Incidence of Influenza in Healthy Adults and Healthcare Workers: A Systematic Review and Meta-Analysis

BACKGROUND: Working in healthcare is often considered a risk factor for influenza; however, this risk has not been quantified. We aimed to systematically review evidence describing the annual incidence of influenza among healthy adults and healthcare workers (HCWs). METHODS AND FINDINGS: We searched OVID MEDLINE (1950 to 2010), EMBASE (1947 to 2010) and reference lists of identified articles. Observational studies or randomized trials reporting full season or annual influenza infection rates for healthy, working age adult subjects and HCWs were included. Influenza infection was defined as a four-fold rise in antibody titer, or positive viral culture or polymerase chain reaction. From 24,707 citations, 29 studies covering 97 influenza seasons with 58,245 study participants were included. Pooled influenza incidence rates (IR) (95% confidence intervals (CI)) per 100 HCWs per season and corresponding incidence rate ratios (IRR) (95% CI) as compared to healthy adults were as follows. All infections: IR 18.7 (95% CI, 15.8 to 22.1), IRR 3.4 (95% CI, 1.2 to 5.7) in unvaccinated HCWs; IR 6.5 (95% CI, 4.6 to 9.1), IRR 5.4 (95% CI, 2.8 to 8.0) in vaccinated HCWs. Symptomatic infections: IR 7.5 (95% CI, 4.9 to 11.7), IRR 1.5 (95% CI, 0.4 to 2.5) in unvaccinated HCWs, IR 4.8 (95% CI, 3.2 to 7.2), IRR 1.6 (95% CI, 0.5 to 2.7) in vaccinated HCWs. CONCLUSIONS: Compared to adults working in non-healthcare settings, HCWs are at significantly higher risk of influenza

BMC Med

BACKGROUND: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). METHODS: We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype. RESULTS: 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. CONCLUSIONS: Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates

In response: Multifactorial basis of epilepsy in patients with neurocysticercosis.

International audienc

Neurocysticercosis: A natural human model of epileptogenesis

ObjectiveTo develop a better understanding of mechanisms of seizures and long-term epileptogenesis using neurocysticercosis.MethodsA workshop was held bringing together experts in epilepsy and epileptogenesis and neurocysticercosis.ResultsHuman neurocysticercosis and parallel animal models offer a unique opportunity to understand basic mechanisms of seizures. Inflammatory responses to degenerating forms and later-stage calcified parasite granulomas are associated with seizures and epilepsy. Other mechanisms may also be involved in epileptogenesis.SignificanceNaturally occurring brain infections with neurocysticercosis offer a unique opportunity to develop treatments for one of the world's most common causes of epilepsy and for the development of more general antiepileptogenic treatments. Key advantages stem from the time course in which an acute seizure heralds a start of the epileptogenic process, and radiographic changes of calcification and perilesional edema provide biomarkers of a chronic epileptic state.Intramural Research Program of the National Institute of Allergy and Infectious Diseases from the National Institutes of HealthOffice of Rare Diseases Research from the National Institutes of HealthNational Center for Advancing Translational Sciences from the National Institutes of HealthFogarty International Center Training Grant from the National Institutes of HealthWellcome Trust Senior International Research Fellowship in Tropical Medicine and Public HealthNatl Inst Allergy & Infect Dis, Natl Inst Hlth, Parasit Dis Lab, Bethesda, MD USAUniv Illinois, Dept Neurol & Rehabil, Chicago, IL USANatl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Epilepsy Sect, Bethesda, MD USABen Gurion Univ Negev, Zlotowski Ctr Neuroscience, Negev, Beer Sheva, IsraelDalhousie Univ, Dept Med Neuroscience, Halifax, NS, CanadaUCL Inst Neurol, NIHR UCL Hosp Biomed Res Ctr, Dept Clin Expt Epilepsy, London, United KingdomNetherlands Fdn, Epilepsy Inst, Heemstede, NetherlandsDept Neurol, Dayan & Med Coll, Ludhiana, Punjab, IndiaUniversidade Federal de São Paulo, Dept Neurol & Neurosurgery, São Paulo, BrazilUniv Espiritu Santo, Sch Med, Guayaquil, EcuadorRibeirAo Preto Med Sch Univ São Paulo, Dept Neurosciences & Behav, Ribeirao Preto, BrazilNatl Autonomous Univ Mexico & Natl Inst Neurol &, Inst Biomed Res, Mexico City, DF, MexicoUniv Peruana Cayetano Heredia, Fac Sci & Philosophy, Dept Cellular & Mol Sci, Lima, PeruUniv Limoges, Inst Neuroepidemiol & Trop Neurol, INSERM, CHU Limoges, Limoges, FranceUS Naval Med Res Unit 6, Callao, PeruHosp Alberto Sabogal, Dept Neurol, Callao, PeruUniv Texas, Div Infect Dis, Dept Internal Med, Galveston, TX USANatl Univ San Marcos, Sch Vet Med, Dept Vet Publ Hlth, Lima, PeruJohns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USAInst Neurol Dis, Cysticercosis Unit, Lima, PeruUniv Peruana Cayetano Heredia, Univ Peruana Cayetano Heredia, Dept Microbiol, Ctr Global Hlth Tumbes, Lima, PeruUniversidade Federal de São Paulo, Dept Neurol & Neurosurgery, São Paulo, BrazilFogarty International Center Training Grant from the National Institutes of Health: D43 TW00114Web of Scienc

Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME program

International audienc

Drug treatments for covid-19 : living systematic review and network meta-analysis

Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 10 August 2020. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a Bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 35 trials with 16 588 patients met inclusion criteria; 12 (24.3%) trials and 6853 (41.3%) patients are new from the previous iteration. Twenty-seven randomised controlled trials were included in the analysis performed on 29 July 2020. Compared with standard care, glucocorticoids probably reduce death (risk difference 31 fewer per 1000 patients, 95% credible interval 55 fewer to 5 fewer, moderate certainty), mechanical ventilation (28 fewer per 1000 patients, 45 fewer to 9 fewer, moderate certainty), and duration of hospitalisation (mean difference −1.0 day, −1.4 to −0.6 days moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, and length of hospital stay is uncertain, but it probably reduces duration of symptoms (−2.6 days −4.3 to −0.6 days, moderate certainty) and probably does not substantially increase adverse effects leading to drug discontinuation (3 more per 1000, 7 fewer to 43 more, moderate certainty). Hydroxychloroquine may not reduce risk of death (13 more per 1000, 15 fewer to 43 more, low certainty) or mechanical ventilation (19 more per 1000, 4 fewer to 45 more, moderate certainty). The certainty in effects for all other interventions was low or very low certainty. Co nclusion Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas hydroxychloroquine may not reduce either. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important limitations. Systematic review registration This review was not registered. The protocol is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the update number and date of access for clarity.Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearcherPostdoctoralGraduat