RESUMO
Despite the vast array of different geochronological tools available, dating the Paleolithic remains one of the discipline's greatest challenges. This review focuses on two different dating approaches: trapped charge and amino acid geochronology. While differing in their fundamental principles, both exploit time-dependent changes in signals found within crystals to generate a chronology for the material dated and hence, the associated deposits. Within each method, there is a diverse range of signals that can be analyzed, each covering different time ranges, applicable to different materials and suitable for different paleoenvironmental and archaeological contexts. This multiplicity of signals can at first sight appear confusing, but it is a fundamental strength of the techniques, allowing internal checks for consistency and providing more information than simply a chronology. For each technique, we present an overview of the basis for the time-dependent signals and the types of material that can be analyzed, with examples of their archaeological application, as well as their future potential.
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Aminoácidos , Datação Radiométrica , Arqueologia/métodos , Fósseis , Datação Radiométrica/métodosRESUMO
OBJECTIVE: A diagnosis of Parkinson's often leads to uncertainty about the future and loss of perceived control. Peer support may offer a means to address these concerns and promote self-management. DESIGN: A programme evaluation of the feasibility and potential effects of 'First Steps', utilising a pragmatic step wedge approach. Comparing First Steps (intervention) to (control) conditions.Setting: In the community at four sites in southern England.Participants: Newly diagnosed (≤ 12months) people with Parkinson's.Intervention: First Steps was a 2-day peer-conceived, developed and led intervention to support self-management.Main measures: At 0, 12 and 24 weeks anxiety and depression (Hospital, Anxiety and Depression Scale, HADS), daily functioning (World Health Organisation Disability Assessment Schedule, WHODAS), physical activity, quality of life (EQ5D), carer strain and service utilisation were assessed. RESULTS: Between February 2018 and July 2019, 36 participants were enrolled into intervention and 21 to control conditions, all were included in statistical analysis. Lost to follow up was n = 1 (intervention) and n = 1 adverse event was reported (control, unrelated). Of the 36 allocated to the intervention n = 22 participants completed both days of First Steps during the study period. Completion of outcome measures was >95% at 24 weeks. Small effects favouring the intervention were found for HADS (odds ratio (OR) = 2.06, 95% confidence interval (CI) 0.24:17.84), Carer Strain Index (OR = 2.22, 95% CI 0.5:9.76) and vigorous (d = 0.42, 95% CI -0.12:0.97) and total physical activity (d = 0.41, 95% CI -0.13:0.95). EQ5D, WHOSDAS and service utilisation, was similar between groups. CONCLUSIONS: First Steps was feasible and safe and we found potential to benefit physical activity, mental health and carer strain. Further research with longer-term follow up is warranted.
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Doença de Parkinson , Autogestão , Humanos , Qualidade de Vida , Avaliação de Programas e Projetos de Saúde , Doença de Parkinson/diagnóstico , Modalidades de FisioterapiaRESUMO
In this study, we synthesize terrestrial and marine proxy records, spanning the past 620 ky, to decipher pan-African climate variability and its drivers and potential linkages to hominin evolution. We find a tight correlation between moisture availability across Africa to El Niño Southern Ocean oscillation (ENSO) variability, a manifestation of the Walker Circulation, that was most likely driven by changes in Earth's eccentricity. Our results demonstrate that low-latitude insolation was a prominent driver of pan-African climate change during the Middle to Late Pleistocene. We argue that these low-latitude climate processes governed the dispersion and evolution of vegetation as well as mammals in eastern and western Africa by increasing resource-rich and stable ecotonal settings thought to have been important to early modern humans.
Assuntos
Evolução Biológica , Mudança Climática/história , El Niño Oscilação Sul/história , África , História Antiga , HumanosRESUMO
Genomic screening is routinely used to guide the treatment of cancer patients in many countries. However, several multi-layered factors make this effort difficult to deliver within a clinically relevant timeframe. Here we share the learnings from the CRUK-funded Stratified Medicine Programme for advanced NSCLC patients, which could be useful to better plan future studies.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Reino UnidoRESUMO
Quantification of in vitro osteoclast cultures (e.g. cell number) often relies on manual counting methods. These approaches are labour intensive, time consuming and result in substantial inter- and intra-user variability. This study aimed to develop and validate an automated workflow to robustly quantify in vitro osteoclast cultures. Using ilastik, a machine learning-based image analysis software, images of tartrate resistant acid phosphatase-stained mouse osteoclasts cultured on dentine discs were used to train the ilastik-based algorithm. Assessment of algorithm training showed that osteoclast numbers strongly correlated between manual- and automatically quantified values (r = 0.87). Osteoclasts were consistently faithfully segmented by the model when visually compared to the original reflective light images. The ability of this method to detect changes in osteoclast number in response to different treatments was validated using zoledronate, ticagrelor, and co-culture with MCF7 breast cancer cells. Manual and automated counting methods detected a 70% reduction (p < 0.05) in osteoclast number, when cultured with 10 nM zoledronate and a dose-dependent decrease with 1-10 µM ticagrelor (p < 0.05). Co-culture with MCF7 cells increased osteoclast number by ≥ 50% irrespective of quantification method. Overall, an automated image segmentation and analysis workflow, which consistently and sensitively identified in vitro osteoclasts, was developed. Advantages of this workflow are (1) significantly reduction in user variability of endpoint measurements (93%) and analysis time (80%); (2) detection of osteoclasts cultured on different substrates from different species; and (3) easy to use and freely available to use along with tutorial resources.
Assuntos
Reabsorção Óssea , Osteoclastos , Camundongos , Animais , Ácido Zoledrônico , Ticagrelor , Técnicas de Cocultura , Células Cultivadas , Fosfatase Ácida/análise , Fosfatase Ácida Resistente a Tartarato , Diferenciação CelularRESUMO
BACKGROUND: Health and social care systems face difficulties in managing multimorbidity, disease burden and complex needs in long-term conditions such as Parkinson's disease. OBJECTIVE: This study aimed to develop a European understanding of how health and social care professionals can collaborate with stakeholders from different organizations and sectors to enhance the management of Parkinson's disease in a community setting by identifying the existing gaps in this process and how people with Parkinson's disease and their family carers could benefit from these partnerships. METHODS: A mixed-methods sequential study was conducted in Denmark, Norway, Spain and the United Kingdom. The findings from the qualitative phase are presented. Individual semistructured interviews were analysed using Braun's and Clarke's thematic analysis. A meta-ethnography approach was used to analyse and synthesize cross-national findings. RESULTS: A total of 41 healthcare professionals and 39 stakeholders from different disciplines and sectors were interviewed in the four countries. The participants acknowledged a lack of awareness of available resources and poor communication between the different support systems in the management of Parkinson's disease. To promote multiagency collaborations, the participants highlighted the need to organize services along the Parkinson's disease journey, patient involvement and strategic involvement of carers in organizing resources and Parkinson's disease care pathways. According to the participants, the benefits from multiagency partnerships could lead to an enhanced continuity of care and specialized knowledge, mobilization of resources in the community, personalized support and improved access to services. CONCLUSIONS: Policymakers are called upon to create formal structures that facilitate multisectoral collaborations to promote an integrated system of care for the management of Parkinson's disease in the community. To address this challenge, we propose five strategies showing how organizations can work together to optimize the use of resources and enhance the management of Parkinson's disease throughout the illness trajectory. PATIENT OR PUBLIC CONTRIBUTION: Patient and Public Involvement groups made up of stakeholders, healthcare professionals, patients with Parkinson's disease and family carers participated in the design of the study, the development of the interview guides and the validation of the findings.
Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Pesquisa Qualitativa , Cuidadores , Pessoal de Saúde , Gerenciamento ClínicoRESUMO
BACKGROUND: A third of older people take five or more regular medications (polypharmacy). Conducting medication reviews in primary care is key to identify and reduce/ stop inappropriate medications (deprescribing). Recent recommendations for effective deprescribing include shared-decision making and a multidisciplinary approach. Our aim was to understand when, why, and how interventions for medication review and deprescribing in primary care involving multidisciplinary teams (MDTs) work (or do not work) for older people. METHODS: A realist synthesis following the Realist And Meta-narrative Evidence Syntheses: Evolving Standards guidelines was completed. A scoping literature review informed the generation of an initial programme theory. Systematic searches of different databases were conducted, and documents screened for eligibility, with data extracted based on a Context, Mechanisms, Outcome (CMO) configuration to develop further our programme theory. Documents were appraised based on assessments of relevance and rigour. A Stakeholder consultation with 26 primary care health care professionals (HCPs), 10 patients and three informal carers was conducted to test and refine the programme theory. Data synthesis was underpinned by Normalisation Process Theory to identify key mechanisms to enhance the implementation of MDT medication review and deprescribing in primary care. FINDINGS: A total of 2821 abstracts and 175 full-text documents were assessed for eligibility, with 28 included. Analysis of documents alongside stakeholder consultation outlined 33 CMO configurations categorised under four themes: 1) HCPs roles, responsibilities and relationships; 2) HCPs training and education; 3) the format and process of the medication review 4) involvement and education of patients and informal carers. A number of key mechanisms were identified including clearly defined roles and good communication between MDT members, integration of pharmacists in the team, simulation-based training or team building training, targeting high-risk patients, using deprescribing tools and drawing on expertise of other HCPs (e.g., nurses and frailty practitioners), involving patents and carers in the process, starting with 'quick wins', offering deprescribing as 'drug holidays', and ensuring appropriate and tailored follow-up plans that allow continuity of care and management. CONCLUSION: We identified key mechanisms that could inform the design of future interventions and services that successfully embed deprescribing in primary care.
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Desprescrições , Idoso , Humanos , Cuidadores , Pessoal de Saúde , Revisão de Medicamentos , Atenção Primária à SaúdeRESUMO
OBJECTIVES: The aim of this study was to understand how people living with Parkinson's and healthcare professionals perceived their care management and interactions with health services were affected during the COVID-19 pandemic. BACKGROUND: During the COVID-19 pandemic, many governments introduced restrictions and services that support Parkinson's care management had to cease or be delivered remotely. These changes may have had an impact on the well-being of people living with Parkinson's. METHODS: A qualitative exploratory UK study was carried out. Semi-structured individual interviews with people living with Parkinson's and health professionals were recorded, transcribed verbatim and analysed using Braun´s and Clarke´s thematic analysis. Eleven patients and 10 health professionals were recruited between April and September 2020. The study was reported using the COREQ. RESULTS: Two main themes were identified. In the first theme, many patients and professionals reported that the COVID-19 pandemic made some people living with Parkinson's feel isolated and vulnerable due to disruptions to their social networks and usual activities related to Parkinson's disease care. However, other patients remained connected with their networks. In the second theme, patients and most professionals mentioned that some clinical practices were cancelled, delayed or transformed to remote consultation. CONCLUSION: The COVID-19 restrictions had an impact on how people living with Parkinson's managed their care and in their interactions with healthcare services. Health professionals should assess the risk of vulnerability, social isolation, physical inactivity and confidence with remote consultations in people living with Parkinson's. This might inform a rethinking of existing clinical interactions with people living with Parkinson's towards a flexible, sustainable, person-centred care model. RELEVANCE TO CLINICAL PRACTICE: This study has shown that Parkinson's care management and interactions with healthcare services should provide personalised and flexible support. To meet this challenge, the design of the organisation of health services should include greater involvement of patients and person-centred care models.
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COVID-19 , Doença de Parkinson , Humanos , COVID-19/epidemiologia , Doença de Parkinson/epidemiologia , Pandemias , Pessoal de Saúde , Isolamento SocialRESUMO
BACKGROUND: sarcopenia and frailty are associated with increased risk of falls and fractures. This study evaluated the feasibility of assessing sarcopenia and frailty among older people attending fracture clinics. METHODS: patients aged 65+ years with an arm fracture attending fracture clinics in one UK city were recruited. Sarcopenia was assessed using gait speed, grip strength, skeletal muscle mass index SMI, SARC-F questionnaire and the European Working Group on Sarcopenia in Older People (EWGSOP) I and II criteria. Frailty was assessed using Fried Frailty Phenotype (FFP), FRAIL scale, PRISMA-7, electronic Frailty Index (e-FI), Clinical Frailty Score (CFS) and Study of Osteoporotic Fracture. The sensitivity and specificity of each tool was calculated against the EWGSOP II criteria (sarcopenia) and FFP (frailty). Patients identified to have either condition were referred for Comprehensive Geriatric Assessment (CGA). Interviews with 13 patients and nine staff explored the acceptability of this process. RESULTS: hundred patients (Mean age 75 years) were recruited. Most sarcopenia and frailty assessments were quick with complete data collection and were acceptable to patients and staff. Sarcopenia was identified among 4-39% participants depending on the tool and frailty among 9-25%. Both conditions were more common among men than women with all tools. The SARC-F and PRISMA-7 had the best sensitivity (100 and 93%, respectively) and specificity (96 and 87%). CGA among 80% of referred participants led to three interventions per participant (e.g. medication changes and investigations). CONCLUSION: SARC-F and PRISMA-7 are recommended for use in fracture clinics to screen for sarcopenia and frailty.
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Fragilidade , Sarcopenia , Idoso , Estudos Transversais , Estudos de Viabilidade , Feminino , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/terapia , Avaliação Geriátrica , Humanos , Masculino , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/terapia , Extremidade SuperiorRESUMO
BACKGROUND: The anorexia of ageing is important in the development of malnutrition, frailty and sarcopenia amongst the older population and is a particular problem for hospital inpatients. This study assessed appetite-related factors in a group of hospitalised older adults, to identify potential preventive strategies. DESIGN: Cross sectional observational study. SETTING: Eleven wards in one large hospital in England. SUBJECTS: Older inpatients aged ≥70 years, admitted non-electively. METHODS: Appetite was assessed using the four-item Simplified Nutritional Appetite Questionnaire (SNAQ). Associations between SNAQ score and appetite-related factors present in the dataset were assessed in continuous analyses, including habitual physical activity, mood, medication, cognition and living circumstances. RESULTS: 200 participants, mean age of 80.7 years (SD 6.9); 40% were women. Prevalence of poor appetite was 43%. In univariate analyses, lower medication count, higher habitual physical activity and better mood were associated with higher SNAQ scores during admission. In a multivariate analysis, independent associations of higher habitual physical activity and better mood with higher SNAQ scores during hospital admission remained. CONCLUSION: In this group of older adults, better mood and higher habitual physical activity were independently associated with better appetite during hospital admission. These are potentially modifiable factors and could be targets for future research into interventions for the anorexia of ageing in the hospitalised older population.
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Apetite , Desnutrição , Masculino , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Anorexia , Estudos Transversais , Exercício FísicoRESUMO
We report results of surveillance between June and mid-September 2022 of pet animals living in households of confirmed human monkeypox (MPX) cases. Since surveillance commenced, 154 animals from 40 households with a confirmed human MPX case were reported to the United Kingdom Animal and Plant Health Agency. No animals with clinical signs of MPX were identified. While a risk of transmission exists to pets from owners with a confirmed MPX virus infection, we assess this risk to be low.
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Mpox , Surtos de Doenças/veterinária , Humanos , Mpox/diagnóstico , Mpox/epidemiologia , Mpox/veterinária , Monkeypox virus , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Older people living with frailty are often exposed to polypharmacy and potential harm from medications. Targeted deprescribing in this population represents an important component of optimizing medication. This systematic review aims to summarise the current evidence for deprescribing among older people living with frailty. METHODS: The literature was searched using Medline, Embase, CINAHL, PsycInfo, Web of Science, and the Cochrane library up to May 2020. Interventional studies with any design or setting were included if they reported deprescribing interventions among people aged 65+ who live with frailty identified using reliable measures. The primary outcome was safety of deprescribing; whereas secondary outcomes included clinical outcomes, medication-related outcomes, feasibility, acceptability and cost-related outcomes. Narrative synthesis was used to summarise findings and study quality was assessed using Joanna Briggs Institute checklists. RESULTS: Two thousand three hundred twenty-two articles were identified and six (two randomised controlled trials) were included with 657 participants in total (mean age range 79-87 years). Studies were heterogeneous in their designs, settings and outcomes. Deprescribing interventions were pharmacist-led (n = 3) or multidisciplinary team-led (n = 3). Frailty was identified using several measures and deprescribing was implemented using either explicit or implicit tools or both. Three studies reported safety outcomes and showed no significant changes in adverse events, hospitalisation or mortality rates. Three studies reported positive impact on clinical outcomes including depression, mental health status, function and frailty; with mixed findings on falls and cognition; and no significant impact on quality of life. All studies described medication-related outcomes and reported a reduction in potentially inappropriate medications and total number of medications per-patient. Feasibility of deprescribing was reported in four studies which showed that 72-91% of recommendations made were implemented. Two studies evaluated and reported the acceptability of their interventions and further two described cost saving. CONCLUSION: There is a paucity of research about the impact of deprescribing in older people living with frailty. However, included studies suggest that deprescribing could be safe, feasible, well tolerated and can lead to important benefits. Research should now focus on understanding the impact of deprescribing on frailty status in high risk populations. TRIAL REGISTRATION: The review was registered on the international prospective register of systematic reviews (PROSPERO) ID number: CRD42019153367 .
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Desprescrições , Fragilidade , Idoso , Idoso de 80 Anos ou mais , Humanos , Polimedicação , Lista de Medicamentos Potencialmente Inapropriados , Qualidade de VidaRESUMO
Appetite loss in later life is common and associated with malnutrition; however, there is limited knowledge on older individuals' perspectives of appetite. This study aimed to explore what 'appetite' means to older adults, how they experience its change and perceived influences on this experience. Semi-structured interviews were conducted with thirteen participants, aged ≥65 years, in their own home, following a recent arm fracture. Transcripts were analysed using reflexive thematic analysis with inductive coding resulting in three themes. 1. 'Appetite as an emotional experience' encompassed positive or negative thoughts and feelings driving or undermining desire to eat. Mood, the appeal of food, cooking and effects of interaction and experiences with other people were factors in this narrative. 2. 'Appetite reflects a physical need' comprised physical bodily sensations or requirements as a driver for appetite with poor appetite resulting from early or over fullness. Declines with age, illness and less activity, were factors in this narrative. 3. 'Adaption to poor appetite aligns with perception of appetite and wider physical health' accounts for how experiential strategies, or practical strategies were used to mitigate poor appetite depending on the narrative of appetite loss, alongside perceptions of physical health and unplanned weight loss. Most individuals used one narrative in their discussions and reflections but for some, perceptions of appetite and its change were more complex. Understanding relationships between these perceptions of appetite and influential factors could facilitate development of multi-component, person-centred, strategies that are optimally meaningful and relevant to address appetite loss in later life.
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Transtornos da Alimentação e da Ingestão de Alimentos , Desnutrição , Idoso , Apetite , Humanos , Percepção , Pesquisa QualitativaRESUMO
OBJECTIVES: To identify early nutritional risk in older populations, simple screening approaches are needed. This study aimed to compare nutrition risk scores, calculated from a short checklist, with diet quality and health outcomes, both at baseline and prospectively over a 2.5-year follow-up period; the association between baseline scores and risk of mortality over the follow-up period was assessed. METHODS: The study included 86 community-dwelling older adults in Southampton, UK, recruited from outpatient clinics. At both assessments, hand grip strength was measured using a Jamar dynamometer. Diet was assessed using a short validated food frequency questionnaire; derived 'prudent' diet scores described diet quality. Body mass index (BMI) was calculated and weight loss was self-reported. Nutrition risk scores were calculated from a checklist adapted from the DETERMINE (range 0-17). RESULTS: The mean age of participants at baseline (n = 86) was 78 (SD 8) years; half (53%) scored 'moderate' or 'high' nutritional risk, using the checklist adapted from DETERMINE. In cross-sectional analyses, after adjusting for age, sex and education, higher nutrition risk scores were associated with lower grip strength [difference in grip strength: - 0.09, 95% CI (- 0.17, - 0.02) SD per unit increase in nutrition risk score, p = 0.017] and poorer diet quality [prudent diet score: - 0.12, 95% CI (- 0.21, - 0.02) SD, p = 0.013]. The association with diet quality was robust to further adjustment for number of comorbidities, whereas the association with grip strength was attenuated. Nutrition risk scores were not related to reported weight loss or BMI at baseline. In longitudinal analyses there was an association between baseline nutrition risk score and lower grip strength at follow-up [fully-adjusted model: - 0.12, 95% CI (- 0.23, - 0.02) SD, p = 0.024]. Baseline nutrition risk score was also associated with greater risk of mortality [unadjusted hazard ratio per unit increase in score: 1.29 (1.01, 1.63), p = 0.039]; however, this association was attenuated after adjustment for sex and age. CONCLUSIONS: Cross-sectional associations between higher nutrition risk scores, assessed from a short checklist, and poorer diet quality suggest that this approach may hold promise as a simple way of screening older populations. Further larger prospective studies are needed to explore the predictive ability of this screening approach and its potential to detect nutritional risk in older adults.
Assuntos
Vida Independente , Desnutrição , Idoso , Estudos Transversais , Dieta , Avaliação Geriátrica , Força da Mão , Humanos , Avaliação de Resultados em Cuidados de SaúdeRESUMO
BACKGROUND: In the UK, about 14% of community-dwelling adults aged 65 and over are estimated to be at risk of malnutrition. Screening older adults in primary care and treating those at risk may help to reduce malnutrition risk, reduce the resulting need for healthcare use and improve quality of life. Interventions are needed to raise older adults' risk awareness, offer relevant and meaningful strategies to address risk and support general practices to deliver treatment and support. METHODS: Using the Person-based Approach and input from Patient and Public Involvement representatives, we developed the 'Eat well, feel well, stay well' intervention. The intervention was optimised using qualitative data from think aloud and semi-structured process evaluation interviews with 23 and 18 older adults respectively. Positive and negative comments were extracted to inform rapid iterative modifications to support engagement with the intervention. Data were then analysed thematically and final adjustments made, to optimise the meaningfulness of the intervention for the target population. RESULTS: Participants' comments were generally positive. This paper focuses predominantly on participants' negative reactions, to illustrate the changes needed to ensure that intervention materials were optimally relevant and meaningful to older adults. Key factors that undermined engagement included: resistance to the recommended nutritional intake among those with reduced appetite or eating difficulties, particularly frequent eating and high energy options; reluctance to gain weight; and a perception that advice did not align with participants' specific personal preferences and eating difficulties. We addressed these issues by adjusting the communication of eating goals to be more closely aligned with older adults' beliefs about good nutrition, and acceptable and feasible eating patterns. We also adjusted the suggested tips and strategies to fit better with older adults' everyday activities, values and beliefs. CONCLUSIONS: Using iterative qualitative methods facilitated the identification of key behavioural and contextual elements that supported engagement, and issues that undermined older adults' engagement with intervention content. This informed crucial revisions to the intervention content that enabled us to maximise the meaningfulness, relevance and feasibility of the key messages and suggested strategies to address malnutrition risk, and therefore optimise engagement with the intervention and the behavioural advice it provided.
Assuntos
Desnutrição , Qualidade de Vida , Idoso , Comunicação , Humanos , Vida Independente , Desnutrição/prevenção & controle , Pesquisa QualitativaRESUMO
BACKGROUND: The periosteum is a highly vascularized, collagen-rich tissue that plays a crucial role in directing bone repair. This is orchestrated primarily by its resident progenitor cell population. Indeed, preservation of periosteum integrity is critical for bone healing. Cells extracted from the periosteum retain their osteochondrogenic properties and as such are a promising basis for tissue engineering strategies for the repair of bone defects. However, the culture expansion conditions and the way in which the cells are reintroduced to the defect site are critical aspects of successful translation. Indeed, expansion in human serum and implantation on biomimetic materials has previously been shown to improve in vivo bone formation. AIM: This study aimed to develop a protocol to allow for the expansion of human periosteum derived cells (hPDCs) in a biomimetic periosteal-like environment. METHODS: The expansion conditions were defined through the investigation of the bioactive cues involved in augmenting hPDC proliferative and multipotency characteristics, based on transcriptomic analysis of cells cultured in human serum. RESULTS: Master regulators of transcriptional networks were identified, and an optimized periosteum-derived growth factor cocktail (PD-GFC; containing ß-estradiol, FGF2, TNFα, TGFß, IGF-1 and PDGF-BB) was generated. Expansion of hPDCs in PD-GFC resulted in serum mimicry with regard to the cell morphology, proliferative capacity and chondrogenic differentiation. When incorporated into a three-dimensional collagen type 1 matrix and cultured in PD-GFC, the hPDCs migrated to the surface that represented the matrix topography of the periosteum cambium layer. Furthermore, gene expression analysis revealed a down-regulated WNT and TGFß signature and an up-regulation of CREB, which may indicate the hPDCs are recreating their progenitor cell signature. CONCLUSION: This study highlights the first stage in the development of a biomimetic periosteum, which may have applications in bone repair.
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Materiais Biomiméticos/farmacologia , Redes Reguladoras de Genes , Periósteo/patologia , Soro/metabolismo , Adolescente , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Células Cultivadas , Condrogênese/efeitos dos fármacos , Colágeno Tipo I/farmacologia , Feminino , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Masculino , Periósteo/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: PDSAFE is an individually-tailored, physiotherapist-delivered, balance, strength and strategy training programme aimed at preventing falls among people with Parkinson's. We evaluated the cost-effectiveness of PDSAFE compared with usual care for people with Parkinson's at higher risk of falling, from a UK National Health Service and Personal Social Service perspective. METHODS: Resource use and quality of life data (EQ-5D-3L) were collected from 238 participants randomised to the PDSAFE intervention and 236 participants randomised to control, at baseline, 3 months, 6 months (primary outcome), and 12 months. Adjusted cost and quality-adjusted life-years (QALYs) were estimated using generalised linear models and uncertainty estimated using a non-parametric bootstrap. RESULTS: Over 6 months, the PDSAFE intervention was associated with an incremental cost of £925 (95% CI £428 to £1422) and a very small and statistically insignificant QALY gain of 0.008 (95% CI - 0.006 to 0.021). The resulting incremental cost-effectiveness ratio (ICER) was £120,659 per QALY and the probability of the intervention being cost-effective at a UK threshold of £30,000/QALY was less than 1%. The ICER varied substantially across subgroups although no subgroup had an ICER lower than the £30,000 threshold. The result was sensitive to the time horizon with the ICER reducing to £55,176 per QALY when adopting a 12-month time horizon and assuming a sustained treatment effect on QoL, nevertheless, the intervention was still not cost-effective according to the current UK threshold. CONCLUSIONS: Evidence from this trial suggests that the PDSAFE intervention is unlikely to be cost-effective at 6 months. The 12-month analysis suggested that the intervention became closer to being cost-effective if quality of life effects were sustained beyond the intervention period, however this would require confirmation. Further research, including qualitative studies, should be conducted to better understand the treatment effect of physiotherapy and its impact on quality of life in people with Parkinson's given existing mixed evidence on this topic. TRIAL REGISTRATION: ISRCTN48152791. Registered 17 April 2014. http://www.isrctn.com/ISRCTN48152791.
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Acidentes por Quedas/prevenção & controle , Análise Custo-Benefício/estatística & dados numéricos , Doença de Parkinson/reabilitação , Modalidades de Fisioterapia/economia , Idoso , Feminino , Humanos , Masculino , Medicina de Precisão/métodos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Appetite drives essential oral nutritional intake. Its regulation is complex, influenced by physiology, hedonism (the reward of eating) and learning from external cues within a person's society and culture. Appetite loss is common in the older population and not always attributable to medical conditions or treatment. Although the physiological basis of the anorexia of ageing (loss of appetite due to the ageing process) has been established, the effect of ageing on hedonism and external cues, which may be equally important, is less well understood. The anorexia of ageing is associated with reductions in dietary diversity and oral intake, and increased risk of malnutrition, sarcopenia and frailty. Early identification of poor appetite could allow timely intervention before weight loss occurs. There is no standardised tool for assessing appetite in clinical settings at present but the 4-item Simplified Nutritional Appetite Questionnaire (SNAQ) has the potential to be used in this way. This review, designed for clinicians, will discuss the regulation of appetite and the pathogenesis of the anorexia of ageing. It will describe the current evidence for interventions to manage the anorexia of ageing, which is limited, with little benefit reported from individual studies of education, physical activity and medication. There is some positive evidence for flavour enhancement, fortified food and oral nutritional supplements but mainly within single studies. Looking ahead, the aim is to develop multicomponent approaches to the treatment of the anorexia of ageing based on growing understanding of the role of physiological signalling, hedonism and external cues.
Assuntos
Apetite , Desnutrição , Envelhecimento , Anorexia/diagnóstico , Anorexia/terapia , Ingestão de Alimentos , HumanosRESUMO
OBJECTIVES: to determine the feasibility and acceptability of a volunteer-led mobility intervention to improve activity levels of older inpatients. DESIGN: pre-post mixed methods study. SETTING: acute medical wards for older people. PARTICIPANTS: one hundred inpatients aged ≥70 years who were mobile prior to hospitalisation: 50 participants were recruited before and 50 after the intervention was established. Twenty-five participants (patients, nurses, therapists and volunteers) were interviewed to determine the acceptability of the intervention. INTERVENTIONS: twice daily volunteer-led mobility and bedside exercises. MAIN OUTCOME MEASURES: the feasibility of delivering a volunteer-led mobility intervention, including the recruitment, training and retention of volunteers and the acceptability of the intervention to patients and healthcare professionals. Secondary outcome measures included objectively measured daily step count, length of stay, 30-day readmission and any adverse events. RESULTS: seventeen volunteers were recruited, 16 completed training and 12 were retained. Fifty participants (mean age 86 years) received the intervention, with a median daily step count of 912 steps (interquartile range [IQR] 295-1824) compared to the baseline group (n = 50, mean age 87 years) of 636 steps (IQR 298-1468). No adverse events were reported. The intervention was acceptable to patients and staff. Facilitating factors of the intervention included the social aspect of the intervention and perceived benefits by stakeholders. Barriers identified included the busy clinical environment and lack of awareness of the intervention among staff. CONCLUSIONS: it was feasible to deliver a volunteer-led mobility intervention including the recruitment, training and retention of volunteers. The intervention was safe and acceptable to healthcare professionals and patients.
Assuntos
Terapia por Exercício/métodos , Exercício Físico , Trabalhadores Voluntários de Hospital , Pacientes Internados , Aceitação pelo Paciente de Cuidados de Saúde , Adolescente , Adulto , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Hospitalização , Humanos , Pacientes Internados/psicologia , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Comprehensive geriatric assessment (CGA) involves the multidimensional assessment and management of an older person. It is well described in hospital and home-based settings. A novel approach could be to perform CGA within primary healthcare, the initial community located healthcare setting for patients, improving accessibility to a co-located multidisciplinary team. AIM: To appraise the evidence on CGA implemented within the primary care practice. METHODS: The review followed PRISMA recommendations. Eligible studies reported CGA on persons aged ≥ 65 in a primary care practice. Studies focusing on a single condition were excluded. Searches were run in five databases; reference lists and publications were screened. Two researchers independently screened for eligibility and assessed study quality. All study outcomes were reviewed. RESULTS: The authors screened 9003 titles, 145 abstracts and 97 full texts. Four studies were included. Limited study bias was observed. Studies were heterogeneous in design and reported outcomes. CGAs were led by a geriatrician (n = 3) or nurse practitioner (n = 1), with varied length and extent of follow-up (12-48 months). Post-intervention hospital admission rates showed mixed results, with improved adherence to medication modifications. No improvement in survival or functional outcomes was observed. Interventions were widely accepted and potentially cost-effective. DISCUSSION: The four studies demonstrated that CGA was acceptable and provided variable outcome benefit. Further research is needed to identify the most effective strategy for implementing CGA in primary care. Particular questions include identification of patients suitable for CGA within primary care CGA, a consensus list of outcome measures, and the role of different healthcare professionals in delivering CGA.