Suchergebnisse

BACKGROUND: Over the last 30 years, South Africa has experienced four 'colliding epidemics' of HIV and tuberculosis, chronic illness and mental health, injury and violence, and maternal, neonatal, and child mortality, which have had substantial effects on health and well-being. Using data from the 2019 Global Burden of Diseases, Injuries and Risk Factors Study (GBD 2019), we evaluated national and provincial health trends and progress towards important Sustainable Development Goal targets from 1990 to 2019. METHODS: We analysed GBD 2019 estimates of mortality, non-fatal health loss, summary health measures and risk factor burden, comparing trends over 1990–2007 and 2007–2019. Additionally, we decomposed changes in life expectancy by cause of death and assessed healthcare system performance. RESULTS: Across the nine provinces, inequalities in mortality and life expectancy increased over 1990–2007, largely due to differences in HIV/AIDS, then decreased over 2007–2019. Demographic change and increases in non-communicable diseases nearly doubled the number of years lived with disability between 1990 and 2019. From 1990 to 2019, risk factor burdens generally shifted from communicable and nutritional disease risks to non-communicable disease and injury risks; unsafe sex remained the top risk factor. Despite widespread improvements in healthcare system performance, the greatest gains were generally in economically advantaged provinces. CONCLUSIONS: Reductions in HIV/AIDS and related conditions have led to improved health since 2007, though most provinces still lag in key areas. To achieve health targets, provincial governments should enhance health investments and exchange of knowledge, resources and best practices alongside populations that have been left behind, especially following the COVID-19 pandemic.

ABSTRACT Objective: There are over 4000 trials conducted in people with COVID-19. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for COVID-19 trials. Design: In an online survey conducted in English, Chinese, Italian, Portuguese and Spanish languages, adults with COVID-19, their family members, health professionals and the general public rated the importance of outcomes using a 9-point Likert scale (7-9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analysed thematically. Setting: International Participants: Adults aged 18 years and over with confirmed or suspected COVID-19, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers). Main Results: In total, 9289 participants from 111 countries (776 people with COVID-19 or family members, 4882 health professionals, and 3631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean >7.5, median ≥ 8, and >70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes. Conclusions: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals. ; The project is funded by the Flinders University and the National COVID-19 Clinical Evidence Taskforce, convened by the Australian Living Evidence Consortium, hosted by Cochrane Australia, School of Public Health and Preventive Medicine, Monash University supported by the Australian Government, Victorian Department of Health and Human Services, Ian Potter Foundation, Walter Cottman Endowment Fund (managed by Equity Trustees) and the Lord Mayor's Charitable Foundation). AT is supported by The University of Sydney Robinson Fellowship. ACM is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z)

Refined baseline inventories of non-indigenous species (NIS) are set per European Union Member State (MS), in the context of the Marine Strategy Framework Directive (MSFD). The inventories are based on the initial assessment of the MSFD (2012) and the updated data of the European Alien Species Information Network, in collaboration with NIS experts appointed by the MSs. The analysis revealed that a large number of NIS was not reported from the initial assessments. Moreover, several NIS initially listed are currently considered as native in Europe or were proven to be historical misreportings. The refined baseline inventories constitute a milestone for the MSFD Descriptor 2 implementation, providing an improved basis for reporting new NIS introductions, facilitating the MSFD D2 assessment. In addition, the inventories can help MSs in the establishment of monitoring systems of targeted NIS, and foster cooperation on monitoring of NIS across or within shared marine subregions. ; Henn Ojaveer and Maiju Lehtiniemi wish to acknowledge the project COMPLETE (Completing management options in the Baltic Sea region to reduce risk of invasive species introduction by shipping), co-financed by the European Union's funding Programme Interreg Baltic Sea Region (European Regional Development Fund). João Canning-Clode was supported by a starting grant in the framework of the 2014 FCT Investigator Programme (IF/01606/2014/CP1230/CT0001) and wish to acknowledge the support of Fundação para a Ciência e Tecnologia (FCT), through the strategic project UID/MAR/04292/2019 granted to MARE.

Refined baseline inventories of non-indigenous species (NIS) are set per European Union Member State (MS), in the context of the Marine Strategy Framework Directive (MSFD). The inventories are based on the initial assessment of the MSFD (2012) and the updated data of the European Alien Species Information Network, in collaboration with NIS experts appointed by the MSs. The analysis revealed that a large number of NIS was not reported from the initial assessments. Moreover, several NIS initially listed are currently considered as native in Europe or were proven to be historical misreportings. The refined baseline inventories constitute a milestone for the MSFD Descriptor 2 implementation, providing an improved basis for reporting new NIS introductions, facilitating the MSFD D2 assessment. In addition, the inventories can help MSs in the establishment of monitoring systems of targeted NIS, and foster cooperation on monitoring of NIS across or within shared marine subregions. ; peer-reviewed

Refined baseline inventories of non-indigenous species (NIS) are set per European Union Member State (MS), in the context of the Marine Strategy Framework Directive (MSFD). The inventories are based on the initial assessment of the MSFD (2012) and the updated data of the European Alien Species Information Network, in collaboration with NIS experts appointed by the MSs. The analysis revealed that a large number of NIS was not reported from the initial assessments. Moreover, several NIS initially listed are currently considered as native in Europe or were proven to be historical misreportings. The refined baseline inventories constitute a milestone for the MSFD Descriptor 2 implementation, providing an improved basis for reporting new NIS introductions, facilitating the MSFD D2 assessment. In addition, the inventories can help MSs in the establishment of monitoring systems of targeted NIS, and foster cooperation on monitoring of NIS across or within shared marine subregions.

This is the final version of the article. It first appeared from Public Library of Science via http://dx.doi.org/ 10.1371/journal.pmed.1002094. ; ${\bf Background:}$ Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. ${\bf Methods~and~Findings:}$ Plasma phospholipid PUFAs were measured by gas-chromatography among 12,132 incident T2D cases and 15,919 sub-cohort participants in EPIC-InterAct study across 8 European countries. Country-specific hazard ratios (HR) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs α-linolenic acid (ALA) was inversely associated with T2D (HR per SD 0.93; 95%CI 0.88,0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 0.77,0.83) and eicosadienoic acid (EDA) (0.89; 0.85,0.94) were inversely related, arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA) and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to 9 studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs. ${\bf Conclusions:}$ These large-scale findings suggest important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA, DHA) with T2D. Moreover they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well investigated PUFAs points to the importance of considering individual fatty acids rather than a focus on fatty acid class. ; Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). In addition, InterAct investigators acknowledge funding from the following sources: Medical Research Council Epidemiology Unit MC_UU_12015/1 and MC_UU_12015/5, and Medical Research Council Human Nutrition Research MC_UP_A090_1006 and Cambridge Lipidomics Biomarker Research Initiative G0800783; FLC and TJK: Cancer Research UK; JMH and MJT: Health Research Fund of the Spanish Ministry of Health; Murcia Regional Government (Nº 6236); MG: Regional Government of Navarre; -IS, DLvdA, AMWS, YTvdS: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands; Verification of diabetes cases in EPIC-NL was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht; PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation; RK: German Cancer Aid, German Ministry of Research (BMBF); KTK: Medical Research Council UK, Cancer Research UK; PMN: Swedish Research Council; KO and AT: Danish Cancer Society; JRQ: Asturias Regional Government; OR: The Västerboten County Council; RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government; ER: Imperial College Biomedical Research Centre.

The fight against infectious diseases often focuses on epidemics and pandemics, which demand urgent resources and command attention from the health authorities and media. However, the vast majority of deaths caused by infectious diseases occur in endemic zones, particularly in developing countries, placing a disproportionate burden on underfunded health systems and often requiring international interventions. The provision of vaccines and other biologics is hampered not only by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, but also by challenges caused by distribution and storage, particularly in regions without a complete cold chain. In this review article, we consider the potential of molecular farming to address the challenges of endemic and re-emerging diseases, focusing on edible plants for the development of oral drugs. Key recent developments in this field include successful clinical trials based on orally delivered dried leaves of Artemisia annua against malarial parasite strains resistant to artemisinin combination therapy, the ability to produce clinical-grade protein drugs in leaves to treat infectious diseases and the long-term storage of protein drugs in dried leaves at ambient temperatures. Recent FDA approval of the first orally delivered protein drug encapsulated in plant cells to treat peanut allergy has opened the door for the development of affordable oral drugs that can be manufactured and distributed in remote areas without cold storage infrastructure and that eliminate the need for expensive purification steps and sterile delivery by injection. ; The authors would like to thank the Spanish Ministry of Economy, Industry and Competitiveness (project AGL2017-85377-R), the Spanish Ministry of Science, Innovation and Universities (projects RTI2018-097613-B-I00 and PGC2018-097655-B-I00), the EU Horizon 2020 project Pharma-Factory (774078) and the Gener- alitat de Catalunya (Grups Consolidats2017-SGR828); Ag encia de Gesti o d'Ajuts Universitaris i de Recerca (AGAUR), Departament d'Empresa i Coneixement de la Generalitat de Catalunya (PAND EMIES 2020); Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular funded by FEDER funds through COMPETE2020)—Programa Operacional Compet- itividade e Internacionalizacß~ao (POCI) and by the FCT (Portugal) through the R&D Unit, UIDB/04551/2020 (GREEN-IT—Biore- sources for Sustainability); UKIERI and the Hotung Foundation for sustained support of the Bharathiar University / St. George's Univ. of London collaboration and the Molecular Immunology Unit at St. George's Univ. of London. The Max Planck Society, the EU Horizon 2020 project Newcotiana (760331-2) and a grant from the European Research Council (ERC-ADG-2014; grant agreement 669982) to RB. KMOC, RMT and STH acknowledge support from the InnCoCells project funded by the European Union's Horizon 2020 research and innovation programme under grant agreement 101000373. PSS, KAM, RF and SN are partially supported by a CRAFT award (COVID-19 Research Accelerator Funding Track) by the University of California Davis. KAM and SN were partially supported by NASA Space Technology Research (award number NNX17AJ31G) and by the Translational Research Institute through NASA (grant number NNX16AO69A); EMBRAPA (Brazilian Agricultural Corporation), INCT BioSyn (National Institute of Science and Technology in Synthetic Biology), CNPq, CAPES, Brazilian Ministry of Health, FAPDFnd Universidade Cat olica de Bras ılia (UCB), Bras ılia, Brazil; BBSRC Grant BB/L020955/1, the JIC Strategic Programme Grant 'Molecules from Nature –Enhanced Research Capacity' (BBS/E/ J/000PR9794), the John Innes Foundation and the Department of Health and Social Care using UK Aid funding managed by the BBSRC; and The Austrian Science Fund FWF (project W1224). TTW Veni Grant 16740 from the Netherlands Organization for Scientific Research. Research in the Daniell laboratory was supported by NIH grants R01 GM 63879, R01 107904, R01 HL 109442, R01 133191 and grants from Bayer, Novo Nordisk and Shire/Takeda. The National Heart Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services, through the Science Moving TowArds Research Trans- lation and Therapy (SMARTT) programme contracts # HHSN268201600014C, HHSN268201600011C supported IND enabling regulatory, toxicology and pharmacokinetic studies. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author (s) and do not necessarily reflect the views of the University of California, Davis, National Aeronautics and Space Administration (NASA) or the Translational Research Institute for Space Health (TRISH). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Views expressed in this article are those of the authors and do not necessarily reflect those of the employing institutions or the UK Department of Health and Social Care

Background Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer. Objective This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates. Study Design In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent–weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use. Results Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more ...

Infectious diseases, also known as transmissible or communicable diseases, are caused by pathogens or parasites that spread in communities by direct contact with infected individuals or contaminated materials, through droplets and aerosols, or via vectors such as insects. Such diseases cause 17% of all human deaths and their management and control places an immense burden on healthcare systems worldwide. Traditional approaches for the prevention and control of infectious diseases include vaccination programmes, hygiene measures and drugs that suppress the pathogen, treat the disease symptoms or attenuate aggressive reactions of the host immune system. The provision of vaccines and biologic drugs such as antibodies is hampered by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, particularly in developing countries where infectious diseases are prevalent and poorly controlled. Molecular farming, which uses plants for protein expression, is a promising strategy to address the drawbacks of current manufacturing platforms. In this review article, we consider the potential of molecular farming to address healthcare demands for the most prevalent and important epidemic and pandemic diseases, focussing on recent outbreaks of high-mortality coronavirus infections and diseases that disproportionately affect the developing world. ; The authors would like to thank the Spanish Ministry of Economy, Industry and Competitiveness (project AGL2017-85377-R), the Spanish Ministry of Science, Innovation and Universities (projects RTI2018-097613-B-I00 and PGC2018-097655-B-I00), the EU Horizon 2020 project Pharma-Factory (774078) and the Gener- alitat de Catalunya (Grups Consolidats 2017-SGR828), Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR), Departa- ment d'Empresa i Coneixement de la Generalitat de Catalunya (PAND EMIES 2020). Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular funded by FEDER funds through COMPETE2020 –Programa Operacional Compet- itividade e Internacionalizacß~ao (POCI) and by the FCT (Portugal) through the R&D Unit, UIDB/04551/2020 (GREEN-IT –Biore- sources for Sustainability). UKIERI and the Hotung Foundation for sustained support of the Bharathiar University / St. George's Univ. of London collaboration and the Molecular Immunology Unit at St. George's Univ of London. The Max Planck Society, the EU Horizon 2020 project Newcotiana, 760331-2) and a grant from the European Research Council (ERC-ADG-2014; grant agree- ment 669982) to RB. KMOC, RMT and STH acknowledge support from the InnCoCells project funded by the European Union's Horizon 2020 research and innovation programme under grant agreement 101000373. PSS, KAM, RF, and SN are partially supported by a CRAFT award (COVID-19 Research Accelerator Funding Track) by the University of California Davis. KAM and SN were partially supported by NASA Space Technology Research (award number NNX17AJ31G) and by the Translational Research Institute through NASA (grant number NNX16AO69A). EMBRAPA (Brazilian Agricultural Corporation), INCT BioSyn (National Institute of Science and Technology in Synthetic Biology), CNPq, CAPES, Brazilian Ministry of Health, FAPDF and Universidade Cat olica de Bras ılia (UCB), Bras ılia, Brazil. BBSRC Grant BB/L020955/1, the JIC Strategic Programme Grant 'Molecules from Nature –Enhanced Research Capacity' (BBS/E/ J/000PR9794), the John Innes Foundation and the Department of Health and Social Care using UK Aid funding managed by the BBSRC. The Austrian Science Fund FWF (project W1224). TTW Veni Grant 16740 from the Netherlands Organization for Scientific Research. Research in the Daniell laboratory was supported by NIH grants R01 GM 63879, R01 107904, R01 HL 109442, R01 133191 and grants from Bayer, Novo Nordisk and Shire/Takeda. The National Heart Lung and Blood Institute, National Institutes of Health, Department of Healthand Human Services, through the Science Moving TowArds Research Trans- lation and Therapy (SMARTT) program contracts # HHSN268201600014C, HHSN268201600011C supported IND enabling regulatory, toxicology and pharmacokinetic studies. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author (s) and do not necessarily reflect the views of the University of California, Davis, National Aeronautics and Space Administration (NASA) or the Translational Research Institute for Space Health (TRISH). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Views expressed in this article are those of the authors and do not necessarily reflect those of the employing institutions or the UK Department of Health and Social Care.

Obstetrical complications, often referred to as the great obstetrical syndromes, are among the most common global causes of mortality and morbidity in young women and their infants. However, treatments for these syndromes are underdeveloped compared with other fields of medicine and are urgently needed. This current paucity of treatments for obstetrical complications is a reflection of the challenges of drug development in pregnancy. The appetite of pharmaceutical companies to invest in research for obstetrical syndromes is generally reduced by concerns for maternal, fetal, and infant safety, poor definition, and high-risk regulatory paths toward product approval. Notably, drug candidates require large investments for development with an unguaranteed return on investment. Furthermore, the discovery of promising drug candidates is hampered by a poor understanding of the pathophysiology of obstetrical syndromes and their uniqueness to human pregnancies. This limits translational extrapolation and de-risking strategies in preclinical studies, as available for other medical areas, compounded with limited fetal safety monitoring to capture early prenatal adverse reactions. In addition, the ethical review committees are reluctant to approve the inclusion of pregnant women in trials, and in the absence of regulatory guidance in obstetrics, clinical development programs are subject to unpredictable regulatory paths. To develop effective and safe drugs for pregnancy complications, substantial commitment, and investment in research for innovative therapies are needed in parallel with the creation of an enabling ethical, legislative, and guidance framework. Solutions are proposed to enable stakeholders to work with a common set of expectations to facilitate progress in this medical discipline. Addressing this significant unmet need to advance maternal and possibly perinatal health requires the involvement of all stakeholders and specifically patients, couples, and cli-nicians facing pregnancy complications in the dearth of appropriate therapies. This paper focused on the key pharmaceutical research and development challenges to achieve effective and safe treatments for obstetrical syndromes.

The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO. ; The BCFR was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the BCFR. CNIO was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish ...

BACKGROUND: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. METHODS: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence. RESULTS: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades. CONCLUSIONS: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field. ; Susanne Röhr was supported by the LIFE—Leipzig Research Center for Civilization Diseases, University of Leipzig, funded by the European Social Fund and the Free State of Saxony (grant number LIFE-103 P1). This work was further supported by a grant from the Hans and Ilse Breuer Foundation. Funding for COSMIC comes from a National Health and Medical Research Council of Australia Program Grant (ID 1093083) (PSS, HB), the National Institute On Aging of the National Institutes of Health under Award Number RF1AG057531 (PSS, MG, RBL, KR, KWK, HB), and philanthropic contributions to The Dementia Momentum Fund (UNSW Project ID PS38235). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funders. Funding for each of the contributing studies is as follows: ActiveAging: no funding; CFAS: major awards from the Medical Research Council and the Department of Health, UK; EAS: Supported in part by National Institutes of Health grants NIA 2 P01 AG03949, the Leonard and Sylvia Marx Foundation, and the Czap Foundation; EPIDEMCA: French National Research Agency (ANR-09-MNPS-009-01); ESPRIT: Novartis; Invece.Ab: Financed with own funds and supported in part by "Federazione Alzheimer Italia", Milan, Italy (AG); KLOSCAD: the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea [Grant No. HI09C1379 (A092077)]; LEILA75+: the Interdisciplinary Centre for Clinical Research at the University of Leipzig (Interdisziplinäres Zentrum für Klinische Forschung/IZKF; grant 01KS9504); LRGS-TUA: Ministry of Education Longterm Research Grant Scheme (LRGS/BU/2012/UKM–UKM/K/01); MAAS: The Netherlands Organization for Scientific Research (NOW). Grant Number: 002.005.019; MoVIES: Grant # R01AG07562 from the National Institute on Aging, National Institutes of Health, United States Department of Health and Human Services; PATH: National Health and Medical Research Council of Australia grants 973302, 179805, 157125 and 1002160; SGS: JSPS KAKENHI Grant Number JP17K09146; SLASII: The SLAS2 study was supported by research grants from the Agency for Science Technology and Research (A*STAR) Biomedical Research Council (BMRC) https://www.a-star.edu.sg/ [Grants 03/1/21/17/214 and 08/1/21/19/567] and the National Medical Research Council http://www.nmrc.gov.sg/ [Grant: NMRC/1108/2007]; ZARADEMP: Supported by grants from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness, Madrid, Spain (grants 94/1562, 97/1321E, 98/0103, 01/0255, 03/0815, 06/0617, G03/128), and the Fondo Europeo de Desarrollo Regional (FEDER) of the European Union and Gobierno de Aragón, Group #19.

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

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.

BACKGROUND: To mitigate SARS-CoV-2 transmission risks from international air travellers, many countries implemented a combination of up to 14 days of self-quarantine upon arrival plus PCR testing in the early stages of the COVID-19 pandemic in 2020. AIM: To assess the effectiveness of quarantine and testing of international travellers to reduce risk of onward SARS-CoV-2 transmission into a destination country in the pre-COVID-19 vaccination era. METHODS: We used a simulation model of air travellers arriving in the United Kingdom from the European Union or the United States, incorporating timing of infection stages while varying quarantine duration and timing and number of PCR tests. RESULTS: Quarantine upon arrival with a PCR test on day 7 plus a 1-day delay for results can reduce the number of infectious arriving travellers released into the community by a median 94% (95% uncertainty interval (UI): 89–98) compared with a no quarantine/no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median > 99%; 95% UI: 98–100). Even shorter quarantine periods can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (mean incubation period) in quarantine and have at least one negative test before release are highly effective (median reduction 89%; 95% UI: 83–95)). CONCLUSION: The effect of different screening strategies impacts asymptomatic and symptomatic individuals differently. The choice of an optimal quarantine and testing strategy for unvaccinated air travellers may vary based on the number of possible imported infections relative to domestic incidence.