Actus Santé

Menée aux Etats-Unis par questionnaire auprès de 29 793 témoins et de 369 adolescents et jeunes adultes ayant survécu à un cancer (âge moyen : 20,5 ans), cette étude analyse leur santé mentale et leur utilisation de soins psychiques (psychothérapie, médicaments)

Actuellement, le traitement des maladies des valves cardiaques repose sur le remplacement de la valve dysfonctionnelle par une prothèse artificielle. Cette intervention ne peut toutefois pas être proposée à tous les patients compte tenu de son caractère invasif. Dans une nouvelle étude, un groupe de chercheurs et chercheuses issus de laboratoires communs à l’Inserm, à l’ESPCI Paris, au CNRS et à Université Paris Cité, en étroite collaboration avec la start-up Cardiawave spin off de l’Hôpital européen Georges Pompidou et du laboratoire Physique pour la Médicine Paris (Inserm/CNRS/ESPCI/PSL), rapportent pour la première fois l’efficacité clinique d’une thérapie « non invasive » par ultrasons focalisés.

L’article Une thérapie par ultrasons non invasive efficace dans le traitement des maladies des valves cardiaques est apparu en premier sur Salle de presse de l'Inserm.

PARIS, 24 novembre 2023 (TecHopital) - L'atelier d'architecture Tolila + Gilliland remporte le prix de l'Equerre d'argent 2023, dans la catégorie lieux d'activité, pour la conception de l'hôpital de jour spécialisé en addictologie, du centre Gilbert-Raby, à Meulan-en-Yvelines, administré par la Fondation L'Elan retrouvé, a annoncé le cabinet d'architecture dans un communiqué diffusé le 21 novembre.

Background: The UK Government intends to implement a 'smokefree generation' policy prohibiting the sale of all tobacco products to people born after 2008. National surveys provide comprehensive data on cigarette smoking, but little is known about patterns of non-cigarette tobacco smoking across key population groups. Methods: Using data from a nationally-representative cross-sectional survey of adults (18+) in England, collected monthly between September-2013 and September-2023 (n=196,721), we estimated time trends in non-cigarette tobacco smoking prevalence, overall and by age, gender, occupational social grade, region, ethnicity, and vaping status. Interviews were conducted face-to-face until March-2020 and via telephone thereafter. Results: From September-2013 to September-2023, there was a non-linear increase in non-cigarette tobacco smoking prevalence (from 0.36% to 1.68%; PR=4.72 [95%CI=3.43-6.48]). Prevalence was relatively stable up to February-2020 (at an average of 0.46%), then increased sharply at the start of the Covid-19 pandemic, to 0.90% [0.82-0.99%] in March-2020. This was followed by a steadier rise, peaking at 1.97% in May-2022, before falling slightly to 1.68% by September-2023. As a result, in 2022/23, one in ten smokers (10.8% [9.64-12.0%]) used non-cigarette tobacco. This rise was observed across all subgroups but was most pronounced among younger adults (e.g., reaching 3.21% of 18-year-olds vs. 1.09% of 65-year-olds). Prevalence was consistently higher among men (2.17% in September-2023 vs. 1.07% women) and current vapers (4.71% vs. 1.25% non-vapers). Conclusions: While exclusive use of non-cigarette combustible tobacco remains rare among adults in England, it increased at the start of the Covid-19 pandemic (at the same time as survey methods changed) but subsequently continued increasing steadily until May-2022. As of September-2023, there were ~772,800 adult non-cigarette tobacco smokers in England; around five times more than a decade earlier. The rise in prevalence differed by age, with a more pronounced rise leading to higher prevalence among younger than older ages.

Background and objectives: Continuous full-channel EEG is the gold standard for electrocortical activity assessment in critically ill children, but its implementation faces challenges, leading to a growing use of amplitude-integrated EEG (aEEG). While suppressed aEEG amplitudes have been linked to adverse outcomes in preterm infants and adults after cardiac arrest, evidence for critically ill children remains limited. This retrospective study aimed to evaluate the association between suppressed aEEG amplitudes in critically ill children and death or poor functional neurological outcomes. Methods: 235 EEGs derived from individual patients < 18 years in the pediatric intensive care unit (PICU) at the University Hospital Essen (Germany) between 04/2014 and 07/2021 were retrospectively converted into aEEGs and amplitudes analyzed with respect to previously defined age-specific percentiles. Adjusted odds ratios for death and poor functional outcome at hospital discharge in patients with bilateral upper or lower amplitude suppression below the 10th percentile were calculated accounting for neurological injuries, acute disease severity, sedation levels, and functional neurological status before acute critical illness. Results: The median time from neurological insult to EEG recording was 2 days. PICU admission occurred due to neurological reasons in 43 % and patients had high overall disease severity. Thirty-three (14 %) patients died and 68 (29 %) had poor outcomes. Amplitude depression below the 10th percentile was frequent (upper amplitude: 27 %, lower amplitude: 34 %) with suppression of only one amplitude less frequent than bilateral suppression. Multivariable regression analyses yielded odds between 6.63 and 15.22 for death, neurological death, and poor neurological outcomes if both upper or both lower amplitudes were suppressed. Model discrimination was excellent with areas under the curve above 0.92 for all models. Discussion: This study found a high prevalence of suppressed aEEG amplitudes in critically ill children early after PICU admission, with suppression being highly associated with death and poor functional outcomes at hospital discharge. These findings emphasize the potential of early identification of high-risk PICU patients through aEEG monitoring if conventional EEG is unavailable, potentially guiding neuroprotective therapies and early neurorehabilitation.

Background: The risk of infection during dental practices is omnipresent for both patients and healthcare workers. Workers within the bucco-dental health services are among the most affected. The most reported infectious agents transmitted through blood and body fluids are Human Immunodeficiency Virus, viral hepatitis B and C. Compliance with standard precautions prevents exposure to hospital associated infections that are acquired through exposure needle sticks and splashes in healthcare settings. The aim of the present investigation was to assess the level of implementation and constraints to the observance of standard precautions in bucco-dental services. Methodology: A cross-sectional study was conducted in five referral hospitals in Yaounde, from March to April 2021, involving a purposeful selection of 40 bucco-dental health workers (BDHW). Workers were submitted to a pre-tested self-administered questionnaire covering their knowledge, level of observance of standard precautions and experiences of occupational exposure to blood and other body fluids. The data collected were analyzed using IBM SPSS software version 26. Results: Out of the 53 bucco-dental health workers (BDHW) who were selected for inclusion, 40 provided responses for a participation rate of 75.5%. The mean age of participants was 30.65 years and the M/F sex ratio was 0.54. Half of participants (58.5%) had a good overall level of knowledge of standard precautions. Less than a quarter of participants (12.5%) were compliant with standard precautions. Only 35% of BDHW had received training on hospital infection control, while 60% reported to have experience a needle stick injury in the last three months. Gaps in the observance of standard precautions included the lack of disinfectants (70%), application of hand washing techniques and use of personal protective equipment (PPE). Less than half of participant (47,5%) were fully vaccinated against hepatitis B. Conclusion: Most bucco-dental health workers had insufficient knowledge of standard precautions, most of whom had experienced needlestick injuries and accidental exposure to body fluids, and were at high risk of hospital acquired infections. There is an urgent need to establish and strengthen hospital-based infection control committees to ensure training and implementation of infection prevention measures in local healthcare settings. A framework for the nationwide scale up of such interventions should be explored.

Maternity is a special period in a woman life that involves substantial physiological, psychological, and hormonal changes. These changes may cause alterations in many clinical measurements during pregnancy, which can be used to monitor and diagnose maternal disorders and adverse postnatal outcomes. Exploring the genetic background of these phenotypes is key to elucidating the pathogenesis of pregnancy disorders. In this study, we conducted a large-scale molecular biology analysis of 104 pregnancy phenotypes based on genotype data from 39,194 Chinses women. Genome-wide association analysis identified a total of 407 trait-locus associations, of which 75.18% were previously reported. Among the 101 novel associations for 37 phenotypes, some were potentially pregnancy-specific and worth further experimental investigation. For example, ESR1 with fasting glucose, hemoglobin, hematocrit, and several leukocytoses; ZSCAN31 with blood urea nitrogen. We further performed pathway-based analysis and uncovered at least one significant pathway for 24 traits, in addition to previously known functional pathways, novel findings included birthweight with Reactome signaling by NODAL, twin pregnancy with Reactome mitotic G1-G1/S phases. The partitioning heritability analysis recapitulated known trait-relevant tissue/cell types, and also discovered interesting results including twin pregnancy with embryoid bodies cell-type enrichment, the delivery type cesarean section with fallopian tube, and birth weight with ovary and embryonic stem cells. In terms of both sample size and the variety of phenotypes, our work is one of the largest genetic studies of pregnancy phenotypes across all populations. We believe that this study will provide a valuable resource for exploring the genetic background of pregnancy phenotypes and also for further research on pregnancy-related diseases and adverse neonatal outcomes.

The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxification of anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are now a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S.. To address this, we examined different clinically relevant anthracycline drugs with respect to a series of features including mode of action (chromatin and DNA damage), bio-distribution, anti-tumor efficacy and cardiotoxicity in pre-clinical models and patients. We show that different anthracycline drugs have surprisingly individual efficacy and toxicity profiles. In particular, aclarubicin stands out in pre-clinical models and clinical trials as it potently kills cancer cells, does not induce therapy-related malignancies or cardiotoxicity, and can be safely administered even after a maximum cumulative dose of either ida- or doxorubicin has been reached. Retrospective analysis of aclarubicin used in second-line treatment of relapsed/refractory AML patients showed similar survival effects to its use in first line, leading to an almost 25% increase in 5-year overall survival. Considering individual anthracyclines as different drugs provides new treatment options that strongly improve survival of cancer patients while limiting the toxic side-effects.

Objective. The identification/development of a machine learning (ML)-based classifier that utilizes metabolic profiles of serum samples to accurately identify individuals with ovarian cancer (OC). Methods. Serum samples collected from 431 OC patients and 133 normal women at four geographic locations were analyzed by mass spectrometry. Reliable metabolites were identified using recursive feature elimination (RFE) coupled with repeated cross-validation (CV) and used to develop a consensus classifier able to distinguish cancer from non-cancer. The probabilities assigned to individuals by the model were used to create a clinical tool that assigns a likelihood that an individual patient sample is cancer or normal. Results. Our consensus classification model is able to distinguish cancer from control samples with 93% accuracy. The frequency distribution of individual patient scores was used to develop a clinical tool that assigns a likelihood that an individual patient does or does not have cancer. Conclusions. An integrative approach using metabolomic profiles and ML-based classifiers has been employed to develop a clinical tool that assigns a probability that an individual patient does or does not have OC. This personalized/probabilistic approach to cancer diagnostics is more clinically informative and accurate than traditional binary (yes/no) tests and represents a promising new direction in the early detection of OC.

Introduction: The efficacy of deep brain stimulation (DBS) has been established to treat several movement and psychiatric disorders. However, several aspects, such as the mechanism of action and tissue changes after treatment are incompletely described. Hence, we aimed to describe the neurohistopathological findings of 9 patients who underwent DBS for movement disorders. Additionally, we performed a systematic literature review on postmortem studies after DBS implantation. Methods: We performed a retrospective study of patients who underwent DBS for movement disorders between 2000-2023 and had postmortem autopsy. Demographic, clinical, and outcomes were collected. Levodopa equivalent daily dose (LEDD) and total electrical energy delivered (TEED) were calculated. Neurohistopathological assessments were performed from autopsies. A systematic literature review was conducted to summarize the literature. Results: Postmortem neurohistopathologic assessment of 9 patients who underwent DBS for movement disorders (8 Parkinson's disease [multiple system atrophy was final diagnosis in 1], and 1 parkinsonism) was performed. Median age at DBS implantation was 65 years (range, 54-69), and most were male (8 patients, 89%). Most common DBS target was the subthalamic nucleus (8 patients, 89%). Median DBS duration was 65 months (range, 7-264 months). Reduction in LEDD was found in 6/8 patients and TEED was increased 4/6 patients. No patients died due to DBS. Neurohistopathological assessment showed gliosis in 7 (77.7%) patients and activated microglial infiltration in 1 (11%). Additionally, postmortem findings (after DBS) of 59 patients (between 1977-2021) were identified in the literature: 26 (44.1%) for Parkinson's disease, 20 (33.9%) for pain, and 13 (22%) for other conditions. Conclusion: Our findings confirm the presence of a local tissue reaction, including gliosis and activated microglial infiltration around the implanted DBS electrodes. The effect of the local changes on the clinical efficacy of DBS is not established. Further DBS postmortem studies and standardization of tissue processing are needed.

Intellectual Disability (ID) is characterised by substantial limitations in cognitive function and adaptive behaviour, affecting 1-3% of the population. Protein O-GlcNAcylation is a posttranslational modification of nucleocytoplasmic proteins regulated by two opposing enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Recently, missense mutations in OGT have been shown to segregate with ID, associated with compensatory reduction of OGA expression, although it is unclear whether this is mechanistically linked to the disease. Here, we report a patient with a K885N de novo missense mutation in the C-terminal pseudo histone acetyltransferase domain of OGA, associated with ID, infantile spasms and autism. While the K885N mutation does not affect protein stability or activity in vitro, this residue sits in the canonical GCN5 acetyltransferase family acceptor binding cleft. Strikingly, mouse embryonic stem cells edited to harbour the K885N mutation show increased OGA turnover and defects in neurogenesis. Taken together, these data suggest a link between missense mutations in OGA and ID.

Summary (248/250) Introduction: Pregnant women and their offspring are often at increased direct and indirect risks of adverse outcomes during epidemics and pandemics. A coordinated research response is paramount to ensure that this group is offered at least the same level of disease prevention, diagnosis, treatment, and care as the general population. We conducted a landscape analysis and held expert consultations to identify research efforts relevant to pregnant women affected by disease outbreaks, highlight gaps and challenges, and propose solutions to addressing them in a coordinated manner. Methods: Literature searches were conducted from 1 January 2015 to 22 March 2022 using Web of Science, Google Scholar, and PubMed augmented by key informant interviews. Findings were reviewed and Quid analysis was performed to identify clusters and connectors across research networks followed by two expert consultations. Results: Ninety-four relevant research efforts were identified. Although well-suited to generating epidemiological data, the entire infrastructure to support a robust research response remains insufficient, particularly for use of medical products in pregnancy. Limitations in global governance, coordination, funding, and data-gathering systems have slowed down research responses. Conclusion: Leveraging current research efforts while engaging multinational and regional networks may be the most effective way to scale up maternal and perinatal research preparedness and response. The findings of this landscape analysis and proposed operational framework will pave the way for developing a roadmap to guide coordination efforts, facilitate collaboration, and ultimately promote rapid access to countermeasures and clinical care for pregnant women and their offspring in the future.

Automated segmentation of brain white matter lesions is crucial for both clinical assessment and scientific research in multiple sclerosis (MS). Over a decade ago, we introduced a lesion segmentation tool, LST, engineered with a lesion growth algorithm (LST-LGA). While recent lesion segmentation approaches have leveraged artificial intelligence (AI), they often remain proprietary and difficult to adopt. Here, we present LST-AI, an advanced deep learning-based extension of LST that consists of an ensemble of three 3D-UNets. LST-AI specifically addresses the imbalance between white matter (WM) lesions and non-lesioned WM. It employs a composite loss function incorporating binary cross-entropy and Tversky loss to improve segmentation of the highly heterogeneous MS lesions. We train the network ensemble on 491 MS pairs of T1w and FLAIR images, collected in-house from a 3T MRI scanner, and expert neuroradiologists manually segmented the utilized lesion maps for training. LST-AI additionally includes a lesion location annotation tool, labeling lesion location according to the 2017 McDonald criteria (periventricular, infratentorial, juxtacortical, subcortical). We conduct evaluations on 270 test cases - comprising both in-house (n=167) and publicly available data (n=103) - using the Anima segmentation validation tools and compare LST-AI with several publicly available lesion segmentation models. Our empirical analysis shows that LST-AI achieves superior performance compared to existing methods. Its Dice and F1 scores exceeded 0.5, outperforming LST-LGA, LST-LPA, SAMSEG, and the popular nnUNet framework, which all scored below 0.45. Notably, LST-AI demonstrated exceptional performance on the MSSEG-1 challenge dataset, an international WM lesion segmentation challenge, with a Dice score of 0.65 and an F1 score of 0.63 - surpassing all other competing models at the time of the challenge. With increasing lesion volume, the lesion detection rate rapidly increased with a detection rate of >75% for lesions larger than 60mm3. Given its higher segmentation performance, we recommend that research groups currently using LST-LGA transition to LST-AI. To facilitate broad adoption, we are releasing LST-AI as an open-source model, available as a command-line tool, dockerized container, or Python script, enabling diverse applications across multiple platforms.

Background: Racism is a fundamental cause of health inequities for Aboriginal and Torres Strait Islander children. We aimed to examine the potential to reduce inequities in Aboriginal and Torres Strait Islander children's mental health and sleep problems through eliminating interpersonal racial discrimination. Methods: We drew on cross-sectional data from the Speak Out Against Racism (SOAR; N=2818) and longitudinal data from the Longitudinal Study of Australian Children (LSAC; N=8627). The SOAR survey was completed in 2017 and the LSAC followed children from 2004 to 2014 in the kindergarten cohort and from 2008 to 2018 in the birth cohort. Exposure was measured by Aboriginal and Torres Strait Islander status (Aboriginal and Torres Strait Islander or Anglo-European), as a proxy measure of structural racism (SOAR: 10-15 years; LSAC: 4-5 years). Mediator was measured by interpersonal racial discrimination (yes/no) (SOAR: 10-15 years; LSAC: 12-13 years). Outcomes were measured by mental health problems (yes/no) and sleep problems (yes/no) (SOAR: 10-15 years; LSAC: 14-15 years). An interventional effects approach was conducted, adjusting for baseline and intermediate confounders. Findings: Aboriginal and Torres Strait Islander children had higher prevalence of mental health problems (SOAR: 40.1% versus 13.5%; LSAC: 25.3% versus 7.6%) and sleep problems (SOAR: 28.5% versus 18.4%; LSAC: 14.0% versus 9.9%) than their Anglo-European peers. Hypothetical interventions to eliminate Aboriginal and Torres Strait Islander children's experiences of interpersonal racial discrimination could reduce up to 42.4% of mental health inequities (equivalent to 11.2% absolute reduction) and up to 48.5% of sleep inequities (equivalent to 4.7% absolute reduction). Interpretation: Targeted policy interventions that eliminate racial discrimination against Aboriginal and Torres Strait Islander children have high potential to reduce inequities in mental health and sleep problems. Addressing racism and racial discrimination needs a multi-component and multi-level approach directed by Aboriginal and Torres Strait Islander communities.

Background: Codeine is a widely available opioid medicine that is on the World Health Organisations list of essential medicines. However, widespread access to codeine has led to its misuse, abuse, dependence, and deaths. Some countries, including France and Australia, have successfully reclassified codeine to prescription only, which is encouraging other regulators, including the UK, to reconsider the status of codeine. However, little is known about how much codeine is sold in the UK. Aim: To assess national trends in sales and expenditure of codeine-containing products sold over the counter (OTC) between 2013 and 2019. Methods: We conducted a retrospective observational study using electronic point-of-sales data from the human data science company IQVIA and population statistics from the UK Office of National Statistics (ONS). Descriptive statistics were used to examine the quantity, trends over time, and types of OTC codeine-containing products sold. Results: 4.75 billion dosage units of codeine were sold OTC in the UK between April 2013 and March 2019, an average of 72 dosage units per UK resident. Over time, sales of codeine fell by 8%, from 12.54 dosage units per resident in 2013 to 11.48 dosage units per resident in 2019. Codeine was often sold in combination with other analgesics, amounting to 1711 tonnes of paracetamol and 96 tonnes of ibuprofen. The public spent 638 million GBP on OTC codeine-containing products, which increased by 12% over the study period. There were 83 different types of codeine-containing products sold. Conclusion: Large volumes of codeine-containing products were purchased OTC in the UK in 2013-19. To improve the safety of opioids, OTC codeine sales data should be made accessible for public health surveillance. The trends presented in this study should inform policy for the future status of codeine availability in the UK.

Question We examined the effect of study characteristics, risk of bias and publication bias on efficacy of pharmacotherapy in randomized controlled trials (RCTs) for obsessive-compulsive disorder (OCD). Study selection and analysis We conducted a systematic search for double-blinded, placebo controlled short-term RCTs with selective serotonergic reuptake inhibitors (SSRIs) or clomipramine. We performed a random-effect meta-analysis, using change of the Yale-Brown Obsessive-Compulsive scale (YBOCS) as primary outcome. We performed meta-regression for key study characteristics, and for risk of bias. Furthermore, we analyzed publication bias using a Bayesian selection model. Findings We screened 3729 articles and included 21 studies, containing 4102 participants. Meta-analysis showed an effect size of -0.59 (Hedges G, 95% CI -0.73 to -0.46), equaling 4.2 point reduction on the YBOCS compared to placebo. The most recent trial was performed in 2007 and most trials were at risk of bias. In our meta-regression, we found that high risk of bias was associated with a larger effect size. Clomipramine was more effective than SSRIs, even after correcting for risk of bias. We found an indication for publication bias subsequent correction for this bias resulted in a depleted effect size. Conclusions Our findings reveal superiority of clomipramine over SSRIs, even after adjusting for risk of bias. Effect sizes may be attenuated when considering publication bias and methodological rigor, emphasizing the importance of robust studies to guide clinical utility of OCD pharmacotherapy.

Glucagon receptor-like peptide receptor agonists, GLP-1 RAs, are one of the most commonly used drugs for type-2 diabetes mellitus. The clinical guidelines recommend GLP-1 RAs as adjunct to diabetes therapy in patients with chronic kidney disease, presence or risk of atherosclerotic cardiovascular disease, obesity, and other cardiometabolic conditions. The weight loss seen in clinical trials has been explored further in healthy individuals, putting GLP-1 RAs on track to be the next weight loss treatment. Although the adverse event profile is relatively safe, most GLP-1 RAs come with a labeled black boxed warning of the risk of thyroid cancers, based on animal models and some postmarketing case reports in humans. Considering the increasing popularity of this drug class and its expansion into a new popular indication, a further review of most recent postmarketing safety data is warranted to quantify thyroid hyperplasia and neoplasms instances. In this study we analyzed over eighteen million reports from United States Food and Drug Administration Adverse Event Reporting System and identified 17,653 relevant GLP-1 RA monotherapy reports to provide the evidence of significantly increased propensity for thyroid hyperplasias and neoplasms in patients taking GLP-1 RA as monotherapy when compared to patients taking sodium-glucose cotransporter-2 inhibitor monotherapy.