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Both the incidence and prevalence of well‐differentiated neuroendocrine tumours from the small intestine (Si‐NET) are gradually increasing. Most patients have non‐functioning tumours with subtle GI symptoms and tumours are often discovered incidentally by endoscopy or at advanced disease stages by imaging depicting mesenteric lymph node and /or liver metastases while around 30% of the patients present with symptoms of the carcinoid syndrome. Adequate biochemical assessment and staging including functional imaging is crucial for treatment‐related decision‐making that should take place in an expert multidisciplinary team setting. Preferably, patients should be referred to specialised ENETS Centres of Excellence or centres of high expertise in the field. This guidance paper provides the current evidence and best knowledge for the management of Si‐NET grade (G) 1–3 following 10 key questions of practical relevance for the diagnostic and therapeutic decision making. [ABSTRACT FROM AUTHOR]

A variety of terms, such as "antiepileptic," "anticonvulsant," and "antiseizure" have been historically applied to medications for the treatment of seizure disorders. Terminology is important because using terms that do not accurately reflect the action of specific treatments may result in a misunderstanding of their effects and inappropriate use. The present International League Against Epilepsy (ILAE) position paper used a Delphi approach to develop recommendations on English‐language terminology applicable to pharmacological agents currently approved for treating seizure disorders. There was consensus that these medications should be collectively named "antiseizure medications". This term accurately reflects their primarily symptomatic effect against seizures and reduces the possibility of health care practitioners, patients, or caregivers having undue expectations or an incorrect understanding of the real action of these medications. The term "antiseizure" to describe these agents does not exclude the possibility of beneficial effects on the course of the disease and comorbidities that result from the downstream effects of seizures, whenever these beneficial effects can be explained solely by the suppression of seizure activity. It is acknowledged that other treatments, mostly under development, can exert direct favorable actions on the underlying disease or its progression, by having "antiepileptogenic" or "disease‐modifying" effects. A more‐refined terminology to describe precisely these actions needs to be developed. [ABSTRACT FROM AUTHOR]

The endometrium undergoes cyclical changes in response to hormones and there is a certain degree of heterogeneity among individuals. In vivo identification of the physiologic changes of the endometrium and the pathologic process of related diseases is challenging. There have been recent advances in the use of organoids that mimic the characteristics of the corresponding organs and the morphologic, functional, and personalized characteristics involved in different stages of diseases. In this paper, we discuss the process of creating endometrial organoids, cell sources, types of extracellular matrices, and their application in the study of physiologic endometrial states and various diseases. Synopsis: The paper explores endometrial organoids, their use in studying physiologic states and diseases, and recent advancements in this field. [ABSTRACT FROM AUTHOR]

Summary Background Methods Results Conclusions Poor wellbeing and stress in UK anaesthetic trainees impacts significantly on clinical performance, workforce retention and patient care. This study aimed to provide an overview of the evidence in this field and to explore the factors affecting wellbeing and stress in UK anaesthetic trainees.MEDLINE, Embase, PsycINFO, and ERIC were searched, in addition to organisational websites. Literature reporting factors affecting wellbeing and stress in UK anaesthetic trainees from 2009 to present were included.Following exclusions, 45 studies were identified. Only five papers included qualitative analyses. Within these studies, 28 different phenomena related to wellbeing and stress were investigated. Thirty‐one different factors affecting anaesthetic trainees' wellbeing and stress were identified in this review. These have been summarised as individual; training; clinical role; progression; work patterns; resources; rest; support; and cultural factors. External factors were described as affecting wellbeing and stress more frequently than internal factors. The most frequently cited individual factors were fatigue and pre‐existing health status.The wide scope of phenomena of interest and measurement tools emphasises the challenge of defining and researching the concept of wellbeing. Despite these limitations, we have created a novel conceptual model of individual and external factors affecting UK anaesthetic trainees' wellbeing and stress. This supports an increased awareness and understanding of these factors, so that improvements can be made to practice and policy. [ABSTRACT FROM AUTHOR]

Benign natural killer cell enteropathy (NKCE) was first identified in the gastrointestinal (GI) tract. Notably, instances of NKCE have previously been observed at various sites other than the GI tract, including the gallbladder, lymph nodes, esophagus, and female genital tract. Typical NKCE manifests as an NK‐cell immunohistological phenotype, with or without TCR rearrangement, and is characterized by the absence of Epstein–Barr virus (EBV) infection and protracted clinical progression. The misdiagnosis of NKT‐cell lymphoma has resulted in some patients receiving chemotherapy, while in other instances, the patients' conditions resolved without treatment and showed no evidence of disease recurrence or progression during follow‐up examinations. In this paper, we describe a unique case of EBV‐negative NKCE occurring in the oral cavity, the first time such a case has been documented. The tumor completely resolved after an excisional biopsy, and subsequent follow‐up did not reveal any signs of disease recurrence. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease. Curcumin—an integral component of traditional medicine in numerous cultures worldwide—has garnered interest as a promising AD treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti‐inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in AD. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in AD and summarizes recent evidence of the biological efficiency of curcumins in vivo. [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: Students who are blind are integrated into public schools in many countries, yet are often excluded from full participation in science since most learning materials are visual. To create a compensatory route, an existing model‐based inquiry‐learning environment was adapted by means of sonification (addition of non‐speech sounds that represent dynamic information). The learning environment uses agent‐based models and a complex systems approach to teach the Kinetic Molecular Theory (KMT) and Gas Laws. The models are accompanied by a workbook consisting of text (printed or auditory) and images (printed or tactile). Objectives: The current research examined whether such perceptual compensation creates a comparable learning environment for learners who are blind compared with learners who are sighted using the original learning environment. The aim of the study is to expand knowledge about how the auditory channel may compensate the visual channel among individuals who are blind. Methods: Conceptual learning in science and reasoning about complex systems were assessed using pre‐ and post‐questionnaires. To explore learners' learning progression throughout the unit, four progression analysis 'windows' were selected. These were groups of adjacent or nearly adjacent items in the workbook that permitted a glimpse of learners' progression. Results: The sonified environment not only supported the learning of learners who are blind compared with the learning of learners who are sighted using visual material, but even furthered their learning with respect to diffusion, one of the more challenging concepts in KMT. It seems the types of sonified representations used in this study increased listeners' sensitivity to the micro‐level interactions in a way less accessible in visual representations. Takeaways: Sonified environments can be provide learners who are blind with equitable participation by compensating and complementing the visual channel. Sonification can have implications for students who are blind as well as students who are sighted. Lay Description: What is already known: Sonification is the use of non‐speech sounds to represent dynamic information. Sonification can potentialy be used to allow equitable participation for students who are blind. What this paper adds: To test this, the study compared the outcomes of learners who are blind who used a sonified learning environment (L2C) to that of learners who are sighted who used a visual environment. Implications for practice: Learners who are blind showed equal or better learning outcomes using the sonified models compared with the learners who are sighted using the visual models. There are major implications for integrating students who are blind in public school classrooms. [ABSTRACT FROM AUTHOR]

Living organisms experience a range of stresses. To cope effectively with these stresses, eukaryotic cells have evolved a sophisticated mechanism involving the formation of stress granules (SGs), which play a crucial role in protecting various types of RNA species under stress, such as mRNAs and long non‐coding RNAs (lncRNAs). SGs are non‐membranous cytoplasmic ribonucleoprotein (RNP) granules, and the RNAs they contain are translationally stalled. Importantly, SGs have been thought to contribute to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD). SGs also contain multiple RNA‐binding proteins (RBPs), several of which have been implicated in AD progression. SGs are transient structures that dissipate after stress relief. However, the chronic stresses associated with aging lead to the persistent formation of SGs and subsequently to solid‐like pathological SGs, which could impair cellular RNA metabolism and also act as a nidus for the aberrant aggregation of AD‐associated proteins. In this paper, we provide a comprehensive summary of the physical basis of SG‐enriched RNAs and SG‐resident RBPs. We then review the characteristics of AD‐associated gene transcripts and their similarity to the SG‐enriched RNAs. Furthermore, we summarize and discuss the functional implications of SGs in neuronal RNA metabolism and the aberrant aggregation of AD‐associated proteins mediated by SG‐resident RBPs in the context of AD pathogenesis. Geriatr Gerontol Int 2024; 24: 7–14. [ABSTRACT FROM AUTHOR]

Objective: Late‐onset GM2 gangliosidosis (LOGG) subtypes late‐onset Tay‐Sachs (LOTS) and Sandhoff disease (LOSD) are ultra‐rare neurodegenerative lysosomal storage disorders presenting with weakness, ataxia, and neuropsychiatric symptoms. Previous studies considered LOTS and LOSD clinically indistinguishable; recent studies have challenged this. We performed a scoping review to ascertain whether imaging and clinical features may differentiate these diseases. Methods: We examined MEDLINE/non‐MEDLINE databases up to May 2022. Articles reporting brain imaging findings in genetically/enzymatically confirmed LOGG, symptom onset at age ≥ 10 years (or evaluated at least once ≥18 years) were included, yielding 170 LOGG patients (LOTS = 127, LOSD = 43) across 68 papers. We compared LOTS versus LOSD and performed regression analyses. Results were corrected for multiple comparisons. Results: Age of onset was lower in LOTS versus LOSD (17.9 ± 8.2 vs. 23.9 ± 14.4 years, p = 0.017), although disease duration was similar (p = 0.34). LOTS more commonly had psychosis/bipolar symptoms (35.0% vs. 9.30%, p = 0.011) but less frequent swallowing problems (4.10% vs. 18.60%, p = 0.041). Cerebellar atrophy was more common in LOTS (89.0%) versus LOSD (60.5%), p < 0.0001, with more severe atrophy in LOTS (p = 0.0005). Brainstem atrophy was documented only in LOTS (14.2%). Independent predictors of LOTS versus LOSD (odds ratio [95% confidence interval]) included the presence of psychosis/bipolar symptoms (4.95 [1.59–19.52], p = 0.011), no swallowing symptoms (0.16 [0.036–0.64], p = 0.011), and cerebellar atrophy (5.81 [2.10–17.08], p = 0.0009). Lower age of onset (0.96 [0.93–1.00], p = 0.075) and tremor (2.50 [0.94–7.43], p = 0.078) were marginally statistically significant but felt relevant to include in the model. Interpretation: These data suggest significant differences in symptomatology, disease course, and imaging findings between LOTS and LOSD. [ABSTRACT FROM AUTHOR]

Aim: Tissue factor pathway inhibitor 2 (TFPI2) is a structural homolog of tissue factor pathway inhibitor 1 (TFPI1). Since TFPI2 is a placenta‐derived protein, dynamic changes in TFPI2 levels may be related to pregnancy‐related diseases. Furthermore, TFPI2 has been reported to be a novel serum biomarker for detecting ovarian cancer, especially clear cell carcinoma (CCC). This review aims to summarize the current knowledge on the biological function of TFPI2, highlight the major challenges that remain to be addressed, and discuss future research directions. Methods: Papers published up to March 31, 2023 in the PubMed and Google Scholar databases were included in this review. We also provide novel complementary information to what is known about the action of TFPI2. Results: Since TFPI2 concentrations in the blood of pregnant women, preeclampsia patients, and cancer patients vary greatly, its pathophysiological functions have attracted attention. Downregulation of TFPI2, a tumor‐suppressor gene, by hypermethylation may contribute to the progression of several cancers. On the other hand, TFPI2 overexpressed in CCC is a risk factor for the development of thrombosis, possibly through inhibition of plasmin activity. However, agreement on the biological function of TFPI2 is still lacking and there are many scientific questions to be addressed. In particular, the lack of international standardization for the quantification of TFPI2 concentrations makes it difficult for researchers and clinicians to evaluate, pool, and compare data from different studies across countries. Discussion: This review summarizes current understandings and challenges in TFPI2 research and discusses future perspectives. [ABSTRACT FROM AUTHOR]

Background: Communication and cognitive impairments are known barriers to shared decision‐making. Most people diagnosed with motor neurone disease (MND) will develop a motor speech impairment over the disease course. Some will develop cognitive, linguistic or behavioural disturbance. Despite this, the impact of communication and cognitive impairment on personal healthcare decision‐making in MND is not well known. Aims: This exploratory, longitudinal study aimed to capture the perspectives of people living with MND (plwMND) and family members on managing their healthcare with, or in anticipation of, a communication impairment. Methods & Procedures: Semi‐structured interviews and functional assessments were conducted with plwMND and family members over one to three time points between December 2017 and January 2020. Participants were recruited from a specialist MND clinic using a maximum variation sampling approach. Interview transcripts were analysed using trajectory data analysis: a matrix‐based approach for thematic analysis of longitudinal data. The study was underpinned by interpretive descriptive methodology. Outcomes & Results: A total of 19 plwMND with a range of MND phenotypes and 15 family members were recruited. Disease progression and participant withdrawal resulted in attrition, however 12 plwMND and seven family members participated at all three time points. Consistent cognitive screening was not feasible, which limited the opportunity to explore the impact of cognitive change. An overarching theme 'Communicating takes effort' was identified and illustrates the efforts required to compensate for, or circumnavigate, impairments to maintain involvement in healthcare. Assistance from family and accommodation from healthcare professionals (HCPs) was needed for ongoing engagement. Where plwMND were dependent on alternative communication devices, this assistance was essential and primarily carried out by family members. Despite these efforts, the quality, quantity and accuracy of communication were sometimes compromised. Participants equated good communication with receiving good healthcare, and some expressed anxiety in the anticipation of being unable to express their needs to healthcare workers. Conclusion & Implications: Communication impairment has a direct impact on healthcare involvement. This study demonstrates the effort required by plwMND and their carers to maintain or maximize ongoing involvement. This effort may not always be visible to HCPs. This information may prompt clinicians to consider the best ways to conduct clinical consultations to accommodate patients' abilities. Compromised communication experiences can be moderated by accommodations and support from HCPs and appropriate adjustments in the health system. Asking patients about their communication preferences and needs, allowing extra time and conducting multidisciplinary sessions are examples of such support. What this paper adds: What is already known on this subject?: Communication and cognitive impairments are known contributors to negative health outcomes and barriers to shared decision‐making generally. The existing literature in decision‐making in MND does not address the specific impact of these impairments on personal healthcare involvement for plwMND and their carers. What this paper adds to existing knowledge?: This paper reports the findings of a research project that interviewed 19 plwMND and 15 carers on one to three occasions over a 26‐month period to obtain their perspectives of the impact of communication on healthcare involvement. Whilst a priori the intention was to look at both communicative and cognitive decline, only the former was achieved. The effort and often 'invisible' activity undertaken to manage or maintain involvement in healthcare is identified. Communication impairment requires support and accommodation, otherwise healthcare involvement can be compromised. Results show participants may associate effective communication with good healthcare. What are the potential or actual clinical implications of the work?: Clinicians may wish to use these insights from plwMND and their carers to guide adjustments to their professional practice to maximize healthcare involvement for their patients. Tailored education for different healthcare groups is needed to improve understanding of MND‐related communication impairments and supportive strategies so that involvement in healthcare is not compromised. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Kaur et al papers. To view these articles, visit https://doi.org/10.1111/apt.18202 and https://doi.org/10.1111/apt.18238 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Kaur et al papers. To view these articles, visit https://doi.org/10.1111/apt.18202 and https://doi.org/10.1111/apt.18279 [ABSTRACT FROM AUTHOR]

In their paper, Klaassen et al. present their findings on the revised Kids ITP Tools (KIT). This important work provides an update to the validated measure for evaluating health‐related quality of life (HRQoL) in children with immune thrombocytopenia (ITP). ITP, an acquired autoimmune disorder, results in thrombocytopenia and places children at risk for significant bleeding. Thankfully, the majority of children with ITP will have a brief disease course and no or mild bleeding symptoms. The rarity of severe bleeding events or the development of chronic disease provides a challenge with regard to clinical trial design, making alternative measures of pharmacological efficacy extremely important. Commentary on: Dhir et al. Quality of life in childhood immune thrombocytopenia: Revision of the Kids' ITP Tools (KIT). Br J Haematol 2024; 205:1489‐1496. [ABSTRACT FROM AUTHOR]

Background: Galectins are β‐galactoside‐binding proteins. Galectin‐4 has shown an effect on cancer progression/metastasis, especially in cancers of the digestive system. This can be attributed to altered glycosylation pattern of cell membrane molecules, which is a characteristic attribute of oncogenesis. The aim of this paper is to systematically review galectin‐4 in different cancers and its role in disease progression. Methods: The study was designed on the basis of Preferred Reporting Items for Systematic Review and Meta‐Analysis (PRISMA) guidelines. PubMed, Scopus, Web of Science, and Science Direct were used to search relevant literature with keywords "galectin‐4 AND cancer", "galectin‐4", "LGALS4", and "LGALS4 AND cancer". Inclusion criteria for study selection were availability of full‐text articles, articles in English language and articles relevant to current topic, that is, galectin‐4 and cancer. Exclusion criteria were studies that investigated other disease conditions, interventions unrelated to cancer or galectin‐4 and bias outcome. Results: A total of 73 articles were retrieved after removing duplication from databases, out of which 40 studies were included in the review that followed the inclusion criteria, including low to moderate bias. These included 23 studies in digestive system, 5 in reproductive system, 4 in respiratory system, and 2 in brain and urothelial cancers. Conclusions: A differential expression of galectin‐4 was observed in different cancer stages/ and types. Furthermore, galectin‐4 was found to modulate disease progression. A meta‐analysis and comprehensive mechanistic studies, pertaining to different aspects of galectin‐4 biology, could give statistically driven correlations, elucidating multifaceted role of galectin‐4 in cancer. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is one of the common complications of diabetes mellitus, which usually progresses to end‐stage renal disease and causes great damage to the health of patients. Endothelin‐1 (ET‐1), a molecule closely associated with the progression of DKD, has increased expression in response to high glucose stimulation and is involved in hemodynamic changes, inflammation, glomerular and tubular dysfunction in the kidney, causing an increase in proteinuria and a decrease in glomerular filtration function, ultimately leading to glomerulosclerosis and renal failure. This paper aims to review the molecular level changes, regulatory mechanisms, and mechanisms of action of ET‐1 under DKD, clinical trials of ET‐1 receptor antagonists in recent years and current problems, to provide basic information and new research directions and ideas for the treatment of DKD and ET‐1‐related research. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a severe mental condition characterized by episodes of elevated mood and depression. Being a heritable condition, it features a complex genetic architecture, although it is not still clear how genes contribute to the onset and course of the disease. In this paper, we adopted an evolutionary‐genomic approach to this condition, focusing on changes occurred during human evolution as a source of our distinctive cognitive and behavioural phenotype. We show clinical evidence that the BD phenotype can be construed as an abnormal presentation of the human self‐domestication phenotype. We further demonstrate that candidate genes for BD significantly overlap with candidates for mammal domestication and that this common set of genes is enriched in functions that are important for the BD phenotype, especially neurotransmitter homeostasis. Finally, we show that candidates for domestication are differentially expressed in brain regions involved in BD pathology, particularly, the hippocampus and the prefrontal cortex, which have been subject to recent changes in our species. Overall, this link between human self‐domestication and BD should facilitate a better understanding of the BD etiopathology. [ABSTRACT FROM AUTHOR]

Dysphagia (impaired swallowing) is known to contribute to decreased quality of life, and increased length of hospital stay and mortality post‐stroke. Despite the advancements in stroke treatment with the introduction of thrombolysis and endovascular clot retrieval (ECR), patients continue to present with high rates of dysphagia. Speech and language therapists and stroke teams should consider the presence of haemorrhagic transformation, success of reperfusion and presence of communication deficits as risk factors for dysphagia post‐ECR and/or thrombolysis. Purpose: To establish incidence rates and patterns of dysphagia following the administration of reperfusion therapies in acute ischaemic stroke management. Method: A retrospective review of 193 patients admitted with acute ischaemic stroke to a quaternary stroke unit in Australia over a three year period was completed. Clinical information extracted included demographics, type (thrombolysis and/or endovascular clot retrieval) and success of reperfusion therapy, and the progression of dysphagia and related factors. Results: Over half of all patients treated with reperfusion therapies presented with dysphagia on initial assessment by speech‐language pathology (SLP). The type of reperfusion therapy administered was not significantly correlated with the presence of dysphagia. Dysphagia on initial assessment was significantly correlated with the presence of aphasia on initial assessment, the presence of haemorrhagic transformation, and the success of reperfusion. Increased rates of enteral feeding were also found in this study compared to figures reported in literature. Conclusion: This study identified ongoing high rates of dysphagia amongst this patient population regardless of treatment type, demonstrating the need for ongoing SLP management post stroke. Further research is required in this area to develop an evidence‐base for SLPs and the wider medical team and to inform clinical practice guidelines. What this paper adds: What is already known on the subject: Stroke is one of the leading causes of disability and death internationally. Dysphagia (impaired swallowing), a common sequalae of stroke, is known to contribute to decreased quality of life, increased length of hospital stay and mortality. With advancements in technology, treatments for acute ischaemic stroke (endovascular clot retrieval and thrombolysis) are increasing in popularity. However, limited research exists exploring the impact of these therapies on dysphagia. What this paper adds: Despite the advancements in stroke treatment, patients continue to present with high rates of dysphagia. Dysphagia following thrombolysis and/or ECR was found to be significantly correlated to the presence of aphasia, haemorrhagic transformation, and the success of reperfusion (regardless of treatment type). Additionally, increased rates of enteral feeding were found amongst this patient population compared to figures reported in the literature for patients following traditional stroke management. Clinical implications of this study: Speech‐language pathologists and the wider medical team should consider dysphagia as an ongoing consequence of stroke following reperfusion therapies, with consideration for success of reperfusion and adverse outcomes i.e., haemorrhagic transformation. Further research is required to provide an evidence‐base and specific guidelines for the management of dysphagia post reperfusion therapies, including use of enteral feeding. [ABSTRACT FROM AUTHOR]

This review provides recommendations for the evaluation and management of individuals with beta‐propeller protein‐associated neurodegeneration (BPAN). BPAN is one of several neurodegenerative disorders with brain iron accumulation along with pantothenate kinase‐associated neurodegeneration, PLA2G6‐associated neurodegeneration, mitochondrial membrane protein‐associated neurodegeneration, fatty acid hydroxylase‐associated neurodegeneration, and COASY protein‐associated neurodegeneration. BPAN typically presents with global developmental delay and epilepsy in childhood, which is followed by the onset of dystonia and parkinsonism in mid‐adolescence or adulthood. BPAN is an X‐linked dominant disorder caused by pathogenic variants in WDR45, resulting in a broad clinical phenotype and imaging spectrum. This review, informed by an evaluation of the literature and expert opinion, discusses the clinical phenotype and progression of the disease, imaging findings, epilepsy features, and genetics, and proposes an approach to the initial evaluation and management of disease manifestations across the life span in individuals with BPAN. What this paper addsThe complex epilepsy profile of beta‐propeller protein‐associated neurodegeneration (BPAN) often resolves in adolescence.The treatment for an individual with BPAN is supportive, with attention to sleep disorders, complex epilepsy, and behavioral problems.Individuals with BPAN have shifting needs throughout their life span requiring multidisciplinary care. What this paper adds: The complex epilepsy profile of beta‐propeller protein‐associated neurodegeneration (BPAN) often resolves in adolescence.The treatment for an individual with BPAN is supportive, with attention to sleep disorders, complex epilepsy, and behavioral problems.Individuals with BPAN have shifting needs throughout their life span requiring multidisciplinary care. podcast : (https://youtu.be/NUF4DJXVlWw) [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) leads to changes in verbal communications. The focus of most studies to date has been on speech impairment, which is specifically referred to as dysarthria. Although these studies are crucial to understanding the impact of PD on verbal communication, they do not focus on the features of dialogues between people with PD (PwPD) and other people in communicative contexts. Aims: To investigate whether PwPD produce less feedback than typical people during dialogue, thus potentially making it more difficult for them to reach mutual comprehension (i.e., common ground) with their conversational partner. Methods & Procedures: A matching task experiment was conducted during which an experimenter described abstract pictures to a participant, who was either a PwPD or a typical participant, so that he or she could organize these pictures in a grid. The participants could produce as much feedback as they liked. Outcomes & Results: PwPD were less likely to produce feedback than typical participants. This effect was mainly driven by two specific types of feedback: acknowledgment tokens and hesitations. Conclusions & Implications: The results suggest that PD impacts feedback production. This could decrease the communicative abilities of PwPD in interactive contexts by affecting grounding, that is, the ability to build common ground with others. This paper is one of the first to specifically document the production of feedback markers in PwPD. Future studies should examine the extent to which our results, which were obtained in a controlled dialogue task, may be generalized to daily‐life conversions. From a clinical perspective, our study points to the necessity of assessing feedback production, and more generally abilities related to common ground construction and use, during PD progression. What is already known on the subject: A few studies to date have analyzed conversational interactions between people with Parkinson's disease (PwPD) and others. The main focus is usually on potential difficulties of PwPD and their partners during the interaction and the strategies adopted to "repair" these problems. Another important feature of any interaction is the production of feedback. Feedback production plays a key role in building and using common ground to ensure mutual comprehension between interlocutors. The impact of Parkinson's disease on feedback production has received little attention in the literature to date. What this study adds: The purpose of this study was to compare feedback production in a dialogue task (i.e., goal‐oriented interaction) in PwPD versus typical controls. Our results revealed that PwPD produced less feedback for their dialogue partners than did typical participants. This effect was mainly driven by two specific types of feedback: acknowledgment tokens and hesitations. This paper is one of the firsts to specifically document the production of feedback markers in PwPD and to illustrate that PwPD and their dialogue partners may require more time and effort to establish common ground. Clinical implications of this study: Our findings suggest that an appropriate evaluation of feedback production by speech and language therapists, as well the management of potential deficits, would be beneficial. More broadly, we believe that the evaluation and management of PwPD should take into account the theoretical framework used in this study, in particular the role of common ground in communication. [ABSTRACT FROM AUTHOR]

An immunotherapy trial often uses the phase I/II design to identify the optimal biological dose, which monitors the efficacy and toxicity outcomes simultaneously in a single trial. The progression‐free survival rate is often used as the efficacy outcome in phase I/II immunotherapy trials. As a result, patients developing disease progression in phase I/II immunotherapy trials are generally seriously ill and are often treated off the trial for ethical consideration. Consequently, the happening of disease progression will terminate the toxicity event but not vice versa, so the issue of the semi‐competing risks arises. Moreover, this issue can become more intractable with the late‐onset outcomes, which happens when a relatively long follow‐up time is required to ascertain progression‐free survival. This paper proposes a novel Bayesian adaptive phase I/II design accounting for semi‐competing risks outcomes for immunotherapy trials, referred to as the dose‐finding design accounting for semi‐competing risks outcomes for immunotherapy trials (SCI) design. To tackle the issue of the semi‐competing risks in the presence of late‐onset outcomes, we re‐construct the likelihood function based on each patient's actual follow‐up time and develop a data augmentation method to efficiently draw posterior samples from a series of Beta‐binomial distributions. We propose a concise curve‐free dose‐finding algorithm to adaptively identify the optimal biological dose using accumulated data without making any parametric dose–response assumptions. Numerical studies show that the proposed SCI design yields good operating characteristics in dose selection, patient allocation, and trial duration. [ABSTRACT FROM AUTHOR]

This paper reports the presentation and management of an older female patient who was diagnosed with Coronavirus disease (COVID‐19) and discharged from an intensive care unit (ICU) after prolonged hospitalization. The patient's COVID‐19 test was negative; therefore, she was monitored in the COVID‐19 general clinic with normal levels of oxygen saturation (SpO2). The patient had been taking Plaquenil for rheumatoid arthritis for a long time. Azithromycin was administered first, and then, the treatment continued with favipiravir according to the national treatment protocol in Turkey. On the third day in the COVID‐19 general clinic, she was transferred to the ICU because of decreased saturation levels. Owing to worsening respiratory status and SpO2 <70%, the patient was intubated on the sixth day in the ICU, and every day, she was nursed in a prone position for >16 hours. We believe that the treatment and care activities under qualified and effective nursing care, such as providing appropriate respiratory support at the right time, early initiation and maintenance of anticoagulant therapy, long‐term prone positioning, maintaining sufficient fluid resuscitation, and early commencement of balanced enteral nutrition, contributed to the successful discharge of the patient from the ICU. The patient was finally extubated on the 23rd day. Respiratory support was continued with oxygen administered at 2 lt/min through a nasal canula with SpO2 at 94%. We believe that by combining all these factors, the patient's results improved. She was discharged from the ICU after 25 days without any organ dysfunction. During the 25 days of care in the ICU, infectious disease protection and isolation rules were strictly adhered to, and personal protective equipment was worn. [ABSTRACT FROM AUTHOR]

Background: Huntington's disease (HD) is a neurodegenerative disease characterized by a triad of motor, cognitive and psychological symptoms, leading to a gradual breakdown of communication skills. Few studies have investigated how people affected by HD and their professional caregivers, for example, medical doctors, physiotherapists and nurses, experience the patients' gradual loss of speech and language. Aims: To examine communication‐related experiences of patients and professional caregivers. Experiences with speech therapy and the use of augmentative and alternative communication aids (AAC) were also investigated. Methods & Procedures: Seven individuals with HD and seven professional caregivers were interviewed individually, using a semi‐structured interview guide. Transcripts were analysed using a conventional content analysis, and the results presented in three main categories. Outcomes & Results: Most individuals with HD were aware of having communication difficulties, struggling with understanding others as well as being understood. This was confirmed by professional caregivers, who also raised ethical issues encountered when patients struggled with communication. Both groups talked about external factors (such as noise or crowded social settings) as disrupting communication, and shared recommendations on how people in general, and speech and language therapists (SLTs) in particular, could optimize communication. Very few patients had received information about communication aids, and none was using AACs. Professional caregivers underlined the importance of interdisciplinary collaborations, including SLTs, in order to optimize care. Conclusions & Implications: Findings shed a light on everyday communication challenges faced by people with HD and their professional caregivers, and the lack of implementation of communication aids in this group. The dramatic impact of HD on patients' communication skills underscores the need to include SLTs in the follow‐up of this patient group, ideally from the early stages of the disease, while the patient is still capable of voicing his/her own wishes and thoughts. Future research that explores how to optimize communication and implement the use of AACs for individuals with HD is needed. What this paper addsWhat is already known on this subjectAlthough the ability to communicate gradually deteriorates in individuals affected by Huntington's disease (HD), there is little knowledge about how affected individuals experience the loss of speech and language skills. Interdisciplinary care is recognised as essential for this patient group. However, professional caregivers' thoughts and experiences of communicating with their patients have not been fully explored. Recent years have seen a rapid growth of available communication supporting technologies that could potentially be helpful for individuals with HD, but limited attention has been given to this subject.What this paper adds to existing knowledgeWhat do we now know as a result of this study that we did not know before the results highlight that patients are aware of problems with speech and language even in early phases of the disease, and include patients' personal outlook on problems with communication. Professional caregivers raised ethical issues encountered when patients struggled with communication. Both groups described specific strategies that could facilitate communication. There was a significant lack of experience and knowledge about augmentative and alternative communication aids (AACs).What are the potential or actual clinical implications of this work?Clinical implications of this study. The introduction of communication aids in the follow‐up of patients with HD needs to be discussed with the patients in the early phases of the disease, and implemented while the individual still has the capacity to learn and take advantage of alternative communication support. Results underline the importance of including speech and language therapists (SLTs) into multidisciplinary care of patients with HD. SLTs should be available also for professional caregivers who need advice on how to facilitate conversations and social interactions, in order to optimise care of patients with HD. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is prevalent and burdensome among older adults in the United States. CKD affects at least 15% of the US population, and adults over 65 comprise the largest subset within this group. In this special article, we highlight key findings of three recent original investigations in nephrology and describe each study, relevance to the care of older adults, and current areas of uncertainty that warrant further investigation. Articles relate to removal of the race adjustment in the estimation of kidney function, the use of novel therapeutics to halt CKD progression and improve cardiovascular outcomes, and medication management for short‐term pain control in CKD. See other related Clin‐star papers by Mody et al. and Advani et al. in this issue. [ABSTRACT FROM AUTHOR]

Objective: Among patients living with advanced, life‐limiting illness, reconciling the prospect of disease progression with future goals and expectations is a key psychological task, integral to treatment decision‐making and emotional well‐being. To date, this psychological process remains poorly understood with no available measurement tools. The present paper develops and validates a measurement model for operationalizing this psychological process. Methods: In Phase 1, concept elicitation interviews were conducted among Stage IV lung, gastrointestinal, and gynecologic cancer patients, their caregivers, and experts (N = 19), to further develop our conceptual framework centered on assimilation and accommodation coping. In Phase 2, draft self‐report items of common assimilation and accommodation coping strategies were evaluated via patient cognitive interviews (N = 11). Results: Phase 1 interviews identified several coping strategies, some of which aimed to reduce the perceived likelihood of disease progression (assimilation), and others aimed to integrate the likelihood into new goals and expectations (accommodation). The coping strategies appeared to manifest in patients' daily lives, and integrally related to their emotional well‐being and how they think about treatments. Phase 2 cognitive interviews identified items to remove and modify, resulting in a 31‐item measure assessing 10 assimilation and accommodation coping strategies. Conclusions: The present work derived a content‐valid measure of the psychological process by which patients reconcile the prospect of disease progression with their goals and expectations. Further psychometric validation and use of the scale could identify intervention targets for enhancing patient decision‐making and well‐being. [ABSTRACT FROM AUTHOR]

Background: Whilst dysphagia is a commonly reported complication of stroke, it has received relatively little attention in the literature for patients following non‐traumatic subarachnoid haemorrhage (SAH). Aims: To investigate dysphagia incidence, risk factors, clinical progression and recovery in patients following non‐traumatic SAH. Methods & Procedures: A prospective cohort study of 49 patients admitted to a tertiary neurosurgical referral unit with non‐traumatic SAH over a 12‐month period was conducted. Swallowing function was assessed by a speech–language pathologist within 72 h of medical stability and monitored throughout the acute inpatient admission. Outcomes & Results: Dysphagia incidence was 16.33% (n = 8/49). Risk factors associated with dysphagia included; Glasgow Coma Scale (GCS) score on admission, need for intensive care unit (ICU) admission, length of ICU stay, need for intubation and ventilation, and hydrocephalus. Participants with dysphagia were admitted to hospital 1.9 times longer than those without dysphagia (p < 0.05) and were more likely to be transferred to another inpatient facility for ongoing care (p < 0.05). Dysphagia remained present at hospital discharge for over half (62.5%) of participants who developed this complication. Conclusions & Implications: Care pathways for patients admitted to hospital with non‐traumatic SAH should include early screening for dysphagia risk. Further research using a larger prospective cohort is required to validate dysphagia incidence and risk factors in this patient cohort. What this paper addsWhat is already known on this subjectDysphagia is a negative complication following non‐traumatic SAH, and can occur as a result of primary injury or secondary to treatment complications (e.g., intubation and ventilation, surgical intervention). However, limited evidence regarding its incidence, risk factors, clinical progression and recovery in a prospective cohort exists.What this paper adds to existing knowledgeThis study is the first to examine prospectively patients with non‐traumatic SAH within 72 h of medical stability. It identifies dysphagia incidence, risk factors, clinical characteristics and recovery during the acute hospital admission for this patient cohort.What are the potential or actual clinical implications of this work?Early and regular screening for dysphagia in the presence of associated risk factors is essential for patients admitted with non‐traumatic SAH. Speech–language pathologist resources in the neurocritical care context should be available to support the assessment and management of dysphagia in this cohort. [ABSTRACT FROM AUTHOR]

The National Institute of Mental Health (NIMH) proposed the Research Domain Criteria (RDoC) initiative as an alternate way to organize research of mental illnesses, by looking at dimensions of functioning rather than being tied to categorical diagnoses. This paper briefly discusses the motivation for and organization of RDoC, and then explores the NIMH portfolio and recent work to monitor the utility and progress that RDoC has afforded developmental research. To examine how RDoC has influenced the NIMH developmental research portfolio over the last decade, we employed a natural language processing algorithm to identify the number of developmental science grants classified as incorporating an RDoC approach. Additional portfolio analyses examine temporal trends in funded RDoC‐relevant grants, publications and citations, and research training opportunities. Reflecting on how RDoC has influenced the focus of grant applications, we highlight examples from research on Attention‐Deficit Hyperactivity Disorder (ADHD), childhood irritability, and Autism Spectrum Disorder (ASD). Lastly, we consider how the dimensional and transdiagnostic approaches emphasized in RDoC have facilitated research on personalized intervention for heterogeneous disorders and preventive/early interventions targeting emergent or subthreshold psychopathology. [ABSTRACT FROM AUTHOR]

The rapid spread of the novel coronavirus disease 2019 (COVID‐19) causes a significant impact on public health. It is critical to diagnose COVID‐19 patients so that they can receive reasonable treatments quickly. The doctors can obtain a precise estimate of the infection's progression and decide more effective treatment options by segmenting the CT images of COVID‐19 patients. However, it is challenging to segment infected regions in CT slices because the infected regions are multi‐scale, and the boundary is not clear due to the low contrast between the infected area and the normal area. In this paper, a coarse‐refine segmentation network is proposed to address these challenges. The coarse‐refine architecture and hybrid loss is used to guide the model to predict the delicate structures with clear boundaries to address the problem of unclear boundaries. The atrous spatial pyramid pooling module in the network is added to improve the performance in detecting infected regions with different scales. Experimental results show that the model in the segmentation of COVID‐19 CT images outperforms other familiar medical segmentation models, enabling the doctor to get a more accurate estimate on the progression of the infection and thus can provide more reasonable treatment options. [ABSTRACT FROM AUTHOR]

Background and Aim: Endoscopic surveillance for dysplasia in Barrett's esophagus (BE) with random biopsies is the primary diagnostic tool for monitoring clinical progression into esophageal adenocarcinoma. As an alternative, narrow‐band imaging (NBI) endoscopy offers targeted biopsies that can improve dysplasia detection. This study aimed to evaluate NBI‐guided targeted biopsies' diagnostic accuracy for detecting dysplasia in patients undergoing endoscopic BE surveillance compared with the widely used Seattle protocol. Methods: Cochrane DTA Register, MEDLINE/PubMed, EMBASE, OpenGrey, and bibliographies of identified papers were searched until 2018. Two independent investigators resolved discrepancies by consensus, study selection, data extraction, and quality assessment. Data on sensitivity, specificity, and predictive values were pooled and analyzed using a random‐effects model. Results: Of 9528 identified articles, six studies comprising 493 participants were eligible for quantitative synthesis. NBI‐targeted biopsy showed high diagnostic accuracy in detection of dysplasia in BE with a sensitivity of 76% (95% confidence interval [CI]: 0.61–0.91), specificity of 99% (95% CI: 0.99–1.00), positive predictive value of 97% (95% CI: 0.96–0.99), and negative predictive value of 84% (95% CI: 0.69–0.99) for detection of all grades of dysplasia. The receiver‐operating characteristic curve for NBI model performance was 0.8550 for detecting all dysplasia. Conclusion: Narrow‐band imaging‐guided biopsy demonstrated high diagnostic accuracy and might constitute a valid substitute for random biopsies during endoscopic surveillance for dysplasia in BE. [ABSTRACT FROM AUTHOR]

Background: Aortic stenosis (AS) prevalence is estimated to reach 4.5 million cases worldwide by the year 2030. AS is a progressive disease without a pharmacological treatment. In the current review, we aimed to investigate novel therapeutic approaches for non‐surgical AS treatment, at least in patients with mild‐to‐moderate AS. Materials and Methods: The most recent and relevant papers concerned with novel molecular pathways that have potential as therapeutic targets in AS were selected from searches of PubMed and Web of Science up to February 2021. Results: Growing evidence indicates that therapies using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, simvastatin/ezetimibe combination, cholesteryl ester transfer protein inhibitors or antisense oligonucleotides targeting apolipoprotein(a) reduce the risk of AS progression. It has been shown that enhanced valvular lipid oxidation may drive AS development by leading to the activation of valvular interstitial cells (VICs), the most abundant valvular cells having a major contribution to valve calcification. Since VICs are able to release pro‐inflammatory cytokines, clotting factors and proteins involved in calcification, strategies targeting these cell activations seem promising as therapeutic interventions. Recently, non‐vitamin K antagonist oral anticoagulants (NOACs) have been shown to inhibit activation of VICs. Conclusion: Several novel molecular pathways of AS development have been identified over the past few years. Therapies using PCSK9 inhibitors, simvastatin/ezetimibe combination, lipoprotein(a)‐lowering therapy are highly promising candidates as therapeutics in the prevention of mild AS progression, while preclinical studies show that NOACs may inhibit valvular inflammation and coagulation activation and slower the rate of AS progression. [ABSTRACT FROM AUTHOR]

Aim: To determine if walking ability and presence of intellectual disability and epilepsy change from childhood to 50 years of age in individuals with cerebral palsy (CP), and if such changes are related to age, sex, or CP subtype.Method: This was a population-based follow-up study of 142 adults born from 1959 to 1978 (82 males, 60 females; mean age 48y 4mo, range 37-58y; 44% unilateral, 35% bilateral, 17% dyskinetic, and 4% ataxic CP) listed in the CP register of western Sweden. We compared childhood data with a follow-up assessment in 2016.Results: At follow-up, walking ability had changed significantly (p<0.001). The proportion of participants walking without aids had decreased from 71% to 62%, and wheelchair ambulation increased from 18% to 25%. Walking ability was related to subtype (p=0.001), but not to age, sex, pain, fatigue, or body mass index. The proportion classified as having intellectual disability had increased from 16% to 22% (p=0.039) and the proportion with epilepsy from 9% to 18% (p=0.015). Of those with childhood epilepsy, 46% were seizure-free without medication.Interpretation: Walking ability and the presence of intellectual disability and epilepsy had changed significantly since childhood. Life-long access to specialized health care is warranted for re-evaluation of impairments, treatment, and assistance. What this paper adds Changes in impairments in individuals with cerebral palsy (CP) over time are related to CP subtype. After 50 years, walking ability in CP may have deteriorated or improved. Intellectual disability in CP may not always be detected in early childhood assessments. Epilepsy in CP may develop after childhood or may be outgrown. [ABSTRACT FROM AUTHOR]

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non‐invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non‐invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), known to be the causative agent of COVID‐19, has led to a worldwide pandemic. At presentation, individual clinical laboratory blood values, such as lymphocyte counts or C‐reactive protein (CRP) levels, may be abnormal and associated with disease severity. However, combinatorial interpretation of these laboratory blood values, in the context of COVID‐19, remains a challenge. Methods: To assess the significance of multiple laboratory blood values in patients with SARS‐CoV‐2 and develop a COVID‐19 predictive equation, we conducted a literature search using PubMed to seek articles that included defined laboratory data points along with clinical disease progression. We identified 9846 papers, selecting primary studies with at least 20 patients for univariate analysis to identify clinical variables predicting nonsevere and severe COVID‐19 cases. Multiple regression analysis was performed on a training set of patient studies to generate severity predictor equations, and subsequently tested on a validation cohort of 151 patients who had a median duration of observation of 14 days. Results: Two COVID‐19 predictive equations were generated: one using four variables (CRP, D‐dimer levels, lymphocyte count, and neutrophil count), and another using three variables (CRP, lymphocyte count, and neutrophil count). In adult and pediatric populations, the predictive equations exhibited high specificity, sensitivity, positive predictive values, and negative predictive values. Conclusion: Using the generated equations, the outcomes of COVID‐19 patients can be predicted using commonly obtained clinical laboratory data. These predictive equations may inform future studies evaluating the long‐term follow‐up of COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Resilience and recovery are of increasing importance in the field of alcohol dependence (AD). This paper describes how imaging studies in man can be used to assess the neurobiological correlates of resilience and, if longitudinal, of disease trajectories, progression rates and markers for recovery to inform treatment and prevention options. Methods: Original papers on recovery and resilience in alcohol addiction and its neurobiological correlates were identified from PubMed and have been analyzed and condensed within a systematic literature review. Results: Findings deriving from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) studies have identified links between increased resilience and less task‐elicited neural activation within the basal ganglia, and benefits of heightened neural pre‐frontal cortex (PFC) engagement regarding resilience in a broader sense; namely, resilience against relapse in early abstinence of AD. Furthermore, findings consistently propose at least partial recovery of brain glucose metabolism and executive and general cognitive functioning, as well as structural plasticity effects throughout the brain of alcohol‐dependent patients during the course of short‐, medium‐ and long‐term abstinence, even when patients only lowered their alcohol consumption to a moderate level. Additionally, specific factors were found that appear to influence these observed brain recovery processes in AD, e.g. genotype‐dependent neuronal (re)growth, gender‐specific neural recovery effects, critical interfering effects of psychiatric comorbidities, additional smoking or marijuana influences or adolescent alcohol abuse. Conclusions: Neuroimaging research has uncovered neurobiological markers that appear to be linked to resilience and improved recovery capacities that are furthermore influenced by various factors such as gender or genetics. Consequently, future system‐oriented approaches may help to establish a broad neuroscience‐based research framework for alcohol dependence. [ABSTRACT FROM AUTHOR]

Background: Dementia can have a profound impact on decision making. People living with dementia (PLwD) often need to make decisions about health care, and, as dementia progresses, decisions may need to be made on their behalf. Specific interventions may support this process. Review Question: What interventions are effective in improving shared decision making or surrogate decision making on the health care of PLwD? Methods: A narrative systematic review of existing literature was conducted. Seven databases, grey literature and key journals were searched. After exclusion by title, abstracts then full texts were reviewed collaboratively to manage any disagreements. Results: Eight studies met the inclusion criteria. Two articles, including one RCT, evaluated decision aids regarding the use of enteral feeding in advanced dementia. Six further articles, including five RCTs, were found which evaluated the effectiveness of interventions supporting patients or carers with advance care planning. Conclusion: Decision‐making interventions typically consist of multiple components which aim to establish preferences for future health care. Advance care planning interventions supported aspects of the decision‐making processes but their impact on decision quality was rarely evaluated. Interventions did not increase the concordance of decisions with a person's values. The decision‐specific interventions are unlikely to produce benefit in other decision contexts. Patient Involvement: Two caregivers, a public stakeholder group and a carer group were consulted in the design of the wider study to which this review relates. Six PLwD refined the research questions addressed in this paper. [ABSTRACT FROM AUTHOR]

In this paper, we consider a stochastic epidemic model with relapse, reinfection, and a general incidence function. Using stochastic tools, we establish a stochastic threshold Rs0 and prove the extinction of the disease when its value is equal or less than unity. We also show the persistence in mean of the disease when Rs0>1. Moreover, we prove the existence and uniqueness of a stationary distribution. Finally, numerical simulations are presented to show the effectiveness of theoretical results. [ABSTRACT FROM AUTHOR]

Aim: To analyse the development of motor skill and executive function in school-aged children with and without developmental coordination disorder (DCD).Method: Using a longitudinal design, 186 children (86 males, 100 females) aged 6 to 11 years at Time 1 were tested over a 2-year period, 52 of whom were diagnosed with DCD at Time 1 (27 males, 25 females; mean age 8y 5mo, SD 1y 6mo) using DSM-5 criteria. The McCarron Assessment of Neuromuscular Development assessed motor status at Time 1 and at 2-year follow-up (Time 2). Executive function was assessed using a well-validated measure, the Groton Maze Learning Test.Results: The DCD cohort at Time 1 had moderate incidence of executive function deficit (41%). Most importantly, at a group level, children with persisting DCD (across Times 1 and 2) also showed significantly lower levels of executive function than children with typical motor development at both time points. At an individual level, around 26% of children in this group had persisting executive function deficits relative to normal ranges of performance.Interpretation: Children with persisting DCD are at significant risk of executive function issues. The combination of motor and cognitive issues as a potential risk factor in the longer-term development of children is discussed.What This Paper Adds: Around half of children initially diagnosed with developmental coordination disorder (DCD) had the same diagnosis at 2-year follow-up. 41% of children with DCD have impaired executive function. Children with persisting DCD show poorer executive function than those with typical motor development or remitting DCD. [ABSTRACT FROM AUTHOR]

Peri-implant diseases are prevalent with a weighted mean prevalence rate of 43% across Europe and 22% across South and North America. Although the main etiologic agent is bacterial biofilm, a myriad of factors influence the initiation and progression of the disease. Unfortunately, the treatment of peri-implant diseases is at best favorable in the short term with a high rate of persistent inflammation and recurrence. Therefore, it is sensible to consider and control all potential factors that may predispose an implant to peri-implant tissue inflammation in an attempt to avoid the disease. This paper reviews recent evidence on factors that may predispose implants to peri-implantitis and measures that can be taken to prevent it. [ABSTRACT FROM AUTHOR]

Oxidative stress has a significant impact on neurodegenerative diseases. The present paper reviewed the role of oxidative stress in disease progression of Alzheimer's disease (AD) and measurement of the oxidative stress markers in cerebrospinal fluid (CSF) in AD in vivo. Oxidative stress measurement in CSF in AD provides knowledge of underlying pathophysiology, to be a counterpart of oxidative stress neuroimaging, and to help differentiating AD from other neurodegenerative diseases. In addition, these findings warrant future studies to see whether antioxidant intervention might help preventing progression of neurodegenerative diseases including AD. [ABSTRACT FROM AUTHOR]

Summary: Background: 5‐aminosalicylates (5‐ASA) are widely used in inflammatory bowel disease (IBD), but emerging evidence suggests that they may be safely withdrawn in significant subsets of patients. This is important to address: 5‐ASA therapy accounts for up to 25% of total healthcare costs in ulcerative colitis (UC), while almost a third of patients with Crohn's disease (CD) receive long‐term 5‐ASA despite no clear evidence of benefit. Further, rationalising medication burden may improve overall adherence and outcome. Aims: To summarise the rationale for 5‐ASA withdrawal, review the current evidence in both UC and CD and consider the data surrounding colorectal cancer (CRC) prevention, guiding an evidence‐based withdrawal strategy. Methods: PubMed was searched to identify relevant studies. Only papers published in English were reviewed, with priority given to randomised clinical trials and meta‐analyses. Results: For patients with UC, consideration of 5‐ASA withdrawal should be made on a case‐by‐case basis, but it appears safest for those in deep remission without any of the following risk factors: younger age (<40 years), remission for less than 2 years, a history of multiple flares, extensive disease. 5‐ASA withdrawal should also be considered in patients with UC escalated to biologic therapy who have achieved remission and in all patients with CD. Although 5‐ASA therapy may have chemopreventive benefits for CRC, the cost‐benefit ratio appears significant, and this indication is not justified by evidence in those who have achieved remission and are continuing therapy with other agents, or in those in sustained remission without a history of extensive disease. Conclusions: Although the majority of patients with IBD receive 5‐ASA during their disease course, safe withdrawal appears possible in many, with important implications for both health economics and patient experience. A number of unanswered questions, however, remain. [ABSTRACT FROM AUTHOR]

A clinical hold order by the Food and Drug Administration (FDA) to the sponsor of a clinical trial is a measure to delay a proposed or to suspend an ongoing clinical investigation. The phase III clinical trial START serves as motivating data example to explore implications and potential statistical approaches for a trial continuing after a clinical hold is lifted. In spite of a modified intention‐to‐treat (ITT) analysis introduced to account for the clinical hold by excluding patients potentially affected most by the clinical hold, results of the trial did not show a significant improvement of overall survival duration, and the question remains whether the negative result was an effect of the clinical hold. In this paper, we propose a multistate model incorporating the clinical hold as well as disease progression as intermediate events to investigate the impact of the clinical hold on the treatment effect. Moreover, we consider a simple counterfactual censoring approach as alternative strategy to the modified ITT analysis to deal with a clinical hold. Using a realistic simulation study informed by the START data and with a design based on our multistate model, we show that the modified ITT analysis used in the START trial was reasonable. However, the censoring approach will be shown to have some benefits in terms of power and flexibility. [ABSTRACT FROM AUTHOR]

Objective: This treatment concept paper introduces a risk assessment tool, the Implant Disease Risk Assessment, (IDRA) which estimates the risk for a patient to develop peri‐implantitis. Materials and methods: The functional risk assessment diagram was constructed incorporating eight parameters, each with documented evidence for an association with peri‐implantitis. Results: The eight vectors of the diagram include (1) assessment of a history of periodontitis (2) percentage of sites with bleeding on probing (BOP) (3) number of teeth/implants with probing depths (PD) ≥5 mm (4) the ratio of periodontal bone loss (evaluated from a radiograph) divided by the patient's age (5) periodontitis susceptibility as described by the staging and grading categories from the 2017 World Workshop on the Classification of Periodontal and Peri‐implant Diseases (Journal of Periodontology, 89 Suppl 1, S159‐S172, 2018) (6) the frequency/compliance with supportive periodontal therapy (7) the distance in mm from the restorative margin of the implant‐supported prosthesis to the marginal bone crest and (8) prosthesis‐related factors including cleanability and fit of the implant‐supported prosthesis. Conclusion: The combination of these factors in a risk assessment tool, IDRA, may be useful in identifying individuals at risk for development of peri‐implantitis. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the utility of Ability Captured Through Interactive Video Evaluation (ACTIVE) scaled scores to quantify meaningful change in individuals with spinal muscular atrophy (SMA) types 2 or 3 due to disease progression or treatment.Method: ACTIVE is a custom-designed video game that measures workspace volume (WSV). Participants included 62 individuals with SMA (mean age [SD] 10y 9mo [5y], range 2y 9mo-24y) and 362 frequency-matched controls (mean age [SD] 10y 9mo [3y 6mo], range 3y 2mo-24y 9mo). Participants completed ACTIVE, other traditional assessments, and patient-reported outcomes. Responsiveness to change was evaluated by comparing longitudinal data on untreated participants to those receiving Spinraza.Results: ACTIVE was significantly correlated to the Hammersmith Functional Motor Scales Expanded and Revised Upper Limb Module (ρ=0.85 and ρ=0.92 respectively; p<0.001). Relevance to patients and families was established by strong correlations to the Patient Reported Outcomes Measurement Information System self- and parent proxy-measures of upper extremity ability (ρ=0.63 and ρ=0.70 respectively; p<0.001). Responsiveness to change was demonstrated by significant change in scaled scores after treatment (median 15.9 points, Wilcoxon signed-rank test p<0.01). A preliminary minimum clinically important difference is presented.Interpretation: These results suggest that ACTIVE WSV scores are a meaningful assessment with which to quantify change over time in individuals with SMA types 2 and 3.What This Paper Adds: Ability Captured Through Interactive Video Evaluation (ACTIVE) quantifies upper extremity function in spinal muscular atrophy. ACTIVE's scaled workspace volume strongly correlates to self- and parent-report of function. ACTIVE quantifies meaningful change after treatment. [ABSTRACT FROM AUTHOR]

With the advent of combined antiretroviral therapies, the face of HIV infection has changed dramatically from a disease with almost certain mortality from serious comorbidities, to a manageable chronic condition with an extended lifespan. In this paper we present the more recent investigations into the epidemiology, microbiology, and pathogenesis of periodontal diseases in patients with HIV, and the effects of combined antiretroviral therapies on the incidence and progression of these diseases both in adults and perinatally infected children. In addition, comparisons and potential interactions between the HIV-associated microbiome, host responses, and pathogenesis in the oral cavity with the gastrointestinal tract and other areas of the body are presented. Also, the effects of HIV and combined antiretroviral therapies on comorbidities such as hyposalivation, dementia, and osteoporosis on periodontal disease progression are discussed. [ABSTRACT FROM AUTHOR]

Aim: To collect preliminary functional data on ataxia telangiectasia and create a disease specific scale: the Ataxia Telangiectasia Functional Scale (ATFS).Method: Retrospective information on patients with ataxia telangiectasia referred to the Assistive Technology Unit was included. Functional mobility scales (the Gross Motor Function Classification System [GMFCS] and the Functional Mobility Scale [FMS]-5, FMS-50, FMS-500) and activities of daily living [ADL] parameters were recorded. We created a 51-point ATFS, that consisted of three ambulation items adapted for ataxia telangiectasia in the frame of FMS (home, school, outdoors), five ADL items, and one schooling item.Results: Twenty-seven participants (17 males, 10 females; mean age 10y 8mo [SD 5y 1mo], range 1y 9mo-25y 6mo), were enrolled; 168 measurements were recorded. Patients walked at a mean age of 1 year 4 months (SD 5y 4mo) and lost ambulatory capacity at 8 years 8 months (SD 2y 1mo). GMFCS level and FMS-5, FMS-50, FMS-500 assessments correlated with age (Spearman's correlations r=0.555, -0.617, -0.639, -0.662 respectively, p<0.01 for all), but plateaued after 12 years of age. ATFS mean score was 37.46 (SD 7.88) and increased with age (Spearman's correlation r=0.585, p<0.01). The scale showed three stages of disease progression.Interpretation: In this pilot study we show longitudinal functional data of ambulation and ADL skills in ataxia telangiectasia, and created a framework for a functional scale. This functional scale closely approximated disease course, but further validation is required.What This Paper Adds: The Gross Motor Function Classification System and the Functional Mobility Scale are ill-suited for ataxia telangiectasia assessments. Three functional mobility scales (home, school, outdoors) suited to ataxia telangiectasia were created. The Ataxia Telangiectasia Functional Scale (ATFS) combines mobility and items of activities of daily living. The ATFS closely approximates the three-stage progression of the disorder. [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic hepatitis delta is a severe liver disease with rapid progression to cirrhosis. The impact of hepatitis delta virus (HDV)‐RNA on disease progression and interferon treatment in a real‐world cohort has been barely explored. Aim: To assess the development of clinical events in a cohort of chronic hepatitis delta patients according to the presence or absence of HDV‐RNA Methods: Multicentre study at four academic hospitals in Spain included anti‐HDV‐positive patients with compensated liver disease with a follow‐up ≥12 months. Results: Among 2888 HBsAg‐positive subjects, 151 (5.2%) tested positive for anti‐HDV, and 118 were included (58% men; median age, 49 years; 73% detectable HDV‐RNA and 30% cirrhosis, most often in subjects with HDV‐RNA). After a median follow‐up of 8 years, subjects with initially detectable HDV‐RNA were more prone to developing cirrhosis (31% vs 0%, P =.002) and/or liver decompensation (28% vs 3%, P =.019). Mortality rate was 0.44 per 1000 person‐months. The probability of a clinical event was 6%, 25%, and 80% according to initial baseline‐event‐anticipation score. HDV‐RNA became undetectable in 21 (24%) subjects either due to interferon or spontaneously (48% vs 52%, P =.29). Liver decompensation was reduced in interferon‐treated patients (13% vs 38%, P =.026). Conclusions: Subjects with persistently positive HDV‐RNA had a worse prognosis in terms of clinical events. Baseline‐event‐anticipation score is useful in predicting the risk of developing liver decompensation and hepatocellular carcinoma. Interferon was beneficial in reducing liver decompensation, even in the absence of virological response. LINKED CONTENT This article is linked to Sonneveld and de Knegt and Palom et al papers. To view these articles, visit https://doi.org/10.1111/apt.15549 and https://doi.org/10.1111/apt.15558. [ABSTRACT FROM AUTHOR]

On a global scale, myopia is one of the most common causes of visual impairment. Given the increasing prevalence of myopia, it is vital to understand the pathogenesis and to identify potential interventions. Some studies have described physical activity as a potential correlation for myopia. The objective of this study was to make a systematic review regarding the correlation between physical activity and myopia. A total of 263 papers were identified in a systematic database search of PubMed/Medline and Embase. Five steps of screening removed studies of a low evidence quality and animal studies. Studies included had refractive error and physical activity (as measured by questionnaires, accelerometers and cycle ergometers) as separate, well-defined outcomes. Nine studies (six cross-sectional, two cohorts and one case-control study) with a total of 17 634 subjects were included. Six studies demonstrated a reverse association between physical activity and myopia. Three studies supported this, but also attributed the results to time spent outdoors and not physical activity per se. One cross-sectional study found no relation. We could not identify trends among the papers regarding the type of studies, population sizes, ethnicity or age of study subjects. A consistent relationship between more physical activity and less myopia was observed. No evidence of physical activity as an independent risk factor for myopia was seen. Evidence suggests that time outdoors remain the most important factor. Future studies should include objective measurements of physical activity to determine a potential independent effect. Distinction between physical activity and outdoor exposure remains important. [ABSTRACT FROM AUTHOR]

This paper is motivated by combining serial neurocognitive assessments and other clinical variables for monitoring the progression of Alzheimer's disease (AD). We propose a novel framework for the use of multiple longitudinal neurocognitive markers to predict the progression of AD. The conventional joint modeling longitudinal and survival data approach is not applicable when there is a large number of longitudinal outcomes. We introduce various approaches based on functional principal component for dimension reduction and feature extraction from multiple longitudinal outcomes. We use these features to extrapolate the health outcome trajectories and use scores on these features as predictors in a Cox proportional hazards model to conduct predictions over time. We propose a personalized dynamic prediction framework that can be updated as new observations collected to reflect the patient's latest prognosis, and thus intervention could be initiated in a timely manner. Simulation studies and application to the Alzheimer's Disease Neuroimaging Initiative dataset demonstrate the robustness of the method for the prediction of future health outcomes and risks of target events under various scenarios. [ABSTRACT FROM AUTHOR]