, Ninez A

Subjects
Prevention, Clinical Research, Health Services, Generic health relevance, Good Health and Well Being, Partnerships for the Goals, Adult, Humans, Capacity Building, Global Health, Philippines, Delivery of Health Care, Primary Health Care, Capacity building, research collaboration, primary care, non-communicable diseases, Public Health and Health Services
Abstract

Building fair, equitable, and beneficial partnerships between institutions collaborating in research in low- and middle-income countries (LMIC) and high-income countries (HIC) has become an integral part of research capacity building in global health in recent years. In this paper, we offer an example of an academic collaboration between the University of California Los Angeles, Center for Health Policy and Research (UCLA CHPR) and the University of Philippines, Manila, College of Public Health (UPM CPH) that sought to build an equitable partnership between research institutions. The partnership was built on a project to build capacity for research and produce data for policy action for the prevention and care of non-communicable diseases (NCDs) through primary healthcare in the Philippines. The specific objectives of the project were to: (1) locally adapt the Primary Care Assessment Tool for the Philippines and use the adapted tool to measure facility-level primary care delivery, (2) conduct focus group discussions (FGDs) to gather qualitative observations regarding primary care readiness and capacity, and (3) conduct a comprehensive population-based health survey among adults on NCDs and prior healthcare experience. We describe here the progression of the partnership between these institutions to carry out the project and the elements that helped build a stronger connection between the institutions, such as mutual goal setting, cultural bridging, collaborative teams, and capacity building. This example, which can be used as a model depicting new directionality and opportunities for LMIC-HIC academic partnerships, was written based on the review of shared project documents, including study protocols, and written and oral communications with the project team members, including the primary investigators. The innovation of this partnership includes: LMIC-initiated project need identification, LMIC-based funding allocation, a capacity-building role of the HIC institution, and the expansion of scope through jointly offered courses on global health.

Published
2023

5. Simvastatin in Critically Ill Patients with Covid-19.

Author

Hills, Thomas, Lorenzi, Elizabeth, Berry, Lindsay, Shyamsundar, Murali, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Aryal, Diptesh, Au, Carly, Beane, Abigail, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Burrell, Aidan, Buxton, Meredith, Calfee, Carolyn, Cecconi, Maurizio, Cheng, Allen, Cove, Matthew, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goligher, Ewan, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Harrison, David, Hashmi, Madiha, Higgins, Alisa, Huang, David, Ichihara, Nao, Jayakumar, Deva, Kruger, Peter, Lamontagne, François, Lampro, Lamprini, Lawler, Patrick, Marshall, John, Mason, Alexina, McGlothlin, Anna, McGuinness, Shay, McQuilten, Zoe, McVerry, Bryan, Mouncey, Paul, Murthy, Srinivas, Neal, Matthew, Nichol, Alistair, OKane, Cecilia, Parke, Rachael, Parker, Jane, Rabindrarajan, Ebenezer, Reyes, Luis, Rowan, Kathryn, Saito, Hiroki, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Shankar-Hari, Manu, Sinha, Pratik, Thompson, B, Turgeon, Alexis, Turner, Anne, van de Veerdonk, Frank, Weis, Sebastian, Young, Ian, Zarychanski, Ryan, McArthur, Colin, Angus, Derek, Berry, Scott, Derde, Lennie, Webb, Steve, Gordon, Anthony, McAuley, Daniel, and Lewis, Roger

Subjects
Humans, Bayes Theorem, COVID-19, COVID-19 Drug Treatment, Critical Illness, Hospital Mortality, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Treatment Outcome
Abstract

BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was

Published
2023

6. PrEP Use and HIV Incidence Among Youth At-Risk for HIV Infection in Los Angeles and New Orleans: Findings From ATN 149

Author

Aryal, Anu, Leibowitz, Arleen A, Comulada, Warren Scott, Rotheram-Borus, Mary Jane, Bolan, Robert, Ocasio, Manuel A, Swendeman, Dallas, and Team, the ATN CARES Study

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Social Determinants of Health, Pediatric, Sexually Transmitted Infections, Prevention, Pediatric AIDS, HIV/AIDS, Infectious Diseases, Health Disparities, Behavioral and Social Science, Clinical Research, Sexual and Gender Minorities (SGM/LGBT*), Adolescent Sexual Activity, Minority Health, Infection, Good Health and Well Being, Male, Humans, Adolescent, Female, HIV Infections, Incidence, Los Angeles, New Orleans, Anti-HIV Agents, Homosexuality, Male, HIV Seropositivity, Pre-Exposure Prophylaxis, Transgender Persons, HIV prevention, PrEP adherence, adolescents, men who have sex with men, cohort studies, ATN CARES Study Team, Clinical Sciences, Public Health and Health Services, Virology, Clinical sciences, Epidemiology, Public health
Abstract

IntroductionExpanding HIV pre-exposure prophylaxis (PrEP) use is key to goals for lowering new HIV infections in the U.S. by 90% between 2022 and 2030. Unfortunately, youth aged 16-24 have the lowest PrEP use of any age group and the highest HIV incidence rates.MethodsTo examine the relationship between HIV seroconversion and PrEP uptake, adherence, and continuity, we used survival analysis and multivariable logistic regression on data of 895 youth at-risk for HIV infection enrolled in Adolescent Trials Network for HIV Medicine protocol 149 in Los Angeles and New Orleans, assessed at 4-month intervals over 24 months.ResultsThe sample was diverse in race/ethnicity (40% Black, 28% Latine, 20% White). Most participants (79%) were cis-gender gay/bisexual male but also included 7% transgender female and 14% trans masculine and nonbinary youth. Self-reported weekly PrEP adherence was high (98%). Twenty-seven participants acquired HIV during the study. HIV incidence among PrEP users (3.12 per 100 person year [PY]) was higher than those who never used PrEP (2.53/100 PY). The seroconversion incidence was highest among PrEP users with discontinuous use (3.36/100 PY). If oral PrEP users were adherent using 2-monthly long-acting injectables, our estimate suggests 2.06 infections per 100 PY could be averted.ConclusionsDiscontinuous use of PrEP may increase risk of HIV acquisition among youth at higher risk for HIV infection and indications for PrEP. Thus, to realize the promise of PrEP in reducing new HIV infections, reducing clinical burdens for PrEP continuation are warranted.

Published
2023

7. Defining Collective Priorities: Research and Learning Agendas for Family Planning Across 6 Countries.

Author

Brittingham, Sarah, Zan, Trinity, Andoh, Kouakou, Aryal, Kabita, Chissano, Marcos, Ferguson, Olivia, Fotso, Jean, Harou, Issoufa, Khatri, Sangita, Kourouma, Kadidiatou, Kiwanuka, Suzanne, Lal, Bibek, Govo, Alda, Malkin, Morrisa, Mkandawire, Philip, Phiri, Mary, Olaro, Charles, Pryor, Shannon, Shrestha, Bhagawan, Thapa, Basant, Touré, Fatoumata, and Prata, Ndola

Subjects
Adolescent, Humans, Family Planning Services, Learning, Consensus, Cote dIvoire, Evidence Gaps
Abstract

Evidence should be the foundation for a well-designed family planning (FP) program, but existing evidence is rarely aligned with and/or synthesized to speak directly to FP programmatic needs. Based on our experience cocreating FP research and learning agendas (FP RLAs) in Côte dIvoire, Malawi, Mozambique, Nepal, Niger, and Uganda, we argue that FP RLAs can drive the production of coordinated research that aligns with national priorities.To cocreate FP RLAs, stakeholders across 6 countries conducted desk reviews of 349 documents and 106 key informant interviews, organized consultation meetings in each country to prioritize evidence gaps and generate research and learning questions, and, ultimately, formed 6 FP RLAs comprising 190 unique questions. We outline the process for consensus-driven development of FP RLAs and communicate the results of an analysis of the questions in each FP RLA across 4 technical areas: self-care, equity, high impact practices, and youth. Each question was categorized as a learning versus research question, the former indicating an opportunity to synthesize existing evidence and the latter to conduct new research to answer the question. Themes emerging from the data shed light on shared evidence gaps across the 6 countries. We argue that similarities and differences in the questions in each FP RLA reflect the unique implementation experience and context, as well as each countrys placement on the FP S-curve. Early uses of the FP RLAs include informing the development of FP costed implementation plans and FP2030 commitments. FP RLAs have also been discussed in multiple thematic working groups. For FP stakeholders, these FP RLAs represent a consensus-based agenda that can guide the generation and synthesis of evidence to answer each countrys most pressing questions, ultimately driving progress toward increasingly evidence-based programming and policy.

Published
2023

8. Meeting report: The first soil viral workshop 2022

Author

Buivydaitė, Živilė, Aryal, Laxman, Corrêa, Felipe Borim, Chen, Tingting, Langlois, Valérie, Elberg, Christine Lorenzen, Netherway, Tarquin, Wang, Ruiqi, Zhao, Tianci, Acharya, Basistha, Emerson, Joanne B, Hillary, Luke, Khadka, Ram B, Mason-Jones, Kyle, Sapkota, Rumakanta, Sutela, Suvi, Trubl, Gareth, White, Richard Allen, Winding, Anne, and Carreira, Cátia

Subjects
Biological Sciences, Humans, Viruses, Ecology, Food Chain, Genome, Viral, Soil, Virus -host interactions, Biogeochemistry, Soil food web, Virus–host interactions, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

Soil viral ecology is a growing research field; however, the state of knowledge still lags behind that of aquatic systems. Therefore, to facilitate progress, the first Soil Viral Workshop was held to encourage international scientific discussion and collaboration, suggest guidelines for future research, and establish soil viral research as a concrete research area. The workshop took place at Søminestationen, Denmark, between 15 and 17th of June 2022. The meeting was primarily held in person, but the sessions were also streamed online. The workshop was attended by 23 researchers from ten different countries and from a wide range of subfields and career stages. Eleven talks were presented, followed by discussions revolving around three major topics: viral genomics, virus-host interactions, and viruses in the soil food web. The main take-home messages and suggestions from the discussions are summarized in this report.

Published
2023

9. Double burden of malnutrition in Nepal: A trend analysis of protein-energy malnutrition and High Body Mass Index using the data from Global Burden of Disease 2010–2019

Author

Pradhananga, Priza, Shrestha, Archana, Adhikari, Nabin, Shrestha, Namuna, Adhikari, Mukesh, Ide, Nicole, Dhungel, Saurya, Bajracharya, Swornim, and Aryal, Anu

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Clinical Research, Nutrition, Pediatric, Zero Hunger, Good Health and Well Being, Aged, Aged, 80 and over, Body Mass Index, Child, Female, Global Burden of Disease, Humans, Male, Malnutrition, Nepal, Protein-Energy Malnutrition, Trans Fatty Acids, General Science & Technology
Abstract

BackgroundThe co-existence of undernutrition and overnutrition is a global public health threat. We aim to report the burden of both nutritional deficiency (Protein-Energy Malnutrition) and overweight (high Body Mass Index) in Nepal over a decade (2010-2019) and observe the changes through trend charts.MethodsWe did a secondary data analysis using the Institute for Health Metrics and Evaluation (IHME)'s Global Burden of Disease (GBD) database to download age-standardized data on Protein Energy Malnutrition (PEM) and high Body Mass Index (BMI). We presented the trend of death, Disability Adjusted Life Years (DALYs), Years of Life Lost (YLL), and Years Lost due to Disability (YLD) of PEM and high BMI in Nepal from 2010 to 2019 and also compared data for 2019 among South Asian countries.ResultsBetween 2010 and 2019, in Nepal, the Disability Adjusted Life Years (DALYs) due to PEM were declining while high BMI was in increasing trend. Sex-specific trends revealed that females had higher DALYs for PEM than males. In contrast, males had higher DALYs for high BMI than females. In 2019, Nepal had the highest death rate for PEM (5.22 per 100,000 populations) than any other South Asian country. The burden of PEM in terms of DALY was higher in under-five children (912 per 100,000 populations) and elderly above 80 years old (808.9 per 100,000 populations), while the population aged 65-69 years had the highest burden of high BMI (5893 per 100,000 populations). In the last decade, the DALYs for risk factors contributing to PEM such as child growth failure (stunting and wasting), unsafe water, sanitation and handwashing, and sub-optimal breastfeeding have declined in Nepal. On the contrary, the DALYs for risk factors contributing to high BMI, such as a diet high in sugar-sweetened beverages, a diet high in trans fatty acid, and low physical activity, have increased. This could be a possible explanation for the increasing trend of high BMI and decreasing trend of PEM.ConclusionRapidly growing prevalence of high BMI and the persistent existence of undernutrition indicate the double burden of malnutrition in Nepal. Public health initiatives should be planned to address this problem.

Published
2022

10. The field of human building interaction for convergent research and innovation for intelligent built environments

Author

Becerik-Gerber, Burcin, Lucas, Gale, Aryal, Ashrant, Awada, Mohamad, Bergés, Mario, Billington, Sarah, Boric-Lubecke, Olga, Ghahramani, Ali, Heydarian, Arsalan, Höelscher, Christoph, Jazizadeh, Farrokh, Khan, Azam, Langevin, Jared, Liu, Ruying, Marks, Frederick, Mauriello, Matthew Louis, Murnane, Elizabeth, Noh, Haeyoung, Pritoni, Marco, Roll, Shawn, Schaumann, Davide, Seyedrezaei, Mirmahdi, Taylor, John E, Zhao, Jie, and Zhu, Runhe

Subjects
Information and Computing Sciences, Architecture, Built Environment and Design, Humans, Consensus, Forecasting, Built Environment
Abstract

Human-Building Interaction (HBI) is a convergent field that represents the growing complexities of the dynamic interplay between human experience and intelligence within built environments. This paper provides core definitions, research dimensions, and an overall vision for the future of HBI as developed through consensus among 25 interdisciplinary experts in a series of facilitated workshops. Three primary areas contribute to and require attention in HBI research: humans (human experiences, performance, and well-being), buildings (building design and operations), and technologies (sensing, inference, and awareness). Three critical interdisciplinary research domains intersect these areas: control systems and decision making, trust and collaboration, and modeling and simulation. Finally, at the core, it is vital for HBI research to center on and support equity, privacy, and sustainability. Compelling research questions are posed for each primary area, research domain, and core principle. State-of-the-art methods used in HBI studies are discussed, and examples of original research are offered to illustrate opportunities for the advancement of HBI research.

Published
2022

11. Lung Transplantation for Patients With COVID-19

Author

King, Christopher S, Mannem, Hannah, Kukreja, Jasleen, Aryal, Shambhu, Tang, Daniel, Singer, Jonathan P, Bharat, Ankit, Behr, Juergen, and Nathan, Steven D

Subjects
Rare Diseases, Acute Respiratory Distress Syndrome, Lung, Transplantation, Clinical Research, Organ Transplantation, Respiratory, Good Health and Well Being, COVID-19, Humans, Lung Transplantation, Pandemics, Pneumonia, Viral, Pulmonary Fibrosis, SARS-CoV-2, ARDS, lung transplantation, pulmonary fibrosis, Clinical Sciences, Respiratory System
Abstract

The COVID-19 pandemic has caused acute lung injury in millions of individuals worldwide. Some patients develop COVID-related acute respiratory distress syndrome (CARDS) and cannot be liberated from mechanical ventilation. Others may develop post-COVID fibrosis, resulting in substantial disability and need for long-term supplemental oxygen. In both of these situations, treatment teams often inquire about the possibility of lung transplantation. In fact, lung transplantation has been successfully employed for both CARDS and post-COVID fibrosis in a limited number of patients worldwide. Lung transplantation after COVID infection presents a number of unique challenges that transplant programs must consider. In those with severe CARDS, the inability to conduct proper psychosocial evaluation and pretransplantation education, marked deconditioning from critical illness, and infectious concerns regarding viral reactivation are major hurdles. In those with post-COVID fibrosis, our limited knowledge about the natural history of recovery after COVID-19 infection is problematic. Increased knowledge of the likelihood and degree of recovery after COVID-19 acute lung injury is essential for appropriate decision-making with regard to transplantation. Transplant physicians must weigh the risks and benefits of lung transplantation differently in a post-COVID fibrosis patient who is likely to remain stable or gradually improve in comparison with a patient with a known progressive fibrosing interstitial lung disease (fILD). Clearly lung transplantation can be a life-saving therapeutic option for some patients with severe lung injury from COVID-19 infection. In this review, we discuss how lung transplant providers from a number of experienced centers approach lung transplantation for CARDS or post-COVID fibrosis.

Published
2022

12. Cross-cultural adaptation of motivational interviewing for use in rural Nepal

Author

Rimal, Pragya, Khadka, Sonu, Bogati, Bhawana, Chaudhury, Jamuna, Rawat, Laxmi Kumari, Bhat, Kumari Chhaya, Manandhar, Pramita, Citrin, David, Maru, Duncan, Ekstrand, Maria L, Swar, Sikhar Bahadur, Aryal, Anu, Kohrt, Brandon, Shrestha, Srijana, and Acharya, Bibhav

Subjects
Biological Psychology, Clinical and Health Psychology, Psychology, Applied and Developmental Psychology, Behavioral and Social Science, Clinical Research, Health and social care services research, 8.1 Organisation and delivery of services, Generic health relevance, Cross-Cultural Comparison, Family, Humans, Motivational Interviewing, Nepal, Rural Population, LMICs, Cultural adaptation, Global Mental Health, Applied and developmental psychology, Biological psychology, Clinical and health psychology
Abstract

BackgroundMotivational Interviewing (MI) has a robust evidence base in facilitating behavior change for several health conditions. MI focuses on the individual and assumes patient autonomy. Cross-cultural adaptation can face several challenges in settings where individualism and autonomy may not be as prominent. Sociocultural factors such as gender, class, caste hinder individual decision-making. Key informant perspectives are an essential aspect of cross-cultural adaptation of new interventions. Here, we share our experience of translating and adapting MI concepts to the local language and culture in rural Nepal, where families and communities play a central role in influencing a person's behaviors.MethodsWe developed, translated, field-tested, and adapted a Nepali MI training module with key informants to generate insights on adapting MI for the first time in this cultural setting. Key informants were five Nepali nurses who supervise community health workers. We used structured observation notes to describe challenges and experiences in cross-cultural adaptation. We conducted this study as part of a larger study on using MI to improve adherence to HIV treatment.ResultsParticipants viewed MI as an effective intervention with the potential to assist patients poorly engaged in care. Regarding patient autonomy, they initially shared examples of family members unsuccessfully dictating patient behavior change. These discussions led to consensus that every time the family members restrict patient's autonomy, the patient complies temporarily but then resumes their unhealthy behavior. In addition, participants highlighted that even when a patient is motivated to change (e.g., return for follow-up), their family members may not "allow" it. Discussion led to suggestions that health workers may need to conduct MI separately with patients and family members to understand everyone's motivations and align those with the patient's needs.ConclusionsMI carries several cultural assumptions, particularly around individual freedom and autonomy. MI adaptation thus faces challenges in cultures where such assumptions may not hold. However, cross-cultural adaptation with key informant perspectives can lead to creative strategies that recognize both the patient's autonomy and their role as a member of a complex social fabric to facilitate behavior change.

Published
2021

13. Essential Emergency and Critical Care: a consensus among global clinical experts

Author

Schell, Carl Otto, Khalid, Karima, Wharton-Smith, Alexandra, Oliwa, Jacquie, Sawe, Hendry R, Roy, Nobhojit, Sanga, Alex, Marshall, John C, Rylance, Jamie, Hanson, Claudia, Kayambankadzanja, Raphael K, Wallis, Lee A, Jirwe, Maria, Baker, Tim, Asghar, Adam, Laytin, Adam D, Holloway, Adrian J, Adib, Ahmed Rhassane El, Michaelides, Alexia, Munoz, Alvaro Coronado, Muzuka, Amos, Fernández, Analía, Pembe, Andrea B, Wellhagen, Andreas, Smith, Andrew G, Gadgil, Anita, Hvarfner, Anna, Abayadeera, Anuja, Agulnik, Asya, Godard, Aurélie, Venkatesh, Balasubramanian, Yousif, Bargo Mahamat, Morton, Bhakti Sarang Ben, Kumar, Bharath, Vijayaraghavan, Tirupakuzhi, King, Bobby, Rice, Brian, Thwaites, C Louise, Tai, Chian Wern, Owoo, Christian, Sendagire, Cornelius, Petersen, Dan Brun, Tatay, Daniel, Skinner, David Lee, Kinyua, Denis, Ghosh, Dhruva, Aryal, Diptesh, Mlombwa, Donald, Thi, Duyen, Bui, Hanh, Lugazia, Edwin R, Riviello, Elisabeth, Molyneux, Elizabeth M, Heyns, Ellena, Nsutebu, Emmanuel Fru, Montalvo, Erika, Moreno, Ernesto Gerardo, Kanyangira, Esther Banda, Muttalib, Fiona, Mupeta, Francis, Diaz, Franco, Bulamba, Fred, Nzanzu, Furaha, Pascal, Blaise, Wooldridge, Gavin, Mwakisambwe, Gibonce, Richards, Guy A, Ammar, Hala, Mangat, Halinder S, Ghali, Hasanein H, Shah, Hiral A, Shum, Hoi Ping, Abdullahi, Ibrahim Salim, Martin-Loeches, Ignacio, von der Osten, Ingrid T, Mcknight, Jacob, Lee, James S, Namagga, Jane Kasozi, Eriksen, Jaran, Armour-Marshall, Jasmine, Kellett, John, Metcalfe, John Z, Moore, Jolene, Blixt, Jonas, Langton, Josephine, Mejia, Juan Gutierrez, Silesky-Jiménez, Juan Ignacio, Soni, Kapil Dev, Kohne, Karl Martin, Rowan, Kathryn, Yokobatake, Kazuhiro, Doi, Kent, Rudd, Kristina E, Akuamoah-Boateng, Kwame Asante, Irestedt, Lars, Losonczy, Lia I, Zhang, Lina, Kurland, Lisa, Guinness, Lorna, and Bains, Lovenish

Subjects
Health Services and Systems, Health Sciences, Health Services, Clinical Research, Emergency Care, Generic health relevance, Good Health and Well Being, COVID-19, Consensus, Critical Care, Emergency Medical Services, Humans, SARS-CoV-2, EECC Collaborators, EECC Collaborators*, health policy, health services research, health systems, surgery, Health services and systems, Public health
Abstract

BackgroundGlobally, critical illness results in millions of deaths every year. Although many of these deaths are potentially preventable, the basic, life-saving care of critically ill patients are often overlooked in health systems. Essential Emergency and Critical Care (EECC) has been devised as the care that should be provided to all critically ill patients in all hospitals in the world. EECC includes the effective care of low cost and low complexity for the identification and treatment of critically ill patients across all medical specialties. This study aimed to specify the content of EECC and additionally, given the surge of critical illness in the ongoing pandemic, the essential diagnosis-specific care for critically ill patients with COVID-19.MethodsIn a Delphi process, consensus (>90% agreement) was sought from a diverse panel of global clinical experts. The panel iteratively rated proposed treatments and actions based on previous guidelines and the WHO/ICRC's Basic Emergency Care. The output from the Delphi was adapted iteratively with specialist reviewers into a coherent and feasible package of clinical processes plus a list of hospital readiness requirements.ResultsThe 269 experts in the Delphi panel had clinical experience in different acute medical specialties from 59 countries and from all resource settings. The agreed EECC package contains 40 clinical processes and 67 requirements, plus additions specific for COVID-19.ConclusionThe study has specified the content of care that should be provided to all critically ill patients. Implementing EECC could be an effective strategy for policy makers to reduce preventable deaths worldwide.

Published
2021

14. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

Author

Goligher, Ewan C, Bradbury, Charlotte A, McVerry, Bryan J, Lawler, Patrick R, Berger, Jeffrey S, Gong, Michelle N, Carrier, Marc, Reynolds, Harmony R, Kumar, Anand, Turgeon, Alexis F, Kornblith, Lucy Z, Kahn, Susan R, Marshall, John C, Kim, Keri S, Houston, Brett L, Derde, Lennie PG, Cushman, Mary, Tritschler, Tobias, Angus, Derek C, Godoy, Lucas C, McQuilten, Zoe, Kirwan, Bridget-Anne, Farkouh, Michael E, Brooks, Maria M, Lewis, Roger J, Berry, Lindsay R, Lorenzi, Elizabeth, Gordon, Anthony C, Ahuja, Tania, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Baumann Kreuziger, Lisa, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Contreras, Aira, Costantini, Todd W, de Brouwer, Sophie, Detry, Michelle A, Duggal, Abhijit, Džavík, Vladimír, Effron, Mark B, Eng, Heather F, Escobedo, Jorge, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Froess, Joshua D, Fu, Zhuxuan, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, Girard, Timothy D, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Haniffa, Rashan, Hegde, Sheila M, Hendrickson, Carolyn M, Higgins, Alisa M, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Huang, David T, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei, King, Andrew J, Knudson, M Margaret, Kornblith, Aaron E, Kutcher, Matthew E, Laffan, Michael A, Lamontagne, Francois, and Le Gal, Grégoire

Subjects
Clinical Trials and Supportive Activities, Clinical Research, Comparative Effectiveness Research, Cardiovascular, Good Health and Well Being, Aged, Anticoagulants, COVID-19, Critical Illness, Female, Hemorrhage, Heparin, Hospital Mortality, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Respiration, Artificial, Thrombosis, Treatment Failure, COVID-19 Drug Treatment, REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundThrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.MethodsIn an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.ResultsThe trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio

Published
2021

15. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

Author

Lawler, Patrick R, Goligher, Ewan C, Berger, Jeffrey S, Neal, Matthew D, McVerry, Bryan J, Nicolau, Jose C, Gong, Michelle N, Carrier, Marc, Rosenson, Robert S, Reynolds, Harmony R, Turgeon, Alexis F, Escobedo, Jorge, Huang, David T, Bradbury, Charlotte A, Houston, Brett L, Kornblith, Lucy Z, Kumar, Anand, Kahn, Susan R, Cushman, Mary, McQuilten, Zoe, Slutsky, Arthur S, Kim, Keri S, Gordon, Anthony C, Kirwan, Bridget-Anne, Brooks, Maria M, Higgins, Alisa M, Lewis, Roger J, Lorenzi, Elizabeth, Berry, Scott M, Berry, Lindsay R, Aday, Aaron W, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Baumann Kreuziger, Lisa, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Costantini, Todd W, de Brouwer, Sophie, Derde, Lennie PG, Detry, Michelle A, Duggal, Abhijit, Džavík, Vladimír, Effron, Mark B, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, García-Madrona, Sebastian, Girard, Timothy D, Godoy, Lucas C, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Hamburg, Naomi M, Haniffa, Rashan, Hanna, George, Hanna, Nicholas, Hegde, Sheila M, Hendrickson, Carolyn M, Hite, R Duncan, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Iyer, Vivek N, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei L, King, Andrew J, Knudson, M Margaret, Kornblith, Aaron E, and Krishnan, Vidya

Subjects
Cardiovascular, Clinical Trials and Supportive Activities, Clinical Research, Hematology, Transplantation, Good Health and Well Being, Adult, Aged, Anticoagulants, COVID-19, Female, Hemorrhage, Heparin, Heparin, Low-Molecular-Weight, Hospital Mortality, Humans, Male, Middle Aged, Survival Analysis, Thrombosis, COVID-19 Drug Treatment, ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundThrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.MethodsIn this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.ResultsThe trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.ConclusionsIn noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).

Published
2021

16. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.

Author

REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Goligher, Ewan C, Bradbury, Charlotte A, McVerry, Bryan J, Lawler, Patrick R, Berger, Jeffrey S, Gong, Michelle N, Carrier, Marc, Reynolds, Harmony R, Kumar, Anand, Turgeon, Alexis F, Kornblith, Lucy Z, Kahn, Susan R, Marshall, John C, Kim, Keri S, Houston, Brett L, Derde, Lennie PG, Cushman, Mary, Tritschler, Tobias, Angus, Derek C, Godoy, Lucas C, McQuilten, Zoe, Kirwan, Bridget-Anne, Farkouh, Michael E, Brooks, Maria M, Lewis, Roger J, Berry, Lindsay R, Lorenzi, Elizabeth, Gordon, Anthony C, Ahuja, Tania, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Baumann Kreuziger, Lisa, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Contreras, Aira, Costantini, Todd W, de Brouwer, Sophie, Detry, Michelle A, Duggal, Abhijit, Džavík, Vladimír, Effron, Mark B, Eng, Heather F, Escobedo, Jorge, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Froess, Joshua D, Fu, Zhuxuan, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, Girard, Timothy D, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Haniffa, Rashan, Hegde, Sheila M, Hendrickson, Carolyn M, Higgins, Alisa M, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Huang, David T, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei, King, Andrew J, Knudson, M Margaret, Kornblith, Aaron E, and Kutcher, Matthew E

Subjects
REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Humans, Thrombosis, Critical Illness, Hemorrhage, Heparin, Anticoagulants, Treatment Failure, Respiration, Artificial, Hospital Mortality, Logistic Models, Odds Ratio, Aged, Middle Aged, Female, Male, COVID-19, Clinical Research, Cardiovascular, Clinical Trials and Supportive Activities, Comparative Effectiveness Research, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundThrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.MethodsIn an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.ResultsThe trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio

Published
2021

17. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.

Author

ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, Lawler, Patrick R, Goligher, Ewan C, Berger, Jeffrey S, Neal, Matthew D, McVerry, Bryan J, Nicolau, Jose C, Gong, Michelle N, Carrier, Marc, Rosenson, Robert S, Reynolds, Harmony R, Turgeon, Alexis F, Escobedo, Jorge, Huang, David T, Bradbury, Charlotte A, Houston, Brett L, Kornblith, Lucy Z, Kumar, Anand, Kahn, Susan R, Cushman, Mary, McQuilten, Zoe, Slutsky, Arthur S, Kim, Keri S, Gordon, Anthony C, Kirwan, Bridget-Anne, Brooks, Maria M, Higgins, Alisa M, Lewis, Roger J, Lorenzi, Elizabeth, Berry, Scott M, Berry, Lindsay R, Aday, Aaron W, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Baumann Kreuziger, Lisa, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Costantini, Todd W, de Brouwer, Sophie, Derde, Lennie PG, Detry, Michelle A, Duggal, Abhijit, Džavík, Vladimír, Effron, Mark B, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, García-Madrona, Sebastian, Girard, Timothy D, Godoy, Lucas C, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Hamburg, Naomi M, Haniffa, Rashan, Hanna, George, Hanna, Nicholas, Hegde, Sheila M, Hendrickson, Carolyn M, Hite, R Duncan, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Iyer, Vivek N, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei L, and King, Andrew J

Subjects
ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, Humans, Thrombosis, Hemorrhage, Heparin, Heparin, Low-Molecular-Weight, Anticoagulants, Hospital Mortality, Survival Analysis, Adult, Aged, Middle Aged, Female, Male, COVID-19, Hematology, Clinical Trials and Supportive Activities, Transplantation, Clinical Research, Cardiovascular, General & Internal Medicine, Medical and Health Sciences
Abstract

BackgroundThrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.MethodsIn this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.ResultsThe trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.ConclusionsIn noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).

Published
2021

18. Mapping routine measles vaccination in low- and middle-income countries

Author

Sbarra, Alyssa N, Rolfe, Sam, Nguyen, Jason Q, Earl, Lucas, Galles, Natalie C, Marks, Ashley, Abbas, Kaja M, Abbasi-Kangevari, Mohsen, Abbastabar, Hedayat, Abd-Allah, Foad, Abdelalim, Ahmed, Abdollahi, Mohammad, Abegaz, Kedir Hussein, Abiy, Hailemariam Abiy Alemu, Abolhassani, Hassan, Abreu, Lucas Guimaraes, Abrigo, Michael RM, Abushouk, Abdelrahman I, Accrombessi, Manfred Mario Kokou, Adabi, Maryam, Adebayo, Oladimeji M, Adekanmbi, Victor, Adetokunboh, Olatunji O, Adham, Davoud, Afarideh, Mohsen, Aghaali, Mohammad, Ahmad, Tauseef, Ahmadi, Raman, Ahmadi, Keivan, Ahmed, Muktar Beshir, Alanezi, Fahad Mashhour, Alanzi, Turki M, Alcalde-Rabanal, Jacqueline Elizabeth, Alemnew, Birhan Tamene, Ali, Beriwan Abdulqadir, Ali, Muhammad, Alijanzadeh, Mehran, Alinia, Cyrus, Alipoor, Reza, Alipour, Vahid, Alizade, Hesam, Aljunid, Syed Mohamed, Almasi, Ali, Almasi-Hashiani, Amir, Al-Mekhlafi, Hesham M, Altirkawi, Khalid A, Amare, Bekalu, Amini, Saeed, Amini-Rarani, Mostafa, Amiri, Fatemeh, Amit, Arianna Maever L, Amugsi, Dickson A, Ancuceanu, Robert, Andrei, Catalina Liliana, Anjomshoa, Mina, Ansari, Fereshteh, Ansari-Moghaddam, Alireza, Ansha, Mustafa Geleto, Antonio, Carl Abelardo T, Antriyandarti, Ernoiz, Anvari, Davood, Arabloo, Jalal, Arab-Zozani, Morteza, Aremu, Olatunde, Armoon, Bahram, Aryal, Krishna K, Arzani, Afsaneh, Asadi-Aliabadi, Mehran, Asgari, Samaneh, Atafar, Zahra, Ausloos, Marcel, Awoke, Nefsu, Quintanilla, Beatriz Paulina Ayala, Ayanore, Martin Amogre, Aynalem, Yared Asmare, Azadmehr, Abbas, Azari, Samad, Babaee, Ebrahim, Badawi, Alaa, Badiye, Ashish D, Bahrami, Mohammad Amin, Baig, Atif Amin, Bakhtiari, Ahad, Balakrishnan, Senthilkumar, Banach, Maciej, Banik, Palash Chandra, Barac, Aleksandra, Baradaran-Seyed, Zahra, Baraki, Adhanom Gebreegziabher, Basu, Sanjay, Bayati, Mohsen, Bayou, Yibeltal Tebekaw, Bedi, Neeraj, Behzadifar, Masoud, Bell, Michelle L, Berbada, Dessalegn Ajema, Berhe, Kidanemaryam, Bhattarai, Suraj, Bhutta, Zulfiqar A, and Bijani, Ali

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Human Society, Pediatric, Immunization, Clinical Research, Prevention, Vaccine Related, 3.4 Vaccines, Prevention of disease and conditions, and promotion of well-being, Good Health and Well Being, Child, Child, Preschool, Developed Countries, Geographic Mapping, Healthcare Disparities, Humans, Internationality, Measles, Rural Health, Uncertainty, Urban Health, Vaccination, Vaccination Refusal, Local Burden of Disease Vaccine Coverage Collaborators, General Science & Technology
Abstract

The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)1-4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)5-8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km2 pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.

Published
2021

19. Improving nutrition and immunity with dry chain and integrated pest management food technologies in LMICs

Author

Dahal, Peetambar, Dhimal, Meghnath, Belbase, Krishna, Tiwari, Sundar, Groopman, John, West, Keith, Pollock, Bradley, Pyakurel, Subodh, Acharya, Ganga, Aryal, Sunil, Ghimire, Yug Nath, Neupane, Manish, Poudel, Rosina, Van Ashbrouck, Johan, Kunusoth, Keshavulu, De Saeger, Sarah, De Boevre, Marthe, Gharti-Chhetri, Gokarna, Gurung, Tek Bahadur, and Bradford, Kent J

Subjects
Climate Change Impacts and Adaptation, Environmental Management, Environmental Sciences, Public Health, Health Sciences, Zero Hunger, Developing Countries, Food Technology, Humans, Immunity, Nutritional Status, Pest Control, Climate change impacts and adaptation, Environmental management, Public health
Published
2020

20. Costing Analysis of a Pilot Community Health Worker Program in Rural Nepal

Author

Nepal, Prajwol, Schwarz, Ryan, Citrin, David, Thapa, Aradhana, Acharya, Bibhav, Acharya, Yubraj, Aryal, Anu, Baum, Aaron, Bhandari, Ved, Bhatt, Laxman, Bhattarai, Dipak, Choudhury, Nandini, Dangal, Binod, Dhimal, Meghnath, Dhungana, Santosh Kumar, Gauchan, Bikash, Halliday, Scott, Kalaunee, SP, Kunwar, Lal Bahadur, Maru, Duncan, Nirola, Isha, Paudel, Rashmi, Raut, Anant, Rayamazi, Hari Jung, Sapkota, Sabitri, Schwarz, Dan, Thapa, Poshan, Thapa, Pratistha, Tiwari, Aparna, Tuitui, Roshani, Walter, Eric, and Maru, Sheela

Subjects
Health Services and Systems, Public Health, Health Sciences, Prevention, Cost Effectiveness Research, Clinical Research, Health Services, 8.1 Organisation and delivery of services, Health and social care services research, Good Health and Well Being, Quality Education, Community Health Workers, Cost-Benefit Analysis, Delivery of Health Care, Female, Government Programs, Health Care Costs, Humans, Nepal, Organizations, Politics, Pregnancy, Prenatal Care, Primary Health Care, Public-Private Sector Partnerships, Retrospective Studies, Rural Health Services, Rural Population, Universal Health Insurance, Health services and systems, Public health
Abstract

Community health workers (CHWs) are essential to primary health care systems and are a cost-effective strategy to achieve the Sustainable Development Goals (SDGs). Nepal is strongly committed to universal health coverage and the SDGs. In 2017, the Nepal Ministry of Health and Population partnered with the nongovernmental organization Nyaya Health Nepal to pilot a program aligned with the 2018 World Health Organization guidelines for CHWs. The program includes CHWs who: (1) receive regular financial compensation; (2) meet a minimum education level; (3) are well supervised; (4) are continuously trained; (5) are integrated into local primary health care systems; (6) use mobile health tools; (7) have consistent supply chain; (8) live in the communities they serve; and (9) provide service without point-of-care user fees. The pilot model has previously demonstrated improved institutional birth rate, antenatal care completion, and postpartum contraception utilization. Here, we performed a retrospective costing analysis from July 16, 2017 to July 15, 2018, in a catchment area population of 60,000. The average per capita annual cost is US$3.05 (range: US$1.94 to US$4.70 across 24 villages) of which 74% is personnel cost. Service delivery and administrative costs and per beneficiary costs for all services are also described. To address the current discourse among Nepali policy makers at the local and federal levels, we also present 3 alternative implementation scenarios that policy makers may consider. Given the Government of Nepal's commitment to increase health care spending (US$51.00 per capita) to 7.0% of the 2030 gross domestic product, paired with recent health care systems decentralization leading to expanded fiscal space in municipalities, this CHW program provides a feasible opportunity to make progress toward achieving universal health coverage and the health-related SDGs. This costing analysis offers insights and practical considerations for policy makers and locally elected officials for deploying a CHW cadre as a mechanism to achieve the SDG targets.

Published
2020

21. Mapping disparities in education across low- and middle-income countries

Author

Graetz, Nicholas, Woyczynski, Lauren, Wilson, Katherine F, Hall, Jason B, Abate, Kalkidan Hassen, Abd-Allah, Foad, Adebayo, Oladimeji M, Adekanmbi, Victor, Afshari, Mahdi, Ajumobi, Olufemi, Akinyemiju, Tomi, Alahdab, Fares, Al-Aly, Ziyad, Alcalde Rabanal, Jacqueline Elizabeth, Alijanzadeh, Mehran, Alipour, Vahid, Altirkawi, Khalid, Amiresmaili, Mohammadreza, Anber, Nahla Hamed, Andrei, Catalina Liliana, Anjomshoa, Mina, Antonio, Carl Abelardo T, Arabloo, Jalal, Aremu, Olatunde, Aryal, Krishna K, Asadi-Aliabadi, Mehran, Atique, Suleman, Ausloos, Marcel, Awasthi, Ashish, Ayala Quintanilla, Beatriz Paulina, Azari, Samad, Badawi, Alaa, Banoub, Joseph Adel Mattar, Barker-Collo, Suzanne Lyn, Barnett, Anthony, Bedi, Neeraj, Bennett, Derrick A, Bhattacharjee, Natalia V, Bhattacharyya, Krittika, Bhattarai, Suraj, Bhutta, Zulfiqar A, Bijani, Ali, Bikbov, Boris, Britton, Gabrielle, Burstein, Roy, Butt, Zahid A, Cardenas, Rosario, Carvalho, Felix, Castaneda-Orjuela, Carlos A, Castro, Franz, Cerin, Ester, Chang, Jung-Chen, Collison, Michael L, Cooper, Cyrus, Cork, Michael A, Daoud, Farah, Das Gupta, Rajat, Weaver, Nicole Davis, De Neve, Jan-Walter, Deribe, Kebede, Desalegn, Beruk Berhanu, Deshpande, Aniruddha, Desta, Melaku, Dhimal, Meghnath, Diaz, Daniel, Dinberu, Mesfin Tadese, Djalalinia, Shirin, Dubey, Manisha, Dubljanin, Eleonora, Duraes, Andre R, Dwyer-Lindgren, Laura, Earl, Lucas, Kalan, Mohammad Ebrahimi, El-Khatib, Ziad, Eshrati, Babak, Faramarzi, Mahbobeh, Fareed, Mohammad, Faro, Andre, Fereshtehnejad, Seyed-Mohammad, Fernandes, Eduarda, Filip, Irina, Fischer, Florian, Fukumoto, Takeshi, Garcia, Jose A, Gill, Paramjit Singh, Gill, Tiffany K, Gona, Philimon N, Gopalani, Sameer Vali, Grada, Ayman, Guo, Yuming, Gupta, Rajeev, Gupta, Vipin, Haj-Mirzaian, Arvin, Haj-Mirzaian, Arya, Hamadeh, Randah R, Hamidi, Samer, Hasan, Mehedi, Hassen, Hamid Yimam, Hendrie, Delia, and Henok, Andualem

Subjects
Pediatric, Aetiology, 2.3 Psychological, social and economic factors, Good Health and Well Being, Bayes Theorem, Developing Countries, Education, Female, Health Status, Humans, Male, Socioeconomic Factors, Local Burden of Disease Educational Attainment Collaborators, General Science & Technology
Abstract

Educational attainment is an important social determinant of maternal, newborn, and child health1-3. As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting4-6. The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness7,8; however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health9-11. Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of individuals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but-to our knowledge-no analysis has examined the subnational proportions of individuals who completed specific levels of education across all low- and middle-income countries12-14. By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations.

Published
2020

22. An integrated intervention for chronic care management in rural Nepal: protocol of a type 2 hybrid effectiveness-implementation study.

Author

Schwarz, Dan, Dhungana, Santosh, Kumar, Anirudh, Acharya, Bibhav, Agrawal, Pawan, Aryal, Anu, Baum, Aaron, Choudhury, Nandini, Citrin, David, Dangal, Binod, Dhimal, Meghnath, Gauchan, Bikash, Gupta, Tula, Halliday, Scott, Karmacharya, Biraj, Kishore, Sandeep, Koirala, Bhagawan, Kshatriya, Uday, Levine, Erica, Maru, Sheela, Rimal, Pragya, Sapkota, Sabitri, Schwarz, Ryan, Shrestha, Archana, Thapa, Aradhana, and Maru, Duncan

Subjects
Humans, Chronic Disease, Alcohol Drinking, Risk Reduction Behavior, Tobacco Use Cessation, Decision Support Systems, Clinical, Allied Health Personnel, Rural Population, Disease Management, Nepal, Medication Adherence, Community Health Workers, Motivational Interviewing, Noncommunicable Diseases, Implementation Science, Chronic illness, Community health workers, Decision support systems, Motivational interviewing, Noncommunicable diseases, Rural health, Clinical Research, Clinical Trials and Supportive Activities, Health Services, Behavioral and Social Science, Prevention, Health and social care services research, 8.1 Organisation and delivery of services, Cardiovascular, Good Health and Well Being, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology, General & Internal Medicine
Abstract

BACKGROUND:In Nepal, the burden of noncommunicable, chronic diseases is rapidly rising, and disproportionately affecting low and middle-income countries. Integrated interventions are essential in strengthening primary care systems and addressing the burden of multiple comorbidities. A growing body of literature supports the involvement of frontline providers, namely mid-level practitioners and community health workers, in chronic care management. Important operational questions remain, however, around the digital, training, and supervisory structures to support the implementation of effective, affordable, and equitable chronic care management programs. METHODS:A 12-month, population-level, type 2 hybrid effectiveness-implementation study will be conducted in rural Nepal to evaluate an integrated noncommunicable disease care management intervention within Nepal's new municipal governance structure. The intervention will leverage the government's planned roll-out of the World Health Organization's Package of Essential Noncommunicable Disease Interventions (WHO-PEN) program in four municipalities in Nepal, with a study population of 80,000. The intervention will leverage both the WHO-PEN and its cardiovascular disease-specific technical guidelines (HEARTS), and will include three evidence-based components: noncommunicable disease care provision using mid-level practitioners and community health workers; digital clinical decision support tools to ensure delivery of evidence-based care; and training and digitally supported supervision of mid-level practitioners to provide motivational interviewing for modifiable risk factor optimization, with a focus on medication adherence, and tobacco and alcohol use. The study will evaluate effectiveness using a pre-post design with stepped implementation. The primary outcomes will be disease-specific, "at-goal" metrics of chronic care management; secondary outcomes will include alcohol and tobacco consumption levels. DISCUSSION:This is the first population-level, hybrid effectiveness-implementation study of an integrated chronic care management intervention in Nepal. As low and middle-income countries plan for the Sustainable Development Goals and universal health coverage, the results of this pragmatic study will offer insights into policy and programmatic design for noncommunicable disease care management in the future. TRIAL REGISTRATION:ClinicalTrials.gov, NCT04087369. Registered on 12 September 2019.

Published
2020

23. Transition to active learning in rural Nepal: an adaptable and scalable curriculum development model

Author

Mehanni, Stephen, Wong, Lena, Acharya, Bibhav, Agrawal, Pawan, Aryal, Anu, Basnet, Madhur, Citrin, David, Dangal, Binod, Deukmedjian, Grace, Dhungana, Santosh Kumar, Gauchan, Bikash, Gupta, Tula Krishna, Halliday, Scott, Kalaunee, SP, Kshatriya, Uday, Kumar, Anirudh, Maru, Duncan, Maru, Sheela, Nguyen, Viet, Paudel, Jhalak Sharma, Rimal, Pragya, Saleh, Marwa, Schwarz, Ryan, Swar, Sikhar Bahadur, Thapa, Aradhana, Tiwari, Aparna, White, Rebecca, Wu, Wan-Ju, and Schwarz, Dan

Subjects
Curriculum and Pedagogy, Education, Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Quality Education, Curriculum, Education, Medical, Continuing, Educational Measurement, Feedback, Health Services Research, Humans, Needs Assessment, Nepal, Problem-Based Learning, Program Development, Program Evaluation, Rural Health Services, Teaching, Active learning, Continuing medical education, Curriculum development, Learners as teachers, Limited resource, Rural, Public Health and Health Services, Medical Informatics, Clinical sciences, Curriculum and pedagogy, Specialist studies in education
Abstract

BackgroundTraditional medical education in much of the world has historically relied on passive learning. Although active learning has been in the medical education literature for decades, its incorporation into practice has been inconsistent. We describe and analyze the implementation of a multidisciplinary continuing medical education curriculum in a rural Nepali district hospital, for which a core objective was an organizational shift towards active learning.MethodsThe intervention occurred in a district hospital in remote Nepal, staffed primarily by mid-level providers. Before the intervention, education sessions included traditional didactics. We conducted a mixed-methods needs assessment to determine the content and educational strategies for a revised curriculum. Our goal was to develop an effective, relevant, and acceptable curriculum, which could facilitate active learning. As part of the intervention, physicians acted as both learners and teachers by creating and delivering lectures. Presenters used lecture templates to prioritize clarity, relevance, and audience engagement, including discussion questions and clinical cases. Two 6-month curricular cycles were completed during the study period. Daily lecture evaluations assessed ease of understanding, relevance, clinical practice change, and participation. Periodic lecture audits recorded learner talk-time, the proportion of lecture time during which learners were talking, as a surrogate for active learning. Feedback from evaluation and audit results was provided to presenters, and pre- and post-curriculum knowledge assessment exams were conducted.ResultsLecture audits showed a significant increase in learner talk-time, from 14% at baseline to 30% between months 3-6, maintained at 31% through months 6-12. Lecture evaluations demonstrated satisfaction with the curriculum. Pre- and post-curriculum knowledge assessment scores improved from 50 to 64% (difference 13.3% ± 4.5%, p = 0.006). As an outcome for the measure of organizational change, the curriculum was replicated at an additional clinical site.ConclusionWe demonstrate that active learning can be facilitated by implementing a new educational strategy. Lecture audits proved useful for internal program improvement. The components of the intervention which are transferable to other rural settings include the use of learners as teachers, lecture templates, and provision of immediate feedback. This curricular model could be adapted to similar settings in Nepal, and globally.

Published
2019

24. 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

25. 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

26. 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

27. 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

28. 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

29. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Author

Griswold, Max G, Fullman, Nancy, Hawley, Caitlin, Arian, Nicholas, Zimsen, Stephanie RM, Tymeson, Hayley D, Venkateswaran, Vidhya, Tapp, Austin Douglas, Forouzanfar, Mohammad H, Salama, Joseph S, Abate, Kalkidan Hassen, Abate, Degu, Abay, Solomon M, Abbafati, Cristiana, Abdulkader, Rizwan Suliankatchi, Abebe, Zegeye, Aboyans, Victor, Abrar, Mohammed Mehdi, Acharya, Pawan, Adetokunboh, Olatunji O, Adhikari, Tara Ballav, Adsuar, Jose C, Afarideh, Mohsen, Agardh, Emilie Elisabet, Agarwal, Gina, Aghayan, Sargis Aghasi, Agrawal, Sutapa, Ahmed, Muktar Beshir, Akibu, Mohammed, Akinyemiju, Tomi, Akseer, Nadia, Asfoor, Deena H Al, Al-Aly, Ziyad, Alahdab, Fares, Alam, Khurshid, Albujeer, Ammar, Alene, Kefyalew Addis, Ali, Raghib, Ali, Syed Danish, Alijanzadeh, Mehran, Aljunid, Syed Mohamed, Alkerwi, Ala'a, Allebeck, Peter, Alvis-Guzman, Nelson, Amare, Azmeraw T, Aminde, Leopold N, Ammar, Walid, Amoako, Yaw Ampem, Amul, Gianna Gayle Herrera, Andrei, Catalina Liliana, Angus, Colin, Ansha, Mustafa Geleto, Antonio, Carl Abelardo T, Aremu, Olatunde, Ärnlöv, Johan, Artaman, Al, Aryal, Krishna K, Assadi, Reza, Ausloos, Marcel, Avila-Burgos, Leticia, Avokpaho, Euripide F, Awasthi, Ashish, Ayele, Henok Tadesse, Ayer, Rakesh, Ayuk, Tambe B, Azzopardi, Peter S, Badali, Hamid, Badawi, Alaa, Banach, Maciej, Barker-Collo, Suzanne Lyn, Barrero, Lope H, Basaleem, Huda, Baye, Estifanos, Bazargan-Hejazi, Shahrzad, Bedi, Neeraj, Béjot, Yannick, Belachew, Abate Bekele, Belay, Saba Abraham, Bennett, Derrick A, Bensenor, Isabela M, Bernabe, Eduardo, Bernstein, Robert S, Beyene, Addisu Shunu, Beyranvand, Tina, Bhaumik, Soumyadeeep, Bhutta, Zulfiqar A, Biadgo, Belete, Bijani, Ali, Bililign, Nigus, Birlik, Sait Mentes, Birungi, Charles, Bizuneh, Hailemichael, Bjerregaard, Peter, Bjørge, Tone, Borges, Guilherme, Bosetti, Cristina, Boufous, Soufiane, Bragazzi, Nicola Luigi, Brenner, Hermann, and Butt, Zahid A

Subjects
Epidemiology, Public Health, Health Sciences, Alcoholism, Alcohol Use and Health, Substance Misuse, Women's Health, Behavioral and Social Science, Aging, Prevention, 2.4 Surveillance and distribution, Cancer, Stroke, Oral and gastrointestinal, Good Health and Well Being, Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Alcohol Drinking, Cause of Death, Commerce, Female, Global Burden of Disease, Global Health, Humans, Male, Middle Aged, Observational Studies as Topic, Population Surveillance, Prevalence, Prospective Studies, Quality-Adjusted Life Years, Retrospective Studies, Risk Assessment, Risk Factors, Sex Distribution, Young Adult, GBD 2016 Alcohol Collaborators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundAlcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.MethodsUsing 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.FindingsGlobally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2·2% (95% uncertainty interval [UI] 1·5-3·0) of age-standardised female deaths and 6·8% (5·8-8·0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3·8% (95% UI 3·2-4·3) of female deaths and 12·2% (10·8-13·6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2·3% (95% UI 2·0-2·6) and male attributable DALYs were 8·9% (7·8-9·9). The three leading causes of attributable deaths in this age group were tuberculosis (1·4% [95% UI 1·0-1·7] of total deaths), road injuries (1·2% [0·7-1·9]), and self-harm (1·1% [0·6-1·5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27·1% (95% UI 21·2-33·3) of total alcohol-attributable female deaths and 18·9% (15·3-22·6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0-0·8) standard drinks per week.InterpretationAlcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.FundingBill & Melinda Gates Foundation.

Published
2018

30. 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

31. Accuracy, repeatability, and interplatform reproducibility of T1 quantification methods used for DCE‐MRI: Results from a multicenter phantom study

Author

Bane, Octavia, Hectors, Stefanie J, Wagner, Mathilde, Arlinghaus, Lori L, Aryal, Madhava P, Cao, Yue, Chenevert, Thomas L, Fennessy, Fiona, Huang, Wei, Hylton, Nola M, Kalpathy‐Cramer, Jayashree, Keenan, Kathryn E, Malyarenko, Dariya I, Mulkern, Robert V, Newitt, David C, Russek, Stephen E, Stupic, Karl F, Tudorica, Alina, Wilmes, Lisa J, Yankeelov, Thomas E, Yen, Yi‐Fei, Boss, Michael A, and Taouli, Bachir

Subjects
Engineering, Biomedical Engineering, Patient Safety, Biomedical Imaging, Brain, Breast, Contrast Media, Female, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Neoplasms, Phantoms, Imaging, Prostate, Reproducibility of Results, Signal Processing, Computer-Assisted, T-1 mapping, DCE-MRI, phantom, multicenter, T1 mapping, Nuclear Medicine & Medical Imaging, Biomedical engineering
Abstract

PurposeTo determine the in vitro accuracy, test-retest repeatability, and interplatform reproducibility of T1 quantification protocols used for dynamic contrast-enhanced MRI at 1.5 and 3 T.MethodsA T1 phantom with 14 samples was imaged at eight centers with a common inversion-recovery spin-echo (IR-SE) protocol and a variable flip angle (VFA) protocol using seven flip angles, as well as site-specific protocols (VFA with different flip angles, variable repetition time, proton density, and Look-Locker inversion recovery). Factors influencing the accuracy (deviation from reference NMR T1 measurements) and repeatability were assessed using general linear mixed models. Interplatform reproducibility was assessed using coefficients of variation.ResultsFor the common IR-SE protocol, accuracy (median error across platforms = 1.4-5.5%) was influenced predominantly by T1 sample (P

Published
2018

32. Palmitic Acid Hydroxystearic Acids Activate GPR40, Which Is Involved in Their Beneficial Effects on Glucose Homeostasis

Author

Syed, Ismail, Lee, Jennifer, Moraes-Vieira, Pedro M, Donaldson, Cynthia J, Sontheimer, Alexandra, Aryal, Pratik, Wellenstein, Kerry, Kolar, Matthew J, Nelson, Andrew T, Siegel, Dionicio, Mokrosinski, Jacek, Farooqi, I Sadaf, Zhao, Juan Juan, Yore, Mark M, Peroni, Odile D, Saghatelian, Alan, and Kahn, Barbara B

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Diabetes, Obesity, Nutrition, Underpinning research, 1.1 Normal biological development and functioning, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Metabolic and endocrine, Adiposity, Animals, Eating, Glucose, HEK293 Cells, Homeostasis, Humans, Inflammation, Insulin Resistance, Mice, Inbred C57BL, Palmitic Acid, Receptors, G-Protein-Coupled, Stearic Acids, FAHFA, GLP-1 receptor, GPR40, glucose-insulin homeostasis, human islets, insulin secretion, palmitic acid hydroxystearic acid, type 2 diabetes, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism, Biochemistry and cell biology, Medical biochemistry and metabolomics
Abstract

Palmitic acid hydroxystearic acids (PAHSAs) are endogenous lipids with anti-diabetic and anti-inflammatory effects. PAHSA levels are reduced in serum and adipose tissue of insulin-resistant people and high-fat diet (HFD)-fed mice. Here, we investigated whether chronic PAHSA treatment enhances insulin sensitivity and which receptors mediate PAHSA effects. Chronic PAHSA administration in chow- and HFD-fed mice raises serum and tissue PAHSA levels ∼1.4- to 3-fold. This improves insulin sensitivity and glucose tolerance without altering body weight. PAHSA administration in chow-fed, but not HFD-fed, mice augments insulin and glucagon-like peptide (GLP-1) secretion. PAHSAs are selective agonists for GPR40, increasing Ca+2 flux, but not intracellular cyclic AMP. Blocking GPR40 reverses improvements in glucose tolerance and insulin sensitivity in PAHSA-treated chow- and HFD-fed mice and directly inhibits PAHSA augmentation of glucose-stimulated insulin secretion in human islets. In contrast, GLP-1 receptor blockade in PAHSA-treated chow-fed mice reduces PAHSA effects on glucose tolerance, but not on insulin sensitivity. Thus, PAHSAs activate GPR40, which is involved in their beneficial metabolic effects.

Published
2018

33. Drug Delivery Nanoparticles with Locally Tunable Toxicity Made Entirely from a Light-Activatable Prodrug of Doxorubicin

Author

Schutt, Carolyn, Ibsen, Stuart, Zahavy, Eran, Aryal, Santosh, Kuo, Stacey, Esener, Selin, Berns, Michael, and Esener, Sadik

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Rare Diseases, Nanotechnology, Bioengineering, Orphan Drug, Biotechnology, Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, A549 Cells, Antineoplastic Agents, Biotin, Cell Line, Tumor, Doxorubicin, Drug Carriers, Drug Liberation, Humans, Hydrogen-Ion Concentration, Light, Nanoparticles, Particle Size, Polyethylene Glycols, Prodrugs, Surface Properties, DNA intercalation, Light-activatable, Nanoparticle drug delivery vehicle, Prodrug, Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

PurposeA major challenge facing nanoparticle-based delivery of chemotherapy agents is the natural and unavoidable accumulation of these particles in healthy tissue resulting in local toxicity and dose-limiting side effects. To address this issue, we have designed and characterized a new prodrug nanoparticle with controllable toxicity allowing a locally-delivered light trigger to convert the payload of the particle from a low to a high toxicity state.MethodsThe nanoparticles are created entirely from light-activatable prodrug molecules using a nanoprecipitation process. The prodrug is a conjugate of doxorubicin and photocleavable biotin (DOX-PCB).ResultsThese DOX-PCB nanoparticles are 30 times less toxic to cells than doxorubicin, but can be activated to release pure therapeutic doxorubicin when exposed to 365 nm light. These nanoparticles have an average diameter of around 100 nm and achieve the maximum possible prodrug loading capacity since no support structure or coating is required to prevent loss of prodrug from the nanoparticle.ConclusionsThese light activatable nanoparticles demonstrate tunable toxicity and can be used to facilitate future therapy development whereby light delivered specifically to the tumor tissue would locally convert the nanoparticles to doxorubicin while leaving nanoparticles accumulated in healthy tissue in the less toxic prodrug form.

Published
2017

34. 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

35. 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, Burden of Illness, Social Determinants of Health, Clinical Research, Behavioral and Social Science, Prevention, 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

36. 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

37. 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

38. 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, Aging, Brain Disorders, Burden of Illness, Women's Health, Mental Health, Behavioral and Social Science, Neurosciences, 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

39. Structure-based discovery of opioid analgesics with reduced side effects

Author

Manglik, Aashish, Lin, Henry, Aryal, Dipendra K, McCorvy, John D, Dengler, Daniela, Corder, Gregory, Levit, Anat, Kling, Ralf C, Bernat, Viachaslau, Hübner, Harald, Huang, Xi-Ping, Sassano, Maria F, Giguère, Patrick M, Löber, Stefan, Da Duan, Scherrer, Grégory, Kobilka, Brian K, Gmeiner, Peter, Roth, Bryan L, and Shoichet, Brian K

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Pain Research, Opioids, Brain Disorders, Neurosciences, Drug Abuse (NIDA only), Opioid Misuse and Addiction, Chronic Pain, Substance Misuse, Lung, 5.1 Pharmaceuticals, Good Health and Well Being, Analgesia, Analgesics, Opioid, Animals, Drug Discovery, GTP-Binding Protein alpha Subunits, Gi-Go, HEK293 Cells, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Molecular Docking Simulation, Pain, Receptors, Opioid, mu, Spiro Compounds, Structure-Activity Relationship, Thiophenes, Urea, General Science & Technology
Abstract

Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids-which include fatal respiratory depression-are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21-a potent Gi activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle μOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids.

Published
2016

40. Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY)

Author

Obbina Abani, Ali Abbas, Fatima Abbas, Joshua Abbas, Kasim Abbas, Mustafa Abbas, Sadia Abbasi, Hakam Abbass, Alfie Abbott, Alison Abbott, Nabeel Abdallah, Ammar Abdelaziz, Ashraf Abdelaziz, Mohamed Abdelfattah, Bushra Abdelqader, Audrey Abdul, Basir Abdul, Siddiqui Abdul, Althaf Abdul Rasheed, Ajibode Abdulakeem, Rezan Abdul-Kadir, Abdullah Abdullah, Abdulfatahi Abdulmumeen, Rasheed Abdul-Raheem, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer Abeer Ul Amna, Lynn Abel, Katrina Abernethy, Movin Abeywickrema, Chandra Abhinaya, Affyarsyah Abidin, Adebanke Aboaba, Abigail Aboagye-Odei, Christopher Aboah, Heba Aboelela, Hani Abo-Leyah, Karim Abouelela, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Ahmed Abousamra, Mona Abouzaid, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Rebecca Abrams, Hyacinth-John Abu, Ahmed Abu-Arafeh, Syed M Abubacker, Akata Abung, Yousuf Abusamra, Yaa Aceampong, Amaka Achara, Devikumar Acharya, Faustina Acheampong, Prince Acheampong, Sarah Acheampong, Janet Acheson, Shiella Achieng, Andres Acosta, Rebecca Acquah, Catherine Acton, Jacqueline Adabie-Ankrah, Paul Adair, Fiona Adam, Matthew Adam, Huzaifa Adamali, Marta Adamczyk, Carol Adams, Charlotte Adams, Daniel Adams, Kate Adams, Laura Adams, Nikkita Adams, Richard Adams, Tim Adams, Laura Adamu-Ikeme, Krishma Adatia, Kirsty Adcock, Lawrence Addai-Boampong, Afua Addo, Oluwatobi Adeagbo, Ade Adebiyi, Ogunlana Adedeji, Yewande Adegeye, Ken Adegoke, Vicki Adell, Sherna Adenwalla, Femi W Adeoye, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Adedamola Adeyanju, Joyce Adeyemi, Tenifayo Adeyemo, Binay Adhikari, Shanti A Adhikari, Rina Adhikary, Adhikarla Aditya, Patience Adjepong, Gabrielle Adkins, Adnan Adnan, Marguerite Adriaanse, John Aeron-Thomas, Debbie Affleck, Carmel Afnan, Muhammad Afridi, Patricia Afrim, Felicia Akua Afriyie, Zainab A Aftab, Meenakshi Agarwal, Rachel Agbeko, Chris Agbo, Sunil Aggarwal, Arameh Aghababaie, Laura Aguilar Jimenez, Jacqueline Afrakomah Agyekum, Kwame Agyen, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Mohammad Ahmad, Syed Ahmad, Afshan Ahmed, Ashar Ahmed, Asim Ahmed, Basheer A R Ahmed, Bilal Ahmed, Forizuddin Ahmed, Hamze Ahmed, Hanad Ahmed, Irshad Ahmed, Khaled Ahmed, Khalil Ahmed, Liban Ahmed, Mahin Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rawya Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sana G Ahmed, Syed Ahmed, Syed H Ahmed, Roa Ahmed Ali, Bilal Ahmed Mohamud, Sana Ahmed, Sana Ahmer, Augustine Ahonia, Christine Aiken, Dhiraj Ail, Mark Ainsworth, Myriam Aissa, Lindianne Aitken, Bini Ajay, Abdulakeem Ajibode, Ayesha Ajmi, Nasim Akhtar, Nauman Akhtar, Suha Akili, Bolutito Akinbiyi, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Mohammad Akram, Olugbenro Aktinade, Uzayr Akudi, Ahmad S A R Al Aaraj, Asma Al Balushi, Majd Al Dakhola, Aladdin Al Swaifi, Eslam Al-Abadi, Adegoke Alabi, Narendra Aladangady, Mohamed Alafifi, Ayaz Alam, Sajid Alam, Abbas Al-Asadi, Kyriaki Alatzoglou, Paul Albert, Albertus Albertus, Lorraine Albon, Angela Alcala, Gemma Alcorn, Stephen Alcorn, Aggie Aldana, David Alderdice, Abdullah Aldesouki, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ram Maya Ale, Ana Alegria, Alison Alexander, Courtney Alexander, John Alexander, Peter D G Alexander, Julyan Al-fori, Laith Alghazawi, Osama Alhabsha, Bahij Al-Hakim, Rafil Alhameed, Mohammed Al-Hayali, Shams Al-Hity, Ali Ali, Amanda Ali, Asad Ali, Fawzia R Ali, Jawad Ali, Mariam Ali, Mohamed Ali, Mohammad Ali, Muhammad S Ali, Nayab Ali, Oudai Ali, Ramla Ali, Sakina Ali, Syed Ali, Emilio Aliberti, Jade Alin, Abid Alina, Analyn Alipustain, Bachti Alisjahbana, Fine Aliyuda, Katrin Alizadeh, Maithem Al-Jibury, Saba Al-Juboori, Majid Al-Khalil, Abdullah Alkhudhayri, Moutaz Alkhusheh, Fiona Allan, Nataliya Allan, Alison Allanson, Robert Allcock, Eireann Allen, Jade Allen, Kerry Allen, Louise Allen, Poppy Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Tania Allen, Abiola Alli, Kathryn Allison, Bethan Allman, Helen K Allsop, Lynne Allsop, David Allsup, Amal F T Almahroos, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Riyam Al-Sammarraie, Inji Alshaer, Rustam Al-Shahi Salman, Warkaq Al-Shamkhani, Fadia Alsheikh, Bashar Al-Sheklly, Sara Altaf, Amanda Alty, Mary Alvarez, Maria Alvarez Corral, Edward Alveyn, Maysaa Alzetani, Susan Amamou, Noor Amar, Sakkarai Ambalavanan, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Amel Amelia Ganefianty, Katharine Ames, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Syed Amin, Tara Amin, Badshah Amit, Amjad Amjad, Neelma Amjad, James Amoah-Dankwa, Victoria Amosun, Muhammad Amsal, Khaled Amsha, John Amuasi, Noelia Amutio Martin, Pugh Amy, Ann Anada, Atul Anand, Samantha Anandappa, Satya D Anantapatnaikuni, Ellen Anderson, Julie Anderson, Laura Anderson, Marina Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rebecca Anderson, Rory Anderson, Samantha Anderson, Wendy Anderson, Prematie Andreou, Angela Andrews, Antonette Andrews, Jill Andrews, Joyann Andrews, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Aramburo Angela, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Jessica Annett, Louise Anning, Maldwyn Ansah, Patrick J Anstey, Rebekah Anstey, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, Elena Apetri, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Maia F Aquino, Bianca Araba, Samuel Aransiola, Mariana Araujo, Ann Archer, Denise Archer, Samuel Archer, Simon Archer, Daniele Arcoria, Christian Ardley, Ana-Maria Arias, Oluwatoyin Aribike, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Jennifer Armistead, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Wendy Armstrong, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Andrew Arnott, Dhawal Arora, Kavan Arora, Pardeep Arora, Rishi Arora, Arslam Arter, Armena Arumaithurai, Ayush Arya, Rita Arya, Diptesh Aryal, Denisa Asandei, Adeeba Asghar, Malik Asghar, Arif Ashab, Catherine Ashbrook-Raby, Helen Ashby, Jan Ashcroft, John Ashcroft, Samuel Ashcroft, Georgia Asher, Zakariya Ashfak, Ayesha Ashfaq, Abdul Ashish, Dawn Ashley, Sally Ashman-Flavell, Sundar Ashok, Abd-El-Aziz Ashour, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Fiona J Ashworth, Rebecca Ashworth, Arshia Aslam, I Aslam, Suhail Aslam, Laura Aslett, Harshini Asogan, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Deborah Athorne, Billie Atkins, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Abolaji Atomode, Brygitta Atraskiewicz, Abdul A Attia, Eva Attubato, Marie Attwood, Paula Aubrey, Zoltan Auer, Avinash Aujayeb, Aye Chan Thar Aung, Hnin Aung, Hnin Wint Wint Aung, Ko Ko Aung, Kyaw Thu Aung, Nwe Aung, Yin Aung, Zaw Myo Aung, Emily Austin, Karen Austin, Abdusshakur Auwal, Malcolm Avari, Miriam Avery, Nicholas Aveyard, Joanne Avis, Georgina Aviss, Cristina Avram, Paula Avram, Abuzar Awadelkareem, Gabriel Awadzi, Mahmoud Awaly, Atia Awan, Aszad Aya, Eman Ayaz, John Maximilian Ayerh, Amanda Ayers, Jawwad Azam, Ahmed Azeem, Mohammed Azharuddin, Ammar Aziz, Ghazala Aziz, Imran Aziz, N Aziz, Ali Azkoul, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Marta Babores, Adetona O Babs-Osibodu, Sammy Bacciarelli, Roudi Bachar, Michel-Elie Bachour, Alisjahbana Bachti, Gina Bacon, Jenny Bacon, Bibi Badal, Aysha Badat, Maryuma Bader, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph P Bae, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Lynsey Bagshaw, Kasra Bahadori, Angela Bailey, James Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Lucy Bailey, Maria A Bailey, Morgan Bailey, Pippa Bailey, Sarah Bailey, Hamish Baillie, J Kenneth Baillie, Jennifer Bain, Vikram Bains, David Baird, Eilidh Baird, Kevin Baird, Susan Baird, Tracy Baird, Yolanda Baird, Aiysha Bajandouh, Danielle C Baker, Evelyn Baker, Johanne Baker, Josephine Baker, Kenneth Baker, Mark Baker, Rebecca Baker, Terri-Anne Baker, Victoria Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Ameet Bakhai, Nauman Bakhtiar, Panos Bakoulas, Dhanalakshmi Bakthavatsalam, Niranjan Balachandran, Andrea Balan, Prasath Balasingam, Theodosios Balaskas, Madhu Balasubramaniam, Nicola Balatoni, Alison Balcombe, Alexander Baldwin, Ashley Baldwin, Caron Baldwin, Danielle Baldwin, Fiona Baldwin, Rebekah Baldwin-Jones, Nichola Bale, James Balfour, Matthew Ball, Robert Ball, K Ballard, Ismael Balluz, Craig Balmforth, Emese Balogh, Abeir Baltmr, Amir Baluwala, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Elizabeth Bancroft, Hollie Bancroft, Joyce Banda, Krishna Bandaru, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Amit Banerjee, Ritwik Banerjee, Santosh Baniya, Omar Bani-Saad, Harrison Banks, Luke Banks, Paul Banks, Claudia Bann, Helen Bannister, Oliver Bannister, Laura Banton, Tran Bao, Mariamma Baptist, Tanya Baqai, Ananya M Baral, Sharad Chandra Baral, Desislava Baramova, Russel Barber, Emma Barbon, Monica Barbosa, Jamie Barbour, Alexander Barclay, Amanda Barclay, Claire Barclay, George Bardsley, Stephanie Bareford, Shahedal Bari, Morris Barimbing, Amy Barker, Debbie Barker, Erandi Barker, Helen Barker, Joseph Barker, Leon Barker, Lesley Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, Valerie Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Rory Barnes, Theresa Barnes, Calum Barnetson, Amy Barnett, Ashton Barnett-Vanes, Prince Gyenti Barning, William Barnsley, Andrew Barr, David Barr, James Barr, Charlotte Barr, Nina Barratt, Shaney Barratt, Manuella Barrera, Amy Barrett, Fiona Barrett, Jessica Barrett, Sue Barrett, Esther Barrow, Jazz Bartholomew, Claire Bartlett, Georgina Bartlett, James Bartlett, Louise Bartlett, Shauna Bartley, Sandra Bartolmeu-Pires, Anna Barton, Greg Barton, Jill Barton, Lorna Barton, Rachael Barton, Rosaleen Baruah, Sonia Baryschpolec, Hannah Bashir, Archana Bashyal, Betsy Basker, Sudha Basnet, Buddha Basnyat, Ayten Basoglu, Alexander Basran, John Bassett, G Bassett, Chris Bassford, Bengisu Bassoy, Victoria Bastion, Anup Bastola, Anupam Basumatary, Precious Basvi, Jireh A Batac, Vipula R Bataduwaarachchi, Tristan Bate, Harry J Bateman, Kathryn Bateman, Vhairi Bateman, Eleanor Bates, Hayley Bates, Michelle Bates, Simon Bates, Sally Batham, Ana Batista, Amit Batla, Dushyant Batra, Harry Batty, Thomas Batty, Alice Batty, Miranda Baum, Rachel Baumber, Carina Bautista, Fareha Bawa, Tanveer Bawa, Fatima S Bawani, Simon Bax, Matt Baxter, Nicola Baxter, Zachary Baxter, Hannah Bayes, Lee-Ann Bayo, Farid Bazari, Rohit Bazaz, Ahmad Bazli, Laura Beacham, Wendy Beadles, Kirsten Beadon, Philip Beak, Andy Beale, Kathy Beard, Jack Bearpark, Alanna Beasley, Sandee Beattie, Karen Beaumont, Dawn Beaumont-Jewell, Theresa Beaver, Sarah Beavis, Christy Beazley, Sarah Beck, Virginia Beckett, Rosie Beckitt, Sarah Beckley, Heidi Beddall, Seonaid Beddows, Deborah Beeby, Sophia Beeby, Gail Beech, Michelle Beecroft, Nigel Beer, Sally Beer, Jane Beety, Gabriela Bega, Alison Begg, Susan Begg, Sara Beghini, Ayesha Begum, Salman Begum, Selina Begum, Teresa Behan, Roya Behrouzi, Jon Beishon, Claire Beith, James Belcher, Holly Belfield, Katherine Belfield, Ajay Belgaumkar, Dina Bell, Gareth Bell, Gillian Bell, Jessica Bell, Lauren Bell, Louise Bell, Nicholas Bell, Pippa Bell, Stephanie Bell, Jennifer Bellamu, Mary Bellamy, Tammy Bellamy, Arianna Bellini, Amanda Bellis, Fionn Bellis, Lesley Bendall, Naveena Benesh, Nicola Benetti, Leonie Benham, Guy Benison-Horner, Sarah Benkenstein, Tracey Benn, Ann Bennett, Caroline Bennett, Denise Bennett, Gillian Bennett, Kaytie Bennett, Kristopher Bennett, Lorraine Bennett, Miriam R Bennett, Sara Bennett, Karen Bennion, Gautham Benoy, Vivienne Benson, Andrew Bentley, James Bentley, Ian Benton, Eva Beranova, Matthew Beresford, Colin Bergin, Malin Bergstrom, Jolanta Bernatoniene, Thomas Berriman, Zoe Berry, Frida Best, Kimberley Best, Ans-Mari Bester, Yvonne Beuvink, Emily Bevan, Sarah Bevins, Tom Bewick, Andrew Bexley, Sonay Beyatli, Fenella Beynon, Arjun Bhadi, Sanjay Bhagani, Shiv Bhakta, Rekha Bhalla, Khushpreet Bhandal, Kulbinder Bhandal, Ashwin Bhandari, Lila Nath Bhandari, Sangam Bhandari, Jennifer Bhanich Supapol, Aashutosh Bhanot, Ravina Bhanot, Swati Bhasin, Abdul Bhat, Prashanth Bhat, Rahul Bhatnagar, Karan Bhatt, Janki Bhayani, Deepika Bhojwani, Parminder Bhuie, M S Bhuiyan, Salimuzzaman Bhuiyan, Anna Bibby, Fatima Bibi, Naheeda Bibi, Salma Bibi, Tihana Bicanic, Sarah Bidgood, Julie Bigg, Sarah Biggs, Alphonsa Biju, Andras Bikov, Sophie Billingham, Jessica Billings, Prof Binh, Alice Binns, Muhammad BinRofaie, Oliver Bintcliffe, Catherine Birch, Janine Birch, Jenny Birch, Katherine Birchall, Sam Bird, Sumedha Bird, Sarah Bird, Mark Birt, Claire Bishop, Kilanalei Bishop, Linda Bishop, Lisa Bishop, Karen Bisnauthsing, Nibedan Biswas, Mustapha Bittaye, Sahar Biuk, Karen Blachford, Ethel Black, Helen Black, Karen Black, Mairead Black, Polly Black, Virginia Black, Hayley Blackgrove, Bethan Blackledge, Joanne Blackler, Samantha Blackley, Helen Blackman, Caroline Blackstock, Cameron Blair, Francesca Blakemore, Helen Blamey, Alison Bland, Sujata Blane, Simon Blankley, Parry Blaxill, Katie Blaylock, Jane Blazeby, Natalie Blencowe, Ben Bloom, Jack Bloomfield, Angela Bloss, Alex Blowers, Samuel Blows, Hannah Bloxham, Susan Blrd, Louise Blundell, Andrew Blunsum, Mark Blunt, Tadhg Blunt, Ian Blyth, Kevin Blyth, Andrew Blythe, Karen Blythe, Kwabena Appiah Boahen, Marilyn Boampoaa, Sarah Board, Boniface Bobie, Karen Bobruk, Pritesh N Bodalia, Neena Bodasing, Marianne Boden, Tanya Bodenham, Gabriele Boehmer, Marta Boffito, Katherine Bohanan, Kristyna Bohmova, Niamh Bohnacker, Sumit Bokhandi, Maria Bokhar, Saba Bokhari, Sakina Bokhari, Syed O Bokhari, Idan Bokobza, Ambrose Boles, Clare Bolger, Candice Bonaconsa, Charlotte Bond, Helena Bond, Stuart Bond, Thomas Bond, Alice Bone, Georgia Boniface, Joseph Bonney, Lizzy Bonney, Lauren Booker, Sarah Boot, Matthew Boothroyd, Joanne Borbone, Naomi Borman, Samantha Bosence, Kirsty Bostock, Neil Botting, Fiona Bottrill, Hannah Bouattia, Laura Bough, Hayley Boughton, Zoe Boult, Tarek Boumrah, Miriam Bourke, Stephen Bourke, Michelle Bourne, Rachel Bousfield, Lucy Boustred, Alexandra Bowes, Amy Bowes, Philip Bowker, Tabitha Bowker, Helen Bowler, Louise Bowman, Simon Bowman, Rachel Bowmer, Angie Bowring, Helen Bowyer, Aileen Boyd, Jenny Boyd, Laura Boyd, Nicola Boyer, Namoi Boyle, Pauline Boyle, Rosalind Boyle, Louise Boyles, Leanna Brace, Abbey Bracken, Jodie Bradder, Clare J Bradley, Pamela Bradley, Patrick Bradley, Paul Bradley, Joanne Bradley-Potts, Lynne Bradshaw, Zena Bradshaw, Clare Brady, Rebecca Brady, Shirin Brady, Pedro Braga Sardo, Denise Braganza, Megan Braithwaite, Susan Brammer, Marie Branch, Thomas Brankin-Frisby, Jamie Brannigan, Sophie Brattan, Fiona Bray, Nancy Bray, Manny Brazil, Lucy Brear, Tracy Brear, Stephen Brearey, Laura Bremner, Morwenna Brend, Carolin Bresges, Catherine Bressington, Giovanna Bretland, Chris Brewer, Michael Bridgett, Gavin Bridgwood, Sara Brigham, John Bright, Christopher Brightling, Tracey Brigstock, Lutece Brimfield, Philip Brinksman, Elaine Brinkworth, Robin Brittain-Long, Vianne Britten, Hannah Britton, Lauren Broad, Sarah Broadhead, Rosie Broadhurst, Andrew Broadley, Marie Broadway, Christopher Brockelsby, Megan Brocken, Tomos Brockley, Mary Brodsky, Fiona Brogan, Liz Brohan, Felicity Brokke, Jacob Brolly, David Bromley, Hannah Brooke-Ball, Verity Brooker, Matthew Brookes, Deirdre Brooking, Alison Brooks, Daniel Brooks, Jolene Brooks, Karen Brooks, Nicole Brooks, Philip Brooks, Rachel Brooks, Samuel Brooks, Sophie Brooks, Malcolm Broom, Natalie Broomhead, Chloe Broughton, Nathaniel Broughton, Matt Brouns, Alison Brown, Ammani Brown, Andrew Brown, Ashley Brown, Caitlin Brown, Carly Brown, Catrin Brown, Ellen Brown, Heather Brown, Janet Brown, Jo Brown, Louise Brown, Niall Brown, Nicola Brown, Pauline Brown, Richard Brown, Robert Brown, Steven Brown, Tom Brown, Bria Browne, Charlotte Browne, Duncan Browne, Mitchell Browne, Stephen Brownlee, Alba Brraka, Johanna Bruce, Michelle Bruce, Wojciech Brudlo, Andrei Brunchi, Nigel Brunskill, Alan Brunton, Margaret Brunton, Meera Bryant, Emma Bryden, Hannah Brzezicki, April Buazon, Maya H Buch, Ruaridh Buchan, Ruaridh Buchanan, Danielle Buche, Amanda Buck, Lisa Buck, Matthew Buckland, Clare Buckley, Laura Buckley, Philip Buckley, Sarah Buckley, Carol Buckman, Alex Budds, George Bugg, Ramadan Bujazia, Marwan Bukhari, Shanze Bukhari, Richard Bulbulia, Alex Bull, Damian Bull, Kate Bull, Rhian Bull, Thomas Bull, Emily Bullock, Susan Bullock, Naomi Bulteel, Kasun Bumunarachchi, Roneleeh Bungue-Tuble, Oliver Burbidge, Caroline Burchett, Dorota Burda, Christy Burden, Thomas G Burden, Mika Burgess, Richard Burgess, Sophia Burgess, Erlina Burhan, Hasan Burhan, Hannah Burke, Kerry Burke, Adrian Burman, Sara Burnard, Caroline Burnett, Sharon Burnett, Amy Burns, Collette Burns, James Burns, Karen Burns, Kiki Burns, Daniel Burrage, Kate Burrows, Claire Burston, Anna Burton, Ben Burton, Fiona Burton, Helen Burton, Matthew Burton, Mannaria Butar butar, Deborah Butcher, Aaron Butler, Emily Butler, Jessica Butler, Joanne Butler, Joshua Butler, Peter Butler, Susan Butler, Jenny Butler, Al-Tahoor Butt, Massawer Butt, Mohammad M Butt, Caryl Butterworth, Nicola Butterworth-Cowin, Robert Buttery, Tom Buttle, Heather Button, Daniel Buttress, Hannah Bye, Jane Byrne, Wendy Byrne, Victoria Byrne-Watts, Amanda Cabandugama, Luisa Cabrero, Simone Caddy, Ruth Cade, Anthony Cadwgan, Zhen Cahilog, Ajeng Cahyareny, Donna Cairney, James Calderwood, Darren Caldow, Emily Cale, Giorgio Calisti, Debbie Callaghan, Jennifer Callaghan, Claire Callens, Donaldson Callum, Caroline Calver, Melissa Cambell-Kelly, Tracey Camburn, David R Cameron, Eleanor Cameron, Fraser Cameron, Sheena Cameron, Christian Camm, Renee F D Cammack, Alison Campbell, Amy Campbell, Barbara Campbell, Bridget Campbell, Debbie Campbell, Helen Campbell, Hilary Campbell, Jonathan Campbell, Karen Campbell, Marion Campbell, Mark Campbell, Rachael Campbell, Robyn Campbell, Wynny Campbell, Quentin Campbell Hewson, Julie Camsooksai, Lisa Canclini, Shaula M Candido, Janie Candlish, Cielito Caneja, Alexandra Cann, Johnathon Cann, Ruby Cannan, Abigail Cannon, Emma Cannon, Michael Cannon, Petra Cannon, Vivienne Cannons, Ebnier Canonizado, Jane Cantliff, Ben Caplin, Santino Capocci, Noemi Caponi, Angelika Capp, Richard Capstick, Thomas Capstick, Catalin Caraenache, Aimee Card, Mary Cardwell, Charles Carey, Rachel Carey, Simon Carley, Ffion Carlin, Tammy Carlin, Samantha Carmichael, Margaret Carmody, Mandy Carnahan, Charlotte Caroline, Jodi Carpenter, Sharon Carr, Anna Carrasco, Zoe Carrington, Amy Carroll, Anne Carroll, Paul Carroll, Rachel Carson, Cindy Cart, Emma Carter, Jonathan Carter, Michael Carter, Natasha Carter, Paul Carter, Penny Carter, Douglas Cartwright, Jo-Anne Cartwright, Claire Carty, Lotoyah Carty, Jaime Carungcong, Charlotte Carver, Emma Carver, Rachel Carver, Susan Casey, Annie Cassells, Teresa Castiello, Gail Castle, Bridget Castles, Melanie Caswell, Ana Maria Catana, Heidi Cate, Anelise Catelan Zborowski, Susanne Cathcart, Katrina Cathie, Darwin Catibog, Christine Catley, Laura Catlow, Matthew Caudwell, Anna Cavazza, Ashleigh Cave, Luke Cave, Simon Cavinato, Frianne Cawa, Kathryn Cawley, Chloe Caws, Kay Cawthorne, Hankins Cendl, Hannah Century, Jeva Cernova, Mansur Cesay, Ed Cetti, Stephanie Chabane, Manish Chablani, Cathleen Chabo, Cyril J Chacko, David Chadwick, Julie Chadwick, Robert Chadwick, Ela Chakkarapani, Arup Chakraborty, Mallinath Chakraborty, Mollika Chakravorty, Petya Chalakova, Bimal Sharma Chalise, James Chalmers, Richard Chalmers, Georgina Chamberlain, Sarah Chamberlain, Emma Chambers, Jonathan Chambers, Lucy Chambers, Naomi Chambers, Alex Chan, Carmen Chan, Cheuk Chan, Evelyn Chan, Jay Marie Chan, Kawai Chan, Kayen Chan, Kimberley Chan, Ping Chan, Rebekah (Pui-Ching) Chan, Xin H S Chan, Chris Chandler, Heidi Chandler, Kim J Chandler, Stuart Chandler, Zoe Chandler, Sumit Chandra, Navin Chandran, Badrinathan Chandrasekaran, Yvonne Chang, Ho Quang Chanh, Grace Chaplin, Josephine Chaplin, Graeme Chapman, John Chapman, Katie Chapman, Laura Chapman, Lianne Chapman, Matthew Chapman, Polly Chapman, Timothy Chapman, Lucy Chappell, Amanda Charalambou, Bethan Charles, Dianne Charlton, Sam Charlton, Kevin Chatar, Calvin Chatha, Debra Chatterton, Ritesh Chaube, Muhammad Y N Chaudhary, Netra B Chaudhary, Iram Chaudhry, Zain Chaudhry, Nazia Chaudhuri, Muhammad Chaudhury, Anoop Chauhan, Ruchi S Chauhan, Alexander Chavasse, Nicola Chavasse, Vipal Chawla, Lindsay Cheater, James Cheaveau, Charlotte Cheeld, Michelle Cheeseman, Fang Chen, Hui Min Chen, Terence Chen, Floria Cheng, Lok Yin Cheng, Zhihang Cheng, Helen Chenoweth, Chun How Cheong, Shiney Cherian, Mary Cherrie, Helen Cheshire, Chee Kay Cheung, Elaine Cheung, Kayan Cheung, Michelle Cheung, Claire Cheyne, Swati Chhabra, Wei Ling Chia, Eric Chiang, Angela Chiapparino, Rosavic Chicano, Moses Chikungwa, Zviedzo A Chikwanha, Gemma Chilcott, Sam Chilcott, Alison Chilvers, Phillipa Chimbo, KokWai Chin, Wen Jie Chin, Rumbidzai Chineka, Amol Chingale, Ezomike Chinonso, Chloe Chin-Saad, Margaret Chirgwin, Heather Chisem, Claire Chisenga, Catherine Chisholm, Ben Chisnall, Carolyn Chiswick, Sunder Chita, Nihil Chitalia, Matthew Chiu, Laura Chiverton, Brenda Chivima, Catherine Chmiel, Soha Choi, Willy Choon Kon Yune, Meena Chopra, Michelle Chopra, Vandana Choudhary, Omur Choudhury, Sarah Choudhury, Bing-Lun Chow, Mahibbur Chowdhury, Shahid Chowdhury, Angela Chrisopoulou, Victoria Christenssen, Peter Christian, Alexander Christides, Fiona Christie, Daniel Christmas, Georgios Christoforou, Thereza Christopherson, Anna Christou, Mark Christy, Paris Chrysostomou, Yunli Chua, Dip Chudgar, Richard Chudleigh, Srikanth Chukkambotla, Michael E Chukwu, Izu Chukwulobelu, Chi Yee Chung, Elaine Church, Sara R Church, David Churchill, Nicole Cianci, Paola Cicconi, Paola Cinardo, Zdenka Cipinova, Bessie Cipriano, Sarah Clamp, Bridget Clancy, Melanie Clapham, Edel Clare, Sarbjit Clare, Andrew Clark, Charlotte Clark, Diane Clark, Emma Clark, Felicity Clark, Gabrielle Clark, James Clark, Julia Clark, Katherine Clark, Kaylea Clark, Louise Clark, Lucy Clark, Martyn Clark, Matthew Clark, Nicola Clark, Patricia Clark, Richard Clark, Thomas Clark, Tonia Clark, Zoe Clark, Alison Clarke, Andrea Clarke, Jude Clarke, Paul Clarke, Robert Clarke, Roseanne Clarke, Samantha Clarke, Sheron Clarke, Alleyna Claxton, Louis Claxton, Kate Clay, Catherine Clayton, Elizabeth Clayton, Olivia Clayton, Jill Clayton-Smith, Bethan Clearyb, Chris Cleaver, Rose Cleeton, Ian Clement, Carlota Clemente de la Torre, Jayne Clements, Suzanne Clements, Sue Clenton, Sheryl Cliff, Rachael Clifford, Sarah Clifford, Amelia Clive, Jonathan Clouston, Vincent Clubb, Samantha Clueit, Lisa Clutterbuck, Andrea Clyne, Michelle Coakley, Peter G L Coakley, Kathryn Cobain, Alexandra Cochrane, Patricia Cochrane, Laura Cockayne, Maeve Cockerell, Helen Cockerill, Shirley Cocks, Rachel Codling, Adam Coe, Samantha Coetzee, David Coey, Danielle Cohen, Jonathan Cohen, Oliver Cohen, David Cohen, Mike Cohn, Louise Coke, Olutoyin Coker, Nicholas Colbeck, Roghan Colbert, Esther Cole, Jade Cole, Joby Cole, Garry Coleman, Matt Coleman, Nick Coleman, Holly Coles, Macleod Colin, Alicia Colino-Acevedo, Julie Colley, Kathleen Collie, Alexandra Collier, Danielle Collier, Dawn Collier, Heather Collier, Terry Collingwood, Paul Collini, Emma Collins, Jaimie Collins, Joanne Collins, Kayleigh Collins, Megan Collins, Nicola Collins, Sally Collins, Vicky Collins, Andrew Collinson, Bernadette Collinson, Jennifer Collinson, Matthew Collis, Madeleine Colmar, Hayley E Colton, James Colton, Katie Colville, Carolyn Colvin, Edward Combes, David Comer, Alison Comerford, Dónal Concannon, Alison Condliffe, Robin Condliffe, Emma Connell, Lynne Connell, Natalie Connell, Karen Connelly, Gavin Connolly, Emma Connor, Antonia Conroy, Kevin Conroy, Veronica Conteh, Rory Convery, Francesca Conway, Grainne Conway, Rhiannon Conway, Robert Conway, Jo-Anna Conyngham, Amanda Cook, Amber Cook, Colette Cook, Eloise Cook, Gemma Cook, Helen Cook, Julie Cook, Martin Cook, Sarah Cook, Danielle Cooke, Graham Cooke, Hannah Cooke, Justin Cooke, Katrina Cooke, Tim Cooke, Vikki Cooke, Adele Cooper, Chris Cooper, David Cooper, Helen Cooper, Jamie Cooper, Lauren Cooper, Nick Cooper, Rowena Cooper, Samantha Cooray, Thomas Cope, Sinead Corbet, Carolyn Corbett, Ailsa Corbishley, John Corcoran, Chris Cordell, Jessica Cordle, Alasdair Corfield, John Corless, Alison Corlett, Joe Cornwell, Michael Cornwell, Diana Corogeanu, Aisling Corr, Mirella Corredera, Ruth Corrigan, P Corry, Rita Corser, Jon Cort, Denise Cosgrove, Tracey Cosier, Patricia Costa, Telma Costa, Charlie Coston, Susannah Cotgrove, Zoe Coton, Lisa-Jayne Cottam, Rhiannon Cotter, Donna Cotterill, Caroline Cotton, George Couch, Martina Coulding, Andrew Coull, David Counsell, David Counter, Cherry Coupland, Ellie Courtney, Julia Courtney, Rebecca Cousins, Amanda J Coutts, Alexander Cowan, Elena Cowan, Richard Cowan, Richard Cowell, Louise Cowen, Steve Cowman, Amanda Cowton, Ellie Cox, Emma Cox, Giles Cox, Helen Cox, Karina Cox, Miriam Cox, Karen Coy, Andrea Cradduck-Bamford, Hannah Craig, Jayne Craig, John Craig, Victoria Craig, Felicity Craighead, Matthew Cramp, Hayley Cranston, Sheetal S Crasta, Jacolene Crause, Angie Crawford, Emma Crawford, Isobel Crawford, Sarah Crawshaw, Ben Creagh-Brown, Andrew Creamer, Amanda Creaser-Myers, Joanne Cremona, Saveria Cremona, Anna Crepet, Janet Cresswell, Mark Cribb, Charles Crichton, Declan Crilly, Lauren Crisp, Nikki Crisp, Dominic Crocombe, Maria Croft, Jennifer Crooks, Harriet Crosby, Elizabeth Cross, Tim Cross, Amy Crothers, Stephen Crotty, Susan Crouch, Madeleine Crow, Amanda Crowder, Kate Crowley, Teresa Crowley, Rebecca Croysdill, Callum Cruickshank, Conor Cruickshank, Irena Cruickshank, James Cruise, Carina Cruz, Trino Cruz Cervera, Dominic Cryans, Guanguo Cui, Helen Cui, Lorraine Cullen, Gillian Cummings-Fosong, Victoria Cunliffe, Neil Cunningham, Nicola Cunningham, Jason Cupitt, Hollie Curgenven, Gerens Curnow, David Curran, Simon Curran, Craig Currie, Jacqueline Currie, Scarlett Currie, Susan Currie, Susie Currie, Jonathan Curtis, Katrina Curtis, Matthew Curtis, Olivia Curtis, Thomas Curtis, Rebecca Cuthbertson, Jennifer Cuthill, Sean Cutler, Sarah Cutts, Marta Czekaj, Patrycja Czylok, Shane D'Souza, Joana da Rocha, Mohammed Dafalla, Andrew Dagens, Helen Daggett, Jacqui Daglish, Sandeep Dahiya, Anne Dale, Katie Dale, Michaela Dale, Sam Dale, Susan Dale, Jolyon Dales, Umberto D'Alessandro, Helen Dalgleish, Helen Dallow, Carlo D'aloia, Dermot Dalton, Morag Dalton, Zoe Daly, Mansi Damani, Eleanor Damm, Akila Danga, Joanne Dangerfield, Amelia Daniel, Priya Daniel, Allison Daniels, Adela Dann, Kwaku Gyasi Danso, Sandra Danso-Bamfo, Quang Tung Dao, Suzanne Darby, Alex Darbyshire, Janet Darbyshire, Paul Dargan, Paul Dark, Kate Darlington, Sarah Darnell, Thomas Darton, Guledew Darylile, Avisnata Das, Manjusha Das, Sukamal Das, Martin Daschel, Joanne Dasgin, Dibyendu Datta, Anna Daunt, Vaishali Dave, Emily Davenport, Mark Davey, Miriam Davey, Molly Davey, Mini David, Alexander Davidson, Laura Davidson, Neil Davidson, Richard Davidson, Albert Davies, Alison Davies, Amanda Davies, Amy Davies, Angela Davies, Bethan Davies, Caroline Davies, Carolyn Davies, Catrin Davies, Dawn Davies, Drew Davies, Elaine Davies, Elinor Davies, Ellie Davies, Ffyon Davies, Gwyneth Davies, Helen Davies, Jennifer Davies, Jim Davies, Karen Davies, Kelly Davies, Kim Davies, Llinos Davies, Louisa Davies, Matthew Davies, Michelle Davies, Nina Davies, Owen Davies, Patrick Davies, Rachel Davies, Rhys Davies, Ruth Davies, Sally Davies, Sarah Davies, Simon Davies, Sue Davies, Alison Davis, Julie-Ann Davis, Katherine Davis, Peter Davis, Andrea Davis-Cook, Alexander Davison, Christine Dawe, H Dawe, Mark Dawkins, Angela Dawson, Danielle Dawson, Elizabeth Dawson, Joy Dawson, Lucinda Dawson, Mike Dawson, Susan Dawson, Tom Dawson, Isla Dawson, Andrew Daxter, Andrew Day, Jacob Day, Jeremy N Day, Jamie D'Costa, Parijat De, Pradip De, Duneesha de Fonseka, Toni de Freitas, Pamela De Los Santos Dominguez, Roberta De Pretto, Frederico De Santana Miranda, Eleanor de Sausmarez, Shanika de Silva, Thushan de Silva, Jessica De Sousa, Paulo De Sousa, James de Souza, Phillip De Souza, Anthony De Soyza, Natasha de Vere, Johannes de Vos, Bethan Deacon, Sharon Dealing, Anna Dean, Julie Dean, Katrina Dean, Stephen Dean, Tessa Dean, Jill Deane, James Dear, Effie Dearden, Catherine Deas, Samuel Debbie, Gabor Debreceni, Vashist Deelchand, Matthew Deeley, Joanne Deery, Emmanuel Defever, Manuela Del Forno, Arnold Dela Rosa, Gonzalo De-La-Cedra, Amanda Dell, Carrie Demetriou, David DeMets, Jane Democratis, Jacqueline Denham, Emmanuelle Denis, Laura Denley, Craig Denmade, Alexandra Dent, Kathy Dent, Martin Dent, Elise Denton, Tom Denwood, Nishigandh Deole, Darshita Depala, Maria Depante, Susan Dermody, Amisha Desai, Asmita Desai, Purav Desai, Sanjeev Deshpande, Vai Deshpande, Sirjana Devkota, Usha Devkota, Debbie Devonport, Matthew Devonport, Prakash Dey, Vishal Dey, Rogin Deylami, Kevin Dhaliwal, Sundip Dhani, Amandeep Dhanoa, Mili Dhar, Ankush Dhariwal, Dawpadee Dharmasena, Devesh Dhasmana, Ekanjali Dhillon, Reiss Dhillon, Syra Dhillon, Meghnath Dhimal, Dipali Dhiru, Trupti Dhorajiwala, Priya Dias, Stephanie Diaz, Kayleigh Diaz-Pratt, Mohammed Dibas, Debbie Dickerson, Pamela Dicks, Matt Dickson, Stuart Dickson, J Digby, Ronneil Digpal, Sean Dillane, Sarah Diment, Paul Dimitri, Georgios Dimitriadis, Sajeel Din, Thai H Dinh, Thi T T Dinh, Alex Dipper, Sabiq Dipro, Laura Dirmantaite, Lorelle Dismore, Lisa Ditchfield, Sarah Diver, Lavanya Diwakar, Preeti Diwan, Caroline Dixon, Giles Dixon, Kate Dixon, Brice Djeugam, Sipho Dlamini, Petr Dlouhy, Andrea D'Mello, Paul Dmitri, Thi Tien Do, Laurence Dobbie, Marinela Dobranszky Oroian, Charlotte Dobson, Lee Dobson, Marie Docherty, David Dockrell, Jacqueline Dodd, James Dodd, Jackie Dodds, Rebecca Dodds, Steve Dodds, Richi Dogra, Conor Doherty, Erin Doherty, Warren Doherty, Yumiko Doi, Iain Doig, Eleanor Doke, Daniel Dolan, Mark Dolman, Rozzie Dolman, Lisa Donald, Katie Donald, Callum Donaldson, Christopher Donaldson, Denise Donaldson, Gillian Donaldson, Kate Donaldson, Phu Khiem Dong, Martha Donkor, Sinead Donlon, Joanne Donnachie, Eilish Donnelly, Ronan Donnelly, Phil Donnison, Aravindhan Donohoe, Gemma Donohoe, Bryan Donohue, Emma Dooks, Reece J Doonan, Rogier Van Doorn, Grainne Doran, Rachael Dore, Kane Dorey, Sharon Dorgan, Kataryna Dos Santos, Moonira Dosani, Davinder Dosanjh, Paula Dospinescu, Isabelle Doss, Theonymfi Doudouliaki, Andrew Dougherty, Jill Doughty, Katie Douglas, Jonathan Douse, Allyn Dow, Lucy Dowden, Michelle Dower, Sud Dowling, Nicola Downer, Charlotte Downes, Rob Downes, Thomas Downes, Damian Downey, Robert Downey, Caroline Downing, Louise Downs, Simon Dowson, Cornel Dragan, Cristina Dragos, Maire Drain, Chelsea Drake, Victoria Drew, Olivia Drewett, Anthony Drexel, Celine Driscoll, Helena Drogan, Odysseas Drosos, Graham Drummond, Katie Drury, Kay Druryk, Ronald Druyeh, Jack Dryburgh-Jones, Simon Drysdale, An Du Thinh, Hazel Dube, Judith Dube, Stephen Duberley, Paige K Duckenfield, Hayley Duckles-Leech, Nicola Duff, Emma Duffield, Heather Duffy, Helen Duffy, Katharine Duffy, Lionel Dufour, Annette Duggan, Parveen Dugh, Rauand Duhoky, Janice Duignan, Jennifer Dulay, Simon Dummer, Alexis Duncan, Andrew Duncan, Christopher Duncan, Fullerton Duncan, Gregory Duncan, Holly Duncan, Robert Duncan, Stephanie Dundas, Do Van Dung, Aileen Dunleavy, Julia Dunleavy, Alessia Dunn, Charlotte Dunn, Damian Dunn, Laura Dunn, Paul Dunn, Charlene Dunne, Karen Dunne, Fiona Dunning, Aidan Dunphy, Tran Thi Hai Duong, Venkat Duraiswamy, Beatriz Duran, Ingrid DuRand, Leanne Durdle, Natalie Duric, Alison Durie, Emily Durie, Samuel Durogbola, Chris Durojaiye, Laura Durrans, Katie Durrant, Hannah Durrington, Iheukwumere Duru, Haris Duvnjak, Akshay Dwarakanath, Laasya Dwarakanath, Dennis Dwomoh Nkrumah, Ellen Dwyer, Zara Dyar, Claudia Dyball, Kristyn Dyer, Harvey Dymond, Tom Dymond, Chris Eades, Lauren Eadie, Rebekah Eadie, Laura Eagles, Beena Eapen, Naomi Earl, Joanne Early, Melissa Earwaker, Nicholas Easom, Clare East, Amy Easthope, Fraser Easton, Jack Easton, Patrick Easton, Ruth Eatough, Oluwadamilola Ebigbola, Martin Ebon, Alison Eccles, Sinan Eccles, Chloe Eddings, Michael Eddleston, Maureen Edgar, Katharine Edgerley, Nicholas Edmond, Mary Edmondson, Tracy Edmunds, Abby Edwards, Alexandra Edwards, Catherine Edwards, Joy Edwards, Kennedy Edwards, Mandy Edwards, Martin Edwards, Sophie Edwards, Jenny Eedle, Aline Eggink, Dawn Egginton, Sam Eggleston, Loveth Ehiorobo, Sarah Eisen, Ugochukwu Ekeowa, Mohamed Ekoi, Ayomide Ekunola, Soha El Behery, Nagla Elashhar, Lisa Elawamy, Mohamed Elbeshy, Kate El-Bouzidi, Jennifer Elder, Mohammed El-Din, Emma Eldridge, Diana Eleanor, Uchenna Elenwa, Ibrahim Eletu, Eman Elfar, Mayy Magdy Elgamal, Amr Elgohary, Mohamed A A Elhadi, Stellios Elia, Jennifer Elias, Tania Elias, Nadia Elkaram, Andrew V Elkins, Julie Ellam, Nikki Ellard, Laura N Ellerton, Lucy Elliot, Amy Elliott, Fiona Elliott, Kerry Elliott, Scott Elliott, Sian Elliott, Annie Ellis, Christine Ellis, Kaytie Ellis, Leila Ellis, Rupert Ellis, Tak-Yan Ellis, Yvette Ellis, Alison C Ellwood, Rahma Elmahdi, Einas Elmahi, Hannah-May Elmasry, Mohammed El-Naggar, Najla Elndari, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Mohammed A S A Elsayed, Sally El-Sayeh, Hana El-Sbahi, Mohammad Elsebaei, Tarek Elsefi, Karim El-Shakankery, Alguili Elsheikh, Hosni El-Taweel, Sarah Elyoussfi, Jonathan Emberey, Jonathan R Emberson, John Emberton, Anna Emery, Julian Emmanuel, Ingrid Emmerson, Michael Emms, Florence Emond, Marieke Emonts, Nicu Enachi, Dickson Enenche, Angila Engden, Katy English, Emma Entwistle, Hene Enyi, Marios Erotocritou, Peter Eskander, Hanif Esmail, Fatheha Essa, Brynach Evans, Chris Evans, Debra Evans, E Evans, Emrys Evans, Gail Evans, Gareth Evans, Isabel Evans, Jack Evans, Jacqueline Evans, Jennifer Evans, John Evans, Jolanta Evans, Lisa Evans, Lynn Evans, Mim Evans, Morgan Evans, Ranoromanana Evans, Sharon Evans, Sian Evans, Teriann Evans, Tomos Evans, Caroline Everden, Serenydd Everden, Lynette Every, Hayley Evison, Lynsey Evison, Chiamaka Ezenduka, Jacqueline Faccenda, Leila Fahel, Youstina Fahmay, Ian Fairbairn, Sara Fairbairn, Terry Fairbairn, Andy Fairclough, Louise Fairlie, Mark Fairweather, Anne Fajardo, Naomi Falcone, Euan Falconer, John Fallon, Andrea Fallow, David Faluyi, Victoria Fancois, Ayaan Farah, Muna Farah, Qayyum Farah, Nowin Z Fard, Leila Fares, Amr Farg, Adam Farmer, Katie Farmer, Toni Farmery, Samantha Farnworth, Faiyaz Farook, Hadia Farooq, Sidrah Farooq, Fiona Farquhar, Holly Farr, Aaron Farrell, Barbara Farrell, Fayed Farrukh, James Farthing, Syeda Farzana, Rahmatu Fasina, Azam Fatemi, Mina Fatemi, Suman Fathima, Nibah Fatimah, Maria Faulkner, Saul N Faust, Clair Favager, Joe Fawke, Sinmidele Fawohunre, Abul Fazal, Aisthath Fazleen, Simon Fearby, Connie Fearnley, Alex Feben, Federico Fedel, Daria Fedorova, Christopher Fegan, Mae Felongo, Lynsey Felton, Tim Felton, Kate Fenlon, Andrea Fenn, Ruth Fennelly, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Gloria Ferenando, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil Fernandes, Candida Fernandez, Eduardo Fernandez, Maria Fernandez, Sonia Fernandez Lopez, Jaime Fernandez Roman, Callum J Fernando, Jessica Fernando, Ahmed Feroz, Pietro Ferranti, Thais Ferrari, Eleanor Ferrelly, Alexandra Ferrera, Emma Ferriman, Sheldon Ferron, Nicholas Fethers, Ben Field, Janet Field, Rebecca Field, Karen Fielder, Lindsey Fieldhouse, Andra Fielding, Julie Fielding, Sarah Fielding, Asma Fikree, Santos Filipa, Sarah A Filson, Shona Finan, Sarah Finbow, Deborah J Finch, Joanne Finch, Laurie Finch, Simon Finch, Spencer Finch, Natalie Fineman, Jim Finlayson, Lauren Finlayson, Adam Finn, Joanne Finn, Dylan Finnerty, Clare Finney, Deborah Finucane, Sofia Fiouni, Jo Fiquet, Promise Firi, James Fisher, Neil Fisher, Daniel Fishman, Krystofer Fishwick, Carolyn Fitton, Felicity Fitzgerald, Fiona Fitzgerald, Karen Fitzjohn, Jan Flaherty, Michael Flanagan, Charles Flanders, Nikolaos Flaris, Gail Fleming, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Anna Fletcher, Jonathan Fletcher, Lucy Fletcher, Simon Fletcher, Sophie Fletcher, Fiona Flett, Karen Flewitt, Sarah Flockhart, Christopher Flood, Ian Floodgate, Jonathan Flor, Vincent Florence, Mary Flowerdew, Sharon Floyd, Margaret J Flynn, Rachel Flynn, Claire Foden, Adama Fofana, Georgina Fogarty, Paul Foley, Linda Folkes, Tracey Fong, Daniela M Font, Aiwyne Foo, Jane Foo, Andrew Foot, Helen R Foot, Jayne Foot, Jane Forbes, Amber Ford, Jamie Ford, Imogen Fordham, Jennifer Foreman, Matthew Forester, Mohammad Forkan, Caroline Fornolles, Adam Forrest, Ellie Forsey, Miranda Forsey, Thomas Forshall, Elliot Forster, Abigail Forsyth, Julian Forton, Conrad Foster, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Angela Foulds, Ian Foulds, Folakemi Fowe, Natasha Fowkes, Emily Fowler, Robert Fowler, Stephen Fowler, Amy Fox, Claire Fox, Heather Fox, Jonathan Fox, Laura Fox, Lauren Fox, Natalie Fox, Olivia Fox, Simon Fox, Sarah-Jane Foxton, Eva Fraile, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Theodora Francis-Bacon, Helen Frankland, Jessica Franklin, Siobhan Franklin, Catherine Fraser, Andi Fratila, Sharon Frayling, Martyn Fredlund, Anna Freeman, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Eleanor French, Thomas French, Karen Freshwater, Matthew Frise, Renate Fromson, Adam Frosh, John Frost, Victoria Frost, Oliver Froud, Rachel Frowd, Arun Fryatt, Andrzej Frygier, Bridget Fuller, Liz Fuller, Lucy Fuller, Tracy Fuller, Duncan Fullerton, Carrie Fung, Gayle Fung, Sarah Funnell, John Furness, Andrew Fyfe, Nytianandan G, Elizabeth Gabbitas, Claire Gabriel, Zoë Gabriel, Hadiza Gachi, Sophie Gaffarena, Sarah Gage, Joshua Gahir, Sarveen Gajebasia, Katarzyna Gajewska-Knapik, Babita Gajmer, Zacharoula Galani, Christopher Gale, Hugo Gale, Linda Gale, Rebecca Gale, Swetha Gali, Bernadette Gallagher, Jude Gallagher, Rosie Gallagher, William Gallagher, Feroze Gallam, Joanne Galliford, Catherine Galloway, Chris Galloway, Emma Galloway, Jacqui Galloway, James Galloway, Anna Galvin, Victoria Galvis, Gareth Gamble, Laura Gamble, Liz Gamble, Brian Gammon, Chien N Gan, Muhammad B Ganaie, Jaikumar Ganapathi, Ramesh Ganapathy, Kaminiben Gandhi, Sarah Gandhi, Usha Ganesh, Thenugan Ganeshanathan, Saibal Ganguly, Abrar Gani, Pauline Ganley, Ukraina Garcia, Emma-James Garden, Antoni D Gardener, Emma Gardiner, Michael Gardiner, Phil Gardiner, Siobhan Gardiner, Caroline Gardiner-Hill, Jonathan Gardner, Louis Gardner, Mark Garfield, Atul Garg, Isha Garg, Nathan Garlick, Daniel Garner, Justin Garner, Lucie Garner, Zoe Garner, Rosaline Garr, Kathryn A Garrero, Manisha Gartaula, Florence Garty, Rachel Gascoyne, Hyeriju Gashau, Aoife Gatenby, Erin Gaughan, Alok Gaurav, Mariana Gavrila, Jane Gaylard, Sophie Gayle, Catherine Geddie, Ian Gedge, Sarah Gee, Fartuun Geele, Kalaichelvi Geerthan, Minnie Gellamucho, Karzan Gelly, Leila Gelmon, Sandra Gelves-Zapata, Gemma Genato, Neal Gent, Susan Gent, Natalie Geoghegan, Aparna George, Bini George, Sam George, Susan George, Tina George, Valerie P George, Simon Georges, Domonique Georgiou, Peter Gerard, Leigh Gerdes, Louise Germain, Helen Gerrish, Abel Getachew, Louise Gethin, Siobhan Gettings, Hisham Ghanayem, Bijan Ghavami Kia, Shaista Ghazal, Anca Gherman, Alison Ghosh, Dipansu Ghosh, Justin Ghosh, Subhamay Ghosh, Sarra Giannopoulou, Malick Gibani, Chris Gibb, Ben Gibbison, Kerry Gibbons, Alex Gibson, Bethan Gibson, Jamie Gibson, Kimberley Gibson, Kirsty Gibson, Sian Gibson, Mary Gigi, Cat Gilbert, Jeanette Gilbert, Kayleigh Gilbert, Benjamin Giles, James Gilham, Mandy Gill, Lynne Gill, Paul Gillen, Annelies Gillesen, Katherine Gillespie, Elizabeth Gillham, Andrew Gillian, Deborah Gilliland, Robert Gillott, Danielle Gilmour, Kate Gilmour, Lesley Gilmour, Louis Ginn, Franciscus Ginting, Theodora Giokanini-Royal, Anna Gipson, Barbie Giri, Joanna Girling, Rhian Gisby, Angelena Gkioni, Aikaterini Gkoritsa, Effrossyni Gkrania-Klotsas, Amy Gladwell, James Glanville, Jessica Glasgow, Susannah Glasgow, Jon Glass, Lynn Glass, Sharon Glaysher, Lisa Gledhill, Eleanor Glenday, Ana Glennon, Jodie Glossop, John Glover, Kyle Glover, Michelle Glover, Jan Glover Bengtsson, Deborah Glowski, Sharon Glynn, Chevanthy Gnanalingam, Julie Goddard, Wendy Goddard, Emily Godden, Jo Godden, Sarah Godlee, Emma Godson, Gillian Godwin, Sukanya Gogoi, Aiky Goh, Manjinder Gohel, Rebeca Goiriz, Sriya Gokaraju, Raphael Goldacre, Arthur Goldsmith, Portia Goldsmith, Darren Gomersall, Lucia Gomez, Raquel Gomez-Marcos, Ali Gondal, Celia Gonzalez, Jack Goodall, Vicky Goodall, Bob Goodenough, Anna Goodfellow, Laura Goodfellow, James Goodlife, Camelia Goodwin, Elizabeth Goodwin, Jayne Goodwin, Paula Goodyear, Rajiv Gooentilleke, Michelle Goonasekara, Sheila Gooseman, Shameer Gopal, Chris Gordon, Sally Gordon, Robin Gore, Hugh Gorick, Caitlin Gorman, Claire Gorman, Stuart Gormely, Maria Gorniok, Diana Gorog, Michelle Gorst, Thomas Gorsuch, Jayshreebahen Gosai, Rebecca Gosling, Sally Gosling, Georgina Gosney, Vanessa Goss, Dzintars Gotham, Naomi Gott, Elizabeth Goudie, Nicole Gould, Susan Gould, Charlotte Goumalatsou, Lysander Gourbault, Abha Govind, Rajesh Govindan, Sharon Gowans, Girish Gowda, Rohit Gowda, Hannah Gower, Pankaj Goyal, Sunil Goyal, Sushant Goyal, Cheryl Graham, Clive Graham, Jonathan Graham, Justin Graham, Libby Graham, Rachel Graham, Sharon Graham, Matthew Graham-Brown, Julia Grahamslaw, Gianluca Grana, Tracyanne Grandison, Louis Grandjean, Alison Grant, Ann Grant, David Grant, Kirstie Grant, Matthew Grant, Pauleen Grant, Rhys Gravell, Jenny Graves, Alasdair Gray, Catherine Gray, Georgina Gray, Glaxy Gray, Jackie Gray, Karen Gray, Nicola Gray, Roxanne Gray, Sebastian Gray, Alan Grayson, Fiona Greaves, Paul Greaves, Alastair Green, Amy Green, Amy S Green, Charlotte Green, Christopher A Green, David Green, Frederick Green, Joel Green, Marie Green, Nicola Green, Stacey Green, Diarra Greene, Philippa Greenfield, Alan Greenhalgh, Daniel Greenwood, Sandra Greer, James Gregory, Jane Gregory, Katie Gregory, Tamsin Gregory, Jill Greig, Julia Greig, Rebecca Grenfell, Teena Grenier, Jack Grenville, Jo Gresty, Susan Grevatt, Glaxy Grey, Samuel Gribben, Andrew Gribbin, Amy Gribble, Natasha Grieg, Douglas Grieve, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Mark Griffiths, Nicola Griffiths, Oliver Griffiths, Sandra Griffiths, Sarah Griffiths, Scott Griffiths, Yvonne Griffiths, Sofia Grigoriadou, Steph Grigsby, Paul Grist, Evelina Grobovaite, Dorothy Grogono, Clarissa Grondin, Rachel Groome, Pauline Grose, Liliana Grosu, Jenny Grounds, Margaret Grout, Helen Grover, Jayne Groves, Neil Grubb, Julie Grundy, Francesca Guarino, Sharada Gudur, Jacinta Guerin, Sharazeq 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Hale, Jennie Hale, Carmel Halevy, Paul Halford, William Halford, Alaina Halim, Alistair Hall, Anthony Hall, Claire Hall, Elizabeth Hall, Fiona Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Laura Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Jackie Halliday, Akmal Hallman, Heather Halls, Maryam Hamdollah-Zadeh, Ifedadepo A Hamed-Adekale, Bilal Hameed, Mohammed Hameed, Raph L Hamers, Imran Hamid, Mohamad Hamie, Raymond Hamill, Bethany Hamilton, Fergus Hamilton, Gus Hamilton, Leigh Hamilton, Melanie Hamilton, Nicola Hamilton, Sara Hamilton, Ruth Hamlin, Eleanor Hamlyn, Beatrice Hammans, Shirley Hammersley, Kate Hammerton, Bev Hammond, Emily Hammond, Leah Hammond, Sally Hammond, Fiona Hammonds, Ibrahim Hamoodi, Karen Hampshire, James A Hampson, Jude Hampson, Lucy Hampson, Lisa Hamzah, Jenny Han, Ozan Hanci, Sadiyah Hand, Lala Handayani, Jasmine Handford, Soran Handrean, Nina K Handzewniak, Sarah Haney, Vu Thi Kim Hang, Sheharyar Hanif, E Hanison, Esther Hanison, Jennifer Hannah, Amy Hannington, Merhej Hannun, Aidan Hanrath, Helena Hanratty, Daniel Hansen, Anita Hanson, Ashley Hanson, Helen Hanson, Jane Hanson, Kathryn Hanson, Steve Hanson, Ala Haqiqi, Monjurul Haque, Henry Harcourt, Lesley Harden, Zoe Harding, Simon Hardman, Marc Hardwick, Gareth Hardy, Joanna Hardy, Yasmine Hardy, Kumar Haresh, Rachel Harford, Beverley Hargadon, James Hargraves, Carolyn Hargreaves, Alice Harin, Mohammed Haris, Edward Harlock, Paula Harman, Tracy Harman, Mark Harmer, Muhammad A Haroon, Charlie Harper, Heather Harper, James Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Kate Harrington, Sian Harrington, Yasmin Harrington-Davies, Jade Harris, Jess Harris, John Harris, Laura Harris, Marie-Clare Harris, Nichola Harris, Sophie Harris, David Harrison, Laura Harrison, Melanie Harrison, Olakunbi A Harrison, Rachael Harrison, Rowan Harrison, Susie Harrison, Thomas Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Jessica Hartley, Lisa Hartley, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Phillipa Hartridge, Stuart Hartshorn, Alice Harvey, Angela Harvey, Anna Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Zoe Harzeli, Brigitte Haselden, Kazi Hashem, Mohammed Hashimm, Tadaaki Hashimoto, Imranullah Hashmi, Jack Haslam, Zena Haslam, Grace Hasnip, Adil Hassan, Ali Hassan, Amro Hassan, Awab Hassan, Zeinab Hassan, Sapna Hassasing, Jane Hassell, Philip Hassell, Alex Hastings, Bethany Hastings, Janice Hastings, Sarah Hathaway-Lees, Jonathan Hatton, Jennifer Hau, May Havinden-Williams, Stefan Havlik, Daniel B Hawcutt, Kadean Hawes, Liz Hawes, Nicola Hawes, Lydia Hawker, Annie Hawkins, Joe Hawkins, Nancy Hawkins, W John Hawkins, Dan Hawley, Ed Hawley-Jones, Edward Haworth, Alasdair W Hay, Cathy Hay, Amna Hayat, Jamal Hayat, Mohamed-Riyal Hayathu, Anne Hayes, Jonas Hayes, Kate Hayes, Melony Hayes, Fiona Hayes, Patrick Hayle, Chloe Haylett, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard Haynes, Rachel Hayre, Carole Hays, Sarah Haysom, James Hayward, Patrick Haywood, Hazel Haywood Hasford, Tracy Hazelton, Phoebe Hazenberg, Zhengmai He, Elizabeth Headon, Carrie Heal, Brendan Healy, Jessica L Healy, Amy Hearn, David Heasman, Angela Heath, Debbie Heath, Rowan Heath, Diane Heaton, Adam Heavens, Kerry Hebbron, Catherine Heckman, Gemma Hector, Sadie Heddon, Andy Hedges, Katrine Hedges, Cheryl Heeley, Elaine Heeney, Richard Heinink, Rajdeep Heire, Ingvild Helgesen, Joanne Hemingway, Ulla Hemmila, Beth Hemmings, Scott Hemphill, Deborah Hemsley, Abigail Henderson, Eilidh Henderson, Jennifer Henderson, Steven Henderson, Joanne Henry, Karol Henry, Lavinia Henry, Margo Henry, Natalie Henry, David Henshall, Gillian Herdman, Rosaleen Herdman-Grant, Morag Herkes, Lucas E Hermans, Fe Marie Hernandez, Emma Heron, Lisa Heron, William Herrington, Emilia Heselden, Peta Heslop, Tracey Heslop, Simon Hester, Emily Hetherington, Joseph Hetherington, Chamila Hettiarachchi, Pramodh Hettiarachchi, Hayley Hewer, John Hewertson, 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Elizabeth Horsley, Sarah Horton, Jane Hosea, Toby Hoskins, Muhammad S Hossain, Rashed Hossain, Maxine Hough, Sarah Hough, Catherine Houghton, Kathryn Houghton, Rebecca Houlihan, Kay Housely, Hamish Houston, Roseanna Hovvels, Lee How, Laura Howaniec, Joanne Howard, Kate Howard, Laura Howard, Linda Howard, Lucy Howard, Megan Howard, Sarah Howard, Stuart Howard, Richard Howard-Griffin, Louise Howard-Sandy, Serena Howe, Alice Howell, Mark Howells, Lyn Howie, Kerry Howlett, Sophie Howlett, Ruth Howman, Josh Hrycaiczuk, Hein Htet, Naing Z Htoon, Su Htwe, Ying Hu, Chiang O H Huah, Sylvia Huang, Kelly Hubbard, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Heather Hudson, Suzanne Hudson, Oli Hudson, Alison Hufton, Connor Huggins, Alistair Hughes, Caitlin Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Martin Hughes, Rachel Hughes, Rebecca Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Grace Hull, 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McCann, Erin McCann, Alexandra McCarrick, Brendan McCarron, Eoghan McCarthy, Michelle McCarthy, Natalie McCarthy, Sinead McCaughey, Tara McClay, Beverley McClelland, Declan McClintock, Michael McCloskey, Kirsten McCollum, Alasdair McCorkindale, Patricia McCormack, Jacqueline McCormick, Jake McCormick, Wendy McCormick, Paul McCourt, Jame McCrae, Sharon McCready, Gordan McCreath, Helen McCreedy, Claire McCue, Iain J McCullagh, Liz McCullagh, Megan McCullagh, Conor McCullough, Katherine McCullough, Nicola McCullough, Sarah McCullough, Fiona McCurrach, John McDermott, Paula McDermott, Rory McDermott, Katharine McDevitt, Helen McDill, Basil McDonald, Carly McDonald, Claire McDonald, Debbie McDonald, Rob McDonald, Sam McDonald, Damhnaic McDonald, Natasha McDonnell, Catherine McDougall, Lilly McDougall, Rowan McDougall, Irene McEleavy, Fred McElwaine, Julie McEntee, Evanna McEvoy, Claire McEwan, Ruth McEwen, Margaret McFadden, Denise McFarland, Margaret McFarland, Rachel McFarland, Joe McFlynn, Erin McGarry, Lorcan McGarvey, Alex McGeachan, Frederick McGee, Laura McGenily, Clodagh McGettigan, Michael McGettrick, Christopher McGhee, Fiona McGill, Sarah McGinnity, Neil McGlinchey, Phil McGlone, Deborah McGlynn, Claire McGoldrick, Clare McGoldrick, Elizabeth McGough, Christopher McGovern, Roisin McGovern, Angela McGowan, Anne McGown, Brendan McGrath, Amanda McGregor, Annemarie McGregor, Michael P McGuigan, Heather McGuinness, Sean McGuire, Tara McHugh, Caroline McInnes, Neil McInnes, Jerome McIntosh, Karen McIntyre, Mhairi McIntyre, Lorna McKay, Conor P McKeag, Jacqueline McKeane, Madeleine McKee, Joseph McKeever, Judith McKenna, Shirley McKenna, Mary McKenzie, Donogh McKeogh, Caroline McKerr, Anthony M McKie, Hayley Mckie, Laura Mckie, Gerard McKnight, Heather McLachlan, Andrew McLaren, Barbara McLaren, Nicola McLarty, Danielle Mclaughlan, Maria McLaughlin, James McLay, Mary McLeish, Tina McLennan, Stewart McLure, Anne Marie McMahon, Genevieve McMahon, Mike McMahon, Stephen McMahon, Terence McManus, Moyra McMaster, P McMaster, Paddy McMaster, Faye Mcmeeken, Samuel McMeekin, Nicola McMillan, Katherine McMillen, Jason McMinn, Liam McMorrow, Heather McMullen, Christopher McMurran, Helen McNally, Fiona McNeela, Lynne McNeil, Claire McNeill, Jessica McNeill, Shea McNeill, Una McNelis, Melanie McNulty, Roisin McNulty, Christopher McParland, Mark McPhail, Alison McQueen, Anna McSkeane, Denise McSorland, Therese McSorley, Gini McTaggart, Jacqueline McTaggart, Joanna Mead, Paul Mead, Emma Meadows, Olivia Meakin, Ben Mearns, Claire Mearns, Kim Mears, William Mears, Manjula Meda, Ayren Mediana, Ross Medine, Thomas Medveczky, Sharon Meehan, Emily Meeks, Abbi Megan, Nevan Meghani, Salim Meghjee, Sharon Megson, Amina Mehar, Mehr N Mehmood, Rohan Mehra, Rohan Mehta, Graeme Meintjes, James Meirill, James Meiring, Rayane Mejri, Ellen Mekonnen, Sabina Melander, Adriana-Stefania Melinte, Jennifer Mellersh, Lucy Melling, Christie Mellish, Francesca Mellor, Joe S 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Eoin Murtagh, Mithun Murthy, Catherine Murton, Rosie Murton, Neeka Muru, Rosemary Musanhu, Maimuna Mushabe, Omaisa Mushtaq, Sohmal Musini, Ahmed M M Mustafa, Elhaytham Mustafa, Mustafa Mustafa, Ibrahim Mustapha, Naveed Mustfa, Zhain Mustufvi, Callum Mutch, Rachel Mutch, Eric Mutema, Balakumar Muthukrishnan, Sheree Mutton, Natasha Muzengi, Memory Mwadeyi, Bettina Mwale, Esther Mwaura, Raji Myagerimath, Alice Myers, Sam Myers, James S Myerson, Khin Swe Myint, Yadee Myint, Georgina Mynott, Libor Myslivecek, Patricia Nabayego, Evelyn Nadar, Iftikhar Nadeem, Moosa Nadheem, Behzad Nadjm, Asma Naeem, Hassan Naeem, Salman Naeem, Samraiz Nafees, Mohamed Nafei, Widya Naftalia, Thapas Nagarajan, Leah Naglik, Imrun Nagra, Deepak Nagra, Mina Naguib, Kirushthiga Naguleswaran, K Shonit Nagumantry, Kevin Naicker, Sarveshni Naidoo, Gireesha Naik, Rishi Naik, Samir Naik, Devu S Nair, Rajiv Nair, Tanushree Nair, Jay Naisbitt, Kerry Naismith, Deborah Nakiboneka-Ssenabulya, Sri Nallapareddy, Soum 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Chloe Vansomeren, William Van't Hoff, Sejal Vara, Stehen J Vardy, Anu Varghese, Maria Varghese, William Varney, Giulia Varnier, Anna-Nektaria Varouxaki, Resti Varquez, Valeria Vasadi, Olivia Vass, Katherine Vassell, Vimal Vasu, Vasanthi Vasudevan, Manu Vatish, Sue Vaughan, Heloyes Vayalaman, Darini Vayapooree, Christopher Vaz, Niki Veale, Sachuda Veerasamy, Swati Velankar, Luxmi Velauthar, Neyme Veli, Nicola Vella, Aravind Velugupati, Anitha Velusamy, Ian Venables, Mavi Venditti, Ramya Venkataramakrishnan, Richard Venn, Robert Venn, Michelle Venter, Lyn Ventilacion, Joanne Vere, Mark Veres, Stefania Vergnano, Will Verling, Amit Verma, Rachel Vernall, Britney Vernon, Mark Vertue, Liberty Verueco, Jerik Verula, Anna Veterini, Natalie Vethanayagam, Shambavi Vettikumaran, Lucy Veys, Carinna Vickers, Saji Victor, SImpson Victoria, Celine P Vidaillac, Jennifer Vidler, Bavithra Vijayakumar, Vinod W Vijayaraghavan Nalini, Brigita Vilcinskaite, Alicija Vileito, Neringa Vilimiene, Lynn Vinall, Sylvia Vinay, Latha Vinayakarao, Olivia Vincent, Rachel Vincent, Rosie Vincent, Pritpal Virdee, Emma Virgilio, Abdullah M Virk, Elisa Visentin, Martina Vitaglione, Karunakaran Vithian, Sorice Vittoria, Sankkita Vivekananthan, Elena Vlad, Ben Vlies, Linda von Oven, Claire Vooght, Kim Thi Vu Thai, Kritchai Vutipongsatorn, Alain Vuylsteke, Eleftheria Vyras, Richard Wach, Beverley Wadams, Susan Wadd, Natalia Waddington, Phillip Wade, Jonathan Wadsley, Kirsten Wadsworth, Syed E I Wafa, Daniel Wagstaff, Lynda Wagstaff, Dalia Wahab, Zaroug Wahbi, Abiodun Waheed Adigun, Sawan Waidyanatha, Alicia Waite, Rachel Wake, Alice Wakefield, William Wakeford, Fiona Wakinshaw, Emma Waldeck, Andrew Walden, Lorna Walding, Alexandria Waldron, Joanne Waldron, Emma Wales, Batool Wali, Danielle Walker, Gemma Walker, Harriet Walker, Ian Walker, Kevin Walker, Kim Walker, Lauren Walker, Linda Walker, Lynne Walker, Olivia Walker, Rachel Walker, Rebecca Walker, Sara Walker, Susan Walker, Gillian Wallace, Rebecca Wallbutton, Jessica Wallen, Karl Wallendszus, Arabella Waller, Rosemary Waller, Gabiel Wallis, Gabriel Wallis, Louise Wallis, Matthew Wallis, Emma Walmsley, Donna Walsh, Elizabeth Walsh, Livia Walsh, Deborah Walstow, Daniel Walter, Alex Walters, Holt Walters, James Walters, Jocelyn Walters, Eileen Walton, Lucy Walton, Maisie Walton, Michael Walton, Olivia Walton, Sharon Walton, Susan Walton, Mandy Wan, Junita Wanda, Mary Wands, Rachel Wane, Frank Wang, Nick Wang, Ran Wang, Shentong Wang, Deborah Warbrick, Samantha Warburton, Christopher Ward, Deborah Ward, Emma Ward, Hannah Ward, Janice Ward, Joanna Ward, Luke Ward, Nicola Ward, Rachael Ward, Thomas Ward, Tom Ward, Scott A Warden, Gibril Wardere, Steve Wardle, Hassan Wardy, Gareth Waring, Scott Waring, Jenny Warmington, Ben Warner, Christian Warner, Lewis Warnock, Sarah Warran, Jade Warren, Lisa Warren, Rebecca Warren, Yolanda Warren, Davina Warrender, Hannah Warren-Miell, Adilia Warris, Gill Warwick, Helen Wassall, Sean Wasserman, Elizabeth Wasson, Hazel J Watchorn, Holly Waterfall, Abby Waters, Donald Waters, Mark Waterstone, Abigail Watkin, Catherine Watkins, Catrin Watkins, Eleanor Watkins, Karen Watkins, Lynn Watkins, Abigail Watson, Adam J R Watson, Ekaterina Watson, Eleanor Watson, Felicity Watson, J G R Watson, Louisa Watson, Paul Watson, Rebecca Watson, Robert Watson, Kathleen Watson, Malcolm Watters, Donna Watterson, Khairiah Wattimena, Daniel Watts, John Watts, Merlin Watts, Victoria Waugh, Emma Wayman, Matthew Wayman, Akhlaq Wazir, Mark Weatherhead, Nick Weatherly, Chloe Webb, Claire Webb, Hayley Webb, Kathryn Webb, Kylie Webb, Stephen Webb, Cheryl Websdale, Deborah Webster, Ian Webster, Jemma Webster, Tim Webster, Jordan Wedlin, Ling Wee, Rebecca Weerakoon, Thanuja Weerasinghe, Janaka Weeratunga, Maria Weetman, Shuying Wei, Immo Weichert, Emma Welch, Hugh Welch, James Welch, Leanne Welch, Steven Welch, Benjamin Welham, Samantha Weller, Lucy Wellings, Brian Wells, Susan Wellstead, Berni Welsh, Richard Welsh, Ingeborg Welters, Rachael Welton, Victoria Wenn, Lauren Wentworth, Joan Wesonga, Kate Wesseldine, Joe West, Magdelena West, Raha West, Ruth West, Sophie West, Luke Western, Ruth Westhead, Heather Weston, Alice Westwood, Kelly Westwood, Sharon Westwood, Bill Wetherill, Sharon Wheaver, Helen Wheeler, Ben Whelan, Matthew Whelband, Amanda Whileman, Alison Whitcher, Andrew White, Ayesha White, Benjamin White, Catherine White, Christopher White, Duncan White, James White, Jonathan White, Katie White, Marie White, Nick White, Nikki White, Sarah White, Sonia White, Tracey White, Catherine Whitehead, Kelly Whitehorn, Anne Whitehouse, Claire Whitehouse, Tony Whitehouse, Julia Whiteley, Louiza Whiteley, Sophie Whiteley, Rachael Whitham, Gabriel Whitlingum, David Whitmore, Elizabeth Whittaker, Lindsay Whittam, Ashley Whittington, Helen Whittle, Robert Whittle, Eunice Wiafe, Lou Wiblin, Olivia Wickens, John Widdrington, Jason Wieboldt, Hannah Wieringa, Cornelia Wiesender, Laura Wiffen, Andrew Wight, Ashleigh Wignall, Christopher Wignall, Annamaria Wilce, Danielle Wilcock, Emma Wilcock, Louise Wilcox, Ben Wild, Laura Wild, Stephen Wild, Michael Wilde, Laura Wilding, Peter Wilding, Tracey Wildsmith, Joe Wileman, Joy Wiles, Kate Wiles, Elva Wilhelmsen, Thomas Wiliams, Janet Wilkie, David Wilkin, Hannah Wilkins, Joy Wilkins, Suzanne Wilkins, Iain Wilkinson, Lesley Wilkinson, Nicola Wilkinson, Sophia Wilkinson, Susan Wilkinson, Tim Wilkinson, Sylvia Willetts, Aimee Williams, Alexandra Williams, Alison Williams, Angharad Williams, Anna Williams, Ava Williams, Carl Williams, Caroline V Williams, Claire Williams, Dewi Williams, Eleri Williams, Gail Williams, Gemma Williams, Gina Williams, Hannah Williams, Heledd Williams, James Williams, Jennie Williams, Jill Williams, John Williams, Joseph Williams, Karen Williams, Kathryn Williams, Mandy Williams, Marie Williams, Mark Williams, Matthew Williams, Patricia Williams, Penny Williams, Rachel Williams, Robin Williams, Rupert Williams, Samson Williams, Sarah Williams, Sophie Williams, Steffan Williams, Tamanna Williams, Tania Williams, Annie Williamson, Cath Williamson, Catherine Williamson, Dawn Williamson, James D Williamson, Jodie Williamson, Rachel Williamson, Helen Williamson, Elaine Willis, Elizabeth Willis, Emily Willis, Heather Willis, Herika Willis, Joanna Willis, Louise Wills, Lucy Willsher, Catherine Willshire, Francesca Willson, Jayne Willson, Alison Wilson, Andrea Wilson, Anna Wilson, Antoinette Wilson, Billy Wilson, David Wilson, Imogen Wilson, James Wilson, Karen Wilson, Kate Wilson, Kristy-Ann Wilson, Lucinda Wilson, Mark Wilson, Stephen Wilson, Toni Wilson, John Wilson, Khin Lei Yee Win, Marlar Win, Than Win, Tin Tin Win, Wut Yee Win Win, Lucinda Winckworth, Laura Winder, Piers Winder, Stuart Winearl, Helen Winmill, Simon Winn, Carmen Winpenny, Helen Winslow, Helen Winter, Jonathan Winter, Barbara Winter-Goodwin, Joseph Winterton, Hannah Winwood, Jack Wischhusen, Stephen Wisdom, Matthew Wise, Martin Wiselka, Rebecca Wiseman, Sophie Wiseman, Steven Wishart, Tabitha WIshlade, Eric Witele, Nicholas Withers, Janet Wittes, Donna Wixted, Therese Wodehouse, Will Wolf, Nicola Wolff, Kirsten Wolffsohn, Rebecca Wolf-Roberts, Elena Wolodimeroff, Adam Wolstencroft, Alan Wong, Charlotte Wong, Chi-Hung Wong, Chi-Man Wong, Edwin Wong, Jessica S Y Wong, Kit Y Wong, Mei Yin Wong, Nick Wong, Sam Wong, Ting Wong, Aaron B Wongkyezeng, Amanda Wood, Caroline Wood, Dianne Wood, Fiona Wood, Gordon Wood, Hannah Wood, Jennifer Wood, Joe Wood, Lisa Wood, Louise Wood, Madeleine Wood, Stephen Wood, Tracy Wood, Katharine Woodall, Rebecca Woodfield, Christopher Woodford, Elizabeth Woodford, Jill Woodford, Louise Woodhead, Timothy Woodhead, Philip Woodland, Marc Woodman, Myles Woodman, Stephen Woodmansey, Charlotte Woods, Jane Woods, Katherine Woods, Sarah Woods, Zoe Woodward, Megan Woolcock, Gemma Wooldridge, Rebecca Woolf, Chris Woollard, Christopher Woollard, Louisa Woollen, Emma Woolley, Jade Woolley, Daniel Woosey, Dan Wootton, Joanne Wootton, Daniel Worley, Stephy Worton, Jonathan Wraight, Maria Wray, Kim Wren, Lynn Wren, Caroline Wrey Brown, Catherine Wright, Demi Wright, Francesca Wright, Holly Wright, Imogen Wright, Lianne Wright, Rachel Wright, Sarah Wright, Stephanie Wright, Tim Wright, Caroline Wroe, Hannah Wroe, Henry Wu, Peishan Wu, Pensee Wu, Jonathan Wubetu, Fitria Wulandari, Retno Wulandari, Subie Wurie, Craig Wyatt, Frederick Wyn-Griffiths, Inez Wynter, Bindhu Xavier, Arnold Xhikola, Bingru E Xia, Zhongyang Xia, Effua Yacoba, Santosh Yadav, Masseh Yakubi, May Yan, Yuuki Yanagisawa, Freda Yang, Yingjia Yang, Michael Yanney, Woei Lin Yap, Nabil Yaqoob, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Thomas Yates, Mark Yates, Jessica Ye, Charlotte Yearwood Martin, Khin Yein, Fiona Yelnoorkar, Lam Minh Yen, Alastair Yeoh, Chun Yu Yeung, Peter Yew, Durgesh Yewatkar, Laura Ylquimiche Melly, Inez Ynter, H Yong, Jemma Yorke, Jasmine Youens, Abdel Younes Ibrahim, Eoin Young, Gail Young, Louise Young, Asfand Yousafzar, Sajeda Youssouf, Ahmed Yousuf, Hartantri Yovita, Chrissie Yu, Jack S J Yuan, Nindya Yufaniaputri, Bernard Yung, Daniel Yusef, Said Yusef, Intekhab Yusuf, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Aqsa Zahoor, Mahrukh Zainab, Thornton Zak, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Marcelina Zawadzka, Mohammed Zayed, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Darius Zeinali, Jing Zhang, Xiaobei Zhao, Dongling Zheng, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei Thankt Zin, Eva Zincone, Garikai Zindoga, Eleanor Zinkin, Vivian Zinyemba, Christos Zipitis, Letizia Zitter, Arkadiusz Zmierczak, Garazi Zubikarai, Azam Zubir, Naz Zuhra, Rasha Zulaikha, Sabrina Zulfikar, Carol Zullo, Ana Zuriaga-Alvaro, University of St Andrews. Infection and Global Health Division, University of St Andrews. School of Medicine, and Group, RECOVERY Collaborative

Subjects
Adult, Male, Hypoxia/etiology, SARS-CoV-2, COVID-19, 3rd-DAS, General Medicine, Adrenal Cortex Hormones/therapeutic use, AC, Dexamethasone/therapeutic use, Hospitals, Oxygen, Treatment Outcome, SDG 3 - Good Health and Well-being, MCP, Humans, Female
Abstract

Background Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. Methods This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation Findings Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20–2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7–6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2–11·5]). Interpretation In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. Funding UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.

Published
2023
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41. Erythrocyte membrane-cloaked polymeric nanoparticles for controlled drug loading and release

Author

Aryal, Santosh, Hu, Che-Ming J, Fang, Ronnie H, Dehaini, Diana, Carpenter, Cody, Zhang, Dong-Er, and Zhang, Liangfang

Subjects
Bioengineering, Nanotechnology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Cell Line, Tumor, Cell Survival, Delayed-Action Preparations, Doxorubicin, Drug Delivery Systems, Erythrocyte Membrane, Humans, Leukemia, Myeloid, Acute, Nanoparticles, Polymers, biomimetic nanoparticle, drug delivery, nanomedicine, polymeric nanoparticle, red blood cell membrane, sustained release, Physical Chemistry (incl. Structural), Medical Biotechnology, Nanoscience & Nanotechnology
Abstract

AimPolymeric nanoparticles (NPs) cloaked by red blood cell membrane (RBCm) confer the combined advantage of both long circulation lifetime and controlled drug release. The authors carried out studies to gain a better understanding of the drug loading, drug-release kinetics and cell-based efficacy of RBCm-cloaked NPs.Materials & methodsTwo strategies for loading doxorubicin into the RBCm-cloaked NPs were compared: physical encapsulation and chemical conjugation. In vitro efficacy was examined using the acute myeloid leukemia cell line, Kasumi-1.ResultsIt was found that the chemical conjugation strategy resulted in a more sustained drug release profile, and that the RBCm cloak provided a barrier, retarding the outward diffusion of encapsulated drug molecules. It was also demonstrated that RBCm-cloaked NPs exhibit higher toxicity in comparison with free doxorubicin.ConclusionThese results indicate that the RBCm-cloaked NPs hold great promise to become a valuable drug-delivery platform for the treatment of various diseases such as blood cancers.

Published
2013

42. Lung nodules due to

Author

Mary Bryson, Piechowiak, Anne Whitney, Brown, Shambhu, Aryal, and Shalika Basnayake, Katugaha

Subjects
Adult, Male, Candida parapsilosis, Cystic Fibrosis, Humans, Lung, Anti-Bacterial Agents, Lung Transplantation
Abstract

We present the first reported case of

Published
2023

43. Efficacy and safety of olaparib according to age in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer: Analysis of the phase III SOLO2/ENGOT-Ov21 study

Author

Fabian Trillsch, Sven Mahner, Beyhan Ataseven, Rebecca Asher, Nanda Aryal, Coraline Dubot, Andrew Clamp, Richard T. Penson, Amit Oza, Amnon Amit, Tomasz Huzarski, Antonio Casado, Giovanni Scambia, Michael Friedlander, Nicoletta Colombo, Keiichi Fujiwara, Gabe S. Sonke, Hannelore Denys, Elizabeth S. Lowe, Chee K. Lee, Eric Pujade-Lauraine, Trillsch, F, Mahner, S, Ataseven, B, Asher, R, Aryal, N, Dubot, C, Clamp, A, Penson, R, Oza, A, Amit, A, Huzarski, T, Casado, A, Scambia, G, Friedlander, M, Colombo, N, Fujiwara, K, Sonke, G, Denys, H, Lowe, E, Lee, C, and Pujade-Lauraine, E

Subjects
Ovarian Neoplasms, Age dependency, Quality of life, BRCA1 Protein, Obstetrics and Gynecology, Carcinoma, Ovarian Epithelial, Piperazines, Settore MED/40 - GINECOLOGIA E OSTETRICIA, Olaparib, PARP inhibitor, Oncology, Ovarian cancer, Child, Preschool, Mutation, Humans, Phthalazines, Female, Neoplasm Recurrence, Local, PARP inhibitors, Aged
Abstract

Background: Olaparib has significantly improved outcome and patient-centered endpoints in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer (PSOC). Specific information on efficacy and safety of olaparib for older patients appears of special interest. Methods: 295 patients from the SOLO2 trial randomly assigned to olaparib or placebo were categorized according to age-cutoff at 65 years. Efficacy, tolerability, and quality of life (QoL) of olaparib relative to placebo within in each age group was analyzed. Results: Baseline characteristics were similar in patients ≥65 years (N = 62;21.0%) compared to patients

Published
2022
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44. Self-care management of bothersome symptoms as recommended by clinicians for patients with a chronic condition: A Delphi study

Author

Heleen Westland, Shayleigh Dickson Page, Michelle van Rijn, Subhash Aryal, Kenneth E. Freedland, Christopher Lee, Anna Strömberg, Ercole Vellone, Douglas J. Wiebe, Tiny Jaarsma, and Barbara Riegel

Subjects
Pulmonary and Respiratory Medicine, Chronic Obstructive, Consensus, Delphi Technique, Omvårdnad, Nursing, Critical Care and Intensive Care Medicine, Delphi study, Self-care management, Pulmonary Disease, Self Care, Settore MED/45, Pulmonary Disease, Chronic Obstructive, Diabetes Mellitus, Type 2, Symptoms, Chronic Disease, Diabetes Mellitus, Humans, Self-care, Chronic care, Cardiology and Cardiovascular Medicine, Type 2
Abstract

Background: Chronically medically ill patients often need clinical assistance with symptom management, as well as self-care interventions that can help to reduce the impact of bothersome symptoms. Experienced clinicians can help to guide the development of more effective self-care interventions. Objective: To create a consensus-based list of common bothersome symptoms of chronic conditions and of self-care management behaviors recommended to patients by clinicians to reduce the impact of these symptoms. Methods: A two-round Delphi study was performed among an international panel of 47 clinicians using online surveys to identify common and bothersome symptoms and related self-care management behaviors recommended to patients with heart failure, chronic obstructive pulmonary disease, asthma, type 2 diabetes, or arthritis. Results: A total of 30 common bothersome symptoms and 158 self-care management behaviors across the five conditions were listed. Each chronic condition has its own bothersome symptoms and self-care management behaviors. Consensus was reached on the vast majority of recommended behaviors. Conclusions: The list of common bothersome symptoms and self-care management behaviors reflect consensus across four countries on many points but also disagreement on others, and a few recommendations are inconsistent with current guidelines. Efforts to encourage clinicians to recommend effective self-care management behaviors may reduce symptom impact in chronically ill patient populations.(C) 2022 The Author(s). Published by Elsevier Inc. Funding Agencies|Australian Catholic University, Australia

Published
2022
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45. Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Author

Kartsonaki, Christiana, Baillie, J Kenneth, Barrio, Noelia García, Baruch, Joaquín, Beane, Abigail, Blumberg, Lucille, Bozza, Fernando, Broadley, Tessa, Burrell, Aidan, Carson, Gail, Citarella, Barbara Wanjiru, Dagens, Andrew, Dankwa, Emmanuelle A, Donnelly, Christl A, Dunning, Jake, Elotmani, Loubna, Escher, Martina, Farshait, Nataly, Goffard, Jean-Christophe, Gonçalves, Bronner P, Hall, Matthew, Hashmi, Madiha, Sim Lim Heng, Benedict, Ho, Antonia, Jassat, Waasila, Pedrera Jiménez, Miguel, Laouenan, Cedric, Lissauer, Samantha, Martin-Loeches, Ignacio, Mentré, France, Merson, Laura, Morton, Ben, Munblit, Daniel, Nekliudov, Nikita A, Nichol, Alistair D, Singh Oinam, Budha Charan, Ong, David, Panda, Prasan Kumar, Petrovic, Michele, Pritchard, Mark G, Ramakrishnan, Nagarajan, Ramos, Grazielle Viana, Roger, Claire, Sandulescu, Oana, Semple, Malcolm G, Sharma, Pratima, Sigfrid, Louise, Somers, Emily C, Streinu-Cercel, Anca, Taccone, Fabio, Vecham, Pavan Kumar, Kumar Tirupakuzhi Vijayaraghavan, Bharath, Wei, Jia, Wils, Evert-Jan, Ci Wong, Xin, Horby, Peter, Rojek, Amanda, Olliaro, Piero L, ISARIC Clinical Characterisation Group: Ali Abbas, Sheryl Ann Abdukahil, Nurul Najmee Abdulkadir, Ryuzo Abe, Laurent Abel, Lara Absil, Subhash Acharya, Andrew Acker, Elisabeth Adam, Diana Adrião, Saleh Al Ageel, Shakeel Ahmed, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Eman Al Qasim, Razi Alalqam, Angela Alberti, Tala Al-Dabbous, Senthilkumar Alegesan, Cynthia Alegre, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Huda Alfoudri, Imran Ali, Adam Ali, Naseem Ali Shah, Kazali Enagnon Alidjnou, Jeffrey Aliudin, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Aneela Altaf, João Alves, Rita Alves, João Melo Alves, Maria Amaral, Nur Amira, Phoebe Ampaw, Roberto Andini, Claire Andréjak, Andrea Angheben, François Angoulvant, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Muhammad Ashraf, Namra Asif, Mohammad Asim, Jean Baptiste Assie, Amirul Asyraf, Anika Atique, A M Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Laurène Azemar, Cecile Azoulay, Benjamin Bach, Delphine Bachelet, Claudine Badr, Nadia Baig, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Andriy Bal, Mohanaprasanth Balakrishnan, Valeria Balan, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Audrey Barrelet, Cleide Barrigoto, Marie Bartoli, Mustehan Bashir, Romain Basmaci, Muhammad Fadhli Hassin Basri, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Dehbia Benkerrou, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Delphine Bergeaud, Hazel Bergin, José Luis Bernal Sobrino, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Claudia Bianco, Farah Nadiah Bidin, Moirangthem Bikram Singh, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, François Bissuel, Patrick Biston, Laurent Bitker, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Alice Bogaarts, Debby Bogaert, Anne-Hélène Boivin, Pierre-Adrien Bolze, François Bompart, Aurelius Bonfasius, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Dounia Bouhmani, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Jason Bouziotis, Bianca Boxma, Marielle Boyer-Besseyre, Maria Boylan, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Patrick Breen, Dorothy Breen, Kathy Brickell, Shaunagh Browne, Alex Browne, Nicolas Brozzi, Marjolein Brusse-Keizer, Nina Buchtele, Christian Buesaquillo, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Ingrid G Bustos, Denis Butnaru, André Cabie, Susana Cabral, Eder Caceres, Cyril Cadoz, Mia Callahan, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Pauline Caraux-Paz, Sheila Cárcel, Chiara Simona Cardellino, Sofia Cardoso, Filipe Cardoso, Filipa Cardoso, Nelson Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Henry Castrillón, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Christelle Chantalat Auger, Jean-Marc Chapplain, Julie Chas, Allegra Chatterjee, Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Marie-Charlotte Chopin, Ting Soo Chow, Yock Ping Chow, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Emma Clarke, Rolando Claure-Del Granado, Sara Clohisey, Perren J Cobb, Cassidy 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Munblit, Daniel, Nekliudov, Nikita A, Nichol, Alistair D, Singh Oinam, Budha Charan, Ong, David, Panda, Prasan Kumar, Petrovic, Michele, Pritchard, Mark G, Ramakrishnan, Nagarajan, Ramos, Grazielle Viana, Roger, Claire, Sandulescu, Oana, Semple, Malcolm G, Sharma, Pratima, Sigfrid, Louise, Somers, Emily C, Streinu-Cercel, Anca, Taccone, Fabio, Vecham, Pavan Kumar, Kumar Tirupakuzhi Vijayaraghavan, Bharath, Wei, Jia, Wils, Evert-Jan, Ci Wong, Xin, Horby, Peter, Rojek, Amanda, Olliaro, Piero L, ISARIC Clinical Characterisation Group: Ali Abbas, Sheryl Ann Abdukahil, Nurul Najmee Abdulkadir, Ryuzo Abe, Laurent Abel, Lara Absil, Subhash Acharya, Andrew Acker, Elisabeth Adam, Diana Adrião, Saleh Al Ageel, Shakeel Ahmed, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Eman Al Qasim, Razi Alalqam, Angela Alberti, Tala Al-Dabbous, Senthilkumar Alegesan, Cynthia Alegre, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman 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Bakar, Andriy Bal, Mohanaprasanth Balakrishnan, Valeria Balan, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Audrey Barrelet, Cleide Barrigoto, Marie Bartoli, Mustehan Bashir, Romain Basmaci, Muhammad Fadhli Hassin Basri, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Dehbia Benkerrou, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Delphine Bergeaud, Hazel Bergin, José Luis Bernal Sobrino, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Claudia Bianco, Farah Nadiah Bidin, Moirangthem Bikram Singh, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, François Bissuel, Patrick Biston, Laurent Bitker, 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Cruz Rojo, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, Darren Dahly, Heidi Dalton, Jo Dalton, Seamus Daly, Nick Daneman, Corinne Daniel, Jorge Dantas, Frédérick D'Aragon, Menno de Jong, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Lauren Deconninck, Romain Decours, Eve Defous, Isabelle Delacroix, Eric Delaveuve, Karen Delavigne, Nathalie M Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Mehul Desai, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhanger, Alpha Diallo, Sylvain Diamantis, André Dias, Juan Jose Diaz, Priscila Diaz, Rodrigo Diaz, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Félix Djossou, Annemarie B Docherty, Helen Doherty, Arjen M Dondorp, Andy Dong, Maria Donnelly, Sean Donohue, Yoann Donohue, Chloe Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, James Joshua Douglas, Renee Douma, Nathalie Dournon, Triona Downer, Joanne Downey, Mark Downing, Tom Drake, Aoife Driscoll, Murray Dryden, Murray Dryden, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Marco Echeverria-Villalobos, Siobhan Egan, Carla Eira, Mohammed El Sanharawi, Subbarao Elapavaluru, Brigitte Elharrar, Jacobien Ellerbroek, Philippine Eloy, Tarek Elshazly, Iqbal Elyazar, Isabelle Enderle, Tomoyuki Endo, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Mariano Esperatti, Hélène Esperou, Marina Esposito-Farese, João Estevão, Manuel Etienne, Nadia Ettalhaoui, Anna Greti Everding, Mirjam Evers, Marc Fabre, Isabelle Fabre, Amna Faheem, Arabella Fahy, Cameron J Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Arie Zainul Fatoni, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Laura Feeney, Jorge Fernandes, Marília Andreia Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Sílvia Ferreira, Isabel Ferreira, Benigno Ferreira, Ricard Ferrer-Roca, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Juan Fiorda, Thomas Flament, Clara Flateau, Tom Fletcher, Letizia Lucia Florio, Deirdre Flynn, Claire Foley, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Simon Forsyth, Denise Foster, Giuseppe Foti, Erwan Fourn, Robert A 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Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Christopher A Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Anja Grosse Lordemann, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Dewi Guellec, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Hannah Habraken, Ali Hachemi, Amy Hackmann, Nadir Hadri, Fakhir Haidri, Sheeba Hakak, Adam Hall, Sophie Halpin, Jawad Hameed, Ansley Hamer, Raph L Hamers, Rebecca Hamidfar, Terese Hammond, Lim Yuen Han, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Mohd Shahnaz Hasan, Junaid Hashmi, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ross Hendry, Martina Hennessy, Aquiles Henriquez-Trujillo, Maxime Hentzien, Jaime Hernandez-Montfort, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhilin Higgins, Dawn Higgins, Rupert Higgins, Rita Hinchion, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Koji Hoshino, Ikram Houas, Catherine L Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Stella Huo, Abby Hurd, Iqbal Hussain, Samreen Ijaz, Hajnal-Gabriela Illes, Patrick Imbert, Mohammad Imran, Rana Imran Sikander, Aftab Imtiaz, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Elias Iosifidis, Mariachiara Ippolito, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Julien Jabot, Clare Jackson, Nina Jamieson, Victoria Janes, Pierre Jaquet, Coline Jaud-Fischer, Stéphane Jaureguiberry, Jeffrey Javidfar, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth N Jorge García, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Hanna Jung, Anna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Alina Kalicinska, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Paul Kambiya, Kavita Kamineni, Darshana Hewa Kandamby, Chris Kandel, Kong Yeow Kang, Darakhshan Kanwal, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Anant Kataria, Kevin Katz, Aasmine Kaur, Christy Kay, Hannah Keane, Seán Keating, Pulak Kedia, Claire Kelly, Yvelynne Kelly, Andrea Kelly, Niamh Kelly, Aoife Kelly, Sadie Kelly, Maeve Kelsey, Ryan Kennedy, Kalynn Kennon, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Imrana Khalid, Osama Khalid, Antoine Khalil, Coralie Khan, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Amin Khawaja, Krish Kherajani, Michelle E Kho, Saye Khoo, Ryan Khoo, Denisa Khoo, Nasir Khoso, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Alexander King, Nobuya Kitamura, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R Knight, Robin Kobbe, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Caroline Kosgei, Arsène Kpangon, Karolina Krawczyk, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G Laffey, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Antonio Lalueza, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Teresa Lawrence, Cassie Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Paul Le Turnier, Ema Leal, Marta Leal Santos, Todd C Lee, James Lee, Jennifer Lee, Heng Gee Lee, Biing Horng Lee, Yi Lin Lee, Su Hwan Lee, Gary Leeming, Laurent Lefebvre, Bénédicte Lefebvre, Benjamin Lefevre, Sylvie LeGac, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Michela Leone, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Wei Shen Lim, Kah Chuan Lim, Chantre Lima, Lim Lina, Bruno Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Jose W Lopez-Revilla, Anthony L Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos Lumbreras Bermejo, Carlos M Luna, Olguta Lungu, Liem Luong, Nestor Luque, Dominique Luton, Nilar Lwin, Ruth Lyons, Olavi Maasikas, Oryane Mabiala, Moïse Machado, Gabriel Macheda, Hashmi Madiha, Guillermo Maestro de la Calle, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S Maier, Mylène Maillet, Thomas Maitre, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Ceila Maria Sant Ana Malaque, Flávio Marino, Daniel Marino, Samuel Markowicz, Charbel Maroun Eid, Ana Marques, Catherine Marquis, Brian Marsh, Laura Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Martin Martinot, Alejandro Martin-Quiros, João Martins, Ana Martins, Nuno Martins, Caroline Martins Rego, Gennaro Martucci, Olga Martynenko, Eva Miranda Marwali, Marsilla Marzukie, David Maslove, Sabina Mason, Sobia Masood, Basri Mat Nor, Moshe Matan, Meghena Mathew, Daniel Mathieu, Mathieu Mattei, Romans Matulevics, Laurence Maulin, Michael Maxwell, Javier Maynar, Thierry Mazzoni, Natalie Mc Evoy, Lisa Mc Sweeney, Colin McArthur, Colin McArthur, Anne McCarthy, Aine McCarthy, Colin McCloskey, Rachael McConnochie, Sherry McDermott, Sarah E McDonald, Aine McElroy, Samuel McElwee, Victoria McEneany, Allison McGeer, Chris McKay, Johnny McKeown, Kenneth A McLean, Paul McNally, Bairbre McNicholas, Elaine McPartlan, Edel Meaney, Cécile Mear-Passard, Maggie Mechlin, Maqsood Meher, Omar Mehkri, Ferruccio Mele, Luis Melo, Kashif Memon, Joao Joao Mendes, Ogechukwu Menkiti, Kusum Menon, Alexander J Mentzer, Emmanuelle Mercier, Noémie Mercier, Antoine Merckx, Mayka Mergeay-Fabre, Blake Mergler, António Mesquita, Roberta Meta, Osama Metwally, Agnès Meybeck, Dan Meyer, Alison M Meynert, Vanina Meysonnier, Amina Meziane, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Efstathia Mihelis, Vladislav Mihnovit, Hugo Miranda-Maldonado, Nor Arisah Misnan, Tahira Jamal Mohamed, Nik Nur Eliza Mohamed, Asma Moin, David Molina, Elena Molinos, Brenda Molloy, Mary Mone, Agostinho Monteiro, Claudia Montes, Giorgia Montrucchio, Shona C Moore, Sarah Moore, Lina Morales Cely, Lucia Moro, Catherine Motherway, Ana Motos, Hugo Mouquet, Clara Mouton Perrot, Julien Moyet, Caroline Mudara, Aisha Kalsoom Mufti, Ng Yong Muh, Dzawani Muhamad, Jimmy Mullaert, Fredrik Müller, Karl Erik Müller, Syed Muneeb, Nadeem Munir, Laveena Munshi, Aisling Murphy, Lorna Murphy, Aisling Murphy, Marlène Murris, Srinivas Murthy, Himed Musaab, Himasha Muvindi, Gugapriyaa Muyandy, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Dave Nagpal, Alex Nagrebetsky, Mangala Narasimhan, Nageswaran Narayanan, Rashid Nasim Khan, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Erni Nelwan, Raul Neto, Emily Neumann, Pauline Yeung Ng, Wing Yiu Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Marion Noret, Nurul Faten Izzati Norharizam, Lisa Norman, Alessandra Notari, Mahdad Noursadeghi, Karolina Nowicka, Adam Nowinski, Saad Nseir, Jose I Nunez, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Fionnuala O Brien, Annmarie O Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Shinichiro Ohshimo, Agnieszka Oldakowska, João Oliveira, Larissa Oliveira, Jee Yan Ong, Wilna Oosthuyzen, Anne Opavsky, Peter Openshaw, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Jamel Ortoleva, Javier Osatnik, Linda O'Shea, Miriam O'Sullivan, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Eric Oziol, Maïder Pagadoy, Justine Pages, Mario Palacios, Amanda Palacios, Massimo Palmarini, Giovanna Panarello, Hem Paneru, Lai Hui Pang, Mauro Panigada, Nathalie Pansu, Aurélie Papadopoulos, Rachael Parke, Melissa Parker, Briseida Parra, Taha Pasha, Jérémie Pasquier, Bruno Pastene, Fabian Patauner, Drashti Patel, Mohan Dass Pathmanathan, Luís Patrão, Patricia Patricio, Juliette Patrier, Lisa Patterson, Rajyabardhan Pattnaik, Mical Paul, Christelle Paul, Jorge Paulos, William A Paxton, Jean-François Payen, Kalaiarasu Peariasamy, Giles J Peek, Florent Peelman, Nathan Peiffer-Smadja, Vincent Peigne, Mare Pejkovska, Paolo Pelosi, Ithan D Peltan, Rui Pereira, Daniel Perez, Luis Periel, Thomas Perpoint, Antonio Pesenti, Vincent Pestre, Lenka Petrou, Ventzislava Petrov-Sanchez, Frank Olav Pettersen, Gilles Peytavin, Scott Pharand, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Carola Pierobon, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Isabelle Pironneau, Lionel Piroth, Ayodhia Pitaloka, Riinu Pius, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Maria Pokorska-Spiewak, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Jolanta Popielska, Diego Bastos Porto, Andra-Maris Post, Douwe F Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Oriane Puéchal, Bambang Pujo Semedi, Mathew Pulicken, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Víctor Quirós González, Else Quist-Paulsen, Mohammed Quraishi, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Gabrielle Ragazzo, Mutia Rahardjani, Rozanah Abd Rahman, Ahmad Kashfi Haji Ab Rahman, Arsalan Rahutullah, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Ahmad Afiq Ramli, Blandine Rammaert, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Liadain Reid, Liadain Reid, Dag Henrik Reikvam, Renato Reis, Jordi Rello, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Luis Felipe Reyes, Tiago Reyes, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Jordi Riera, Ana L Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Nicholas Rizer, Chiara Robba, André Roberto, Stephanie Roberts, David L Robertson, Olivier Robineau, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Pierre-Marie Roger, Emmanuel Roilides, Juliette Romaru, Roberto Roncon-Albuquerque, Mélanie Roriz, Manuel Rosa-Calatrava, Michael Rose, Dorothea Rosenberger, Nurul Hidayah Mohammad Roslan, Andrea Rossanese, Matteo Rossetti, Bénédicte Rossignol, Patrick Rossignol, Stella Rousset, Carine Roy, Benoît Roze, Desy Rusmawatiningtyas, Clark D Russell, Maria Ryan, Maeve Ryan, Steffi Ryckaert, Aleksander Rygh Holten, Isabela Saba, Sairah Sadaf, Musharaf Sadat, Valla Sahraei, Maximilien Saint-Gilles, Pranya Sakiyalak, Nawal Salahuddin, Leonardo Salazar, Jodat Saleem, Gabriele Sales, Stéphane Sallaberry, Charlotte Salmon Gandonniere, Hélène Salvator, Olivier Sanchez, Angel Sanchez-Miralles, Vanessa Sancho-Shimizu, Gyan Sandhu, Zulfiqar Sandhu, Pierre-François Sandrine, Marlene Santos, Shirley Sarfo-Mensah, Bruno Sarmento Banheiro, Iam Claire E Sarmiento, Benjamine Sarton, Ankana Satya, Sree Satyapriya, Rumaisah Satyawati, Egle Saviciute, Parthena Savvidou, Yen Tsen Saw, Justin Schaffer, Tjard Schermer, Arnaud Scherpereel, Marion Schneider, Stephan Schroll, Michael Schwameis, Gary Schwartz, Brendan Scicluna, Janet T Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Caroline Semaille, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Pablo Serrano Balazote, Ellen Shadowitz, Syamin Asyraf Shahidan, Mohammad Shamsah, Anuraj Shankar, Shaikh Sharjeel, Catherine A Shaw, Victoria Shaw, Ashraf Sheharyar, Rohan Shetty, Rajesh Mohan Shetty, Haixia Shi, Nisreen Shiban, Mohiuddin Shiekh, Nobuaki Shime, Hiroaki Shimizu, Keiki Shimizu, Sally Shrapnel, Pramesh Sundar Shrestha, Shubha Kalyan Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Jeanne Sibiude, Atif Siddiqui, Piret Sillaots, Catarina Silva, Rogério Silva, Maria Joao Silva, Wai Ching Sin, Dario Sinatti, Punam Singh, Budha Charan Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Michelle Smyth, Michelle Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Joshua Solomon, Tom Solomon, Agnès Sommet, Rima Song, Tae Song, Jack Song Chia, Michael Sonntagbauer, Azlan Mat Soom, Alberto Sotto, Edouard Soum, Marta Sousa, Ana Chora Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Alexandra Sperry, Elisabetta Spinuzza, B P Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Adrian Streinu-Cercel, David Stuart, Ami Stuart, Decy Subekti, Gabriel Suen, Jacky Y Suen, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Suwarti Suwarti, Andrey Svistunov, Sarah Syahrin, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Lysa Tagherset, Shahdattul Mawarni Taib, Ewa Talarek, Sara Taleb, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Taku Tanaka, Hiroyuki Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Richard S Tedder, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Pleun Terpstra, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Shaun Thompson, Emma C Thomson, David Thomson, Surain Raaj Thanga Thurai, Ryan S Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S Timashev, Jean-François Timsit, Noémie Tissot, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Margarida Torres, Antoni Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Michael Towers, Tony Trapani, Théo Treoux, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Jean-Marie Turmel, Lance C W Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, P G Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Timothy M Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Amélie Valran, Stijn Van de Velde, Marcel van den Berge, Machteld Van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Frank van Someren Greve, Ilonka van Veen, Hugo Van Willigen, Noémie Vanel, Henk Vanoverschelde, Pooja Varghese, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, James Vickers, José Ernesto Vidal, César Vieira, Deepak Vijayan, Joy Ann Villanueva, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Sanne Wesselius, T Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Suzette Willems, Virginie Williams, Calvin Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Gan Ee Xian, Lim Saio Xian, Kuan Pei Xuan, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Konrad Zawadka, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, David Zucman, University of Oxford, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This work was made possible by the UK Foreign, Commonwealth and Development Office, Wellcome (215091/Z/18/Z, 205228/Z/16/Z, 220757/Z/20/Z), Bill & Melinda Gates Foundation (OPP1209135), UK Medical Research Council Clinical Research Training Fellowship (MR/V001671/1), the philanthropic support of the donors to the University of Oxford’s COVID-19 Research Response Fund, CIHR Coronavirus Rapid Research Funding Opportunity (OV2170359) and the co-ordination in Canada by Sunnybrook Research Institute, endorsement of the Irish Critical Care—Clinical Trials Group, co-ordination in Ireland by the Irish Critical Care—Clinical Trials Network at University College Dublin and funding by the Health Research Board of Ireland (CTN-2014–12), the Rapid European COVID-19 Emergency Response research (RECOVER) (H2020 project 101003589) and European Clinical Research Alliance on Infectious Diseases (ECRAID) (965313), the COVID clinical management team, AIIMS, Rishikesh, India, the COVID-19 Clinical Management team, Manipal Hospital Whitefield, Bengaluru, India, Cambridge NIHR Biomedical Research Centre, the dedication and hard work of the Groote Schuur Hospital Covid ICU Team, support by the Groote Schuur nursing and University of Cape Town registrar bodies co-ordinated by the Division of Critical Care at the University of Cape Town, the Liverpool School of Tropical Medicine and the University of Oxford, the dedication and hard work of the Norwegian SARS-CoV-2 study team, the Research Council of Norway (grant no. 312780) and a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner, Imperial NIHR Biomedical Research Centre, the Comprehensive Local Research Networks of which PJMO is an NIHR Senior Investigator (NIHR201385), Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115523 COMBACTE, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007– 2013) and EFPIA companies, in-kind contribution, the French COVID cohort (NCT04262921) is sponsored by INSERM and is funded by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n 20–0424), Stiftungsfonds zur Förderung der Bekämpfung der Tuberkulose und anderer Lungenkrankheiten of the City of Vienna (project no. APCOV22BGM), Italian Ministry of Health ‘Fondi Ricerca corrente–L1P6’ to IRCCS Ospedale Sacro Cuore–Don Calabria, Australian Department of Health grant (3273191), Gender Equity Strategic Fund at University of Queensland, Artificial Intelligence for Pandemics (A14PAN) at University of Queensland, the Australian Research Council Centre of Excellence for Engineered Quantum Systems (EQUS, CE170100009), the Prince Charles Hospital Foundation, Australia, grants from Instituto de Salud Carlos III, Ministerio de Ciencia, Spain, Brazil, National Council for Scientific and Technological Development (scholarship no. 303953/2018–7), the Firland Foundation, Shoreline, Washington, USA, a grant from foundation Bevordering Onderzoek Franciscus, the South Eastern Norway Health Authority and the Research Council of Norway, and preparedness work conducted by the Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection. Data and Material provision was supported by grants from the National Institute for Health Research (NIHR, award CO-CIN-01), the Medical Research Council (MRC, and grant MC_PC_19059) and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with PHE (award no. 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award no. 200927), Liverpool Experimental Cancer Medicine Centre (grant no. C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award no. IS-BRC-1215–20013) and NIHR Clinical Research Network providing infrastructure support.

Subjects
Male, Epidemiology, MESH: Hospitalization, MESH: Proportional Hazards Models, MESH: Risk Factors, Risk Factors, MESH: Child, cohort study, MESH: COVID-19, Humans, MESH: SARS-CoV-2, Child, Proportional Hazards Models, MESH: Humans, MESH: Middle Aged, SARS-CoV-2, COVID-19, risk of death, General Medicine, Middle Aged, co-morbidities, symptoms, treatments, MESH: Male, Hospitalization, Intensive Care Units, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19/therapy
Abstract

Background We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

Published
2023
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46. Randomized Phase II Study of Physiologic MRI-Directed Adaptive Radiation Boost in Poor Prognosis Head and Neck Cancer

Author

Michelle L. Mierzwa, Madhava Aryal, Choonik Lee, Matthew Schipper, Monica VanTil, Krystal Morales, Paul L. Swiecicki, Keith A. Casper, Kelly M. Malloy, Matthew E. Spector, Andrew G. Shuman, Steven B. Chinn, Mark E.P. Prince, Chaz L. Stucken, Andrew J. Rosko, Theodore S. Lawrence, J. Chad Brenner, Benjamin Rosen, Caitlin A. Schonewolf, Jennifer Shah, Avraham Eisbruch, Francis P. Worden, and Yue Cao

Subjects
Cancer Research, Oncology, Head and Neck Neoplasms, Humans, Radiotherapy Dosage, Magnetic Resonance Imaging, Article, Disease-Free Survival
Abstract

Purpose: We conducted a randomized phase II multicenter clinical trial to test the hypothesis that physiologic MRI-based radiotherapy (RT) dose escalation would improve the outcome of patients with poor prognosis head and neck cancer. Patients and Methods: MRI was acquired at baseline and at RT fraction 10 to create low blood volume/apparent diffusion coefficient maps for RT boost subvolume definition in gross tumor volume. Patients were randomized to receive 70 Gy (standard RT) or 80 Gy to the boost subvolume (RT boost) with concurrent weekly platinum. The primary endpoint was disease-free survival (DFS) with significance defined at a one-sided 0.1 level, and secondary endpoints included locoregional failure (LRF), overall survival (OS), comparison of adverse events and patient reported outcomes (PRO). Results: Among 81 randomized patients, neither the primary endpoint of DFS (HR = 0.849, P = 0.31) nor OS (HR = 1.19, P = 0.66) was significantly improved in the RT boost arm. However, the incidence of LRF was significantly improved with the addition of the RT boost (HR = 0.43, P = 0.047). Two-year estimates [90% confidence interval (CI)] of the cumulative incidence of LRF were 40% (27%–53%) in the standard RT arm and 18% (10%–31%) in the RT boost arm. Two-year estimates (90% CI) for DFS were 48% (34%–60%) in the standard RT arm and 57% (43%–69%) in the RT boost arm. There were no significant differences in toxicity or longitudinal differences seen in EORTC QLQ30/HN35 subscales between treatment arms in linear mixed-effects models. Conclusions: Physiologic MRI-based RT boost decreased LRF without a significant increase in grade 3+ toxicity or longitudinal PRO differences, but did not significantly improve DFS or OS. Additional improvements in systemic therapy are likely necessary to realize improvements in DFS and OS.

Published
2022
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47. The socioeconomic gradient of alcohol use: an analysis of nationally representative survey data from 55 low-income and middle-income countries

Author

Yuanwei Xu, Pascal Geldsetzer, Jen Manne-Goehler, Michaela Theilmann, Maja-E Marcus, Zhaxybay Zhumadilov, Sarah Quesnel-Crooks, Omar Mwalim, Sahar Saeedi Moghaddam, Sogol Koolaji, Khem B Karki, Farshad Farzadfar, Narges Ebrahimi, Albertino Damasceno, Krishna K Aryal, Kokou Agoudavi, Rifat Atun, Till Bärnighausen, Justine Davies, Lindsay M Jaacks, Sebastian Vollmer, and Charlotte Probst

Subjects
Male, Alcohol Drinking, Socioeconomic Factors, Income, Humans, Female, General Medicine, Developing Countries, Poverty
Abstract

Alcohol is a leading risk factor for over 200 conditions and an important contributor to socioeconomic health inequalities. However, little is known about the associations between individuals' socioeconomic circumstances and alcohol consumption, especially heavy episodic drinking (HED; ≥5 drinks on one occasion) in low-income or middle-income countries. We investigated the association between individual and household level socioeconomic status, and alcohol drinking habits in these settings.In this pooled analysis of individual-level data, we used available nationally representative surveys-mainly WHO Stepwise Approach to Surveillance surveys-conducted in 55 low-income and middle-income countries between 2005 and 2017 reporting on alcohol use. Surveys from participants aged 15 years or older were included. Logistic regression models controlling for age, country, and survey year stratified by sex and country income groups were used to investigate associations between two indicators of socioeconomic status (individual educational attainment and household wealth) and alcohol use (current drinking and HED amongst current drinkers).Surveys from 336 287 participants were included in the analysis. Among males, the highest prevalence of both current drinking and HED was found in lower-middle-income countries (L-MICs; current drinking 49·9% [95% CI 48·7-51·2] and HED 63·3% [61·0-65·7]). Among females, the prevalence of current drinking was highest in upper-middle-income countries (U-MIC; 29·5% [26·1-33·2]), and the prevalence of HED was highest in low-income countries (LICs; 36·8% [33·6-40·2]). Clear gradients in the prevalence of current drinking were observed across all country income groups, with a higher prevalence among participants with high socioeconomic status. However, in U-MICs, current drinkers with low socioeconomic status were more likely to engage in HED than participants with high socioeconomic status; the opposite was observed in LICs, and no association between socioeconomic status and HED was found in L-MICs.The findings call for urgent alcohol control policies and interventions in LICs and L-MICs to reduce harmful HED. Moreover, alcohol control policies need to be targeted at socially disadvantaged groups in U-MICs.Deutsche Forschungsgemeinschaft and the National Center for Advancing Translational Sciences of the US National Institutes of Health.

Published
2022
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48. Nursing Home Resident Admission Characteristics and Potentially Preventable Emergency Department Transfers

Author

Komal Aryal, Fabrice Mowbray, Andrea Gruneir, Lauren E. Griffith, Michelle Howard, Amina Jabbar, Aaron Jones, Peter Tanuseputro, Lauren Lapointe-Shaw, and Andrew P. Costa

Subjects
Ontario, Patient Transfer, Health Policy, Humans, Female, General Medicine, Geriatrics and Gerontology, Emergency Service, Hospital, General Nursing, Nursing Homes, Retrospective Studies
Abstract

To determine which nursing home (NH) resident-level admission characteristics are associated with potentially preventable emergency department (PPED) transfers.We conducted a population-level retrospective cohort study on NH resident data collected using the Resident Assessment Instrument-Minimum Data Set Version 2.0 and linked to the National Ambulatory Care Reporting System for ED transfers.We used all NH resident admission assessments from January 1, 2017, to December 31, 2018, in Ontario.The cohort included the admission assessment of 56,433 NH residents.PPED transfers were defined based on the International Classification of Disease, Version 10 (Canadian) We used logistic regression with 10-fold cross-validation and computed average marginal effects to identify the association between resident characteristics at NH admission and PPED transfers within 92 days after admission.Overall, 6.2% of residents had at least 1 PPED transfer within 92 days of NH admission. After adjustment, variables that had a prevalence of 10% or more that were associated with a 1% or more absolute increase in the risk of a PPED transfer included polypharmacy [of cohort (OC) 84.4%, risk difference (RD) 2.0%], congestive heart failure (OC 29.0%, RD 3.0%), and renal failure (OC 11.6%, RD 1.2%). Female sex (OC 63.2%, RD -1.3%), a do not hospitalize directive (OC 24.4%, RD -2.6%), change in mood (OC 66.9%, RD -1.2%), and Alzheimer's or dementia (OC 62.1%, RD -1.2%) were more than 10% prevalent and associated with a 1% or more absolute decrease in the risk of a PPED.Though many routinely collected resident characteristics were associated with a PPED transfer, the absence of sufficiently discriminating characteristics suggests that emergency department visits by NH residents are multifactorial and difficult to predict. Future studies should assess the clinical utility of risk factor identification to prevent transfers.

Published
2022
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49. Anxiety, Depression, Quality of Life, Caregiver Burden, and Perceptions of Caregiver-Centered Communication among Black and White Hospice Family Caregivers

Author

Karen Bullock, Lauren T Starr, Karla T. Washington, Debra Parker Oliver, Subhash Aryal, and George Demiris

Subjects
Gerontology, Adolescent, media_common.quotation_subject, Caregiver Burden, Anxiety, Quality of life (healthcare), Perception, medicine, Humans, General Nursing, Depression (differential diagnoses), media_common, Randomized Controlled Trials as Topic, White (horse), Family caregivers, business.industry, Depression, Communication, Hospices, General Medicine, Caregiver burden, Original Articles, Mental health, Anxiety Disorders, Anesthesiology and Pain Medicine, Caregivers, Quality of Life, medicine.symptom, business
Abstract

BACKGROUND: Anxiety, depression, and reduced quality of life (QOL) are common problems for hospice family caregivers, but it is unknown if disparities in these experiences exist among Black and White caregivers. OBJECTIVES: To compare anxiety, depression, QOL, caregiver burden, and perceptions of caregiver-centered hospice team communication between Black and White hospice family caregivers. DESIGN: Secondary analysis of baseline data from two randomized clinical trials. SETTING/SUBJECTS: Seven hundred twenty-two Black and White hospice family caregivers ages 18+ from Midwestern and Northeastern United States. MEASUREMENTS: Measures included the Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire (PHQ-9), Caregiver Quality-of-Life Index–Revised (CQLI-R), Zarit Burden Interview (ZBI-7), and Caregiver-Centered Communication Questionnaire (CCCQ). RESULTS: Black and White caregivers differed across demographic and socioeconomic variables. Nearly one-third of hospice family caregivers reported moderate-to-severe anxiety (32.1%) and moderate-to-severe depressive symptoms (32.0%). White caregivers reported lower QOL than Black caregivers (p = 0.04), specifically in emotional (p = 0.02) and social (p = 0.0005) domains. In multiple regression analyses controlling for caregiver and patient factors, we found no racial differences in depression, anxiety, QOL, caregiver burden, or perceptions of caregiver-centered hospice communication. CONCLUSIONS: Despite demographic and socioeconomic differences, Black and White hospice family caregivers experience similarly high levels of anxiety, depression, burden, and perceptions of hospice communication. Interventions to support hospice family caregivers across racial groups and research that identifies factors that mediate social determinants of health in this population are needed. The development and validation of culture-concordant mental health screening tools in racially diverse populations is recommended. Trial registration: ClinicalTrials.gov NCT02929108 and ClinicalTrials.gov NCT01444027.

Published
2023

50. Data Resource Profile: The Global Health and Population Project on Access to Care for Cardiometabolic Diseases (HPACC)

Author

Jennifer Manne-Goehler, Michaela Theilmann, David Flood, Maja E Marcus, Glennis Andall-Brereton, Kokou Agoudavi, William Andres Lopez Arboleda, Krishna K Aryal, Brice Bicaba, Pascal Bovet, Luisa Campos Caldeira Brant, Garry Brian, Grace Chamberlin, Geoffrey Chen, Albertino Damasceno, Maria Dorobantu, Matthew Dunn, Cara Ebert, Farshad Farzadfar, Mongal Singh Gurung, David Guwatudde, Corine Houehanou, Dismand Houinato, Nahla Hwalla, Jutta M Adelin Jorgensen, Khem B Karki, Demetre Labadarios, Nuno Lunet, Deborah Carvalho Malta, João S Martins, Mary T Mayige, Roy Wong McClure, Sahar Saeedi Moghaddam, Kibachio J Mwangi, Omar Mwalim, Bolormaa Norov, Sarah Quesnel-Crooks, Sabrina Rhode, Jacqueline A Seiglie, Abla Sibai, Bahendeka K Silver, Lela Sturua, Andrew Stokes, Adil Supiyev, Lindiwe Tsabedze, Zhaxybay Zhumadilov, Lindsay M Jaacks, Rifat Atun, Justine I Davies, Pascal Geldsetzer, Sebastian Vollmer, and Till W Bärnighausen

Subjects
Metabolic Syndrome, Risk Factors, Cardiovascular Diseases, Epidemiology, Humans, General Medicine, Global Health, Health Services Accessibility
Published
2022
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