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OBJECTIVES: Researchers face numerous challenges when recruiting participants for health and social care research. This study reports on the challenges faced recruiting older adults for Being Your Best, a co-designed holistic intervention to manage and reduce frailty, and highlights lessons learnt amidst the COVID-19 pandemic. DESIGN: A qualitative study design was used. Referrer interviews were conducted to explore the recruitment challenges faced by the frontline workers. An audit of the research participant (aged ≥65) database was also undertaken to evaluate the reasons for refusal to participate and withdrawal from the study. SETTING: Hospital emergency departments (EDs) and a home care provider in Melbourne, Australia. PARTICIPANTS: Frontline workers and older adults. RESULTS: From May 2022 to June 2023, 71 referrals were received. Of those referrals, only 13 (18.3%) agreed to participate. Three participants withdrew immediately after baseline data collection, and the remaining 10 continued to participate in the programme. Reasons for older adult non-participation were (1) health issues (25.3%), (2) ineligibility (18.3%), (3) lack of interest (15.5%), (4) perceptions of being 'too old' (11.2%) and (5) perceptions of being too busy (5.6%). Of those participating, five were female and five were male. Eleven referrer interviews were conducted to explore challenges with recruitment, and three themes were generated after thematic analysis: (1) challenges arising from the COVID-19 pandemic, (2) characteristics of the programme and (3) health of older adults. CONCLUSION: Despite using multiple strategies, recruitment was much lower than anticipated. The ED staff were at capacity associated with pandemic-related activities. While EDs are important sources of participants for research, they were not suitable recruitment sites at the time of this study, due to COVID-19-related challenges. Programme screening characteristics and researchers' inability to develop rapport with potential participants also contributed to low recruitment numbers. TRIAL REGISTRATION NUMBER: ACTRN12620000533998; Pre-results.
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COVID-19 , Fragilidad , Selección de Paciente , Investigación Cualitativa , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Anciano , Masculino , Femenino , Australia/epidemiología , Anciano de 80 o más Años , Salud Holística , Pandemias , Victoria , Anciano FrágilRESUMEN
BACKGROUND AND OBJECTIVES: Public health concerns surrounding social isolation and loneliness heightened during the coronavirus disease 2019 (COVID-19) pandemic, as infection prevention measures led to increased feelings of loneliness and depression. Our objective was to evaluate the implementation of the HOW-R-U? program, during the pandemic (March 2020-December 2021). HOW-R-U? is a weekly volunteer-delivered telephone program designed to facilitate social connection and ease feelings of social isolation, loneliness, and depression in older people. RESEARCH DESIGN AND METHODS: This pragmatic study used the Implementation Framework for Aged Care to adapt and implement HOW-R-U? in an Australian aged and community care organization and a tertiary health service in Melbourne. The evaluation involved analysis of program data, semistructured interviews, and surveys with program recipients, volunteers, and referrers. A process evaluation was conducted alongside an assessment of outcomes including pre- and post-symptoms of isolation, depression, and loneliness. RESULTS: The implementation evaluation indicated that codesigned systems and processes effectively supported the ongoing implementation of HOW-R-U? with transition into business as usual across both organizations. Recipients reported that telephone calls had a positive impact on their lives, whereas volunteers reported enjoyment of supporting others. Several challenges were identified, namely in program reach and fidelity. DISCUSSION AND IMPLICATIONS: HOW-R-U? was well regarded by all involved, and evaluation learnings have informed implementation into business as usual by both organizations.
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COVID-19 , Soledad , Aislamiento Social , Apoyo Social , Teléfono , Voluntarios , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Voluntarios/psicología , Soledad/psicología , Anciano , Aislamiento Social/psicología , Masculino , Femenino , SARS-CoV-2 , Depresión/prevención & control , Depresión/psicología , Australia , Evaluación de Programas y Proyectos de Salud , PandemiasRESUMEN
Small interfering RNAs (siRNAs) are widely used in biomedical research and in clinical trials. Here, we demonstrate that siRNA treatment is commonly associated with significant sensitization to ferroptosis, independently of the target protein knockdown. Genetically targeting mitochondrial antiviral-signaling protein (MAVS) reversed the siRNA-mediated sensitizing effect, but no activation of canonical MAVS signaling, which involves phosphorylation of IkBα and interferon regulatory transcription factor 3 (IRF3), was observed. In contrast, MAVS mediated a noncanonical signal resulting in a prominent increase in mitochondrial ROS levels, and increase in the BACH1/pNRF2 transcription factor ratio and GPX4 up-regulation, which was associated with a 50% decrease in intracellular glutathione levels. We conclude that siRNAs commonly sensitize to ferroptosis and may severely compromise the conclusions drawn from silencing approaches in biomedical research. Finally, as ferroptosis contributes to a variety of pathophysiological processes, we cannot exclude side effects in human siRNA-based therapeutical concepts that should be clinically tested.
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Ferroptosis , Transducción de Señal , Humanos , ARN Interferente Pequeño/genética , Ferroptosis/genética , Regulación hacia Arriba , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Early Detection of Deterioration in Elderly Residents (EDDIE +) is a multi-modal intervention focused on empowering nursing and personal care workers to identify and proactively manage deterioration of residents living in residential aged care (RAC) homes. Building on successful pilot trials conducted between 2014 and 2017, the intervention was refined for implementation in a stepped-wedge cluster randomised trial in 12 RAC homes from March 2021 to May 2022. We report the process used to transition from a small-scale pilot intervention to a multi-site intervention, detailing the intervention to enable future replication. METHODS: The EDDIE + intervention used the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to guide the intervention development and refinement process. We conducted an environmental scan; multi-level context assessments; convened an intervention working group (IWG) to develop the program logic, conducted a sustainability assessment and deconstructed the intervention components into fixed and adaptable elements; and subsequently refined the intervention for trial. RESULTS: The original EDDIE pilot intervention included four components: nurse and personal care worker education; decision support tools; diagnostic equipment; and facilitation and clinical support. Deconstructing the intervention into core components and what could be flexibly tailored to context was essential for refining the intervention and informing future implementation across multiple sites. Intervention elements considered unsustainable were updated and refined to enable their scalability. Refinements included: an enhanced educational component with a greater focus on personal care workers and interactive learning; decision support tools that were based on updated evidence; equipment that aligned with recipient needs and available organisational support; and updated facilitation model with local and external facilitation. CONCLUSION: By using the i-PARIHS framework in the scale-up process, the EDDIE + intervention was tailored to fit the needs of intended recipients and contexts, enabling flexibility for local adaptation. The process of transitioning from a pilot to larger scale implementation in practice is vastly underreported yet vital for better development and implementation of multi-component interventions across multiple sites. We provide an example using an implementation framework and show it can be advantageous to researchers and health practitioners from pilot stage to refinement, through to larger scale implementation. TRIAL REGISTRATION: The trial was prospectively registered with the Australia New Zealand Clinical Trial Registry (ACTRN12620000507987, registered 23/04/2020).
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Hogares para Ancianos , Casas de Salud , Anciano , Humanos , Investigación sobre Servicios de Salud , Manejo de DatosRESUMEN
AIMS: To explore stakeholders' perceptions of a facilitator's role in supporting carers when embedding iSupport for Dementia psychoeducation program, in care services. METHODS: A qualitative descriptive study design was applied. Data were collected from workshops and interviews with carers of people living with dementia (PLWD)and with health and social care professionals from two tertiary hospitals and two community aged care organisations across three Australian states between October 2021 and March 2022. A thematic analysis was used to analyse data. The COREQ guideline was followed to report our findings. RESULTS: A total of 30 family carers and 45 health and social care professionals participated in the study. Three main themes and seven subthemes were identified from the data. We described the main themes as (1) the facilitator's role at the time of dementia diagnosis, (2) the facilitator's role throughout the everyday dementia care journey and (3) the facilitator's role during transition moments. CONCLUSIONS: Caring for family members with dementia is demanding and stressful for carers. Embedding a facilitator-enabled iSupport for Dementia program in hospital and community aged care settings has the potential to mitigate sources of stress associated with care recipient factors, carer factors and care service factors, and improve the health and well-being of carers and those for whom they care. RELEVANCE TO CLINICAL PRACTICE: Our findings will inform the establishment of iSupport facilitators appointed by dementia care providers in hospital and community care settings and help determine their roles and responsibilities in delivering the iSupport program. Our findings relate to nurse-led and coordinated dementia care in hospital and community aged care settings. PATIENT OR PUBLIC CONTRIBUTION: This study was co-designed with stakeholders from two aged care organisations and two tertiary hospitals. The study participants were staff employed by these organisations and carers of PLWD who were service users.
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Cuidadores , Demencia , Humanos , Anciano , Australia , Investigación Cualitativa , Servicios de SaludRESUMEN
BACKGROUND: Falls are a major concern for community-dwelling older adults. The Otago Exercise Program (OEP) is an evidence-based home program that reduces risk of falls. Exercise participation and program adherence can be challenging. Home care workers (HCWs) are well positioned to provide support for older adults. METHODS: This feasibility study included: HCW training; HCW in-home support of a physiotherapist-tailored OEP; online physiotherapy consultations; older participant questionnaires and functional outcome measures; and HCW and older participant interviews. RESULTS: Twelve older adults, eight HCWs and one physiotherapist participated. A small falls risk reduction, and improvement in falls efficacy, quality of life and functional improvement were noted. Thematic analysis showed formal and informal support was valued by older adults and HCWs. A role-ordered matrix synthesis highlighted variable ongoing independent program participation. CONCLUSIONS: By Your Side, a physiotherapist-led and home care worker-supported modified OEP provides a feasible and acceptable option for falls prevention in home care services. Collaborative teamwork, and both formal and informal support, are key aspects to optimising engagement and benefits.
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Terapia por Ejercicio , Servicios de Atención de Salud a Domicilio , Humanos , Anciano , Calidad de Vida , Estudios de Factibilidad , Accidentes por Caídas/prevención & controlRESUMEN
BACKGROUND: Informal caregivers of people living with dementia experience a higher level of physical and mental stress compared with other types of caregivers. Psychoeducation programs are viewed as beneficial for building caregivers' knowledge and skills and for decreasing caregiver stress. OBJECTIVE: This review aimed to synthesize the experiences and perceptions of informal caregivers of people with dementia when participating in web-based psychoeducation programs and the factors that enable and impede informal caregivers' engagement in web-based psychoeducation programs. METHODS: This review followed the Joanna Briggs Institute protocol of systematic review and meta-aggregation of qualitative studies. We searched 4 English databases, 4 Chinese databases, and 1 Arabic database in July 2021. RESULTS: A total of 9 studies written in English were included in this review. From these studies, 87 findings were extracted and grouped into 20 categories. These categories were further synthesized into 5 findings: web-based learning as an empowering experience, peer support, satisfactory and unsatisfactory program content, satisfactory and unsatisfactory technical design, and challenges encountered in web-based learning. CONCLUSIONS: High-quality and carefully designed web-based psychoeducation programs offered positive experiences for informal caregivers of people living with dementia. To meet broader caregiver education and support needs, program developers should consider information quality and relevancy, the support offered, individual needs, flexibility in delivery, and connectedness between peers and program facilitators.
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RATIONALE: Challenges associated with translating evidence into practice are well recognised and calls for effective strategies to reduce the time lag and successfully embed evidence-based practices into usual care are loud and clear. While a plethora of nonpharmacological interventions for people with dementia exist; few are based on strong evidence and there is little consideration for programme operationalisation in the complex environment of long-term care. AIMS AND OBJECTIVES: This paper describes the preparation for the implementation of the Weaving Evidence into Action for Veterans with dementia project, incorporating the codesign of delivery of four evidence-based, nonpharmacological interventions. METHOD: Implementation preparation for this type 2 hybrid effectiveness-implementation project was underpinned by the Implementation Framework for Aged Care (IFAC). A sociocultural-political contextual scan was undertaken, and reflection on the IFAC question 'why change?' with key stakeholders. Delivery of the four interventions of music therapy, exercise, reminiscence therapy and sensory modulation was explored using codesign methodology. Preparation of both intervention delivery personnel and recipients was via training, establishment of a change team and promotional/awareness-raising strategies. RESULTS: The contextual scan revealed Australian government reforms and organisational imperatives facing long-term care services, while reflections on 'why change' flagged best practice dementia care at the local care home level. Several codesign sessions involved veterans with dementia, family members, care home staff members and volunteers to ensure programme alignment with needs and preferences, accounting for existing activities. Training was designed and delivered before programme commencement. A change team was established and strategies to support behaviour change instigated. Implementation evaluation is reported elsewhere. CONCLUSION: The extended preparatory period for implementation, afforded by the COVID-19 pandemic on programme commencement, enabled time for widespread understanding of the programme and necessary upskill of staff. Comprehensive codesign with all stakeholders of programme components identified core and flexible elements necessary for fidelity of implementation.
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COVID-19 , Demencia , Veteranos , Humanos , Anciano , Pandemias , Australia , Demencia/terapiaRESUMEN
RATIONALE: Veterans living with dementia in long-term care have complex needs, with variable manifestation of symptoms of dementia that interact with their lived experience. Best practice dementia care prioritises nonpharmacological interventions; of which few have strong evidence. Implementation of evidence is complex, with evaluation of outcomes and processes necessary. AIMS AND OBJECTIVES: This paper details the evaluation of implementation, at veteran and organisational level, of the Weaving Evidence into Action for Veterans with Dementia (WEAVE) programme. METHODS: A Type 2 hybrid effectiveness-implementation design was used, underpinned by the Implementation Framework for Aged Care (IFAC). Programme intervention incorporated music therapy, exercise, reminiscence therapy and/or sensory modulation, offered over a 24-week period. Evaluation components included: (1) programme effectiveness for veterans with dementia for responsive behaviour, physical wellbeing, cognitive status, emotional state, medications and falls (at baseline, 8-week, 16-week and 24-week); and (2) implementation outcomes of reach and adoption, feasibility and acceptability, fidelity (via interviews) and a preliminary cost analysis. RESULTS: Thirty-eight veterans participated in the 24-week programme, with high levels of engagement in interventions of their choice. Statistically significant improvements were seen across all veteran-level outcome measures, for functional capacity and reduced neuro-psychiatric and depressive symptoms. Ten staff members were interviewed, highlighting co-designed core elements were feasible and acceptable, and the momentum generated by resident and staff enthusiasm. Cost analysis included costs of programme set-up and running the 24-week intervention. CONCLUSION: Key components of programme success were the therapeutic leaders, adherence to core elements of programme design, and veterans' choice in meaningful activity. Cost analysis supports deliberations for upscale across further care homes.
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Demencia , Veteranos , Humanos , Anciano , Cuidados a Largo Plazo , Demencia/terapia , Demencia/psicología , Psicoterapia , Evaluación de Resultado en la Atención de SaludRESUMEN
OBJECTIVE: The objectives of this systematic review and meta-analysis were to identify the characteristics of internet-based psychoeducational programs for caregivers of people living with dementia and to synthesise program effectiveness. METHOD: Five English databases and four Chinese databases were searched in June 2021 with no time limit applied. A narrative summary was performed to describe the characteristics of studies reviewed. Meta-analysis was applied to synthesise the pooled effects where data were available. RESULTS: A total of 14352 articles were identified from the database search and 19 were included in the final review. Interventions comprised educational, psychological, and behavioural training relevant to dementia care. Program duration ranged from 3 weeks to 12 months. Meta-analysis of 13 RCTs showed that internet-based psychoeducational programs had a significant effect on reducing caregivers' depressive symptoms (SMD -0.19; 95% CI -0.03 - 0.35) and stress (SMD -0.29; 95% CI -0.03 -0.54). However, these programs did not show an effect on quality of life, anxiety, burden or self-efficacy in caregivers. CONCLUSION: Internet-based psychoeducational programs can improve some aspects of caregivers' mental health and emotional wellbeing. The effects of programs on self-efficacy, anxiety, burden and quality of life for caregivers remain inconclusive.
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Demencia , Calidad de Vida , Humanos , Depresión/terapia , Cuidadores/psicología , Ansiedad , Demencia/terapia , Demencia/psicologíaRESUMEN
The home care workforce provides essential support for older people with dementia to live a life of fulfillment. "Enabling Choices," an evidence-informed conversation tool, aims to negotiate risk around everyday activities between home care workers, people with dementia and their informal carers. This paper describes tool conversion into electronic format and preparation for implementation throughout a large Australian health and aged care service provider, utilizing the Implementation Framework for Aged Care (IFAC). Using codesign principles, the tool was converted from paper-based to electronic format involving frontline, operational and Information Management Services staff, and people with dementia/carers. Focus groups and interviews identified tool acceptability, feasibility, and appropriateness. For implementation preparation, the wider socio-cultural-political context was mapped, and key questions of the IFAC addressed. Environment, workflow, and training requirements were determined, and strategies for behavior change ascertained. Numerous opportunities and challenges exist for the widespread upscale of an evidence-informed tool into practice.
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Background: A steep increase in new drug applications has increased the overhead of writing technical documents such as medication guides. Natural language processing can contribute to reducing this burden. Objective: To generate medication guides from texts that relate to prescription drug labeling information. Materials and Methods: We collected official drug label information from the DailyMed website. We focused on drug labels containing medication guide sections to train and test our model. To construct our training dataset, we aligned "source" text from the document with similar "target" text from the medication guide using three families of alignment techniques: global, manual, and heuristic alignment. The resulting source-target pairs were provided as input to a Pointer Generator Network, an abstractive text summarization model. Results: Global alignment produced the lowest ROUGE scores and relatively poor qualitative results, as running the model frequently resulted in mode collapse. Manual alignment also resulted in mode collapse, albeit higher ROUGE scores than global alignment. Within the family of heuristic alignment approaches, we compared different methods and found BM25-based alignments to produce significantly better summaries (at least 6.8 ROUGE points above the other techniques). This alignment surpassed both the global and manual alignments in terms of ROUGE and qualitative scoring. Conclusion: The results of this study indicate that a heuristic approach to generating inputs for an abstractive summarization model increased ROUGE scores, compared to a global or manual approach when automatically generating biomedical text. Such methods hold the potential to significantly reduce the manual labor burden in medical writing and related disciplines.
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This study examined the potential for effect of a six-week gait aid training program for people with dementia on spatiotemporal gait outcomes, perception of use, and falls with gait aid use. The program utilised four 30-min physiotherapy home visits, scheduled at weeks 1/2/3/6, and was enhanced by carer-supervised practice. Falls and the physiotherapist's clinical judgement of participants achieving safe gait aid use during and after the program were described. Perception ratings at each visit were measured using Likert scales which, along with the spatiotemporal outcomes using the gait aid (Time-Up-and-Go-Test, 4-m-walk-test, Figure-of-8-Walk-Test with/without a cognitive task) at weeks 1 and 6, and at weeks 6 and 12 (6-week post-program), were examined with ordinal logistic regression analyses. Twenty-four community-dwelling older people with dementia and their carers participated. Twenty-one (87.5%) older people achieved safe gait aid use. Twenty falls occurred, and only one faller was using their gait aid when they fell. Walking speed, step length, and cadence significantly improved when walking with the gait aid at week 6 compared with week 1. No significant improvements in spatiotemporal outcomes were retained at week 12. Physiotherapists were more likely to agree that gait aid use had improved walking safety among older people with dementia with subsequent training visits. Larger studies of the gait aid training program are needed for this clinical group.
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INTRODUCTION: The Early Detection of Deterioration in Elderly residents (EDDIE+) programme is a theory-informed, multi-component intervention aimed at upskilling and empowering nursing and personal care staff to identify and manage early signs of deterioration in residents of aged care facilities. The intervention aims to reduce unnecessary hospital admissions from residential aged care (RAC) homes. Alongside a stepped wedge randomised controlled trial, an embedded process evaluation will be conducted to assess the fidelity, acceptability, mechanisms of action and contextual barriers and enablers of the EDDIE+ intervention. METHODS AND ANALYSIS: Twelve RAC homes in Queensland, Australia are participating in the study. A comprehensive mixed-methods process evaluation, informed by the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework, will assess intervention fidelity, contextual barriers and enablers, mechanisms of action, and the acceptability of the programme from various stakeholder perspectives. Quantitative data will be collected prospectively from project documentation, including baseline context mapping of participating sites, activity tracking and regular check-in communication sheets. Qualitative data will be collected postintervention via semi-structured interviews with a range of stakeholder groups. The i-PARIHS constructs of innovation, recipients, context and facilitation will be applied to frame the analysis of quantitative and qualitative data. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the Bolton Clarke Human Research Ethics Committee (approval number: 170031) with administrative ethical approval granted by the Queensland University of Technology University Human Research Ethics Committee (2000000618). Full ethical approval includes a waiver of consent for access to residents' demographic, clinical and health services de-identified data. A separate health services data linkage based on RAC home addresses will be sought through a Public Health Act application. Study findings will be disseminated through multiple channels, including journal publications, conference presentations and interactive webinars with a stakeholder network. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trial Registry (ACTRN12620000507987).
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Hospitalización , Casas de Salud , Anciano , Humanos , Hogares para Ancianos , Australia , Queensland , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Limited data exist on pregnant women living with HIV exposed to cabotegravir + rilpivirine (CAB + RPV). Outcomes in pregnant participants exposed to CAB + RPV, and pharmacokinetic washout data in those exposed to CAB + RPV long-acting (LA) with live births, are presented. METHODS: Women exposed to one or more doses of CAB + RPV (oral/LA) from ViiV Healthcare-sponsored phase 2b/3/3b clinical trials and the compassionate use programme who became pregnant were included. Upon pregnancy in the trial programme, CAB + RPV was discontinued, an alternative antiretroviral regimen was initiated, and quarterly pharmacokinetic sampling for 52 weeks post-last injection was obtained. CAB + RPV continuation or alternative antiretroviral regimen initiation was decided by pregnant compassionate use programme participants and their treating physicians. RESULTS: As of 31 March 2021, 25 pregnancies following CAB + RPV exposure at conception were reported (five oral, 20 LA), including four who conceived during pharmacokinetic washout following treatment discontinuation. There were eight elective abortions, six miscarriages (five in first trimester), one ectopic pregnancy, and 10 live births (one oral, nine LA), including one infant born with congenital ptosis. Among participants exposed to CAB + RPV LA at conception with live births, plasma CAB and RPV washout concentrations during pregnancy were within the range of those observed in non-pregnant women. CONCLUSION: In this first analysis of pregnancy outcomes following CAB + RPV exposure at conception, 10 live births, including one with congenital anomaly, were reported. Plasma CAB and RPV washout concentrations during pregnancy were within the range of those in non-pregnant women. Pregnancy surveillance within ViiV Healthcare-sponsored clinical trials is ongoing, with dedicated pregnancy studies planned.
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Fármacos Anti-VIH , Infecciones por VIH , Femenino , Humanos , Embarazo , Rilpivirina , Infecciones por VIH/tratamiento farmacológico , Resultado del Embarazo , Antirretrovirales/uso terapéuticoRESUMEN
PURPOSE: To determine gait aid use and decision-making related to usage in people with dementia, and examine factors influencing (1) gait aid use or not; and (2) falls in past year. MATERIALS AND METHODS: A survey of informal carers of older people with dementia in the community. Closed questions on gait aid use, falls, timing and sources of gait aid acquisition, and advice received to support use were used. Chi-squared tests (Fisher's Exact) compared: (1) gait aid users vs non-users and carers' report of (i) unsteadiness in walking/turning, (ii) dementia severity, (iii) falls in past year, and (2) fallers vs non-fallers and (i) timing of gait aid commencement relative to dementia diagnosis, (ii) whether health professional advice was received regarding use, and iii) regularity of use. RESULTS: Forty-seven completed surveys, 63.8% of care recipients used a gait aid; 56.9% had ≥2 falls in past year; 66.7% commenced use after dementia diagnosis; 25% acquired their aids from non-health professionals; and 37% did not receive advice regarding use. Gait aid users and non-users differed on carer ratings of unsteadiness in walking/turning (p = 0.02). CONCLUSION: Carers reported important aspects regarding gait aid acquisition, safe gait aid use and benefits which warrant further investigation.IMPLICATIONS FOR REHABILITATIONIn our small sample, use of gait aids by people with dementia was related to the level of unsteadiness in walking and/or turning, and not associated with falling in the past year.People with dementia do not routinely receive professional advice about how to use gait aids, highlighting the potential value of maximizing health professional involvement in gait aid prescription and training.Deterioration in the ability of gait aid use after the diagnosis of dementia indicates a need for re-assessment or re-training of gait aid use over time.Clinical guidelines to facilitate decision-making regarding under what conditions gait aids are beneficial, what duration and aspects require instruction to ensure effective use by people with dementia are needed.
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Cuidadores , Demencia , Humanos , Anciano , Marcha , Caminata , Personal de SaludRESUMEN
During development of a drug, the requirement of evaluating the proarrhythmic risk and delayed repolarization needs to be fulfilled. Would it be possible to create an alternative to a thorough QT (TQT) study or is there a need to perform a dedicated TQT study? How is an alternative approach generated, what information is available, and which instructions are considered missing today to generate such an approach? This tutorial describes the considerations and path followed to create an early and feasible alternative to a TQT study using experience-based insights from a successful application to the US Food and Drug Administration for GLPG1972, an ADAMTS-5 inhibitor, and discusses the approach used in light of the current guidelines and literature.
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Síndrome de QT Prolongado , Humanos , Relación Dosis-Respuesta a Droga , Electrocardiografía , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/diagnóstico , Preparaciones Farmacéuticas , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Percolomonads (Heterolobosea) are aquatic heterotrophic flagellates frequently found in saline waters up to hypersaline environments. We isolated and cultivated seven strains of percolomonad flagellates from marine waters and sediments as well as from a hypersaline inland lake in the Atacama Desert. Morphological characterizations, comprising light and scanning electron microscopy, revealed only slight differences between the strains mainly limited to the cell shape, length of flagella, and length of the ventral feeding groove. Phylogenetic analyses of the 18S and 28S rDNA genes showed the formation of three fully supported clades within the Percolomonadida: the Percolomonadidae, the Barbeliidae fam. nov. and the Lulaidae fam. nov. We describe two new families (Barbeliidae fam. nov., Lulaidae fam. nov.), a new genus (Nonamonas gen. nov.), and five new species (Percolomonas adaptabilis sp. nov., Lula levis sp. nov., Barbelia pacifica sp. nov., Nonamonas montiensis gen. et sp. nov., Nonamonas santamariensis gen. et sp. nov.). Salinity experiments showed that P. adaptabilis sp. nov. from the Atlantic was better adapted to high salinities than all other investigated strains. Moreover, comparisons of our cultivation-based approach with environmental sequencing studies showed that P. adaptabilis sp. nov. seems to be globally distributed in marine surface waters while other species seem to be more locally restricted.
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Filogenia , Humanos , ADN Ribosómico/genética , Análisis de Secuencia de ADN , ARN Ribosómico 16S/genéticaRESUMEN
Signaling pathways of regulated necrosis, such as necroptosis and ferroptosis, contribute to acute kidney injury (AKI), but the role of pyroptosis is unclear. Pyroptosis is mediated by the pore-forming protein gasdermin D (GSDMD). Here, we report a specific pattern of GSDMD-protein expression in the peritubular compartment of mice that underwent bilateral ischemia and reperfusion injury (IRI). Along similar lines, the GSDMD-protein expression in whole kidney lysates increased during the first 84 h following cisplatin-induced AKI. Importantly, unlike whole kidney lysates, no GSDMD-protein expression was detectable in isolated kidney tubules. In IRI and cisplatin-induced AKI, GSDMD-deficient mice exhibited hypersensitivity to injury as assessed by tubular damage, elevated markers of serum urea, and serum creatinine. This hypersensitivity was reversed by a combined deficiency of GSDMD and the necroptosis mediator mixed lineage kinase domain-like (MLKL). In conclusion, we demonstrate a non-cell autonomous role for GSDMD in protecting the tubular compartment from necroptosis-mediated damage in IRI.
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Lesión Renal Aguda , Hipersensibilidad , Lesión Renal Aguda/metabolismo , Animales , Cisplatino/efectos adversos , Creatinina , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones , Proteínas de Unión a Fosfato/genética , Proteínas de Unión a Fosfato/metabolismo , UreaRESUMEN
Social Worker's undertake psycho-social assessments and facilitate access to evidence-informed psychological and practical supports to optimize the physical, psychological, and social wellbeing of the community members in their care. Social workers employed at an aged and community care organization undertook a review of the gray and peer reviewed literature and did not identify any existing evidence-based tools. However, 10 key domains were identified from the search. Gaps in the domains were discovered, together with the need for guidance and prompts for less experienced staff and students. Five Social Workers, using co-design principles, reviewed the domains, and added further domains from their social work practice. An evidence-based assessment tool was developed which incorporated 11 domains. The tool can be used to assess the needs of people living in the community who are older and/or have compromised health and wellbeing. Further work is required to pilot test the tool.