Risultati per: Studio REDUCE-IT e appropriatezza prescrittiva degli acidi grassi omega-3

Objectives
This study sought to determine the prevalence and associated factors of hepatitis B virus (HBV) infection ever in life and chronic HBV infection in Armenia.

Design
A population-based cross-sectional seroprevalence study combined with a phone survey of tested individuals.

Setting
All administrative units of Armenia including 10 provinces and capital city Yerevan.

Participants
The study frame was the general adult population of Armenia aged ≥18 years.

Primary and secondary outcome measures
The participants were tested for anti-HBV core antibodies (anti-HBc) and HBV surface antigen (HBsAg) using third-generation enzyme immunoassays. In case of HBsAg positivity, HBV DNA and hepatitis D virus (HDV) RNA PCR tests were performed. Risk factors of HBV infection ever in life (anti-HBc positivity) and chronic HBV infection (HBsAg positivity) were identified through fitting logistic regression models.

Results
The seroprevalence study included 3838 individuals 18 years and older. Of them, 90.7% (3476 individuals) responded to the phone survey. The prevalence of anti-HBc positivity was 14.1% (95% CI 13.1% to 15.2%) and HBsAg positivity 0.8% (95% CI 0.5% to 1.1%). The viral load was over 10 000 IU/mL for 7.9% of HBsAg-positive individuals. None of the participants was positive for HDV. Risk factors for HBsAg positivity included less than secondary education (aOR=6.44; 95% CI 2.2 to 19.1), current smoking (aOR=2.56; 95% CI 1.2 to 5.6), and chronic liver disease (aOR=8.44; 95% CI 3.0 to 23.7). In addition to these, risk factors for anti-HBc positivity included age (aOR=1.04; 95% CI 1.04 to 1.05), imprisonment ever in life (aOR=2.53; 95% CI 1.41 to 4.56), and poor knowledge on infectious diseases (aOR=1.32; 95% CI 1.05 to 1.67), while living in Yerevan (vs provinces) was protective (aOR=0.74; 95% CI 0.59 to 0.93).

Conclusion
This study provided robust estimates of HBV markers among general population of Armenia. Its findings delineated the need to revise HBV testing and treatment strategies considering higher risk population groups, and improve population knowledge on HBV prevention.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Introduction
Group B streptococcus (GBS), or Streptococcus agalactiae, remains a leading cause of neonatal morbidity and mortality. Canadian guidelines advise universal maternal screening for GBS colonisation in pregnancy in conjunction with selective antibiotic therapy. This results in over 1000 pregnant individuals receiving antibiotic therapy to prevent one case of early-onset neonatal GBS disease, and over 20 000 pregnant individuals receiving antibiotic therapy to prevent one neonatal death. Given the growing concern regarding the risk of negative sequela from antibiotic exposure, it is vital that alternative approaches to reduce maternal GBS colonisation are explored.
Preliminary studies suggest some probiotic strains could confer protection in pregnancy against GBS colonisation.

Methods and analysis
This double-blind parallel group randomised trial aims to recruit 450 pregnant participants in Vancouver, BC, Canada and will compare GBS colonisation rates in those who have received a daily oral dose of three strains of probiotics with those who have received a placebo. The primary outcome will be GBS colonisation status, measured using a vaginal/rectal swab obtained between 35 weeks’ gestation and delivery. Secondary outcomes will include maternal antibiotic exposure and urogenital infections. Analysis will be on an intention-to-treat basis.

Patient or public involvement
There was no patient or public involvement in the design of the study protocol.

Ethics and dissemination
This study protocol received ethics approval from the University of British Columbia’s Clinical Research Ethics Board, Dublin City University and Health Canada. Findings will be presented at research rounds, conferences and in peer-reviewed publications.

Trial registration number
NCT03407157.

Introduction
Concerns about falling (CaF) are common in older people and have been associated with avoidance of activities of daily life. Exercise designed to prevent falls can reduce CaF, but the effects are usually short-lived. Cognitive behavioural therapy (CBT) can reduce CaF for longer but is not readily available in the community and unlikely to prevent falls. A multidomain intervention that combines CBT, motivational interviewing and exercise could be the long-term solution to treat CaF and reduce falls in older people with CaF. This paper describes the design of a randomised controlled trial to test the effectiveness of two different 12 week self-managed eHealth programmes to reduce CaF compared with an active control.

Methods
A total of 246 participants (82 per group) aged 65 and over, with substantial concerns about falls or balance will be recruited from the community. They will be randomised into: (1) myCompass-Own Your Balance (OYB) (online CBT programme) intervention or (2) myCompass-OYB plus StandingTall intervention (an eHealth balance exercise programme), both including motivational interviewing and online health education or (3) an active control group (online health education alone). The primary outcome is change in CaF over 12 months from baseline of both intervention groups compared with control. The secondary outcomes at 2, 6 and 12 months include balance confidence, physical activity, habitual daily activity, enjoyment of physical activity, social activity, exercise self-efficacy, rate of falls, falls health literacy, mood, psychological well-being, quality of life, exercise self-efficacy, programme adherence, healthcare use, user experience and attitudes towards the programme. An intention-to-treat analysis will be applied. The healthcare funder’s perspective will be adopted for the economic evaluation if appropriate.

Ethics and dissemination
Ethical approval was obtained from the South Eastern Sydney Local Health District Human Research Ethics Committee (2019/ETH12840). Results will be disseminated via peer-reviewed journals, local and international conferences, community events and media releases.

Trial registration number
ACTRN12621000440820.

Stroke, Volume 55, Issue Suppl_1, Page AWP296-AWP296, February 1, 2024. Introduction:Stroke patients with type-2 diabetes exhibit exacerbated cerebrovascular dysfunction and increased neurological deficits compared to non-diabetic stroke patients. Vascular smooth muscle cells (VSMCs) play an important role in mediating neurovascular function, however, how VSMCs communicate with cerebral endothelial cells (CECs) has not been studied. In this study, we tested the hypothesis that small extracellular vesicles (sEVs) derived from healthy human VSMCs (VSMC-sEVs) reduce diabetes- and ischemia-neurovascular damage.Methods and Results:VSMC-sEVs were characterized. In vitro CEC permeability assay showed that treatment of hypoxia-challenged human brain microvascular endothelial cells (BMECs) or primary CECs isolated from type-2 diabetic mice (n=6/group) with VSMC-sEVs significantly reduced and augmented cell permeability and trans-endothelial electrical resistance, respectively, compared to non VSMC-sEVs control. Inhibition of sEV endocytosis in BMECs with clathrin (CPZ) or caveolin (Nystatin) inhibitors abrogated the effect of VSMC-sEVs on CEC proliferation and migration. We then examined the effect of VSMC-sEVs on diabetic ischemia in which diabetic mice, with diabetes induced by a high fat diet and streptozotocin, were subjected to permanent MCAo. Middle-age diabetic male mice (10-12m old) were treated with intranasal administration of VSMC-sEVs (1x109particles per injection) or saline (n=12/group) at 24h after cerebral ischemia. We found that VSMC-sEVs treatment significantly increased regional cerebral blood flow and FITC-dextran perfused functional microvessels (17.55% vs 13.32% control) as well as decreased brain hemorrhage and BBB leakage (1.51% vs 1.76% of albumin, p

Stroke, Volume 55, Issue Suppl_1, Page AWMP120-AWMP120, February 1, 2024. Introduction:Loneliness and social isolation (SI) are associated with increased risk of stroke and other vascular disorders, along with all-cause mortality. However, it is unknown what mechanisms mediate how social factors affect stroke recovery.Methods:To investigate the negative effects of post-stroke SI on brain miRNA profiles, aged (18-20 months) C57BL/6 male mice were utilized. Three days following a 60-minute transient right middle cerebral artery occlusion (MCAO), mice were randomly assigned to pair housing (PH) or single housing (SI). At post-stroke timepoints (specifically day 3 after the stroke), the infarct was equal between groups, reducing the possibility of differential effects resulting from different infarct sizes. At two-time intervals (post-stroke SI D4 and D27), temporal miRNA profiling of the ipsilateral hemisphere was performed.Results:Distinct miRNA candidates were significantly altered in post-stroke SI, within the brain across both acute and chronic time points (n=4/grp, FDR adjusted *p

Stroke, Volume 55, Issue Suppl_1, Page ATP35-ATP35, February 1, 2024. Background:White matter hyperintensities (WMH) are associated with risk of dementia and stroke, so are an important therapeutic target for clinical trials. The cost of broad MRI screening to identify those individuals with significant WMH, however, limits the feasibility of designing clinical trials which target WMH presence and which test treatments that slow progression.Hypothesis:A low-cost retinal or clinical screening measure prior to an MRI screening stage reduces the cost of recruiting persons with significant WMH burden in a hypothetical clinical trial vs an MRI-only screening design.Method:Data were from participants in the Atherosclerosis Risk in Communities-Neurocognitive study with clinical, retinal and WMH measurements (N= 1311) at ages 53-70 years. Significant WMH burden was defined as a Cardiovascular Health Study score >2. Three low-cost pre-screening measures were assessed: (1)retinal:a score incorporating multiple markers of abnormal retinal vasculature, (2)clinical:a score incorporating hypertension, diabetes, and age, (3)combined retinal-clinical:a score incorporating retinal and clinical factors. Given a prior published target sample for a WMH clinical trial (N= 646), we calculated a theoretical screening sample size based on the proportion of each pre-screening measure in the population multiplied by the proportion of significant WMH burden among those with a prevalent pre-screening feature. Total recruitment cost was calculated using standard retinal ($32.50) and MRI ($650) cost estimates.Results:Compared to the estimated cost of MRI-only screening ( >$4.24M, requiring MRI screening 6,526 participants), pre-screening for a high clinical score reduced total cost to $2.47M, but increased the initial screening group to 52,778 participants, of whom 3,801 would be screened by MRI). A high retinal-clinical score cutoff reduced costs to $2.9M while only requiring 13,572 screened participants (of these only 3,801 would require MRI).Conclusion:A 2-stage recruitment design with a low-cost pre-screening retinal and clinical measure is a promising approach, resulting in a reduction of theoretical recruitment costs for recruiting persons with significant WMH burden compared to an MRI-only design.

Stroke, Volume 55, Issue Suppl_1, Page AWP19-AWP19, February 1, 2024. Objective:The presence of left atrial thrombus (LAT) in acute stroke patients with nonvalvular atrial fibrillation (NVAF) is the major embolic source for recurrent stroke. The aim of this study was to investigate whether direct oral anticoagulants (DOAC) is more effective than warfarin to reduce the size of LAT detected in acute stroke patients with NVAF.Methods:Among acute stroke patients admitted to five major comprehensive stroke centers from January 2017 to December 2022, acute stroke patients with both AF and LAT detected by transesophageal echocardiography (TEE) were selected, and patients with follow-up evaluation were enrolled. All patients were treated with anticoagulation such as DOAC or warfarin for LAT. Thus, patients were classified into two groups according to the type of anticoagulation; the DOAC group and the warfarin group. We compared the clinical characteristics, the dissolution of LAT, and recurrent stroke within three months after stroke onset evaluated between the two groups.Results:63 patients (median age 77, male 33 [52%]) were enrolled. DOAC and warfarin groups had 22 (35%) and 41(65%) patients, respectively. Age, gender, NIHSS scores on admission were not different between the two groups. Age was 77 years (IQR, 68-81) in the DOAC group and 76 years (IQR, 68-81) in the warfarin group (P=0.644). 10 men (46%) were in the DOAC group, and 23 (56%) were in the warfarin group (P=0.442). The NIHSS score at admission was 3 (IQR, 1-18) in the DOAC group and 4 (IQR, 2-14) in the warfarin group (P=0.393). Initial LAT size was 0.83 (IQR, 0.41-1.27) cm2 in DOAC and 0.88 (IQR, 0.40-1.56) cm2 in warfarin (p=0.48). On follow-up evaluation (10 [IQR, 7-15] days after initial TEE), the disappearance of LAT was more frequently seen in DOAC group than warfarin group (13/22 [59%] vs. 14/41 [34%], P=0.016). Recurrent stroke within three months after stroke was 1/22 (5%) in DOAC and 3/41 (7%) in warfarin (P=1.000), which was not different.Conclusion:In acute stroke patients with NVAF, DOAC should be more effective than warfarin to dissolve LAT detected by TEE.

Introduction
Heavy alcohol use among people living with HIV in sub-Saharan Africa can hinder the success of HIV treatment programmes, impacting progress towards United Nations Programme on HIV/AIDS goals. Primary partners can provide critical forms of social support to reduce heavy drinking and could be included in motivational interviewing (MI) interventions to address heavy drinking; however, few studies have evaluated MI interventions for couples living with HIV in sub-Saharan Africa. We aim to evaluate the feasibility and acceptability of a couple-based MI intervention with mobile breathalyser technology to reduce heavy alcohol use and improve HIV treatment outcomes among HIV-affected couples in South Africa.

Methods and analysis
We will employ a three-arm randomised controlled trial to assess the efficacy of couple-based MI (MI-only arm) and in conjunction with mobile breathalysers (MI-plus arm) to address alcohol use and HIV outcomes, as compared with enhanced usual care (control arm). We will enrol heterosexual couples aged 18–49 in a primary relationship for at least 6 months who have at least one partner reporting hazardous alcohol use and on antiretroviral therapy for 6 months. Participants in both MI arms will attend three manualised counselling sessions and those in the MI-plus arm will receive real-time feedback on blood alcohol concentration levels using a mobile breathalyser. Couples randomised in the control arm will receive enhanced usual care based on the South African ART Clinical Guidelines. Feasibility and acceptability indicators will be analysed descriptively, and exploratory hypotheses will be examined through regression models considering time points and treatment arms.

Ethics and dissemination
The study was approved by the University of California, San Francisco (HRPP; protocol number 21-35034) and Human Sciences Research Council Research Ethics Committee (REC: protocol number 1/27/20/21). We will disseminate the results at local community meetings, community-level health gatherings and conferences focused on HIV and alcohol use.

Trial registration number
NCT05756790.

Young Investigator Award a potenzialità nanovescicole staminali

We studied saffron as an additional intervention to improve clinical manifestations of Ulcerative colitis (UC) patients,

New England Journal of Medicine, Ahead of Print.

Introduction
Pleural effusion is present in half of the patients hospitalised with acute heart failure. The condition is treated with diuretics and/or therapeutic thoracentesis for larger effusions. No evidence from randomised trials or guidelines supports thoracentesis to alleviate pleural effusion due to acute heart failure. The Thoracentesis to Alleviate cardiac Pleural effusion Interventional Trial (TAP-IT) will investigate if a strategy of referring patients with acute heart failure and pleural effusion to up-front thoracentesis by pleural pigtail catheter insertion in addition to pharmacological therapy compared with pharmacological therapy alone can increase the number of days the participants are alive and not hospitalised during the 90 days following randomisation.

Methods and analysis
TAP-IT is a pragmatic, multicentre, open-label, randomised controlled trial aiming to include 126 adult patients with left ventricular ejection fraction ≤45% and a non-negligible pleural effusion due to heart failure. Participants will be randomised 1:1, stratified according to site and anticoagulant treatment, and assigned to referral to up-front ultrasound-guided pleural pigtail catheter thoracentesis in addition to standard pharmacological therapy or to standard pharmacological therapy only. Thoracentesis is performed according to local guidelines and can be performed in participants in the pharmacological treatment arm if their condition deteriorates or if no significant improvement is observed within 5 days. The primary endpoint is how many days participants are alive and not hospitalised within 90 days from randomisation and will be analysed in the intention-to-treat population. Key secondary outcomes include 90-day mortality, complications, readmissions, and quality of life.

Ethics and dissemination
The study has been approved by the Capital Region of Denmark Scientific Ethical Committee (H-20060817) and Knowledge Center for Data Reviews (P-2021–149). All participants will sign an informed consent form. Enrolment began in August 2021. Regardless of the nature, results will be published in a peer-reviewed medical journal.

Trial registration number
NCT05017753.