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

Introduction
A variety of hypoglycaemic drugs are used to treat polycystic ovarian syndrome (PCOS), but their efficacy remains insufficient. Glucokinase activators (GKAs) are a unique class of hypoglycaemic medications with emerging potential, notably in significantly reducing insulin resistance (IR). Nevertheless, the efficacy of GKAs in treating PCOS, particularly in the absence or presence of IR, remains uncertain. The meta-analysis protocol aims to address this knowledge gap, furnish evidence-based data to support potential revisions in PCOS treatment guidelines and promote the utilisation of GKAs in clinical settings.

Methods and analysis
A comprehensive search will be conducted across the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Embase, Medline, Scopus, CNKI, Wanfang and VIP databases to identify randomised controlled trials investigating the use of GKAs in the treatment of PCOS, irrespective of the presence of IR. The search will encompass all available studies without language restrictions and cover the period from the inception of each database to 10 April 2024. Disputes will be resolved by talking with a third expert following the screening of articles and data extraction by two reviewers. The primary outcomes of interest encompass changes in anthropometric parameters, menstrual frequency, sex hormone levels, and glucose metabolism, while secondary objectives include lipid metabolism and adverse events. The methodological quality of each study will be assessed using Version 2 of the Cochrane Collaboration tool for assessing Risk of Bias (RoB 2.0), and the Grade of Recommendations, Assessment, Development and Evaluation (GRADE) technique will be used to assess the quality of evidence and degree of recommendation. The study duration of this study will be from 5 April 2024 to 10 April 2025.

Ethics and dissemination
Since this study just analyses data that are readily available to the public and does not directly involve patient participation, ethical approval is not necessary. The findings will be made public by being published in a medical journal that is subject to peer review.

PROSPERO registration number
CRD42024535633.

Objective
Examine how the characteristics of border communities along the US southern land border impact Emergency Medical Services (EMS) personnel in these border communities.

Design
Using phenomenological approach, we conducted face-to-face, one-on-one interviews using a semistructured interview methodology.

Setting
All participants worked as EMS providers in a city fire department along the Texas-Mexico border.

Participants
28 EMS providers participated in the study. 93% of participants were male and 7% were female. 50% of participants had more than 10 years of experience working as an EMS provider.

Findings
We found that local EMS personnel frequently provide medical support for Border Patrol due to the lack of medical capability within the agency. This care provision creates negative impacts for both the community and EMS personnel. These findings were shown through the overarching theme that the presence of federal law enforcement in the community is the primary characteristic that impacts the experiences and perspectives of EMS personnel. Additional primary themes include: (1) Customs and Border Protection (CBP) utilisation of local EMS strains the system, (2) CBP utilisation of local EMS is the result of a lack of medical training and (3) the presence of the international boundary creates a unique work environment.

Conclusion
The lack of medical support within Border Patrol and relevant federal agencies creates a burden on local EMS resources and causes stress among EMS personnel.

Introduction
Colposcopy is a standard procedure for evaluating cervical abnormalities and collecting cervical biopsies. The procedure is associated with intra- and inter-observer variation. A colposcopic scoring system, Swedescore, has been designed to standardise and facilitate colposcopy training. Swedescore has performed well in a routine clinical setting when used by expert colposcopists to find or exclude high-grade lesions. Danish clinical guidelines for colposcopy differ from other countries, as they recommend collecting four cervical biopsies in all women regardless of risk factors or colposcopy findings. Swedescore has never been examined to assess the reduction of cervical biopsies in a real-world clinical setting. This study aims to investigate whether the implementation of Swedescore can optimise the diagnostic work-up for whom the collection of biopsies can be safely omitted or reduced.

Methods and analysis
The design is a clinical multicentre non-randomised intervention study in Denmark. According to a power calculation, we will need to include 586 women referred for colposcopy. Colposcopy with Swedescore will be compared with conventional colposcopy with no Swedescore. Cervical biopsies will be divided into two separate vials (target and random biopsies). The primary outcome will be normal or cervical intraepithelial neoplasia grade 1 detected in cervical biopsies. 2 and logistic regression will be used to compare estimates between arms.

Ethics and dissemination
The study protocol has been submitted to the Ethical Committee in Central Denmark region and is not notifiable to the Committee (j.no.: 1-10-72-124-22). Results will be published in a peer-reviewed journal and presented at scientific meetings.

Trial registration number
NCT05870787.

Protocol version
Version 3 (date 12. November 2024).

Circulation, Ahead of Print. BACKGROUND:Heart failure with preserved ejection fraction (HFpEF) is a major health concern. Pathological stimuli and interactions between cardiac fibroblasts (CFs) and other cell types may lead to cardiac fibrosis and diastolic dysfunction, which are hallmarks of HFpEF. Interstitial and perivascular cardiac fibrosis correlates with poor prognosis in HFpEF; however, mechanisms of fibrosis remain poorly elucidated, and targeted therapies are lacking. Cardiac reprogramming is a promising therapeutic approach for myocardial infarction that facilitates cardiac regeneration and antifibrosis action throughMef2c/Gata4/Tbx5/Hand2(MGTH) overexpression in resident CFs. However, the efficacy of this approach on HFpEF is yet to be established.METHODS:Herein, we examined the effects of cardiac reprogramming in HFpEF using Tcf21iCre/Tomato/MGTH2A transgenic mice, which expressed both MGTH and reporter expression in CFs for cardiac reprogramming and lineage tracing upon tamoxifen administration. To establish HFpEF model mice, we used a combination of a high-fat diet and nitric oxide synthase inhibition. Bulk RNA-sequencing, single-cell RNA-sequencing, and spatial transcriptomics were conducted to determine fibrotic mechanisms and the efficacy of cardiac reprogramming in HFpEF. We generated new tamoxifen-inducible transgenic mice overexpressing each reprogramming factor in CFs to investigate the effect of single factors. Last, we analyzed the effect of reprogramming factors in human CFs.RESULTS:Cardiac reprogramming with MGTH overexpression improved diastolic dysfunction, cardiac hypertrophy, fibrosis, inflammation, and capillary loss in HFpEF. Cardiac reprogramming converted approximately 1% of resident CFs into induced cardiomyocytes. Bulk RNA-seq indicated that MGTH overexpression upregulated genes related to heart contraction and suppressed the fetal gene program (NppaandNppb) and proinflammatory and fibrotic signatures. Single-cell RNA-sequencing and spatial transcriptomics revealed that multiple CF clusters upregulated fibrotic genes to induce diffuse interstitial fibrosis, whereas distinct CF clusters generated focal perivascular fibrosis in HFpEF. MGTH overexpression reversed these profibrotic changes. Among 4 reprogramming factors, only Gata4 overexpression in CFs reduced fibrosis and improved diastolic dysfunction in HFpEF by suppressing CF activation without generating new induced cardiomyocytes. Gata4 overexpression also suppressed profibrotic signatures in human CFs.CONCLUSIONS:Overexpressing Gata4 in CFs may be a promising therapeutic approach for HFpEF by suppressing fibrosis and improving diastolic dysfunction

New England Journal of 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.

Annals of Internal Medicine, Ahead of Print.

Objective
This study evaluates the effectiveness of Taiwan’s nationwide oral cancer screening programme in reducing late-stage diagnosis, treatment delays and mortality.

Design
A retrospective cohort study was conducted.

Setting
The study utilized Nationally representative datasets, including the Cancer Registry, Oral Mucosal Screening and National Health Insurance databases in Taiwan.

Participants
The study included patients with oral cancer diagnosed between 1 January 2010 and 31 December 2013, with follow-up through 31 December 2018. The final analysis included 16 430 patients.

Intervention
The intervention was Taiwan’s nationwide oral cancer screening programme which provides visual inspection and palpation of the oral mucosa.

Primary outcome measures
The primary outcomes measured were late-stage diagnosis (stages III and IV), treatment delay (time from diagnosis to treatment >30 days) and all-cause mortality.

Results
Oral cancer screening was statistically significantly associated with a reduced likelihood of late-stage diagnosis (adjusted OR (AOR)=0.85, 95% CI 0.80 to 0.91, p

In Reply We appreciate the thoughtful comments to this Viewpoint by Karahan et al that emphasize the importance of considering additional predictive parameters when determining immunotherapy treatment strategies for patients with advanced melanoma. In patients with treatment-naive unresectable or metastatic melanoma and no central nervous system metastases, various clinical and molecular biomarkers, including programmed cell death ligand 1 (PD-L1) status (1% cut-off), liver metastases, BRAF mutational status, and the number of involved metastatic organs may help guide the shared decision-making process for dual checkpoint inhibition with ipilimumab plus nivolumab vs anti–programmed cell death 1 (PD-1) monotherapy. In addition, acknowledging the challenges in precisely defining this population in clinical trials and clinical studies, patients with rapidly progressing and/or symptomatic disease, very high tumor burden, or disease localization in organs at high risk (eg, close to critical anatomic structures like the spinal cord or upper airways) might obtain superior benefit from combination therapy with ipilimumab plus nivolumab due to the fast kinetics of response. To our knowledge, no defined biomarkers, other than PD-L1 at the 1% cut-off, exist for guiding the choice between the combination of relatlimab plus nivolumab and anti-PD-1 monotherapy.

This randomized clinical trial investigates if direct-to-patient mailed interventions reduce sedative use and improve sleep outcomes in patients.

To the Editor We read with great interest the comments by Donia and Prasad suggesting that for patients with tumors exhibiting positive staining (≥1%) for programmed cell death ligand 1 (PD-L1), nivolumab monotherapy offers maximal benefit while cautioning against the necessity of the combination therapy due to toxic effects and cost. However, we wish to address certain points and express our reservations regarding this stance.

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