Navigating from cellular phenotypic screen to clinical candidate: selective targeting of the NLRP3 inflammasome.

The NLRP3 inflammasome plays a pivotal role in host defense and drives inflammation against microbial threats, crystals, and danger-associated molecular patterns (DAMPs). Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with NLRP3 mutations suffer from Cryopyrin-Associated Periodic Syndrome (CAPS) emphasizing the clinical significance of modulating NLRP3.

Vaccine hesitancy about the HPV vaccine among French young women and their parents: a telephone survey.

Background: The human papillomavirus (HPV) vaccine reduces the burden of cervical and other cancers. In numerous countries, a slow uptakeof this vaccine persists, calling for a better understanding of the structural factors leading to vaccine acceptation. We aimed to assess the attitudes toward HPV vaccination among its intended public to explore its specific characteristics.

Answering Hospital Caregivers' Questions at Any Time: Proof-of-Concept Study of an Artificial Intelligence-Based Chatbot in a French Hospital.

Background: Access to accurate information in health care is a key point for caregivers to avoid medication errors, especially with the reorganization of staff and drug circuits during health crises such as the COVID‑19 pandemic. It is, therefore, the role of the hospital pharmacy to answer caregivers' questions. Some may require the expertise of a pharmacist, some should be answered by pharmacy technicians, but others are simple and redundant, and automated responses may be provided.

[Not Available].

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.

[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].

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.

Complement component 4 variations may influence psychopathology risk in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

CYP21A2 defects result in congenital adrenal hyperplasia (CAH), an autosomal recessive disorder characterized by impaired adrenal steroidogenesis. CYP21A2 lies within the major histocompatibility complex in an area of the genome highly susceptible to genetic variation. Alterations in the neighboring complement component 4 isotypes C4A and C4B have been associated with psychiatric and autoimmune disease.

[Relevance of the health insurance databases to study spatial disparities in asthma prevalence: A study in southeastern France].

Background: Data on asthma prevalence at a small-area level would be useful to set up and monitor French local public health policies. This study, based on drug reimbursement databases in southeastern France, aimed to (1) compare asthma-like disorders prevalence estimated by using three different indicators; (2) study sociodemographic characteristics associated with these indicators; (3) verify whether these indicators are equivalent to study geographical disparities of the asthma-like disorders prevalence at a small-area level.

Methods: The study was conducted among the beneficiaries of the National Health Insurance Fund aged 18-44 years residing in southeastern France in 2010 (n=1,371,816).

Characteristics and patterns of elective admissions to for-profit and not-for-profit hospitals in France in 2009 and 2010.

In the mid 2000s, in an effort to increase competition among hospitals in France - and thereby reduce hospital care costs - policymakers implemented a prospective payment system and created incentives to promote use of for-profit hospitals. But such policies might incentivize 'upcoding' to higher-reimbursed procedures or overuse of preference-sensitive elective procedures, either of which would offset anticipated cost savings. To explore either possibility, we examined the relative use and costs of admissions for ten common preference-sensitive elective surgical procedures to French not-for profit and for-profit sector hospitals in 2009 and 2010.

Geographic variation in admissions for knee replacement, hip replacement, and hip fracture in France: evidence of supplier-induced demand in for-profit and not-for-profit hospitals.

Introduction: We sought to determine whether there was evidence of supplier-induced demand in mainland France, where health care is mainly financed by a public and compulsory health insurance and provided by both for-profit and not-for-profit hospitals.

Methods: Using a dataset of all admissions to French hospitals for 2009 and 2010, we calculated department-level age-adjusted and sex-adjusted per capita admission rates for hip replacement, knee replacement, and hip fracture for 2 age groups (45-64 and 65-99 y old), for-profit and not-for-profit hospitals. We used spatial regression analysis to examine the relationship between ecological variables, procedure rates, and supply of surgeons or sector-specific surgical beds.

[Potentially inappropriate prescriptions for the elderly: a study of health insurance reimbursements in Southeastern France].

Background: This study conducted in the region of Provence-Alpes-Côte d'Azur (PACA) sought to assess the feasibility of constructing and using indicators of potentially inappropriate prescriptions for the elderly from health insurance reimbursement data. We present and discuss different indicators of inappropriate prescriptions for people aged 70 years or older (at-risk prescriptions, dangerous or at-risk coprescriptions, absence of necessary coprescriptions) and reports their prevalence in PACA.

Methods: The indicators were constructed from the French list of inappropriate prescriptions, national agency guidelines, and the advice of experts in the field.

[Evaluation of hospital stays linkage quality to study health spatial variation. a feasibility study in three French regions].

Background: Since 2001, the French hospital stay databases (Programme de médicalisation des systèmes d'information, PMSI) have included a unique and anonymous identifier in order to cross-link discharge abstracts from a given patient, within and across hospitals. These data could be used to estimate prevalence for some diseases at a territorial level provided that linkage quality is good enough. Few morbidity data are available at this scale.

Feedback and lessons from the prescription of rimonabant, a drug to be used under strict guidelines, in southeastern France, March 2007 through June 2008.

Background: To provide feedback on the initial market authorization of rimonabant, a drug to be used under strict guidelines, we conducted a study with information from the National health insurance reimbursements database for southeastern France. The aims of this study were to: (1) describe the characteristics of subjects who have had one rimonabant prescription reimbursed; (2) study the frequency of prescriptions that did not comply with reimbursement criteria; (3) study the frequency of prescriptions for patients simultaneously treated with antidepressants; and (4) analyse the factors associated with both types of prescription (patient and prescriber characteristics).

Methods: Using the database of drug reimbursements maintained by the southeastern France general health insurance fund, we studied the characteristics of outpatients with at least one reimbursement for rimonabant, compared them to the rest of the population, and analysed compliance with the indications, contraindications, and regulations for rimonabant prescription with multivariate logistic regressions.

Prevalence of treated diabetes: Geographical variations at the small-area level and their association with area-level characteristics. A multilevel analysis in Southeastern France.

Aim: This study estimated geographical variations in the prevalence of treated diabetes (TD) at the small-area level in Southeastern France to determine whether or not the characteristics of these areas (in particular, socioeconomic status or "SES") are associated with TD independent of person-level factors.

Methods: The study used drug reimbursement data for 2008 from the General Health Insurance Scheme in Southeastern France for beneficiaries aged 18 years or over. TD patients were defined as those to whom oral antidiabetic drugs or insulin had been dispensed at least three times within the year.

Identification of a series of substituted 2-piperazinyl-5-pyrimidylhydroxamic acids as potent histone deacetylase inhibitors.

Pursuing our efforts in designing 5-pyrimidylhydroxamic acid anti-cancer agents, we have identified a new series of potent histone deacetylase (HDAC) inhibitors. These compounds exhibit enzymatic HDAC inhibiting properties with IC(50) values in the nanomolar range and inhibit tumor cell proliferation at similar levels. Good solubility, moderate bioavailability, and promising in vivo activity in xenograft model made this series of compounds interesting starting points to design new potent HDAC inhibitors.

JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity.

Purpose: Histone deacetylase (HDAC) inhibitors have shown promising clinical activity in the treatment of hematologic malignancies, but their activity in solid tumor indications has been limited. Most HDAC inhibitors in clinical development only transiently induce histone acetylation in tumor tissue. Here, we sought to identify a "second-generation" class I HDAC inhibitor with prolonged pharmacodynamic response in vivo, to assess whether this results in superior antitumoral efficacy.

[Impact of the estimation of the medically insured population on the pharmacological prevalence of diabetes at the regional and small area level].

Background: Data derived from Health Insurance databases are very useful for health observation. These data are however still underused, particularly for small local areas. This may be partly explained by the lack of reliable data on the number of insured people.

Effect of efflux inhibition on brain uptake of itraconazole in mice infected with Cryptococcus neoformans.

Itraconazole is a fungistatic agent that, although highly lipophilic, shows poor transport through the blood brain barrier that may be due to efflux proteins. The combined administration of an efflux inhibitor with itraconazole should increase cerebral itraconazole concentrations and therefore, improve the treatment of Cryptococcus neoformans meningitis with this antifungal agent. To test this hypothesis, we have studied the influence of murine cerebral infection with C.

Aortic anastomotic pseudoaneurysms: US, CT, MR, and angiography.

Correlation of imaging and anatomic findings in seven men with abdominal aortic graft prostheses (four "end-to-end" anastomoses and three "end-to-side" anastomoses) was done to compare the value of different imaging modalities in detecting postoperative complications, especially aortic anastomotic pseudoaneurysms (AAPs). In all cases, angiographic and CT studies were carried out. In six patients ultrasound and MR examinations were also performed.

[Alveolar proteinosis in a facade plasterer. A sequential study of bronchoalveolar lavage and thoracic computerized tomography].

Alveolar proteinosis is a rare disease. We report a case occurring in a patient who smoked and was a facade plasterer who was treated with repeated pulmonary lavage. A mineral analysis of the lavage fluid recovered a significant amount of silica and iron oxide confirming the massive exposure of the patient to these minerals.

Evaluation of vein of Galen arteriovenous malformation in newborns by two dimensional ultrasound, pulsed and colour Doppler method.

Two babies with severe cardiac failure caused by a large arteriovenous malformation of the vein of Galen were evaluated with 2-dimensional ultrasound, pulsed and colour Doppler techniques. In both cases similar findings were recorded: dilated right cardiac chambers with high cardiac output in superior vena cava and ascending aorta; retrograde diastolic flow in descending aorta and continuous forward flow in arch arteries reflecting low resistance to flow in cerebral arteries; recirculation of microbubbles through the superior vena cava after passage unchanged through the cerebral malformation following contrast injection of saline into a peripheral vein or an arterial umbilical line. In addition, colour Doppler study of the brain clearly showed the malformation and the dilated straight sinus.

[Value of nuclear magnetic resonance in the detection of false aneurysm of the abdominal aorta].

Among the long-term complications that jeopardize bilateral aorto-femoral prostheses, the development of a false aneurysm on the aortic suture line, is indeed one of the most severe. Its frequency, approximately 1 p. cent of cases, is probably underestimated, since its diagnosis, with usual exploration methods, is difficult.

Control of hemoptysis: systemic angiography and anastomoses of the internal mammary artery.

Twenty-three patients with massive and recurrent hemoptysis were examined with angiography. Particular attention was directed to the internal mammary arteries. Specific causes for the bleeding were tuberculosis (n = 9), aspergilloma (n = 8), bronchiectasis (n = 1), primary systemic amyloidosis (n = 1), congenital and acquired pulmonary venous obstruction (n = 2), chronic pulmonary embolism (n = 1), and bilateral congenital pulmonary artery stenosis (n = 1).

Segmental bronchovascular anatomy of the lower lobes: CT analysis.

A systematic evaluation of the anatomic relationships of the segmental bronchi, arteries, and veins of 107 right and 113 left lower lobes was made from CT scans of patients with normal chest radiographs. The classic taxonomies of Boyden and Jackson and Huber were used for nomenclature. Identification of individual structures was based primarily on careful analysis of contiguous CT slices.