Impact of rituximab on humoral response to SARS-CoV-2 vaccination in previously vaccinated patients with autoimmune diseases.

SARS-CoV-2 infection is more severe in patients undergoing rituximab (RTX) treatment. Humoral response to vaccination is severely impaired in patients already treated with RTX, but data on antibody persistence in patients initiating RTX are lacking. We evaluated the impact of RTX initiation on humoral response to SARS-CoV-2 vaccination in previously vaccinated patients with immune-mediated inflammatory diseases. We performed a retrospective, multicenter study evaluating the evolution of anti-spike antibodies and breakthrough infections after initiation of RTX in previously vaccinated patients with protective levels of anti-SARS-CoV-2 antibodies. Threshold for anti-S antibodies positivity and protection were 30 and 264 BAU/mL, respectively. We included 31 previously vaccinated patients initiating RTX (21 female, median age 57 years). At first RTX infusion, 12 (39%) patients had received 2 doses of vaccine, 15 (48%) had received 3 doses, and 4 (13%) had received 4 doses. The most frequent underlying diseases were ANCA-associated vasculitis (29%) and rheumatoid arthritis (23%). Median anti-S antibody titers at RTX initiation, 3 months, and 6 months were 1620 (589-2080), 1055 (467-2080), and 407 (186-659) BAU/mL, respectively. Overall, antibody titers waned by almost two-fold at 3 months and four-fold at 6 months. Median antibody titers were significantly higher in patients who received ≥3 doses compared to those who received only 2 doses. Three patients developed SARS-CoV-2 infection without any severe symptom. Anti-SARS-CoV-2 antibody titers in previously vaccinated patients decline after RTX initiation similarly to general population. Specific monitoring is useful to anticipate prophylactic strategies. Key Points • Anti-SARS-CoV-2 antibody titers in previously vaccinated patients decline after rituximab initiation similarly to the general population. • The number of dose of vaccine before rituximab initiation is associated with higher antibody titers at month 3. • Monitoring antibody levels is mandatory to initiate prophylactic strategies in this population.

State of the fight against informal market of medicines in Togo: approaches and limitations.

The extent of medicines sales and consumption in the informal market in Togo raises many ethical and public health issues. In order to report on the situation of public action in the fight against this practice, we conducted a qualitative survey from 15 to 25 February 2016 in the commune of Lomé and in the Maritime Region among the actors of control system and resource people in the general population. This was supplemented by an analysis of Togo's pharmaceutical and health policy documents and a literature review on the illicit drug market issues relating to public health, political science, the social sciences applied to health. In spite of the existence of national and international tools, household poverty, cultural self-medication, ignorance of the population concerning the health risks of informal market medicines, weak political commitment, weakness regulation and enforcement, corruption, constitute obstacles to the success of actions to combat this practice.

Public Health and Epidemiology Informatics.

OBJECTIVES: The aim of this manuscript is to provide a brief overview of the scientific challenges that should be addressed in order to unlock the full potential of using data from a general point of view, as well as to present some ideas that could help answer specific needs for data understanding in the field of health sciences and epidemiology. METHODS: A survey of uses and challenges of big data analyses for medicine and public health was conducted. The first part of the paper focuses on big data techniques, algorithms, and statistical approaches to identify patterns in data. The second part describes some cutting-edge applications of analyses and predictive modeling in public health. RESULTS: In recent years, we witnessed a revolution regarding the nature, collection, and availability of data in general. This was especially striking in the health sector and particularly in the field of epidemiology. Data derives from a large variety of sources, e.g. clinical settings, billing claims, care scheduling, drug usage, web based search queries, and Tweets. CONCLUSION: The exploitation of the information (data mining, artificial intelligence) relevant to these data has become one of the most promising as well challenging tasks from societal and scientific viewpoints in order to leverage the information available and making public health more efficient.

[Overmedicalization: When too much medicine harms]. / La surmédicalisation: quand trop de médecine nuit à la santé.

Overmedicalization refers to non-validated medical practices, with no clear benefits, potentially harmful and therefore unnecessarily costly. Awareness is growing with respect to this serious public health problem. Permanent expansion of diagnostic or therapeutic interventions, disease mongering, inadequate management of diagnostic uncertainty, conflict of interest or lack of commitment by physicians and patients in shared decision making. Overmedicalization is made possible by a lack of training of health professionals and users on medical decision process. Only a multidisciplinary research program, involving medical and non-medical worlds, will allow the implementation of corrective actions.

Policy summary 10: addressing needs in the public health workforce in Europe

Health systems in Europe face a number of increasingly complex challenges. Globalization, evolving health threats, an ageing society, fi nancial constraints on government spending, and social and health inequalities are some of the most pressing. Such challenges require not only different funding and organizational approaches to health services, but also demand a multidisciplinary public health workforce supported by new skills and expertise. This policy summary aims to outline these needs and to consider measures and options towards meeting them. First, the aims of the public health workforce in Europe (noting that many elements of this discussion should not be seen as unique to Europe) and the importance of public health are described. The importance of public health professionals who can fi ll information, prevention, social and regulatory defi cits is explained. This is followed by a picture of the current workforce and training provisions. Although the Bologna Process and the WHO Regional Offi ce for Europe's Health 2020 policy provide a conducive backdrop for change and promote positive developments, public health training and education lag behind. Large gaps are apparent in both the numbers of professionals trained and the kind of training that exists. Education is still largely characterized by a traditional and limited public health focus.

An interdisciplinary approach to controlling chikungunya outbreaks on French islands in the south-west Indian ocean.

The outbreak of chikungunya that occurred on French Island territories in the southwest Indian Ocean in 2005 and 2006 caused severe morbidity and mortality. In the aftermath, French authorities set up a scientific task force including experts in epidemiology, public health, entomology, virology, immunology, sociology, animal health, community and hospital medicine. The mission of the task force was to conceive and propose research programs needed to increase understanding of the disease and epidemic and to help public health officials in improving epidemic response measures. The purpose of this article is to describe the findings of the task force at the end of its two-year existence and initial outcomes in the the areas studied. Discussion emphasizes topics requiring further study.

A seroepidemiological study of pandemic A/H1N1(2009) influenza in a rural population of Mali.

The swine-origin H1N1 influenza A virus (pH1N1(2009)) started to circulate worldwide in 2009, and cases were notified in a number of sub-Saharan African countries. However, no epidemiological data allowing estimation of the epidemic burden were available in this region, preventing comprehensive comparisons with other parts of the world. The CoPanFlu-Mali programme studied a cohort of 202 individuals living in the rural commune of Dioro (southern central Mali). Pre-pandemic and post-pandemic paired sera (sampled in 2006 and April 2010, respectively) were tested by the haemagglutination inhibition (HI) method. Different estimates of pH1N1(2009) infection during the 2009 first epidemic wave were used (increased prevalence of HI titre of ≥1/40 or ≥1/80, seroconversions) and provided convergent attack rate values (12.4-14.9%), the highest values being observed in the 0-19-year age group (16.0-18.4%). In all age groups, pre-pandemic HI titres of ≥1/40 were associated with complete absence of seroconversion; and geometric mean titres were <15 in individuals who seroconverted and >20 in others. Important variations in seroconversion rate existed among the different villages investigated. Despite limitations resulting from the size and composition of the sample analysed, this study provides strong evidence that the impact of the pH1N1(2009) first wave was more important than previously believed, and that the determinants of the epidemic spread in sub-Saharan populations were quite different from those observed in developed countries.

Serological study of the 2009 pandemic due to influenza A H1N1 in the metropolitan French population.

We looked for evidence of antibodies to the 2009 influenza A/H1N1 pandemic virus in panels of sera from individuals living in metropolitan France, obtained either before, during or after the epidemic, using standard haemagglutination inhibition and microneutralization tests. The difference between seroprevalence values measured in post- and pre-epidemic panels was used as an estimate of seroconversion rate in different age groups (23.4% (0-24 years, age-group 0); 16.5% (25-34); 7.9% (35-44); 7.2% (45-54); 1.6% (55-64); and 3.1% (>65)), confirming that the distribution of cases in different age groups was similar to that of the seasonal H1N1 virus. During the pre-pandemic period low-titre cross-reactive antibodies were present in a large proportion of the population (presumably acquired against seasonal H1N1) whereas cross-reactive antibodies were detected in individuals over the age of 65 years with significantly higher prevalence and serological titres (presumably acquired previously against Spanish flu-related H1N1 strains). Clinical data and analysis of post-pandemic seroprevalence showed that few of these latter patients were infected by the influenza virus during the epidemic. In contrast, the majority of both clinical cases and seroconversions were recorded in the 0-24 age group and a global inverse relationship between prevalence of antibodies to pH1N1 in the pre-pandemic period and rate of seroconversion was observed amongst age groups. Our results emphasize the complex relationships involved in antigenic reactivity to pandemic and seasonal H1N1 viral antigens; hence the difficulty in distinguishing between low-titre specific and cross-reactive antibodies, establishing precise seroprevalence numbers and fully understanding the relationship between previous immunity to seasonal viruses and protection against the novel variant.

Micro and macro population effects in disease transmission: the case of varicella.

Profiles of varicella-zoster virus (VZV) seroprevalence have shown large variability in European countries in which vaccination has not been implemented. Differences in micro and macro population structures (e.g. household and municipality, respectively) may explain such variability, which is the focus of a population-based study of varicella in 12,000 children from 7800 French households in Corsica. The cumulative incidence was 89% at age 11 years, as the median age at infection was 5 years in first-born children, but decreased to 3.9 years in younger siblings. Hazard of infection in households increased as the first-born child initially enrolled in primary school. Age at infection was higher in less populated areas. Household attack rates increased with age (55% in <6 months, >90% in >3 years) and household secondary attack rate was approximately 70%. Several levels of population structure independently affect age at varicella infection.

Histology after lumpectomy in women with epithelial atypia on stereotactic vacuum-assisted breast biopsy.

BACKGROUND: Large-core needle biopsy of the breast (LCNB) and vacuum-assisted breast biopsy (VABB) are widely used as alternatives to open surgical biopsy (OSB) for initial diagnosis of mammographic abnormalities. Between 18% and 80% of cases in which such specimens show atypical lobular hyperplasia (ALH) or atypical ductal hyperplasia (ADH) are found to be malignant at surgery. DESIGN: From 1999 to 2005, 68 women with mammographic abnormalities were sampled by stereotactic VABB and presented atypical epithelial hyperplasia. Immunohistochemical staining with anti-cytokeratin 5/6 and anti-E-cadherin antibodies was performed. All women underwent a lumpectomy. Clinical, radiological or histological factors predictive of the risk of finding malignancy at surgery were sought. RESULTS: VABB initially showed 28 cases of ADH, 32 cases of ALH, one case of flat epithelial atypia, five cases of mixed atypia, and two cases of Lobular Carcinoma In Situ (LCIS). After slide review with immunohistochemical staining, two cases of ADH were reclassified as simple hyperplasia and two cases of ALH were reclassified as mixed atypia. Seven lesions (10.3%) that appeared to be benign on VABB were found to be malignant on OSB (Ductal Carcinoma In Situ (DCIS) in six cases and invasive ductal carcinoma in one case). ADH was the only predictive factor of malignancy on OSB (p=0.04 versus ALH). CONCLUSION: ADH diagnosed by vacuum-assisted breast biopsy frequently corresponds to cancer on open surgical biopsy. Surgical excision of all breast lesions containing atypical hyperplasia on percutaneous biopsy can be recommended.

[Profile of active investigators involved in a clinical trial in general medical practice]. / Profil des investigateurs actifs au cours d'un essai clinique en médecine générale.

INTRODUCTION: Depiscan was the pilot phase of a large trial to evaluate low dose computed tomography as a screening method for lung cancer (GranDepiscan). The goal of the study presented in this manuscript was to predict the activity of general practitioners (GPs) involved as investigators in a clinical trial. METHODS: A questionnaire about GP's socio-demographic characteristics, initial involvement and perception of difficulties was sent to 189 GPs volunteers after enrollment into the Depiscan trial was complete. RESULTS: Among the 97 respondents, 61 were active investigators. Age lower than 50 years and presence during the initiation visit were significantly associated with the participation of investigators. Two other factors at the limit of significance were: the status and the type of initiation visit. The following factors: gender, type of practice, membership of a medical society, parallel activity in the public sector and knowledge of the referring pulmonary oncologist were not associated with the level of recruitment, as well as the difficulties mentioned by the investigators. CONCLUSIONS: These results will help for selection of investigators for future clinical trials in general medical practice, particularly for the GranDépiscan trial.

Enhancing global capacity in the surveillance, prevention, and control of chronic diseases: seven themes to consider and build upon.

BACKGROUND: Chronic diseases are now a major health problem in developing countries as well as in the developed world. Although chronic diseases cannot be communicated from person to person, their risk factors (for example, smoking, inactivity, dietary habits) are readily transferred around the world. With increasing human progress and technological advance, the pandemic of chronic diseases will become an even bigger threat to global health. METHODS: Based on our experiences and publications as well as review of the literature, we contribute ideas and working examples that might help enhance global capacity in the surveillance of chronic diseases and their prevention and control. Innovative ideas and solutions were actively sought. RESULTS: Ideas and working examples to help enhance global capacity were grouped under seven themes, concisely summarised by the acronym "SCIENCE": Strategy, Collaboration, Information, Education, Novelty, Communication and Evaluation. CONCLUSION: Building a basis for action using the seven themes articulated, especially by incorporating innovative ideas, we presented here, can help enhance global capacity in chronic disease surveillance, prevention and control. Informed initiatives can help achieve the new World Health Organization global goal of reducing chronic disease death rates by 2% annually, generate new ideas for effective interventions and ultimately bring global chronic diseases under greater control.

Investigating transmission in a two-wave epidemic of Chikungunya fever, Réunion Island.

An epidemic of Chikungunya fever, a mosquito-borne viral disease, spectacularly swept through Réunion Island (population 780,000) in 2005-2006. There were 3,000 cases in a first wave (March-June 2005) and more than 250,000 cases in a second (December 2005-April 2006). Adapting newly developed epidemiological tools to vector-borne diseases, we show that despite this massive difference in magnitude, the transmission potential as measured by the number of secondary cases per index case (or reproduction number), remained similar during the two consecutive waves. The best estimate for the initial reproduction number R(0) was 3.7, with a possible range from 2 to 11 depending on incubation duration and lifespan of the mosquito. We conclude that an increase in virulence between the two seasons was not necessary to explain the change in magnitude of the epidemics, and that the attack rate may be well over 50% in Chikungunya fever epidemics in the absence of intervention.

Dual infections by influenza A/H3N2 and B viruses and by influenza A/H3N2 and A/H1N1 viruses during winter 2007, Corsica Island, France.

BACKGROUND: The investigation of dual influenza infection human cases is of major interest specifically for the control of new emerging influenza strains. OBJECTIVES: Using RT-PCR assays, we retrospectively assessed the prevalence of dual influenza virus infections that occurred in patients during the 2006-2007 winter season in Corsica Island (France). STUDY DESIGN: One hundred and thirty-four nasal swabbing samples taken from patients suffering from influenza-like illness between February and March 2007 were analysed using a rapid influenza antigen detection test, cell culture and RT-PCR assays. RESULTS AND CONCLUSION: Influenza viruses were detected in 93 (69.4%) of 134 patients with influenza-like illness using the combination of classical and molecular assays. Dual respiratory infections by influenza viruses were detected in 3 (3.2%) of the 93 influenza positive patients, including two cases of infection by influenza A/H3N2 and B viruses and one case of dual infection by influenza A/H3N2 and A/H1N1 viruses. In the present report, human co-infection cases by two influenza viruses appeared as a rare event in symptomatic patients. However, the virological and epidemiological mechanisms that determine the occurrence of dual influenza infections remain to be fully investigated in further prospective multicentric studies.

[Natural history of corticosteroid-induced lipodystrophy: a prospective follow-up of 37 patients]. / Histoire naturelle de la lipodystrophie cervicofaciale cortico-induite: suivi prospectif d'une cohorte de 37 patients.

PURPOSE: No data is available about the natural history of the corticosteroid-induced lipodystrophy. The purpose of this study is to describe the natural history of corticosteroid-induced lipodystrophy in a selected and homogenous population. METHODS: We conducted a cohort study between June 2003 and September 2005 and enrolled all consecutive patients starting long-term systemic corticosteroid therapy for giant cell arteritis (because of a standardized therapeutic schedule). After enrollment, patients were seen every month until the end of the corticosteroid therapy. After the drug withdrawal, they consulted every 3 months during 6 months. At each consultation, they were photographed in a standardized way. At the end of the study, the development of lipodystrophy was assessed by analyzing these photographs. We evaluated the incidence of corticosteroid-induced lipodystrophy during the course of giant cell arteritis therapy and the time between initiation of therapy and its apparition. Lastly, we evaluated the time between the prednisone withdrawal and the disappearance of lipodystrophy (or the mean prednisone dosage if the disappearance was observed under treatment). RESULTS: Thirty-seven patients were included (women: 73%; mean age: 75+/-7 years; mean initial daily prednisone dosage: 44+/-13 mg). The mean duration of follow-up was 23.6+/-7.4 months. Incidence of corticosteroid-induced lipodystrophy was 48% after 3 months and 60% after 12 months of therapy. The median time between treatment initiation and appearance of lipodystrophy was short (3 months [1-4]). During the decrease of the therapy or the 6 months following its end, we observed a regression of lipodystrophy in 71% of the patients. The median time between corticosteroids initiation and disappearance of lipodystrophy was 19 months [16-22] (concomitant median daily dosage of prednisone: 4 mg [0-7]). CONCLUSION: Lipodystrophy is frequently observed in corticosteroid-treated old patients. It appears precociously after the initiation of therapy and is usually reversible.

Study of partner-related and situational risk factors for symptomatic male urethritis.

During the last decade, the incidence of male urethritis stopped declining in France. Risk factors associated with unprotected intercourse have been extensively studied in men who have sex with men, but not in men in general. The purpose of the study was to determine major risk factors for urethritis among men and to describe the sociodemographic and medical characteristics of this population in 2005. We conducted a prospective case-crossover study of sexual behaviors among men with acute urethritis attending at general practitioners or sexually transmitted infection (STI) clinics in France. Each patient filled out a selfcompleted questionnaire focusing on sociodemographic characteristics, and on sexual behaviors for the month before urethritis onset and for the preceding 3 months. The doctor reported medical information on a separate questionnaire. Between January and September 2005, 121 cases of male urethritis, defined as recent-onset pain on micturition and/or purulent or mucoid discharge, were included. Median age was 33 years, 22.3% were MSM, 55.1% were single, and 72.0% had at least high school education. Conditional logistic regression analysis showed that intercourse with only casual partners or with both casual and steady partners (OR = 2.6, CI 95%: 0.8-8.7, and OR = 8.7, CI 95%: 2.7-28.0), as well as inconsistent condom use (OR = 5.8, CI 95%: 1.7-19.2) significantly increased the risk of male urethritis. STI prevention campaigns should continue to focus on consistent condom use and should not neglect men over 30 years of age.

Influenza vaccine: the challenge of antigenic drift.

Influenza continues to have a major worldwide impact, resulting in considerable human suffering and economic burden. The regular recurrence of influenza epidemics is thought to be caused by antigenic drift, and a number of studies have shown that sufficient changes can accumulate in the virus to allow influenza to reinfect the same host. To address this, influenza vaccine content is reviewed annually to ensure protection is maintained, despite the emergence of drift variants; however, it is not always possible to capture every significant drift, partly due to the timing of the recommendations. Vaccine mismatch can impact on vaccine effectiveness, and has significant epidemiological and economical consequences, as was seen most apparently in the 1997-1998 influenza season. To meet the challenge of antigenic drift, vaccines that confer broad protection against heterovariant strains are needed against seasonal, epidemic and pandemic influenza. In addition to the use of vaccine adjuvants, emerging research areas include development of a universal vaccine and the use of vaccines that exploit mechanisms of cross-protective immunity.

Corticosteroid-induced clinical adverse events: frequency, risk factors and patient's opinion.

BACKGROUND: More than 50 years after the introduction of corticosteroids, few studies have focused on corticosteroid-induced adverse events after long-term systemic therapy. OBJECTIVES: To assess the frequency, risk factors and patient's opinion regarding clinical adverse events occurring early during prednisone therapy. PATIENTS AND METHODS: We conducted a cohort study in two French centres. All consecutive patients starting long-term (> oir = 3 months), high dosage (> or = 20 mg day(-1)) prednisone therapy were enrolled. The main clinical adverse events attributable to corticosteroids were assessed after 3 months of therapy, by comparison with baseline status. The patient's opinion regarding the disability induced by these adverse events was recorded. Risk factors of frequently observed adverse effects were identified by using logistic regression. RESULTS: Eighty-eight patients were enrolled and 80 were monitored for at least 3 months (women 76%; mean age 59.1 +/- 18.7 years; giant cell arteritis 39%; mean baseline prednisone dosage 54 +/- 17 mg day(-1)). Lipodystrophy was the most frequent adverse event [63.0% (51.0-73.1)], was considered the most distressing by the patients and was most frequent in women and young patients. Neuropsychiatric disorders occurred in 42 patients [52.5% (41.0-63.8)], necessitating hospitalization in five cases. Skin disorders were noted by 37 patients [46.2% (35.0-57.7)] and were more frequent in women. Muscle cramp and proximal muscle weakness were reported by 32.5% (22.5-43.9) and 15% (8.0-24.7) of patients, respectively. Newly developed hypertension occurred in 8.7% (2.9-20.3) of patients. Lastly, 39% (19.7-61.4) of the premenopausal women reported menstrual disorders. CONCLUSIONS: Lipodystrophy and neuropsychiatric disorders are common adverse events of long-term prednisone therapy and are particularly distressing for the patients concerned. The impact of these adverse events on adherence to corticosteroid therapy is not known.