Thalamic neural activity and epileptic network analysis using stereoelectroencephalography: a prospective study protocol

Introduction
Epilepsy is a prevalent chronic neurological disorder, with approximately one-third of patients experiencing intractable epilepsy, often necessitating surgical intervention. Deep brain stimulation (DBS) of the thalamus has been introduced as a palliative surgical option for seizure control; however, its precise mechanisms remain largely unclear. The thalamus plays a crucial role in coordinating neural networks, both in normal brain function and the propagation of epileptic activity. This study aims to investigate the involvement of the thalamus in epilepsy networks using stereoelectroencephalography (SEEG) to monitor thalamic activity during epileptic seizures in patients with drug-resistant epilepsy.

Methods and analysis
This single-arm, non-randomised, prospective, exploratory study will be conducted at Nagoya University Hospital, involving 10 patients undergoing SEEG for presurgical evaluation of drug-resistant epilepsy. Participants must be 18 years or older, have normal cognitive function and provide informed consent. Between 7 and 14 SEEG electrodes, including 2 in the bilateral thalamus, will be implanted in key thalamic nuclei (anterior, dorsomedial, centromedian and pulvinar) using a robotic system. The primary outcome focuses on electroencephalographic findings from the thalamus, emphasising waveform and frequency changes around seizures. Secondary outcomes include postoperative seizure frequency, changes in cognitive function and neuroimaging results. SEEG data will be recorded continuously for 1–2 weeks to capture both ictal and interictal activity. Data analysis will employ t-tests to compare ictal and interictal periods, with p values

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Protocol for the development of a transdiagnostic core outcome set for mental health disorders in adults: the Patient Important Outcomes in Psychiatry (PIO-Psych) Initiative

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).

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Exploring perspectives regarding death cafes for people experiencing homelessness: a qualitative study

Background
People experiencing homelessness (PEH) often die at a younger age than the general population. Advanced ill-health often occurs late in its trajectory (if at all), leaving many PEH to die without adequate support from hospital-based, hospice-based or community-based palliative care services. Despite the high rate of bereavement and exposure to death among PEH, there are rarely opportunities for them to reflect on their experiences, thoughts and preferences around death or receive bereavement support. Death cafés are a global social franchise, providing a space for people to participate in an open group discussion about death, dying and bereavement. They are free to attend and unstructured but facilitated.

Objectives
To explore the perspectives of PEH and the professionals that support them with regards to the potential acceptability, benefits and challenges of death cafes.

Methods
A qualitative study comprising of interviews with nine homelessness and/or palliative care professionals with experience of running death cafés for, or supporting PEH in other ways, and two focus groups with nine people with lived experience of homelessness. The research was co-produced with a lived experience co-researcher forming a core part of the research team. Reflexive thematic analysis was utilised to develop themes.

Results
Five themes were developed to highlight the perspectives and experiences of death cafés for PEH: choice; expertise in facilitation: recognising risk and the unstructured nature; promoting safety against potential risk; potential benefits and potential practical considerations. Themes highlight the need for a trauma-informed approach. Death cafés could be impactful, where done well, but they are not without risk.

Conclusions
Death cafés for PEH pose risks that require comprehensive consideration and trauma-informed, expert facilitation. However, this research highlighted that a low-pressure space to explore thoughts around death, dying and bereavement is currently an unmet need within this population.

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Balancing burden and bond: challenges and motivations of family caregivers of patients with end-stage liver disease in Northern Ghana–a qualitative inquiry

Objective
This study explored the burdens and motivations of family caregivers (FCs) for patients with end-stage liver disease (ESLD) in a tertiary hospital in Ghana.

Design
A qualitative exploratory, descriptive approach with a purposive sampling technique was adopted. Data were collected through face-to-face semi-structured interviews. The interviews were audio-recorded, transcribed verbatim and analysed using content analysis.

Setting
Participants were recruited from a tertiary hospital in the Northern Region of Ghana.

Participants
15 FCs aged between 18 and 50 years caring for patients with ESLD were recruited.

Results
The study’s findings revealed that FCs of individuals with ESLD encountered considerable challenges, including sleep deprivation, physical exhaustion, family conflicts, financial difficulties and social restrictions. These difficulties contributed to a sense of being overwhelmed as caregivers strived to fulfil their duties. Family bonds, reciprocal relationships and religious obligations were the motivation/driving force for FCs caring for relatives with ESLD.

Conclusion
Integrating palliative care services in tertiary health facilities will reduce the burdens FCs of patients with ESLD face. Relevant stakeholders in the health sector need to develop culturally sensitive interventions to support FCs caring for patients with ESLD in Ghana.

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Rectal diclofenac versus indomethacin for prevention of post-ERCP pancreatitis (DIPPP): a multicentre, double-blind, randomised, controlled trial

Background
Recent meta-analyses suggested diclofenac may be superior to indomethacin in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). The aim of our study was to compare the efficacy of 100 mg rectal indomethacin versus diclofenac on PEP incidences.

Design
This multicentre, double-blinded, randomised controlled trial was conducted in nine tertiary centres in China. Patients with low and high risk for PEP and native papilla were randomly allocated (1:1) to receive 100 mg diclofenac or 100 mg indomethacin rectally before ERCP. The primary outcome was the occurrence of PEP defined by the Cotton consensus. The intention-to-treat principle was conducted for the analysis.

Results
The trial was terminated early for futility after the predetermined first interim analysis. Between June 2023 and May 2024, 1204 patients were randomised into the diclofenac group (n=600) or indomethacin group (n=604). Baseline characteristics were balanced. The primary outcome occurred in 53 patients (8.8%) of 600 patients allocated to the diclofenac group and 37 patients (6.1%) of 604 patients allocated to the indomethacin group (relative risk 1.44; 95% CI 0.96 to 2.16, p=0.074). PEP occurred in 35 (14.2%) of 247 high-risk patients in the diclofenac group and 26 (9.8%) of 266 high-risk patients in the indomethacin group (p=0.124). PEP incidences were also comparable in low-risk patients between the two groups (18/353 (5.1%) vs 11/338 (3.3%), p=0.227). Other ERCP-related complications did not differ between the two groups.

Conclusion
Pre-procedure 100 mg rectal diclofenac was not superior to the same dose of rectal indomethacin regarding preventing PEP. These findings supported current clinical practice guidelines of 100 mg indomethacin or diclofenac for PEP prophylaxis in patients without contraindications.

Trial registration number
ClinicalTrials.gov (NCT05947461).

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Experiences of stigma and access to care among long COVID patients: a qualitative study in a multi-ethnic population in the Netherlands

Objective
This study explored the experience of stigma and access to healthcare by persons with long COVID from the majority Dutch and two ethnic minority populations (Turkish and Moroccan) living in the Netherlands.

Design
This was a cross-sectional qualitative study that employed inductive and deductive thematic approaches to data analysis using MAXQDA.

Setting and participants
Between October 2022 and January 2023, 23 semi-structured interviews were conducted with participants of Dutch, Moroccan and Turkish ethnic origins with long COVID living in the Netherlands. Participants were men and women aged 30 years and above.

Results
Guided by the concepts of stigma and candidacy, the findings are structured according to the broader themes of stigma and access to care. The findings show that people with long COVID suffer self and public stigma resulting from the debilitating illness and symptoms. Especially among Turkish and Moroccan ethnic minority participants, strong filial obligations and gendered expectations of responsibility and support within their communities further worsen self-stigma. This experience of stigma persisted within healthcare where lack of information and appropriate care pathways led to feelings of frustration and abandonment, especially for participants with pre-existing health conditions which further complicate candidacy. Under the access to healthcare theme, the findings show multiple challenges in accessing healthcare for long COVID due to several multifaceted factors related to the various stages of candidacy which impacted access to care. Particularly for Turkish and Moroccan ethnic minority participants, additional challenges resulting from limited access to information, pre-existing structural challenges and experience of stereotyping based on ethnicity or assumed migrant identity by health professionals further complicate access to health information and long COVID care.

Conclusions
The findings call for urgent attention and research to identify and coordinate healthcare for long COVID. There is also a need for accessible, informative and tailored support systems to facilitate patients’ access to information and care pathways for long COVID. Providing tailored information and support, addressing the various barriers that hinder optimal operating conditions in healthcare and leveraging on social networks is crucial for addressing stigma and facilitating candidacy for persons with long COVID towards improving access to care.

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Cohort profile: characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19 – providing the evidence base for health care services (CONVALESCENCE) in the UK

Purpose
The pathogenesis of the long-lasting symptoms which can follow an infection with the SARS-CoV-2 virus (‘long covid’) is not fully understood. The ‘COroNaVirus post-Acute Long-term EffectS: Constructing an evidENCE base’ (CONVALESCENCE) study was established as part of the Longitudinal Health and Wellbeing COVID-19 UK National Core Study. We performed a deep phenotyping case-control study nested within two cohorts (the Avon Longitudinal Study of Parents and Children and TwinsUK) as part of CONVALESCENCE.

Participants
From September 2021 to May 2023, 349 participants attended the CONVALESCENCE deep phenotyping clinic at University College London. Four categories of participants were recruited: cases of long covid (long covid(+)/SARS-CoV-2(+)), alongside three control groups: those with neither long covid symptoms nor evidence of prior COVID-19 (long covid(-)/SARS-CoV-2(-); control group 1), those who self-reported COVID-19 and had evidence of SARS-CoV-2 infection, but did not report long covid (long covid(-)/SARS-CoV-2(+); control group 2) and those who self-reported persistent symptoms attributable to COVID-19 but no evidence of SARS-CoV-2 infection (long covid(+)/SARS-CoV-2(-); control group 3). Remote wearable measurements were performed up until February 2024.

Findings to date
This cohort profile describes the baseline characteristics of the CONVALESCENCE cohort. Of the 349 participants, 141 (53±15 years old; 21 (15%) men) were cases, 89 (55±16 years old; 11 (12%) men) were in control group 1, 75 (49±15 years old; 25 (33%) men) were in control group 2 and 44 (55±16 years old; 9 (21%) men) were in control group 3.

Future plans
The study aims to use a multiorgan score calculated as the cumulative total for each of nine domains (ie, lung, vascular, heart, kidney, brain, autonomic function, muscle strength, exercise capacity and physical performance). The availability of data preceding acute COVID-19 infection in cohorts may help identify the consequences of infection independent of pre-existing subclinical disease and also provide evidence of determinants that influence the development of long covid.

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Understanding peer support among healthcare assistants delivering hospice care at home: a protocol for a realist review

Introduction
Globally, the demand for community palliative care, delivered within the home setting, is rising. Hospice support workers, also referred to as healthcare assistants, play a crucial role in providing this care, but evidence indicates they face challenges relating to inadequate training, isolation and emotional labour. This realist review aims to understand how peer support interventions can support healthcare assistants in delivering hospice care at home.

Methods and analysis
The realist review will follow a five-step process to explore the research question: (1) locating existing initial programme theories, (2) searching for evidence, (3) selecting and appraising evidence, (4) extracting and organising data and (5) synthesising evidence and drawing conclusions. Comprehensive searches of academic databases (CINAHL, MEDLINE, AMED, Scopus) and grey literature sources will be conducted between November and December 2024, with no restrictions on publication date applied. Search strategies will be iteratively refined, with evidence selected based on relevance and rigour. Data will be extracted and coded using a realist logic model of analysis. The review will develop an explanatory programme theory for peer-to-peer interventions which would identify what, how, for whom, why and in what circumstances peer-to-peer interventions may support delivery of hospice care at home. It will explore the contexts, mechanisms and outcomes of these interventions using context-mechanism-outcome configurations.

Ethics and dissemination
Ethical approval is not required as the review involves no primary data collection. This review aims to clarify research gaps, inform next stages of a wider study, policy and practice. Reporting of the findings will adhere to RAMESES publication standards for realist syntheses, ensuring transparency and rigour in reporting. Results will be disseminated through peer-reviewed publications, conference presentations and other strategies identified by the stakeholder group.

PROSPERO registration number
CRD42024606133.

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Protocol for a global menopause priority setting partnership

Introduction
All those born with functioning ovaries will eventually experience menopause, and many will be symptomatic. However, significant gaps in the evidence base for menopause care remain. This National Institute for Health and Care Research James Lind Alliance Menopause Priority Setting Partnership (MAPS) will engage with clinicians and those with lived experience globally to determine the leading priorities for future menopause research.

Methods and analysis
MAPS will follow the established James Lind Alliance methodology which has already resulted in over 100 ‘top 10’ research priorities across health domains. It will be led by a steering group comprised of clinicians and lived experience members. Leveraging the networks of steering group members and partner organisations, the priority setting partnership will identify evidence uncertainties using an online survey. Evidence checking will be undertaken to determine which questions have already been answered. Prioritisation will be done in two stages, initially by online survey and then at a face-to-face workshop.

Ethics and dissemination
Ethical approval was not required. The final top 10 priorities for menopause, as ranked by stakeholders at the final consensus workshop, will be disseminated in the relevant peer-reviewed journals. A final report will be available on the MAPS and James Lind Alliance websites. The leading priorities will inform the future global research agenda for menopause.

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Burden of Cardiovascular Outcomes After SARS-CoV-2 Infection in South Korea and Japan: A Binational Population-Based Cohort Study

Circulation, Ahead of Print. BACKGROUND:Despite the significant global impact of the COVID-19 pandemic, limited studies have investigated the long-term cardiovascular sequelae of SARS-CoV-2 infection, particularly among Asian populations. This large-scale, population-based binational cohort study with long-term follow-up aimed to investigate the association between SARS-CoV-2 infection and the risk of cardiovascular events.METHODS:We used binational, large-scale, and population-based cohorts, including a Korean nationwide cohort (K-COV-N; discovery cohort; n=18 989 129) and a Japanese nationwide cohort (Japan Medical Data Center; validation cohort; n=12 218 680). Individuals aged 20 years or older were included from January 1, 2020, to December 31, 2022. We assessed the long-term risk of incident cardiovascular outcomes after SARS-CoV-2 infection. The primary outcome was the risk of cardiovascular diseases based onInternational Classification of Diseases, Tenth Revisioncode diagnosis. After propensity score–based overlap weighting, Cox proportional hazard models were used to estimate adjusted hazard ratios for cardiovascular outcomes. We assessed the time attenuation effect of cardiovascular outcomes after SARS-CoV-2 infection. Multiple subgroup analyses were conducted by 16 cardiovascular outcomes, COVID-19 severity, vaccination, and SARS-CoV-2 strain.RESULTS:In the overlap-weighted discovery cohort, 7 960 357 individuals were included (mean age, 48.52 years [SD, 9.33]; men, 4 283 878 [53.82%]). SARS-CoV-2 infection was associated with a long-term increased risk of overall cardiovascular outcomes (adjusted hazard ratio, 1.62 [95% CI, 1.60–1.64]), particularly ischemic heart disease (1.81 [95% CI, 1.77–1.84]), heart failure (1.79 [95% CI, 1.73–1.85]), cerebrovascular disorders (1.65 [95% CI, 1.60–1.69]), major adverse cardiovascular events (1.65 [95% CI, 1.60–1.70]), inflammatory heart diseases (1.53 [95% CI, 1.31–1.80]), dysrhythmia (1.44 [95% CI, 1.42–1.46]), and thrombotic disorders (1.42 [95% CI, 1.35–1.48]). The increased risk persisted up to 18 months, with the highest association observed for 1 to 6 months after infection. The risk of cardiovascular diseases was pronounced with COVID-19 severity; however, it decreased with the administration of complete vaccination and subsequent booster doses. A similar risk of cardiovascular outcomes existed across every SARS-CoV-2 era (pre-delta, delta, and omicron). Similar patterns were observed in the validation cohort. The absolute risk of cardiovascular disease events after SARS-CoV-2 infection remained remarkably low (2.12% versus 1.31% in the noninfected population), particularly stroke (0.24% versus 0.13%) and ischemic heart disease (0.73% versus 0.39%).CONCLUSIONS:This binational study observed associations between SARS-CoV-2 infection and cardiovascular events during extended follow-up across viral eras. Complete vaccination was linked to lower cardiovascular events. However, the absolute risk of cardiovascular disease events after SARS-CoV-2 infection remained remarkably low, particularly for stroke and ischemic heart disease. Although these findings suggest ongoing vigilance and preventive measures remain crucial, they should be interpreted within the context of these low absolute risks when considering long-term cardiovascular complications.

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Attitudes towards euthanasia and assisted suicide: a cross-sectional study among physicians in Estonia

Objective
This study aimed to analyse the attitudes of physicians working in Estonia towards the legalisation of euthanasia and assisted suicide, their willingness to perform these practices and the association of these factors with a range of physician characteristics.

Design
Cross-sectional study design using a web-based anonymous questionnaire comprising 31 questions or statements.

Setting
Estonia, April–October 2022; data collection via a web-based survey of physicians.

Participants
526 physicians (74% female, 49% under 40 years old).

Primary and secondary outcome measures
The primary outcome was the attitudes of Estonian physicians towards the legalisation of euthanasia and assisted suicide. Secondary outcomes included their self-reported willingness to personally perform euthanasia and their willingness to personally assist in suicide.

Results
Most of the participants (73%) agreed that euthanasia and assisted suicide should be legal in Estonia. Non-religious physicians were significantly more likely to support both (OR 8.0; 95% CI: 3.8, 16.8 for euthanasia; OR 9.7; 95% CI: 4.7, 20.2 for assisted suicide). Physicians who attended palliative care courses were less likely to support euthanasia (OR 0.3; 95% CI: 0.1, 0.8). Over half had not participated in any specialised palliative medicine courses.

Conclusions
This research indicates that the Estonian physician community demonstrates a predominantly accepting view of the legalisation of euthanasia and assisted suicide.

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