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1.
Psychol Health ; : 1-18, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32924891

RESUMO

OBJECTIVE: To describe the process of developing a cognitive rehabilitation intervention for patients with post-stroke cognitive impairment (PSCI) and to describe the intervention prior to evaluation in a pilot randomised controlled trial (RCT). Method: The Medical Research Council framework, 'Developing and evaluating complex interventions', was used to develop the cognitive rehabilitation intervention. We conducted a combined analysis of the existing evidence base for PSCI rehabilitation alongside qualitative exploration of the perspectives of stroke survivors, their families, and healthcare professionals providing stroke care, on the necessary components for a cognitive rehabilitation intervention for PSCI. The Template for Intervention Description and Replication checklist was used as a structural framework for the description of the intervention. Results: The intervention comprises a five-week intervention integrating group-based activities, supported by a clinical neuropsychologist, with home-based activities to encourage self-efficacy through the practice of adjustment and compensatory strategies learned in the group format to achieve the patients' identified goals in managing their PSCI. Conclusion: A cognitive rehabilitation intervention for patients with PSCI has been developed and described. We are in the process of developing a structured intervention manual to standardise the content and delivery of the intervention for further testing in a pilot RCT.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32879954

RESUMO

CONTEXT: Fluid restriction (FR) is the recommended first-line treatment for syndrome of inappropriate antidiuresis (SIAD), despite the lack of prospective data to support its efficacy. DESIGN: A prospective non-blinded randomised controlled trial of FR versus no treatment in chronic SIAD. INTERVENTIONS AND OUTCOME: 46 patients with chronic asymptomatic SIAD were randomised to either FR (1 liter/day) or no specific hyponatremia treatment (NoTx) for one month. The primary endpoints were change in plasma sodium concentration (pNa) at days 4 and 30. RESULTS: Median baseline pNa was similar in the two groups [127 mmol/L (IQR 126-129) FR and 128 mmol/L (IQR 126-129) NoTx, p=0.36]. pNa rose by 3 mmol/L (IQR 2-4) after three days FR, compared with 1 mmol/L (IQR 0-3) NoTx, p=0.005. There was minimal additional rise in pNa by day 30; median pNa increased from baseline by 4 mmol/L (IQR 2-6) in FR, compared with 1 mmol/L (IQR 0-1) NoTx, p=0.04. 17% of FR had a rise in pNa of ≥5 mmol/L after three days, compared with 4% NoTx, RR 4.0 (95% CI 0.66-25.69), p=0.35. 61% of FR corrected pNa to ≥130 mmol/L after three days, compared with 39% of NoTx, RR 1.56 (95% CI 0.87-2.94), p=0.24. CONCLUSION: FR induces a modest early rise in pNa in patients with chronic SIAD, with minimal additional rise thereafter, and is well-tolerated. More than one third of patients fail to reach a pNa ≥130 mmol/L after three days of FR, emphasising the clinical need for additional therapies for SIAD, in some patients.

3.
Cerebrovasc Dis ; 49(4): 404-411, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32777785

RESUMO

BACKGROUND: The harmful effects of outdoor air pollution on stroke incidence are becoming increasingly recognised. We examined the impact of different air pollutants (PM2.5, PM10, NO2, ozone, and SO2) on admission for all strokes in two Irish urban centres from 2013 to 2017. METHODS: Using an ecological time series design with Poisson regression models, we analysed daily hospitalisation for all strokes and is-chaemic stroke by residence in Dublin or Cork, with air pollution level monitoring data with a lag of 0-2 days from exposure. Splines of temperature, relative humidity, day of the week, and time were included as confounders. Analysis was also performed across all four seasons. Data are presented as relative risks (RRs) and 95% confidence intervals (95% CI) per interquartile range (IQR) increase in each pollutant. RESULTS: There was no significant association between all stroke admission and any individual air pollutant. On seasonal analysis, during winter in the larger urban centre (Dublin), we found an association between all stroke cases and an IQR increase in NO2 (RR 1.035, 95% CI: 1.003-1.069), PM10 (RR 1.032, 95% CI: 1.007-1.057), PM2.5 (RR 1.024, 95% CI: 1.011-1.039), and SO2 (RR 1.035, 95% CI: 1.001-1.071). There was no significant association found in the smaller urban area of Cork. On meta-analysis, there remained a significant association between NO2 (RR 1.013, 95% CI: 1.001-1.024) and PM2.5 (1.009, 95% CI 1.004-1.014) per IQR increase in each. DISCUSSION: Short-term air pollution in winter was found to be associated with hospitalisation for all strokes in a large urban centre in Ireland. As Ireland has relatively low air pollution internationally, this highlights the need to introduce policy changes to reduce air pollution in all countries.

4.
Ir J Med Sci ; 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32562218

RESUMO

BACKGROUND: There are no previously published reports regarding the epidemiology and characteristics of moyamoya disease or syndrome in Ireland. AIMS: To examine patient demographics, mode of presentation and the outcomes of extracranial-intracranial bypass surgery in the treatment of moyamoya disease and syndrome in Ireland. METHODS: All patients with moyamoya disease and syndrome referred to the National Neurosurgical Centre during January 2012-January 2019 were identified through a prospective database. Demographics, clinical presentation, radiological findings, surgical procedures, postoperative complications and any strokes during follow-up were recorded. RESULTS: Twenty-one patients were identified. Sixteen underwent surgery. Median age at diagnosis was 19 years. Fifteen were female. Mode of presentation was ischaemic stroke in nine, haemodynamic TIAs in eight, haemorrhage in three and incidental in one. Sixteen patients had Moyamoya disease, whereas five patients had moyamoya syndrome. Surgery was performed on 19 hemispheres in 16 patients. The surgical procedures consisted of ten direct (STA-MCA) bypasses, five indirect bypasses and four multiple burr holes. Postoperative complications included ischaemic stroke in one patient and subdural haematoma in one patient. The median follow-up period in the surgical group was 52 months; there was one new stroke during this period. Two patients required further revascularisation following recurrent TIAs. One patient died during follow-up secondary to tumour progression associated with neurofibromatosis type 1. CONCLUSIONS: Moyamoya is rare but occurs in Caucasians in Ireland. It most commonly presents with ischaemic symptoms. Surgical intervention in the form of direct and indirect bypass is an effective treatment in the majority of cases.

5.
Toxins (Basel) ; 12(2)2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093386

RESUMO

The phospholipase A2 (PLA2) inhibitor Varespladib (LY315920) and its orally bioavailable prodrug, methyl-Varespladib (LY333013) inhibit PLA2 activity of a wide variety of snake venoms. In this study, the ability of these two forms of Varespladib to halt or delay lethality of potent neurotoxic snake venoms was tested in a mouse model. The venoms of Notechis scutatus, Crotalus durissus terrificus, Bungarus multicinctus, and Oxyuranus scutellatus, all of which have potent presynaptically acting neurotoxic PLA2s of variable quaternary structure, were used to evaluate simple dosing regimens. A supralethal dose of each venom was injected subcutaneously in mice, followed by the bolus intravenous (LY315920) or oral (LY333013) administration of the inhibitors, immediately and at various time intervals after envenoming. Control mice receiving venom alone died within 3 h of envenoming. Mice injected with O. scutellatus venom and treated with LY315920 or LY333013 survived the 24 h observation period, whereas those receiving C. d. terrificus and B. multicinctus venoms survived at 3 h or 6 h with a single dose of either form of Varespladib, but not at 24 h. In contrast, mice receiving N. scutatus venom and then the inhibitors died within 3 h, similarly to the control animals injected with venom alone. LY315920 was able to reverse the severe paralytic manifestations in mice injected with venoms of O. scutellatus, B. multicinctus, and C. d. terrificus. Overall, results suggest that the two forms of Varespladib are effective in abrogating, or delaying, neurotoxic manifestations induced by some venoms whose neurotoxicity is mainly dependent on presynaptically acting PLA2s. LY315920 is able to reverse paralytic manifestations in severely envenomed mice, but further work is needed to understand the significance of species-specific differences in animal models as they compare to clinical syndromes in human and for potential use in veterinary medicine.

6.
Hypertens Pregnancy ; 39(1): 56-63, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31910697

RESUMO

Objective: To determine whether family history of pre-eclampsia and cardiovascular disease is consistently associated with the occurrence of pre-eclampsia sub-phenotypes and fetal growth restriction (FGR).Material and Methods: We conducted a case-control study in which cases of pre-eclampsia and healthy pregnant controls were recruited at the time of delivery from eight Colombian cities between 2000 and 2012. Odds of pre-eclampsia among women with a positive family history of pre-eclampsia or cardiovascular disease were compared to women without affected relatives (logistic regression modeling and multinomial logistic regression model [Ajusted]).Results: A total of 3510 pre-eclampsia cases and 4512 controls with data on family history of pre-eclampsia were included in analyses. A subsample of 3086 cases and 3888 controls also provided information on family history of cardiovascular disease. Women whose mothers had pre-eclampsia had 3.38 (95% CI 2.89, 3.96) higher odds than those who did not, and having an affected sister increased pre-eclampsia odds by 2.43 (95% CI 2.02, 2.93). The effect of having both mother and sister affected with pre-eclampsia was stronger than the two independent risk factors (OR 4.17 [95% CI 2.60, 6.69]). Women with parental history of cardiovascular disease also had an increased risk of pre-eclampsia (OR 1.58 [95% CI 1.24, 2.01]).Conclusions: Family history of pre-eclampsia increased the risk of PE. The impact of family history of cardiovascular disease on pre-eclampsia was more conservative, but serves to support the hypothesis that pre-eclampsia may reflect the premature exposure of underlying cardiovascular dysfunction, precipitated by the stress test of pregnancy.

7.
Stroke ; 51(3): 838-845, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31948355

RESUMO

Background and Purpose- In randomized trials of symptomatic carotid endarterectomy, only modest benefit occurred in patients with moderate stenosis and important subgroups experienced no benefit. Carotid plaque 18F-fluorodeoxyglucose uptake on positron emission tomography, reflecting inflammation, independently predicts recurrent stroke. We investigated if a risk score combining stenosis and plaque 18F-fluorodeoxyglucose would improve the identification of early recurrent stroke. Methods- We derived the score in a prospective cohort study of recent (<30 days) non-severe (modified Rankin Scale score ≤3) stroke/transient ischemic attack. We derived the SCAIL (symptomatic carotid atheroma inflammation lumen-stenosis) score (range, 0-5) including 18F-fluorodeoxyglucose standardized uptake values (SUVmax <2 g/mL, 0 points; SUVmax 2-2.99 g/mL, 1 point; SUVmax 3-3.99 g/mL, 2 points; SUVmax ≥4 g/mL, 3 points) and stenosis (<50%, 0 points; 50%-69%, 1 point; ≥70%, 2 points). We validated the score in an independent pooled cohort of 2 studies. In the pooled cohorts, we investigated the SCAIL score to discriminate recurrent stroke after the index stroke/transient ischemic attack, after positron emission tomography-imaging, and in mild or moderate stenosis. Results- In the derivation cohort (109 patients), recurrent stroke risk increased with increasing SCAIL score (P=0.002, C statistic 0.71 [95% CI, 0.56-0.86]). The adjusted (age, sex, smoking, hypertension, diabetes mellitus, antiplatelets, and statins) hazard ratio per 1-point SCAIL increase was 2.4 (95% CI, 1.2-4.5, P=0.01). Findings were confirmed in the validation cohort (87 patients, adjusted hazard ratio, 2.9 [95% CI, 1.9-5], P<0.001; C statistic 0.77 [95% CI, 0.67-0.87]). The SCAIL score independently predicted recurrent stroke after positron emission tomography-imaging (adjusted hazard ratio, 4.52 [95% CI, 1.58-12.93], P=0.005). Compared with stenosis severity (C statistic, 0.63 [95% CI, 0.46-0.80]), prediction of post-positron emission tomography stroke recurrence was improved with the SCAIL score (C statistic, 0.82 [95% CI, 0.66-0.97], P=0.04). Findings were confirmed in mild or moderate stenosis (adjusted hazard ratio, 2.74 [95% CI, 1.39-5.39], P=0.004). Conclusions- The SCAIL score improved the identification of early recurrent stroke. Randomized trials are needed to test if a combined stenosis-inflammation strategy improves selection for carotid revascularization where benefit is currently uncertain.


Assuntos
Estenose das Carótidas , Placa Aterosclerótica , Tomografia por Emissão de Pósitrons , Acidente Vascular Cerebral , Idoso , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/fisiopatologia , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia
8.
Nat Commun ; 10(1): 5484, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792213

RESUMO

Type VI secretion systems (T6SSs) are nanomachines widely used by bacteria to deliver toxic effector proteins directly into neighbouring cells. However, the modes of action of many effectors remain unknown. Here we report that Ssp6, an anti-bacterial effector delivered by a T6SS of the opportunistic pathogen Serratia marcescens, is a toxin that forms ion-selective pores. Ssp6 inhibits bacterial growth by causing depolarisation of the inner membrane in intoxicated cells, together with increased outer membrane permeability. Reconstruction of Ssp6 activity in vitro demonstrates that it forms cation-selective pores. A survey of bacterial genomes reveals that genes encoding Ssp6-like effectors are widespread in Enterobacteriaceae and often linked with T6SS genes. We conclude that Ssp6 and similar proteins represent a new family of T6SS-delivered anti-bacterial effectors.


Assuntos
Proteínas de Bactérias/metabolismo , Cátions/metabolismo , Serratia marcescens/metabolismo , Sistemas de Secreção Tipo VI/metabolismo , Antibacterianos/metabolismo , Antibacterianos/toxicidade , Proteínas de Bactérias/genética , Proteínas de Bactérias/toxicidade , Membrana Celular/efeitos dos fármacos , Membrana Celular/genética , Membrana Celular/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano , Transporte Proteico , Serratia marcescens/genética , Sistemas de Secreção Tipo VI/genética , Sistemas de Secreção Tipo VI/toxicidade
9.
Regen Med ; 14(11): 1029-1046, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31718498

RESUMO

Aim: Understanding blood component variation as a function of healthy population metrics is necessary to inform biomanufacturing process design. Methods: UK Biobank metrics were examined for variation in white blood cell count as an analog to potential manufacturing starting material input. Results: White blood cell count variation of four orders of magnitude (6.65 × 109 cells/l) was found. Variation increased with age, increased with weight up to 80 kg then decreased. Health state showed a greater absolute number of participants with elevated count. Female range was greater than male. Cell count/distributions were different between centers. Conclusion: This variation and range of process input signals a requirement for new strategies for manufacturing process design and control.

10.
Eur J Appl Physiol ; 119(11-12): 2685-2699, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31654124

RESUMO

PURPOSE: This study aimed to identify a safe, rapid, and accessible method of estimating muscle volume of key lower limb muscle groups to reduce the time-demand of acquiring this measurement and potentially facilitate its application as a clinical monitoring tool. METHODS: Unilateral MRI images were acquired from the 12th thoracic vertebrae to the base of the foot in 18 recreationally active males. Panoramic B-mode ultrasound images were acquired from the same leg at the mid-hip, 25%, 50%, and 75% of thigh length, and 25% of shank length. Body mass, height, limb lengths, and circumferences at the sites corresponding to the ultrasound images were acquired. A single investigator manually analysed all images. Regression analyses were conducted to identify models for estimating volume of the hip extensor, knee extensor and flexor, and ankle plantarflexor muscle groups. RESULTS: Models were developed for estimating hip extensor (SEE = 8.92%, R2 = 0.690), knee extensor (SEE = 5.24%, R2 = 0.707) and flexor (SEE = 7.89%, R2 = 0.357), and ankle plantarflexor (SEE = 10.78%, R2 = 0.387) muscle group volumes. The hip and knee extensor models showed good potential for generalisation. Systematic error was observed for the knee flexor and ankle plantarflexor models. CONCLUSIONS: Hip extensor, knee extensor and flexor, and ankle plantarflexor muscle group volumes can be estimated using B-mode ultrasound images and anthropometric measurements. The error shown for each of the models was sufficient to identify previously reported differences in muscle volume due to training or injury, supporting their clinical application.


Assuntos
Músculo Esquelético/fisiologia , Adulto , Tornozelo/fisiologia , Articulação do Tornozelo/fisiologia , Pé/fisiologia , Quadril/fisiologia , Articulação do Quadril/fisiologia , Humanos , Joelho/fisiologia , Articulação do Joelho/fisiologia , Masculino , Contração Muscular/fisiologia , Ultrassonografia
11.
PLoS One ; 14(10): e0223997, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622438

RESUMO

BACKGROUND: Control of vascular risk factors is essential for secondary stroke prevention. However, adherence to secondary prevention medications is often suboptimal, and may be affected by cognitive impairment. Few studies to date have examined associations between cognitive impairment and medication adherence post-stroke, and none have considered whether adherence to secondary prevention medications might affect subsequent cognitive function. The aim of this study was to explore prospective associations between cognitive impairment and medication non-adherence post-stroke. METHODS: A five-year follow-up of 108 stroke survivors from the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) prospective observational cohort study. Cognitive function was assessed using the Montreal Cognitive Assessment at 6 months, and a neuropsychological test battery at 5 years. Adherence to antihypertensive, antithrombotic and lipid-lowering medications was assessed using prescription refill data. RESULTS: The prevalence of cognitive impairment at five years was 35.6%. The prevalence of non-adherence ranged from 15.1% for lipid-lowering agents to 30.2% for antithrombotics. There were no statistically significant associations between medication non-adherence in the first year post-stroke and cognitive impairment at 5 years, nor between cognitive impairment at 6 months and non-adherence at 5 years. Stroke survivors with cognitive impairment were significantly more likely to report receiving help with taking medications [OR (95% CI): 4.84 (1.17, 20.07)]. CONCLUSIONS: This is the first study to explore the potential impact of non-adherence to secondary prevention medications on cognitive impairment in stroke survivors. Findings highlight the role of family members and caregivers in assisting stroke survivors with medication administration, particularly in the context of deficits in cognitive function. Involving family members and caregivers may be a legitimate and cost-effective strategy to improve medication adherence in stroke survivors.


Assuntos
Disfunção Cognitiva/patologia , Adesão à Medicação/estatística & dados numéricos , Acidente Vascular Cerebral/patologia , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Cuidadores/psicologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/epidemiologia , Estudos de Coortes , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Humanos , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prevalência , Prevenção Secundária , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Reabilitação do Acidente Vascular Cerebral
14.
Eur Stroke J ; 4(2): 160-171, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31259264

RESUMO

Introduction: Increasing attention is being paid to interventions for cognitive impairment (CI) post-stroke, including for CI that does not meet dementia criteria. The aim of this paper was to conduct a systematic review and meta-analysis of the prevalence of cognitive impairment no dementia (CIND) within one year post-stroke. Patients and methods: Pubmed, EMBASE and PsychInfo were searched for papers published in English in 1995-2017. Included studies were population or hospital-based cohort studies for first-ever/recurrent stroke, assessing CIND using standardised criteria at 1-12 months post-stroke. Abstracts were screened, followed by full text review of potentially relevant articles. Data were extracted using a standard form, and study quality was appraised using the Crowe Critical Appraisal Tool. A pooled prevalence of CIND with 95% confidence intervals (CI) was estimated using random-effects meta-analysis. Heterogeneity was measured using the I2 statistic. Results: A total of 7000 abstracts were screened, followed by 1028 full text articles. Twenty-three articles were included in the systematic review, and 21 in the meta-analysis. The pooled CIND prevalence was 38% [95% CI = 32-43%] (I2=92.5%, p < 0.01). Study quality emerged as one source of heterogeneity. The five studies with the highest quality scores had no heterogeneity (I2=0%, p = 0.99), with a similar pooled prevalence (39%, 95%CI = 35-42%). Other sources of heterogeneity were stroke type, inclusion of pre-stroke CI, and age at assessment time.Discussion and conclusion: Meta-analysis of available studies indicates that in the first year post-stroke, 4 in 10 patients display a level of cognitive impairment that does not meet the criteria for dementia.

15.
Regen Med ; 14(5): 465-488, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31210581

RESUMO

Cell-based therapies must achieve clinical efficacy and safety with reproducible and cost-effective manufacturing. This study addresses process development issues using the exemplar of a human pluripotent stem cell-based dopaminergic neuron cell therapy product. Early identification and correction of risks to product safety and the manufacturing process reduces the expensive and time-consuming bridging studies later in development. A New Product Introduction map was used to determine the developmental requirements specific to the product. Systematic Risk Analysis is exemplified here. Expected current value-based prioritization guides decisions about the sequence of process studies and whether and if an early abandonment of further research is appropriate. The application of the three tools enabled prioritization of the development studies.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Neurônios Dopaminérgicos , Doenças Neurodegenerativas/terapia , Células-Tronco Pluripotentes , Ensaios Clínicos como Assunto , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Neurônios Dopaminérgicos/transplante , Humanos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/patologia , Medição de Risco
16.
Physiol Meas ; 40(6): 064005, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31108485

RESUMO

OBJECTIVE: Muscle volume (MV) analysis from magnetic resonance imaging (MRI) is time-intensive, and limited measurement reliability data are available. This study investigated a method to reduce lower limb MV analysis time demands, established reliability of these measurements, and applied the findings to quantify muscle size and symmetry in healthy adult males. APPROACH: Bilateral MRI images were acquired from 15 healthy males (age: 26.5 ± 4.6 years, height: 1.81 ± 0.09 m, body mass: 80.4 ± 12.4 kg) for the entire lower limb. In two participants, the individual gluteals, quadriceps, hamstrings, and triceps surae were manually outlined every 5 mm and MV calculated using 5, 10, 15, 20, 25, and 30 mm distances between images to determine an appropriate distance for reducing analysis time. For all 15 participants, 35 muscles in each limb were manually outlined every 15 mm for use in MV calculations. Reliability of muscle cross-sectional area (CSA) measurement was determined within- and between-sessions and MV measurement reliability determined between-sessions. Between-limb symmetry was calculated using symmetry indices. MAIN RESULTS: A 15 mm inter-slice distance was appropriate for measuring MV (mean difference compared to reference method: 0.7% ± 0.7%). Between-session measurement reliability was good for MV (Typical Error preferred kicking limb (TEP): 1.2%, non-preferred kicking limb (TENP): 0.8%) and CSA (TEP: 3.4% ± 2.9%, TENP: 3.2% ± 1.9%) although CSA Typical Error was larger with increased between-session time (TEP: 4.1% ± 3.1%, TENP: 4.7% ± 4.0%). Between-limb differences in MV were small (mean symmetry index: 0.4% ± 4.1%). Absolute differences in individual MV were larger (mean: 12.6% ± 2.6%), but representing muscles as functional anatomical groups showed smaller absolute between-limb differences (mean: 4.7% ± 1.8%). SIGNIFICANCE: MV analysis time demand can be reduced by increasing the distance between analysed MRI slices, although participant height, muscle length and muscle shape require consideration. Small between-limb muscle size differences have been reported in adult males.


Assuntos
Imagem por Ressonância Magnética , Músculo Esquelético/anatomia & histologia , Adulto , Humanos , Masculino , Tamanho do Órgão , Fatores de Tempo
17.
Disabil Rehabil ; : 1-11, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30971135

RESUMO

PURPOSE: Exploring the views of those impacted by stroke is key to the design of an effective and appropriate cognitive rehabilitation intervention for post-stroke cognitive impairment. This qualitative study examined the perspectives and preferences of stroke survivors, carers, and healthcare professionals to inform the design of a cognitive rehabilitation intervention. DESIGN AND METHODS: The research employed a qualitative study design and thematic analysis of data. In-depth semi-structured interviews were conducted with stroke survivors (n = 14), carers (n = 11), and healthcare professionals involved in providing stroke care (n = 19). Interviews were audio-recorded and transcribed. Coding was conducted and themes were developed both inductively and deductively. RESULTS: Themes address five broad areas relevant for the design and implementation of the intervention: (i) activities to include; (ii) when it takes place; (iii) location; (vi) format; (v) who the intervention should include. CONCLUSIONS: Qualitative work with stroke survivors, carers and healthcare professionals provided vital information for the intervention design. Issues identified by participants as being key to intervention development included: (i) implications of post-stroke cognitive impairment survivors' confidence; (ii) their individual capacity in terms of fatigue and metacognition; and (iii) practical issues such as intervention location. The inclusion of psychoeducation regarding consequences of stroke was recommended. Implications for rehabilitation Stroke survivors, carers, and rehabilitation professionals who provide stroke care can provide valuable insights and ideas to inform the development of a cognitive rehabilitation intervention. A cognitive rehabilitation intervention should be tailored to patient-specified goals, incorporating both group and individualized activities. Information, education, and communication are required to help stroke survivors and carers understand the cognitive, emotional, and behavioral consequences of stroke. Intervention content should be considerate of stroke survivors' capacity in terms of cognitive impairment and fatigue levels.

18.
Toxicol In Vitro ; 58: 97-109, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30910521

RESUMO

Snakebite is a neglected tropical disease that disproportionately affects the poor. Antivenom is the only specific and effective treatment for snakebite, but its distribution is severely limited by several factors, including the prohibitive cost of some products. Papua New Guinea (PNG) is a snakebite hotspot but the high costs of Australian antivenoms (thousands of dollars per treatment) makes it unaffordable in PNG. A more economical taipan antivenom has recently been developed at the Instituto Clodomiro Picado (ICP) in Costa Rica for PNG and is currently undergoing clinical trials for the treatment of envenomations by coastal taipans (Oxyuranus scutellatus). In addition to potentially having the capacity to neutralise the effects of envenomations of non-PNG taipans, this antivenom may have the capacity to neutralise coagulotoxins in venom from closely related brown snakes (Pseudonaja spp.) also found in PNG. Consequently, we investigated the cross-reactivity of taipan antivenom across the venoms of all Oxyuranus and Pseudonaja species. In addition, to ascertain differences in venom biochemistry that influence variation in antivenom efficacy, we tested for relative cofactor dependence. We found that the new ICP taipan antivenom exhibited high selectivity for Oxyuranus venoms and only low to moderate cross-reactivity with any Pseudonaja venoms. Consistent with this genus level distinction in antivenom efficacy were fundamental differences in the venom biochemistry. Not only were the Pseudonaja venoms significantly more procoagulant, but they were also much less dependent upon the cofactors calcium and phospholipid. There was a strong correlation between antivenom efficacy, clotting time and cofactor dependence. This study sheds light on the structure-function relationships of the procoagulant toxins within these venoms and may have important clinical implications including for the design of next-generation antivenoms.


Assuntos
Antivenenos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Venenos Elapídicos/toxicidade , Animais , Elapidae , Fator Xa/metabolismo , Feminino , Humanos , Masculino
19.
Top Stroke Rehabil ; 26(3): 180-186, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30907273

RESUMO

BACKGROUND: Family members frequently provide long-term care for stroke survivors, which can lead to psychological strain, particularly in the presence of cognitive decline. OBJECTIVES: To profile anxious and depressive symptoms of family caregivers at 5 years post-stroke, and to explore associations with stroke survivor cognitive decline. METHODS: As part of a 5-year follow-up of the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) cohort of stroke survivors, family members completed a self-report questionnaire. Symptoms of anxiety and depression were assessed using the HADS-A and CES-D. Cognitive decline in stroke survivors was assessed from the caregiver's perspective using the IQCODE, with cognitive performance assessed by the MoCA. Data were analyzed using logistic regression models. RESULTS: 78 family members participated; 25.5% exhibited depressive symptoms, 19.4% had symptoms of anxiety. Eleven stroke survivors (16.7%) had evidence of cognitive decline according to both the IQCODE and MoCA. Family members of stroke survivors with cognitive decline were significantly more likely to report symptoms of depression [age-adjusted OR (95% CI): 5.94 (1.14, 30.89)] or anxiety [age-adjusted OR (95% CI): 5.64 (1.24, 25.54)] than family members of stroke survivors without cognitive decline. CONCLUSIONS: One-fifth of family caregivers exhibited symptoms of anxiety and one-quarter symptoms of depression at 5 years post-stroke. Stroke survivor cognitive decline was significantly associated with both depressive and anxious symptoms of family caregivers. Family members play a key role in the care and rehabilitation of stroke patients; enhancing their psychological wellbeing and identifying unmet needs are essential to improving outcomes for stroke survivors and families.


Assuntos
Cuidadores/psicologia , Disfunção Cognitiva/psicologia , Acidente Vascular Cerebral/psicologia , Idoso , Ansiedade/psicologia , Estudos de Coortes , Estudos Transversais , Depressão/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Autorrelato , Reabilitação do Acidente Vascular Cerebral , Inquéritos e Questionários , Sobreviventes
20.
BMJ Open ; 9(2): e024429, 2019 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-30819706

RESUMO

OBJECTIVE: Cognitive impairment is a pervasive outcome of stroke, reported in over half of patients 6 months post-stroke and is associated with increased disability and a poorer quality of life. Despite the prevalence of post-stroke cognitive impairment, the efficacy of existing psychological interventions for the rehabilitation of cognitive impairment following stroke has yet to be established. The aim of this study is to identify psychological interventions from non-randomised studies that intended to improve post-stroke cognitive function and establish their efficacy. DESIGN: Systematic review and meta-analysis of non-randomised studies of psychological interventions addressing post-stroke cognitive impairment. DATA SOURCES: Electronic searches were performed in the Pubmed, EMBASE and PsycINFO databases, the search dating from inception to February 2017. ELIGIBILITY CRITERIA: All non-randomised controlled studies and quasi-randomised controlled trials examining psychological interventions to improve cognitive function following stroke were included, such as feasibility studies, pilot studies, experimental studies, and quasi-experimental studies. The primary outcome was cognitive function. The prespecified secondary outcomes were functional abilities in daily life and quality of life. METHODS: The current meta-analyses combined the findings of seven controlled studies, examining the efficacy of psychological interventions compared with treatment-as-usual controls or active controls, and 13 one-group pre-post studies. RESULTS: Results indicated an overall small effect on cognition across the controlled studies (Hedges' g=0.38, 95% CI=0.06 to 0.7) and a moderate effect on cognition across the one-group pre-post studies (Hedges' g=0.51, 95% CI=0.3 to 0.73). Specific cognitive domains, such as memory and attention also demonstrated a benefit of psychological interventions. CONCLUSIONS: This review provides support for the potential of psychological interventions to improve overall cognitive function post-stroke. Limitations of the study, in terms of risk of bias and quality of included studies, and future research directions are explored. PROSPERO REGISTRATION NUMBER: CRD42017069714.


Assuntos
Disfunção Cognitiva/etiologia , Acidente Vascular Cerebral/complicações , Disfunção Cognitiva/reabilitação , Disfunção Cognitiva/terapia , Humanos , Psicoterapia
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