Risultati per: Quali armi contro l'infiammazione alla base dell'artite psoriasica?

Circulation, Ahead of Print. Background: VERVE-101 is an investigationalin vivoCRISPR base editing medicine designed to alter a single DNA base in thePCSK9gene, permanently turn off hepatic protein production, and thereby durably lower LDL-cholesterol (LDL-C). We test the efficacy, durability, tolerability, and potential for germline editing of VERVE-101 in studies of non-human primates and a murine F1 progeny study.Methods: Cynomolgus monkeys were dosed with a single intravenous infusion of a vehicle control (N=10) or VERVE-101 at a dose of 0.75 mg/kg (N=4) or 1.5 mg/kg (N=22) with subsequent follow-up out to 476 days. Two studies assessed the potential for germline editing, including sequencing sperm samples from sexually mature male non-human primates treated with VERVE-101 and genotyping offspring from female mice treated with the murine surrogate of VERVE-101 (VERVE-101mu).Results: Liver biopsies 14 days after dosing noted meanPCSK9editing of 46% and 70% in monkeys treated with VERVE-101 at 0.75 and 1.5 mg/kg, respectively. This translated into mean reductions in blood PCSK9 of 67% and 83% and reductions of LDL-C of 49% and 69% at the 0.75 and 1.5 mg/kg doses, respectively, assessed as time-weighted average change from baseline between day 28 and up to 476 days following dosing. Liver safety monitoring noted a transient rise in ALT and AST concentrations following infusion that fully resolved by day 14 with no accompanying change in total bilirubin. In a subset of monkeys necropsied 1 year after dosing, no findings related to VERVE-101 were identified on macroscopic and histopathologic assessment of the liver and other organs. In the study to assess potential germline editing of male non-human primates, sperm samples collected after VERVE-101 dosing showed no evidence ofPCSK9editing. Among 436 offspring of female mice treated with a saturating dose of VERVE-101mu, thePCSK9edit was transmitted in 0 of 436 animals.Conclusions: VERVE-101 was well-tolerated in in non-human primates and led to 83% lower blood PCSK9 protein and 69% lower LDL-C with durable effects up to 476 days following dosing. These results have supported initiation of a first-in-human clinical trial in patients with heterozygous familial hypercholesterolemia and atherosclerotic cardiovascular disease.

Circulation, Volume 146, Issue Suppl_1, Page A15524-A15524, November 8, 2022. Background and Objective:The published cardiology literature is critical for scientific communication, and we sought to determine if the published clinical cardiology evidence base has evolved over time.Methods:We evaluated the cardiology related publications in the medical journals (M) JAMA (J) and the New England Journal of Medicine (N) and all publications by the specialty journals (CA) Circulation (Ci) and the European Heart Journal (E) in 2000, 2010, and 2020 and added 2001, 2011, and 2021 for JAMA to account for potential annual variability.Results:Publication information is shown in the graph. For the M journals there has been an increase in the percentage of randomized controlled trials (RCT). For the CA journals there has been a significant decrease in single center studies (Si) and a proportionate increase in reanalysis (Re) of data whether from subanalysis of an RCT, registry, or meta-analysis. For CA journals there has been an increase in the size of clinical studies mainly due to the use of larger datasets from registries or claims (Ci: 2000: 4,500/study; 2010: 9,298/study; 2020: 258,725/study and E: 2000: 2,282/study; 2010: 12,652/study; 2020: 249,388/study). CA journals have an increased of studies with patients from multiple continents (Ci: 2000: 5.5%; 2010: 13%; 2020: 35% and E: 2000: 7%; 2010: 14.8%; 2020: 18.8%). There has been an increase in the percentage of clinical studies with documentation of different populations by region or color (In 2020, 58% for all Ci articles and 52% for US and multicontinental EHJ articles), although the number of nonwhites remains small in most studies unless the study was specifically addressing disparities in care.Conclusions:Over the last two decades, the published evidence base has changed with more RCT in the Med journals and more studies that reanalyze large datasets in CA journals. Published studies are now larger, more likely to involve multiple continents, and document population details.

Introduction
Despite a higher risk of severe COVID-19 disease in individuals with HIV, the interactions between SARS-CoV-2 and HIV infections remain unclear. To delineate these interactions, multicentre Electronic Health Records (EHR) hold existing promise to provide full-spectrum and longitudinal clinical data, demographics and sociobehavioural data at individual level. Presently, a comprehensive EHR-based cohort for the HIV/SARS-CoV-2 coinfection has not been established; EHR integration and data mining methods tailored for studying the coinfection are urgently needed yet remain underdeveloped.

Methods and analysis
The overarching goal of this exploratory/developmental study is to establish an EHR-based cohort for individuals with HIV/SARS-CoV-2 coinfection and perform large-scale EHR-based data mining to examine the interactions between HIV and SARS-CoV-2 infections and systematically identify and validate factors contributing to the severe clinical course of the coinfection. We will use a nationwide EHR database in the USA, namely, National COVID Cohort Collaborative (N3C). Ultimately, collected clinical evidence will be implemented and used to pilot test a clinical decision support prototype to assist providers in screening and referral of at-risk patients in real-world clinics.

Ethics and dissemination
The study was approved by the institutional review boards at the University of South Carolina (Pro00121828) as non-human subject study. Study findings will be presented at academic conferences and published in peer-reviewed journals. This study will disseminate urgently needed clinical evidence for guiding clinical practice for individuals with the coinfection at Prisma Health, a healthcare system in collaboration.

Objective
To review the evidence on the economic evaluations of workplace-based interventions that are designed to reduce prolonged periods of occupational sitting.

Design
An integrative review.

Data sources
The search was conducted in 11 databases, including PubMed, Scopus, PsychINFO, NHS-EED, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ProQuest, Cochrane library, Sportdiscus, Research Paper in Economics (RePeC), the International Health Economic Association (IHEA) and EconLit. The databases were searched for articles published from inception to January 2022. Subsequent citation searches were also conducted in Google Scholar. The items of the Consensus Health Economic Criteria (CHEC) checklist were used for quality appraisal of the included studies.

Results
This review included five randomised control trails, including 757 office-based workers in high-income countries. The median quality appraisal score based on the CHEC items was 14 points (a range of 9–18). The mean duration of interventions was 33 weeks (a range of 4–52 weeks). Overall, the studies reported economic benefit when implemented to reduce occupational sitting time but no effect on absenteeism. From the societal perspective, the interventions (eg, the use of a sit–stand desk) were cost-effective.

Conclusion
The economic impact of workplace interventions implemented to reduce occupational sitting time is evident; however, the existing evidence is limited, which precludes strong conclusions. Cost-effectiveness is not often evaluated in the studies exploring workplace interventions that address occupational sitting time. Workplace interventions are still in the development and testing phase; thus, the challenge for future studies is to include economic evaluation of interventions addressing sedentary behaviour in workplaces.

PROSPERO registration number
CRD42021226275.

L’Inps accoglierà le domande in base alle risorse disponibili e il beneficio sarà erogato in base all’ordine di arrivo della domanda, prioritariamente alle persone con Isee più basso

Medici di medicina generale in luoghi di cultura diffusi sul territorio cittadino, quali musei, biblioteche e poli culturali: a Torino prende il via il progetto Cultura di Base, che si propone di dimostrare che l’esperienza della visita medica in luoghi di senso e bellezza, concorre a depotenziare lo stress correlato all’attesa, aumentando il benessere e il comfort psico-fisico dei pazienti e dei curanti, migliorando la loro relazione

Comunicato del 22/02/2022 n°10