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1.
PLoS One ; 18(11): e0292128, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37948455

RESUMEN

Social work plays an important role in the assessment and treatment of people with acquired brain injury. Acquired brain injury is a complex and highly prevalent condition which can impact on cognitive, emotional and social domains. As acquired brain injury is a hidden disability it can be misdiagnosed or classified as another condition entirely. We sought to systematically explore the evidence base to examine how social workers have been prepared to work with their clients with brain injury. Employing six electronic databases (Social Policy & Practice, Web of Science, Scopus, PubMed, PsycINFO, CINAHL Plus) we reviewed 1071 papers. After applying eligibility criteria 17 papers were included in this review. We utilised standardised data extraction and quality appraisal tools to assess all included papers. Following appraisal, 9 papers were judged as possessing high methodological quality whilst 8 were judged as medium. Employing narrative synthesis, we identified four themes which captured the key findings of these papers. Themes were named as (i) advocacy and social work (ii) training and multidisciplinary team working (iii) inclusion of social networks and (iv) societal barriers. In order to meet their statutory responsibilities to practice safely, social workers must receive training in how to identify ABI and develop understanding of its consequences and subsequent need for provision. Social workers are also in a unique position to advocate for their clients and should make every effort to ensure their needs are met.


Asunto(s)
Lesiones Encefálicas , Trabajadores Sociales , Humanos , Servicio Social , Empleo , Lesiones Encefálicas/diagnóstico
2.
BMC Med ; 21(1): 445, 2023 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-37974189

RESUMEN

BACKGROUND: Acquired brain injury (ABI) is linked to increased depression risk. Existing therapies for depression in ABI (e.g., cognitive behavioural therapy) have mixed efficacy. Behavioural activation (BA), an intervention that encourages engaging in positively reinforcing activities, shows promise. The primary aims were to assess feasibility, acceptability, and potential efficacy of two 8-week BA groups. METHODS: Adults (≥ 18 years) recruited from local ABI services, charities, and self-referral via social media were randomised to condition. The Activity Planning group (AP; "traditional" BA) trained participants to plan reinforcing activities over 8 weeks. The Activity Engagement group (AE; "experiential" BA) encouraged engagement in positive activities within session only. Both BA groups were compared to an 8-week Waitlist group (WL). The primary outcomes, feasibility and acceptability, were assessed via recruitment, retention, attendance, and qualitative feedback on groups. The secondary outcome, potential efficacy, was assessed via blinded assessments of self-reported activity levels, depression, and anxiety (at pre- and post-intervention and 1 month follow-up) and were compared across trial arms. Data were collected in-person and remotely due to COVID-19. RESULTS: N = 60 participants were randomised to AP (randomised n = 22; total n = 29), AE (randomised n = 22; total n = 28), or re-randomised following WL (total n = 16). Whether in-person or remote, AP and AE were rated as similarly enjoyable and helpful. In exploring efficacy, 58.33% of AP members had clinically meaningful activity level improvements, relative to 50% AE and 38.5% WL. Both AP and AE groups had depression reductions relative to WL, but only AP participants demonstrated anxiety reductions relative to AE and WL. AP participants noted benefits of learning strategies to increase activities and learning from other group members. AE participants valued social discussion and choice in selecting in-session activities. CONCLUSIONS: Both in-person and remote group BA were feasible and acceptable in ABI. Though both traditional and experiential BA may be effective, these may have different mechanisms. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03874650. Protocol version 2.3, May 26 2020.


Asunto(s)
Acer , Lesiones Encefálicas , Terapia Cognitivo-Conductual , Adulto , Humanos , Lesiones Encefálicas/terapia , Terapia Cognitivo-Conductual/métodos , Estudios de Factibilidad , Satisfacción Personal , Proyectos Piloto
3.
BMJ Open ; 13(11): e072150, 2023 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-38011964

RESUMEN

INTRODUCTION: Attributing musculoskeletal (MSK) pain to normal and commonly occurring imaging findings, such as tendon, cartilage and spinal disc degeneration, has been shown to increase people's fear of movement, reduce their optimism about recovery and increase healthcare costs. Interventions seeking to reduce the negative effects of MSK imaging reporting have had little effect. To understand the ineffectiveness of these interventions, this study seeks to scope their behavioural targets, intended mechanisms of action and theoretical underpinnings. This information alongside known barriers to helpful reporting can enable researchers to refine or create new more targeted interventions. METHODS AND ANALYSIS: The scoping review will be conducted in accordance with the JBI methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Search terms will be devised by the research team. Searches of MEDLINE, EMBASE, CINAHL, AMED and PsycINFO from inception to current day will be performed. The review will include studies, which have developed or evaluated interventions targeting the reporting of MSK imaging. Studies targeting the diagnosis of serious causes of MSK pain will be excluded. Two independent authors will extract study participant data using predefined extraction templates and intervention details using the Template for Intervention Description and Replication checklist. Interventions will be coded and mapped to the technique, mechanism of action and behavioural target according to the Capability, Opportunity, Motivation-Behaviour (COM-B) model categories. Any explicit models or theories used to inform the selection of interventions will be extracted and coded. The study characteristics, behaviour change techniques identified, behavioural targets according to the COM-B and context specific theories within the studies will be presented in narrative and table form. ETHICS AND DISSEMINATION: The information from this review will be used to inform an intervention design process seeking to improve the communication of imaging results. The results will also be disseminated through a peer-reviewed publication, conference presentations and stakeholder events.


Asunto(s)
Motivación , Dolor Musculoesquelético , Humanos , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Literatura de Revisión como Asunto
4.
EClinicalMedicine ; 61: 102059, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37409323

RESUMEN

Background: The utility of early metabolic response assessment to guide selection of the systemic component of definitive chemoradiotherapy (dCRT) for oesophageal cancer is uncertain. Methods: In this multi-centre, randomised, open-label, phase II substudy of the radiotherapy dose-escalation SCOPE2 trial we evaluated the role of 18F-Fluorodeoxyglucose positron emission tomography (PET) at day 14 of cycle 1 of three-weekly induction cis/cap (cisplatin (60 mg/m2)/capecitabine (625 mg/m2 days 1-21)) in patients with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC). Non-responders, who had a less than 35% reduction in maximum standardised uptake value (SUVmax) from pre-treatment baseline, were randomly assigned to continue cis/cap or switch to car/pac (carboplatin AUC 5/paclitaxel 175 mg/m2) for a further induction cycle, then concurrently with radiotherapy over 25 fractions. Responders continued cis/cap for the duration of treatment. All patients (including responders) were randomised to standard (50Gy) or high (60Gy) dose radiation as part of the main study. Primary endpoint for the substudy was treatment failure-free survival (TFFS) at week 24. The trial was registered with International Standard Randomized Controlled Trial Number 97125464 and ClinicalTrials.govNCT02741856. Findings: This substudy was closed on 1st August 2021 by the Independent Data Monitoring Committee on the grounds of futility and possible harm. To this point from 22nd November 2016, 103 patients from 16 UK centres had participated in the PET-CT substudy; 63 (61.2%; 52/83 OSCC, 11/20 OAC) of whom were non-responders. Of these, 31 were randomised to car/pac and 32 to remain on cis/cap. All patients were followed up until at least 24 weeks, at which point in OSCC both TFFS (25/27 (92.6%) vs 17/25 (68%); p = 0.028) and overall survival (42.5 vs. 20.4 months, adjusted HR 0.36; p = 0.018) favoured cis/cap over car/pac. There was a trend towards worse survival in OSCC + OAC cis/cap responders (33.6 months; 95%CI 23.1-nr) vs. non-responders (42.5 (95%CI 27.0-nr) months; HR = 1.43; 95%CI 0.67-3.08; p = 0.35). Interpretation: In OSCC, early metabolic response assessment is not prognostic for TFFS or overall survival and should not be used to personalise systemic therapy in patients receiving dCRT. Funding: Cancer Research UK.

5.
BMC Biol ; 21(1): 114, 2023 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-37208758

RESUMEN

This paper is a response to Polinski, M. P. et al. Innate antiviral defense demonstrates high energetic efficiency in a bony fish. BMC Biology 19, 138 (2021). https://doi.org/10.1186/s12915-021-01069-2.


Asunto(s)
Enfermedades de los Peces , Orthoreovirus , Infecciones por Reoviridae , Animales , Infecciones por Reoviridae/veterinaria , Orthoreovirus/fisiología , Salmón
6.
Sci Rep ; 13(1): 5473, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-37016008

RESUMEN

Although infectious agents can act as strong population regulators, knowledge of their spatial distributions in wild Pacific salmon is limited, especially in the marine environment. Characterizing pathogen distributions during early marine residence, a period considered a survival bottleneck for Pacific salmon, may reveal where salmon populations are exposed to potentially detrimental pathogens. Using high-throughput qPCR, we determined the prevalence of 56 infectious agents in 5719 Chinook, 2032 Coho and 4062 Sockeye salmon, sampled between 2008 and 2018, in their first year of marine residence along coastal Western Canada. We identified high prevalence clusters, which often shifted geographically with season, for most of the 41 detected agents. A high density of infection clusters was found in the Salish Sea along the east coast of Vancouver Island, an important migration route and residence area for many salmon populations, some experiencing chronically poor marine survival. Maps for each infectious agent taxa showing clusters across all host species are provided. Our novel documentation of salmon pathogen distributions in the marine environment contributes to the ecological knowledge regarding some lesser known pathogens, identifies salmon populations potentially impacted by specific pathogens, and pinpoints priority locations for future research and remediation.


Asunto(s)
Oncorhynchus , Animales , Colombia Británica/epidemiología , Salmón
7.
Clin Transl Radiat Oncol ; 40: 100614, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36949958

RESUMEN

Background and purpose: Radical concurrent chemoradiotherapy (CRT) for oesophageal cancer is associated with significant morbidity and is unsuitable for some patients. Olaparib, an inhibitor of the DNA repair enzyme poly-(ADP)-ribose polymerase (PARP) has radiosensitising properties and may be better tolerated than chemotherapy. Materials and methods: We performed a phase 1 study of olaparib with radiotherapy (RT) in oesophageal cancer patients unsuitable for conventional CRT to determine its maximum tolerated dose (MTD) in this setting. Results: Eight patients were recruited. One of 5 patients receiving olaparib 50 mg twice daily and two of 3 receiving 100 mg twice daily experienced dose limiting toxicity (DLT). Conclusions: Olaparib 100 mg twice daily exceeded the MTD in combination with RT in these patients. 50 mg twice daily may be the MTD but this cannot be stated with certainty as the study closed before full recruitment.

8.
Health Promot Int ; 38(1)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36795097

RESUMEN

From the year 2003 when the first walkability scale was published to date, person-environment fit models and empirical research, some of which was published in Health Promotion International, have encapsulated healthy communities in 'neighborhood walkability'. While there is no doubt that neighborhood walkability positively influences health-seeking behaviors and health, recent models suggest that their measurement and conceptualization have not emphasized the role played by psychosocial and personal factors in aging in place. Thus, the development of scales measuring human ecosystem factors has not recognized all critical factors suited for older adults. In this paper, we aim to draw on relevant literature to frame a more holistic construct, hereby referred to as Socially Active Neighborhoods (SAN), that would better support aging in place in older populations. Through a narrative review based on a systematic search of the literature, we define the scope of SAN and delineate some contextual implications for gerontology, health promotion and psychometric testing. SAN, unlike neighborhood walkability in its current measurement and conceptualization, incorporates critical theory-informed psychosocial factors (i.e. safety and disability friendliness of neighborhood infrastructure) that can encourage older adults with physiological and cognitive limitations to maintain physical and social activities as well as health in later life. The SAN is the result of our adaptation of key person-environment models, including the Context Dynamics in Aging (CODA) framework, that recognizes the role of context in healthy aging.


Asunto(s)
Vida Independiente , Caminata , Humanos , Anciano , Psicometría , Ecosistema , Características de la Residencia , Promoción de la Salud , Planificación Ambiental
9.
Artículo en Inglés | MEDLINE | ID: mdl-36360952

RESUMEN

Several studies have compared physical activity (PA) levels between countries, but none of these studies focused on older adults and occupational PA. This study aimed to assess potential inequalities in older adults' occupational PA across six countries and to ascertain whether having multiple jobs is a factor that interacts with country of residence to modify inequalities. This study adopted a cross-sectional design with a statistical technique screening for potential covariates. Older adults (mean age = 64 years; range = 50-114 years) from six countries (Russia, Mexico, China, India, Ghana, and South Africa) participated in the study. We utilised data from the first wave of the Study on Global AGEing and Adult Health (SAGE). These data were collected from 2007 to 2010. A random sample of 34,114 older adults completed the survey. We analysed the data with a two-way multivariate analysis of variance after screening for the ultimate covariates. There were differences in occupational PA levels (i.e., vigorous and moderate PA) among the six countries. Occupational PA levels were not significantly associated with having multiple jobs. However, having multiple jobs interacted with country of residence to influence vigorous occupational PA. Older adults from most countries who had more than one job reported more vigorous occupational PA. Older adults' occupational PA differed among the six countries, and having multiple jobs was associated with more vigorous occupational PA. Older adults who keep multiple jobs at a time may be more active than their counterparts who had one job or were unemployed.


Asunto(s)
Países en Desarrollo , Ejercicio Físico , Estudios Transversales , India , China
10.
EClinicalMedicine ; 53: 101664, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36187722

RESUMEN

Background: Effective surveillance strategies are required for patients diagnosed with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC) for whom chemoradiotherapy (CRT) is used as a potentially-curative, organ-sparing, alternative to surgery. In this study, we evaluated the safety, acceptability and tolerability of a non-endoscopic immunocytological device (the Cytosponge™) to assess treatment response following CRT. Methods: This multicentre, single-arm feasibility trial took place in 10 tertiary cancer centres in the UK. Patients aged at least 16 years diagnosed with OSCC or OAC, and who were within 4-16 weeks of completing definitive or neo-adjuvant CRT, were included. Participants were required to have a Mellow-Pinkas dysphagia score of 0-2 and be able to swallow tablets. All patients underwent a single Cytosponge™ assessment in addition to standard of care (which included post-treatment endoscopic evaluation with biopsy for patients undergoing definitive CRT; surgery for those who received neo-adjuvant CRT). The primary outcome was the proportion of consented, evaluable patients who successfully underwent Cytosponge™ assessment. Secondary and tertiary outcomes included safety, study consent rate, acceptance rate, the suitability of obtained samples for biomarker analysis, and the comparative efficacy of Cytosponge™ to standard histology (endoscopy and biopsy or post-resection specimen) in assessing for residual disease. The trial is registered with ClinicalTrials.gov, NCT03529669. Findings: Between 18th April 2018 and 16th January 2020, 41 (42.7%; 95% confidence interval (CI) 32.7-53.2) of 96 potentially eligible patients consented to participate. Thirty-nine (95.1%, 95% CI 83.5-99.4) successfully carried out the Cytosponge™ procedure. Of these, 37 (95%) would be prepared to repeat the procedure. There were only two grade 1 adverse events attributed to use of the Cytosponge™. Thirty-five (90%) of the completed Cytosponge™ samples were suitable for biomarker analysis; 29 (83%) of these were concordant with endoscopic biopsies, three (9%) had findings suggestive of residual cancer on Cytosponge™ not found on endoscopic biopsies, and three (9%) had residual cancer on endoscopic biopsies not detected by Cytosponge™. Interpretation: Use of the CytospongeTM is safe, tolerable, and acceptable for the assessment of treatment response following CRT in OAC and OSCC. Further evaluation of Cytosponge™ in this setting is warranted. Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council.

12.
Neuropsychol Rev ; 32(4): 974-1016, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35349054

RESUMEN

Minimal but increasing number of assessment instruments for Executive functions (EFs) and adaptive functioning (AF) have either been developed for or adapted and validated for use among children in low and middle income countries (LAMICs). However, the suitability of these tools for this context is unclear. A systematic review of such instruments was thus undertaken. The Systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist (Liberati et al., in BMJ (Clinical Research Ed.), 339, 2009). A search was made for primary research papers reporting psychometric properties for development or adaptation of either EF or AF tools among children in LAMICs, with no date or language restrictions. 14 bibliographic databases were searched, including grey literature. Risk of bias assessment was done following the COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) guidelines (Mokkink et al., in Quality of Life Research, 63, 32, 2014). For EF, the Behaviour Rating Inventory of Executive Functioning (BRIEF- multiple versions), Wisconsin Card Sorting Test (WCST), Go/No-go and the Rey-Osterrieth complex figure (ROCF) were the most rigorously validated. For AFs, the Vineland Adaptive Behaviour Scales (VABS- multiple versions) and the Child Function Impairment Rating Scale (CFIRS- first edition) were most validated. Most of these tools showed adequate internal consistency and structural validity. However, none of these tools showed acceptable quality of evidence for sufficient psychometric properties across all the measured domains, particularly so for content validity and cross-cultural validity in LAMICs. There is a great need for adequate adaptation of the most popular EF and AF instruments, or alternatively the development of purpose-made instruments for assessing children in LAMICs.Systematic Review Registration numbers: CRD42020202190 (EF tools systematic review) and CRD42020203968 (AF tools systematic review) registered on PROSPERO website ( https://www.crd.york.ac.uk/prospero/ ).


Asunto(s)
Países en Desarrollo , Calidad de Vida , Adolescente , Niño , Humanos , Encéfalo , Función Ejecutiva , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
13.
Front Hum Neurosci ; 16: 767367, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35308604

RESUMEN

Aims: The aim of this study was to assess the psychometric properties of the revised self-rated version of the Dysexecutive Questionnaire (DEX-R) within a non-clinical sample. Methods: The study was hosted online, with 140 participants completing the DEX-R, GAD-2 and PHQ-2. Sixty participants also completed the FrSBe, with 99 additionally completing the DEX-R again 3 weeks later. Correlations with demographic factors and symptoms of anxiety and depression were conducted. Rasch and factor analysis were also used to explore underlying subconstructs. Results: The DEX-R correlated highly with the FrSBe, indicating sound concurrent validity. Internal consistency, split-half reliability and test-retest reliability were excellent. Age and symptoms of depression and anxiety correlated with DEX-R scores, with older age associated with less dysexecutive problems. The Rasch analysis confirmed the multidimensionality of the rating scale, and a three-factor structure was found relating to activation-self-regulatory, cognitive and social-emotional processes. Frequencies of responses on DEX-R items varied, many were not fully endorsed indicating specific relevance of most but not all items to patients. Conclusion: Interpretations of DEX-R ratings of dysexecutive problems should consider mood and individual variation. Systematic comparison of DEX-R responses between healthy and clinical groups could help identify a suitable cut off for dysexecutive symptoms.

14.
Sci Rep ; 12(1): 4775, 2022 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-35347162

RESUMEN

Parasitic salmon lice (Lepeophtheirus salmonis) threaten the economic and ecological sustainability of salmon farming, and their evolved resistance to treatment with emamectin benzoate (EMB) has been a major problem for salmon farming in the Atlantic Ocean. In contrast, the Pacific Ocean, where wild salmon are far more abundant, has not seen widespread evolution of EMB-resistant lice. Here, we use EMB bioassays and counts of lice on farms from the Broughton Archipelago, Canada-a core region of salmon farming in the Pacific-to show that EMB sensitivity has dramatically decreased since 2010, concurrent with marked decrease in the field efficacy of EMB treatments. Notably, these bioassay data were not made available through public reporting by industry or by the federal regulator, but rather through Indigenous-led agreements that created a legal obligation for salmon-farming companies to provide data to First Nations. Our results suggest that salmon lice in the Pacific Ocean have recently evolved substantial resistance to EMB, and that salmon-louse outbreaks on Pacific farms will therefore be more difficult to control in the coming years.


Asunto(s)
Copépodos , Parásitos , Animales , Antiparasitarios/farmacología , Antiparasitarios/uso terapéutico , Océano Pacífico , Salmón/parasitología
15.
Neuropsychol Rehabil ; 32(10): 2603-2627, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34505555

RESUMEN

Cognitive difficulties are common following stroke and can have widespread impacts on everyday functioning. Technological advances offer the possibility of individualized cognitive training for patients at home, potentially providing a low-cost, low-intensity adjunct to rehabilitation services. Using this approach, we have previously demonstrated post-training improvements in attention and everyday functioning in fronto-parietal stroke patients. Here we examine whether these benefits are observed more broadly in a community stroke sample. Eighty patients were randomized to either 4 weeks of online adaptive attention training (SAT), working memory training (WMT) or waitlist (WL). Cognitive and everyday function measures were collected before and after the intervention, and after 3 months. During training, weekly measures of patients' subjective functioning were collected. The training was well received and compliance good. No differences in our primary end-point, spatial bias, or other cognitive functions were observed. However, on patient-reported outcomes, SAT participants showed greater levels of improvement in everyday functioning than WMT or WL participants. In line with our previous work, everyday functioning improvements were greatest for patients with spatial impairments and those who received SAT training. Whether attention training can be recommended for stroke survivors depends on whether cognitive test performance or everyday functioning is considered more relevant.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Entrenamiento Cognitivo , Cognición , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/psicología , Memoria a Corto Plazo , Atención
16.
Neuropsychol Rehabil ; 32(8): 2147-2169, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34596002

RESUMEN

The effectiveness of holistic neuropsychological rehabilitation for people with acquired brain injury has previously been demonstrated by means of standardized and routinely administered outcome measures. However, the most important outcomes from the perspective of former clients are largely unknown. This study explored the experience of participating in a holistic neuropsychological rehabilitation programme by conducting three focus groups with twelve former clients who had sustained a brain injury. Data were transcribed verbatim and analysed using thematic analysis. "It is an ongoing process" emerged as the overarching theme for the experience of recovery from brain injury. Four subthemes, or phases, were identified. Participants went through (1) a phase of confrontation, after which they (2) trained their skills and strategies, and (3) experimented with these in daily life. In the end, clients reached a phase of (4) coming to terms with their injury. Participants described increased levels of self-esteem, sense of competence, and adaptation as the most important outcomes of the programme, as these factors helped them regain a sense of identity. The results indicate that including these factors in outcome evaluations of complex interventions after brain injury may be important as they appear essential for capturing the client's perspective on change.


Asunto(s)
Lesiones Encefálicas , Lesiones Encefálicas/rehabilitación , Humanos , Estudios Longitudinales , Autoimagen
17.
Neuropsychol Rev ; 32(3): 459-482, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34870774

RESUMEN

Several tools have been developed to assess executive function (EFs) and adaptive functioning, although in mainly Western populations. Information on tools for low-and-middle-income country children is scanty. A scoping review of such instruments was therefore undertaken.We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis- Scoping Review extension (PRISMA-ScR) checklist (Tricco et al., in Annals of Internal Medicine 169(7), 467-473, 2018). A search was made for primary research papers of all study designs that focused on development or adaptation of EF or adaptive function tools in low-and-middle-income countries, published between 1st January 1894 to 15th September 2020. 14 bibliographic databases were searched, including several non-English databases and the data were independently charted by at least 2 reviewers.The search strategy identified 5675 eligible abstracts, which was pruned down to 570 full text articles. These full-text articles were then manually screened for eligibility with 51 being eligible. 41 unique tools coming in 49 versions were reviewed. Of these, the Behaviour Rating Inventory of Executive Functioning (BRIEF- multiple versions), Wisconsin Card Sorting Test (WCST), Go/No-go and the Rey-Osterrieth complex figure (ROCF) had the most validations undertaken for EF tests. For adaptive functions, the tools with the most validation studies were the Vineland Adaptive Behaviour Scales (VABS- multiple versions) and the Child Function Impairment Rating Scale (CFIRS- first edition).There is a fair assortment of tests available that have either been developed or adapted for use among children in developing countries but with limited range of validation studies. However, their psychometric adequacy for this population was beyond the scope of this paper.


Asunto(s)
Países en Desarrollo , Función Ejecutiva , Encéfalo , Niño , Humanos , Pruebas Neuropsicológicas , Psicometría
19.
Proc Natl Acad Sci U S A ; 118(25)2021 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-34140407

RESUMEN

In 2006, GRN mutations were first linked to frontotemporal dementia (FTD), the leading cause of non-Alzheimer dementias. While much research has been dedicated to understanding the genetic causes of the disease, our understanding of the mechanistic impacts of GRN deficiency has only recently begun to take shape. With no known cure or treatment available for GRN-related FTD, there is a growing need to rapidly advance genetic and/or small-molecule therapeutics for this disease. This issue is complicated by the fact that, while lysosomal dysfunction seems to be a key driver of pathology, the mechanisms linking a loss of GRN to a pathogenic state remain unclear. In our attempt to address these key issues, we have turned to the nematode, Caenorhabditis elegans, to model, study, and find potential therapies for GRN-deficient FTD. First, we show that the loss of the nematode GRN ortholog, pgrn-1, results in several behavioral and molecular defects, including lysosomal dysfunction and defects in autophagic flux. Our investigations implicate the sphingolipid metabolic pathway in the regulation of many of the in vivo defects associated with pgrn-1 loss. Finally, we utilized these nematodes as an in vivo tool for high-throughput drug screening and identified two small molecules with potential therapeutic applications against GRN/pgrn-1 deficiency. These compounds reverse the biochemical, cellular, and functional phenotypes of GRN deficiency. Together, our results open avenues for mechanistic and therapeutic research into the outcomes of GRN-related neurodegeneration, both genetic and molecular.


Asunto(s)
Autofagia/genética , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Lisosomas/genética , Progranulinas/metabolismo , Acetofenonas/farmacología , Animales , Benzopiranos/farmacología , Vías Biosintéticas , Caenorhabditis elegans/citología , Proteínas de Caenorhabditis elegans/genética , Evaluación Preclínica de Medicamentos , Demencia Frontotemporal/genética , Demencia Frontotemporal/patología , Mutación/genética , Fenotipo , Progranulinas/genética , Rivastigmina/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Esfingolípidos/metabolismo
20.
Eur J Cancer ; 153: 153-161, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34157617

RESUMEN

AIM: This is the first randomised study to evaluate toxicity and survival outcomes of two neoadjuvant chemoradiotherapy (CRT) regimens for patients with localised oesophageal adenocarcinoma (OAC) or gastro-oesophageal junction (GOJ) adenocarcinoma. The initial results showed comparable toxicity between regimens and pathological complete response (pCR) rate favouring CarPacRT. Herein, we report survival, progression patterns, and long-term toxicity after a median follow-up of 40.7 months. METHODS: NeoSCOPE was an open-label, UK multicentre, randomised, phase II trial. Eighty-five patients with resectable OAC or GOJ adenocarcinoma, ≥cT3 and/or ≥cN1 (TNM v7), suitable for neoadjuvant CRT, were recruited between October 2013 and February 2015. Patients were randomised to OxCapRT (oxaliplatin 85 mg/m2 on Days 1, 15, and 29; capecitabine 625 mg/m2 orally twice daily on days of radiotherapy [RT]) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2 on Days 1, 8, 15, 22, and 29). RT dose was 45 Gy/25 fractions/5 weeks. Both arms received induction chemotherapy (two cycles oxaliplatin 130 mg/m2 on Day 1, capecitabine 625 mg/m2 orally twice daily on Days 1-21) before CRT. Surgery was performed 6-8 weeks after CRT. The primary end-point was pCR. Secondary end-points were toxicity, progression-free survival (PFS), overall survival (OS), and patterns of progression. RESULTS: Eighty-five patients were recruited from 17 UK centres. The median OS was 41.7 months (95% confidence interval [CI] 19.6 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable hazard ratio [HR] = 0.48, 95% CIs: 0.24-0.95, P = 0.035). The median PFS was 32.6 months (95% CIs: 17.1 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable HR = 0.54, 95% CIs: 0.29-1.01, P = 0.053). In both arms, the distant progression was twice as common as locoregional progression. CONCLUSIONS: OS and PFS favoured neoadjuvant CarPacRT over OxCapRT. Distant was more common than locoregional progression; therefore, priority should be given to optimising the systemic treatment component. CLINICAL TRIAL INFORMATION: EudraCT Number: 2012-000640-10; ClinicalTrials.gov: NCT01843829.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Capecitabina/uso terapéutico , Carboplatino/uso terapéutico , Quimioradioterapia Adyuvante/métodos , Neoplasias Esofágicas/tratamiento farmacológico , Oxaliplatino/uso terapéutico , Paclitaxel/uso terapéutico , Anciano , Capecitabina/farmacología , Carboplatino/farmacología , Femenino , Humanos , Masculino , Oxaliplatino/farmacología , Paclitaxel/farmacología
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