First Observations of a Potential Association Between Accumulation of Per- and Polyfluoroalkyl Substances in the Central Nervous System and Markers of Alzheimer's Disease.

The entire human population is exposed to persistent organic pollutants throughout their lives. Among them, per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in industrial and consumer products that are known to exert adverse effects on human health. As they bioaccumulate in the human brain and are known to be neurotoxic in experimental models, they are assumed to be involved in neurodegenerative processes. In this proof-of-concept study, we measured the level of 18 PFAS in cerebrospinal fluid (CSF) from 8 patients hospitalized with suspected normal pressure hydrocephalus. We then analyzed whether PFAS levels could be related to both biological and clinical markers of Alzheimer's disease. We showed that PFAS and perfluorooctanesulfonate were found in all CSF samples from a French region without fluorochemical industries. Moreover, we observed a significant difference between the levels of PFAS and perfluorooctanesulfonate in the CSF of patients with both Alzheimer's disease markers and cognitive impairment compared with those with only 1 or neither. Two previous studies have shown that PFAS levels in human CSF increase with age and are linked to impaired blood-brain barrier integrity. Our results provide the first evidence of a link between PFAS accumulation in the central nervous system and clinical and biological markers of Alzheimer's disease.

Influence of deprivation on hospital care pathways and costs for people with ischaemic stroke: A trajectory modelling study.

BACKGROUND: Socioeconomic characteristics have a strong impact on the incidence of stroke. The highest levels of morbidity and mortality are associated with the lowest socioeconomic positions. Moreover, the health insurance budget for stroke is significant. OBJECTIVES: To describe typical Hospital Care Pathways (HCPs) and their costs 1 year after acute stroke and to assess the impact of individuals' socioeconomic characteristics on HCPs and costs. METHODS: This retrospective observational study used hospital data on people with primary ischaemic stroke in a region of France (Haute-Garonne). HCPs were identified by sequential analysis. Multinomial logistic regression was used to analyse the impact of socioeconomic characteristics on HCPs as measured using an ecological index of deprivation, and a gamma regression model was used to analyse costs. RESULTS: The analysis identified 4 typical HCPs. The first HCP consisted exclusively of consultations, the second was composed of consultations and hospitalisations, the third included hospitalisations during the first 2 months after stroke followed by consultations, and the fourth included long-term hospitalisations. After adjustment, deprivation was associated with HCPs and determined its costs: a high level of social disadvantage determined the type of pathway and increased the costs. CONCLUSIONS: This study is one of the first to assess the impact of social inequalities in health on post-stroke HCPs in France and their corresponding costs. Our results confirm the hypothesis that healthcare costs differ according to the level of deprivation.

Gamma-hydroxybutyrate (GHB), 1,4-butanediol (1,4BD), and gamma-butyrolactone (GBL) intoxication: A state-of-the-art review.

γ-hydroxybutyrate (GHB) is synthesized endogenously from γ-aminobutyric acid (GABA) or exogenously from 1,4-butanediol (butane-1,4-diol; 1,4-BD) or γ-butyrolactone (GBL). GBL, and 1,4-BD are rapidly converted to GHB. The gastric absorption time, volume of distribution, and half-life of GHB are between 5 and 45 min, 0.49 ± 0.9 L/kg, and between 20 and 60 min, respectively. GHB and its analogues have a dose-dependent effect on the activation of GHB receptor, GABA-B, and GABA localized to the central nervous system. After ingestion, most patients present transient neurological disorders (lethal dose: 60 mg/kg). Chronic GHB consumption is associated with disorders of use and a withdrawal syndrome when the consumption is discontinued. GHB, GBL, and 1,4-BD are classified as narcotics but only the use of GHB is controlled internationally. They are used for drug facilitated (sexual) assault, recreational purposes, slamsex, and chemsex. To confirm an exogenous intake or administration of GHB, GBL, or 1-4-BD, the pre-analytical conservation is crucial. The antemortem cutoff doses for detection are 5 and 5-15 mg/L, with detection windows of 6 and 10 h in the blood and urine, respectively Control of GHB is essential to limit the number of users, abuse, associated risks, and death related to their consumption.

Mechanical Thrombectomy with Intravenous Thrombolysis versus Thrombolysis Alone for the Treatment of Stroke: A Systematic Review of Economic Evaluations.

Mechanical thrombectomy has revolutionized the management of stroke by improving the recanalization rates and reducing deleterious consequences. It is now the standard of care despite the high financial cost. A considerable number of studies have evaluated its cost effectiveness. Therefore, this study aimed to identify economic evaluations of mechanical thrombectomy with thrombolysis compared with thrombolysis alone to provide an update of existing evidence, focusing on the period after proof of effectiveness of mechanical thrombectomy. Twenty-one studies were included in the review: 18 were model-based economic evaluations to simulate long-term outcomes and costs, and 19 were conducted in high-income countries. Incremental cost-effectiveness ratios ranged from -$5,670 to $74,216 per quality-adjusted life year. Mechanical thrombectomy is cost-effective in high-income countries and in the populations selected for clinical trials. However, most of the studies used the same data. There is a lack of real-world and long-term data to analyze the cost effectiveness of mechanical thrombectomy in treating the global burden of stroke.

From hospitalisation to primary care: integrative model of clinical pharmacy with patients implanted with a PICC line-research protocol for a prospective before-after study.

INTRODUCTION: Clinical pharmacy improves patient safety and secures drug management using information, education and good clinical practices. However, medical device management is still unexplored, and proof of effectiveness is needed. A PICC line (peripherally inserted central catheter) is a medical device for infusion. It accesses the central venous system after being implanted in a peripheral vein. However, complications after implantation often interfere with smooth execution of the treatment. We hypothesise that clinical pharmacy for medical devices could be as effective as clinical pharmacy for medications. The main objective is to assess the effectiveness of clinical pharmacy activities on the complication rate after PICC line implantation. METHODS AND ANALYSIS: This is a before-after prospective study. The study will begin with an observational period without clinical pharmacy activities, followed by an interventional period where pharmacists will intervene on drug and medical device management and provide personalised follow-up and advice. Sixty-nine adult patients will be recruited in each 6-month period from all traditional care units. The main inclusion criteria will be the implantation of a PICC line. The primary outcome is the decrease in the number of complications per patient and per month. Secondary outcomes are the consultation and hospital readmission rates, the acceptance rate of pharmaceutical interventions, the patients' quality of life, the direct hospital induced or avoided costs and the participants' satisfaction. Data will be collected using case report forms during hospitalisation and telephone follow-up after discharge. The analysis will compare these criteria during the two periods. ETHICS AND DISSEMINATION: The study has received the approval of our Ethics Committee (Clermont-Ferrand Southeast VI, France, number AU1586). Results will be made available to the patients or their caregivers, the sponsor and other researchers when asked, as described in the consent form. TRIAL REGISTRATION NUMBER: NCT04359056.