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This ENETS guidance paper for well‐differentiated nonfunctioning pancreatic neuroendocrine tumours (NF‐Pan‐NET) has been developed by a multidisciplinary working group, and provides up‐to‐date and practical advice on the management of these tumours. Using the extensive experience of centres treating patients with NF‐Pan‐NEN, the authors of this guidance paper discuss 10 troublesome questions in everyday clinical practice. Our many years of experience in this field are still being verified in the light of the results of new clinical, which set new ways of proceeding in NEN. The treatment of NF‐Pan‐NEN still requires a decision of a multidisciplinary team of specialists in the field of neuroendocrine neoplasms. This ENETS guidance paper provides up‐to‐date practical advice on the NF‐Pan‐NET diagnosis and treatment. Management of NF‐Pan‐NET patients requires a NET‐dedicated MDT decision. ENETS Centres of Excellence should be strongly considered to be involved in the diagnostic‐therapeutic strategy of these patients. Further studies are needed to fulfil the unmet needs in this field focusing on prognostic molecular markers, dilemmas concerning the selection of a therapeutic approach as well as the sequence of their use to achieve success in the management of NF‐Pan‐NETs patients. [ABSTRACT FROM AUTHOR]

This ENETS guidance paper, developed by a multidisciplinary working group, provides up‐to‐date and practical advice on the diagnosis and management of digestive neuroendocrine carcinoma, based on recent developments and study results. These recommendations aim to pave the road for more standardized care for our patients resulting in improved outcomes. Prognosis is generally poor for digestive NEC, most are advanced at diagnosis and median survival in metastatic disease is 11–12 months. Surgery can be of benefit for localized disease after extensive preoperative imaging. Carboplatin in combination with etoposide is recommended as first‐line treatment for metastatic disease. Irinotecan with fluoropyrimidines has the best evidence as second‐line treatment. Immunotherapy plays a minor role in biomarker‐unselected patients. Molecular profiling if available is encouraged to identify new targets. More prospective clinical trials are highly needed to fulfil the unmet needs in this field, especially on new predictive and prognostic biomarkers and to improve survival of patients with advanced disease. [ABSTRACT FROM AUTHOR]

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug‐induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work‐up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) first emerged in China in November 2019. Most governments have responded to the COVID-19 pandemic by imposing a lockdown. Some evidence suggests that a period of isolation might have led to a spike in alcohol misuse, and in the case of patients with alcohol use disorder (AUD), social isolation can favour lapse and relapse. The aim of our position paper is to provide specialists in the alcohol addiction field, in psychopharmacology, gastroenterology and in internal medicine, with appropriate tools to better manage patients with AUD and COVID-19,considering some important topics: (a) the susceptibility of AUD patients to infection; (b) the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) the reorganization of the Centre for Alcohol Addiction Treatment for the management of AUD patients in the COVID-19 era (group activities, telemedicine, outpatients treatment, alcohol-related liver disease and liver transplantation, collecting samples); (d) AUD and SARS-CoV-2 vaccination. Telemedicine/telehealth will undoubtedly be useful/practical tools even though it remains at an elementary level; the contribution of the family and of caregivers in the management of AUD patients will play a significant role; the multidisciplinary intervention involving experts in the treatment of AUD with specialists in the treatment of COVID-19 disease will need implementation. Thus, the COVID-19 pandemic is rapidly leading addiction specialists towards a new governance scenario of AUD, which necessarily needs an in-depth reconsideration, focusing attention on a safe approach in combination with the efficacy of treatment. [ABSTRACT FROM AUTHOR]

Background: Self‐harm is a major public health concern. Lifetime prevalence is high, and rates of self‐harm are rising; however, available interventions do not benefit everyone, and engagement with therapy can be low. Qualitative accounts allow for a greater understanding of what is helpful to individuals. This study aimed to synthesize the experiences of interventions for self‐harm, from participants who have participated in these themselves. Methods: Participants had self‐harmed at least once and undergone an individual psychotherapeutic intervention for self‐harm. Papers not written or translated to the English language were excluded. Four databases (Medline, CINAHL, Web of Science and PsycINFO) were systematically searched and each paper was assessed using the CASP quality appraisal tool. A meta‐ethnographic approach to the synthesis was taken. Results: Ten studies encompassing 104 participants were included. Four overarching themes were developed and the importance of recognizing the person beyond the self‐harm emerged through a line of argument synthesis. Building a trusted, therapeutic relationship founded on patience and without judgement was essential for the perceived success of therapy, which was unique to each person and often went beyond reducing self‐harming behaviours. Limitations: Papers included in the study showed a lack of diversity with regard to ethnicity and gender. Conclusions: The findings illustrate the importance of the therapeutic alliance when working with self‐harm. Clinical implications of this paper include the importance of utilizing key therapeutic competencies which should be considered fundamental to change within psychotherapeutic interventions for self‐harm, with the uniqueness of each patient recognized throughout. [ABSTRACT FROM AUTHOR]

Desomorphine is a composite of the self‐made illicit drug "krokodil", which is popular in Eastern Europe and other parts of the world. It causes toxic damage of different organs including bones. In this paper, a clinical portrait of the patient with drug‐induced osteonecrosis of mandible who refused surgical treatment in the early stages of the disease, is presented. At the time of first presentation, the patient displayed swelling of oral soft tissues and purulent discharge in the molar area of the right mandible. Radiographic examination demonstrated several small radiolucent lesions in the body of the mandible. The patient gave consent for surgical treatment and rehabilitation only after 12 months of the diagnosis. During this period of time, the necrosis of the mandibular bone progressed and a pathological fracture of the jaw was developed. Patient underwent surgical treatment – resection of the mandible. Management of drug‐induced jaw osteonecrosis is challenging as the necessity of dental and surgical treatment as well as treatment and rehabilitation of substance use disorder arises. Involvement of a multidisciplinary healthcare professionals team is essential in successful treatment of this pathology. The latter includes early surgical intervention/medical treatment and rehabilitation from drug addiction. [ABSTRACT FROM AUTHOR]

Background: miRNA‐based strategies have recently emerged as a promising therapeutic approach in several neurodegenerative diseases. Unregulated cation influx is implicated in several cellular mechanisms underlying neural cell death during ischemia. The brain constitutively active isoform of transient receptor potential melastatin 7 (TRPM7) represents a glutamate excitotoxicity‐independent pathway that significantly contributes to the pathological Ca2+ overload during ischemia. Aims: In the light of these premises, inhibition of TRPM7 may be a reasonable strategy to reduce ischemic injury. Since TRPM7 is a putative target of miRNA135a, the aim of the present paper was to evaluate the role played by miRNA135a in cerebral ischemia. Therefore, the specific objectives of the present paper were: (1) to evaluate miR135a expression in temporoparietal cortex of ischemic rats; (2) to investigate the effect of the intracerebroventricular (icv) infusion of miR135a on ischemic damage and neurological functions; and (3) to verify whether miR135a effects may be mediated by an alteration of TRPM7 expression. Methods: miR135a expression was evaluated by RT‐ PCR and FISH assay in temporoparietal cortex of ischemic rats. Ischemic volume and neurological functions were determined in rats subjected to transient middle cerebral artery occlusion (tMCAo) after miR135a intracerebroventricular perfusion. Target analysis was performed by Western blot. Results: Our results demonstrated that, in brain cortex, 72 h after ischemia, miR135a expression increased, while TRPM7 expression was parallelly downregulated. Interestingly, miR135a icv perfusion strongly ameliorated the ischemic damage and improved neurological functions, and downregulated TRPM7 protein levels. Conclusions: The early prevention of TRPM7 activation is protective during brain ischemia. [ABSTRACT FROM AUTHOR]

Background: Competent clinical reasoning forms the foundation for effective and efficient clinical swallowing examination (CSE) and consequent dysphagia management decisions. While the nature of initial CSEs has been evaluated, it remains unclear how new information gathered by speech–language therapists (SLTs) throughout a patient's acute‐care journey is integrated into their initial clinical reasoning and management processes and used to review and revise initial management recommendations. Aims: To understand how SLTs' clinical reasoning and decision‐making regarding dysphagia assessment and management evolve as patients transition through acute hospital care from referral to discharge. Methods & Procedures: A longitudinal, qualitative approach was employed to gather information from two SLTs who managed six patients at a metropolitan acute‐care hospital. A retrospective 'think‐aloud' protocol was utilized to prompt SLTs regarding their clinical reasoning and decision‐making processes during initial and subsequent CSEs and patient interactions. Three types of concept maps were created based on these interviews: a descriptive concept map, a reasoning map and a hypothesis map. All concept maps were evaluated regarding their overall structure, facts gathered, types of reasoning engaged in (inductive versus deductive), types of hypotheses generated, and the diagnosis and management recommendations made following initial CSE and during subsequent dysphagia management. Outcomes & Results: Initial CSEs involved a rich process of fact‐gathering, that was predominantly led by inductive reasoning (hypothesis generation) and some application of deductive reasoning (hypothesis testing), with the primary aims of determining the presence of dysphagia and identifying the safest diet and fluid recommendations. During follow‐up assessments, SLTs engaged in increasingly more deductive testing of initial hypotheses, including fact‐gathering aimed at determining the tolerance of current diet and fluid recommendations or the suitability for diet and/or fluid upgrade and less inductive reasoning. Consistent with this aim, SLTs' hypotheses were focused primarily on airway protection and medical status during the follow‐up phase. Overall, both initial and follow‐up swallowing assessments were targeted primarily at identifying suitable management recommendations, and less so on identifying and formulating diagnoses. None of the patients presented with adverse respiratory and/or swallowing outcomes during admission and following discharge from speech pathology. Conclusions & Implications: Swallowing assessment and management across the acute‐care journey was observed as a high‐quality, patient‐centred process characterized by iterative cycles of inductive and deductive reasoning. This approach appears to maximize efficiency without compromising the quality of care. The outcomes of this research encourage further investigation and translation to tertiary and post‐professional education contexts as a clear understanding of the processes involved in reaching diagnoses and management recommendations can inform career‐long refinement of clinical skills. WHAT THIS PAPER ADDS: What is already known on the subject: SLTs' clinical reasoning processes during initial CSE employ iterative cycles of inductive and deductive reasoning, reflecting a patient‐centred assessment process. To date it is unknown how SLTs engage in clinical reasoning during follow‐up assessments of swallowing function, how they assess the appropriateness of initial management recommendations and how this relates to patient outcomes. What this paper adds to the existing knowledge: Our longitudinal evaluation of clinical reasoning and decision‐making patterns related to swallowing management in acute care demonstrated that SLTs tailored their processes to each patient's presentation. There was an emphasis on monitoring the suitability of the initial management recommendations and the potential for upgrade of diet or compensatory swallowing strategies. The iterative cycles of inductive and deductive reasoning reflect efficient decision‐making processes that maintain high‐quality clinical care within the acute environment. What are the potential or actual clinical implications of this work?: Employing efficient and high‐quality clinical reasoning is a hallmark of good dysphagia practice in maximizing positive patient outcomes. Developing approaches to understanding and making explicit clinical reasoning processes of experienced clinicians may assist SLTs of all developmental stages to provide high standards of care. [ABSTRACT FROM AUTHOR]

Severe acute malnutrition (SAM) remains a major global public health problem. SAM cases are treated using ready‐to‐use therapeutic food (RUTF) at a dosage of ∼200 kcal/kg/day per the standard treatment protocol (STD). Emerging evidence on simplifications to the standard protocol, which among other adaptations, includes reducing the daily RUTF dosage, indicates that it is effective and safe for treating children with SAM. In response to a foreseen stock shortage of RUTF, the government of Afghanistan endorsed the temporary use of a modified treatment protocol in which the daily RUTF dosage was prescribed at 1000 kcal/day (irrespective of body weight) until the child achieved moderate acute malnutrition status (weight‐for‐height z‐score ≥ −3 or mid‐upper arm circumference [MUAC] ≥ 115 mm), at which point 500 kcal/day was prescribed until cured (modified treatment protocol [MTP]). In this paper, we report the results of this nonweight‐based daily RUTF dosage experience. Data of 2042 children with SAM, treated using either the STD protocol (n = 269) or the MTP protocol (n = 1773) from August 2019 to March 2021 in five provinces, were analyzed. The per‐protocol analyses confirmed noninferiority of MTP protocol when compared to STD protocol for recovery rate [93.3% vs. 90.2%; ∆ (95% confidence interval, CI) = 3.1 (−0.9; 7.2) %] and length‐of‐stay [82.6 vs. 75.6 days; ∆ (95% CI) = 6.9 (3.3; 10.5) days], considering the margin of noninferiority of −10% and +14 days, respectively. Weight gain velocity was smaller in the MTP protocol group than in the STD protocol group [3.7 (1.7) vs. 5.2 (2.9) g/kg/day; ∆ (95% CI) = −1.5 (−1.8, −1.2); p < 0.001]. The STD group had a significantly higher mean than the MTP group for absolute MUAC gain [∆ (95% CI) = 1.7 (1.0; 2.3) mm; p < 0.001] and the MUAC velocity [∆ (95% CI) = 0.29 (0.20; 0.37) mm/week; p < 0.001]. Our results confirm the noninferiority of a nonweight‐based daily dosage and support the endorsement of this modification as an alternative to the standard protocol in resource‐constrained contexts. Key messages: More evidence supporting the use of the nonweight‐based daily ready‐to‐use therapeutic food (RUTF) dosage for treating uncomplicated severe acute malnutrition (SAM), in specific contexts, is needed.Our real‐world prospective nonrandomized study showed that the fixed nonweight‐based daily RUTF dosage protocol is as effective as the standard weight‐based protocol for treating uncomplicated SAM in children <5 in the Afghanistan context.Our findings support the reflection of a nonweight‐based daily RUTF dosage in resource‐constrained contexts in national and global policies and guidelines to improve coverage of all children in need of treatment. [ABSTRACT FROM AUTHOR]

Decellularized matrices derived from diseased tissues/organs have evolved in the most recent years, providing novel research perspectives for understanding disease occurrence and progression and providing accurate pseudo models for developing new disease treatments. Although decellularized matrix maintaining the native composition, ultrastructure, and biomechanical characteristics of extracellular matrix (ECM), alongside intact and perfusable vascular compartments, facilitates the construction of bioengineered organ explants in vitro and promotes angiogenesis and tissue/organ regeneration in vivo, the availability of healthy tissues and organs for the preparation of decellularized ECM materials is limited. In this paper, we review the research advancements in decellularized diseased matrices. Considering that current research focuses on the matrices derived from cancers and fibrotic organs (mainly fibrotic kidney, lungs, and liver), the pathological characterizations and the applications of these diseased matrices are mainly discussed. Additionally, a contrastive analysis between the decellularized diseased matrices and decellularized healthy matrices, along with the development in vitro 3D models, is discussed in this paper. And last, we have provided the challenges and future directions in this review. Deep and comprehensive research on decellularized diseased tissues and organs will promote in‐depth exploration of source materials in tissue engineering field, thus providing new ideas for clinical transformation. [ABSTRACT FROM AUTHOR]

Objective: Acromegaly is a condition characterized by an overproduction of growth hormone which infers high morbidity and mortality if left untreated. The objective of this review is to analyse and appraise the current evidence for the generalized use of preoperative medications and the various surgical approaches as described in the literature. Design: A thorough search from MEDLINE via PubMed, EMBASE, and Cochrane Library has been performed which identified a total of 37 papers. Conclusion: The preoperative use of somatostatin receptor agonists (SAs) in acromegaly is a controversial topic with current guidelines suggesting against their generalized routine use. Most authors noticed an insignificant long‐term remission of acromegaly when given SAs compared with nil preoperative therapy, except for invasive macroadenomas as SAs have been found to reduce the tumour volume and aid towards the total resection of the adenoma. Furthermore, according to the evidence available, endoscopic transsphenoidal surgery is the optimum method for hypophysectomy in terms of its remission and safety profile. [ABSTRACT FROM AUTHOR]

Since its publication in 2014, L. A. Paul's book Transformative Experience has sparked many discussions in philosophy and beyond. Her main argument is that experiences we have not had before can transform us epistemically (i.e., we learn something we could not learn without the experience) and personally (i.e., our point of view changes radically). This has implications for decision theory in particular, but also for other fields. The present paper provides an overview of how transformative experiences are thought to challenge rational choice and how authors have responded to this challenge (with a focus on the epistemic transformation). Furthermore, it also shows how the concept of transformative experience has been fruitful beyond the decision‐theoretical context, with a particular focus on illness, medical treatment, and the ethical issues involved. Finally, the paper presents open questions in the literature on transformative experiences. [ABSTRACT FROM AUTHOR]

Background: Stroke profoundly affects quality of life (QOL), including loss of employment, reduced social activity, shrinking social networks and low mood. Dysgraphia (impaired writing) is a common symptom of aphasia yet is rarely targeted in rehabilitation. Recent technological advances might challenge this, since much communication is now conducted digitally through writing. The rehabilitation of writing may therefore help to address the wider consequences of stroke and aphasia. Aims: Can assistive technology (AT) training for people with dysgraphia: (1) improve written output, and are gains achieved only with AT? (2) improve reading comprehension scores, and are gains achieved only with AT? and (3) affect social participation, mood or QOL Methods and Procedures: Design A mixed‐methods, repeated measures, small group study design was adopted (qualitative outcomes will be reported elsewhere). Participants: Recruited from community settings, for example, Stroke Association communication support groups. Inclusion criteria: over 18 years old, aphasia due to stroke, acquired dysgraphia, writing more impaired than speech, fluent English prior to stroke, access to computer and Internet. Exclusion criteria: currently receiving speech and language therapy, significant cognitive impairment, neuromuscular/motor‐speech impairments/structural abnormalities, developmental dyslexia, uncorrected visual/auditory impairments. Procedures: Screening and diagnostic assessments at time T1 (first baseline). Outcome measures at T1; repeated at T2 (second baseline), T3 (end of intervention), T4 (3‐month follow up). Social participation assessment and cognitive monitoring at T2, T3, T4. Intervention: Seven–ten hours individual therapy weekly and additional email support. Participants were trained to operate Dragon NaturallySpeaking (speech to text package) and ClaroRead (read writing aloud). Outcome measures were administered on pen and paper (control) and on computer, with AT enabled only at T3, T4. Outcomes and Results: Computer narrative writing was significantly improved by AT training (Friedman's χ2 (3) = 8.27, p = 0.041), indicating a compensatory effect of AT. Though reading comprehension significantly improved in the computer condition (Friedman's χ2 (3) = 21.07, p = 0.001), gains could not be attributed to the AT. Gains were achieved only when measures were administered on the keyboard, with AT enabled. Thus, a compensatory rather than remediatory effect was suggested. Social network size significantly increased; there were no significant changes in mood/QOL. Individual success rates varied. Conclusion and Implications: The customisable AT training was acceptable to participants and resulted in significantly improved narrative writing. Compensatory AT interventions are a useful adjunct to remediatory writing interventions and may particularly support functional writing. WHAT THIS PAPER ADDS: What is already known on this subject: Writing is rarely spared in aphasia and may present as the most impaired communication modality. Yet, people with aphasia report that writing is seldom included in their rehabilitation. Many communication activities are now conducted digitally through writing, therefore rehabilitation of this is more important than ever before. This study sought to address whether an assistive technology (AT) software package can improve writing and whether any changes were compensatory or remediatory. What this study adds to existing knowledge: This group study found that AT training led to gains in written discourse and social network in people with aphasia and dysgraphia. Gains were not replicated in handwritten tasks, suggesting this was a compensatory therapeutic approach. What are the clinical implications of this work?: AT programs such as this may present speech and language therapists with a practical, pragmatic adjunct to writing or typing therapy, particularly for clients with chronic, intractable impairments for whom remediatory therapy may have a low chance of success. [ABSTRACT FROM AUTHOR]

Background and Aim: The traditional drug delivery approach involves systemic administration of a drug that could be nonspecific in targeting, low on efficacy, and with severe side‐effects. To address such challenges, the field of smart drug delivery has emerged aiming at designing and developing delivery systems that can target specific cells, tissues, and organs and have minimal off‐target side‐effects. Methods: A literature search was done to collate papers and reports about the currently available various strategies for smart nano‐inspired drug delivery. The databases searched were PubMed, Scopus, and Google Scholar. Based on selection criteria, the most pertinent and recent items were included. Results: Smart drug delivery is a cutting‐edge revolutionary intervention in modern medicines to ensure effective and safe administration of therapeutics to target sites. These hold great promise for targeted and controlled delivery of therapeutic agents to improve the efficacy with reduced side‐effects as compared to the conventional drug delivery approaches. Current smart drug delivery approaches include nanoparticles, liposomes, micelles, and hydrogels, each with its own advantages and limitations. The success of these delivery systems lies in engineering and designing them, and optimizing their pharmacokinetics and pharmacodynamics properties. Conclusion: Development of drug delivery systems that can get beyond various physiological and clinical barriers, as observed in conventionally administered chemotherapeutics, has been possible through recent advancements. Using multifunctional targeting methodologies, smart drug delivery tries to localize therapy to the target location, reduces cytotoxicity, and improves the therapeutic index. Rapid advancements in research and development in smart drug delivery provide wider and more promising avenues to guarantee a better healthcare system, improve patient outcomes, and achieve higher levels of effective medical interventions like personalized medicine. [ABSTRACT FROM AUTHOR]

If Parkinson's disease patients only present motorically when 50% of their dopamine cells are lost, then the condition must have been slowly evolving over 25 to 50 years. Thereafter, the pathology progresses at the rate of 1% to 2% of dopamine cells per year even though the pathological species was there from day zero- given the cells were placed into the brains of patients with moderately advanced PD. I would say this paper has fundamentally challenged the long-held view that the pathogenesis of PD is primarily a cell-autonomous process - although even at the time it was published this was being challenged both for PD and other proteinopathies of the brain. [Extracted from the article]

Progression‐free survival (PFS) is an important clinical metric for comparing and evaluating similar treatments for the same disease within oncology. After the completion of a clinical trial, a descriptive analysis of the patients' PFS is often performed post hoc using the Kaplan–Meier estimator. However, to perform predictions, more sophisticated quantitative methods are needed. Tumor growth inhibition models are commonly used to describe and predict the dynamics of preclinical and clinical tumor size data. Moreover, frameworks also exist for describing the probability of different types of events, such as tumor metastasis or patient dropout. Combining these two types of models into a so‐called joint model enables model‐based prediction of PFS. In this paper, we have constructed a joint model from clinical data comparing the efficacy of FOLFOX against FOLFOX + panitumumab in patients with metastatic colorectal cancer. The nonlinear mixed effects framework was used to quantify interindividual variability (IIV). The model describes tumor size and PFS data well, and showed good predictive capabilities using truncated as well as external data. A machine‐learning guided analysis was performed to reduce unexplained IIV by incorporating patient covariates. The model‐based approach illustrated in this paper could be useful to help design clinical trials or to determine new promising drug candidates for combination therapy trials. [ABSTRACT FROM AUTHOR]

Background: People with motor neuron disease (pwMND) are routinely offered gastrostomy feeding tube placement and (non‐invasive and invasive) ventilation to manage the functional decline associated with the disease. This study aimed to synthesise the findings from the qualitative literature to understand how individual, clinical team and organisational factors influence pwMND decisions about these interventions. Methods: The study design was guided by the enhancing transparency in reporting the synthesis of qualitative research (ENTREC) statement. The search of five bibliography databases and an extensive supplementary search strategy identified 27 papers that included qualitative accounts of pwMND, caregivers and healthcare professionals' (HCPs) experiences of making decisions about gastrostomy and ventilation. The findings from each study were included in a thematic synthesis. Findings: Making decisions about interventions is an emotional rather than simply a functional issue for pwMND. The interventions can signal an end to normality, and increasing dependence, where pwMND consider the balance between quality of life and extending survival. Interactions with multiple HCPs and caregivers can influence the process of decision‐making and the decisions made. These interactions contribute to the autonomy pwMND are able to exert during decision‐making. HCPs can both promote and threaten pwMND perceived agency over decisions through how they approach discussions about these interventions. Though there is uncertainty over the timing of interventions, pwMND who agree to interventions report reaching a tipping point where they accept the need for change. Conclusion: Discussion of gastrostomy and ventilation options generate an emotional response in pwMND. Decisions are the consequence of interactions with multiple external agents, including HCPs treading a complex ethical path when trying to improve health outcomes while respecting pwMND right to autonomy. Future decision support interventions that address the emotional response and seek to support autonomy have the potential to enable pwMND to make informed and timely decisions about gastrostomy placement and ventilation. Patient or Public Contribution: The lead author collaborated with several patient and participant involvement (PPI) groups with regards to the conceptualisation and design of this project. Decisions that have been influenced by discussions with multiple PPI panels include widening the scope of decisions about ventilation in addition to gastrostomy placement and the perceptions of all stakeholders involved (i.e., pwMND, caregivers and HCPs). [ABSTRACT FROM AUTHOR]

Background: : Dysphagia is prevalent in subjects with Parkinson's disease (PD). Swallowing intervention to improve or maintain swallowing function is of major importance as dysphagia may considerably impact physical and psycho‐social health. Aims: : A mixed methods systematic review was conducted to summarize and appraise literature reporting (1) effects of behavioural interventions for swallowing in individuals with PD; and (2) participants' perspectives of swallowing interventions. Methods & Procedures: : Electronic databases were searched systematically in July 2020 for articles published between 2014 and 2020. In addition, studies published between 2000 and 2014 were identified non‐systematically through previous reviews. Peer‐reviewed quantitative and qualitative research in English or German documenting behavioural interventions for swallowing in individuals with a diagnosis of PD was eligible for inclusion. Participants at all disease stages were included. Behavioural interventions included rehabilitative and compensatory strategies. Studies reporting swallowing outcomes with and without a comparative group were included. For each study, the National Health and Medical Research Council level of evidence was defined. Included studies were critically appraised using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields. An integrated synthesis was performed after separate analysis of effect data and data reflecting participants' experiences. This review was conducted based on published JBI methodology and the guideline from the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis system was followed. Main Contribution: : A total of 33 studies published in English met the inclusion criteria. Thirty‐one studies reported quantitative data, one was qualitative and one was mixed methods. Intervention effects on swallowing function, swallowing safety and swallowing‐related quality of life were reported for various treatment approaches. Three studies explored how participants perceived the intervention. Overriding themes including subjects' views regarding treatment schedules and levels of effort or comfort associated with the intervention were identified across these studies. Combining evidence of intervention effects and subjects' experiences was possible for one rehabilitative and one compensatory intervention. Conclusions & Implications: : Beneficial effects of swallowing interventions have been reported; however, most experiments were case studies of variable methodological quality. Randomized‐controlled trials with robust methodology to explore treatment effects in larger samples is needed to guide clinical practice. Research reporting subjects' views is scarce. More studies exploring how individuals perceive behavioural interventions for swallowing are necessary to inform clinical decision‐making. WHAT THIS PAPER ADDS: What is already known on the subject: Dysphagia is common in individuals with PD. Swallowing intervention is of major importance as dysphagia may negatively affect physical and psycho‐social health of subjects with PD. What this study adds: Beneficial effects of behavioural interventions for swallowing, including rehabilitative and compensatory strategies, have been reported; however, available data are mostly based on case studies of variable quality. Data on how participants perceive specific behavioural interventions are lacking. Based on the available data, integration of efficacy data and individuals' experiences is limited. What are the clinical implications of this work?: Given the current evidence of intervention effects and individuals' views on behavioural treatment strategies, interventions implemented into clinical practice require careful evaluation on a case‐by‐case basis. More high‐quality research is needed to examine interventions' short‐ and long‐term effects in larger samples to guide clinical practice. In addition to studies evaluating intervention effects, research exploring participants' experiences with interventions is required as a foundation for clinical decision‐making. [ABSTRACT FROM AUTHOR]

This document provides abstracts of papers presented at the 2024 Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics. The papers cover a wide range of topics related to clinical pharmacology and therapeutics, including the use of machine learning in predicting adverse events, the integration of brain- and blood-derived markers in antidepressant pharmacotherapy, and the use of NLP-powered topic modeling in drug repurposing. Other studies focused on the pharmacokinetics and safety of different drugs, the development of population pharmacokinetic models, and potential drug-drug interactions involving cannabidiol. These studies offer valuable insights into drug behavior and can help guide personalized treatment strategies in different populations. The document also discusses the use of computational tools and machine learning techniques to improve drug pharmacokinetics and clinical trial design. Overall, these studies contribute to our understanding of how drugs interact with the body and can inform more effective and personalized treatment approaches. [Extracted from the article]

The aptness of machine learning (ML) to learn from large datasets, discover trends, and make predictions has demonstrated its potential to metamorphose the medical field. Medical data analysis with ML algorithms can improve patient outcomes in terms of both treatment and diagnosis. This paper investigates the numerous possibilities of ML in the medical industries, including radiology, pathology, genomics, and clinical decision‐making. It also goes over the benefits and drawbacks of ML in various sectors as well as the limitations that come with its application. It illustrates the potential advantages of ML, such as better accuracy and efficiency in diagnosis and individualized treatment programs, through a review of previous studies. Lastly, it provides perspectives on prospective advancements and prospects for the discipline. This study also intends to investigate the applications of deep learning (DL) in the medical field. DL algorithms have performed exceptionally satisfactorily in several healthcare‐related fields. The main conclusions of the study are summarized, and their ramifications for the healthcare sector are discussed in this paper's conclusion. This paper intends to contribute to a greater understanding of the prevailing state of the discipline and the possibility for future developments by emphasizing the prospects of these methodologies to alter medical study and clinical practice. [ABSTRACT FROM AUTHOR]

This paper examines cyberbullying concerning therapeutic interventions. A section on bullying and how bullying impacts the therapeutic environment is included. The author provides his definition of bullying to incorporate cyberbullying and how it is no longer a "new issue" but an evolving one. The current status of therapeutic interventions used to support victims of cyberbullying has been explored, emphasising their effectiveness in assisting those experiencing bullying. A segment has been implemented to comprehend whether practitioners fully understand the potential implications of cyberbullying on clients, whether bullying is still seen as a "rite of passage" and what the possible consequences of this could be. Peer interventions and support groups concerning cyberbullying have been referenced, including The KiVa Programme, the Shared Concern Method and The Circle of Friends Method. These have highlighted specific examples of therapeutic and nontherapeutic approaches to intervene with cyberbullying. A section on potential further training is presented for practitioners working within educational environments. Moreover, physical, psychological, sexual and relational bullying are discussed in the article when applicable, with the umbrella term "bullying" used to discuss all forms of bullying at once. The paper has uncovered two key messages: (1) cyberbullying requires more awareness in counselling and is no longer a new issue and (2) more extensive training is required to assist therapists to work with cyberbullying victims. [ABSTRACT FROM AUTHOR]

Background: Research is beginning to shed light on the practices employed by speech‐language therapists (SLTs) for the management of acquired dysarthria. However, studies that explore SLTs' satisfaction with the effectiveness of current therapies and their interest in new treatment methods for this population have not been carried out. One potential new method is neuromuscular electrical stimulation (NMES): the pool of evidence for its use in rehabilitation is increasing, yet it has not been widely explored for use with dysarthria. Aim: To extend the understanding of acquired dysarthria management practices employed by SLTs across the globe and determine their satisfaction with current therapy options. To explore their interest in using NMES with this population. Methods and Procedures: A cross‐sectional international online survey was developed and disseminated to SLTs working with adults with acquired dysarthria through international professional associations. The survey collected information on demographic characteristics, dysarthria management practices, satisfaction with treatment effectiveness and interest in and knowledge of NMES. Survey responses were analysed using descriptive and inferential statistics, and quantitative content analysis. Outcomes and Results: A total of 211 SLTs (North America, 48.8%; Europe, 36%; Asia, 8.1%; Oceania, 5.7%; Africa, 0.9%; South America, 0.5%) completed the survey in full. Management practices varied considerably. There was a clear preference for informal assessments, mainly oral‐motor examinations, focusing on body functions and structures. The majority of respondents rejected the use of non‐speech oral motor exercises as a clinical or carryover exercise. Variable satisfaction with current speech subsystem treatments was noted; however, overall, there was a general dissatisfaction. Whilst a strong interest in the use of NMES for dysarthria was evidenced, it was noted that most SLTs lacked fundamental knowledge of NMES principles and application. Conclusion: SLTs' management practices and satisfaction with acquired dysarthria treatments differed substantially. Investigations of the potential use of NMES for dysarthria treatment are of interest. WHAT THIS PAPER ADDS: What is already known on the subject: Recent country‐specific surveys have explored speech‐language therapists' (SLTs') assessment and intervention practices for acquired dysarthria. These studies indicate that although clinical management for this speech disorder mainly involves informal assessment tools and impairment‐focused treatment, communication beyond the impairment, such as the activity and participation domains, is also frequently assessed and treated. What this paper adds to existing knowledge: The majority of SLTs are dissatisfied with the overall benefits of current acquired dysarthria treatment. Phonatory, respiration and speech rate therapies are perceived to be more effective than prosody, articulation and resonance treatments. Despite a general lack of theoretical knowledge, most SLTs are interested in neuromuscular electrical stimulation treatment for acquired dysarthria. What are the potential or actual clinical implications of this work?: New, evidence‐based treatments are needed for SLTs to be confident in the effectiveness of their acquired dysarthria treatment. [ABSTRACT FROM AUTHOR]

Background: In order to conduct research that is meaningful to speech and language therapy services and their patients, it is often desirable to conduct the research within routine clinical services. This can require considerable time and commitment from speech and language therapists (SLTs). It is therefore important to understand the impact that such participation in research can have. Aims: To explore the impact of research participation in the Big CACTUS study of self‐managed computerized aphasia therapy conducted in 21 UK NHS speech and language therapy departments. Methods & Procedures: An online survey was sent to SLTs who took the lead role for the study at their NHS Trust to evaluate the impact of study participation in three domains: capacity‐building, research development and health services. The questionnaire, based on the VICTOR framework for evaluating research impact, included Likert scale statements and closed and open‐ended questions. The results from open‐ended questions were coded and analysed using framework analysis in NVivo 12 and the data from closed questions were analysed descriptively. Outcomes & Results: A total of 12 SLTs returned the survey. Nine codes were identified from open‐ended questions and 20 predefined from the literature. Analysis of the responses demonstrated the perceived impact including improvements in practices and access to therapy, investments in infrastructure, increased SLT profile, and impact on research culture among SLTs. The usefulness of the intervention during the COVID‐19 pandemic was also highlighted. Conclusions & Implications: The results suggest participation in Big CACTUS has resulted in improvements in patient care and SLT research capacity and culture in speech and language therapy departments. What This Paper Adds: What is already known on the subject: Practice‐based research is encouraged to assist with the clinical relevance of the research findings. Participation in research can be seen as an activity that is additional to the core business of patient care and it can be difficult to secure time to participate or conduct research in clinical settings. Impact evaluation initiatives of individual trials facilitate early identification of benefits beyond the trial. What this paper adds to existing knowledge: This study describes specific examples of the impact on services, staff and patients from SLT participation and leadership in the Big CACTUS speech and language therapy trial in clinical settings. What are the potential or actual clinical implications of this study?: Clinical services participating in research may benefit from improved clinical care for patients both during and after the study, an improved professional reputation, and increased research capacity and culture within the clinical settings. [ABSTRACT FROM AUTHOR]

This study focussed on evaluating the status of recent research on medical decision‐making for adolescents with depression and identifying research hotspots and frontiers via CiteSpace. We extracted studies that were concerned with medical decision‐making for adolescents with depression from the Web of Science Core Collection (WoSCC), covering the period from 1 January 1999 to 20 September 2022. We used CiteSpace to generate online maps of worldwide cooperation among countries, institutions, and authors. Hotspots and frontiers were systematically summarized. A total of 368 papers related to medical decision‐making for adolescents with depression were obtained from WoSCC. The most prolific author was Nick Midgley (seven papers). The United States and University College London were the leading country and institution in this research area, with 177 and 17 papers, respectively. Countries, institutions, and authors all actively collaborated. Main recent research trends include the preference or attitude towards medical treatment in adolescents with depression; approaches for adolescents with depression to seeking medical help; and the key role of parent, family, and primary care in medical decision‐making for adolescents. Thus, further attention should be paid to determining how to promote the role of parents, families, and primary care in the decision‐making process and create appropriate online help‐seeking tools and decision aids to facilitate shared decision‐making in the future. [ABSTRACT FROM AUTHOR]

Background: While the relationship between speech, language and communication needs (SLCN) and mental health difficulties has been recognized, speech and language therapists (SLTs), and mental health professionals face challenges in assessing and treating children with these co‐occurring needs. There exists a gap in the evidence base for best practice for professionals working with children and young people (CYP) who experience difficulties in both areas. Aims: To explore the views of SLTs and mental health clinicians about their experiences of working with CYP exhibiting co‐occurring SLCN and mental health difficulties. Methods & Procedures: Semi‐structured interviews were conducted with eight SLTs and six mental health professionals, including psychotherapists, clinical psychologists, play therapists and counsellors, with experience working with CYP with SLCN. Interviews were analysed using reflexive thematic analysis and themes were identified from the data. Outcomes & Results: Participants felt that SLCN and mental health difficulties frequently co‐occur. Participants described how CYP with SLCN and mental health issues commonly experience difficulties across and between the domains of language and cognition, emotional well‐being and challenging behaviour. Findings suggest that there are organizational limitations in the fields of SLT and mental health that have implications for the efficacy of assessment and treatment of CYP with SLCN and mental health difficulties. Traditional talking therapies were perceived to be inaccessible and ineffective for CYP with SLCN and mental health difficulties. Interventions blending behaviour and emotion programmes with language and communication interventions were considered potentially beneficial. Conclusions & Implications: Future research should explore and evaluate current services and service set‐up in SLT and mental health. The findings from this study have important implications for the efficacy of treatments provided to this population suggesting that more research needs to be done into effective diagnosis and interventions for this population. WHAT THIS PAPER ADDS: What is already known on the subject: Research suggests that CYP with SLCN, such as developmental language disorder (DLD), are likely to experience mental health difficulties including depression, anxiety and poor emotional well‐being. CYP who experience difficulties with SLCN and poor mental health are not well understood and this area remains under‐researched. This has implications for clinician knowledge and therefore the effective diagnosis and treatment of children and adolescents experiencing SLCN and mental health difficulties. In addition, little is known about the accessibility of talking therapies to CYP presenting with SLCN and mental health difficulties. What this paper adds to existing knowledge: SLCN issues are understood by SLTs and mental health issues are understood by mental health professionals, but where these co‐occur difficulties exist for the diagnostic process, with professionals perceiving that CYP in this category are often undiagnosed or misdiagnosed. Organizational boundaries between SLT and mental health were perceived to contribute to a lack of understanding of SLCN and mental health needs, which has implications for effective diagnosis and treatment. Traditional talking therapies were thought to be inaccessible for CYP with SLCN and mental health difficulties. Interventions used in both SLT and psychotherapy were perceived as clinically useful if combined. What are the potential or actual clinical implications of this work?: This paper highlights implications for the accessibility and efficacy of the assessment and treatment provided to this population and to the organization of services currently treating this group of CYP. A direction for future research would be to undertake service evaluations and intervention‐based studies. [ABSTRACT FROM AUTHOR]

Alzheimer's disease, often known as dementia, is a severe neurodegenerative disorder that causes irreversible memory loss by destroying brain cells. People die because there is no specific treatment for this disease. Alzheimer's is most common among seniors 65 years and older. However, the progress of this disease can be reduced if it can be diagnosed earlier. Recently, artificial intelligence has instilled hope in the diagnosis of Alzheimer's disease by performing sophisticated analyses on extensive patient datasets, enabling the identification of subtle patterns that may elude human experts. Researchers have investigated various deep learning and machine learning models to diagnose this disease at an early stage using image datasets. In this paper, a new Deep learning (DL) methodology is proposed, where MRI images are fed into the model after applying various pre‐processing techniques. The proposed Alzheimer's disease detection approach adopts transfer learning for multi‐class classification using brain MRIs. The MRI Images are classified into four categories: mild dementia (MD), moderate dementia (MOD), very mild dementia (VMD), and non‐dementia (ND). The model is implemented and extensive performance analysis is performed. The finding shows that the model obtains 97.31% accuracy. The model outperforms the state‐of‐the‐art models in terms of accuracy, precision, recall, and F‐score. [ABSTRACT FROM AUTHOR]

Acupuncture points have a positive effect on the auxiliary prevention and treatment of diseases, so medical devices such as acupuncture robots often need to combine acupuncture points to improve the treatment effect when working, however, intelligent acupoint selection technology is not yet mature, the automatic rapid and accurate positioning of acupoints is still challenging. Therefore, this paper proposes a method of back acupoint location and an evaluation index of acupoint location. First, we propose an improved Keypoint RCNN network for the preliminary location of back acupoints and introduce a channel and spatial attention mechanism module (CBAM) to improve the performance of the model. Then, we set up a posterior median line positioning method to improve the accuracy of acupoint positioning. Finally, expand and locate other acupoints according to the prior information of acupoints. According to the experimental results, the accuracy of acupoint positioning was 87.32%. After the correction of acupoint positioning, the accuracy was increased by 2.8%, which was 90.12%. In this paper, the application of depth learning in automatic location of back acupoints is realized for the first time. Only one image can be used to locate the back acupoints, with an accuracy of 90.12%. [ABSTRACT FROM AUTHOR]

Xanthotoxin (XAT) is a natural furanocoumarins, a bioactive psoralen isolated from the fruit of the Rutaceae plant Pepper, which has received increasing attention in recent years due to its wide source and low cost. By collecting and compiling literature on XAT, the results show that XAT exhibits significant activity in the treatment of various diseases, including neuroprotection, skin repair, osteoprotection, organ protection, anticancer, antiinflammatory, antioxidative stress and antibacterial. In this paper, we review the pharmacological activity and potential molecular mechanisms of XAT for the treatment of related diseases. The data suggest that XAT can mechanistically induce ROS production and promote apoptosis through mitochondrial or endoplasmic reticulum pathways, regulate NF-κB, MAPK, JAK/STAT, Nrf2/HO-1, MAPK, AKT/mTOR, and ERK1/2 signaling pathways to exert pharmacological effects. In addition, the pharmacokinetics properties and toxicity of XAT are discussed in this paper, further elucidating the relationship between structure and efficacy. It is worth noting that data from clinical studies of XAT are still scarce, limiting the use of XAT in the clinic, and in the future, more in-depth studies are needed to determine the clinical efficacy of XAT. [ABSTRACT FROM AUTHOR]

Many believe that we ought to treat people as individuals and that this form of treatment is in some sense incompatible with treating people as members of groups. Yet, the relation between these two kinds of treatments is elusive. In this paper, we develop a novel account of the normative requirement to treat people as individuals. According to this account, treating people as individuals requires treating people as agents in the appropriate capacity. We call this the Agency Attunement Account. This view has the surprising implication that it's not only possible to fail in treating people as individuals but also possible to fail in treating people as members of groups, on the presumption that people's agency is sometimes nested in, and exercised via, agential groups. [ABSTRACT FROM AUTHOR]

Interleukin‐41 (IL‐41) is a newly discovered cytokine, named Cometin, Subfatin, meteorin‐like transcription (Metrnl), and so forth. It is widely expressed in animals and can exert its biological roles through autocrine and paracrine forms. It has functions such as anti‐inflammatory, improving body metabolism, regulating immunity, regulating fat metabolism and participates in the process of autoimmune disease or inflammatory injury. It plays an important role in psoriasis, diabetes, Crohn's disease (CD), osteoarthritis, Kawasaki disease (KD), Graves' disease, autoimmune hepatitis, infertility, obesity, sepsis, cardiovascular diseases and respiratory diseases. This paper reviews the biological functions of IL‐41, the relationship between IL‐41 and diseases, the effects of IL‐41 in the cytokine network and the possible signalling pathways. In order to explore the same target or the same drug for the treatment of different diseases from the perspective of homotherapy for heteropathy, cytokine strategies based on IL‐41 have been put forward for the precise treatment of immune diseases and inflammatory diseases. It is worth noting that IL‐41 related preparations for lung protection and smoking cessation are interesting research fields. [ABSTRACT FROM AUTHOR]

In cancer and other medical studies, time‐to‐event (eg, death) data are common. One major task to analyze time‐to‐event (or survival) data is usually to compare two medical interventions (eg, a treatment and a control) regarding their effect on patients' hazard to have the event in concern. In such cases, we need to compare two hazard curves of the two related patient groups. In practice, a medical treatment often has a time‐lag effect, that is, the treatment effect can only be observed after a time period since the treatment is applied. In such cases, the two hazard curves would be similar in an initial time period, and the traditional testing procedures, such as the log‐rank test, would be ineffective in detecting the treatment effect because the similarity between the two hazard curves in the initial time period would attenuate the difference between the two hazard curves that is reflected in the related testing statistics. In this paper, we suggest a new method for comparing two hazard curves when there is a potential treatment time‐lag effect based on a weighted log‐rank test with a flexible weighting scheme. The new method is shown to be more effective than some representative existing methods in various cases when a treatment time‐lag effect is present. [ABSTRACT FROM AUTHOR]

The medicalisation of marijuana has occurred rapidly, albeit nonuniformly, across the US and around the world over the past 3 decades. This paper centres on the medicalisation of marijuana in Minnesota—which has one of the most restrictive programs in the country—as a case for evaluating the negotiation of institutional boundaries with the shift from criminalisation to medicalisation after nearly a century of criminal prohibition. Drawing upon Foucauldian discourse analyses of the medical and law enforcement associations' position statements and legislative hearings that shaped medical marijuana policy in Minnesota, this paper demonstrates a symbiotic convergence between medicine and law enforcement through the deployment of shared discursive strategies in their opposition to medical marijuana that reinforce marijuana's criminalised status by solidifying the boundaries between proper medicine and dangerous drugs. Criminal justice and medical institutions draw upon one another's definitions, logics, and practices in a mutually constitutive manner, while still maintaining distinct user subjects and institutional interventions for each based on the user's access to state‐approved forms of marijuana. The consequences for the governing of marijuana in Minnesota are explored, as well as the broader implications for the sociological study of medicalisation and criminalisation with respect to the governance of drugs and health. [ABSTRACT FROM AUTHOR]

Background: Speech and language therapists and nurses need to work together to keep patients with swallowing difficulties safe throughout their acute stroke admission. Speech and language therapists make recommendations for safe swallowing following assessment and nurses put recommendations into practice and monitor how patients cope. There has been little research into the everyday realities of ongoing swallow safety management by these two disciplines. Patient safety research in other fields of healthcare indicates that safety can be enhanced through understanding the cultural context in which risk decisions are made. Aims: To generate new understanding for how speech and language therapists (SLTs) and nurses share information for ongoing management of swallows safety on stroke units. Methods & Procedures: An ethnographic methodology involving 40 weeks of fieldwork on three stroke wards in England between 2015 and 2017. Fieldwork observation (357 h) and interviews with 43 members of SLT and nursing staff. Observational and interview data were analysed iteratively using techniques from the constant comparative method to create a thematically organized explanation. Outcomes & Results: An explanation for how disciplinary differences in time and space influenced how SLT and nursing staff shared information for ongoing management of swallow safety, based around three themes: (1) SLTs and nurses were aligned in concern for swallow safety across all information‐sharing routes; however, (2) ambiguity was introduced by the need for the information contained in swallowing recommendations to travel across time, creating dilemmas for nurses. Patients could improve or deteriorate after recommendations were made and nurses had competing demands on their time. Ambiguity had consequences for (3) critical incident reporting and relationships. SLTs experienced dilemmas over how to act when recommendations were not followed. Conclusions & Implications: This study provides new understanding for patient safety dilemmas associated with the enactment and oversight of swallowing recommendations in context, on stroke wards. Findings can support SLTs and nurses to explore together how information for ongoing dysphagia management can be safely implemented within ward realities and kept up to date. This could include considering nursing capacity to act when SLTs are not there, mealtime staffing and SLT 7‐day working. Together they can review their understanding of risk and preferred local and formal routes for learning from it. What this paper adds: What is already known on the subject: It is known that information to keep swallowing safe is shared through swallowing recommendations, which are understood to involve a balance of risks between optimizing the safety of the swallow mechanism and maintaining physiological and emotional health. There is increasing appreciation from patient safety research, of the importance of understanding the context in which hospital staff make decisions about risk and patient safety. What this paper adds to existing knowledge: The paper provides new empirical understanding for the complexities of risk management associated with SLT and nursing interactions and roles with respect to ongoing swallow safety. What are the potential or actual clinical implications of this work?: Findings can underpin SLT and nurse discussion about how swallow safety could be improved in their own settings. [ABSTRACT FROM AUTHOR]

Background and Aims: Long‐acting injectable buprenorphine (LAIB) is a new treatment for opioid use disorder that is generating positive outcomes. Negative effects are typically mild and transient, but can occasionally be serious, resulting in treatment discontinuation/non‐adherence. This paper aims to analyse patients' accounts of how they felt during the first 72 h after initiating LAIB. Methods: Semi‐structured interviews were conducted (June 2021–March 2022) with 26 people (18 males and 8 females) who had started LAIB within the previous 72 h. Participants were recruited from treatment services in England and Wales and were interviewed by telephone using a topic guide. Interviews were audio‐recorded, transcribed and coded. The concepts of embodiment and embodied cognition framed the analyses. Data on participants' substance use, initiation onto LAIB and feelings were tabulated. Next, participants' accounts of how they felt were analysed following the stages of Iterative Categorization. Results: Participants reported complex combinations of changing negative and positive feelings. Bodily experiences included withdrawal symptoms, poor sleep, injection‐site pain/soreness, lethargy and heightened senses inducing nausea ('distressed bodies'), but also enhanced somatic wellbeing, improved sleep, better skin, increased appetite, reduced constipation and heightened senses inducing pleasure ('returning body functions'). Cognitive responses included anxiety, uncertainties and low mood/depression ('the mind in crisis') and improved mood, greater positivity and reduced craving ('feeling psychologically better'). Whereas most negative effects reported are widely recognized, the early benefits of treatment described are less well‐documented and may be an overlooked distinctive feature of LAIB. Conclusions: During the first 72 h after initiating long‐acting injectable buprenorphine, new patients report experiencing a range of interconnected positive and negative short‐term effects. Providing new patients with information about the range and nature of these effects can prepare them for what to expect and help them manage feelings and reduce anxiety. In turn, this may increase medication adherence. [ABSTRACT FROM AUTHOR]

An addendum of the ICH E9 guideline on Statistical Principles for Clinical Trials was released in November 2019 introducing the estimand framework. This new framework aims to align trial objectives and statistical analyses by requiring a precise definition of the inferential quantity of interest, that is, the estimand. This definition explicitly accounts for intercurrent events, such as switching to new anticancer therapies for the analysis of overall survival (OS), the gold standard in oncology. Traditionally, OS in confirmatory studies is analyzed using the intention‐to‐treat (ITT) approach comparing treatment groups as they were initially randomized regardless of whether treatment switching occurred and regardless of any subsequent therapy (treatment‐policy strategy). Regulatory authorities and other stakeholders often consider ITT results as most relevant. However, the respective estimand only yields a clinically meaningful comparison of two treatment arms if subsequent therapies are already approved and reflect clinical practice. We illustrate different scenarios where subsequent therapies are not yet approved drugs and thus do not reflect clinical practice. In such situations the hypothetical strategy could be more meaningful from patient's and prescriber's perspective. The cross‐industry Oncology Estimand Working Group (www.oncoestimand.org) was initiated to foster a common understanding and consistent implementation of the estimand framework in oncology clinical trials. This paper summarizes the group's recommendations for appropriate estimands in the presence of treatment switching, one of the key intercurrent events in oncology clinical trials. We also discuss how different choices of estimands may impact study design, data collection, trial conduct, analysis, and interpretation. [ABSTRACT FROM AUTHOR]

Summary: Background: Metabolic dysfunction‐associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Its prevalence is increasing with the epidemic of obesity and metabolic syndrome. MASLD progression into metabolic dysfunction‐associated steatohepatitis (MASH) and advanced fibrosis may lead to decompensated cirrhosis and development of liver‐related events, hepatocellular carcinoma and death. Monitoring disease progression is critical in decreasing morbidity, mortality, need for transplant and economic burden. Assessing for treatment response once FDA‐approved medications are available is still an unmet clinical need. Aims: To explore the most up‐to‐date literature on testing used for monitoring disease progression and treatment response Methods: We searched PubMed from inception to 15 August 2023, using the following MeSH terms: 'MASLD', 'Metabolic dysfunction‐associated steatotic liver disease', 'MASH', 'metabolic dysfunction‐associated steatohepatitis', 'Non‐Alcoholic Fatty Liver Disease', 'NAFLD', 'non‐alcoholic steatohepatitis', 'NASH', 'Biomarkers', 'clinical trial'. Articles were also identified through searches of the authors' files. The final reference list was generated based on originality and relevance to this review's broad scope, considering only papers published in English. Results: We have cited 101 references in this review detailing methods to monitor MASLD disease progression and treatment response. Conclusion: Various biomarkers can be used in different care settings to monitor disease progression. Further research is needed to validate noninvasive tests more effectively. [ABSTRACT FROM AUTHOR]

Background: Person‐centred services are inherently related to patients/caregivers' needs. However, the extent to which dysphagia services within Singapore meet consumer needs is largely unknown. Involving patients/caregivers in service evaluation/redesign deepens the understanding of consumer needs. This process also increases the success of implementing service enhancements through relevant and meaningful change. Aim: This study aimed to identify aspects of dysphagia services, within acute and subacute settings in Singapore, perceived as highly important and easy to change by patients/caregivers. Methods & Procedures: Using concept mapping methodology, 5 patients and 11 caregivers reflected on their experiences of receiving dysphagia care and proposed 59 unique suggestions to improve dysphagia services within Singapore. Then, each individual sorted the suggestions into groups based on similarity and rated each statement for its perceived importance and changeability for service enhancement. Data were analysed using multidimensional scaling, hierarchical cluster analysis, and bivariate analysis to generate clusters of conceptually similar suggestions and a prioritised list of suggestions for service enhancement. Results: Twelve clusters were identified, with most rated as more important than changeable for service improvement. Participants prioritised 23 (39%) of the suggestions as highly important and easy to change, and these focused on ensuring effective communication among consumers and healthcare team, enhancing patients and carers' access to support at home, increasing patients and carers' access to educational resources, and improving service quality and access through technology. Conclusion: These findings provide future directions on how to develop and implement dysphagia services in Singapore to better meet the needs of patients/caregivers. WHAT THIS PAPER ADDS: What is already known on this subject: Little is known about patients and caregivers' experiences and expectations of receiving dysphagia services in Singapore. Consulting them in service review and improvement deepens understanding of their needs and increases the success of implementing meaningful service enhancements. What this study adds to existing knowledge: This study shows that patients and caregivers in Singapore identified a wide range of dysphagia service issues and prioritised a list of suggestions for service improvement. They prioritised four key areas for service optimisation: ensuring effective communication among consumers and healthcare team, enhancing patients and carers' access to support at home, increasing patients and carers' access to educational resources, and improving service quality and access through technology. What are the clinical implications of this work?: This research highlights the importance of considering the consumers' perspectives in service review and redesign. Patients and caregivers in Singapore identified four prioritised areas for service enhancements. These findings provide future directions on how to develop and implement dysphagia services in Singapore to better meet the needs of patients and caregivers. [ABSTRACT FROM AUTHOR]

Objective: The study investigated adherence with MMF treatment among patients attending rheumatology clinics at University Hospitals Coventry and Warwickshire NHS Trust (UHCW) with Autoimmune inflammatory rheumatic diseases (AIIRDs). Methods: This retrospective study collated hospital pharmacy data in patients who requested the prescription for MMF between January 2015 and December 2018. Clinical data were obtained from paper and electronic notes. Data were analysed using Microsoft Excel. Ethical approval was obtained through Coventry University. Results: We recruited 144 patients into this study with age range from 18 to 91 years, including 100 females and 44 males. There were 112 White patients, 22 of South Asian origin, 3 East Asian and 4 black patients. SLE (56), scleroderma (18), mixed connective tissue disease (15), myositis (13), vasculitis (13) were the commonest diagnoses. Overall adherence with Mycophenolate mofetil was 62%. The adherence rates were below 80% for all age groups with ∼60% of patients having adherence levels of >60%. Poor adherence with MMF correlated with 3‐fold increase in risk of flares compared to good adherence (p = 0.002). We also found a significant difference between Asian patients (mean adherence 47%) and White patients (mean adherence 65%, p < 0.001). Conclusion: Adherence with MMF has improved considerably compared to historical studies, although these remain suboptimal. Certain population groups such as young adults, elderly and Asian patients continue to have lower adherence and higher risk of flares. Strategies are needed to improve adherence levels overall and specifically in the high‐risk groups to reduce risk of flares and organ damage. [ABSTRACT FROM AUTHOR]

Objectives: This paper aimed to explore the experiences of depressed adolescents who completed but did not 'respond' to standard psychotherapy, based on a lack of improvement in pre‐post symptoms scores. Design: This was a qualitative study employing interpretative phenomenological analysis (IPA). Method: Seventy‐seven adolescents with moderate to severe depression were interviewed as part of a qualitative arm of a randomised controlled trial. Five adolescents' post‐treatment interviews were purposively sampled, based on lack of improvement on pre‐post symptom scores, and adolescents still scoring above the clinical threshold for depression. The interviews were analysed using IPA. Results: Adolescents made sense of their depression as part of their identity and held negative expectations of therapy. Some aspects of therapy brought up intolerable feelings that contributed to disengagement in the therapeutic process and culminated in disappointing and hopeless endings. On the other hand, where a stronger therapeutic relationship was developed, some participants experienced certain improvements. Conclusions: Findings highlight how actively exploring the adolescent's therapy expectations, developing a strong early therapeutic relationship and being mindful of the potential impact of endings are important in therapeutic work with adolescents with depression, especially where they may have a strong sense of hopelessness and self‐criticism. Moreover, the finding that adolescents experienced improvements in other domains despite a lack of symptom reduction highlights the need to review how treatment outcomes are currently defined. Integrating individual perspectives of therapy with quantitative outcome measures can provide a more nuanced insight of treatment effects. [ABSTRACT FROM AUTHOR]

Background: Studies suggest swallow intervention programmes that incorporate visual biofeedback and motor programming principles can improve swallowing and quality of life for people with idiopathic Parkinson's disease (IPD) and dysphagia. Few studies have examined outcomes using instrumentation. Aims: Using fibreoptic endoscopic examination of swallowing (FEES), this study examines the effectiveness of a neurorehabilitation intervention involving biofeedback via surface electromyography (sEMG) to improve swallowing in people with IPD, and to explore the feasibility of the intervention approach. Methods & Procedures: We recruited 12 participants with IPD and dysphagia. A total of 10 completed the study. Intervention was delivered for 1 h per day, 5 days per week, for 4 weeks (20 h). Swallowing tasks using sEMG biofeedback incorporated principles of motor learning and neuroplasticity. Instrumental and non‐instrumental assessment, including quality‐of‐life measures carried out at four different time points (two pre‐treatment and two post‐treatment). The final assessment was at 3 months post‐intervention. Outcome & Results: Statistically significant improvement (p < 0.05) in oral intake methods (95% confidence interval (CI) = 4.70–5.50) and in pharyngeal residue from saliva (95% CI = 2.14–3.15) and solids (95% CI = 2.4–3.5) post‐intervention were confirmed using FEES with improvements at 3 months. The intervention protocol was well tolerated. Participants reported positive change in saliva control and duration of mealtimes as well as unanticipated improvements in voice and cognitive attention. Conclusions & Implications: An intensive neurorehabilitation with biofeedback shows positive effects in improving swallow function in IPD. This protocol is feasible with amendments to inform a larger clinical trial. What this paper adds: What is already known on the subject: Biofeedback has positive effects on increasing swallowing function and quality of life in people with IPD and dysphagia. sEMG is the most common method used to deliver swallowing biofeedback in this population. The quality of the evidence on the intervention, based on findings from a recent systematic review, is low. Included studies in this review were heterogeneous in terms of type and frequency of biofeedback, study design and outcome measures. The majority of outcome measures were subjective and higher quality studies to examine the efficacy of biofeedback using sEMG are needed. What this study adds: Recognizing the limitations of earlier studies, this within‐subject feasibility study examined the efficacy and effectiveness of an intensive biofeedback intervention using sEMG in a sample of people with dysphagia and IPD. Valid and reliable outcome measures were used and repeated after a 3‐month period. The feasibility of the methodological approach was also tested and a qualitative component was included in the study. Positive findings were evident. Qualitative information added new perspectives and provided direction for new outcomes to be included in future studies. This study helps to inform further research trials as well as clinical practice. Clinical implications of this study: This intensive intervention using principles of neuroplasticity and motor programming with sEMG biofeedback led not only to positive swallowing outcomes but also to unexpected benefits such as improved voice production and general attention skills. No adverse events were reported. Improvement in function was retained at 3 months post‐intervention. Despite the small sample size, participants described the benefits of the treatment, and enjoyed sEMG biofeedback tasks, especially using an sEMG game mode. This suggests that intensive biofeedback not only improved swallowing but also was acceptable to these participants. This intensive protocol has merit and is worth considering further in clinical practice. [ABSTRACT FROM AUTHOR]

Accumulating evidence during the last two decades has addressed the potential anti‐inflammatory properties of berberine (BBR), a bioactive alkaloid compound isolated from Coptidis rhizoma, in controlling or treating several inflammatory diseases. Periodontitis is one of the most common chronic and serious inflammatory diseases, in which uncontrolled and unabated host immune responses against periodontopathic pathogens play critical and crucial roles in the disease pathogenesis. Hence, regulating inflammatory responses in periodontitis has a valuable approach and holds promise in treating periodontitis. For the first time, this paper reviews the evidence from in vitro and in vivo experimental models to explore the anti‐inflammatory effects of BBR in periodontitis and exhibits that BBR has the high potency to exert anti‐inflammatory effects by reducing expression and secretion of pro‐inflammatory mediators including TNF‐α, IL‐1β, IL‐17, RANKL, MMP‐2, MMP‐9 and MCP‐1. The BBR‐mediated anti‐inflammatory actions could translate into the inhibition of the periodontal tissues and alveolar bone destruction and the control of the disease in vivo. As the second aim of this paper, we also paid attention to the therapeutic potential of BBR in treating human diseases regarding its anti‐inflammatory properties. [ABSTRACT FROM AUTHOR]

The novel coronavirus has created one of the biggest social and economic challenges in recent decades. Since a critical issue in overcoming a large‐scale pandemic involves finding effective treatments for the disease, there is typically urgent pressure on the health‐care sector to develop innovations to combat the pandemic. Recently, scholars have argued that repurposing – that is, reusing an existing innovation in a different context – allows for such rapid innovation responses and can reduce costs, as the groundwork has already been laid. In this paper, we compare these benefits with the considerable disadvantages associated with innovation repurposing, including lowered barriers to entry, which can lead to declining average quality and duplicate work. Using data on 2,456 COVID‐19‐related clinical trials initiated between December 2019 and July 2020, we find that merely one‐third of the trials actually investigated drugs or vaccines, whereas the rest focused on diagnostics and crisis management issues. In the trials concerning drug testing, we find that drug repurposing is a predominant innovation strategy, but many trials tested the same (combination of) drugs. This indicates an inefficient use of resources and reductions in the average variety and novelty of clinical trials. Furthermore, the small percentage of biopharmaceutical firms involved in the search for COVID‐19 treatments raises the question of whether firms may have insufficient incentives to redirect innovation efforts to respond to the pandemic. Our paper contributes to crisis management research, the nascent debate on COVID‐19, and the emerging literature on innovation repurposing. [ABSTRACT FROM AUTHOR]

Aims: EEC is a rare syndrome characterized by the triad of ectrodactyly, ectodermal dysplasia, and orofacial clefting, along with other clinical manifestations mainly in hair, skin, and teeth. The present paper aimed to perform a scoping review to collect the most relevant studies and focused on the diagnosis and oral management of EEC syndrome in the pediatric dental setting. This review also pretended to make recommendations and map the gaps in this clinical topic. Methods: An exhaustive electronic and manual search was conducted in four databases (PubMed, EMBASE, Google Scholar, and Dentistry & Oral Sciences Source/EBSCO) according to previously established eligibility criteria, using different combinations of keywords, MeSH terms, and Boolean operators. Titles, abstracts, and full‐text articles were screened and selected by precalibrated reviewers. A data charting was also accomplished for summarizing the overview of the evidence. Results: A total of 37 references were identified, and 32 titles remained after removing duplicates; then, 25 potential full‐text articles were carefully reviewed. Finally, 15 relevant and most informative studies were included. Most studies were single clinical case reports. Only one descriptive retrospective study was detected. None randomized clinical trials or comparative observational studies were found. A medical/dental multidisciplinary approach is needed for the management of EEC syndrome. Conclusions: Diverse dental specialists must be involved. Pediatric dentists must play a principal role in the prevention and treatment of oral diseases; particularly the preservation of the primary and mixed dentitions, trying to achieve normal orofacial growth. [ABSTRACT FROM AUTHOR]

Rett syndrome (RTT) is an X‐linked neurogenetic disorder caused by mutations of the MECP2 (methyl‐CpG‐binding protein 2) gene. Over two decades of work established MeCP2 as a protein with pivotal roles in the regulation of the epigenome, neuronal physiology, synaptic maintenance, and behaviour. Given the genetic aetiology of RTT and the proof of concept of its reversal in a mouse model, considerable efforts have been made to design therapeutic approaches to re‐express MeCP2. By being at the forefront of the development of innovative gene therapies, research on RTT is of paramount importance for the treatment of monogenic neurological diseases. Here we discuss the recent advances and challenges of promising genetic strategies for the treatment of RTT including gene replacement therapies, gene/RNA editing strategies, and reactivation of the silenced X chromosome. What this paper adds: Recent advances shed light on the promises of gene replacement therapy with new vectors designed to control the levels of MeCP2 expression.New developments in DNA/RNA editing approaches or reactivation of the silenced X chromosome open the possibility to re‐express the native MeCP2 locus at endogenous levels.Current strategies still face limitations in transduction efficiency and future work is needed to improve brain delivery. [ABSTRACT FROM AUTHOR]

Aim: To evaluate early dystonic features in children and adolescents with SGCE‐myoclonus–dystonia. Method: In this cross‐sectional study, 49 patients (26 females and 23 males) with SGCE‐myoclonus–dystonia (aged 15y 2mo, SD 12y) with childhood‐onset (2y 10mo, SD 1y 10mo) dystonia were examined using a standardized video recorded protocol. Dystonia was rated using the Writer's Cramp and Gait Dystonia Rating Scales. Disability and impairment for handwriting and walking were also rated. Results: Dystonia was present at rest (n=1), posture (n=12), and during specific motor tasks (n=45) such as writing (n=35), walking (n=23), and running (n=20). Most children reported disability while performing these tasks. Early dystonic patterns were identified for writer's cramp and gait dystonia, the latter named the 'circular shaking leg', 'dragging leg', and 'hobby‐horse gait' patterns. Sensory tricks were used by five and eight children to improve dystonia and myoclonus during writing and walking respectively. The rating scales accurately measured the severity of action dystonia and correlated with self‐reported disability. Interpretation: Children with SGCE‐myoclonus–dystonia show recognizable dystonic patterns and sensory tricks that may lead to an early diagnosis and timely therapeutic approach. Isolated writer's cramp is a key feature in childhood and should prompt SCGE analysis. The proposed action dystonia scales could be used to monitor disease course and response to treatment. What this paper adds: Most children with SGCE‐myoclonus–dystonia got writer's cramp and had walking and running dystonia.Writer's cramp was a key feature and should prompt SGCE genetic investigation.'Circular shaking leg', 'dragging leg', and 'hobby‐horse gait' were recognized as early gait patterns.Children used sensory tricks to improve myoclonus and dystonia, suggesting common pathophysiological mechanisms.Action dystonia rating scales are valid tools to assess severity in children. [ABSTRACT FROM AUTHOR]

Objectives: Blue rubber bleb nevus syndrome (BRBNS) is a rare challenging cause of gastrointestinal bleeding. We performed a systematic review of case reports and case series on BRBNS to gather information on the treatment options currently available. Methods: All studies reporting a case of BRBNS in humans were evaluated. Papers were ruled out if CARE criteria and explanations on patient's selection, ascertainment, causality, and reporting were not respected or identified. PROSPERO 2021 CRD 42021286982. Results: Blue rubber bleb nevus syndrome was treated in 106 cases from 76 reports. 57.5% of the population was under 18 years old, and up to 50% of the cases reported a previous treatment. Clinical success was achieved in 98 patients (92.4%). Three main types of interventions were identified: systemic drug therapy, endoscopy, and surgery. After BRBNS recurrence or previous therapy failure, systemic drug therapy emerged as a preferred second‐line treatment over endoscopy (P = 0.01), but with a higher rate of reported adverse events when compared with surgery and endoscopy (P < 0.001). Endoscopic treatment was associated with a higher number of required sessions to achieve complete eradication when compared with surgery (P < 0.001). No differences between the three main areas were found in the overall follow‐up time (P = 0.19) or in the recurrence rate (P = 0.45). Conclusion: Endoscopy, surgery, and systemic drug therapy are feasible treatment options for BRBNS. Systemic drug therapy was the favorite second‐line treatment after endoscopic failure or recurrence of BRBNS, but adverse events were more frequently reported. [ABSTRACT FROM AUTHOR]

Purpose: Management of children following a drowning incident is based on specific interventions which are used in the prehospital environment, the emergency department (ED) and the Paediatric Intensive Care Unit (PICU). This paper presents a review of the literature to map and describe the management and interventions used by healthcare professionals when managing a child following a drowning incident. Of specific interest was to map, synthesise and describe the management and interventions according to the different clinical domains or practice areas of healthcare professionals. Design and Methods: A traditional review of the literature was performed to appraise, map and describe information from 32 relevant articles. Four electronic databases were searched using search strings and the Boolean operators AND as well as OR. The included articles were all published in English between 2010 and 2022, as it comprised a timeline including current guidelines and practices necessary to describe management and interventions. Results: Concepts and phrases from the literature were used as headings to form a picture or overview of the interventions used for managing a child following a drowning incident. Information extracted from the literature was mapped under management and interventions for prehospital, the ED and the PICU and a figure was constructed to display the findings. It was evident from the literature that management and interventions are well researched, evidence‐informed and discussed, but no clear arguments or examples could be found to link the interventions for integrated management from the scene of drowning through to the PICU. Cooling and/or rewarming techniques and approaches and termination of resuscitation were found to be discussed as interventions, but no evidence of integration from prehospital to the ED and beyond was found. The review also highlighted the absence of parental involvement in the management of children following a drowning incident. Practice Implications: Mapping the literature enables visualisation of management and interventions used for children following a drowning incident. Integration of these interventions can collaboratively be done by involving the healthcare practitioners to form a link or chain for integrated management from the scene of drowning through to the PICU. [ABSTRACT FROM AUTHOR]

The objective of this paper was to investigate the published evidence regarding effects of cannabinoids (natural and synthetic) on post‐operative and/or out‐of‐office pain management in patients suffering from orofacial pain that presents in the dental setting. Three online databases (Ovid (MEDLINE), PubMed (MEDLINE), Scopus) were searched (July 2021). Additional studies were sought through grey literature searching (Cochrane Library Trials and ClinicalTrials.gov) and hand‐searching the reference lists of included articles. All studies that analysed cannabinoid products and pain management of conditions that present in the general or specialist dental setting in the English language were included. Of the five articles included, one reported a significant effect on temporomandibular disorder pain relief using a topical cannabidiol formulation compared to a placebo. Four articles reported no significant effects of cannabinoids for pain management across various orofacial pain conditions. Although one study reported a positive effect, insufficient evidence exists to support a tangible clinical benefit of cannabinoids in managing orofacial pain, further research is recommended to investigate the benefits of cannabinoids' use. © 2022 Australian Dental Association. [ABSTRACT FROM AUTHOR]

Background: As part of a multifaceted approach to patient and public involvement and engagement (PPIE), alongside traditional methods, a closed Facebook group was established to facilitate PPIE feedback on various aspects of a project that used video‐recording to examine risk communication in NHS Health Checks between June 2017 and July 2019. Objective: To explore the process and impact of conducting PPIE through a closed Facebook group and to identify the associated benefits and challenges. Methods: Supported by reflections and information from project meetings used to document how this engagement informed the project, we describe the creation and maintenance of the Facebook Group and how feedback from the group members was obtained. Facebook data were used to investigate levels and types of engagement in the closed Facebook group. We reflect on the challenges of using this method of engaging the public in health research. Results: A total of 289 people joined the 'Risk Communication of Cardiovascular disease in NHS Health Checks' PPIE closed Facebook group. They provided feedback, which was used to inform aspects of the study, including participant‐facing documents, recruitment, camera position and how the methodology being used (video‐recorded Health Checks and follow‐up interviews) would be received by the public. Discussion: Using a closed Facebook group to facilitate PPIE offered a flexible approach for both researchers and participants, enabled a more inclusive method to PPIE (compared with traditional methods) and allowed rapid feedback. Challenges included maintaining the group, which was more labour intensive than anticipated and managing members' expectations. Suggestions for best practice include clear communication about the purpose of the group, assigning a group co‐ordinator to be the main point of contact for the group, and a research team who can dedicate the time necessary to maintain the group. Conclusion: The use of a closed Facebook group can facilitate effective PPIE. Its flexibility can be beneficial for researchers, patients and public who wish to engage in the research process. Dedicated time for sustained group engagement is important. Patient or Public Contribution: Patient representatives were engaged with the development of the research described in this paper and a patient representative reviewed the manuscript. [ABSTRACT FROM AUTHOR]

Summary: Mesenchymal stromal cells (MSCs) are non‐haematopoietic cells found in fetal and adult organs, that play important roles in tissue repair, inflammation and immune modulation. MSCs residing in the bone marrow interact closely with haematopoietic cells and comprise an important component of the microenvironment supporting haematopoiesis, in both health and disease states. Since their identification in 1970, basic scientific and preclinical research efforts have shed light on the role of MSCs in the regulation of haematopoiesis and evoked interest in their clinical application in haematopoietic stem cell transplantation (HSCT) and malignant haematology. Over the last two decades, these research efforts have led to numerous clinical trials, which have established the safety of MSC therapy; however, the optimal mode of administration and the benefit remain inconclusive. In this paper, we will review the clinical experience with use of MSCs in HSCT for enhancement of engraftment, prevention and treatment of graft‐versus‐host disease and haemorrhagic cystitis. Then, we will discuss the contradictory evidence regarding tumour‐promoting versus tumour‐suppressing effects of MSCs in haematological malignancies, which may have relevance for future clinical applications. [ABSTRACT FROM AUTHOR]