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Introduction
Persistent musculoskeletal pain is a leading cause of disability and need for rehabilitation globally. Many people with the condition attend pain management programmes (PMPs) for rehabilitation and support with self-management. Physical activity (PA) is an essential self-management strategy facilitated on PMPs as it benefits symptoms, general health and well-being. PA needs to be maintained in the long term to continue to be beneficial. However, while many patients increase their PA during or immediately after a PMP, they commonly find it difficult to maintain it in the long term. This study aims to address this problem by developing an intervention to support PA maintenance after a PMP.

Methods and analysis
This mixed-methods study will be guided by the Medical Research Council guidelines for developing complex interventions and the Behaviour Change Wheel intervention development framework. Participants will be recruited from multiple UK National Health Service PMPs. Participants will include patients with persistent musculoskeletal pain who have completed PMPs, their PA partners (people who support them with PA) and healthcare professionals who facilitate PA on PMPs. The study will be conducted in three phases. In phase 1, qualitative interviews will explore the experiences, barriers and facilitators of PA maintenance after a PMP and potential characteristics for a PA maintenance intervention from patient, PA partner and healthcare professional perspectives. Phase 2 will consist of a prospective longitudinal pilot study to identify factors associated with PA maintenance after a PMP. Phase 3 will involve developing a logic model and co-designing the intervention with patient, PA partner and healthcare professional stakeholder groups.

Ethics and dissemination
The project received research ethics committee (REC) and Health Research Authority approval on 4 June 2024 (REC: North West—Liverpool Central, REC reference: 24/NW/0174, IRAS Project ID: 340674). Findings will be disseminated by peer-reviewed publications, conference presentations, social media and lay summaries for patients and the public.

Background
The lack of interoperability has been a well-recognised limitation associated with the use of electronic health records (EHR). However, less is known about how it manifests for frontline NHS staff when delivering care, how it impacts patient care and what its implications are on care efficiency.

Objectives
(1) To capture the perceptions of NHS physicians regarding the current state of EHR interoperability, (2) to investigate how poor interoperability affects patient care and safety and (3) to explore the effects it has had on care efficiency in the NHS.

Methods
An online Qualtrics survey was conducted between June and October 2021 to explore how NHS physicians perceived the present state of interoperability among EHR in service, its effects on patient safety and its impact on care efficiency in NHS healthcare facilities. Recruitment was performed via convenience sampling and snowballing in collaboration with contacts at Health Education England deaneries and the Royal College of General Practitioners. Descriptive statistics were used to report any notable findings observed.

Results
A total of 636 NHS physicians participated, of which 218 (34.3%) completed the survey fully. Participants reported that EHR interoperability is rudimentary across much of the NHS, with limited ability to read but not edit data from within their organisation. Negative perceptions were most pronounced among specialties in secondary care settings and those with less than 1 year of EHR experience or lower self-reported EHR skills. Limited interoperability prolonged hospital stays, lengthened consultation times and frequently necessitated repeat investigations to be performed. Limited EHR interoperability impaired physician access to clinical data, hampered communication between providers and was perceived to threaten patient safety.

Conclusion
As healthcare data continues to increase in complexity and volume, EHR interoperability must evolve to accommodate these growing changes and ensure the continued delivery of safe care. The experiences of physicians provide valuable insight into the practical challenges limited interoperability poses and can contribute to future policy solutions to better integrate EHR in the clinical environment.

This JAMA Insights explores factor V Leiden, an inherited thrombophilia, and its association with venous and arterial thrombosis, how it affects pregnancy outcomes, and testing.

A scientific marvel, the process of DNA methylation in neurons plays a crucial role in memory formation and storage, influencing how synaptic connections are first established and later reinforced. Although this esoteric process might seem outright incredible to non-neurobiologists, in “A Blessing for Methylation,” the ingenuity of poetry becomes a useful entrée into grasping it. The brilliant opening couplet “memory/is physical” immediately bridges what might at first seem a yawning chasm between intangible humanity and hard science. The simplicity and elegance of the language throughout the poem evoke the fundamentally logical nature of the biochemical reactions that give rise to memory; the short lines with their frequent enjambment further contribute to an appreciation of the stepwise fashion in which such reactions occur. The poem also imparts a more ethereal sense of how such scientific mechanisms are translated into the wonder of our ability to remember, the last lines at once continuing the enacted metaphor of molecule-by-molecule, brick-by-brick building while surprising us with a luminous recollection of the speaker, a concrete neural product that seemingly miraculously transcends time. “… I/see my hand in/your hair again//not grey and wiry/but golden — it holds/the light like the sky//holds summer stars” arises from the cellular basis of neural plasticity evinced, surely, but also as a summative expression of a design even more astonishing and grand.

In Reply We thank the letter writers for their interest in the PLUSS trial, which was designed to determine if early prophylactic intratracheal budesonide mixed with surfactant would prevent BPD in infants born prior to 28 weeks’ gestation. Budesonide was not administered to treat or modify established preterm lung disease or evolving BPD, when treatment with systemic postnatal corticosteroids, such as dexamethasone, is typically considered. Prior to PLUSS, Yeh et al reported that early intratracheal budesonide, 0.25 mg/kg (the same dose used in PLUSS), resulted in a large reduction in the risk of death or BPD. As discussed in our article, it remains unclear why early intratracheal budesonide had little to no effect on survival without BPD in PLUSS.

Introduction
Mental health problems are important causes of disability and economic costs worldwide. Randomised clinical trials examining the treatment of mental health disorders measure heterogeneous outcomes, causing difficulties in data synthesis, interpretation and translation into clinical practice. The aim of the Patient Important Outcomes in Psychiatry (PIO-Psych) Initiative is to develop an overarching, transdiagnostic research-based and consensus-based core outcome set for adult mental health disorders.

Methods and analysis
The development of the PIO-Psych transdiagnostic core outcome set will include three phases: (1) a systematic scoping review of the literature to develop the initial list of outcomes for the Delphi study; (2) a Delphi study in three rounds including people with lived experience of mental health disorders and their relatives, clinicians, researchers and others (administrators, mental healthcare policymakers, philosophers); (3) a hybrid consensus meeting to agree on the final overarching, transdiagnostic core outcome set and corresponding time points of assessment of each outcome.

Ethics and dissemination
Ethical approval is not applicable to this study according to the Research Ethics Committee of the Capital Region of Denmark, as it is not an interventional study. All data will be reported anonymously, and it will not be possible to identify study participants. Results will be disseminated via stakeholder and research networks and peer-reviewed publications.

Trial registration details
The PIO-Psych Initiative was pre-registered with COMET (Core Outcome Measures for Effectiveness Trials) on 17 May 2024 (https://www.comet-initiative.org/Studies/Details/3125).

Objective
To provide insight into how people cope with living with atrial fibrillation (AF) and taking oral anticoagulants (OACs), informing how services and healthcare delivery could be improved to offer the appropriate support patients require, thereby optimising their quality of life and well-being.

Design
A qualitative study employing focus group discussions (FGDs).

Setting
11 primary care units in a socioeconomically deprived area of the Butantan district in São Paulo, Brazil.

Participants
Adults (≥18 years) with AF purposively recruited based on sex, age and socioeconomic status.

Results
Saturation was met with three FGDs comprising seven, five and five participants, respectively. Theme one focused on self-management, where many participants discussed their methods for adhering to dietary restrictions and alternative medications, including plant-based options and specific foods, and how they modified their daily activities to reduce AF complications and symptoms. Theme two was rationality, where participants described three main ways that they cope with taking long-term medication (often warfarin): thinking that it controls their AF symptoms; it is an obligation; it prevents morbidity and premature death. Theme three was attitude and emotions, where participants described their initial reactions of shock and fear after diagnosis and ongoing emotions of sadness and frustration due to required self-management activities and regular blood tests. Theme four was medication regimen, where participants discussed difficulties with polypharmacy, changes to AF medication (particularly from non-vitamin K antagonist OACs (NOACs) to warfarin), side effects from taking warfarin and various methods of medication management.

Conclusions
This study presents three key findings with implications for patient care and support. First, the shock and fear experienced during diagnosis due to a lack of knowledge about AF suggests that improvements in public knowledge about AF are needed. Second, people with additional chronic conditions may need improved care and support, given the concern participants had regarding when and how to take their medications safely. Third, improved access to NOACs may reduce the difficulties, frustrations and concerns participants had regarding warfarin use (eg, diet, dose adjustments, self-management and monthly international normalised ratio tests).

Introduction
In countries with access to the electronic health record (EHR), both patients and healthcare professionals have reported finding errors in the EHR, so-called EHRrors. These can range from simple typos to more serious cases of missing or incorrect health information. Despite their potential detrimental effect, the evidence on EHRrors has not been systematically analysed. It is unknown how common EHRrors are or how they impact patients and healthcare professionals.

Methods and analysis
A mixed systematic review will be carried out to address the research gap. We will search PubMed, Web of Science and CINAHL for studies published since 2000, which report original research data on patient-identified and healthcare professional-identified EHRrors. We will analyse (1) the prevalence of EHRrors, (2) the types of EHRrors and (3) their impact on care. Quantitative and qualitative findings will be synthesised following the Joanna Briggs Institute Framework for Mixed Systematic Reviews. Identified studies will be critically appraised for meta-biases and risk of bias in individual studies. The confidence in the emerging evidence will be further assessed through the Grading of Recommendations Assessment, Development and Evaluation approach. Findings will be contextualised and interpreted involving an international team of patient representatives and practising healthcare professionals.

Ethics and dissemination
The study will not involve collection or analysis of individual patient data; thus, ethical approval is not required. Results will be published in a peer-reviewed publication and further disseminated through scientific events and educational materials.

PROSPERO registration number
CRD42024622849.

Introduction
Referrals for gender-affirming healthcare services have surged in recent decades, presumably driven by increased visibility, acceptance and reduced barriers to care. Despite these advances, transgender and gender-diverse individuals continue to face significant mental health challenges, including elevated rates of anxiety, depression as well as high prevalence of autistic traits. Gender-affirming hormonal treatment (GAHT) has been suggested to improve mental health and quality of life (QoL) among transgender individuals; however, the short- and long-term treatment effects of GAHT are not yet fully understood. Therefore, this study aims to establish a comprehensive cohort of transgender individuals at the Centre for Gender Identity (CGI), Aalborg University Hospital, Denmark, to enhance understanding and treatment outcomes.

Methods and analysis
The Transgender Cohort (TraCK) will recruit participants from February 14, 2024, with recruitment occurring continuously alongside yearly follow-up. This single-centre cohort study will include both retrospective and prospective data collection. Transgender individuals referred to CGI will be invited to participate in the study via the Danish digital mail system called e-Boks. Participants must provide informed consent and complete a baseline questionnaire. Data will be collected from self-reported questionnaires and medical records across multiple specialists. Self-reported questionnaires include WHO-Quality of Life BREF, Eating Disorders Examination Questionnaire, Autism Spectrum Quotient, Transgender Congruence Scale, and Gender Minority Stress and Resilience Measure. Medical records will provide information on demographics, mental health, physical health, and gender-affirming treatment details. Data will be managed using REDCap, ensuring compliance with GDPR and the National Data Protection Act.

Ethics and dissemination
While recognising the potential privacy risks associated with data collection, the study considers these outweighed by the benefits of advancing knowledge on gender diversity and the impacts of gender-affirming care. The North Jutland Region Ethics Committee reviewed the project, determining no formal approval was needed, but it was registered and approved (no. F2024-012) by the North Jutland Region. Findings will be disseminated through peer-reviewed journals, conferences, and accessible reports for participants.

Registration details
This study is registered with the North Jutland Region (no. F2024-012). Recruitment and data collection began on February 14, 2024, and will continue alongside yearly follow-up. Keywords Transgender individuals, transgender and gender-diverse, transgender cohort, transgender health, transgender research, cohort study, gender-affirming care.

The evidence of the heterogeneity of WAS and XLT outcomes could be instrumental to draw updated recommendations for the management of the patients affected by these rare conditions. It would be desirable to expand the tools to estimate the risk of infectious and autoimmune events in patients with XLT and the impact of their treatment, including HSCT over time.

Circulation, Ahead of Print. Alcohol is one of the most commonly consumed substances in the world, exhibiting complex relationships with multiple aspects of cardiovascular health and disease. The majority of the research on the topic is observational and therefore prone to bias and confounding. The available evidence suggests no risk to possible risk reduction when alcohol is consumed in low amounts (such as no more than 1 to 2 drinks a day) in regard to coronary artery disease, stroke, sudden death, and possibly heart failure. The risk associated with consuming 1 to 2 drinks a day on atrial fibrillation remains unknown. More randomized trials of low to moderate alcohol consumption are needed for more definitive conclusions. In stark contrast, heavier alcohol consumption such as binge drinking or consuming on average ≥3 drinks/d is consistently associated with worse outcomes in every cardiovascular disease entity studied. Considering the level of evidence, it remains unknown whether drinking is part of a healthy lifestyle and therefore clinicians should reinforce healthy lifestyle behaviors such as regularly engaging in physical activity, avoiding tobacco use, and maintaining healthy body weight.

Circulation, Volume 151, Issue 23, Page 1667-1685, June 10, 2025. BACKGROUND:Cardiac hypertrophy, as an important pathological change, contributes to heart failure. Recent studies indicate that the mitochondria-associated endoplasmic reticulum membranes (MAMs) play key roles in this pathological process. However, the molecular mechanism remains unclear. This study aims to elucidate the effects and mechanisms of MAM-resident FMO2 (flavin-containing monooxygenase 2) in cardiac hypertrophy and heart failure.METHODS:We performed bulk RNA-sequencing analysis using heart tissue from patients with cardiac hypertrophy and carried out MAM-targeted mass spectrometry analysis using heart tissue from a mouse model of pathological cardiac hypertrophy. In vitro cell culture using neonatal rat cardiomyocytes was used to study how MAMs formation affected cardiomyocyte functions. By generating different genetic mouse models combined with using adeno-associated virus 9 under the cardiac troponin T promoter techniques, we further investigated and confirmed the effects of MAM structure changes on cardiac hypertrophy.RESULTS:We detected an unexpected component of MAMs structure, which was the FMO2, an endoplasmic reticulum–resident protein. FMO2 levels decreased during pathological cardiac hypertrophy. The deletion and overexpression of FMO2 can either worsen or prevent the pathological heart failure progression in vivo, respectively. Our data further demonstrated that FMO2 localizes to MAM structure, where it binds to inositol 1,4,5-trisphosphate type 2 receptor (IP3R2) as a component of the IP3R2–Grp75 (glucose-regulated protein 75)–VDAC1 (voltage-dependent anion channel protein 1) complex, maintaining endoplasmic reticulum–mitochondria contact and regulating mitochondrial Ca2+signaling for bioenergetics. Last, we showed that a synthetic peptide-enhancing endoplasmic reticulum–mitochondria contact promoted Ca2+transfer and prevented pathological cardiac hypertrophy.CONCLUSIONS:Our findings reveal a key role of FMO2 in myocardial hypertrophy and that FMO2 plays a pivotal role in maintaining MAM structure and function, which may represent a novel mechanism and therapeutic target for cardiac hypertrophy and heart failure.

Introduction
Type 1 diabetes is a chronic autoimmune disease that often presents with diabetic ketoacidosis at diagnosis. Since detection of type 1 diabetes risk is possible using genetic risk scores and autoantibody assays, prevention of diabetic ketoacidosis or delayed onset of type 1 diabetes may be possible and may improve outcomes. Several pilot screening programmes for type 1 diabetes risk have emerged worldwide but outcomes measured in these screening programmes are heterogeneous, making it difficult to compare and synthesise findings across studies. To improve the standardisation of outcome reporting and measurement, we aim to develop a patient-oriented core outcome set for studies of type 1 diabetes risk screening.

Methods and analysis
This five-step protocol was developed in alignment with the COS-STAndardised Protocol Statement and the Core Outcome Measures in Effectiveness Trials framework. The five steps will include: (1a) conducting a rapid literature review, (1b) gathering input on candidate outcomes from members of the public, (2) combining literature and public input to prepare a preliminary list of outcomes, (3) conducting Delphi surveys with a range of stakeholders to begin to establish consensus on outcomes, (4) holding a final consensus meeting to establish consensus on outcomes and (5) establishing the outcome measurement instruments for the core outcome set.

Ethics and dissemination
Ethics approval has been provided by The Hospital for Sick Children Research Ethics Board. The core outcome set will be distributed to researchers and clinicians involved in diabetes screening and clinical care, patient and family networks, research funders, journal editors, public health experts, and policymakers. Disseminated materials will be tailored to the various end users in the form of publication through academic journals, policy briefs, conferences, educational webinars, websites and social media.

Objective
To explore primary care patients’ and practitioners’ views and experiences of remote consulting for common mental disorders (CMDs), to optimise their management in primary care.

Design
Qualitative study using in-depth interviews and thematic analysis. A topic guide was used to ensure consistency across interviews. The interviews were audio-recorded, transcribed verbatim and analysed thematically. There was patient and public input throughout.

Setting
Participants were recruited from general practices. Interviews were held by telephone or videocall between March 2023 and October 2023.

Participants
We interviewed 20 practitioners and 21 patients.

Results
Interviewees suggested benefits included convenience, increased anonymity and were easier for those feeling very low or anxious. Challenges included practitioners finding it hard to assess risk, which lengthened consultation duration or led to further contact, increasing practice workload and patients feeling anxious waiting for the practitioner to call. In-person appointments were viewed as important for initial consultations and providing a safe space. Continuity of care and practitioner training were identified as facilitators for telephone consultations, and both patients and practitioners identified training needs around how to deliver mental healthcare remotely.

Conclusions
Practitioners should aim to offer continuity of care and in-person appointments when patients initially seek help. Remote consultations may not be more time or cost-efficient for individuals with CMDs as risk is harder to assess. There is a need to evaluate existing training on delivering remote consultations to identify whether remote mental healthcare is included or should be incorporated in the future.

Objectives
To understand healthcare professionals’ and patients’ views and experiences of septoplasty and medical management (ie, nasal steroid and saline sprays) for nasal obstruction.

Design
Nested qualitative study as part of the Nasal Airway Obstruction Study (NAIROS) trial. We used in-depth interviews to develop a coding framework based on thematic analysis.

Setting
NAIROS was a trial based in the UK from January 2018 to December 2020 that aimed to compare the effectiveness of septoplasty versus medical management.

Participants
We purposively sampled and interviewed 14 healthcare professionals (surgeons, research nurses) and 31 patients involved in the NAIROS trial across 14 UK hospital sites.

Results
In usual practice, surgeons’ decisions regarding treatment for nasal obstruction are based on a complex assessment of patients’ symptoms, history and anatomy. Surgeons viewed septoplasty as a complex although routine operation, which is not guaranteed to improve symptoms of nasal obstruction. Some patients saw septoplasty, intuitively, as a ‘fix’ for a bent septum, whereas others were keen to avoid surgery if possible. Healthcare professionals welcomed the increased use of standard measurements if these were shown to provide a reliable guide to patient outcomes. However, they felt that it was important to retain an element of clinical judgement. Despite generally good outcomes from septoplasty, some patients still felt they had received little to no benefit from the operation. Patients also reported being underprepared for postsurgery recovery. Experiences were more varied with medical management, with some experiencing symptom improvement, but others discontinuing treatment due to difficulty or pain using the sprays, or perceived ineffectiveness. Remembering to use the sprays could be perceived as burdensome, although most patients were able to incorporate this into their daily routines.

Conclusions
Our qualitative study demonstrated varied individual experiences among patients undergoing septoplasty and medical management. Surgeons welcomed more standard measurements to guide decision-making for septoplasty. For patients, better information about treatment mechanisms, treatment delivery and aftercare, and the development of decision support tools would enable shared decision-making and help to provide optimal patient experience of the treatments.

Trial registration number
ISRCTN16168569.

Objectives
Hypertension is one of the silent diseases and is the major cause of many chronic conditions. The treatment services for hypertension and its cardiovascular complications impose high costs on society and the health system. However, in LMCs, there is not enough evidence-based information about the costs of high blood pressure. This study aims to assess the economic burden of hypertension in Iran in 2020.

Design
A prevalence-based cost of illness study.

Setting
Data on hypertension and selected diseases, including their prevalence, incidence, mortality risk and death counts, were sourced from literature reviews, the Global Burden of Disease (GDP) and the Non-Communicable Diseases Research Centre. Cost estimates were derived from health insurance data, surveys, research studies and treatment protocols. Additional data, such as population, employment rates, household activity rates, wage rates and GDP per capita, were obtained from the Statistical Centre of Iran and the World Bank.

Participants and methods
A prevalence-based cost of illness study was used to estimate the economic burden of hypertension. The focus was on the most significant diseases associated with high blood pressure, including coronary heart disease, ischaemic stroke, haemorrhagic stroke and the direct costs of hypertension. Subsequently, the total number of patients was multiplied by the average cost per patient for each disease. To calculate the average cost, inpatient and outpatient, direct non-medical and indirect costs of diseases were estimated and multiplied by a population-attributed fraction of high blood pressure. Direct costs (hospitalisation and outpatient costs and direct non-medical costs) of hypertension were calculated using the bottom-up approach, and the human capital approach was used to calculate indirect costs.

Results
According to the results of the study, the total economic burden of hypertension was $ purchasing power parity (PPP) 12 848.22 million, of which the share of direct medical, non-medical and indirect costs of hypertension were $ PPP 7245.13 million (56.4%), $ PPP 1173.42 million (9.1%) and $ PPP 4429.68 million (34.5%), respectively. The total economic burden of high blood pressure was equal to 23% of the total economic burden of four chronic diseases.

Conclusion
The economic burden of high blood pressure in the country is very high and significant, and it was equivalent to about 1% of the country’s gross domestic product in 2020, which shows the necessity of preventive interventions.