Cognitive deficits in treatment-resistant depression: protocol for a systematic review and meta-analysis

Introduction
Major depressive disorder (MDD) is a major global healthcare challenge. This is, in part, due to the lack of treatment response and chronic course of MDD. Such a course of illness is often termed treatment-resistant depression (TRD) and is seen in over one-third of people with MDD. Reasons for treatment resistance are not well established, nor is the definition of TRD. Duration and severity of depression, however, are associated with TRD and are also associated with cognitive deficits. Thus, TRD could be particularly prone to cognitive deficits and at heightened risk for neuroprogression. While the cognitive profile of MDD has been investigated in several systematic reviews, no systematic review of cognition in TRD exists to date. The present study will fill this gap in the literature. It is expected that TRD will show more severe cognitive deficits than generally reported in MDD and deficits in all cognitive functions are expected.

Methods and Analysis
A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be performed of the databases Embase, Pubmed/MEDLINE, PsychINFO and Cochrane including peer-reviewed studies on humans using standardised cognitive tests. Pilot searching was performed in January 2025 and the full search will be commenced in June 2025, with additional searches following completion. Where sufficient data are reported, a meta-analysis comparing deficits in TRD with MDD and healthy control participants will be performed; alternatively, effects based on norms will be calculated. Meta-regression, subgroup and sensitivity analyses will be conducted to explore moderators that are sufficiently reported in the literature. The quality of studies will be assessed by the Newcastle-Ottawa Scale.

Ethics and dissemination
Ethical approval is not necessary to perform the study, and results will be presented at a suitable conference and published in a peer-reviewed journal.

Prospero registration number
CRD42024538898.

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Triangular perspectives of healthcare providers, patients and their families on ICU palliative care: a protocol for a systematic review of qualitative studies

Introduction
In the intensive care unit (ICU), palliative care encounters obstacles such as decision conflicts, psychological stress and cultural differences among patients, families and healthcare providers. The well-being and the care quality of patients are influenced by these factors. The highly technical and curative-focused environment of the ICU presents a challenge for palliative care without appropriate integration. Certainly, it is imperative to comprehend these issues and devise strategies to reconcile curative and palliative needs. This paper employs qualitative metaintegration to appraise the experiences and perspectives of palliative care in the ICU, emphasising its outcomes, barriers and the necessity of balanced care and treatment.

Methods and analysis
This study conducted a comprehensive search of both the published and unpublished literature (such as grey literature) from a variety of databases, concerning PubMed, Google Scholar, Cochrane Library, CINAHL, Web of Science, Embase, Scopus, PsycINFO, CNKI, Wanfang, CBM and VIP, up to 10 July 2024. The articles will be retrieved and incorporated into EndNote X9 to facilitate organisation. Two independent researchers will evaluate the studies using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research, and a third researcher will resolve all discrepancies. Data extraction and results synthesis will be performed independently based on the JBI qualitative data extraction tool. Finally, the ConQual method will be employed to estimate the calibre of the compiled results.

Ethics and dissemination
The systematic review was conducted without the necessity of obtaining ethical clearance from a research committee, as it analysed previously published studies that did not contain any personal identifying information of participants. The review’s findings were presented to key stakeholders and submitted for consideration in peer-reviewed journals.

PROSPERO registration number
CRD42024571594.

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Mis- and disinformation and perceptions of healthcare policy among Latinos in the USA: protocol for a multi-method social media sentiment analysis study

Introduction
It is unclear how mis- and disinformation regarding healthcare policy changes propagate throughout Latino communities via social media. This may lead to chilling effects that dissuade eligible individuals from enrolling in critical safety net programmes such as Medicaid. This study will examine pathways and mechanisms by which sentiment in response to mis- and disinformation regarding healthcare policies on social media differentially impact health disparity populations, thus supporting the design of tailored social media interventions to mitigate this.

Methods and analysis
We will search social media from X/Twitter, Facebook/Instagram and Reddit for keywords relating to health benefit programmes. Demographic, geographical location and other characteristics of users will be used to stratify social media data. Posts will be classified as fake-news-related or fact-related based on curated lists of fake-news-related websites. The number, temporal dissemination and positive or negative sentiment in reacting to posts and threads will be examined using the Python-based Valence Aware Dictionary and sEntiment Reasoner (VADER). Using a crowd-sourcing methodology, a novel Spanish-language VADER (S-VADER) will be created to rate sentiment to social media among Spanish-speaking Latinos. With the proposed approach, we will explore reactions to the dissemination of fake-news- or fact-related social media tweets and posts and their sources. Analyses of social media posts in response to healthcare-related policies will provide insights into fears faced by Latinos and Spanish speakers, as well as positive or negative perceptions relating to the policy over time among social media users.

Ethics and dissemination
Our study protocol was approved by the University of California, Los Angeles IRB (IRB#23–0 01 123). Results from this study will be disseminated in peer-reviewed journals and conference presentations, and S-VADER will be disseminated to public repositories such as GitHub.

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Somatostatin analogue continuation upon progression in patients with gastroenteropancreatic neuroendocrine tumour (SAUNA trial): a randomised controlled trial protocol

Introduction
Gastroenteropancreatic neuroendocrine tumours (GEP NET) are malignant neoplasms that impact survival. Somatostatin analogues (SSA) are used for treating hormonal symptoms caused by GEP NET and have antiproliferative effects. They are used as first-line therapy in patients with advanced GEP NET, but disease control is limited to a median progression-free survival (mPFS) of 14–32 months. Second-line treatment options include targeted therapy (everolimus or sunitinib), or peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. In patients suffering from a NET-related hormonal syndrome, SSA is generally continued life-long. However, there is no consensus on whether it is beneficial to continue SSA in non-functional NET upon disease progression. Due to the ongoing activity of the somatostatin receptor pathway in GEP NET progressing on first-line SSA, we hypothesise that SSA have an added efficacy in second-line therapy.

Methods and analysis
The SAUNA trial is an international, multicentre, open-label, randomised, controlled, pragmatic clinical trial. 270 patients with advanced, non-functional GEP NET and progression under first-line SSA will be included in substudy 1 (PRRT; n=142) or substudy 2 (targeted therapy (everolimus/sunitinib); n=128) per investigator’s choice of second-line therapy and will be randomised (1:1) per substudy between SSA continuation or SSA withdrawal arms. Co-primary endpoints are the difference in progression-free survival (PFS) according to the RECIST (Response Evaluation Criteria In Solid Tumours) V.1.1 criteria and difference in time to deterioration (TTD) in quality of life (QoL) per substudy after initiating second-line therapy with or without SSA. Secondary endpoints include the PFS rate at 18 months, the difference in pooled PFS and TTD combining both substudies, overall survival, response rates, QoL, costs, cost-effectiveness and toxicity. The study design was developed in cooperation with the Belgium and Dutch patient organisations.

Ethics and dissemination
The study has been approved on 31 May 2023 by the Ethical Committees and Regulatory Authorities of the concerned member states (EU CT number 2022-502703-30-00). Both the trial management group and the steering committee will oversee good governance of this trial. Results of the study will be published in peer-reviewed international journals and presented at international conferences.

Trial registration number
NCT05701241.

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[Articles] Evaluation of health impacts of a disability-inclusive graduation programme among ultra-poor people with disabilities in Uganda: secondary analysis of a cluster randomized trial

This first randomized evaluation of a disability-inclusive graduation programme demonstrates that while economic empowerment alone may not reduce overall illness prevalence among people with disabilities, it can progressively improve healthcare access over time. The temporal evolution of effects and emerging sex-differentiated impacts highlight the need for sustained support and gender-sensitive approaches in future disability-inclusive poverty reduction programmes, with additional health-specific components to achieve broader improvements in health outcomes.

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Insurance type and risk of dementia diagnosis after traumatic brain injury: a study of 267 473 US civilians from 2000 to 2022

Objectives
To evaluate how insurance influences the risk of a dementia diagnosis among a large, diverse cohort of US civilian adults with traumatic brain injury (TBI) over a 22-year period.

Design
This is a retrospective cohort study involving individuals diagnosed with TBI.

Setting
The study used the Merative MarketScan Research Database, specifically drawing from the Commercial Claims and Encounters, Medicare Supplemental and Medicaid databases, from 2000 to 2022 in the USA. These databases provide comprehensive insights into healthcare services received by enrollees, including inpatient and outpatient services, outpatient prescription claims, clinical utilisation records and healthcare expenditures.

Participants
267 473 adults aged 55 and older who were diagnosed with a TBI between 1 January 2000 and 31 December 2022. Individuals with unknown TBI severity and dementia claims 2 years preceding TBI were excluded. TBI and dementia diagnoses were identified using International Classification of Disease 9th and 10th editions codes from inpatient and outpatient admission records.

Interventions
None.

Primary and secondary outcome measures
We compared the incidence of all-cause dementia across different insurance types to assess potential disparities in diagnosis following TBI. Cox proportional hazards models, with age as the time scale, were used to study the association between insurance type and dementia diagnosis following a TBI. Models were adjusted for key demographic variables, medical comorbidities and psychiatric conditions to account for potential confounding.

Results
Of the 267 473 individuals with TBI, 12.7% were diagnosed with dementia over a mean follow-up period of 40 months (SD of 42 months). Dementia incidence differed significantly by insurance type, with 18.2% for Medicaid recipients, 17.3% for Medicare beneficiaries and only 2.3% among individuals with commercial insurance. The adjusted HR for dementia was notably higher among individuals enrolled on Medicaid (HR 2.9, 95% CI: 2.8 to 3.1) and Medicare (HR 2.1, 95% CI: 2.0 to 2.2), when compared with those with commercial insurance.

Conclusions
Individuals with TBI covered by Medicaid and Medicare are significantly more likely to be diagnosed with dementia, with a 2.9-fold and 2.1-fold increase risk, respectively, compared with those with commercial insurance. Addressing insurance-related disparities in dementia diagnosis is crucial for building a more equitable healthcare system. It is essential that individuals with TBI cases, regardless of their insurance type, have access to comprehensive care and preventive interventions to achieve the best possible long-term outcomes.

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Epistemologies, methodologies and theories used in qualitative Global North health and social care research: a scoping review protocol

Introduction
In qualitative research, there are different approaches to defining and engaging with social reality. Epistemology, as the study of knowledge and knowledge creation, influences the methodologies and theories used by researchers. A growing literature questions the universality of Western-centric and Global North research methodologies and theories and highlights their Western epistemological roots. While Western frameworks are appropriate for Western contexts, it is a fallacy to assume that they represent global realities, thereby marginalising Global South knowledge systems. Thus, the aim of this scoping review is to analyse the underlying epistemologies, methodologies or theories that are evident in qualitative research conducted by researchers from the Global North in their research on, for or with people from the Global South.

Methods and analysis
The review will be conducted using the Joanna Briggs Institute framework for scoping reviews. A search strategy will be developed to identify published and unpublished literature in CINAHL, Embase, Google Scholar, MEDLINE, ProQuest, PsycINFO and Web of Science. All potential papers will be exported to the reference manager Zotero, and the results will be uploaded to Rayyan. Studies are selected using a three-step process and documented using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart. The abstracted studies will then be collated using the PAGER framework to identify the patterns, advances, gaps, evidence and recommendations that help to understand the review question.

Ethics and dissemination
As this is a secondary analysis, our research does not require ethical approval, but we will scrutinise all included studies for inclusion of an ethical approval statement. We intend to share our findings through peer-reviewed international journals and presentations at conferences, as well as collaborating with colleagues in related fields.

Study registration
The protocol for this scoping review has been registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/5BUZX).

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Consensus-based development and practice testing of a generic quality indicator set for parenteral medication administration at home: a RAND appropriateness method study

Objectives
Due to nursing shortages, an ageing population and increasing care demand, there is a growing interest in parenteral medication administration at home (PMAaH), comprising the administration of parenteral medication in the home situation of patients. The operational design of such PMAaH care pathways is complex, resulting in many variations of adoptions, showing a need for a quality framework. Although quality indicators (QIs) have been proposed to monitor the quality of specific care pathways, a generic quality framework for all types of PMAaH is lacking. Therefore, this study proposes a generic quality set for PMAaH, which includes structure and process QIs, to benchmark and redesign PMAaH care pathways to ensure high quality.

Design
A generic QI set was developed for PMAaH using a systematic RAND appropriateness method adapted at the third phase. This method consisted of a scoping review to identify indicators, an expert panel rating phase including an online questionnaire and subsequent panel meeting to assess the appropriateness of the indicators and a retrospective practice testing to evaluate the feasibility, clarity and measurability of the indicators. After the practice testing, which consisted of an online questionnaire where experts could indicate the implementation state of all indicators in their hospital, a third expert panel adjusted the set to increase the likelihood of implementation in practice.

Setting
The experts, all healthcare professionals involved in PMAaH processes, were recruited using the snowball sampling technique from three large Dutch, teaching hospitals. Subsequently, a practice testing by self-assessment was conducted in seven large Dutch teaching hospitals.

Participants
17 and seven healthcare professionals with diverse backgrounds participated in the online questionnaire and panel meeting, respectively.

Results
The scoping review resulted in 36 QIs for PMAaH. After two expert panel rating rounds (online questionnaire and panel meeting), two indicators were removed: a QI related to travel distance policy since it was irrelevant and redundant, and a QI stating that a clinician should take the lead in a PMAaH-team, which was deemed too restrictive. After the practice testing, two QIs were removed: a QI related to clinical response documentation, which was unclear for the practice testing respondents and already covered by other QIs, and a QI related to survival documentation, which was deemed infeasible and undesirable to measure this differently than other patients by the third expert panel.
The final set consists of 32 indicators (of which 15 were structure indicators and 17 were process indicators). The final set predominately includes QIs that are aimed at patient safety but also QIs focusing on the working conditions of the healthcare workers. 17.6% of the QIs are currently fully implemented in general in all seven hospitals. The practice testing revealed that operational QIs are more frequently implemented in practice than systemic QIs and that a structured quality assurance programme is needed in the hospitals.

Conclusions
This study proposes a generic quality set for PMAaH that hospitals can use to redesign and benchmark PMAaH care pathways to assure high quality. The practice testing confirmed that there is a need for this structured quality set.

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Improving Delirium Identification in Hospitalized Older Adults

Delirium affects one-third of hospitalized older adults and is associated with prolonged length of stay, institutional discharge, long-term functional and cognitive decline, Alzheimer disease and related dementias (AD/ADRD), and death. Moreover, the costs of delirium exceed $182 billion annually in the US alone. Despite these compelling data, accurate identification of delirium remains challenging, with more than half of delirium going unrecognized in routine care. While delirium prevention has advanced substantially, delirium treatment, which relies on early and accurate identification, lags. More than 40 tools are available for delirium assessment, ranging from short structured screens to in-depth reference standards. Evidence on how to implement these tools to improve delirium identification at the bedside, including which tool to use, who should administer it, how often, and how to educate and engage the care team, remains limited.

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Disparities in Trends of Gastroenteropancreatic Neuroendocrine Tumor Incidence

To the Editor Accurate identification of significant sex and age disparities in the trends of gastroenteropancreatic neuroendocrine tumor (GEP-NETs) incidence are crucial for informing public health intervention and policymaking. A recent analysis by Abboud and colleagues reported an increasing incidence rate of GEP-NETs from 2001 to 2020, highlighting a higher rate of increase among female individuals (average annual percentage change [AAPC], 3.8) compared with male individuals (AAPC, 3.6), and among younger adults (AAPC, 5.2) compared with elderly individuals (AAPC, 2.7). However, it remains unclear whether the observed sex and age disparities in the increasing gastroenteropancreatic neuroendocrine tumor incidence are statistically significant. To address this, we revisited and scrutinized the AAPC data in their Table and found no significant difference in the increasing GEP-NETs incidence between sex. This should be clearly clarified to avoid potential misinterpretations by readers.

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Challenges in Shared Care Research in Hematopoietic Cell Transplantation—Reply

In Reply We appreciate the interest from Chan et al in our study. We agree that our work has some of the limitations that they underscore, most of which have been presented and discussed in the article text. Importantly, shared care is an applied care delivery strategy. For those who were randomized to shared care, they had a local team that would begin to follow up with them once engraftment occurred with the plan to alternate follow-up visits with the Dana-Farber Cancer Institute team; however, sometimes they might be seen a bit more often locally (eg, if inclement weather made it difficult to get into Boston, Massachusetts) or at the Dana-Farber Cancer Institute (eg, if they needed follow-up with another Dana-Farber specialty consultant). Although this is admittedly a limitation in terms of absolute standardization of shared care, when we held our preprotocol focus groups with transplant patients and clinicians, they were clear that, given the complexity of posttransplant care, it would never be possible to mandate that patients in the shared care arm rigidly share care every other week. Indeed, we argue this is also a potential strength of our analysis, because shared care, when applied to the routine clinical care delivery setting will also need to have similar flexibility.

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FDA Accepts Application for Oral Version of Wegovy

The US Food and Drug Administration (FDA) recently accepted a new drug application for oral semaglutide. If approved, it would be the first oral glucagon-like peptide-1 (GLP-1) receptor agonist authorized for long-term weight management. The 25-mg semaglutide pill would be marketed as Wegovy, the same name used for Novo Nordisk’s FDA-approved 2.4-mg semaglutide injection.

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Objectivity in Medicine vs Inference in Poetry

A compelling aspect of both medicine and poetry is how each incites us to articulate our perceptions through specific applications of expressive language. In medicine, words are firmly grounded upon what we directly observe; assumptions are discouraged, for concern that unconscious biases might lead to erroneous conclusions. In poetry, on the other hand, what we see is often just a touchstone for what we can infer, our imaginations unbounded by an idiom that senses as much as it describes. These two modes of comprehending are instructively contrasted in “The Morning After the Election.” We are at first dropped into a narrative about a father and a daughter, reckoning momentarily that the daughter “who had once been his son” and now living far away has been rejected by her family—until the poetically appreciated detail of “the mustache obscuring his lip quivered” as he describes her new imperilment leads us to a deeper inference instead that he must accept and love her. Additional surprising implications that further test objectivity follow, from the reference to another “perfect” son whose death during childbirth ended the patient’s marriage, which underscores how the speaker may have wrongly construed that the transgender child caused familial strife, to the oversimplified and also partly true (yet in retrospect not entirely so, and thus all the more poignant) reason for the patient’s clinic visit as solely “because his blood pressure is high.” Poetry, by transcending the ostensible and harkening to the intuited, allows us to more fully grasp the complexities of our patients’ experiences.

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