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Background Workplace absenteeism increases significantly during influenza epidemics. Sick leave records may facilitate more timely detection of influenza outbreaks, as trends in increased sick leave may precede alerts issued by sentinel surveillance systems by days or weeks. Sick leave data have not been comprehensively evaluated in comparison to traditional surveillance methods. The aim of this paper is to study the performance and the feasibility of using a detection system based on sick leave data to detect influenza outbreaks. Methods Sick leave records were extracted from private French health insurance data, covering on average 209,932 companies per year across a wide range of sizes and sectors. We used linear regression to estimate the weekly number of new sick leave spells between 2016 and 2017 in 12 French regions, adjusting for trend, seasonality and worker leaves on historical data from 2010 to 2015. Outbreaks were detected using a 95%-prediction interval. This method was compared to results from the French Sentinelles network, a gold-standard primary care surveillance system currently in place. Results Using sick leave data, we detected 92% of reported influenza outbreaks between 2016 and 2017, on average 5.88 weeks prior to outbreak peaks. Compared to the existing Sentinelles model, our method had high sensitivity (89%) and positive predictive value (86%), and detected outbreaks on average 2.5 weeks earlier. Conclusion Sick leave surveillance could be a sensitive, specific and timely tool for detection of influenza outbreaks.

ObjectivesPromoting active modes of transportation such as cycling may generate important public health, economic, and climate mitigation benefits. We aim to assess mortality and morbidity impacts of cycling in a country with relatively low levels of cycling, France, along with associated monetary benefits; we further assess the potential additional benefits of shifting a portion of short trips from cars to bikes, including projected greenhouse gas emissions savings.MethodsUsing individual data from a nationally-representative mobility survey, we described the French 2019 cycling levels by age and sex. We conducted a burden of disease analysis to assess the incidence of five chronic diseases (breast cancer, colon cancer, cardio-vascular diseases, dementia, and type-2 diabetes) and numbers of deaths prevented by cycling. We assessed the corresponding tangible costs saved based on direct medical costs and intangible costs based on the value of a statistical life year. Lastly, based on individual simulations, we assessed the likely additional benefits of shifting 25% of short (ResultsThe French adult (20-89 years) population was estimated to cycle on average of 1min 17sec pers-1.day-1in 2019, with important heterogeneity across gender and age. This yielded benefits of 1,919 (uncertainty interval, UI: 1,101-2,736) premature deaths and 5,963 (95% UI: 3,178-8,749) chronic disease cases prevented, with males enjoying nearly 75% of these benefits. Direct medical costs prevented were estimated at €191 million (UI: 98-285) annually, while the corresponding intangible costs were nearly 25 times higher (€4.8 billion, UI: 3.0-6.5). Shifting 25% of short car trips to biking would yield approximatively a 3-fold increase in benefits, while also generating important CO2emission reductions (0.688 MtCO2e, UI: 0.524-0.854).ConclusionIn a country of low- to moderate cycling culture, cycling already generates important public health and health-related economic benefits. Further development of active transportation would increase these benefits while also contributing to climate change mitigation targets.

International audience; BackgroundHealthcare settings, where invasive procedures are frequently performed, may play an important role in the transmission dynamics of blood-borne pathogens when compliance with infection control precautions is suboptimal.AimsTo understand and quantify the role of hospital-based invasive procedures on hepatitis C virus (HCV) transmission.MethodsWe conducted a systematic review and meta-analysis to identify recent studies reporting association measures of HCV infection risk that are linked to iatrogenic procedures. Based on expert opinion, invasive procedures were categorised into 10 groups for which pooled measures were calculated. Finally, the relationship between pooled measures and the country-level HCV prevalence or the Healthcare Access and Quality (HAQ) index was assessed by meta-regression.ResultsWe included 71 studies in the analysis. The most frequently evaluated procedures were blood transfusion (66 measures) and surgery (43 measures). The pooled odds ratio (OR) of HCV infection varied widely, ranging from 1.46 (95% confidence interval: 1.14–1.88) for dental procedures to 3.22 (1.7–6.11) for transplantation. The OR for blood transfusion was higher for transfusions performed before 1998 (3.77, 2.42–5.88) than for those without a specified/recent date (2.20, 1.77–2.75). In procedure-specific analyses, the HCV infection risk was significantly negatively associated with the HAQ for endoscopy and positively associated with HCV prevalence for endoscopy and surgery.ConclusionsVarious invasive procedures were significantly associated with HCV infection. Our results provide a ranking of procedures in terms of HCV risk that may be used for prioritisation of infection control interventions, especially in high HCV prevalence settings.

In response to the COVID-19 pandemic, many countries have adopted a broad spectrum of containment measures, from recommendations to stay at home to quarantines of large geographic regions. As part of this response, corporations and governments alike have strongly encouraged workers to telecommute where possible. More than 3.4 billion people in 84 countries have been confined to their homes, as estimated in late March 2020, which potentially translates to many millions of workers temporarily exposed to telecommuting. Since 2000, the emergence of digital and broadband internet has facilitated the development of home telework. Despite limited research interest on its impact on occupational health, several health benefits and risks of telework have been identified in academic or grey literature (table 1) (for a review see Ref. 1). …

BackgroundSince the onset of the COVID-19 pandemic, mathematical models have been widely used to inform public health recommendations regarding COVID-19 control in healthcare settings.ObjectivesTo systematically review SARS-CoV-2 transmission models in healthcare settings, and summarise their contributions to understanding nosocomial COVID-19.MethodsSystematic search and review.Data sourcesPublished articles indexed in PubMed.Study eligibility criteriaModelling studies describing dynamic inter-individual transmission of SARS-CoV-2 in healthcare settings, published by mid-February 2022.Participants and interventionsAny population and intervention described by included models.Assessment of risk of biasNot appropriate for modelling studies.Methods of data synthesisStructured narrative review.ResultsModels have mostly focused on acute care and long-term care facilities in high-income countries. Models have quantified outbreak risk across different types of individuals and facilities, showing great variation across settings and pandemic periods. Regarding surveillance, routine testing – rather than symptom-based testing – was highlighted as essential for COVID-19 prevention due to high rates of silent transmission. Surveillance impacts were found to depend critically on testing frequency, diagnostic sensitivity, and turn-around time. Healthcare re-organization was also found to have large epidemiological impacts: beyond obvious benefits of isolating cases and limiting inter-individual contact, more complex strategies such as staggered staff scheduling and immune-based cohorting reduced infection risk. Finally, vaccination impact, while highly effective for limiting COVID-19 burden, varied substantially depending on assumed mechanistic impacts on infection acquisition, symptom onset and transmission. Studies were inconsistent regarding which individuals to prioritize for interventions, probably due to the high diversity of settings and populations investigated.ConclusionsModelling results form an extensive evidence base that may inform control strategies for future waves of SARS-CoV-2 and other viral respiratory pathogens. We propose new avenues for future models of healthcare-associated outbreaks, with the aim of enhancing their efficiency and contributions to decision-making.

ObjectivesTo quantify the burden of COVID-19-related sick leave during the first pandemic wave in France, accounting for sick leaves due to symptomatic COVID-19 (‘symptomatic sick leaves’) and those due to close contact with COVID-19 cases (‘contact sick leaves’).MethodsWe combined data from a national demographic database, an occupational health survey, a social behaviour survey and a dynamic SARS-CoV-2 transmission model. Sick leave incidence from 1 March 2020 to 31 May 2020 was estimated by summing daily probabilities of symptomatic and contact sick leaves, stratified by age and administrative region.ResultsThere were an estimated 1.70M COVID-19-related sick leaves among France’s 40M working-age adults during the first pandemic wave, including 0.42M due to COVID-19 symptoms and 1.28M due to COVID-19 contacts. There was great geographical variation, with peak daily sick leave incidence ranging from 230 in Corse (Corsica) to 33 000 in Île-de-France (the greater Paris region), and greatest overall burden in regions of north-eastern France. Regional sick leave burden was generally proportional to local COVID-19 prevalence, but age-adjusted employment rates and contact behaviours also contributed. For instance, 37% of symptomatic infections occurred in Île-de-France, but 45% of sick leaves. Middle-aged workers bore disproportionately high sick leave burden, owing predominantly to greater incidence of contact sick leaves.ConclusionsFrance was heavily impacted by sick leave during the first pandemic wave, with COVID-19 contacts accounting for approximately three-quarters of COVID-19-related sick leaves. In the absence of representative sick leave registry data, local demography, employment patterns, epidemiological trends and contact behaviours can be synthesised to quantify sick leave burden and, in turn, predict economic consequences of infectious disease epidemics.

L'enquete europeenne sur les risques nouveaux et emergents en entreprises (ESENER) a montre que les actions preventives sur le lieu de travail sont souvent percues comme un enjeu de satisfaction des contraintes reglementaires. Les benefices economiques et sanitaires de la prevention sont peu documentes et laissent la voie a une perception negative dominante des efforts a allouer en sante et bien-etre au travail comme entrainant des depenses improductives. Dans la perspective d’etudier la relation entre le degre d’implication des entreprises en prevention et l’etat de sante de leurs employes, d’une part et leur performance, d’autre part, une etude qualitative a ete conduite en 2018 en France aupres de 5 medecins du travail, 5 DRH et 5 membres du CHSCT pour tenter de caracteriser au mieux les efforts en prevention. Les resultats des entretiens semi-directifs conduits a la base d’un modele conceptuel hypothetique ont permis d’identifier les principales variables a documenter dans un questionnaire quantitatif qui, a terme servirait de base de construction d’un score d’implication en prevention. Ces travaux ouvrent ainsi la voie vers un instrument a destination des entreprises qu’elles peuvent utiliser comme (i) « thermometre » pour quantifier au mieux leurs efforts en prevention, (ii) « balance » pour allouer pertinemment leurs ressources humaines et materielles en prevention et (iii) « benchmark » pour se positionner par rapport a ce qui est fait dans les autres entreprises de meme taille et meme secteur d’activite.

IntroductionAlthough socioeconomic inequalities in HIV prevention, testing and treatment services have been well documented, their drivers remain poorly understood. Understanding the different pathways between socioeconomic position and HIV testing across different countries could help designing tailored programs aimed at reducing such inequalities.MethodsWe analysed data from Demographic and Health Surveys conducted between 2010 and 2018 in 18 sub-Saharan African countries (Burkina Faso, Cameroon, Côte d’Ivoire, Congo DR, Ethiopia, Guinea, Kenya, Lesotho, Liberia, Malawi, Mali, Niger, Rwanda, Senegal, Sierra Leone, Tanzania, Zambia and Zimbabwe). Using a potential outcomes framework and the product method, we decomposed the total effect linking wealth and recent (< 12 months) HIV testing into i) direct effects, and ii) indirect effects, via demand-related (related to individual’s ability to perceive need for care and inclination to seek care) or supply-related (related to individual’s ability to reach, pay for and engage in health care) mediators. Multivariable gender-specific modified Poisson models were fitted to estimate proportions mediated, while accounting for exposure-mediator interaction when present.ResultsA total of 392,044 participants were included in the analysis. Pro-rich wealth-related inequalities were observed in a majority of countries, with nine countries with high levels of inequalities among women and 15 countries among men.The indirect effects of each mediator varied greatly across countries. The proportion mediated tended to be higher for demand-related than for supply-related mediators. For instance, among women, HIV-related knowledge was estimated to mediate up to 12.1% of inequalities in Côte d’Ivoire; this proportion was up to 31.5% for positive attitudes toward people living with HIV (PLHIV) in Senegal. For the four supply-related mediators, the proportion mediated was systematically below 7%. Similar conclusions were found when repeating analyses on men for the demand-related mediators, with higher proportions mediated by positive attitudes toward PLHIV (up to 39.9% in Senegal).ConclusionsOur findings suggest that socioeconomic inequalities in HIV testing may be mediated by the demand-side more than supply-side characteristics, with important variability across countries. Overall, the important inter-country heterogeneity in pathways of socioeconomic inequalities in HIV testing illustrates that addressing inequalities requires tailored efforts as well as upstream interventions.A French version of the abstract is available upon request from the corresponding author.

IntroductionWe aim to explore spatial variations in socioeconomic inequalities in self-reported recent HIV testing uptake in sub-Saharan Africa (SSA) at different geographical scales, in order to identify potential geographical hotspots of inequalities. Additionally, to evaluate the potential benefits of HIV testing programs, we assess whether local levels of HIV testing match the local levels of HIV prevalence.MethodsWe analyzed data from 25 countries in SSA with Demographic and Health Surveys between 2011 and 2019. We quantified socioeconomic inequalities in self-reported HIV testing in the last 12 months with both the Slope Index of Inequality (SII) and Relative Index of Inequality (RII) in different geographical scales to capture sex-specific within-country spatial variations. We also conducted sampling cluster-level analyses based on the Local Indicator of Spatial Association to consider the autocorrelation in SII and RII across SSA countries. To assess the spatial efficiency of HIV testing programs, we measured the correlation between recent HIV testing uptake and HIV prevalence through Pearson correlation across geographical scales.ResultsWe observed pro-rich inequalities on both absolute and relative scales in recent HIV testing in the majority of SSA countries in female and male participants at the national level. We also identified inequalities at subnational levels. Within- and between-country heterogeneities in sex-specific inequalities on both inequality scales and their respective spatial distributions varied depending on the scale used. Clustering of high absolute and relative inequalities were mostly observed in Western and Central Africa with a few regions in Eastern and Southern Africa. Despite significant sex-specific correlations between HIV testing and HIV prevalence in all countries when assessed at the national level, we report an absence of such a correlation at fine scale in 39 of 50 sex-country combinations.ConclusionsThese findings highlight the importance of investigating the spatial variability of various HIV indicators and related inequalities. Results may help local, national and international policymakers to prioritize areas and socioeconomic subgroups in need of HIV testing services. Our results also show the need to monitor efficiency of HIV testing programs in relation to HIV risk at subnational levels as a complementary to national estimates.

International audience; Objective: To better understand the different pathways linking socioeconomic position and HIV testing uptake in 18 sub-Saharan African countries.Design: We used cross-sectional population-based surveys between 2010 and 2018.Methods: Using a potential outcomes framework and the product method, we decomposed the total effect linking wealth and recent (

Kévin Jean,1,2 Ahmed Tawheed,3 Liem Binh Luong Nguyen,4 Tarek Heikal,5 Usama Eldaly,5 Neveen Elhadidy,6 Ahmed Elghaieb,7 Ahmed Aboudonia,7 Laura Tondeur,1 Amélie Dublineau,4 Arnaud Fontanet,2,4 Mohamed El-Kassas3 1Laboratoire MESuRS, Conservatoire national des arts et métiers, Paris, France; 2Unité PACRI, Institut Pasteur, Conservatoire national des arts et métiers, Paris, France; 3Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt; 4Emerging Diseases Epidemiology Unit, Institut Pasteur, Université Paris-Cité, Paris, France; 5Medical Oncology Department, Damietta Oncology Center, Damietta, Egypt; 6Pharmaceutical Services Department, Damietta Oncology Center, Damietta, Egypt; 7Radiology Department, Damietta Oncology Center, Damietta, EgyptCorrespondence: Kévin Jean, Laboratoire MESuRS, Conservatoire national des arts et métiers, 292 rue Saint Martin, Paris, 75003, France, Email kevin.jean@lecnam.netIntroduction: We aimed to assess temporal changes in the presentation and survival of patients with hepatocellular carcinoma (HCC) in the northern Egypt region, one of the regions reporting the highest incidence of the disease globally.Methods: We conducted a monocentric retrospective study. Patients presenting at the Damietta Oncology referral center between 2007 and 2019 with a diagnosed HCC were eligible. Individual, clinical and tumor characteristics at HCC diagnosis, including the Barcelona Clinic Liver Cancer (BCLC) staging, were retrieved from medical files and patients’ final vital status was ascertained by combining various data sources. Patients were divided into 2 groups based on diagnosis period: pre- and post-2014. Survival was analysed based on Kaplan–Meier curves and differences in restricted mean survival time (RMST).Results: Data from 5097 patients (among 5210 eligible, 97.8%) were analyzed. We observed a significant trend toward HCC diagnosed at earlier stage in the post- vs pre-2014 period (BCLC stage 0/A or B: 37.2% vs 27.1%, p< 10− 3). Overall patient’s survival after the HCC diagnosis was poor, with a median of 8.1 months. The BCLC staging system performed well in predicting survival. Despite a trend toward HCC diagnosed at earlier stages, we did not observe a significant improvement in survival over time. Overall, treatments offered in this medical center were in line with international guidelines, and 16.1% of the patients who received a curative treatment had an improved survival (30.7 months in median). However, HCC recurrence was frequent among patients cured for HCC, with a median time to recurrence of 22 months.Discussion: Overall survival after HCC diagnosis in Egypt remains poor but is significantly improved by curative therapy. Despite a trend toward earlier diagnosis of HCC, we did not observe a general improvement in survival over time, which remains to be clearly understood.Keywords: hepatocellular carcinoma, liver cancer, Egypt, staging system, survival, epidemiology

In addition to its potential contribution to reaching climate targets, cycling may generate substantial population-level health benefits through the physical activity it requires. Due to the lack of nationally representative mobility data, the health impact of current levels of cycling is still unknown for France. Relying on a health impact assessment framework and using recent nationally-representative data on mobility, we assessed the health and related economic benefits of cycling in 2018-2019 in France. We show that such benefits remain moderated and fall short when compared to those estimated in other countries with high cycling levels. We argue that cycling in France did not receive the attention and investments it deserves over the past decade and thus represents a missed opportunity for climate action and public health.

Technological advances in synthetic biology have made in vitro modification, or even creation, of viruses easier and more affordable. Several research studies using synthesis of potential pandemic pathogens led to controversies in the 2010's. More recently, the hypothesis that Covid-19 pandemics could originate from a lab escape is still under debate. In France, a legislative vacuum remains concerning the synthesis of modified pathogens. Initiating a collective reflection process towards setting of a legal framework on this type of work is timely so that research continues to provide profit to society rather than hazard.Recherche à usage dual sur les pathogènes modifiés en laboratoire - Quel encadrement pour quels enjeux ?Les avancées techniques en biologie de synthèse rendent de plus en plus accessibles la modification ou même la fabrication de virus en laboratoire. Plusieurs travaux de recherche fondés sur la synthèse de pathogènes à potentiel pandémique ont créé la polémique au cours des années 2010 et, aujourd’hui encore, l’éventualité qu’une fuite de laboratoire soit à l’origine de la pandémie de Covid-19 fait débat. En France, un vide juridique subsiste concernant la synthèse de pathogènes modifiés. Une réflexion concertée vers un encadrement légal de ce type de recherche apparaît donc nécessaire et urgent pour que la recherche continue de représenter un bénéfice, plutôt qu’un risque, pour la société.

International audience; Les avancées techniques en biologie de synthèse rendent de plus en plus accessibles la modification ou même la fabrication de virus en laboratoire. Plusieurs travaux de recherche fondés sur la synthèse de pathogènes à potentiel pandémique ont créé la polémique au cours des années 2010 et, aujourd’hui encore, l’éventualité qu’une fuite de laboratoire soit à l’origine de la pandémie de Covid-19 fait débat. En France, un vide juridique subsiste concernant la synthèse de pathogènes modifiés. Une réflexion concertée vers un encadrement légal de ce type de recherche apparaît donc nécessaire et urgent pour que la recherche continue de représenter un bénéfice, plutôt qu’un risque, pour la société.

Background Deaths due to vaccine preventable diseases cause a notable proportion of mortality worldwide. To quantify the importance of vaccination, it is necessary to estimate the burden averted through vaccination. The Vaccine Impact Modelling Consortium (VIMC) was established to estimate the health impact of vaccination. Methods We describe the methods implemented by the VIMC to estimate impact by calendar year, birth year and year of vaccination (YoV). The calendar and birth year methods estimate impact in a particular year and over the lifetime of a particular birth cohort, respectively. The YoV method estimates the impact of a particular year’s vaccination activities through the use of impact ratios which have no stratification and stratification by activity type and/or birth cohort. Furthermore, we detail an impact extrapolation (IE) method for use between coverage scenarios. We compare the methods, focusing on YoV for hepatitis B, measles and yellow fever. Results We find that the YoV methods estimate similar impact with routine vaccinations but have greater yearly variation when campaigns occur with the birth cohort stratification. The IE performs well for the YoV methods, providing a time-efficient mechanism for updates to impact estimates. Conclusions These methods provide a robust set of approaches to quantify vaccination impact; however it is vital that the area of impact estimation continues to develop in order to capture the full effect of immunisation.

Background: Healthcare settings, where invasive procedures are frequently performed, may play an important role in the transmission dynamics of blood-borne pathogens when compliance with infection control precautions remains suboptimal. This study aims at better understanding and quantifying the role of hospital-based invasive procedures on hepatitis C virus (HCV) transmission. Methods: We conducted a systematic review and meta-analysis to identify recent studies reporting association measures of HCV infection risk that are linked to iatrogenic procedures performed in hospital settings. Based on expert opinion, invasive procedures were categorized into 10 groups for which pooled measures were calculated. Finally, the relationship between pooled measures and the country-level HCV prevalence or the Healthcare Access and Quality (HAQ) index was assessed in meta-regressions. Findings: A total of 71 studies were included in the analysis. The most frequently evaluated procedures were blood transfusion and surgery (60 and 37 studies, respectively). The pooled odds ratio (OR) of HCV infection varied widely, ranging from 1.46 (95%CI: 1.14-1.88) for dental procedures to 3.84 (2.07-7.12) for wound care. The OR for blood transfusion was higher for transfusions performed before 1998 (3.77, 2.42-5.88) than for those without a specified date (2.26, 1.81-2.81). Finally, the country-level overall risk for all procedures was significantly associated with HCV prevalence, but not with the HAQ index. In procedure-specific analyses, the HCV infection risk was significantly negatively associated with the HAQ for endoscopy and positively associated with HCV prevalence for endoscopy and surgery. Interpretation: Various invasive procedures were documented to be significantly associated with HCV infection. Our results provide a ranking of procedures in terms of HCV risk that may be used for prioritization of infection control measures, especially in high HCV prevalence settings. Funding: INSERM-ANRS (France Recherche Nord and Sud Sida-HIV Hepatites)

Background Cholera outbreaks contribute significantly to diarrhoeal disease mortality, especially in low-income countries. Cholera outbreaks have several social and environmental risk factors and extreme conditions can act as catalysts for outbreaks. A social extreme with known links to infectious disease outbreaks is conflict, causing disruption to services, loss of income and displacement. Methods Here, we explored this relationship in Nigeria and the Democratic Republic of Congo (DRC), by fitting publicly available cholera and conflict data to conditional logistic regression models. We used the self-controlled case series method in a novel application, to understand if an exposure period of excess risk (conflict), increased the relative incidence of cholera. We also used a sensitivity analysis to understand potential lag effects. Results We found that conflict and cholera had a strong positive relationship, especially in the first week after the event, at a national and sub-national level. Conflict increased the risk of cholera in Nigeria by 3.6 times and 2.6 times for the DRC. Conflict was attributed to 19.7% and 12.3% of cholera outbreaks in Nigeria and the DRC, respectively. This was higher for some states/provinces, with a maximum increased risk of 7.5 times. Conclusion The results found that several states/provinces with the strongest positive relationship were also areas of high reported conflict or were neighbouring states/provinces, suggesting a possible spill-over effect. Our results help highlight the importance of rapid and sufficient assistance during social extremes and the need for pre-existing vulnerabilities such as poverty and access to healthcare to be addressed. In fragile states, conflict resolution should be a top priority to avoid excess risk for both cholera and other health and social implications. Funding Natural Environmental Research Council, UK Medical Research Council, and the Department for International Development.

Background Musculoskeletal disorders (MSDs) accounted for nearly 1.71 billion people worldwide in 2019 with an estimate of over 126.6 million Americans (or one in two adults) affected and 40 million European workers in 2017. Since age constitutes an important risk factor for MSDs, the overall aging of the working population is expected to influence the burden of disease. However, factors other than aging may play a role in the global trends in MSDs We conducted a systematic review to summarize the evidence on the role of demographic and temporal changes in the occurrence of MSDs. Methods The study protocol was registered in PROSPERO with the number CRD42020221499. Following the PRISMA guidelines, we searched PubMed, ScienceDirect and Web of Science over the 1990-2020 period for articles reporting temporal trends in MSDs incidence or prevalence in the general working-age population. We only included articles controlling for age in the analysis. To ensure the quality of the articles, the bias risk was assessed using the RoB-SPEO tool. The main indicators we extracted were age-controlled time trends in MSDs incidence or prevalence. Results Among 966 articles, 16 fulfilled the inclusion criteria, representing 23 results according to the indicators extracted. No study was found with a high risk of bias. Nine used a definition of MSDs based on pain and 14 based on repercussions on work or social life. Twelve results presented time trends in prevalence and 11 in incidence. After controlling for age, temporal trends in MSDs presented some heterogeneity. Indeed, 10 results documented increases and 12 reported non-monotonic changes. Only 1 result reported a decreasing trend in the incidence of MSDs. Several factors other than aging were suggested to explain temporal trends in MSDs, mainly trends in obesity, changing occupational exposures, and cultural factors regarding pain tolerance. Conclusion This review shows that factors in addition to aging of the working population may contribute to varying or increasing trends in MSDs. Results also highlight the scarcity of available evidence on time trends in the burden of MSDs and their underlying causes.

In order to reach the first 95 (i.e., 95% of people living with HIV having knowledge of their status) of the 2030 UNAIDS 95-95-95 targets, it is crucial to better understand the contextual or structural factors driving socioeconomic inequalities in HIV testing uptake. It is still unclear whether they are mostly influenced by epidemiological or by macro-economic factors. Here, to shed light on this issue, we measured and decomposed socioeconomic inequalities in HIV testing in sub-Saharan Africa in relation to contextual factors using a novel method, the Recentered Influence Function decomposition method. Indeed, we found that HIV testing uptake was more concentrated among the rich in 12 of 16 sub-Saharan African countries based on population-based surveys. The level of the HIV epidemic seems to drive the level of response of HIV testing programs, rather than the per capita Gross Domestic Product of a country (i.e., national indicator of economic development). Our results suggest that when responding to the HIV epidemic, there is a need to monitor and assess inequalities in addition to monitoring HIV incidence and prevalence.

Background:Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae, and yellow fever over the years 2000–2030 across 112 countries.Methods:Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios.Results:We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000–2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases.Conclusions:This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future.Funding:VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium’s modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

[ES] El trabajo de investigación presentado en esta tesis es el resultado de varios años dedicados al desarrollo, la implementación y la optimización de dos tecnologías combinadas: un concepto de combustión innovador y una arquitectura de motor de nuevo diseño. Esta investigacion se ha realizado en el marco de una colaboración con Renault SA, como continuación de las actividades realizadas en el proyecto europeo POWERFUL (POWERtrain for FUture Light-duty vehicles) por un lado,y en el marco del proyecto europeo REWARD (Real World Advanced technologies foR Diesel engines), devenido como continuación del proyecto POWERFUL en el marco del programa de investigación Horizonte 2020, por otro lado. Los principales objetivos de estos estudios eran evaluar el potencial del concepto de combustión parcialmente premezclada (PPC) operando con gasolina como combustible en un innovador motor de 2 tiempos de válvulas en culata, y luego diseñar una nueva geometría de motor de 2 tiempos utilizando la arquitectura Uniflujo para superar los principales problemas y limitaciones observados durante la primera etapa, que se pueden resumir principalmente en el rendimiento de barrido (especialmente trabajando en cargas elevadas). La metodología diseñada para este trabajo de investigación sigue un enfoque teórico-experimental. La evaluación del concepto de combustión PPC operando con gasolina se llevó a cabo principalmente con un enfoque experimental con el apoyo del análisis en línea directamente en el banco de ensayo, seguido de un exhaustivo tratamiento posterior de los datos y de un análisis detallado del proceso de combustión utilizando herramientas de diagnóstico. Por el contrario, el desarrollo del nuevo motor Uniflujo de 2 tiempos consistió principalmente en iteraciones sobre modelado 3D-CFD, si bien las actividades experimentales fueron fundamentales para validar las diferentes soluciones propuestas y evaluar su sensibilidad ante diferentes parámetros de interés utilizando una metodología de Diseño de Experimentos (DoE). La primera parte del trabajo se ha dedicado a la comprensión de los procesos termodinámicos involucrados en la combustión operando con el concepto PPC en un motor de 2 tiempos de válvulas en culata utilizando gasolina como combustible, y a evaluar su potencial en términos de emisiones contaminantes, consumo de combustible y ruido. Por último, se ha realizado un trabajo de exploración para ampliar en la medida de lo posible el rango de funcionamiento de este concepto de combustión en esta configuración específica del motor, investigando especialmente el rendimiento en cargas bajas en todo el rango de regímenes de giro del motor, y estableciendo también las principales limitaciones para la operación en cargas altas. La segunda parte de la tesis se ha centrado en el desarrollo y optimización teórica de un motor Uniflujo de 2 tiempos de nuevo diseño, incluyendo su fabricación y validación experimental. El objetivo principal era optimizar, utilizando principalmente simulaciones 3D-CFD, el rendimiento de barrido de esta arquitectura de 2 tiempos mediante el diseño de nuevas geometrías de puertos de admisión, permitiendo un gran control sobre el flujo de aire hacia y a través del cilindro para barrer al máximo los gases quemados y minimizar el cortocircuito de aire fresco hacia el escape. Las soluciones óptimas se evaluaron experimentalmente siguiendo la metodología DoE, antes de comparar finalmente los resultados de rendimiento de barrido con la anterior arquitectura de motor de 2 tiempos con válvulas en culata., [CA] El treball de recerca presentat en aquesta tesi és el resultat de diversos anys dedicats al desenvolupament, la implementació i l'optimització de dues tecnologies combinades: un concepte de combustió innovador i una arquitectura de motor de nou disseny. Aquesta recerca s'ha realitzat en el marc d'una col·laboració amb Renault SA, com a continuació de les activitats del projecte europeu *POWERFUL (*POWERtrain *for *FUture Light-*duty *vehicles) d'una banda, i en el marc del projecte europeu *REWARD (Real *World *Advanced *technologies *foR Dièsel *engines), es devingut com a continuació del projecte *POWERFUL en el marc del programa d'investigació Horitzó 2020, d'altra banda. Els principals objectius d'aquests estudis eren avaluar el potencial del concepte de combustió parcialment premesclada (PPC) operant amb gasolina com a combustible en un innovador motor de 2 temps de vàlvules en culata, i després dissenyar una nova geometria de motor de 2 temps utilitzant l'arquitectura Uniflux per a superar els principals problemes i limitacions observats durant la primera etapa, que es poden resumir principalment en el rendiment d'escombratge (especialment treballant en càrregues elevades). La metodologia dissenyada per a realitzar aquests treballs de recerca segueix un enfocament tant experimental com teòric. L'avaluació del concepte de combustió PPC operant amb gasolina es va dur a terme principalment amb un enfocament experimental, però sempre amb el suport de l'anàlisi en línia directament en el banc d'assaig, seguit d'un exhaustiu tractament posterior de les dades combinat amb una anàlisi detallada del procés de combustió utilitzant eines de diagnòstic. Per contra, el desenvolupament i el disseny del nou motor Uniflux de 2 temps va consistir principalment en iteracions sobre modelatge 3D-CFD, si bé les activitats experimentals van ser fonamentals per a validar les diferents solucions proposades i avaluar la seua sensibilitat davant una sèrie de paràmetres d'interés utilitzant una metodologia de Disseny d'Experiments (DoE). La primera part del treball s'ha dedicat a la comprensió dels processos termodinàmics involucrats en la combustió operant amb el concepte de combustió PPC en un motor de 2 temps de vàlvules en culata utilitzant gasolina com a combustible, i a avaluar el seu potencial en termes d'emissions contaminants, consum de combustible i també de soroll. Finalment, s'ha fet un treball d'exploració per a ampliar en la mesura que siga possible el rang de funcionament d'aquest concepte de combustió utilitzant eixa configuració específica del motor, investigant especialment el rendiment en càrregues baixes en tot el rang de règims de gir del motor, i establint també les principals limitacions per a l'operació en càrregues altes. La segona part de la tesi s'ha centrat en el desenvolupament i optimització teòrica d'un motor Uniflux de 2 temps de nou disseny, incloent la seua fabricació i validació experimental. L'objectiu principal era optimitzar, utilitzant principalment simulacions 3D-CFD, el rendiment d'escombratge d'aquesta arquitectura de 2 temps mitjançant el disseny de noves geometries de ports d'admissió, permetent un gran control sobre el flux d'aire cap a i a través del cilindre per a escombrar al màxim els gasos cremats i minimitzar el curtcircuit d'aire fresc cap a l'escapament. Les solucions òptimes es van fabricar i van avaluar experimentalment seguint la metodologia DoE, abans de comparar finalment els resultats de rendiment d'escombratge amb l'anterior arquitectura de motor de 2 temps amb vàlvules en culata., [EN] The research work presented in this thesis is the result of several years dedicated to the development, implementation and optimization of two combined technologies: an innovative combustion concept and a newly designed engine architecture. These investigations have been performed in the framework of a research collaboration with Renault SA following up the activities performed along the European POWERFUL project (POWERtrain for FUture Light-duty vehicles) on the one hand, and in the framework of the European REWARD project (REal World Advanced technologies foR Diesel engines), brought as a continuation of the POWERFUL project in the frame of the Horizon 2020 research program, on the other hand. The main objectives of these studies were to evaluate the potential of the Partially Premixed Combustion (PPC) concept operating with gasoline fuel in an innovative 2-Stroke poppet-valve engine, and then to design a new 2-Stroke engine geometry using the Uniflow architecture to overcome the main problems and limitations observed during the first stage, which can be mainly summarized to the scavenging performance (especially at high loads). The methodology designed for performing these investigation is based on both experimental and theoretical approaches. The evaluation of the gasoline PPC concept was carried out mainly experimentally, but always supported by online analysis directly on the test-bench and followed by a thorough post-processing of the data combined with a detailed analysis of the combustion using combustion diagnostic tools. On the contrary, the development and design of the new 2-Stroke Uniflow engine consisted mainly of 3D-CFD iterations, but experimental testing was crucial to validate the different solutions proposed and evaluate their sensitivity to a set of parameters of interest using a Design of Experiments (DoE) methodology. The first part of the work has been dedicated to the understanding of the thermodynamical processes involved in the combustion in a poppet-valve 2-Stroke engine operating with the gasoline PPC concept, and to evaluate its potential in terms of pollutant emissions, fuel consumption and also noise. Finally, a wide exploration has been performed to extend as much as possible the operating range of this combustion concept using that specific engine configuration, especially investigating the low loads performance throughout the full range of engine speeds, and also laying out the main limitations for high-to-full load operations. The second part of the thesis has been focused on the development and theoretical optimization of a newly designed 2-Stroke Uniflow engine, leading to manufacture and experimental validation. The main objective was to optimize, using mainly 3D-CFD modeling simulations, the scavenging performance of this 2-Stroke architecture by designing new intake ports geometries and to enable a great control over the air flow into and through the cylinder in order to scavenge the burnt gases as much as possible while minimizing the fresh air short-circuit to the exhaust. The optimum solutions were then manufactured and experimentally tested following a DoE methodology, before finally comparing the results of the scavenging performance to the previous 2-Stroke poppet-valve engine architecture.

Background The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, to what extent PMVCs are associated with a decreased risk of outbreak has not yet been quantified. Methods and findings We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for in the SCCS method, this method is an alternative to classical cohort or case–control study designs when the risk of residual confounding is high, in particular confounding by indication. The locations and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, the first outbreak occurred during the pre-PMVC period in 26 (79%) provinces, and during the post-PMVC period in 7 (21%) provinces. At the province level, the post-PMVC period was associated with an 86% reduction (95% CI 66% to 94%, p < 0.001) in the risk of outbreak as compared to the pre-PMVC period. This negative association between exposure to PMVCs and outbreak was robustly observed across a range of sensitivity analyses, especially when using quantitative estimates of vaccination coverage as an alternative exposure measure, or when varying the observation period. In contrast, the results of the cohort-style analyses were highly sensitive to the choice of covariates included in the model. Based on the SCCS results, we estimated that PMVCs were associated with a 34% (95% CI 22% to 45%) reduction in the number of outbreaks in Africa from 2005 to 2018. A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever and possibly improved disease surveillance. Conclusions In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention., In this cohort study, Kévin Jean and colleagues correlate lower risk of disease outbreaks with mass vaccination against yellow fever., Author summary Why was this study done? Yellow fever is a mosquito-borne, vaccine-preventable disease that may cause large urban outbreaks, especially in tropical African regions. Since 2006, preventive mass vaccination campaigns (PMVCs) have been implemented in many African provinces. These are large-scale vaccination campaigns targeting all or most age groups in a specific area. The preventive impact PMVCs may have on the risk of yellow fever outbreak has not been quantified yet. What did the researchers do and find? We used the self-controlled case series (SCCS) method to assess the association between PMVCs and outbreak risk at the province level in 34 African countries between 2005 and 2018. We compared pre- and post-PMVC periods within each province individually, thus implicitly controlling for all possible confounders that do not vary in time, especially the fact that provinces indicated for PMVCs are generally those considered at highest baseline risk of yellow fever (confounding by indication). At the province level, we estimated that implementation of PMVCs was associated with an 86% reduction (95% CI 66% to 94%) in the risk of yellow fever outbreak. A complete cohort analysis provided less reliable results than the SCCS method, likely because of confounding by indication that was not entirely controlled for by adjusting for known drivers of yellow fever. We further estimated that all PMVCs conducted between 2006 and 2018 in Africa may have reduced the total number of yellow fever outbreaks by 34% (95% CI 22% to 45%). What do these findings mean? These results provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. These results may encourage rapid rescheduling of yellow fever PMVCs that have been postponed due to the COVID-19 pandemic. The SCCS design may be advantageously applied at the population level to assess the impact of public health interventions.

ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.ResultsRecurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; pConclusionEffects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.

BackgroundYellow fever (YF) is a viral haemorrhagic fever endemic in tropical regions of Africa and South America. Current intervention policies, namely the Eliminate Yellow fever Epidemics (EYE) strategy are actioned through vaccination. However, the stockpiles and production mean that vaccination can be in short supply. As such, intervention strategies need to be optimised; one of the tools for doing this is mathematical modelling.MethodsWe fit a generalised linear model of YF reports to occurrence data available from 1987 to 2019 in Africa and South America and available serology survey data to estimate the force of infection across the continents. Then, using demographic and vaccination data, we examine the impact of interventions.FindingsWe estimate that in 2018 there were approximately 51,000 (95%CrI [31,000 - 82,000]) deaths due to YF in Africa and South America. When we examine the impact of mass vaccination campaigns in Africa, these amount to approximately 10,000 (95%CrI [6,000 - 17,000]) deaths averted in 2018 due to mass vaccination activities in Africa; this corresponds to a 47% reduction (95%CrI [10% - 77%]).InterpretationWe find that the majority, 92% (95%CrI [89% - 95%]), of global burden occurs in Africa and that mass vaccination activities have significantly reduced the current deaths per year due to YF. This methodology allows us to evaluate the effectiveness of vaccination campaigns past, present and future and illustrates the need for continued vigilance and surveillance of YF.FundingBMGF and MRC

Introduction The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, by how much PMVCs are associated with a decreased risk of outbreak to occur has not yet been quantified. Methods and Findings We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for, the SCCS method is an alternative to classical cohort or case-control study designs when the risk of residual confounding is high, in particular confounding by indication. The location and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the relative incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, outbreaks occurred during the pre-PMVC period in 26 (79%) provinces versus 7 (21%) occurring in the post-PMVC period. At the province level, the post-PMVC period was associated with a 86% reduction (95% Confidence interval 66% to 94%, p-value A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever or possibly improved disease surveillance. Conclusion In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention. AUTHOR SUMMARY Why Was This Study Done? Yellow fever is a mosquito-borne vaccine-preventable disease that may cause large urban outbreaks, especially in tropical African regions. Since 2006, Preventive Mass Vaccination Campaigns (PMVCs) have been implemented in many African provinces. These are large scale vaccination campaigns targeting all or most age group in a specific area. The preventive impact PMVCs may have on the risk of yellow fever outbreak has not been quantified yet. What Did the Researchers Do and Find? We used the self-controlled case series (SCCS) method to assess the association between PMVCs and outbreak risk at the province level over 34 African countries between 2005 and 2018. Using this method, we compared pre- and post-PMVC period are compared within each province individually, thus controlling for all possible confounders that do not vary in time, especially the fact that provinces indicated for PMVCs are generally those considered at highest baseline risk of yellow fever (ie confounding by indication). At the province level, we estimated that implementation of PMVCs was associated with an 86% reduction (66% to 94%) in the risk of yellow fever outbreak. Results from a complete cohort analysis provided less reliable results than the SCCS method, likely because of confounding by indication that was not entirely controlled for by adjusting on known drivers of yellow fever. We further estimated that all PMVCs conducted between 2006 and 2018 in Africa may have reduced the total number of yellow fever outbreaks by 34% (22% to 45%). What Do These Findings Mean? These results provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. These results may encourage rapid re-scheduling of yellow fever PMVCs that have been postponed due to the COVID-19 pandemic. The SCCS design may be advantageously applied at the population level to assess the impact of public health interventions.

Background To counter the increasing global risk of Yellow fever (YF), the World Health Organisation initiated the Eliminate Yellow fever Epidemics (EYE) strategy. Estimating YF burden, as well as vaccine impact, while accounting for the features of urban YF transmission such as indirect benefits of vaccination, is key to informing this strategy. Methods and findings We developed two model variants to estimate YF burden in sub-Saharan Africa, assuming all infections stem from either the sylvatic or the urban cycle of the disease. Both relied on an ecological niche model fitted to the local presence of any YF reported event in 34 African countries. We calibrated under-reporting using independent estimates of transmission intensity provided by 12 serological surveys performed in 11 countries. We calculated local numbers of YF infections, deaths and disability-adjusted life years (DALYs) lost based on estimated transmission intensity while accounting for time-varying vaccination coverage. We estimated vaccine demand and impact of future preventive mass vaccination campaigns (PMVCs) according to various vaccination scenarios. Vaccination activities conducted in Africa between 2005 and 2017 were estimated to prevent from 3.3 (95% CI 1.2–7.7) to 6.1 (95% CI 2.4–13.2) millions of deaths over the lifetime of vaccinees, representing extreme scenarios of none or maximal herd effects, respectively. By prioritizing provinces based on the risk of urban YF transmission in future PMVCs, an average of 37.7 million annual doses for PMVCs over eight years would avert an estimated 9,900,000 (95% CI 7,000,000–13,400,000) infections and 480,000 (180,000–1,140,000) deaths over the lifetime of vaccinees, corresponding to 1.7 (0.7–4.1) deaths averted per 1,000 vaccine doses. Conclusions By estimating YF burden and vaccine impact over a range of spatial and temporal scales, while accounting for the specificity of urban transmission, our model can be used to inform the current EYE strategy., Author summary As large-scale vaccination campaigns are begun or continued with the aim to eliminate yellow fever (YF) epidemics in several countries, estimating disease burden and vaccine impact is timely. We developed two model variants to estimate YF burden in sub-Saharan Africa, each either representing the sylvatic or urban cycle of the disease. Both relied on an ecological niche model fitted to known records of YF in 34 African countries and calibrated using serological survey data. Local numbers of YF infections and deaths were derived while accounting for time-varying vaccination coverage. We estimated vaccine demand and the impact of future preventive mass vaccination campaigns according to various vaccination scenarios. By providing burden and vaccine impact estimates over a range of spatial and temporal scales, and accounting for the specificity of urban transmission, our model can be used to inform the current international strategy to counter the increasing global risk of yellow fever.

Overall increases in the uptake of HIV testing in the past two decades might hide discrepancies across socioeconomic groups. We used data from population-based surveys done in sub-Saharan Africa to quantify socioeconomic inequalities in uptake of HIV testing, and to establish trends in testing uptake in the past two decades.We analysed data from 16 countries in sub-Saharan Africa where at least one Demographic and Health Survey was done before and after 2008. We assessed the country-specific and sex-specific proportions of participants who had undergone HIV testing in the previous 12 months across wealth and education groups, and quantified socioeconomic inequalities with both the relative and slope indices of inequalities. We assessed time trends in inequalities, and calculated mean results across countries with random-effects meta-analyses.We analysed data for 537 784 participants aged 15-59 years (most aged 15-49 years) from 32 surveys done between 2003 and 2016 (16 before 2008, and 16 after 2008) in Cameroon, Côte d'Ivoire, DR Congo, Ethiopia, Guinea, Kenya, Lesotho, Liberia, Malawi, Mali, Niger, Rwanda, Sierra Leone, Tanzania, Zambia, and Zimbabwe. A higher proportion of female participants than male participants reported uptake of HIV testing in the previous 12 months in five of 16 countries in the pre-2008 surveys, and in 14 of 16 countries in the post-2008 surveys. After 2008, in the overall sample, the wealthiest female participants were 2·77 (95% CI 1·42-5·40) times more likely to report HIV testing in the previous 12 months than were the poorest female participants, whereas the richest male participants were 3·55 (1·85-6·81) times more likely to report HIV testing than in the poorest male participants. The mean absolute difference in uptake of HIV testing between the richest and poorest participants was 11·1 (95% CI 4·6-17·5) percentage points in female participants and 15·1 (9·6-20·6) in male participants. Over time (ie, when pre-2008 and post-2008 data were compared), socioeconomic inequalities in the uptake of HIV testing in the previous 12 months decreased in male and female participants, whereas absolute inequalities remained similar in female participants and increased in male participants.Although relative socioeconomic inequalities in uptake of HIV testing in sub-Saharan Africa has decreased, absolute inequalities have persisted or increased. Greater priority should be given to socioeconomic equity in assessments of HIV-testing programmes.INSERM-ANRS (France Recherche Nord and Sud Sida-HIV Hépatites).

SummaryBackgroundOverall increase in the uptake of HIV testing in the past decades may hide discrepancies across socio-economic groups. We used population-based surveys conducted in sub-Saharan Africa to quantify socio-economic inequalities in recent HIV testing uptake, together with their trends over the two past decades.MethodsWe analyzed the data from Demographic and Health Surveys in sub-Saharan African countries where at least one survey was conducted before and after 2008. Country- and gender-specific proportions of recent (FindingsWe analyzed data from 32 surveys conducted between 2003 and 2016 in 16 countries among 537,784 participants. In pre-2008 surveys, women reported higher HIV testing uptake than men in 8 out of 16 countries, and in 15 out of 16 countries in post-2008 surveys. After 2008, the wealthiest women were on average 2.77 (95% CI 1.42-5.40) times more likely to report recent testing than the poorest; and 3.55 (1.85-6.81) times in men. The averaged absolute difference in recent testing between the richest and poorest was 11.1 (4.6-17.5) percentage points in women and 15.1 (9.6-20.6) in men. Over time, relative inequalities in recent HIV testing decreased in both genders, while absolute inequalities plateaued in women and increased in men.InterpretationsThe overall increase in HIV testing uptake that was stimulated by the impetus to scale up HIV treatment in sub-Saharan Africa led to a decrease in relative inequalities, while absolute inequalities persisted. Within most countries, large inequalities still remained, both in absolute and relative scales, especially in West and Central Africa. A greater focus should be put on equity in monitoring HIV testing programs.A French version of this article is available in the Appendices [Une version française de cet article est disponible en appendice].FundingINSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), grant number ANRS-12377.

International audience; In Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct-acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early-phase HCC recurrence in patients with a history of HCV-related liver cancer. This was a prospective cohort study of an HCV-infected population from one Egyptian specialized HCC management centre starting from the time of successful HCC intervention. The incidence rates of HCC recurrence between DAA-exposed and nonexposed patients were compared, starting from date of HCC complete radiological response and censoring after 2 years. DAA exposure was treated as time varying. Two Poisson regressions models were used to control for potential differences in the exposed and nonexposed group; multivariable adjustment and balancing using inverse probability of treatment weighting (IPTW). We included 116 patients: 53 treated with DAAs and 63 not treated with DAAs. There was 37.7% and 25.4% recurrence in each group after a median of 16.0 and 23.0 months of follow-up, respectively. Poisson regression using IPTW demonstrated an association between DAAs and HCC recurrence with an incidence rate ratio of 3.83 (95% CI: 2.02-7.25), which was similar in the multivariable-adjusted model and various sensitivity analyses. These results add important evidence towards the possible role of DAAs in HCC recurrence and stress the need for further mechanistic studies and clinical trials to accurately confirm this role and to identify patient characteristics that may be associated with this event.