-
BMJ Paediatrics Open May 2024In paediatric oncology, 'breaking bad news'-BBN-like cancer diagnosis is perceived as particularly challenging. Enabling a trialogue between children with their...
INTRODUCTION
In paediatric oncology, 'breaking bad news'-BBN-like cancer diagnosis is perceived as particularly challenging. Enabling a trialogue between children with their relatives and health professionals requires profound communication skills. Lacking the skills, experience or adequate support tools might result in negative consequences for both paediatric oncologists as BBN transmitters and BBN receivers as children with cancer and their relatives.In contrast to oncology for adults, multiperspective studies that explore BBN experience and specific support needs are rare, especially in Germany. Systematically developed and practically piloted support instruments, which address the specific needs of paediatric oncology, are missing.
OBJECTIVE
To systematically design and mature in practice an orientation compass for preparing, delivering and following up on BBN conversations in paediatric oncology-so-called Orientierungskompass zur Übermittlung schwerwiegender Nachrichten in der Kinderonkologie (OKRA).
METHODS AND ANALYSIS
OKRA is based on a QUAL-quant mixed study design, comprising two phases. Four groups will contribute (1) experts through personal experience (representatives for children receiving BBN and their parents), (2) medical care providers and representatives of national medical societies, (3) ambulant psychosocial/psychological support providers and (4) researchers. In phase 1, multiperspective knowledge is generated through a participatory group Delphi that involves in-depth interviews, focus group discussions and questionnaires. This process culminates in formulating theses for a high-quality BBN process (output phase 1). In phase 2, based on the theses, a pilot orientation compass is designed. Through iterative cycles with the participatory action research method, this instrument will be piloted in three paediatric oncological settings and consequently optimised.
ETHICS AND DISSEMINATION
OKRA was approved on 19 September 2023 by the ethics committee of the Medical Faculty of the University of Cologne (No. 23-1187). After project completion, the OKRA compass will be distributed to multidisciplinary paediatric oncology teams throughout Germany.
TRIAL REGISTRATION NUMBER
DRKS00031691.
Topics: Humans; Child; Truth Disclosure; Germany; Neoplasms; Medical Oncology; Pediatrics; Communication; Physician-Patient Relations; Parents; Professional-Family Relations
PubMed: 38823801
DOI: 10.1136/bmjpo-2023-002473 -
ENeuro May 2024Alzheimer's disease (AD) is characterized by an initial decline in declarative memory, while non-declarative memory processing remains relatively intact. Error-based...
Alzheimer's disease (AD) is characterized by an initial decline in declarative memory, while non-declarative memory processing remains relatively intact. Error-based motor adaptation is traditionally seen as a form of non-declarative memory, but recent findings suggest that it involves both fast, declarative and slow, non-declarative adaptive processes. If the declarative memory system shares resources with the fast process in motor adaptation, it can be hypothesized that the fast, but not the slow, process is disturbed in AD patients. To test this, we studied 20 early-stage AD patients and 21 age-matched controls of both sexes using a reach adaptation paradigm that relies on spontaneous recovery after sequential exposure to opposing force fields. Adaptation was measured using error clamps and expressed as an adaptation index (AI). Although patients with AD showed slightly lower adaptation to the force field than the controls, both groups demonstrated effects of spontaneous recovery. The time course of the AI was fitted by a hierarchical Bayesian two-state model in which each dynamic state is characterized by a retention and learning rate. Compared to controls, the retention rate of the fast process was the only parameter that was significantly different (lower) in the AD patients, confirming that the memory of the declarative, fast process is disturbed by AD. The slow adaptive process was virtually unaffected. Since the slow process learns only weakly from error, our results provide neurocomputational evidence for the clinical practice of errorless learning of everyday tasks in people with dementia. Experimental and modeling studies of motor adaptation suggest a dual-rate process of motor memory formation. We examined force-field motor adaptation in patients diagnosed with impaired declarative memory due to early-stage Alzheimer's disease. Using hierarchical Bayesian modeling, we show that their fast, but not slow process of adaptation is affected, suggesting that the fast process in motor adaptation shares resources with the declarative memory system.
PubMed: 38821873
DOI: 10.1523/ENEURO.0108-24.2024 -
Global Health, Science and Practice May 2024The concept of empowerment is challenging to operationalize and measure; it is multidimensional, the outcomes are not always directly observable, and meanings of...
BACKGROUND
The concept of empowerment is challenging to operationalize and measure; it is multidimensional, the outcomes are not always directly observable, and meanings of empowerment are highly contextual and socially and culturally situated. This study aimed to explore perspectives of empowerment among adolescent girls in Nepal to identify statements for inclusion in a context-specific empowerment measure.
METHODS
We used a participatory and mixed method research method called concept mapping in 3 districts in Nepal. Three sequential concept mapping sessions were used to solicit, organize, and process how participants responded to the prompt: "The life of an adolescent girl improves when she has/can…" The Concept Systems Global software was used to manage and analyze the concept mapping brainstorming, sorting, and rating data using established tools, such as multidimensional scaling and cluster analysis.
RESULTS
Concept mapping was conducted with 113 participants, including national experts, program staff, adolescents, and their mothers. They identified 105 items that fall into a 4-cluster solution: education and knowledge, decision-making, supports and skills, and physical infrastructure. Rating data uncovered there was some overlap between the top 10 most important items between the national-level experts and other stakeholder groups; however, several components associated with empowerment differed by stakeholder group in terms of importance.
CONCLUSION
This research represents a critical step in exploring definitions of empowerment among adolescent girls in the Nepal context and with expert input. These results led to the development of a contextually specific definition of empowerment. Researchers and practitioners interested in developing context-specific understandings of complex topics that incorporate community voices and perspectives could use a similar concept mapping approach in other countries to explore various topics with diverse populations.
PubMed: 38821870
DOI: 10.9745/GHSP-D-23-00010 -
Journal For Immunotherapy of Cancer May 2024The tissue immune microenvironment is associated with key aspects of tumor biology. The interaction between the immune system and cancer cells has predictive and... (Review)
Review
INTRODUCTION
The tissue immune microenvironment is associated with key aspects of tumor biology. The interaction between the immune system and cancer cells has predictive and prognostic potential across different tumor types. Spatially resolved tissue-based technologies allowed researchers to simultaneously quantify different immune populations in tumor samples. However, bare quantification fails to harness the spatial nature of tissue-based technologies. Tumor-immune interactions are associated with specific spatial patterns that can be measured. In recent years, several computational tools have been developed to increase our understanding of these spatial patterns.
TOPICS COVERED
In this review, we cover standard techniques as well as new advances in the field of spatial analysis of the immune microenvironment. We focused on marker quantification, spatial intratumor heterogeneity analysis, cell‒cell spatial interaction studies and neighborhood analyses.
Topics: Tumor Microenvironment; Humans; Neoplasms; Animals
PubMed: 38821717
DOI: 10.1136/jitc-2023-008589 -
Molecular Pharmacology May 2024Bipolar disorder impacts millions of patients in the United States but the mechanistic understanding of its pathophysiology and therapeutics is incomplete. Atypical...
Bipolar disorder impacts millions of patients in the United States but the mechanistic understanding of its pathophysiology and therapeutics is incomplete. Atypical antipsychotic serotonin (5-HT) receptor antagonists, such as quetiapine and olanzapine, and mood-stabilizing voltage-gated sodium channel (VGSC) blockers, such as lamotrigine, carbamazepine, and valproate, show therapeutic synergy and are often prescribed in combination for the treatment of bipolar disorder. Combination therapy is a complex task for clinicians and patients, often resulting in unexpected difficulties with dosing, drug tolerances, and decreased patient compliance. Thus, an unmet need for bipolar disorder treatment is to develop a therapeutic agent that targets both 5-HT receptors and VGSCs. Towards this goal, we developed a novel small molecule that simultaneously antagonizes 5-HT receptors and blocks sodium current. The new compound, -(4-bromo-2,5-dimethoxyphenethyl)-6-(4-phenylbutoxy)hexan-1-amine (XOB) antagonizes 5-HT-stimulated, G-mediated, calcium flux at 5-HT receptors at low micromolar concentrations while displaying negligible affinity and activity at 5-HT, 5-HT, and 5-HT receptors. At similar concentrations, XOB administration inhibits sodium current in heterologous cells and results in reduced action potential (AP) firing and VGSC-related AP properties in mouse prefrontal cortex layer V pyramidal neurons. Thus, XOB represents a new, proof-of-principle tool that can be used for future preclinical investigations and therapeutic development. This polypharmacology approach of developing a single molecule to act upon two targets, which are currently independently targeted by combination therapies, may lead to safer alternatives for the treatment of psychiatric disorders that are increasingly being found to benefit from the simultaneous targeting of multiple receptors. We synthesized a novel small molecule (XOB) that simultaneously antagonizes two key therapeutic targets of bipolar disorder, 5-HT receptors and voltage-gated sodium channels (VGSCs), in heterologous cells, and inhibits the intrinsic excitability of mouse prefrontal cortex layer V pyramidal neurons in brain slices. XOB represents a valuable new proof-of-principle tool for future preclinical investigations and provides a novel molecular approach to the pharmacological treatment of complex neuropsychiatric disease, which often requires a combination of therapeutics for sufficient patient benefit.
PubMed: 38821630
DOI: 10.1124/molpharm.123.000837 -
BMJ Open May 2024Healthcare systems are confronted with constant challenges and new crisis waves necessitating a transformation of current approaches to healthcare delivery....
UNLABELLED
Healthcare systems are confronted with constant challenges and new crisis waves necessitating a transformation of current approaches to healthcare delivery. Transformation calls for integration, partnerships, interprofessional teamwork and collaboration between all healthcare stakeholders to create improved access and more personalised healthcare outcomes for patients. However, healthcare organisations are complex systems, comprising multiple stakeholders, and the existence of professional silos and functions which have varying degrees of interaction hampering the delivery of effective integrated healthcare. Research investigating the underpinning operations of how the various healthcare stakeholders integrate is lacking. To address this gap, the use of actor-network theory (ANT) can provide insight into underlying dynamics, interactions, interdependencies, governance processes and power dynamics of stakeholders in healthcare. ANT represents a suitable theoretical lens as it helps to appreciate the dynamics and underpinning behaviours of complex organisations and explains how networks are developed and how actors join networks and form associations. Our systematic review will identify and evaluate available evidence to understand the interplay between stakeholders and all associated entities that impact collaboration and integration in healthcare delivery.
METHODS AND ANALYSIS
Using the Population-Intervention-Comparison-Outcome framework, the databases MEDLINE, CINAHL Complete, SCOPUS, PubMed, APA PsycINFO, Business Source Complete and Academic Search Complete will be searched using Boolean terms to identify peer-reviewed literature concerning ANT in healthcare. All relevant articles published between January 2013 and September 2023 will be eligible for inclusion. A thematic approach will be employed to appraise and analyse the extracted data to assess the various definitions of ANT and the use of ANT in healthcare settings, interactions and collaboration.
ETHICS AND DISSEMINATION
Given that no primary data will be captured, ethical approval will not be required for this study. Findings will be shared and ultimately published through open access peer-reviewed journals and reports.
PROSPERO REGISTRATION NUMBER
455283.
Topics: Humans; Systematic Reviews as Topic; Delivery of Health Care; Research Design; Cooperative Behavior
PubMed: 38821575
DOI: 10.1136/bmjopen-2023-079951 -
BMJ Open May 2024Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve...
Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China.
INTRODUCTION
Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC).
METHODS AND ANALYSIS
The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 μs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events.
ETHICS AND DISSEMINATION
This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences.
TRIAL REGISTRATION NUMBER
ChiCTR2300073950.
Topics: Humans; Vagus Nerve Stimulation; Consciousness Disorders; China; Transcutaneous Electric Nerve Stimulation; Consciousness; Randomized Controlled Trials as Topic; Adult; Multicenter Studies as Topic; Recovery of Function; Female; Treatment Outcome; Male
PubMed: 38821572
DOI: 10.1136/bmjopen-2024-083888 -
Stroke and Vascular Neurology May 2024Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery...
BACKGROUND
Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery (ECA), have been observed after revascularisation surgery. However, the origin of these collaterals in patients with stroke with perfusion insufficiency is not yet known. Therefore, we studied the revascularisation patterns and characteristics based on the origin of these collaterals.
METHODS
We employed erythropoietin pretreatment and performed multiple burr holes under local anaesthesia to achieve transdural revascularisation in patients with acute stroke with perfusion insufficiency. After 6 months, we reassessed the transfemoral cerebral angiography to evaluate the revascularisation patterns. The collaterals were categorised into intracalvarial ECA-dominant (originating from the middle meningeal artery), extracalvarial ECA-dominant (originating from the superficial temporal or occipital artery) and balanced groups. We compared various imaging parameters among these groups.
RESULTS
Overall, 87 patients with 103 treated hemispheres were involved. Among them, 57.3% were classified as intracalvarial ECA-dominant, 20.4% as extracalvarial ECA-dominant and 22.3% as balanced. Most of the hemispheres with intracalvarial or extracalvarial collaterals (vs balanced collaterals) showed successful revascularisation (78/80 (97.5%) vs 12/23 (52.1%)), p<0.001). In ultrasonographic haemodynamic changes according to revascularisation pattern, only the intracalvarial ECA-dominant revascularisation was significantly associated with specific changes in ECA blood flow, leading to the conversion to a low-resistance ECA Doppler sonography waveform.
CONCLUSIONS
Our findings suggest that intracalvarial ECA-dominant revascularisation plays a crucial role in the formation of transdural collaterals following combined therapy. These distinct changes in ECA haemodynamics can be non-invasively identified through bedside ultrasound studies.
PubMed: 38821555
DOI: 10.1136/svn-2023-002831 -
BMJ Global Health May 2024Water insecurity-the inability to access and benefit from affordable, reliable and safe water for basic needs-is a considerable global health threat. With the urgent...
INTRODUCTION
Water insecurity-the inability to access and benefit from affordable, reliable and safe water for basic needs-is a considerable global health threat. With the urgent need to target interventions to the most vulnerable, accurate and meaningful measurement is a priority. Households use diverse strategies to cope with water insecurity; however, these have not been systematically characterised nor measured. The Food Insecurity Coping Strategies Index has been insightful for targeting nutrition interventions to the most vulnerable. As a first step towards creating an analogous scale for water, this study characterises the largest empirical data set on water insecurity coping strategies and proposes guidance on measuring it using a novel toolkit.
METHODS
Open-ended responses on water insecurity coping (n=2301) were collected across 11 sites in 10 low- and middle-income countries in the Household Water InSecurity Experiences (HWISE) Scale validation study. Responses were characterised and compared with behaviours identified in the literature to construct an instrument to systematically assess coping.
RESULTS
We identified 19 distinct strategies that households used when experiencing water insecurity. These findings, paired with prior literature, were used to develop a Water Insecurity Coping Strategies Assessment Toolkit with guidance on its piloting to assess coping prevalence, frequency and severity.
CONCLUSIONS
The widespread occurrence of water insecurity coping strategies underscores the importance of understanding their prevalence and severity. The Water Insecurity Coping Strategies Assessment Toolkit offers a comprehensive approach to evaluate these strategies and inform the design and monitoring of interventions targeting those most vulnerable to water insecurity.
Topics: Humans; Adaptation, Psychological; Female; Water Insecurity; Male; Global Health; Family Characteristics; Adult; Water Supply; Developing Countries; Middle Aged; Coping Skills
PubMed: 38821550
DOI: 10.1136/bmjgh-2023-013754 -
JMIR Formative Research May 2024As an established treatment for major depressive disorder (MDD), cognitive behavioral therapy (CBT) is now implemented and assessed in internet-based formats that, when...
BACKGROUND
As an established treatment for major depressive disorder (MDD), cognitive behavioral therapy (CBT) is now implemented and assessed in internet-based formats that, when combined with smartphone apps, enable secure text messaging. As an adjunct to such internet-based CBT (ICBT) approaches, text messaging has been associated with increased adherence and therapeutic alliance.
OBJECTIVE
This study analyzed data from the intervention arm of a randomized control trial evaluating 24-week ICBT for MDD (intervention arm) against standard-care psychiatry (waitlist control). The aim of this secondary analysis was to assess MDD symptom improvement in relation to the frequency and content of text messages sent by ICBT participants to Navigator-Coaches during randomized control trial participation. Higher text frequency in general and in 3 conceptual categories (appreciating alliance, alliance building disclosures, and agreement confirmation) was hypothesized to predict larger MDD symptom improvement.
METHODS
Participants were young adults (18-30 years) from the Centre for Addiction and Mental Health. The frequencies of categorized texts from 20 ICBT completers were analyzed with respect to MDD symptom improvement using linear regression models. Texts were coded by 2 independent coders and categorized using content analysis. MDD symptoms were measured using the Beck Depression Inventory-II (BDI-II).
RESULTS
Participants sent an average of 136 text messages. Analyses indicated that BDI-II improvement was negatively associated with text messaging frequency in general (β=-0.029, 95% CI -0.11 to 0.048) and in each of the 3 categories: appreciating alliance (β=-0.096, 95% CI -0.80 to 0.61), alliance building disclosures (β=-0.098, 95% CI -0.28 to 0.084), and agreement confirmation (β=-0.076, 95% CI -0.40 to 0.25). Altogether, the effect of text messaging on BDI-II improvement was uniformly negative across statistical models. More text messaging appeared associated with less MDD symptom improvement.
CONCLUSIONS
The hypothesized positive associations between conceptually categorized text messages and MDD symptom improvement were not supported in this study. Instead, more text messaging appeared to indicate less treatment benefit. Future studies with larger samples are needed to discern the optimal use of text messaging in ICBT approaches using adjunctive modes of communication.
TRIAL REGISTRATION
Clinical Trials.gov NCT03406052; https://www.clinicaltrials.gov/ct2/show/NCT03406052.
PubMed: 38820586
DOI: 10.2196/40275