Opinion polls on vaccination intentions suggest that COVID-19 vaccine hesitancy is increasing worldwide; however, the usefulness of opinion polls to prepare mass vaccination campaigns for specific new vaccines and to estimate acceptance in a country's population is limited. We therefore aimed to assess the effects of vaccine characteristics, information on herd immunity, and general practitioner (GP) recommendation on vaccine hesitancy in a representative working-age population in France. In this survey experiment, adults aged 18-64 years residing in France, with no history of SARS-CoV-2 infection, were randomly selected from an online survey research panel in July, 2020, stratified by gender, age, education, household size, and region and area of residence to be representative of the French population. Participants completed an online questionnaire on their background and vaccination behaviour-related variables (including past vaccine compliance, risk factors for severe COVID-19, and COVID-19 perceptions and experience), and were then randomly assigned according to a full factorial design to one of three groups to receive differing information on herd immunity (>50% of adults aged 18-64 years must be immunised [either by vaccination or infection]; >50% of adults must be immunised [either by vaccination or infection]; or no information on herd immunity) and to one of two groups regarding GP recommendation of vaccination (GP recommends vaccination or expresses no opinion). Participants then completed a series of eight discrete choice tasks designed to assess vaccine acceptance or refusal based on hypothetical vaccine characteristics (efficacy [50%, 80%, 90%, or 100%], risk of serious side-effects [1 in 10 000 or 1 in 100 000], location of manufacture [EU, USA, or China], and place of administration [GP practice, local pharmacy, or mass vaccination centre]). Responses were analysed with a two-part model to disentangle outright vaccine refusal (irrespective of vaccine characteristics, defined as opting for no vaccination in all eight tasks) from vaccine hesitancy (acceptance depending on vaccine characteristics). Survey responses were collected from 1942 working-age adults, of whom 560 (28·8%) opted for no vaccination in all eight tasks (outright vaccine refusal) and 1382 (71·2%) did not. In our model, outright vaccine refusal and vaccine hesitancy were both significantly associated with female gender, age (with an inverted U-shaped relationship), lower educational level, poor compliance with recommended vaccinations in the past, and no report of specified chronic conditions (ie, no hypertension [for vaccine hesitancy] or no chronic conditions other than hypertension [for outright vaccine refusal]). Outright vaccine refusal was also associated with a lower perceived severity of COVID-19, whereas vaccine hesitancy was lower when herd immunity benefits were communicated and in working versus non-working individuals, and those with experience of COVID-19 (had symptoms or knew someone with COVID-19). For a mass vaccination campaign involving mass vaccination centres and communication of herd immunity benefits, our model predicted outright vaccine refusal in 29·4% (95% CI 28·6-30·2) of the French working-age population. Predicted hesitancy was highest for vaccines manufactured in China with 50% efficacy and a 1 in 10 000 risk of serious side-effects (vaccine acceptance 27·4% [26·8-28·0]), and lowest for a vaccine manufactured in the EU with 90% efficacy and a 1 in 100 000 risk of serious side-effects (vaccine acceptance 61·3% [60·5-62·1]). COVID-19 vaccine acceptance depends on the characteristics of new vaccines and the national vaccination strategy, among various other factors, in the working-age population in France. French Public Health Agency (Santé Publique France).

Alcohol use has been identified as a risk factor for dementia and cognitive decline. However, some patterns of drinking have been associated with beneficial effects. To clarify the relationship between alcohol use and dementia, we conducted a scoping review based on a systematic search of systematic reviews published from January 2000 to October 2017 by using Medline, Embase, and PsycINFO. Overall, 28 systematic reviews were identified: 20 on the associations between the level of alcohol use and the incidence of cognitive impairment/dementia, six on the associations between dimensions of alcohol use and specific brain functions, and two on induced dementias. Although causality could not be established, light to moderate alcohol use in middle to late adulthood was associated with a decreased risk of cognitive impairment and dementia. Heavy alcohol use was associated with changes in brain structures, cognitive impairments, and an increased risk of all types of dementia. Reducing heavy alcohol use may be an effective dementia prevention strategy.

Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count <30×10⁹/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4–24.2, P<.001), serum creatinine level ≤200 µmol/L (OR 23.4, 95% CI 8.8–62.5, P<.001), and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0–8.0, P<.05). When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups.

Dementia is a prevalent condition, affecting 5-7% of people aged 60 years and older, and a leading cause of disability in people aged 60 years and older globally. We aimed to examine the association between alcohol use disorders and dementia risk, with an emphasis on early-onset dementia (1·7) in sensitivity analyses on dementia case definition (including Alzheimer's disease) or older study populations. Also, alcohol use disorders were significantly associated with all other risk factors for dementia onset (all p<0·0001). Alcohol use disorders were a major risk factor for onset of all types of dementia, and especially early-onset dementia. Thus, screening for heavy drinking should be part of regular medical care, with intervention or treatment being offered when necessary. Additionally, other alcohol policies should be considered to reduce heavy drinking in the general population. None.

Background. Empirical antifungal therapy is the standard of care for neutropenic patients with hematological malignancies who remain febrile despite

To assess the efficacy and safety of rituximab in adults responding poorly to standard treatment for severe autoimmune thrombotic thrombocytopenic purpura. Open-label prospective study. Outcomes in the survivors were compared to those of 53 historical survivors who were given therapeutic plasma exchange alone or with vincristine. Hospitals belonging to the Reference Network for Thrombotic Microangiopathies in France. Twenty-two adults with either no response or a disease exacerbation when treated with intensive therapeutic plasma exchange. Add-on rituximab therapy, four infusions over 15 days. One patient died despite two rituximab infusions. In the rituximab-treated patients, the time to a durable remission was significantly shortened (p = .03), although the plasma volume required to achieve a durable remission was not significantly different compared to the controls. Platelet count recovery occurred within 35 days in all 21 survivors, compared to only 78% of the historical controls (p < .02). Of the rituximab-treated patients, none had a relapse within the first year but three relapsed later on. In patients treated with rituximab, a rapid and profound peripheral B-cell depletion was produced, lasting for 9 months and correlating with higher a disintegrin and metalloproteinase with thrombospondin-13 activity and lower anti-a disintegrin and metalloproteinase with thrombospondin-13 antibody titers. These differences were no longer significant after 12 months. No severe side effects occurred. Adults with severe thrombocytopenic purpura who responded poorly to therapeutic plasma exchange and who were treated with rituximab had shorter overall treatment duration and reduced 1-yr relapses than historical controls.