[The impact of the COVID-19 pandemic on first-line primary care in southeastern France: Feedback on the implementation of a real-time monitoring system based on regional health insurance data]. / L'impact de l'épidémie de COVID-19 sur les soins de premier recours en région Provence-Alpes-Côte d'Azur : retour d'expérience sur la mise en place d'un dispositif de surveillance en temps réel à partir des données régionales de l'Assurance maladie.

BACKGROUND: Starting in spring 2020, the COVID-19 pandemic markedly impacted the French healthcare system. Lockdown and risks of exposure to the coronavirus induced patients to modify their ways of use. The objective of this article was to share feedback on the implementation of a real-time monitoring system concerning (a) the activity of private practitioners in southeastern France, and (b) the evolution of reimbursements for drugs prescribed to persons with diabetes, for treatment of mental health disorders, and for performance of some vaccines. METHODS: Data regarding 2019 and 2020 were extracted from regional health insurance databases. They were used to elaborate several indicators relative to the general health insurance scheme, which were calculated and updated each week, starting with week 2. RESULTS: We observed a drop in private physician activity during the lockdown (-23% for general practitioners; -46% for specialist doctors), followed by a return to a semblance of normalcy. Concomitantly, a boom in teleconsultations occurred: at the height of the crisis they represented 30% of medical acts. The initial stage of the lockdown was characterized by peak provisioning for drugs, whereas vaccination strongly declined (-39% regarding measles, mumps and rubella vaccine among children aged less than 5 years; -54% regarding human papillomavirus vaccine among girls aged 10 to 14 years). CONCLUSION: The COVID-19 pandemic could lead to health effects other than those directly attributable to the coronavirus itself. Renouncing care may result in healthcare delays highly deleterious for people and society. Public authorities are preoccupied with these questions; they have set up action plans aimed at encouraging patients to seek treatment without delay. That said, the COVID-19 pandemic crisis has also created opportunities, such as the expansion of telemedicine. Although partial, these indicators can provide useful information enabling public decision makers to be reactive and to implement specific actions to meet the health needs of the population.

The impact of the COVID-19 epidemic on primary care in South-eastern France: implementation of a real-time monitoring system based on regional health insurance system data.

BACKGROUND: The spring 2020 COVID-19 epidemic severely impacted France's healthcare system. The associated lockdown (17 March- 11 May 2020) and the risk of exposure to SARS-CoV-2 led patients to change their use of healthcare. This article presents the development and implementation of a real-time system to monitor i) private doctors' activity in South-eastern France, and ii) changes in prescription of drugs for people with diabetes, mental health disorders and for certain vaccines from Mars 2020 to October 2020. METHODS: Data extracted from the regional healthcare insurance databases for 2019 and 2020 were used to construct indicators of healthcare use. They were calculated on a weekly basis, starting from week 2 2020 and compared for the same period between 2019 and 2020. RESULTS: Private doctors' activity decreased during the spring 2020 lockdown (by 23 % for general practitioners and 46 % for specialists), followed by an almost complete return to normal after it ended until week 41. Over the same period, a huge increase in teleconsultations was observed, accounting for 30 % of private doctors' consultations at the height of the crisis. The start of the lockdown was marked by a peak in drug prescriptions, while vaccinations declined sharply (by 39 % for the measles, mumps and rubella (MMR) vaccine in children under 5 years old, and by 54 % for human papillomavirus vaccine in girls aged 10-14 years old). CONCLUSION: The ongoing COVID-19 epidemic may lead to health consequences other than those directly attributable to the disease itself. Specifically, lockdowns and foregoing healthcare could be very harmful at the individual and population levels. The latter issue is a concern for French public authorities, which have implemented actions aimed at encouraging patients to immediately seek treatment. However, the COVID-19 crisis has also created opportunities, such as the roll-out of teleconsultation and tele-expertise. The indicators described here as part of the monitoring system can help public decision-makers to become more responsive and to implement tailored actions to better meet the general population's healthcare needs.

Health care utilization by men with prostate cancer during the year before their death: A 2015 population-based study.

INTRODUCTION: To study the characteristics and health care utilization of men with prostate cancer (PCa) during their last year and last month of life, as these data have been rarely reported to date. SUBJECTS AND METHOD: Men covered by the national health Insurance general scheme (77% of the French population) treated for PCa (2014-2015), who died in 2015 were identified in the national health data system, including reimbursed hospital and outpatient care, and their causes of death. RESULTS: A total of 11,193 men (mean age: 81 years, SD: 9.6) were included. Almost 58% of these men died in a short-stay hospital (SSH), 4% died in hospital-at-home, 9% died in Rehab, 9% died in skilled nursing homes and 21% died at home. During the last year of life, almost all men were hospitalised at least once in SSH and 47% received hospital palliative care (HPC), immediately prior to death in 8% of cases. During the last month of life, 76% of men were hospitalised at least once in SSH, 43% attended an emergency department and 14% were admitted to intensive care, 7% received a chemotherapy session, and 24% received an antineoplastic agent dispensed by a retail pharmacy. Cancer was the main cause of death for 63% of men, corresponding to PCa in 40% of cases, and cardiovascular disease was the main cause of death for 13% of men with marked variations according to age, place of death, and use of HPC. The mean cost reimbursed per man during the last year of life was €38,750 (€48,601 including HPC). CONCLUSIONS: In France, end-of-life management of men with PCa, regardless of the cause of death, is centered on SSH and HPC, essentially at the time of death. Certain indicators of end-of-life management were particular high. LEVEL OF EVIDENCE: 4.

Kinetically Enhanced Fabrication of Homogeneous Biomimetic and Functional Emulsion Droplets.

Characterized by a fluid and deformable interface, ligand-functionalized emulsion droplets are used as model probes to address biophysical, biological, and developmental questions. Functionalization protocols usually rely on the use of headgroup-modified phospholipids that are dissolved in the oil phase prior to emulsification, leading to a broad range of surface densities within a given droplet population. With the aim to coat particles homogeneously with biologically relevant lipids and proteins (streptavidin, immunoglobulins, etc.), we developed a reliable surface decoration protocol based on the use of polar cosolvents to dissolve the lipids in the aqueous phase after the droplet production. We show that the surface density of the lipids at the interface has a narrow normal distribution for droplets having the same size. We performed titration isotherms for lipids and biologically relevant proteins on these drops. Then, we studied the influence of the presence of surfactants in the medium on lipid insertion and compared the results for a range of polar cosolvents of increasing polarity. To assess both the generality and the biocompatibility of the method, we show that we can produce more sophisticated, monodisperse functional magnetic emulsions with a very high surface homogeneity. Using an oil denser than the surrounding culture medium, we show that IgG-coated droplets can be used as probes for phagocytosis experiments.

Value of a national administrative database to guide public decisions: From the système national d'information interrégimes de l'Assurance Maladie (SNIIRAM) to the système national des données de santé (SNDS) in France.

In 1999, French legislators asked health insurance funds to develop a système national d'information interrégimes de l'Assurance Maladie (SNIIRAM) [national health insurance information system] in order to more precisely determine and evaluate health care utilization and health care expenditure of beneficiaries. These data, based on almost 66 million inhabitants in 2015, have already been the subject of numerous international publications on various topics: prevalence and incidence of diseases, patient care pathways, health status and health care utilization of specific populations, real-life use of drugs, assessment of adverse effects of drugs or other health care procedures, monitoring of national health insurance expenditure, etc. SNIIRAM comprises individual information on the sociodemographic and medical characteristics of beneficiaries and all hospital care and office medicine reimbursements, coded according to various systems. Access to data is controlled by permissions dependent on the type of data requested or used, their temporality and the researcher's status. In general, data can be analyzed by accredited agencies over a period covering the last three years plus the current year, and specific requests can be submitted to extract data over longer periods. A 1/97th random sample of SNIIRAM, the échantillon généraliste des bénéficiaires (EGB), representative of the national population of health insurance beneficiaries, was composed in 2005 to allow 20-year follow-up with facilitated access for medical research. The EGB is an open cohort, which includes new beneficiaries and newborn infants. SNIIRAM has continued to grow and extend to become, in 2016, the cornerstone of the future système national des données de santé (SNDS) [national health data system], which will gradually integrate new information (causes of death, social and medical data and complementary health insurance). In parallel, the modalities of data access and protection systems have also evolved. This article describes the SNIIRAM data warehouse and its transformation into SNDS, the data collected, the tools developed in order to facilitate data analysis, the limitations encountered, and changing access permissions.

[Health care use by free complementary health insurance coverage beneficiaries in France in 2012]. / Consommations de soins des bénéficiaires de la couverture maladie universelle complémentaire (CMUC) ou de l'aide pour une complémentaire santé (ACS) en 2012.

BACKGROUND: The objective was to investigate healthcare use among people covered by one of the two complementary healthcare insurance schemes available for people with low annual income: CMUC (universal complementary healthcare insurance) and, for people whose income exceeds the CMUC ceiling, ACS (aid for complementary healthcare insurance). Comparisons were made between CMUC and ACS beneficiaries versus CMUC and ACS non-beneficiaries and between CMUC beneficiaries and ACS beneficiaries. METHODS: Using the national health insurance information system (SNIIRAM), people less than 60 years old covered by the general national health insurance (86% of the 66 million inhabitants) and with ACS or CMUC coverage in 2012 were selected. Diseases were identified using hospital diagnosis, drugs refunds and long-term chronic disease status. Hospital related diagnoses were categorized in major hospital activity groups. Sex- and age-standardized relative risk (RR) were calculated. RESULTS: There were 4.4 million (9.6%) CMUC beneficiaries and 732,000 (1.6%) ACS beneficiaries (56% and 54% women; mean age: 24 years and 29 years respectively versus 52% and 30 years for CMUC or ACS non-beneficiaries). CMUC or ACS beneficiaries had more often cardiovascular diseases (RR=1.4;2.1) and diabetes (RR=2.2;2.4). Their sex- and age-standardized hospitalisation rates for all diagnosis were higher (18%; 17%, RR=1.3;1.4) than CMUC or ACS non-beneficiaries (13%). This was especially the case for the following major groups: toxicology, intoxications, alcohol major group (RR=3.8;4.0); psychiatry (RR=2.8;4.1); respiratory disease (RR=1.9;2.3); infectious disease (RR=1.9;2.7). Compared with CMUC beneficiaries, ACS beneficiaries had more often cancer (RR=1.5), cardiovascular disease (RR=1.5), neurological disease (RR=2.7), psychiatric illness (RR=2.6), end-stage renal disease (RR=2.8), hemophilia (RR=1.4) or cystic fibrosis (RR=1.6) and they received also more often disability allowance (20%, 4%). CONCLUSION: The disease and hospitalisation rates of ACS beneficiaries are similar or higher than those of CMUC beneficiaries, especially for disabling diseases. Both CMUC and ACS beneficiaries received healthcare for chronic diseases that can be targeted by prevention and screening programs for more optimal healthcare.

Surface decoration of catanionic vesicles with superparamagnetic iron oxide nanoparticles: a model system for triggered release under moderate temperature conditions.

We report the design of new catanionic vesicles decorated with iron oxide nanoparticles, which could be used as a model system to illustrate controlled delivery of small solutes under mild hyperthermia. Efficient release of fluorescent dye rhodamine 6G was observed when samples were exposed to an oscillating magnetic field. Our system provides direct evidence for reversible permeability upon magnetic stimulation.

Directional control of neurite outgrowth: emerging technologies for Parkinson's disease using magnetic nanoparticles and magnetic field gradients.

A challenge in current stem cell therapies for Parkinson's disease (PD) is controlling neuronal outgrowth from the substantia nigra towards the targeted area where connectivity is required in the striatum. Here we present progress towards controlling directional neurite extensions through the application of iron-oxide magnetic nanoparticles (MNPs) labelled neuronal cells combined with a magnetic array generating large spatially variant field gradients (greater than 20 T m-1). We investigated the viability of this approach in both two-dimensional and organotypic brain slice models and validated the observed changes in neurite directionality using mathematical models. Results showed that MNP-labelled cells exhibited a shift in directional neurite outgrowth when cultured in a magnetic field gradient, which broadly agreed with mathematical modelling of the magnetic force gradients and predicted MNP force direction. We translated our approach to an ex vivo rat brain slice where we observed directional neurite outgrowth of transplanted MNP-labelled cells from the substantia nigra towards the striatum. The improved directionality highlights the viability of this approach as a remote-control methodology for the control and manipulation of cellular growth for regenerative medicine applications. This study presents a new tool to overcome challenges faced in the development of new therapies for PD.

Severe clinical toxicities are correlated with survival in patients with advanced renal cell carcinoma treated with sunitinib and sorafenib.

BACKGROUND: In advanced renal cell carcinoma (RCC), sunitinib and sorafenib tyrosine kinase inhibitors (TKI) are associated with several clinical side effects, with no definitive established data concerning their clinical impact. METHODS: From June 2006 to June 2008, main clinical TKI-induced toxicities, including digestive, cardiac, dermatologic and asthenia were retrospectively collected using the NCI-CTC version 3.0 in patients treated with TKI for an RCC. RESULTS: The median overall survival was significantly improved in patients with grade 3-4 clinical toxicities (36 vs 12 months, P=0.009). In multivariate analysis, the Memorial Sloan-Kettering Cancer Center risk groups (good vs intermediate or poor) and clinical toxicities (grade 3-4 vs 1-2) were identified as independent prognostic factors of better survival (P=0.002 and P=0.02, respectively). The Charlson comorbidity index score (>7 vs <7) was identified as independent predictive factor of severe clinical TKI-induced toxicities (P=0.02). CONCLUSION: In this unselected patients of RCC, clinical TKI-related severe toxicities were more frequent in patients with comorbidities and were associated with better survival.

CRMP-2 induces axons in cultured hippocampal neurons.

In cultured hippocampal neurons, one axon and several dendrites differentiate from a common immature process. Here we found that CRMP-2/TOAD-64/Ulip2/DRP-2 (refs. 2-4) level was higher in growing axons of cultured hippocampal neurons, that overexpression of CRMP-2 in the cells led to the formation of supernumerary axons and that expression of truncated CRMP-2 mutants suppressed the formation of primary axon in a dominant-negative manner. Thus, CRMP-2 seems to be critical in axon induction in hippocampal neurons, thereby establishing and maintaining neuronal polarity.

Sterically stabilized superparamagnetic liposomes for MR imaging and cancer therapy: pharmacokinetics and biodistribution.

Pharmacokinetics of magnetic-fluid-loaded liposomes (MFLs) with mean hydrodynamic diameter of 200 nm sterically stabilized by poly(ethylene glycol) (PEG) and labelled by a fluorescent lipid probe, N-(lissamine rhodamine B sulfonyl) phosphatidylethanolamine (Rho-PE) was studied. The loading consisted in an aqueous suspension of maghemite nanocrystals close to 8 nm in size at 1.7 Fe(III)mol/mol total lipids ratio. Double tracking of MFL in blood was performed versus time after intravenous administration in mice. Lipids constituting vesicle membrane were followed by Rho-PE fluorescence spectroscopy while iron oxide was determined independently by relaxometry. MFLs circulating in the vascular compartment conserved their vesicle structure and content. The pharmacokinetic profile was characterized by two first-order kinetics of elimination with distinct plasmatic half-lives of 70 min and 12.5 h. Iron biodistribution and organ histology clearly highlighted preferential MFL accumulation within liver and spleen. The pathway in spleen supported that elimination was governed by the mononuclear phagocyte system (MPS). PEG coating was essential to prolong MFL circulation time whereas iron oxide loading tends to favour uptake by the MPS. Despite partial uptake in the earlier times after administration, MFLs exhibited long circulation behaviour over a 24-h period that, coupled to magnetic targeting, encourages further use in drug delivery.

Design of magnetic molecularly imprinted polymer nanoparticles for controlled release of doxorubicin under an alternative magnetic field in athermal conditions.

An innovative magnetic delivery nanomaterial for triggered cancer therapy showing active control over drug release by using an alternative magnetic field is proposed. In vitro and In vivo release of doxorubicin (DOX) were investigated and showed a massive DOX release under an alternative magnetic field without temperature elevation of the medium.

[Dengue in New Caledonia. Study of 68 pediatric cases]. / La dengue en Nouvelle-Calédonie. Etude de 68 cas pédiatriques.

UNLABELLED: New Caledonia is a French territory of Pacific Ocean, where frequent dengue outbreaks occur. In 1995 and 1996, 3042 cases (including 18.3% children) were diagnosed in Pasteur Institute of Noumea. PATIENTS AND METHODS: This work was a clinical and biological study of 68 in-patients of different ethnical groups in children. Among these young patients, 14 cases of dengue hemorrhagic fever occurred. RESULTS: The children were admitted to hospital after an average of 2.7 days of complaint, and during 6.7 days. The most important symptoms were fever at 39 degrees C (100%) during 2.2 days, sweatings (100%), malaise (57%) and headache (50%). Forty children had, at least, one hemorrhagic symptom. Leucopenia was noticed in 42 children, on an average of 4.2 days. A thrombocytopenia (mean 114,746 platelets/mm3) occurred in 5.3 days in 34 children (six cases with less than 10,000 platelets/mm3). A bacterial infection arised in 23.5% of children. CONCLUSION: Dengue is an important problem of public health, which occurs in all population, including the young children. The fight against dengue fever by a rapid destruction of larvae and adult mosquitoes led to the decrease of the outbreak.

[Perforated gastric ulcer in the child: a rare complication, a case report]. / Perforation d'ulcère gastrique de l'enfant: une complication rare, à propos d'un cas.

UNLABELLED: Perforated gastric ulcer is unusual in children. We report a case in a girl with an unexpected evolution. CASE REPORT: A 13-year-old girl was admitted for abdominal pain. She had no particular personal history but her father had a perforated ulcer. On admission she was not painful, her abdomen was soft on palpation. The white blood cell count was 1.7 x 10(3)/mm3. A right pneumoperitoneum was seen on an abdominal X-ray film. Because of her good general status and the normalization of the abdominal X ray film six hours later, no surgical exploration was performed. On the fourth day, a gastrointestinal endoscopy showed an anterior gastric ulcer which was perforated. Biopsies did not isolate H. pylori. The patient was given a treatment with amoxicillin-metronidazole (7 d) and oméprazole (7 weeks). An endoscopic control, one month later, showed a total healing of the gastric ulcer. CONCLUSION: Peptic ulcerations and their complications are underdiagnosed in childhood. This could lead to delay in diagnosis or inappropriate treatment specially in case of perforation.

[Sudden sight impairment revealing a cat-scratch disease: report of three cases]. / Baisse brutale de l'acuité visuelle révélatrice d'une maladie des griffes du chat: à propos de trois cas.

UNLABELLED: Cat-scratch disease is a frequent but innocuous cause of chronic lymphadenopathy in children. Numerous atypical forms have been described. We report three cases of acute sight impairment revealing a cat-scratch disease. BACKGROUND: A 13 year-old boy and two girls aged 10 and 13 suffered from a sudden bilateral sight impairment with papillary edema, with fever in two cases. Neurological examinations, X-rays and lumbar puncture results were found normal. However, all patients were tested positive to Bartonella Henselae. Antibiotic and anti-inflammatory treatments were efficient in two cases. CONCLUSION: Cat-scratch disease can be characterized by an isolated and acute sight impairment with a stellate neuroretinitis. The potency of antibiotic treatments is debatable.

[Hepatic abscesses in childhood: retrospective study about 33 cases observed in New-Caledonia between 1985 and 2003]. / Les abcès hépatiques de l'enfant: étude rétrospective de 33 cas observés en Nouvelle-Calédonie de 1985 à 2003.

UNLABELLED: Hepatic abscesses in childhood are rarely observed in Europe. The aim of this word was to study how to diagnose and how to treat an hepatic abscess. METHODS: Between 1985 and 2003, we recensed retrospectively 33 cases of hepatic abscesses hospitalised in the paediatric unit of Noumea. RESULTS: Children were mainly melanesians (79%), 7 years old on average, having abdominal pains, a clinical and biological infectious syndrome, and abscesses images on ultrasonography or computed tomography. The identified micro-organisms included Entamoeba histolytica in 30% (10 cases); Staphylococcus aureus in 15% (five cases), Staphylococcus coagulase negative in 6% (two cases), Streptococcus D in 3% (one case); Bartonella henselae in 9% (three cases); ascaris in 6% (two cases); Mycobacterium tuberculosis in 6% (two cases). In eight cases no bacteria was identified (24%) but the good evolution after antibiotics and the negative amoebic serology looked like pyogenic abscesses. Two abscesses were aspirated, two were drained, one child had a surgical intervention. There was no death. Following a mean duration of 1 month for antibiotics treatment, outcome was always favourable. CONCLUSION: Diagnosis of hepatic abscess can be difficult. Ultrasonography shows the abscess but not the causal agent. The amoebic serology is sensible, consequently, its negativity leads to evoke a pyogenic agent. Early antibiotic treatment against pyogenic, anaerobic bacteria, and Entamoeba histolytica is required. Hepatic abscesses in ascaridiosis, tuberculosis and cat-scratch disease are less frequently encountered. If diagnosis remains doubtful or clinical evolution worsens, or if abscess volume increases, a percutaneous aspiration or drainage is needed.

[Procalcitonin and viral meningitis: reduction of unnecessary antibiotics by measurement during an outbreak]. / Procalcitonine et méningites virales: réduction des traitements antibiotiques inutiles par le dosage en routine au cours d'une épidémie.

OBJECTIVE: Viral meningitis are often treated with antibiotics in emergency because routine analysis of CSF is not always efficient for distinguishing between viral and bacterial infection. The aim of the study was to evaluate the usefulness of procalcitonin (PCT) to reduce antibiotic treatments. METHODS AND RESULTS: A blood PCT level < 0.5 ng/mL was prospectively used for the diagnosis of viral origin of meningitis in 58 patients (two months-14 years), in which enterovirus was isolated by culture or PCR during an outbreak (May-June 2000). CSF cells range was 10 to 2800/mL (m: 244), PMN 5 to 2464/mL and CSF proteins range was 0.19 to 0.92 mg/dL (m: 0.37). Seventeen patients received antibiotic therapy in admission. In nine patients, PCT (dosage was routinely measured 3/week) result < 0.5 ng/mL was obtained in 24 h and in 48 h in six: treatment was then stopped and children led hospital. In two patients, PCT was > 1 ng/mL because of bacterial coinfection. CSF and PCT values were similar to those of an already published control group. CONCLUSION: PCT dosage allowed to shorten hospitalization of 4.47 (controls) to 2.06 (patients) days in patients receiving unnecessary antibiotic treatments. During this outbreak, PCT dosage allowed to reduce 40 days of hospitalization.