Sick leave due to COVID-19 during the first pandemic wave in France, 2020.

OBJECTIVES: To 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'). METHODS: We 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. RESULTS: There 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. CONCLUSIONS: France 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.

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis.

OBJECTIVE: The 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. DESIGN: We 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. RESULTS: Recurrence 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; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1). CONCLUSION: Effects 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.

Association between Conflict and Cholera in Nigeria and the Democratic Republic of the Congo.

Cholera outbreaks contribute substantially to illness and death in low- and middle-income countries. Cholera outbreaks are associated with several social and environmental risk factors, and extreme conditions can act as catalysts. A social extreme known to be associated with infectious disease outbreaks is conflict, causing disruption to services, loss of income, and displacement. To determine the extent of this association, we used the self-controlled case-series method and found that conflict increased the risk for cholera in Nigeria by 3.6 times and in the Democratic Republic of the Congo by 2.6 times. We also found that 19.7% of cholera outbreaks in Nigeria and 12.3% of outbreaks in the Democratic Republic of the Congo were attributable to conflict. Our results highlight the value of providing rapid and sufficient assistance during conflict-associated cholera outbreaks and working toward conflict resolution and addressing preexisting vulnerabilities, such as poverty and access to healthcare.

Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study.

BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Assessing the impact of preventive mass vaccination campaigns on yellow fever outbreaks in Africa: A population-level self-controlled case series study.

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.

Monitoring sick leave data for early detection of influenza outbreaks.

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.

How can the public health impact of vaccination be estimated?

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.

Quantifying model evidence for yellow fever transmission routes in Africa.

Yellow fever is a vector-borne disease endemic in tropical regions of Africa, where 90% of the global burden occurs, and Latin America. It is notoriously under-reported with uncertainty arising from a complex transmission cycle including a sylvatic reservoir and non-specific symptom set. Resulting estimates of burden, particularly in Africa, are highly uncertain. We examine two established models of yellow fever transmission within a Bayesian model averaging framework in order to assess the relative evidence for each model's assumptions and to highlight possible data gaps. Our models assume contrasting scenarios of the yellow fever transmission cycle in Africa. The first takes the force of infection in each province to be static across the observation period; this is synonymous with a constant infection pressure from the sylvatic reservoir. The second model assumes the majority of transmission results from the urban cycle; in this case, the force of infection is dynamic and defined through a fixed value of R0 in each province. Both models are coupled to a generalised linear model of yellow fever occurrence which uses environmental covariates to allow us to estimate transmission intensity in areas where data is sparse. We compare these contrasting descriptions of transmission through a Bayesian framework and trans-dimensional Markov chain Monte Carlo sampling in order to assess each model's evidence given the range of uncertainty in parameter values. The resulting estimates allow us to produce Bayesian model averaged predictions of yellow fever burden across the African endemic region. We find strong support for the static force of infection model which suggests a higher proportion of yellow fever transmission occurs as a result of infection from an external source such as the sylvatic reservoir. However, the model comparison highlights key data gaps in serological surveys across the African endemic region. As such, conclusions concerning the most prevalent transmission routes for yellow fever will be limited by the sparsity of data which is particularly evident in the areas with highest predicted transmission intensity. Our model and estimation approach provides a robust framework for model comparison and predicting yellow fever burden in Africa. However, key data gaps increase uncertainty surrounding estimates of model parameters and evidence. As more mathematical models are developed to address new research questions, it is increasingly important to compare them with established modelling approaches to highlight uncertainty in structures and data.

Uptake of HIV testing in Burkina Faso: an assessment of individual and community-level determinants.

BACKGROUND: Previous studies have highlighted a range of individual determinants associated with HIV testing but few have assessed the role of contextual factors. The objective of this paper is to examine the influence of both individual and community-level determinants of HIV testing uptake in Burkina Faso. METHODS: Using nationally representative cross-sectional data from the 2010 Demographic and Health Survey, the determinants of lifetime HIV testing were examined for sexually active women (n = 14,656) and men (n = 5680) using modified Poisson regression models. RESULTS: One third of women (36%; 95% Confidence Interval (CI): 33-37%) reported having ever been tested for HIV compared to a quarter of men (26%; 95% CI: 24-27%). For both genders, age, education, religious affiliation, household wealth, employment, media exposure, sexual behaviors, and HIV knowledge were associated with HIV testing. After adjustment, women living in communities where the following characteristics were higher than the median were more likely to report uptake of HIV testing: knowledge of where to access testing (Prevalence Ratio [PR] = 1.41; 95% CI: 1.34-1.48), willing to buy food from an infected vendor (PR = 2.06; 95% CI: 1.31-3.24), highest wealth quintiles (PR = 1.18; 95% CI: 1.10-1.27), not working year-round (PR = 0.90; 95% CI: 0.84-0.96), and high media exposure (PR = 1.11; 95% CI: 1.03-1.19). Men living in communities where the proportion of respondents were more educated (PR = 1.23; 95% CI: 1.07-1.41) than the median were more likely to be tested. CONCLUSIONS: This study shed light on potential mechanisms through which HIV testing could be increased in Burkina Faso. Both individual and contextual factors should be considered to design effective strategies for scaling-up HIV testing.

What Level of Risk Compensation Would Offset the Preventive Effect of Early Antiretroviral Therapy? Simulations From the TEMPRANO Trial.

Whether risk compensation could offset the preventive effect of early initiation of antiretroviral therapy (ART) on human immunodeficiency virus (HIV) transmission remains unknown. Using virological and behavioral data collected 12 months after inclusion in the TEMPRANO randomized trial of early ART (Abidjan, Côte d'Ivoire, 2009-2012), we estimated the risk of HIV transmission and compared it between the intervention (early ART; n = 490) and control (deferred ART; n = 467) groups. We then simulated increases in various sexual risk behaviors in the intervention group and estimated the resulting preventive effect. On the basis of reported values of sexual behaviors, we estimated that early ART had an 89% (95% confidence interval: 81, 95) preventive effect on the cumulative risk of HIV transmission over a 1-month period. This preventive effect remained significant for a wide range of parameter combinations and was offset (i.e., nonsignificant) only for dramatic increases in different sexual behaviors simulated simultaneously. For example, when considering a 2-fold increase in serodiscordance and the frequency of sexual intercourse together with a 33% decrease in condom use, the resulting preventive effect was 47% (95% confidence interval: -3, 74). An important reduction of HIV transmission may thus be expected from the scale-up of early ART, even in the context of behavioral change.

Effect of early antiretroviral therapy on sexual behaviors and HIV-1 transmission risk among adults with diverse heterosexual partnership statuses in Côte d'Ivoire.

BACKGROUND: The effect of early initiation of antiretroviral therapy (ART; ie, at CD4(+) T-cell counts >350 cells/mm(3)) on sexual behaviors and human immunodeficiency virus type 1 (HIV) transmission risk has not been documented in populations other than HIV-serodiscordant couples in stable relationships. METHODS: On the basis of data from a behavioral study nested in a randomized, controlled trial (Temprano-ANRS12136) of early ART, we compared proportions of risky sex (ie, unprotected sex with a partner of negative/unknown HIV status) reported 12 months after inclusion between participants randomly assigned to initiate ART immediately (hereafter, "early ART") or according to ongoing World Health Organization criteria. Group-specific HIV transmission rates were estimated on the basis of sexual behaviors and viral load-specific per-act HIV transmission probabilities. The ratio of transmission rates was computed to estimate the protective effect of early ART. RESULTS: Among 957 participants (baseline median CD4(+) T-cell count, 478 cells/mm(3)), 46.0% reported sexual activity in the past month; of these 46.0%, sexual activity for 41.5% involved noncohabiting partners. The proportion of subjects who engaged in risky sex was 10.0% in the early ART group, compared with 12.8% in the standard ART group (P = .17). After accounting for sexual behaviors and viral load, we estimated that the protective effect of early ART was 90% (95% confidence interval, 81%-95%). CONCLUSION: Twelve months after inclusion, patients in the early and standard ART groups reported similar sexual behaviors. Early ART decreased the estimated risk of HIV transmission by 90%, suggesting a major prevention benefit among seronegative sex partners in stable or casual relationships with seropositive individuals.

The untapped health and climate potential of cycling in France: a national assessment from individual travel data.

Background: Promoting active modes of transportation such as cycling may generate important public health, economic, and climate mitigation benefits. We aim to assess the 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. Methods: Using 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, cardiovascular diseases, dementia, and type-2 diabetes) and the number of deaths prevented by cycling, based on national incidence and mortality data and dose-response relationships from meta-analyses. We assessed the corresponding direct medical cost savings and the intangible costs prevented 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 (<5 km) car trips to cycling. Findings: The French adult (20-89 years) population was estimated to cycle on average 1 min 17 sec pers-1 day-1 in 2019, with important heterogeneity across sex and age. This yielded benefits of 1,919 (uncertainty interval, UI: 1,101-2,736) premature deaths and 5,963 (UI: 3,178-8,749) chronic disease cases prevented, with males reaping 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). We estimated that on average, €1.02 (UI: 0.59-1.62) of intangible costs were prevented for every km cycled. Shifting 25% of short car trips to cycling would yield approximatively a 2-fold increase in deaths prevented, while also generating important CO2 emissions reductions (0.257 MtCO2e, UI: 0.231-0.288). Interpretation: In a country with a 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. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Preventing iatrogenic HCV infection: A quantitative risk assessment based on observational data in an Egyptian hospital.

When compliance with infection control recommendations is non-optimal, hospitals may play an important role in hepatitis C (HCV) transmission. However, few studies have analyzed the nosocomial HCV acquisition risk based on detailed empirical data. Here, we used data from a prospective cohort study conducted on 500 patients in the Ain Shams hospital (Cairo, Egypt) in 2017 with the objective of identifying (i) high-risk patient profiles and (ii) transmission hotspots within the hospital. Data included information on patient HCV status upon admission, their trajectories between wards and the invasive procedures they underwent. We first performed a sequence analysis to identify different hospitalization profiles. Second, we estimated each patient's individual risk of HCV acquisition based on ward-specific prevalence and procedures undergone, and risk hotspots by computing ward-level risks. Then, using a beta regression model, we evaluated upon-admission factors linked to HCV acquisition risk and built a score estimating the risk of HCV infection during hospitalization based on these factors. Finally, we assessed and compared ward-focused and patient-focused HCV control strategies. The sequence analysis based on patient trajectories allowed us to identify four distinct patient trajectory profiles. The risk of HCV infection was greater in the internal medicine department, compared to the surgery department (0·188% [0·142%-0·235%] vs. 0·043%, CI 95%: [0·036%-0·050%]), with risk hotspots in the geriatric, tropical medicine and intensive-care wards. Upon-admission risk predictors included source of admission, age, reason for hospitalization, and medical history. Interventions focused on the most at-risk patients were most effective to reduce HCV infection risk. Our results might help reduce the risk of HCV acquisition during hospitalization in Egypt by targeting enhanced control measures to ward-level transmission hotspots and to at-risk patients identified upon admission.

A Comparison of Presentation, Treatment, and Survival After Hepatocellular Carcinoma of Viral and Non-Viral Etiology in Damietta, Egypt, 2007-2019.

Context: The difference in prognosis between patients diagnosed with viral versus non-viral hepatocellular carcinoma (HCC) in Egypt remains unclear. Methods: We used data from patients diagnosed with HCC between 2007 and 2019 from a large monocentric retrospective cohort at the Damietta Oncology referral center (northern Egypt). Presentation and treatment were compared between viral versus non-viral etiology HCC patients. Survival was compared relying on univariate and multivariate Cox regressions. Results: Data from 4714 HCC patients were analyzed. Among them, 204 (4.3%) presented with a non-viral etiology. Patients with non-viral versus viral etiology had a similar presentation overall, especially regarding the BCLC stage at HCC diagnosis. After controlling for various individual characteristics, patients with non-viral versus viral etiology had poorer survival (adjusted Hazard Ratio: 1.244; 95% Confidence Interval: 1.069-1.447). Conclusion: Despite similar features, patients with non-viral- related HCC had poorer survival compared to patients with viral-related HCC.

Estimating the health effects of COVID-19-related immunisation disruptions in 112 countries during 2020-30: a modelling study.

BACKGROUND: There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered. METHODS: For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up. FINDINGS: We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073]). INTERPRETATION: Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption. FUNDING: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation. TRANSLATIONS: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section.

Investigating inequalities in HIV testing in sub-Saharan Africa: spatial analysis of cross-sectional population-based surveys in 25 countries.

OBJECTIVES: We aim to explore spatial variations in socioeconomic inequalities in HIV testing uptake in sub-Saharan Africa (SSA) at different geographical scales to identify potential geographical hotspots of inequalities. Additionally, to evaluate the potential benefits of HIV testing programmes, we assess whether local levels of HIV testing match the local levels of HIV prevalence. DESIGN: A multi-country analysis of population-based cross-sectional surveys in SSA. SETTING: We analysed data from 25 SSA countries with Demographic and Health Surveys between 2011 and 2019. PARTICIPANTS: Country-level analysis included 473 775 participants (312 104 women and 161 671 men) and cluster-level analysis included 328 283 individuals (241 084 women and 87 199 men). Women aged 15-49 years and men aged 15-54/59 years in selected households who were tested for HIV in the last 12 months were eligible. We quantified inequalities in self-reported recent HIV testing with the Slope Index of Inequality (SII) and the Relative Index of Inequality (RII) across geographical scales to capture sex-specific within-country spatial variations. We also conducted local Getis-Ord Gi* statistics to consider the autocorrelation in fine-scale SII and RII across countries. To assess the efficiency of HIV testing programmes, we measured the correlation between recent HIV testing and HIV prevalence through Spearman correlation across geographical scales. RESULTS: We observed varying inequalities in recent HIV testing in magnitude and spatial distribution on both absolute and relative scales in many countries for both sexes at national and subnational levels. Hotspots of 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 testing and prevalence in all countries when assessed at the national level, we report an absence of such a correlation at fine scale in 17 of 50 sex-country combinations. CONCLUSIONS: We highlight the importance of investigating the spatial variability of various HIV indicators and related inequalities across different geographical levels. Results may help inform an equitable distribution of HIV testing services.

Changes in Presentation, Treatment, and Survival of Patients with Hepatocellular Carcinoma in Damietta, Egypt, 2007-2019: A Retrospective Monocentric Cohort Study.

Introduction: 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.

[Dual-use research on modified pathogens in the laboratory: What framework for what issue?] / Recherche à usage dual sur les pathogènes modifiés en laboratoire - Quel encadrement pour quels enjeux ?

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.

Title: Recherche à usage dual sur les pathogènes modifiés en laboratoire - Quel encadrement pour quels enjeux ? Abstract: 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.

Can we distinguish the roles of demographic and temporal changes in the incidence and prevalence of musculoskeletal disorders? A systematic review.

OBJECTIVES: Musculoskeletal disorders (MSD) represent a major public health issue, affecting more then 40 million European workers in 2017. The overall aging of the working population is expected to increase the burden of disease, but temporal changes in exposures or diagnosis may also drive the global trends in MSD. We therefore conducted a systematic review to summarize the evidence on the role of demographic and temporal changes in the occurrence of MSD. METHODS: We conducted a systematic review of articles reporting temporal trends in MSD in the general working-age population. Only articles controlling for age in the analysis were included. The risk of bias was assessed. The main indicators extracted were age-controlled time trends in MSD 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. Results presenting time trends in prevalence were found in 12 studies and incidence in 11. After controlling for age, the reported temporal trends varied, mostly between non-monotonic changes (N=12/23) and increases (N=10/23). One article also highlighted an increase among women and non-monotonic changes among men (N=1/23). Several factors other than aging were suggested to explain temporal trends in MSD, mainly trends in obesity, changing occupational exposures, and cultural factors regarding pain tolerance. CONCLUSION: This review shows that different kind of factors in addition to aging may contribute to varying or increasing trends in MSD. This review also highlighted the scarcity of evidence regarding time trends in the burden of MSD and their underlying causes.