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2.
Aust J Rural Health ; 32(2): 286-298, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38337146

RESUMO

OBJECTIVE: Most podiatry-led high-risk foot services (HRFS) in Australia are located in metropolitan areas or large regional centres. In rural areas, where there are limited specialist services, individuals with diabetes-related foot ulceration are more likely to undergo amputation. This study aimed to explore clinicians' perceptions of a recently implemented HRFS in rural New South Wales, Australia, and compare trends of amputation and hospitalisation prior to and post-implementation of the service. SETTING: Rural HRFS in Tamworth, New South Wales, Australia. PARTICIPANTS: Health professionals working within the HRFS were recruited to participate. DESIGN: This was a multiple-methods study. For the qualitative arm, semi-structured interviews were conducted, which were analysed using a reflexive thematic approach. The quantitative arm of the study utilised a retrospective analytic design which applied an interrupted time series to compare amputation and hospitalisation trends pre- and post-implementation of the HRFS utilising diagnostic and procedural ICD codes. RESULTS: The qualitative arm of the study derived three themes: (1) navigating the divide, (2) rural community and rural challenges and (3) professional identity. Results of the interrupted time series indicate that there was a downward trend in major amputations following implementation of the HRFS; however, this was not statistically significant. CONCLUSION: Clinicians were aware of the inequity in DFD outcomes between rural and metropolitan areas and were committed to improving outcomes, particularly with respect to First Nations peoples. Future research will explore service use and amputation rates in the longer term to further evaluate this specialised multidisciplinary care in a rural community.


Assuntos
Amputação Cirúrgica , Pé Diabético , Serviços de Saúde Rural , Humanos , Serviços de Saúde Rural/estatística & dados numéricos , New South Wales , Amputação Cirúrgica/estatística & dados numéricos , Feminino , Masculino , Pesquisa Qualitativa , Estudos Retrospectivos , Podiatria , Adulto , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , População Rural/estatística & dados numéricos
3.
Clin Lung Cancer ; 25(1): 80-84, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37914594

RESUMO

INTRODUCTION: Osimertinib is a central nervous system (CNS)-active, third generation, irreversible, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR-TKI sensitizing and EGFR T790M resistance mutations, with demonstrated efficacy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). We present the rationale and design for TARGET (NCT05526755), which will evaluate the efficacy and safety of 5 years of adjuvant osimertinib in patients with completely resected EGFRm stage II to IIIB NSCLC. MATERIALS AND METHODS: TARGET is a phase II, multinational, open-label, single-arm study. Adults aged ≥18 years (Taiwan ≥20 years), with resected stage II to IIIB NSCLC are eligible; prior adjuvant chemotherapy is allowed. Eligible patients must have locally confirmed common (exon 19 deletion or L858R) or uncommon (G719X, L861Q, and/or S768I) EGFR-TKI sensitizing mutations, alone or in combination. Patients will receive osimertinib 80 mg once daily for 5 years or until disease recurrence, discontinuation or death. The primary endpoint is investigator-assessed disease-free survival (DFS) at 5 years (common EGFR mutations cohort). Secondary endpoints include: investigator-assessed DFS at 3 and 4 years; overall survival at 3, 4, and 5 years (common EGFR mutations cohort); DFS at 3, 4, and 5 years (uncommon EGFR mutations cohort); safety and tolerability, type of recurrence and CNS metastases (both cohorts). Exploratory endpoints include: tissue/plasma concordance; analysis of circulating molecules in plasma samples using different profiling approaches to detect minimal residual disease; incidence and change over time of incidental pulmonary nodules. RESULTS: TARGET is currently recruiting, and completion is expected in 2029.


Assuntos
Acrilamidas , Compostos de Anilina , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Pirimidinas , Adulto , Humanos , Adolescente , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Receptores ErbB , Antineoplásicos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Mutação/genética
4.
J Cardiovasc Magn Reson ; 25(1): 73, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38044439

RESUMO

BACKGROUND: Electrocardiographic imaging (ECGI) generates electrophysiological (EP) biomarkers while cardiovascular magnetic resonance (CMR) imaging provides data about myocardial structure, function and tissue substrate. Combining this information in one examination is desirable but requires an affordable, reusable, and high-throughput solution. We therefore developed the CMR-ECGI vest and carried out this technical development study to assess its feasibility and repeatability in vivo. METHODS: CMR was prospectively performed at 3T on participants after collecting surface potentials using the locally designed and fabricated 256-lead ECGI vest. Epicardial maps were reconstructed to generate local EP parameters such as activation time (AT), repolarization time (RT) and activation recovery intervals (ARI). 20 intra- and inter-observer and 8 scan re-scan repeatability tests. RESULTS: 77 participants were recruited: 27 young healthy volunteers (HV, 38.9 ± 8.5 years, 35% male) and 50 older persons (77.0 ± 0.1 years, 52% male). CMR-ECGI was achieved in all participants using the same reusable, washable vest without complications. Intra- and inter-observer variability was low (correlation coefficients [rs] across unipolar electrograms = 0.99 and 0.98 respectively) and scan re-scan repeatability was high (rs between 0.81 and 0.93). Compared to young HV, older persons had significantly longer RT (296.8 vs 289.3 ms, p = 0.002), ARI (249.8 vs 235.1 ms, p = 0.002) and local gradients of AT, RT and ARI (0.40 vs 0.34 ms/mm, p = 0,01; 0.92 vs 0.77 ms/mm, p = 0.03; and 1.12 vs 0.92 ms/mm, p = 0.01 respectively). CONCLUSION: Our high-throughput CMR-ECGI solution is feasible and shows good reproducibility in younger and older participants. This new technology is now scalable for high throughput research to provide novel insights into arrhythmogenesis and potentially pave the way for more personalised risk stratification. CLINICAL TRIAL REGISTRATION: Title: Multimorbidity Life-Course Approach to Myocardial Health-A Cardiac Sub-Study of the MRC National Survey of Health and Development (NSHD) (MyoFit46). National Clinical Trials (NCT) number: NCT05455125. URL: https://clinicaltrials.gov/ct2/show/NCT05455125?term=MyoFit&draw=2&rank=1.


Assuntos
Coração , Imageamento por Ressonância Magnética , Idoso , Feminino , Humanos , Masculino , Estudos de Viabilidade , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto , Pessoa de Meia-Idade
5.
Crit Care Resusc ; 25(3): 118-125, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37876374

RESUMO

Introduction: Critically ill patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) are at risk of developing severe arterial hyperoxia, which has been associated with increased mortality. Lower saturation targets in this population may lead to deleterious episodes of severe hypoxia. This manuscript describes the protocol and statistical analysis plan for the Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial. Design: The BLENDER trial is a pragmatic, multicentre, registry-embedded, randomised clinical trial., registered at ClinicalTrials.gov (NCT03841084) and approved by The Alfred Hospital Ethics Committee project ID HREC/50486/Alfred-2019. Participants and setting: Patients supported by VA ECMO for cardiogenic shock or cardiac arrest who are enrolled in the Australian national ECMO registry. Intervention: The study compares a conservative oxygenation strategy (target arterial saturations 92-96%) with a liberal oxygenation strategy (target 97-100%). Main Outcome Measures: The primary outcome is the number of intensive care unit (ICU)-free days for patients alive at day 60. Secondary outcomes include duration of mechanical ventilation, ICU and hospital mortality, the number of hypoxic episodes, neurocognitive outcomes, and health economic analyses. The 300-patient sample size enables us to detect a 3-day difference in ICU-free days at day 60, assuming a mean ICU-free days of 11 days, with a risk of type 1 error of 5% and power of 80%. Data will be analysed according to a predefined analysis plan. Findings will be disseminated in peer-reviewed publications. Conclusions: This paper details the protocol and statistical analysis plan for the BLENDER trial, a registry-embedded, multicentre interventional trial comparing liberal and conservative oxygenation strategies in VA ECMO.

6.
Biomed Mater ; 18(4)2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37220760

RESUMO

Constant matrix remodeling and cellular heterogeneity in cancer are key contributors to its development and can profoundly alter treatment efficacy. Developingin-vitromodels containing relevant features that can recapitulate these aspects of the tumor microenvironment and that are well characterized can circumvent the limitations of conventional 2D cultures and animal models. Automated fabrication methods combined with biomimetic biomaterials have provided the opportunity to create platforms that can potentially incorporate a heterogeneous population of cells in a 3D environment that allows cell-cell and cell-ECM interactions with reproducibility. This study used 3D extrusion bioprinting and a composite bioink containing a reinforced decellularized extracellular matrix (ECM) hydrogel to fabricate a head and neck cancerin-vitromodel. The constituents of this model included fibroblasts and active ECM proteins to represent the stroma, along with HNSCC cells to represent the tumor component. The topographical characterization of the bioink showed a fibrous network with nanometer-sized pores. After cell encapsulation and model fabrication, we observed spheroid development and growth over time with cancer cells in the core and fibroblasts in the periphery. Our model is compatible with matrix metalloproteinase (MMP) quantification techniques and showed significant differences in the presence of MMP-9 and MMP-10 compared to the control groups. This characterized model is proposed as a tool for further translational and drug discovery applications since it provides a biomimetic scenario that allows the study of the tumor microenvironmentin-vitrousing nondestructive longitudinal monitoring over time.


Assuntos
Bioimpressão , Neoplasias , Animais , Alicerces Teciduais , Engenharia Tecidual/métodos , Matriz Extracelular Descelularizada , Reprodutibilidade dos Testes , Matriz Extracelular/metabolismo , Neoplasias/metabolismo , Bioimpressão/métodos , Impressão Tridimensional , Microambiente Tumoral
8.
Nature ; 608(7924): 692-698, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35768016

RESUMO

Single-aperture cavities are a key component of lasers that are instrumental for the amplification and emission of a single light mode. However, the appearance of high-order transverse modes as the size of the cavities increases has frustrated efforts to scale-up cavities while preserving single-mode operation since the invention of the laser six decades ago1-8. A suitable physical mechanism that allows single-mode lasing irrespective of the cavity size-a 'scale invariant' cavity or laser-has not been identified yet. Here we propose and demonstrate experimentally that open-Dirac electromagnetic cavities with linear dispersion-which in our devices are realized by a truncated photonic crystal arranged in a hexagonal pattern-exhibit unconventional scaling of losses in reciprocal space, leading to single-mode lasing that is maintained as the cavity is scaled up in size. The physical origin of this phenomenon lies in the convergence of the complex part of the free spectral range in open-Dirac cavities towards a constant governed by the loss rates of distinct Bloch bands, whereas for common cavities it converges to zero as the size grows, leading to inevitable multimode emission. An unconventional flat-envelope fundamental mode locks all unit cells in the cavity in phase, leading to single-mode lasing. We name such sources Berkeley surface-emitting lasers (BerkSELs) and demonstrate that their far-field corresponds to a topological singularity of charge two, in agreement with our theory. Open-Dirac cavities unlock avenues for light-matter interaction and cavity quantum electrodynamics.

9.
Dermatol Surg ; 48(5): 479-485, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35353755

RESUMO

BACKGROUND: Local recurrence (LR) rates of dermatofibrosarcoma protuberans (DFSP) treated with different surgical modalities are unknown. OBJECTIVE: To evaluate the differences in LR rates of DFSP treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS: Pertinent studies of DFSP treated with either WLE or MMS were identified through a search of multiple databases, including Ovid MEDLINE (1946-2018), Embase (1988-2018), Web of Science (1975-2018), and Scopus (1970-2018). Comparative 2-arm and noncomparative single-arm studies were assessed through meta-analyses. RESULTS: Of the 517 studies identified, 88 met inclusion criteria (12 comparative studies; 76 single-arm studies). In the 12 comparative studies, 352 patients with DFSP underwent MMS and 777 patients with DFSP underwent WLE. The LR rate was 1.7% after MMS and 3.7% after WLE (odds ratio, 1.549; 95% CI, 0.710-3.381; p = .27). In the 76 noncomparative studies, 980 patients underwent MMS (LR rate, 1.5%; 95% CI, 0.9%-2.1%; p < .001), and 2,215 patients underwent WLE (LR rate, 9.4%; 95% CI, 7.5%-11.3%; p < .001). CONCLUSION: The LR rate of DFSP in patients treated with MMS is lower than in patients treated with WLE. Because of high rates of postoperative DFSP LR, MMS should be strongly considered when available.


Assuntos
Dermatofibrossarcoma , Neoplasias Cutâneas , Bases de Dados Factuais , Dermatofibrossarcoma/cirurgia , Humanos , Cirurgia de Mohs/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Neoplasias Cutâneas/cirurgia
10.
Front Psychol ; 13: 784471, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35282217

RESUMO

Procrastination is a chronic and widespread problem; however, emerging work raises questions regarding the strength of the relationship between self-reported procrastination and behavioral measures of task engagement. This study assessed the internal reliability, concurrent validity, predictive validity, and psychometric properties of 10 self-report procrastination assessments using responses collected from 242 students. Participants' scores on each self-report instrument were compared to each other using correlations and cluster analysis. Lasso estimation was used to test the self-report scores' ability to predict two behavioral measures of delay (days to study completion; pacing style). The self-report instruments exhibited strong internal reliability and moderate levels of concurrent validity. Some self-report measures were predictive of days to study completion. No self-report measures were predictive of deadline action pacing, the pacing style most commonly associated with procrastination. Many of the self-report measures of procrastination exhibited poor fit. These results suggest that researchers should exercise caution in selecting self-report measures and that further study is necessary to determine the factors that drive misalignment between self-reports and behavioral measures of delay.

11.
Otolaryngol Clin North Am ; 54(5): 839-852, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34538358

RESUMO

The evaluation of dizziness as a chief complaint can be exceptionally challenging to otolaryngologists. The critical piece in evaluating dizzy patients is to have a plan for how to screen and schedule, how to gather data, and to develop a workflow for testing that allows clinical efficiency. This article provides an overview of evidence-based practices on how to screen dizzy patients before being scheduled, how to efficiently move patients through the otolaryngologist's clinic, and strategies for managing a dizzy practice.


Assuntos
Tontura , Vertigem , Tontura/diagnóstico , Tontura/etiologia , Tontura/terapia , Humanos , Vertigem/diagnóstico , Vertigem/terapia
12.
Am J Hematol ; 96(11): 1450-1460, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34390506

RESUMO

Germline predisposition syndromes (GPS) result from constitutional aberrations in tumor suppressive and homeostatic genes, increasing risk for neoplasia in affected kindred. In this study, we present clinical and genomic data on 144 Mayo Clinic patients with GPS; 59 evaluated prospectively using an algorithm-based diagnostic approach in the setting of a dedicated GPS/ inherited bone marrow failure syndrome (IBMFS) clinic. Seventy-two (50%) patients had IBMFS (telomere biology disorders-32,Fanconi anemia-18, Diamond Blackfan Anemia - 11, congenital neutropenia-5, Schwachman-Diamond Syndrome-5 and Bloom Syndrome-1), 27 (19%) had GPS with antecedent thrombocytopenia (RUNX1-FPD-15, ANKRD26-6, ETV6-2, GATA1-1, MPL-3), 28 (19%) had GPS without antecedent thrombocytopenia (GATA2 haploinsufficiency-16, DDX41-10, CBL-1 and CEBPA-1) and 17 (12%) had general cancer predisposition syndromes (ataxia telangiectasia-7, heterozygous ATM variants-3, CHEK2-2, TP53-2, CDK2NA-1, NF1-1 and Nijmegen Breakage Syndrome-1). Homozygous and heterozygous ATM pathogenic variants were exclusively associated with lymphoproliferative disorders (LPD), while DDX41 GPS was associated with LPD and myeloid neoplasms. The use of somatic NGS-testing identified clonal evolution in GPS patients, with ASXL1, RAS pathway genes, SRSF2 and TET2 being most frequently mutated. Fifty-two (91%) of 59 prospectively identified GPS patients had a change in their management approach, including additional GPS-related screening in 42 (71%), referral for allogenic HSCT workup and screening of related donors in 16 (27%), medication initiation and selection of specific conditioning regimens in 14 (24%), and genetic counseling with specific intent of fertility preservation and preconceptual counseling in 10 (17%) patients; highlighting the importance of dedicated GPS screening, detection and management programs for patients with hematological neoplasms.


Assuntos
Evolução Clonal , Neoplasias Hematológicas/genética , Adolescente , Adulto , Idoso , Anemia de Diamond-Blackfan/genética , Criança , Pré-Escolar , Síndrome Congênita de Insuficiência da Medula Óssea/genética , Anemia de Fanconi/genética , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Mol Neurodegener ; 15(1): 70, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213497

RESUMO

INTRODUCTION: The neurovascular unit (NVU) - the interaction between the neurons and the cerebrovasculature - is increasingly important to interrogate through human-based experimental models. Although advanced models of cerebral capillaries have been developed in the last decade, there is currently no in vitro 3-dimensional (3D) perfusible model of the human cortical arterial NVU. METHOD: We used a tissue-engineering technique to develop a scaffold-directed, perfusible, 3D human NVU that is cultured in native-like flow conditions that mimics the anatomy and physiology of cortical penetrating arteries. RESULTS: This system, composed of primary human vascular cells (endothelial cells, smooth muscle cells and astrocytes) and induced pluripotent stem cell (iPSC) derived neurons, demonstrates a physiological multilayer organization of the involved cell types. It reproduces key characteristics of cortical neurons and astrocytes and enables formation of a selective and functional endothelial barrier. We provide proof-of-principle data showing that this in vitro human arterial NVU may be suitable to study neurovascular components of neurodegenerative diseases such as Alzheimer's disease (AD), as endogenously produced phosphorylated tau and beta-amyloid accumulate in the model over time. Finally, neuronal and glial fluid biomarkers relevant to neurodegenerative diseases are measurable in our arterial NVU model. CONCLUSION: This model is a suitable research tool to investigate arterial NVU functions in healthy and disease states. Further, the design of the platform allows culture under native-like flow conditions for extended periods of time and yields sufficient tissue and media for downstream immunohistochemistry and biochemistry analyses.


Assuntos
Artérias/metabolismo , Astrócitos/metabolismo , Células Endoteliais/metabolismo , Doenças Neurodegenerativas/metabolismo , Doença de Alzheimer/metabolismo , Artérias/fisiopatologia , Barreira Hematoencefálica/metabolismo , Técnicas de Cocultura , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Doenças Neurodegenerativas/patologia , Neurônios/metabolismo
15.
Int J Hosp Manag ; 90: 102605, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32834350

RESUMO

Utilizing a sample of 192 hospitality firms, this study investigates the moderating role of a dynamic environment, coupled with business and social networking ties and technology resources, on the relationship between entrepreneurial orientation and organizational performance in hospitality firms. This research is novel in that we adopt business network ties and social network ties as two moderating variables along with technology resources between entrepreneurial orientation and business performance, providing evidence on a topic which has received little attention to date. The results posit that in an uncertain, dynamic environment a higher level of risk and entrepreneurial orientation benefit business performance especially when coupled with strong business and social networks.

16.
Clin Pharmacol Ther ; 108(3): 447-457, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32569424

RESUMO

A 2-day meeting was held by members of the UK Quantitative Systems Pharmacology Network () in November 2018 on the topic of Translational Challenges in Oncology. Participants from a wide range of backgrounds were invited to discuss current and emerging modeling applications in nonclinical and clinical drug development, and to identify areas for improvement. This resulting perspective explores opportunities for impactful quantitative pharmacology approaches. Four key themes arose from the presentations and discussions that were held, leading to the following recommendations: Evaluate the predictivity and reproducibility of animal cancer models through precompetitive collaboration. Apply mechanism of action (MoA) based mechanistic models derived from nonclinical data to clinical trial data. Apply MoA reflective models across trial data sets to more robustly quantify the natural history of disease and response to differing interventions. Quantify more robustly the dose and concentration dependence of adverse events through mathematical modelling techniques and modified trial design.


Assuntos
Antineoplásicos/uso terapêutico , Desenvolvimento de Medicamentos , Oncologia , Modelos Teóricos , Neoplasias Experimentais/tratamento farmacológico , Pesquisa Translacional Biomédica , Animais , Antineoplásicos/efeitos adversos , Linhagem Celular Tumoral , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Determinação de Ponto Final , Humanos , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Projetos de Pesquisa , Critérios de Avaliação de Resposta em Tumores Sólidos , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Mol Neurodegener ; 15(1): 23, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32213187

RESUMO

BACKGROUND: Several lines of evidence suggest that high-density lipoprotein (HDL) reduces Alzheimer's disease (AD) risk by decreasing vascular beta-amyloid (Aß) deposition and inflammation, however, the mechanisms by which HDL improve cerebrovascular functions relevant to AD remain poorly understood. METHODS: Here we use a human bioengineered model of cerebral amyloid angiopathy (CAA) to define several mechanisms by which HDL reduces Aß deposition within the vasculature and attenuates endothelial inflammation as measured by monocyte binding. RESULTS: We demonstrate that HDL reduces vascular Aß accumulation independently of its principal binding protein, scavenger receptor (SR)-BI, in contrast to the SR-BI-dependent mechanism by which HDL prevents Aß-induced vascular inflammation. We describe multiple novel mechanisms by which HDL acts to reduce CAA, namely: i) altering Aß binding to collagen-I, ii) forming a complex with Aß that maintains its solubility, iii) lowering collagen-I protein levels produced by smooth-muscle cells (SMC), and iv) attenuating Aß uptake into SMC that associates with reduced low density lipoprotein related protein 1 (LRP1) levels. Furthermore, we show that HDL particles enriched in apolipoprotein (apo)E appear to be the major drivers of these effects, providing new insights into the peripheral role of apoE in AD, in particular, the fraction of HDL that contains apoE. CONCLUSION: The findings in this study identify new mechanisms by which circulating HDL, particularly HDL particles enriched in apoE, may provide vascular resilience to Aß and shed new light on a potential role of peripherally-acting apoE in AD.


Assuntos
Apolipoproteínas E/metabolismo , Angiopatia Amiloide Cerebral/metabolismo , HDL-Colesterol/metabolismo , Células Cultivadas , Humanos , Técnicas de Cultura de Órgãos , Engenharia Tecidual
18.
Injury ; 51(1): 10-14, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31679829

RESUMO

OBJECTIVE: To quantify the pharmacodynamic (PD) activity of daily subcutaneous (SC) enoxaparin as venous thromboembolism (VTE) prophylaxis in high-risk trauma patients admitted to the intensive care unit (ICU). METHODS: This was a prospective observational PD study conducted in the ICU of a state-wide major trauma referral centre. The study cohort included adult patients admitted to the ICU with a high risk of VTE, as defined by at least one of the following: age > 40 years, prior VTE, spinal cord injury (SCI), traumatic brain injury (TBI), major venous injury, pelvic fractures, spinal fractures requiring treatment, severe lower limb injuries, and major surgery >2 h in duration. Standard prophylactic enoxaparin dosing was 40 mg SC daily, unless amended by the treating clinician. Plasma anti-Xa activity was measured approximately 60 min before dosing (trough activity), and at 3-5 h after dosing (peak activity). Target peak and trough activity were defined as >0.2 IU/mL and >0.1 IU/mL respectively. Clinical data including the development of VTE and haemorrhagic complications were collected. RESULTS: Twenty-five patients were enrolled. Median [IQR] age, weight, and plasma creatinine were 59 years [36,70], 85 kg [76.5,93.5] and 70µmol/L [60.5,109] respectively. Median APACHE III and Injury Severity Score were 54 [42.5,66.5] and 27 [17,34] respectively. Thirteen patients suffered a TBI, in 12 cases surgery extended beyond two hours, and five patients had spinal fractures requiring treatment. Twenty-two patients received enoxaparin 40 mg SC daily, two 60 mg, and one 20 mg. Median peak and trough anti-Xa activity was 0.21 IU/mL [0.125,0.25] and 0.01 IU/mL [0,0.05] respectively. Twelve (12/25; 48%) patients had low peak activity ≤0.2 IU/mL. Twenty-one (21/23; 91%) patients had low trough activity (≤0.1 IU/mL) and in six (6/23; 26%) cases, these were undetectable. Eight (8/25; 32%) patients had documented VTE of whom seven had low trough activity. There were no major haemorrhagic complications. CONCLUSIONS: In a cohort of high risk critically ill trauma patients receiving daily SC enoxaparin as VTE chemoprophylaxis, measured peak and trough plasma anti-Xa activity was inadequate in a significant proportion. On this basis, further systematic investigation concerning dose optimisation in this patient population appears warranted.


Assuntos
Enoxaparina/administração & dosagem , Unidades de Terapia Intensiva , Tromboembolia Venosa/prevenção & controle , Ferimentos e Lesões/complicações , Adulto , Idoso , Anticoagulantes/administração & dosagem , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tromboembolia Venosa/etiologia
19.
Musculoskeletal Care ; 17(3): 170-197, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31373435

RESUMO

OBJECTIVE: A systematic review and meta-analysis of controlled trials was carried out to examine the effect of behavioural counselling on determinants of behaviour change in adults with chronic, painful musculoskeletal conditions. METHODS: Seven databases were searched up to January 2019. Two reviewers independently screened title/abstracts and full texts. Eligible trials included those including participants over 18 years of age with a chronic, painful musculoskeletal condition, a measurement of at least one behavioural determinant and lifestyle behaviour, and where behavioural counselling was the distinguishing intervention. Two reviewers independently extracted data and assessed for risk of bias using the Cochrane Risk of Bias Tool. Meta-analyses were conducted, using standardized mean differences and 95% confidence intervals (CIs) when at least two trials examined the same outcome. The quality of the evidence was evaluated using the Grades of Recommendation, Assessment, Development and Evaluation approach. RESULTS: Fourteen unique trials, reported in 16 publications, were included. Low-quality evidence showed that behavioural counselling has a small effect on increasing self-reported physical activity (standardized mean difference 0.26; 95% CI 0.00, 0.53). Very-low-quality evidence showed that behavioural counselling has a moderate effect on self-efficacy related to physical activity (standardized mean difference 0.69; 95% CI 0.19, 1.18). Low-quality evidence suggested that behavioural counselling has no effect on symptoms of depression and anxiety. CONCLUSIONS: Behavioural counselling may help to increase self-reported physical activity levels in adults with chronic painful musculoskeletal conditions. Self-efficacy may be a behavioural determinant in an underlying causal pathway explaining positive lifestyle change.


Assuntos
Comportamentos Relacionados com a Saúde , Doenças Musculoesqueléticas/psicologia , Doença Crônica/psicologia , Humanos , Entrevista Motivacional , Comportamento de Redução do Risco
20.
Pediatr Rheumatol Online J ; 17(1): 5, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736800

RESUMO

BACKGROUND: Of 37 pediatric rheumatology fellowship training programs in the United States, many have three or fewer fellows at a given time, making large-scale assessment of fellow performance difficult. An objective structured clinical examination (OSCE) is a scenario-based simulation method that assesses individual performance, thus indirectly measuring training program effectiveness. This study describes the development and implementation of two national pediatric rheumatology OSCEs and methods used for programmatic improvement. METHODS: OSCEs for pediatric rheumatology fellows were held in 2009 and 2011 during national rheumatology meetings using scenarios and assessment forms originally developed by a fellowship program director. The seven scenarios tested medical knowledge, physical exam and interpersonal skills. Pediatric rheumatologist evaluators assessed fellows' performance using checklists and gave immediate feedback. Program directors were sent summaries of their fellows' performances. Fellows evaluated the OSCE, providing organizational and scenario improvement suggestions. Programmatic changes to the 2011 OSCE were based on 2009 performance data and program evaluation feedback. RESULTS: Twenty-two fellows participated in 2009 and 19 in 2011. Performance scores in similar scenarios did not change considerably over the two iterations. In 2009, 85.7% of participants reported desire to change clinical behavior. Assessors' 2009 program evaluation data prompted changes in rating scales and removal of invalid or unreliable assessments. Negative evaluation data about individual stations decreased from 60% in 2009 to 15.4% in 2011. Fellows' ratings of the experience's overall value were similar in 2009 and 2011. The average experience ratings were lower among fellows who proposed scenario-specific improvements and higher among those who recommended organizational improvements. CONCLUSIONS: The 2011 examination exhibited programmatic improvement via reduction in fellows' scenario-specific negative feedback. Fellows' overall satisfaction did not change. Further work in scenario selection, assessment validation and inter-rater reliability will improve future pediatric rheumatology OSCEs.


Assuntos
Educação de Pós-Graduação em Medicina/métodos , Avaliação Educacional/métodos , Avaliação de Programas e Projetos de Saúde/métodos , Reumatologia/educação , Competência Clínica , Bolsas de Estudo/métodos , Humanos , Simulação de Paciente , Reprodutibilidade dos Testes , Estados Unidos
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