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Introduction
Childhood tuberculous meningitis (TBM) is a devastating disease. The long-standing WHO recommendation for treatment is 2 months of intensive phase with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E), followed by 10 months of isoniazid and rifampicin. In 2022, WHO released a conditional recommendation that 6 months of intensified antituberculosis therapy (ATT) could be used as an alternative for drug-susceptible TBM. However, this has never been evaluated in a randomised clinical trial. Trials evaluating ATT shortening regimens using high-dose rifampicin and drugs with better central nervous system penetration alongside adjuvant anti-inflammatory therapy are needed to improve outcomes.

Methods and analysis
The Shortened Intensive Therapy for Children with Tuberculous Meningitis (SURE) trial is a phase 3, randomised, partially blinded, factorial trial being conducted in Asia (India and Vietnam) and Africa (Uganda, Zambia and Zimbabwe). It is coordinated by the Medical Research Council Clinical Trial Unit at University College London (MRCCTU at UCL). 400 children (aged 29 days to

Introduction
Ageing right care(fully) is a transnational research study which explores and maps an understanding of the care pathways between ageing in place and hospital at home policy and practices for older adults in Israel, the Netherlands and Sweden. The countries are suited to be compared where they have growing, ageing populations, a focus on healthcare reform and several policies to reduce the cost of care for older populations. Ageing in place is a government-led policy that is often associated with choice; however, there is a recent debate about whether ageing in place is a universal desire for all older adults. Research shows that the care pathway between the hospital and the home, associated with ageing in place, can impact well-being, especially if the built, social and technological environments do not meet the healthcare needs and preferences of older adults. This is significant as new programmes for digital hospital at home innovations are being developed as part of a global transformation in healthcare systems. The aim of the study is to compare different approaches to ageing in place and hospital at home care in different regions. The multiapproach study explores the demographics, policy structure, decision-making process and the crucial role of the built, social and technological environments along the hospital to home care pathways of older adults.

Methods and analysis
The mixed-method, comparative study includes a new multienvironment theoretical contribution explored across a three-phase research method to understand the care pathways of older adults ageing in place receiving hospital at home care. The first phase compares each country’s population and policy structures relating to ageing in place, hospital discharge, home hospitalisation and at-home care for older adults. The second phase maps patient journeys of older adults living in each country through the perspective of the older adult, caregivers and care professionals. The third phase explores the synergies between the knowledge gained through phases 1 and 2—from a policy and a personal level—and mobilises the knowledge into policy recommendations and implementation guidelines.

Ethics and dissemination
The comparative study has been approved by the Sheba Medical Centre in Israel (SMC-1330-24), the Ethics Committee of Tel Aviv University (0009216-2), the Humanities and Social Science Ethics Committee at the University of Twente in the Netherlands (240040) and the Swedish Ethical Review Authority (Dnr 2024-07569-01). The results will be shared with end-users, including citizens, carers, healthcare policymakers, planners, architects and designers, through social media, publications, workshops and international conferences. This future-focused research approach will allow stakeholders to rethink and imagine ways that health and care systems can be personalised and responsive to the future needs of older adult populations.

Objectives
To understand the help-seeking experiences of young people from culturally and linguistically diverse (CALD) backgrounds who have experienced suicidal thoughts and behaviours (STB).

Design
Qualitative study using semistructured interviews and reflexive thematic analysis.

Setting
A specialist, youth-focused Hospital Outreach Post-suicidal Engagement (HOPE) aftercare service delivered by Orygen in North-West Melbourne, Australia.

Participants
Eight young people aged 16–24 years (mean: 18.7±3.1 years, 50% female) from various CALD backgrounds who had been discharged from the HOPE aftercare service within the past 12 months.

Results
Four themes were identified: (1) cultural taboos and generational differences create challenges in communicating with family; (2) isolation is a barrier to reaching out; (3) it’s hard to disclose and discuss STB with clinicians and (4) not being taken seriously in clinical settings.

Conclusion
These findings highlight social, cultural and organisational barriers that shape the help-seeking journeys of young people from CALD backgrounds experiencing STB. Results suggest a need for culturally sensitive suicide prevention strategies, enhanced cultural competency in healthcare settings and efforts to improve mental health literacy within CALD communities.

Objectives
There is a shortage of reliable tools to evaluate general practitioners’ (GPs) ability to recognise and manage depression. The main aim of this study was to develop and validate a reliable tool for assessing the GPs’ ability to recognise and manage depression.

Design
A cross-sectional survey incorporating the GPs’ ability to recognise and manage the depression assessment scale, the work was administered between July 2023 and June 2024. GPs’ ability to recognise and manage the depression assessment scale was developed in four phases: (1) item pool construction, (2) expert consultation, (3) exploratory factor analysis for further item reduction and to identify the factor structure of the revised scale and (4) confirmatory factor analyses to confirm the factors identified within the exploratory factor analysis.

Setting
Primary healthcare in China.

Participants
A total of 421 GPs participated in the study across phases 3 and 4. Phase 3 included 172 GPs, and phase 4 involved 249 GPs. They had been working in primary healthcare, with 44.42% having more than 10 years of experience. Of the participants, 57% were female.

Results
The GPs’ ability to recognise and manage the depression assessment scale comprised two dimensions, with 24 items. Two factors explained 66.62% of the items’ variance through exploratory factor analysis. Confirmatory factor analysis confirmed two dimensions of the scale and produced appropriate Goodness of Fit Indexes. Reliability was robust, with composite reliability coefficients exceeding 0.60, Cronbach’s alpha at 0.96 and a Spearman-Brown coefficient of 0.86.

Conclusions
The newly developed scale is a reliable and valid tool for assessing GPs’ abilities to recognise and manage depression. It is suitable for large-scale surveys, particularly in underdeveloped regions, and can help identify gaps in knowledge. The scale results highlight areas where GPs’ skills are lacking, enabling the design of targeted continuing education programmes. It can also assess the effectiveness of depression training courses, providing a foundation for tailored interventions.

Background
The healthcare workforce is in crisis. Despite a competitive selection process, a substantial number of doctors leave specialty training (ST) programmes prematurely. This attrition causes increased costs for the National Health Service, exacerbates workforce shortages and threatens quality and safety of care. It also increases pressure on trainees who remain, further compounding the risk of attrition. There is an urgent need to understand why doctors leave ST in order to find ways to maintain the training pipeline from ST to consultant.

Objectives
We aimed to understand what is known about why doctors choose to leave ST programmes in secondary care, to map current knowledge and identify avenues for future research.

Eligibility criteria
All studies which investigated why doctors leave ST programmes in secondary care were included.

Sources of evidence
Ovid Medline, Web of Science, SCOPUS and EMBASE were searched until January 2024. Descriptive codes were assigned to the findings of each study. These descriptive codes were reviewed and grouped together in broader categories.

Charting methods
Data was extracted and charted, and a qualitative content approach was used to synthesise data.

Results
A total of 6079 potentially relevant abstracts were retrieved, of which 23 were included in the final analysis. This included the experience of 1896 doctors who have left training and 454 programme directors. Doctors chose to leave training programmes because (1) they felt unsupported and underappreciated, (2) training was associated with unacceptable personal costs and (3) career prospects were unattractive.

Conclusion
There is a mismatch between trainees’ expectations of ST and the reality of being a trainee in ST. Understanding the issues which drive attrition and developing evidence-based solutions, has the potential to both reduce attrition, and improve the training experience for doctors in training more widely.

Introduction
Effective glucose control in surgical patients at risk of hyperglycaemia and hypoglycaemia is crucial, as these conditions can lead to surgical site infections, prolonged hospital stays and death. Fingerstick glucose monitoring (FSGM), the standard measurement of glucose, can be painful for patients and time-consuming for nursing staff, especially with hourly monitoring around surgery. Continuous glucose monitoring systems (CGMS) offer a less invasive alternative with better glucose regulation in outpatients.
The GLUCOSENS study compares the effects of CGMS and FSGM on point-of-care measurements and time-in-range (3.9–10.0 mmol/l) glucose levels (primary outcome), patient satisfaction and experience and nursing staff workload and experience in surgical wards. Furthermore, it evaluates CGMS accuracy during perioperative periods and medical imaging.

Methods and analysis
This Danish two-centre study will be conducted at the general surgical wards of Odense and Zealand University Hospital and will involve 305 patients over 18 months. The study is divided into three periods: first, a standard care period with point-of-care FSGM (110 patients); second, an intervention period with point-of-care CGMS (110 patients); third, another standard care period with point-of-care FSGM combined with a blinded sensor for comparing continuous glucose data from this period with continuous glucose data from the intervention period (85 patients). Furthermore, the study will include 24 nursing staff.
Data will be collected through medical file reviews on glucose levels, patient satisfaction questionnaires, a patient field study, an observation study of the nursing staff’s workload and qualitative interviews of nursing staff.

Ethics and dissemination
The study is registered with the Records of Processing Activities in the Region of Southern Denmark for research and quality projects (ID number: 23/36734) and has been approved by the Regional Scientific Ethical Committee in Southern Denmark (ID number: S-20240041). The results will be published in international peer-reviewed journals.

Trail registration number
ClinicalTrials.gov Registry (NCT06473480)

Objective
To assess HIV testing and status disclosure rates and explore their associated predictors among young adolescents (10–17 years) who received health education through the Orphans and Vulnerable Children programme in Nimule, South Sudan.

Design
A pre–post evaluation study with data collected at baseline (December 2020) and at the endline (December 2022).

Setting
The study was conducted in Nimule, a densely populated periurban town characterised by high HIV prevalence and substantial cross-border movement between Uganda and South Sudan, making it a relevant setting for an HIV prevention project.

Intervention
The primary intervention was HIV risk education delivered through forty peer-led health clubs. Adolescents were screened for HIV risk factors and referred for HIV and other sexually transmitted infection testing at health facilities.

Participants
The study included young adolescents aged 10–17 years recruited from HIV-affected households within 17 neighbourhoods in Nimule periurban town. Informed consent was obtained from both caregivers and adolescents.

Primary and secondary outcome measures
The primary outcome was self-reported HIV testing and status disclosure. Binary logistic regression was used to assess the association between the study outcome variables and associated sociodemographic factors.

Results
A total of 557 (73.0%) of the 768 enrolled adolescents were surveyed at baseline and endline, including 301 (54.0%) females and 276 (46.0%) males. The median age was 14 years (IQR: 11–16) at baseline and 15 years (IQR: 12–17) at endline.
HIV testing increased from 315 (56.7%) at baseline to 557 (100%). The odds of undisclosed HIV status were 49% lower at endline adjusted OR (aOR) 0.51 (95% CI 0.92, 0.67; p

Objectives
To use vignettes to facilitate exploration of the internal dialogue and clinical reasoning processes of general practice healthcare professionals (GPHCPs) during interactions with patients living with obesity.

Design
This study used an exploratory qualitative research design. Data were collected using semistructured interviews. Interviews were transcribed verbatim, and data analysed using Framework Method analysis. Five vignettes were presented to participants, showing a patient’s photograph, name, age and body mass index. Participants were asked to describe their first impressions of each fictionalised patient.

Setting
Interviews were conducted remotely via Skype between August and September 2019.

Participants
A convenience sample of UK GPHCPs was recruited via a targeted social media strategy, using virtual snowball sampling. 20 participants were interviewed (11 general practice nurses and 9 general practitioners).

Results
Five themes were generated: visual assessment, assumed internal contributing factors, assumed external contributing factors, potential clinical contributing factors and potential clinical consequences. A pattern-recognition approach was identified, as GPHCPs’ assumptions around patients’ lifestyles, occupations and eating habits emerged as explanations for their weight, with a mixture of both objective and subjective comments.

Conclusions
While it is part of the diagnostic skill of a clinician to be able to form a clinical picture based on the information available, it is important to be aware of the potential for assumptions made within this process to contribute to unconscious bias/stereotyping. Healthcare professionals need to work to counteract the potential impact of internal bias on their consultations to provide fair and equitable care for people living with obesity, by exercising reflexivity within their clinical practice.

Studio, seguito per 3 giorni a settimana fa eliminare più chili

Circulation, Ahead of Print. BACKGROUND:Gene mutations are responsible for a sizeable proportion of cases of heart failure. However, the number of patients with any specific mutation is small. Repositioning of existing US Food and Drug Administration–approved compounds to target specific mutations is a promising approach to efficient identification of new therapies for these patients.METHODS:The National Institutes of Health Library of Integrated Network-Based Cellular Signatures database was interrogated to identify US Food and Drug Administration–approved compounds that demonstrated the ability to reverse the transcriptional effects ofLMNAknockdown. Top hits from this screening were validated in vitro with patient-specific induced pluripotent stem cell–derived cardiomyocytes combined with force measurement, gene expression profiling, electrophysiology, and protein expression analysis.RESULTS:Several angiotensin receptor blockers were identified from our in silico screen. Of these, olmesartan significantly elevated the expression of sarcomeric genes and rate and force of contraction and ameliorated arrhythmogenic potential. In addition, olmesartan exhibited the ability to reduce phosphorylation of extracellular signal–regulated kinase 1 inLMNA-mutant induced pluripotent stem cell–derived cardiomyocytes.CONCLUSIONS:In silico screening followed by in vitro validation with induced pluripotent stem cell–derived models can be an efficient approach to identifying repositionable therapies for monogenic cardiomyopathies.

Circulation, Ahead of Print. BACKGROUND:TAP-IT (Thoracentesis to Alleviate Cardiac Pleural Effusion–Interventional Trial) investigated the effect of therapeutic thoracentesis in addition to standard medical therapy in patients with acute heart failure and sizeable pleural effusion.METHODS:This multicenter, unblinded, randomized controlled trial, conducted between August 31, 2021, and March 22, 2024, included patients with acute heart failure, left ventricular ejection fraction ≤45%, and non-negligible pleural effusion. Patients with very large effusions (more than two-thirds of the hemithorax) were excluded. Participants were randomly assigned 1:1 to upfront ultrasound-guided pleural pigtail catheter thoracentesis in addition to standard medical therapy or standard medical therapy alone. The primary outcome was days alive out of the hospital over the following 90 days; key secondary outcomes included length of admission and 90-day all-cause mortality. All outcomes were analyzed according to the intention-to-treat principle.RESULTS:A total of 135 patients (median age, 81 years [25th; 75th percentile, 75; 83]; 33% female; median left ventricular ejection fraction, 25% [25th; 75th percentile, 20%; 35%]) were randomized to either thoracentesis (n=68) or standard medical therapy (n=67). The thoracentesis group had a median of 84 days (77; 86) alive out of the hospital over the following 90 days compared with 82 days (73; 86) in the control group (P=0.42). The mortality rate was 13% in both groups, with no difference in survival probability (P=0.90). There were no differences in the duration of the index admission (control group median, 5 days [3; 8]; thoracentesis group median, 5 days [3; 7;P=0.69]). Major complications occurred in 1% of thoracenteses performed during the study period.CONCLUSIONS:For patients with acute heart failure and pleural effusion, a strategy of upfront routine thoracentesis in addition to standard medical therapy did not increase days alive out of the hospital for 90 days, all-cause mortality, or duration of index admission. The current findings lay the groundwork for future research to confirm the results.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT05017753.

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Volume 178, Issue 4, Page JC39, April 2025.

Immunotherapy stands as one of the most transformative breakthroughs in modern cancer treatment. These innovative therapies target signaling pathways used by cancer cells to induce T-cell exhaustion at immune checkpoints, allowing the cancer to evade immune detection. In the last 10 years, immune checkpoint inhibitors have achieved long-lasting responses and, in some cases, even cures for cancers that once had poor prognoses. However, the journey to proving the efficacy of immunotherapy in breast cancer has been anything but straightforward. It took 8 years after the initial approval of an immune checkpoint inhibitor for melanoma before breast cancer saw its first approval in 2019, when atezolizumab received an indication for metastatic triple-negative breast cancer (TNBC) based on the IMpassion130 trial. Shortly thereafter, the US Food and Drug Administration granted approval to pembrolizumab for metastatic TNBC, fueling optimism that patients with this aggressive form of cancer were on the cusp of reaping vast benefits from immune-based therapies. Yet excitement gave way to uncertainty following the negative results of IMpassion131, leading to the voluntary withdrawal of atezolizumab’s indication for TNBC. Although pembrolizumab remained in play, confidence in immune therapy for breast cancer had been shaken.

Barrett’s esophagus (BE) is a precursor lesion for esophageal adenocarcinoma (EA). Surveillance endoscopy aims to detect early malignant progression: though widely practised it has not previously been tested in a randomized trial.

In the first month of the new administration responsible for leading the US, the executive branch has issued a flurry of orders, including ones associated with the dismissal or resignation of tens of thousands of federal employees. Many of these have substantial consequences for science, medicine, and public health. Amidst the dizzying array of actions, it is difficult to know where to focus and how best to respond. However, the silencing of science and health-related communications through suppression or erasure of information, and the corresponding silence by many in the fields of biomedicine and public health, deserve special consideration.