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1.
Contemp Clin Trials Commun ; 41: 101358, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39280786

RESUMO

Background: In this paper we outline the protocol for an implementation-effectiveness trial of ecofit, a multi-component mHealth intervention aimed at increasing participation in resistance and aerobic physical activity using the outdoor built environment (i.e., outdoor gyms) and social support. We have previously demonstrated the efficacy and effectiveness of the ecofit program in insufficiently active people with (or at risk of) type 2 diabetes and community-dwelling adults, respectively. The objective of this trial is to compare the effects of two implementation support models (i.e., 'Low' versus 'Moderate') on the reach (primary outcome), uptake, dose received, impact and fidelity of the ecofit program. Research design and methods: This hybrid type III implementation-effectiveness study will be evaluated using a two-arm randomized controlled trial, including 16 outdoor gym locations in two large regional municipalities in New South Wales, Australia. Outdoor gym locations will be pair-matched, based on an established socio-economic status consensus-based index (high versus low), and randomized to the 'Low' (i.e., ecofit app only) or 'Moderate' (i.e., ecofit app, face-to-face workout sessions and QR codes) implementation support group. The primary outcome of 'reach' will be measured using a modified version of the 'System for Observing Play and Recreation in Communities', capturing outdoor gym use amongst community members. Conclusion: This implementation-effectiveness trial will evaluate the effects of different levels of implementation support on participation in resistance-focused physical activity using mHealth and outdoor gyms across the broader community. This may guide widespread dissemination for councils (municipalities) nation-wide wanting to promote outdoor gym usage. Trial registry: This trial was preregistered with the Australian and New Zealand Clinical Trial Registry (ACTRN12624000261516).

2.
J Pharm Sci ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39173743

RESUMO

The user of a pediatric drug includes not only the patient, but also their caregiver and healthcare provider, including nurses, doctors, and pharmacists. Therefore, adopting a patient-centric approach that focuses on all users is critical for the development of pediatric drug products. This article outlines the quality target product profile parameters and a patient-centric approach for the development of pediatric proteinbased therapies. The use environment, formulation design, and preparation and in use stability considerations are described. An acceptability profile for the various routes of parenteral administration is described with a focus on pediatric age groups. Furthermore, a risk assessment approach is presented for the selection of excipients to be utilized in pediatric protein-based biopharmaceuticals. Several case studies are included which illustrate the selection of drug product parameters such as formulation, dose volume, and route of administration with the pediatric user in mind.

3.
Gait Posture ; 113: 553-560, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39180927

RESUMO

BACKGROUND: Cerebral amyloid angiopathy (CAA) is associated with white matter damage and neurodegeneration. Gait is impaired in CAA; however, the neural basis of this impairment is unclear. RESEARCH QUESTION: Are gait impairments in patients with CAA associated with altered cerebral white matter diffusivity and/or atrophy of cortical and subcortical grey matter. METHODS: Participants with CAA (n=29), Alzheimer's disease (AD; n=16), and normal controls (n=47) were included. Gait was assessed using a 6 m walkway with parameters categorized into rhythm, pace, postural control, and variability domains. The dual-task cost (DTC) of gait speed was calculated for counting backwards, animal fluency, and serial sevens tasks. Whole-brain white matter disruption was quantified using the peak width of skeletonized mean diffusivity (PSMD), and thickness and volume of select cortical, subcortical, and cerebellar regions were quantified using FreeSurfer. RESULTS: In CAA participants, associations were found between PSMD and pace (standardized parameter estimate (ß), 95 % confidence interval (CI): 0.17, 0.03-0.32), and medial orbital frontal cortical thickness and counting backwards DTC (parameter estimate (PE), 95 % CI: -5.7 %/SD, -0.24 to -11.23). Across all groups, including CAA, associations were found between PSMD and pace, variability, counting backwards DTC, and animal fluency DTC; between frontal cortical thickness and pace, counting backwards DTC, and animal fluency DTC; between cortical regions affected by AD (inferior parietal cortex, inferior and middle temporal gyrus) and counting backwards DTC; and between thalamus volume and postural control. SIGNIFICANCE: Reduced white matter structural integrity and grey matter loss is associated with poor overall gait performance in CAA, AD, and normal controls.


Assuntos
Angiopatia Amiloide Cerebral , Substância Cinzenta , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Masculino , Feminino , Idoso , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/fisiopatologia , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Doença de Alzheimer/fisiopatologia , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Atrofia , Pessoa de Meia-Idade
4.
Can J Diabetes ; 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39159783

RESUMO

OBJECTIVES: The aim of this research was to understand the prevalence and impact of long COVID on adults with type 2 diabetes (T2D). Specifically, we sought to identify the proportion of adults with T2D who have had COVID-19 and experienced long COVID symptoms. We also explored how these ongoing symptoms impact diabetes management and physical activity participation. METHODS: Our study was carried out using an online survey of adults in Australia with T2D who had confirmed COVID-19 ≥12 weeks before participation. Respondents were asked to report the presence (and severity) of long COVID-19 symptoms, and, for those with long COVID, the impact of their symptoms on diabetes management (blood glucose, body weight) and physical activity participation (activities of daily living, work/study, exercise). RESULTS: Survey responses were provided by 1,046 adults with T2D (median age 61.0 [interquartile range 49.8 to 70.0] years; 56.0% men, 42.1% women, and 1% nonbinary/transgender; median T2D duration 10.0 [5.0 to 18.0] years and median time since COVID-19 infection 33.0 [20.3 to 36.1] weeks). Almost one third (30%) of respondents reported long COVID symptoms (present ≥12 weeks after most recent infection); 40% of respondents with long COVID symptoms reported a worsening of their diabetes management since their COVID-19 infection, with 29% reporting trouble controlling their blood glucose and 43% reporting a higher body weight. Two thirds of respondents with ongoing symptoms reported that these symptoms moderately to severely impacted their ability to perform activities of daily living, work, and/or exercise. The majority of those with long COVID reported reducing the frequency, duration, and/or intensity of exercise since their COVID-19 infection, with 36.1% not yet returning to their preinfection exercise levels; 66% cited ongoing symptoms as the primary reason for these limitations. CONCLUSIONS: Physical activity is a crucial component of diabetes management. However, the high prevalence of long COVID is hindering participation in this population, as well as deleteriously impacting diabetes management. Developing strategies to support adults with T2D and long COVID to recommence safe levels of physical activity is of critical importance.

5.
Ann Hematol ; 103(9): 3737-3743, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39003390

RESUMO

With advancements in novel therapeutics, it is unclear whether third hematopoietic cell transplantation (HCT3) has a place in the treatment of recurrent hematopoietic malignancies. We evaluated patients with hematologic malignancies who underwent HCT3 between 2000-2020. Nine patients, with a median age of 18 (9-68) years at HCT3 with acute myelogenous leukemia (n = 5), acute lymphoblastic leukemia (n = 2), myelodysplastic syndrome (n = 1), or undifferentiated acute leukemia (n = 1), were identified. The median time between first HCT and HCT3 was 3.9 (0.7-13.6) years. Indication for HCT3 was relapse (n = 8) or graft failure (n = 1) after second HCT. At HCT3, seven of nine patients were in complete remission by flow cytometry. All experienced robust donor engraftment by one month after HCT3 (≥ 90% CD3) while one died at day + 24 of multi-organ failure and was not evaluable for chimerism. In total, eight patients died from relapse (n = 4), non-relapse, (n = 3) or unknown (n = 1) causes at a median of 0.6 (range, 0.1 - 9.9) years after HCT3. After HCT3, estimated overall survival at 6 months, 1 year, and 5 years was 88%, 63%, and 22%, respectively. In this highly selected group, HCT3 provided a treatment option although long-term survival was still dismal.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Adolescente , Idoso , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/mortalidade , Criança , Adulto Jovem , Resultado do Tratamento , Taxa de Sobrevida , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidade , Estudos Retrospectivos
6.
Hosp Pharm ; 59(3): 359-366, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38764999

RESUMO

Background: Volume overload (VO) is common in the intensive care unit (ICU) and associated with negative outcomes. Approaches have been investigated to curtail VO; however, none specifically focused on medication diluent volume optimization. Objective: Investigate the impact of a pharmacist-driven medication diluent volume optimization protocol on fluid balance in critically ill patients. Methods: A prospective, pilot study was conducted in a medical ICU during October 2021 to December 2021 (pre) and February 2022 to April 2022 (post). A pharmacist-driven medication diluent volume optimization protocol focusing on vasopressor and antimicrobial diluent volumes was implemented. Demographics and clinical data were collected during ICU admission up to 7 days. The primary outcome was net fluid balance on day 3. Secondary outcomes were medication volumes administered, net fluid balance, ICU length of stay, and mortality. Results: Supply chain shortages caused the study to stop at the end of February 2022. Overall, 152 patients were included (123 pre group, 29 post group). The most common admission diagnosis was acute respiratory failure (35%). Vasopressors and antimicrobials were utilized in 47% and 66% of patients, respectively. Net fluid balance on day 3 was greater but not significant in the post group (227.1 mL [-1840.3 to 3483.7] vs 2012.3 mL [-2686.0 to 4846.0]; P = .584). Antimicrobial diluent volumes were significantly less in the post group. No differences were seen in other secondary outcomes. Protocol group assignment was not associated with net fluid balance on day 3. Conclusion: Despite decreasing antimicrobial volume contributions, optimizing diluent volumes alone did not significantly impact overall volume status. Future studies should focus on comprehensive approaches to medication diluent optimization and fluid stewardship.

7.
Eur J Appl Physiol ; 124(9): 2819-2833, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38695912

RESUMO

PURPOSE: We compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D). METHODS: Sixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months. RESULTS: After 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [-0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months. CONCLUSIONS: Short-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.


Assuntos
Diabetes Mellitus Tipo 2 , Treinamento Intervalado de Alta Intensidade , Treinamento Resistido , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/fisiopatologia , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Treinamento Intervalado de Alta Intensidade/métodos , Treinamento Resistido/métodos , Rigidez Vascular/fisiologia
9.
Drugs R D ; 23(4): 339-362, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37938531

RESUMO

Buprenorphine has become an important medication in the context of the ongoing opioid epidemic. However, complex pharmacologic properties and varying government regulations create barriers to its use. This narrative review is intended to facilitate buprenorphine use-including non-traditional initiation methods-by providers ranging from primary care providers to addiction specialists. This article briefly discusses the opioid epidemic and the diagnosis and treatment of opioid use disorder (OUD). We then describe the basic and complex pharmacologic properties of buprenorphine, linking these properties to their clinical implications. We guide readers through the process of initiating buprenorphine in patients using full agonist opioids. As there is no single recommended approach for buprenorphine initiation, we discuss the details, advantages, and disadvantages of the standard, low-dose, bridging-strategy, and naloxone-facilitated initiation techniques. We consider the pharmacology of, and evidence base for, buprenorphine in the treatment of pain, in both OUD and non-OUD patients. Throughout, we address the use of buprenorphine in children and adolescent patients, and we finish with considerations related to the settings of pregnancy and breastfeeding.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Gravidez , Feminino , Adolescente , Criança , Humanos , Buprenorfina/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Analgésicos Opioides/efeitos adversos
10.
Artigo em Inglês | MEDLINE | ID: mdl-37848203

RESUMO

Microbial challenge in-use studies are performed to evaluate the potential for microbial proliferation in preservative-free single dose biological products after first puncture and potential accidental contamination during dose preparation (e.g. reconstitution, dilution) and storage. These studies, in addition to physicochemical in-use stability assessments, are used as part of product registration to define in-use hold times in Prescribing Information and in the pharmacy manual in the case of clinical products. There are no formal guidance documents describing regulator expectations on how to conduct microbial challenge in-use studies and interpret microbial data to assign in-use storage hold-times. In lieu of guidance, US Food and Drug Administration (FDA) regulators have authored publications and presentations describing regulator expectations. Insufficient or unavailable microbial challenge data can result in shortened in-use hold times, thus microbial challenge data enables flexibility for health care providers (HCPs) and patients, while ensuring patient safety. A cross-industry/FDA in-use microbial working group was formed through the Innovation & Quality (IQ) Consortium to gain alignment among industry practice and regulator expectations. The working group assessed regulatory guidance, current industry practice via a blinded survey of IQ Consortium member companies, and scientific rationale to align on recommendations for experimental design, execution of microbial challenge in-use studies, and a decision tree for microbial data interpretation to assign in-use hold times. Besides the study execution and data interpretation, additional considerations are discussed including use of platform data for clinical stage products, closed system transfer devices (CSTDs), transport of dose solutions, long infusion times, and the use of USP <797> by HCPs for preparing sterile drugs for administration. The recommendations provided in this manuscript will help streamline biological product development, ensure consistency on assignment of in-use hold times in biological product labels across industry, and provide maximum allowable flexibility to HCPs and patients, while ensuring patient safety.

11.
Vet Rec ; 193(5): ii-iii, 2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37681594

RESUMO

Her ambition was to work in the leisure and tourism industry, but things changed for Emily Cox when she applied for a veterinary receptionist role and soon found a niche in the farm side of the practice.


Assuntos
Indústrias , Turismo , Animais , Feminino , Fazendas
12.
J Clin Transl Hepatol ; 11(5): 1050-1060, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37577222

RESUMO

Background and Aims: High-intensity interval training (HIIT) is a therapeutic option for people with nonalcoholic steatohepatitis (NASH). However, the perspectives and experiences of HIIT for people with NASH are unknown, limiting translation of research. We explored the experiences and perspectives of both professionally supervised and self-directed HIIT in people with NASH and evaluated participant-reported knowledge, barriers, and enablers to commencing and sustaining HIIT. Methods: Twelve participants with NASH underwent 12 weeks of supervised HIIT (3 days/week, 4×4 minutes at 85-95% maximal heart rate, interspersed with 3 minutes active recovery), followed by 12-weeks of self-directed (unsupervised) HIIT. One-on-one, semistructured participant interviews were conducted by exercise staff prior to HIIT and following both supervised and self-directed HIIT to explore prior knowledge, barriers, enablers, and outcomes at each stage. Interviews were audio-recorded, transcribed, coded, and thematically analyzed by two independent researchers. Results: Four dominant themes were identified: (1) no awareness of/experience with HIIT and ambivalence about exercise capabilities; (2) multiple medical and social barriers to commencing and continuing HIIT; (3) exercise specialist support was a highly valued enabler, and (4) HIIT was enjoyed and provided holistic benefits. Conclusions: People with NASH may lack knowledge of and confidence for HIIT, and experience multiple complex barriers to commencing and continuing HIIT. Exercise specialist support is a key enabler to sustained engagement. These factors need to be addressed in future clinical programs to augment the uptake and long-term sustainability of HIIT by people with NASH so they can experience the range of related benefits.

13.
Health Technol (Berl) ; 13(3): 523-533, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37303978

RESUMO

Purpose: The emergence of the COVID-19 (SARS-CoV-2) pandemic has led to public health restrictions and a shift towards virtual care and telehealth. The aim of this study was to explore barriers and facilitators of virtual care from the perspective of neurological and psychiatric patients. Methods: One-on-one interviews were conducted remotely using telephone and online video teleconferencing. There was a total of 57 participants, and a thematic content analysis was conducted using NVivo software. Results: The two main themes were (1) virtual health service delivery and (2) virtual physician/patient interaction, with subthemes around how virtual care improved accessibility of care for patients and improved patient-centered care; how privacy and technical issues impact patients using virtual care; and the need for relationality and connection between health care providers and patients while using virtual care. Conclusions: This study showed that virtual care can increase accessibility and efficiency for patients and providers, indicating its potential for ongoing use in the delivery of clinical care. Virtual care was found to be an acceptable mode of healthcare delivery from the perspective of patients; however, there is a continued need for relationship-building between care providers and patients.

14.
Nat Commun ; 14(1): 3514, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37316535

RESUMO

Here we describe a facile and robust genetic selection for isolating full-length IgG antibodies from combinatorial libraries expressed in the cytoplasm of redox-engineered Escherichia coli cells. The method is based on the transport of a bifunctional substrate comprised of an antigen fused to chloramphenicol acetyltransferase, which allows positive selection of bacterial cells co-expressing cytoplasmic IgGs called cyclonals that specifically capture the chimeric antigen and sequester the antibiotic resistance marker in the cytoplasm. The utility of this approach is first demonstrated by isolating affinity-matured cyclonal variants that specifically bind their cognate antigen, the leucine zipper domain of a yeast transcriptional activator, with subnanomolar affinities, which represent a ~20-fold improvement over the parental IgG. We then use the genetic assay to discover antigen-specific cyclonals from a naïve human antibody repertoire, leading to the identification of lead IgG candidates with affinity and specificity for an influenza hemagglutinin-derived peptide antigen.


Assuntos
Bioensaio , Imunoglobulina G , Humanos , Imunoglobulina G/genética , Citoplasma , Citosol , Escherichia coli/genética , Saccharomyces cerevisiae
15.
Front Neurosci ; 17: 1139988, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37139529

RESUMO

Introduction: Cerebral amyloid angiopathy (CAA) is a small vessel disease that causes covert and symptomatic brain hemorrhaging. We hypothesized that persons with CAA would have increased brain iron content detectable by quantitative susceptibility mapping (QSM) on magnetic resonance imaging (MRI), and that higher iron content would be associated with worse cognition. Methods: Participants with CAA (n = 21), mild Alzheimer's disease with dementia (AD-dementia; n = 14), and normal controls (NC; n = 83) underwent 3T MRI. Post-processing QSM techniques were applied to obtain susceptibility values for regions of the frontal and occipital lobe, thalamus, caudate, putamen, pallidum, and hippocampus. Linear regression was used to examine differences between groups, and associations with global cognition, controlling for multiple comparisons using the false discovery rate method. Results: No differences were found between regions of interest in CAA compared to NC. In AD, the calcarine sulcus had greater iron than NC (ß = 0.99 [95% CI: 0.44, 1.53], q < 0.01). However, calcarine sulcus iron content was not associated with global cognition, measured by the Montreal Cognitive Assessment (p > 0.05 for all participants, NC, CAA, and AD). Discussion: After correcting for multiple comparisons, brain iron content, measured via QSM, was not elevated in CAA compared to NC in this exploratory study.

16.
J Rural Med ; 18(2): 55-61, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37032985

RESUMO

Objective: To determine if distance from our Neonatal Intensive Care Unit (NICU) follow-up clinic exacerbated risk of clinic non-attendance in high-risk groups defined by socioeconomic status or medical complexity, as geographical distance from the hospital can affect attendance rates at NICU follow-up clinics. Patients and Methods: We retrospectively identified infants born between January 2014 and June 2018, and subsequently discharged from our 50-bed level IV NICU, which serves a predominantly rural population. Patients were included in our study if they had at least one NICU clinic follow-up visit scheduled at discharge. Distance to the clinic was calculated based on family ZIP code. Mixed-effects logistic regression analysis of attendance at each scheduled visit was used to identify independent associations and interactions with distance among study covariates. Results: We included 576 patients in our study, with 74% missing at least one clinic appointment, and 30% not attending any of the three appointments. Median distance between our hospital and families was 53 km. On multivariable analysis, neither distance nor other infant or family characteristics were associated with clinic non-attendance. Only interfacility transfer had a statistically significant interaction with distance and this association only reached statistical significance for patients living furthest from our center. Conclusions: NICU follow-up is important, but clinic attendance is poor. For families living furthest away, transfers of care during the infant's hospitalization may be associated with lower completion of recommended post-discharge follow-up. Further research is needed to understand how clinics can mitigate barriers to attendance.

17.
Gerontol Geriatr Med ; 9: 23337214221149274, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36755744

RESUMO

Hospitals and skilled nursing facilities (SNFs) are incentivized to reduce hospital readmissions among patients with heart failure (HF). We used the RE-AIM framework and mixed quantitative and qualitative data to evaluate the implementation of a multimodal HF management protocol (HFMP) administered in a SNF in 2021. Over 90% of eligible patients were enrolled in the HFMP (REACH). Of the 42 enrolled patients (61.9% female, aged 81.9 ± 8.9 years, 9.5% Medicaid), 2 (4.8%) were readmitted within 30 days of hospital discharge and 4 (9.5%) were readmitted within 30 days of SNF discharge compared with historical (2020) rates of 16.7% and 22.2%, respectively (a potential savings of $132,418-$176,573 in hospital costs) (EFFECTIVENESS). Although stakeholder feedback about ADOPTION and IMPLEMENTATION was largely positive, challenges associated with clinical data collection, documentation, and staff turnover were described. Findings will inform refinement of the HFMP to facilitate further testing and sustainability (MAINTENANCE).

18.
Int J Stroke ; 18(1): 78-84, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35473418

RESUMO

BACKGROUND: Cerebral amyloid angiopathy (CAA) is associated with cognitive decline. CAA has diverse impacts on brain structure and function; however, the brain lesions that mediate the association of CAA with cognition are not understood well. AIMS: To determine the degree to which CAA neuroimaging biomarkers mediate the association of CAA with cognitive dysfunction. METHODS: We analyzed cross-sectional data of patients with probable CAA and controls without cognitive impairment from the Functional Assessment of Vascular Reactivity study. Neuropsychological tests were grouped into domains of memory, executive function, and processing speed. Candidate CAA neuroimaging biomarkers were pre-specified based on prior literature, consisting of white matter hyperintensity volume, peak width of skeletonized mean diffusivity (PSMD) on diffusion tensor magnetic resonance imaging (MRI), cerebrovascular reactivity (CVR), cortical thickness, and cortical thickness in a meta-region of interest typically affected by Alzheimer's disease (AD). Cognitive scores and neuroimaging markers were standardized and reported in relation to values in controls. Mediation analysis was used to estimate the total effect of CAA on cognition and the proportion of the total effect that was mediated by neuroimaging biomarkers, controlling for age, sex, and education. RESULTS: There were 131 participants (67 CAA and 64 controls). Mean age was 72.1 ± 7.7 years, and 54.2% were women. As expected, compared to controls, CAA was associated with lower cognition. In mediation analyses, CAA had direct unmediated effects of 48%, 46%, and 52% on all three cognitive domains. The association of CAA with memory was partially mediated by CVR and PSMD, accounting for 18% and 36% of the total effect of CAA. The association of CAA with executive function was partially mediated by PSMD and mean cortical thickness in the AD meta-region of interest (ROI), accounting for 33% and 31% of the total effect of CAA. The association of CAA with processing speed was partially mediated by CVR and PSMD, accounting for 8% and 34% of the total effect of CAA. Among CAA participants, the presence of cortical superficial siderosis was associated with lower processing speed. CONCLUSION: Altered white matter diffusivity (i.e. PSMD), CVR, and atrophy, taken together, account for about half the effect of CAA on cognition.


Assuntos
Angiopatia Amiloide Cerebral , Disfunção Cognitiva , Acidente Vascular Cerebral , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Estudos Transversais , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/complicações , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/complicações , Biomarcadores , Hemorragia Cerebral/complicações
19.
Dig Dis Sci ; 68(5): 2123-2139, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36538276

RESUMO

BACKGROUND: High-Intensity Interval Training (HIIT) involves bursts of high-intensity exercise interspersed with lower-intensity exercise recovery. HIIT may benefit cardiometabolic health in people with nonalcoholic steatohepatitis (NASH). AIMS: We aimed to examine the safety, feasibility, and efficacy of 12-weeks of supervised HIIT compared with a sham-exercise control (CON) for improving aerobic fitness and peripheral insulin sensitivity in biopsy-proven NASH. METHODS: Participants based in the community [(n = 14, 56 ± 10 years, BMI 39.2 ± 6.7 kg/m2, 64% male), NAFLD Activity Score 5 (range 3-7)] were randomized to 12-weeks of supervised HIIT (n = 8, 4 × 4 min at 85-95% maximal heart rate, interspersed with 3 min active recovery; 3 days/week) or CON (n = 6, stretching; 3 days/week). Safety (adverse events) and feasibility determined as ≥ 70% program completion and ≥ 70% global adherence (including session attendance, interval intensity adherence, and duration adherence) were assessed. Changes in cardiorespiratory fitness (V̇O2peak), exercise capacity (time-on-test) and peripheral insulin sensitivity (euglycemic hyperinsulinemic clamp) were assessed. Data were analysed using ANCOVA with baseline value as the covariate. RESULTS: There were no HIIT-related adverse events and HIIT was globally feasible [program completion 75%, global adherence 100% (including adherence to session 95.4 ± 7.3%, interval intensity 95.3 ± 6.0% and duration 96.8 ± 2.4%)]. A large between-group effect was observed for exercise capacity [mean difference 134.2 s (95% CI 19.8, 248.6 s), ƞ2 0.44, p = 0.03], improving in HIIT (106.2 ± 97.5 s) but not CON (- 33.4 ± 43.3 s), and for peripheral insulin sensitivity [mean difference 3.4 mg/KgLegFFM/min (95% CI 0.9,6.8 mg/KgLegFFM/min), ƞ2 0.32, p = 0.046], improving in HIIT (1.0 ± 0.8 mg/KgLegFFM/min) but not CON (- 3.1 ± 1.2 mg/KgLegFFM/min). CONCLUSIONS: HIIT is safe, feasible and efficacious for improving exercise capacity and peripheral insulin sensitivity in people with NASH. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (anzctr.org.au) identifier ACTRN12616000305426 (09/03/2016).


Assuntos
Treinamento Intervalado de Alta Intensidade , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Feminino , Hepatopatia Gordurosa não Alcoólica/terapia , Austrália , Exercício Físico/fisiologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-36497560

RESUMO

This exploratory study aimed to quantify children's engagement behaviors during a mastery-motivational climate intervention. We also completed an exploratory factor analysis to elucidate if child engagement changed across intervention sessions. METHOD: 35 children (17 boys; 18 girls) completed a 10-week mastery-motivational climate motor skill intervention. Engagement was operationalized as the time children were appropriately involved in the intervention and was assessed using momentary time sampling during the motor skill practice portion of the intervention. RESULTS: Overall, children were engaged 36% of the motor skills practice time (37% for boys; 36% for girls). Children who initially had below-average skills engaged for 36% (36% for boys; 35% for girls) of the motor skills practice time, and children who were average or above-average at the start of the intervention engaged in skill practice for 39% (39% for boys; 36% for girls). Differences in engagement in skill type (e.g., locomotor vs. ball skills) and trends over time were observed. CONCLUSION: These findings support that children engage in mastery-motivation climates, but the amount of participation may be influenced by individual factors of sex and initial skill level.


Assuntos
Motivação , Destreza Motora , Criança , Masculino , Feminino , Humanos , Comportamento Infantil
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