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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: 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: 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: 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]

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]

Abstract: UV‐based (PUVA and narrowband UVB) phototherapy is broadly and commonly used in the treatment of Cutaneous T‐cell Lymphomas (CTCL), yet unfortunately, the evidence for the efficacy of these treatments is based only on case series or prospective but non‐randomized studies. Therefore, no internationally approved guidelines exist and no standardization of schedules has been proposed. Recently, consensus guidelines have been published by the United States Cutaneous Lymphoma Consortium. The aim of this study was to review the biological and clinical evidences on PUVA and NB‐UVB in CTCL and to critically evaluate acceptability and feasibility of these guidelines in the real‐life setting from the perspective of the Cutaneous Lymphoma Task Force of the Italian Lymphoma Foundation (Fondazione Italiana Linfomi, FIL). [ABSTRACT FROM AUTHOR]

Background Chronic heart failure ( HF) is a relevant and growing public health problem. Although the prognosis has recently improved, it remains a lethal disease, with a mortality that equals or exceeds that of many malignancies. Furthermore, chronic HF is costly, representing a large and growing drain on healthcare resources. Methods This narrative review is based on the material searched for and obtained via PubMed up to May 2017. The search terms we used were as follows: 'heart failure, echocardiography, natriuretic peptides' in combination with 'treatment, biomarkers, guidelines.' Results Recent studies have supported the value of natriuretic peptides ( NPs) and Doppler echocardiographic biomarkers of increased left ventricular ( LV) filling pressures or pulmonary congestion as tools to scrutinize patients with impending clinically overt HF. Therefore, combination of pulsed-wave tissue and blood flow Doppler with NPs appears valuable in guiding HF management in the outpatient setting. In as much as both the echo and the plasma levels of NPs may reflect the presence of fluid overload and elevations of LV filling pressures, integrating NP and echocardiographic biomarkers with clinical findings may help the cardiologist to identify high-risk patients, that is to recognize whether a patient is stable or the condition is likely to evolve into decompensated HF, to optimize treatment, to improve the prognosis and to reduce rehospitalization. Conclusion We discussed the rationale and the clinical significance of combining follow-up echo and NP assessment to guide management of ambulatory patients with chronic HF. [ABSTRACT FROM AUTHOR]

The American College of Clinical Pharmacy ( ACCP) published an initial white paper on herbal products in 2000. Since then, the global market for natural products has continued to expand, with tens of millions of consumers using such products on an annual basis in the United States alone. However, despite this expansion, natural products remain largely unregulated compared with prescription medications, have moderate- to low-level clinical evidence for efficacy, and continue to have safety concerns, including adulteration and misbranding. As comprehensive medication management experts, clinical pharmacists are uniquely qualified to navigate these concerns and advise patients appropriately. To develop and recommend a suitable care plan involving natural products, clinical pharmacists must establish a strong pharmacist-patient relationship, assess the appropriateness of therapy, educate the patient regarding key issues, and continuously monitor and follow up on the effectiveness of the care plan. This process should not only occur in an individual community or hospital setting, but also whenever a patient transitions from one care setting to another in cooperation with other clinicians. [ABSTRACT FROM AUTHOR]

The Vitiligo Global Issues Consensus Conference ( VGICC), through an international e-Delphi consensus, concluded that 'repigmentation' and 'maintenance of gained repigmentation' are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation, and the second section summarizes the outcomes of international meeting discussions and two e-surveys on vitiligo repigmentation, which had been carried out over 3 yr. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e-surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus. [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]

Background Skin diseases constitute up to 40% of all notified occupational diseases in most European countries, predominantly comprising contact dermatitis, contact urticaria, and skin cancer. While insufficient prevention of work-related skin diseases (WRSD) is a top-priority problem in Europe, common standards for prevention of these conditions are lacking. Objective To develop common European standards on prevention and management of WRSD and occupational skin diseases (OSD). Method Consensus amongst experts within occupational dermatology was achieved with regard to the definition of minimum evidence-based standards on prevention and management of WRSD/OSD. Results By definition, WRSDs/OSDs are (partially or fully) caused by occupational exposure. The definition of OSD sensu stricto additionally includes diverging national legal requirements, with an impact on registration, prevention, management, and compensation. With the implementation of the classification of WRSD/OSD in the International Classification of Diseases (ICD) 11th Revision in future, a valid surveillance and comparability across countries will be possible. Currently, WRDS and OSD are still under-reported. Depending on legislation and regulations, huge differences exist in notification procedures in Europe, although notification is crucial to prevent chronic and relapsing disease. Facilities for early diagnosis, essential for individual patient management, should be based on existing guidelines and include a multidisciplinary approach. Patch testing is essential if contact dermatitis persists or relapses. Workplace exposure assessment of WRSD/OSD requires full labelling of product ingredients on material safety data sheets helping to identify allergens, irritants and skin carcinogens. Comparable standards in primary, secondary and tertiary prevention must be established in Europe to reduce the burden of WRSD/OSD in Europe. Conclusion The adoption of common European standards on prevention of WRSD/OSD will contribute to reduce the incidence of OSD and their socio-economic burden. [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]

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]

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: : 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]

Background: The novel proteasome inhibitor carfilzomib alone or in combination with other agents is already one of the standard therapies for relapsed and/or refractory multiple myeloma (MM) patients and produces impressive response rates in newly diagnosed MM as well. However, carfilzomib-related cardiovascular adverse events (CVAEs) - including hypertension (all grades: 12.2%; grade ≥3: 4.3%), heart failure (all grades: 4.1%; grade ≥3: 2.5%) and ischemic heart disease (all grades: 1.8%; grade ≥3: 0.8%) - may lead to treatment suspensions. At present, there are neither prospective studies nor expert consensus on the prevention, monitoring and treatment of CVAEs in myeloma patients treated with carfilzomib.Methods: An expert panel of the European Myeloma Network in collaboration with the Italian Society of Arterial Hypertension and with the endorsement of the European Hematology Association aimed to provide recommendations to support health professionals in selecting the best management strategies for patients, considering the impact on outcome and the risk-benefit ratio of diagnostic and therapeutic tools, thereby achieving myeloma response with novel combination approaches whilst preventing CVAEs.Results: Patients scheduled to receive carfilzomib need a careful cardiovascular evaluation before treatment and an accurate follow-up during treatment.Conclusions: A detailed clinical assessment before starting carfilzomib treatment is essential to identify patients at risk for CVAEs, and accurate monitoring of blood pressure and of early signs and symptoms suggestive of cardiac dysfunction remains pivotal to safely administer carfilzomib without treatment interruptions or dose reductions. [ABSTRACT FROM AUTHOR]

Glucose-6-phosphate dehydrogenase (G6PD) deficient individuals are at increased risk of developing haemolysis following treatment with various antimalarial drugs. Reliable field tests for G6PD deficiency are thus needed in chemotherapy studies and their validity has to be assessed. In two phase II clinical trials on methylene blue (MB) antimalarial therapy in rural Burkina Faso, paediatric and adult participants were tested for G6PD deficiency. The results of a haemoglobin-adjusted nicotinamide adenine dinucleotide phosphate (NADPH) fluorescence test on paper (NFP test) were compared with polymerase chain reaction (PCR)-based G6PD genotyping also using blood samples on filter papers. This is the first study comparing sensitivity and specificity of the two methods. There was good agreement between the NFP test results and the PCR findings. The estimate of the sensitivity of the NFP test was 98·2% (95·8–99·6%) and the specificity was 97·1% (94·2–99·2%). In conclusion, the NFP assay is a reliable and inexpensive method for large-scale G6PD deficiency screening in rural West Africa. [ABSTRACT FROM AUTHOR]

To examine how countries differ in attitudes to adverse drug reactions by examining published scientific papers.We searched Ovid EMBASE for publications indexed by the category′therapeutic agents′, and the subcategory′adverse effects′, by country for 43 countries.We counted 1 810 202 papers world-wide regarding therapeutic agents during 14 years, of which 195 154 (10.8%) were included in the adverse effects subcategory. There were substantial differences between countries, not explained by population, economic variation, overall publication rate on therapeutic agents, or the presence of large indigenous pharmaceutical companies.Many local cultural factors influence the ratio of papers on adverse reactions to all drug effects, so it may be difficult to improve their recognition and reporting by international efforts. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia is a major risk factor for development of coronary heart disease. Proper diagnosis and adequate treatment are vital to reducing morbidity and mortality associated with elevated serum lipid levels. The amount of literature in this area is overwhelming. To aid practitioners and educators in organizing this large body of information, we compiled key articles, guidelines, and consensus papers relative to the treatment of dyslipidemias. Research articles were chosen based on the significance of findings, relevance to practice, quality of research, and timeliness; recent articles were given priority over earlier ones unless they demonstrated groundbreaking findings. [ABSTRACT FROM AUTHOR]

The article presents information on Rhinosinusitis. Rhinosinusitis is a significant health problem which seems to mirror the increasing frequency of allergic rhinitis and which results in a large financial burden on society. The last decade has seen the development of a number of guidelines, consensus documents and position papers on the epidemiology, diagnosis and treatment of rhinosinusitis and nasal polyposis. The diagnosis of rhinosinusitis is made by a wide variety of practitioners, including allergologists, otolaryngologists, pulmonologists, primary care physicians and many others.

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]

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]

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]

Background: The clinical diagnosis of manifest Huntington's disease (HD) relies on a high level of clinical confidence (99% confidence) of HD‐consistent motor signs. Longitudinal data have reliably identified cognitive and behavioral dysfunction predating clinical motor diagnosis by up to 15 years. Reliance on motor signs to establish a diagnosis of HD increases risk of early misdiagnosis or delayed diagnosis. Clinical neuropsychologists are uniquely positioned to advise on the clinical application of the Movement Disorder Society Task Force's recently proposed non‐motor diagnostic criteria for HD. Objectives: To provide (1) a recommended clinical approach toward non‐motor diagnostic criteria in persons with HD and facilitation of accurate diagnosis; (2) recommended practices for medical treatment providers to screen and longitudinally monitor non‐motor signs of HD. Methods: The Huntington Study Group re‐established the Neuropsychology Working Group, then recruited a multi‐disciplinary group of neuropsychologists, neurologists, and psychiatrists to conduct an unstructured literature review and discuss expert opinions on practice, to facilitate an informal consensus opinion to accomplish the objectives. Results: The opinion and an example protocol for medical treatment providers to screen, monitor, and triage non‐motor signs and symptoms of Huntington's disease is provided. Conclusions: Clinical diagnosis of non‐motor HD is empirically justified and clinically important. Screening and triage by non‐neuropsychologist clinicians can aid in detecting and monitoring non‐motor Huntington's disease manifestation. The Neuropsychology Working Group consensus advances good clinical practice, clinical research, and quality of life. A companion position paper presenting the details of our consensus opinion regarding evidence‐based guidelines for neuropsychological practice is forthcoming. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary factor X deficiency is a rare bleeding disorder, with limited treatment options. This paper describes the approach to pre‐clinical development and characterization of a high‐purity plasma‐derived factor X concentrate, to achieve orphan drug marketing authorization for the treatment of hereditary factor X deficiency. Methods: A chromatographic process was developed, to purify factor X from human plasma for fractionation. The product was characterized using in vitro, in vivo and ex vivo tests for potency, purity, thrombogenicity, immunogenicity, toxicity and stability. Results: The production process complied with good pharmaceutical manufacturing practice. It achieved 6000‐fold purification and 100‐fold concentration of the factor X protein compared to human plasma. The factor X protein was 94%–96% pure. Other residual plasma proteins were well below levels in plasma, minimizing potential interference in hemostasis after therapeutic administration. Effective virus‐reduction during manufacture, and the absence of thrombogenicity, toxicity and immunogenic potential were confirmed, addressing the main safety concerns historically associated with plasma‐derived therapeutics. The freeze‐dried product remained stable between +2°C and +30°C for at least three years. After reconstitution with water for injections, the factor X activity was maintained for at least 48 h at +18°C to +22°C. Conclusion: Targeted pre‐clinical development of the first highly‐purified concentrate to treat hereditary factor X deficiency is described. Following international guidelines for nonclinical safety testing, particular strategies were adopted for unmodified products derived from human blood plasma. This approach may also be relevant to the development of other ultra‐orphan medicinal products. [ABSTRACT FROM AUTHOR]

Transplantation is a high‐risk, high‐cost treatment for end‐stage diseases and is the most strictly regulated area of healthcare in the United States. Thus, achieving success for patients and the program requires skillful and collaborative leadership. Various factors, such as outcomes, volume, and financial health, may measure the success of a transplant program. Strong collaboration between clinical and administrative leaders is key to achieving and maintaining success in those three categories. Clinical leaders of adult programs, such as medical and surgical directors, bear the primary responsibility for a program's volume, outcomes, and patient safety, while administrative directors are focused on business intelligence and regulatory compliance. This paper aims to provide readers with insights into the critical role of collaborative leadership in running a successful program, with a focus on clinical, business, and regulatory perspectives. [ABSTRACT FROM AUTHOR]

This paper presents findings from a qualitative study that explored children's and families' experiences of alternative care in Thailand. The study used arts‐based methods to engage 160 children living in a range of care settings. This included government and NGO‐run residential care settings (RCS), children's villages, Buddhist temples, migrant learning centres and foster care homes. Interviews were also conducted with 20 parents/guardians who had placed their children in care. Findings show that despite the alternative care system presenting significant challenges, the participants revealed how they strived to preserve their family connections, and how they are 'doing family' in adversity. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editor discusses various reports published within the issue on topics including the shift from therapy as a healing relationship to therapy as the application of specific techniques, the specific nature of bureaucracy, and rituals that generate a feeling of mechanical repetition.

Idiopathic constipation in children can be difficult to manage with conventional therapies. The present study aimed to evaluate the efficacy of adjunctive botulinum toxin injection in children attending our regional centre with refractory idiopathic constipation associated with internal anal sphincter hypertonicity. Children suffering refractory constipation after a minimum of 3 months bowel training, dietary and laxative treatments were evaluated by anorectal manometry. Those with idiopathic anal sphincter hypertonicity (resting pressure > 60 mmHg with normal recto-anal reflex) were recruited for botulinum toxin injection. Pretreatment evaluation also included bowel-function score and the degree of megarectum as measured transpubically by ultrasound. Each child received 60 units of Botox intrasphincterically under general anaesthesia. Follow-up evaluations were carried out at 6 weeks and 6 months. Eleven Chinese children, mean age 6.1 years, underwent botulinum toxin treatment. The mean sphincter pressure decreased from 73 mmHg to 55 mmHg and the mean symptom score improved from 2.5 to 6.3 ( P = 0.003, Wilcoxon signed rank-sum test). The mean rectal diameter decreased from 3.7 cm to 3.4 cm. Findings were sustained at 6 months with no treatment complications. Botulinum toxin intrasphincteric injection is a safe, non-invasive and effective adjunct to conventional therapies in managing children with refractory idiopathic constipation associated with sphincter hypertonicity. Timely definitive therapy to facilitate pain-free habitual defecation plays an important role in these children in their potty training, as demonstrated by the sustained 'sphincterotomy' effects outlasting the transient toxin paralysis. [ABSTRACT FROM AUTHOR]

The methodology of randomized clinical trials is essential for the critical assessment and registration of therapeutic interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement was developed to alleviate the problems arising from the inadequate reporting of randomized controlled trials. The present article reflects on the items that we believe should be included in the CONSORT checklist in the context of conducting and reporting trials in allergen-specific immunotherapy. Only randomized, blinded (in particular blinding of patients, health care providers, and outcome assessors), placebo-controlled Phase III studies in this article. Our analysis focuses on the definition of patients’ inclusion and exclusion criteria, allergen standardization, primary, secondary and exploratory outcomes, reporting of adverse events and analysis. [ABSTRACT FROM AUTHOR]

The article presents different studies related to a variety of internal medicines and respective illness that can be treated. These include the early warning score (EWS), which is considered a useful tool in detecting patients who deteriorate their clinical condition. Meanwhile, physicians should also address issues manifesting a poor vascular health. It also notes that benchmarking method have confounded the estimates of the treatment outcomes.

Comments on two research on pharmacologic therapy for prehypertension and therapeutic inertia as a barrier to blood pressure control. Blood pressure values of prehypertension; Results of the Trial of Preventing Hypertension that began in 1999; Definition of therapeutic inertia.

The article comments on the study "Prevention of Cardiovascular Events With an Antihypertensive Regimen of Amlodipine Adding Perindopril as Required Versus Atenolol Adding Bendroflumethiazide as Required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm: A Multicentre Randomised Controlled Trial," by B. Dahlof, P. S. Sever, N. R. Poulter and colleagues. It explains that the trial suggests that atenolol is not an acceptable therapy for the treatment hypertension. Further, it suggests that a strategy using a calcium channel blockers is more effective than the β-blocker atenolol. It argues that the trial was not a trial of combination agent therapy and should not be interpreted as such. It also states the blood pressure in the trial was poorly controlled.

Discusses several research on hypertension. Comments regarding the use of atenolol as a drug for hypertension; Cardiovascular benefits that can be derived from angiotensin-converting enzyme inhibit therapy by low-risk patients with coronary artery disease and preserved left ventricular function; Information on protection against fracture offered by beta blockers.

In the absence of an internationally agreed classification of haemorrhoids, evaluation of the ever increasing number of therapeutic options available is impossible. A new classification is proposed which relates symptoms to our knowledge of haemorrhoidal development, the use of which should provide a more accurate way of comparing treatments and in the evaluation of new techniques. The evidence for such a classification is presented in detail. [ABSTRACT FROM AUTHOR]

Dysregulation of fibroblast growth factor receptor 3 ( FGFR3) by the translocation t(4;14)(p16;q32) occurs in 15% of multiple myeloma (MM) patients and confers a growth and survival advantage to malignant plasma cells. As FGFR3 is a molecular target, we assessed the therapeutic potential of the FGFR-specific tyrosine kinase inhibitors SU5402 and SU10991 in MM. SU5402 inhibited FGFR3 phosphorylation in vitro and in murine MM tumour models. B cells dependent on FGFR3 for survival were specifically sensitive to SU5402. A panel of 11 human myeloma cell lines was studied, five bearing the t(4;14) translocation. The KMS11 human myeloma cell line, which expresses constitutively active mutant FGFR3, displayed an 85% decrease in S-phase cells, a 95% increase in G0/G1 cells, and 4·5-fold increase in apoptotic cells after 72 h treatment with 10 μmol/l SU5402. Activated extracellular signal-regulated kinases  1 and 2 and signal transducer and activator of transcription 3 were rapidly down-regulated after SU5402 treatment. In human myeloma cell lines expressing wild-type FGFR3 the stimulating effect of aFGF ligand was abrogated by SU5402 treatment. Myeloma cells lacking the t(4;14) or with the t(4;14) and a secondary RAS mutation did not respond to therapy. These findings support the development of clinical trials of early intervention with FGFR3 inhibitors in t(4;14) myeloma. [ABSTRACT FROM AUTHOR]

Primary plasma cell leukaemia (PCL) is a rare plasma cell malignancy, which is related to multiple myeloma (MM) and is characterized by a poor prognosis. In a previous study we demonstrated that PCL plasma cells display a high expression of CD27, in contrast to MM plasma cells. The present study was set out to assess the functional properties of CD27 expressed on PCL plasma cells by triggering with its ligand CD70. Using CD27-expressing purified plasma cells from a PCL patient we demonstrated that CD27-triggering modestly inhibited spontaneous and dexamethasone-induced apoptosis. In vitro stimulation and Western blotting showed that activation of p38 and extracellular-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinases (MAPK) was associated with CD27-mediated signal transduction. Specific inhibition of p38 and ERK1/2 MAPK abolished the anti-apoptotic effects of CD27-triggering. Interestingly, simultaneous inhibition of p38 and ERK1/2 strongly sensitized PCL cells for dexamethasone-induced apoptosis. Finally, in dexamethasone-treated PCL cells, CD27-triggering was associated with persistent DNA-binding activity of activator protein 1 (AP-1) but not of nuclear factor- κB. These findings suggest that, in primary PCL, specific anti-apoptotic pathways exist that might provide novel therapeutic targets. [ABSTRACT FROM AUTHOR]

The paper of the Change Process Study Group of Boston addresses an unsolved conceptual problem: How does one codify intersubjective states? The transfer of concepts from infant research to the adult therapeutic dyad is more than an analogy in that certain primitive aspects of mind appear in infancy, but persist throughout life. The regulation of consciousness is one salient example. The adult therapeutic dyad and the mother–infant dyad can be viewed as self-regulating dynamic systems that are also self-reparative. The concept of implicit relational knowledge is offered as an alternative way of thinking about internal object relations. © 1998 Michigan Association for Infant Mental Health [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]

The article discusses metformin therapy for the management of infertility in women with polycystic ovary syndrome (PCOS). Topics discussed include contribution of high levels of circulating insulin to excess androgen production and to anovulation; study comparing metformin with placebo in 320 women with PCOS and recommendation for the use of other insulin sensitisers such as thiazolidinediones.

Our objective was to test a theoretical model that explains quality of life as a function of the intrusiveness of illness encroaching on the different domains of one’s life. The intrusiveness of illness is explained not only by disease and treatment related factors, but also by one’s psychological and social resources (Devins, 1994). To investigate this issue, a sample of 336 women aged 50 and under, recently diagnosed with breast cancer were interviewed in their homes. Consistent with Devins’ model, intrusiveness of illness mediated the effect of disease and treatment factors on quality of life. Contrary to his model, some treatment factors also had direct effects while social and psychological factors had only direct effects on quality of life. Neither time post-diagnosis nor type of treatment affected the psychological component of quality of life. © 1998 John Wiley & Sons, Ltd. [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 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]