Apixaban overdose in children: case report and proposed management. A brief communication from the Pediatric and Neonatal Thrombosis and Hemostasis SSC of ISTH.

BACKGROUND: Direct oral anticoagulants are commonly prescribed for adults and increasingly also for children requiring anticoagulation therapy. While household medications should not be accessible to children, accidental, and intentional overdoses occur. KEY CLINICAL QUESTION: How should apixaban overdose in children be managed?. CLINICAL APPROACH: We present a case of an accidental overdose with the factor Xa antagonist apixaban in a young child and propose an approach to the management of cases of apixaban overdose in children. CONCLUSION: Given the increasing use of direct oral anticoagulants, it is important to have an approach to the management of overdose of these medications

Are physiotherapists expected to be competent in digital health practice? Meta-synthesis of international physiotherapy practice competency standards

BACKGROUND: Digital health technology is progressively transforming physiotherapy practice. Despite a maturing body of literature relating to physiotherapy digital health capability, research examining digital health physiotherapy competency standards is both lacking and lagging. OBJECTIVE: Examine international professional practice competency standards for physiotherapists to identify themes common to digital health practice competency, published by international peak organizations governing physiotherapy practice. METHODS: Systematic meta-synthesis of international peak organization physiotherapy practice competency standards. The study was undertaken over nine stages. Competency statements related to digital health were extracted, and further coded into resultant themes. RESULTS: Eleven documents were analyzed. Fifty-two statements explicitly referenced digital health competency. Identified themes were as follows: 1) digital health data governance; 2) digital health data translation; and 3) digital health technologies. Where digital health-related competency statements do exist, they are skewed toward health information management activities. CONCLUSIONS: Digital health practice is currently under-represented in competency standards for physiotherapists. Workforce advancement in light of the burgeoning impact of digital health will prompt further updates to professional competency standards set by our peak organizations. This will have a flow on effect, whereby education providers (e.g. universities and other professional development providers) should consider curriculum and training that prepares individuals for digitally enabled practice

A naturalistic cohort study of first-episode schizophrenia spectrum disorder: A description of the early phase of illness in the PSYSCAN cohort.

BACKGROUND: We examined the course of illness over a 12-month period in a large, international multi-center cohort of people with a first-episode schizophrenia spectrum disorder (FES) in a naturalistic, prospective study (PSYSCAN). METHOD: Patients with a first episode of schizophrenia, schizoaffective disorder (depressive type) or schizophreniform disorder were recruited at 16 institutions in Europe, Israel and Australia. Participants (N = 304) received clinical treatment as usual throughout the study. RESULTS: The mean age of the cohort was 24.3 years (SD = 5.6), and 67 % were male. At baseline, participants presented with a range of intensities of psychotic symptoms, 80 % were taking antipsychotic medication, 68 % were receiving psychological treatment, with 46.5 % in symptomatic remission. The mean duration of untreated psychosis was 6.2 months (SD = 17.0). After one year, 67 % were in symptomatic remission and 61 % were in functional remission, but 31 % had been readmitted to hospital at some time after baseline. In the cohort as a whole, depressive symptoms remained stable over the follow-up period. In patients with a current depressive episode at baseline, depressive symptoms slightly improved. Alcohol, tobacco and cannabis were the most commonly used substances, with daily users of cannabis ranging between 9 and 11 % throughout the follow-up period. CONCLUSIONS: This study provides valuable insight into the early course of a broad range of clinical and functional aspects of illness in FES patients in routine clinical practice

Inpatients' experiences of falls: A qualitative meta-synthesis

OBJECTIVES: Identify and synthesize published qualitative research reporting inpatient experiences of a fall to determine novel insights and understandings of this longstanding complex problem. RESEARCH DESIGN: Qualitative meta-synthesis. METHODS: Online databases were searched to systematically identify published research reporting inpatient experiences of a fall. The included studies were inductively analysed and interpreted then reported as a meta-synthesis. DATA SOURCES: Databases Ovid MEDLINE, Embase, Ovid Emcare, CINAHL Complete, Scopus and ProQuest Dissertations and Theses Global were searched on 3rd August, 2023. RESULTS: From 10 included publications, four new themes of inpatients' experiences of a fall were constructed. Themes one, two and three related to antecedents of patient falls, and theme four related to consequences. Theme one, 'My foot didn't come with me: Physiological and anatomical changes', encompassed patients' experiences of medical conditions, medication, and anatomical changes. These aspects contributed to alterations in balance and strength, and misconceptions of capability in activities of daily (inpatient) living. Theme two, 'I was in a hurry: Help-seeking', encompassed patients' experiences striving for independence while balancing power and control, minimizing their own needs over care of others', and unavailability of support. Theme three, 'I couldn't find the call light: Environment and equipment', encompassed patients' experiences of not being able to reach or use equipment, and environment changes. Theme four, 'It was my fault too: Blame and confidence', encompassed patients' expressions of blame after their fall, blame directed at both themselves and/or others, and impacts on confidence and fear in mobilizing. CONCLUSIONS: Inpatient falls are embedded in a complexity of individual, relational, and environmental factors, yet there are potential ways forward both informed and led by the patient's voice. Strength-based approaches to address the tenuous balance between independence and support may be one opportunity to explore as a next step in complementing the existing multifaceted interventions. IMPACT: Inpatient falls are a complex and costly health safety and quality problem. Despite global initiatives in the prevention of inpatient falls, they remain intractable. This meta-synthesis provides an in-depth exploration of extant qualitative data on patients' experiences of falls in hospitals. Four themes were constructed expressing the inpatients' experiences: physiological and anatomical changes, help-seeking, environment and equipment, and blame and confidence. Novel considerations for future investigation are offered, drawing from self-determination theory and positive psychological interventions. IMPLICATIONS FOR PATIENT CARE: This meta-synthesis elicits new considerations for future interventions based on people's experiences of their fall in hospital, offering healthcare professionals novel directions in fall prevention. REPORTING METHOD: The review was reported according to the Enhancing transparency in reporting the synthesis of qualitative research statement (ENTREQ; Tong et al., 2012). PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution. REGISTRATION: PROSPERO CRD42023445279

Visualizing Severity of Alopecia Tool (SALT) scores in the clinical setting using patient images from a clinical trial

Abstract Background The Severity of Alopecia Tool (SALT) is a standardized method for quantifying scalp hair loss in alopecia areata (AA). SALT scores can be used to guide treatment decisions and are widely used as eligibility criteria and endpoints for clinical trials in AA. However, clinicians may be unfamiliar with assessing and envisioning SALT scores in practice. Objectives To aid clinicians in the determination and application of SALT scores in a clinical setting, this manuscript seeks to contextualize SALT scores using patient images from a clinical trial of adults with severe AA. Methods Images from 722 patients enrolled in BRAVE‐AA1, a phase 2/3 study of baricitinib in adults with severe AA (SALT score ≥50; ≥50% scalp hair loss), were obtained at baseline and Weeks 12, 36, and 52 and compiled into a repository. Photographs were selected to represent SALT scores across the full range of disease (SALT scores 0–100) and to demonstrate the progression of SALT scores during the course of treatment. Results Images of six patients depict the range of SALT scores (0–100). Photographs are of male and female patients of different ages (21–69) and races (Asian, Black, White) with varying extent, density, and patterns of hair loss. Images of two additional patients demonstrate the use of SALT to monitor treatment progress, showing distinct patterns and timing of clinical response over 52 weeks of therapy. Conclusions The SALT is widely used in clinical trials for AA, but clinicians may lack familiarity. Presented patient images show SALT scores commonly used as eligibility criteria and endpoints in clinical trials, which may be useful in identifying patients eligible for systemic treatment and in visualizing therapeutic response

Association of plasma biomarkers of Alzheimer's disease and related disorders with cognition and cognitive decline: The MYHAT population-based study

INTRODUCTION: Plasma biomarkers of Alzheimer's disease and related dementias predict global cognitive performance and decline over time; it remains unclear how they associate with changes in different dementia syndromes affecting distinct cognitive domains. METHODS: In a prospective study with repeated assessments of a randomly selected population-based cohort (n = 787, median age 73), we evaluated performance and decline in different cognitive domains over up to 8 years in relation to plasma concentrations of amyloid beta 42/40 (Aβ42/40) ratio, phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). RESULTS: Cross-sectionally, memory showed the strongest associations with p-tau181, and attention, executive, and visuospatial functions with NfL. Longitudinally, memory decline was distinguishable with all biomarker profiles dichotomized according to data-driven cutoffs, most efficiently with Aβ42/40. GFAP and Aβ42/40 were the best discriminators of decline patterns in language and visuospatial functions, respectively. DISCUSSION: These relatively non-invasive tests may be beneficial for clinical screening after replication in other populations and validation through neuroimaging or cerebrospinal fluid analysis. HIGHLIGHTS: We performed a prospective study with up to 8 years of repeated domain-specific cognitive assessments and baseline plasma Alzheimer's disease and related dementias biomarker measurements in a randomly selected population-based cohort. We considered distinct growth curves of trajectories of different cognitive domains and survival bias induced by missing data by adding quadratic time and applying joint modeling technique. Cross-sectionally, memory showed the strongest associations with plasma phosphorylated tau181, while attention, executive, and visuospatial functions were most strongly associated with neurofilament light chain. Longitudinally, memory and visuospatial declines were most efficiently distinguished by dichotomized amyloid beta 42/40 profile among all plasma biomarkers, while language was by dichotomized glial fibrillary acidic protein. These relatively non-invasive tests may be beneficial for clinical screening; however, they will need replication in other populations and validation through neuroimaging and/or cerebrospinal fluid assessments

Effect of natural colorants on the quality attributes of pea protein-based meat patties

The effects of natural colorants, i.e., 1.5% (v/v) caramel, 12% (v/v) tomato powder, and 4.7% (v/v) grape skin powder, on the quality attributes of pea protein-based meat patties were investigated. These patties consisted of texturized pea protein, coconut oil and corn flour, serving as plant-based meat alternatives. The changes in quality attributes for 10 days storage at 4 °C and after cooking were analysed. The results showed that the incorporation of natural colorants led to a decrease in lightness (L*) in the patties, with tomato powder causing a significant increase in redness (a*) and yellowness (b*). Furthermore, the addition of natural colorants increased the total phenolic content, DPPH radical scavenging activity, and FRAP activity, which could have contributed to the inhibition of lipid oxidation in the products. This was confirmed by the lower TBARS values in natural colourants added pea protein meat patties. Additionally, the incorporation of natural colorants affected the texture profile of the pea protein meat patties. These findings may expand the application of natural colorants such as tomato powder and grape skin powder in the plant protein-based meat industry

Small molecule drug discovery targeting the JAK-STAT pathway.

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway functions as a central hub for transmitting signals from more than 50 cytokines, playing a pivotal role in maintaining hematopoiesis, immune balance, and tissue homeostasis. Dysregulation of this pathway has been implicated in various diseases, including immunodeficiency, autoimmune conditions, hematological disorders, and certain cancers. Proteins within this pathway have emerged as effective therapeutic targets for managing these conditions, with various approaches developed to modulate key nodes in the signaling process, spanning from receptor engagement to transcription factor activation. Following the success of JAK inhibitors such as tofacitinib for RA treatment and ruxolitinib for managing primary myelofibrosis, the pharmaceutical industry has obtained approvals for over 10 small molecule drugs targeting the JAK-STAT pathway and many more are at various stages of clinical trials. In this review, we consolidate key strategies employed in drug discovery efforts targeting this pathway, with the aim of contributing to the collective understanding of small molecule interventions in the context of JAK-STAT signaling. We aspire that our endeavors will contribute to advancing the development of innovative and efficacious treatments for a range of diseases linked to this pathway dysregulation

Biological invasions are a population-level rather than a species-level phenomenon

Biological invasions pose a rapidly expanding threat to the persistence, functioning and service provisioning of ecosystems globally, and to socio-economic interests. The stages of successful invasions are driven by the same mechanism that underlies adaptive changes across species in general-via natural selection on intraspecific variation in traits that influence survival and reproductive performance (i.e., fitness). Surprisingly, however, the rapid progress in the field of invasion science has resulted in a predominance of species-level approaches (such as deny lists), often irrespective of natural selection theory, local adaptation and other population-level processes that govern successful invasions. To address these issues, we analyse non-native species dynamics at the population level by employing a database of European freshwater macroinvertebrate time series, to investigate spreading speed, abundance dynamics and impact assessments among populations. Our findings reveal substantial variability in spreading speed and abundance trends within and between macroinvertebrate species across biogeographic regions, indicating that levels of invasiveness and impact differ markedly. Discrepancies and inconsistencies among species-level risk screenings and real population-level data were also identified, highlighting the inherent challenges in accurately assessing population-level effects through species-level assessments. In recognition of the importance of population-level assessments, we urge a shift in invasive species management frameworks, which should account for the dynamics of different populations and their environmental context. Adopting an adaptive, region-specific and population-focused approach is imperative, considering the diverse ecological contexts and varying degrees of susceptibility. Such an approach could improve and refine risk assessments while promoting mechanistic understandings of risks and impacts, thereby enabling the development of more effective conservation and management strategies