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1.
Anaesthesia ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39367574

RESUMO

BACKGROUND: Skilled facilitators are essential to drive effective simulation training in healthcare. Competency-based frameworks support the development of facilitation skills but, to our knowledge, there are no frameworks that specifically address context-sensitive priorities developed with practitioners working in low-resource settings. METHODS: We aimed to develop a core competency framework for healthcare simulation facilitation in low-resource settings using a modified Delphi process. We drew on the domain expertise of members of the Vital Anaesthesia Simulation Training Community of Practice, with the study guided by a four-member steering group experienced in the conduct of simulation in low-resource settings. In survey round 1, participants (n = 54) were presented with an initial competency set derived from a previous qualitative study and co-created a set of 57 competencies for effective simulation facilitation in low-resource settings. In survey round 2, participants (n = 52) ranked competencies by relevance into three performance categories: techniques; artistry; and values. In survey round 3, participants (n = 50) ranked competencies on their importance. The steering group collated results and presented a draft core competency framework. In survey round 4, participants (n = 50) voted with 98% agreement that this framework represented the most relevant and important competencies for effective facilitation of simulation sessions in low-resource settings. RESULTS: The final 32-item framework encompasses core competencies found in existing standards and includes important new concepts such as demonstration of cultural sensitivity; humility; ability to recognise and respond to potential language barriers; facilitation team collaboration; awareness of logistics; and contingency planning. DISCUSSION: This competency-based framework highlights specific practices required for effective simulation facilitation in low-resource settings. Further work is required to refine and validate this tool to train simulation facilitators to deliver effective training to improve patient safety.

2.
Age Ageing ; 53(9)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39238124

RESUMO

BACKGROUND: Hip fracture is a common and serious traumatic injury for older adults characterised by poor outcomes. OBJECTIVE: This systematic review aimed to synthesise qualitative evidence about the psychosocial impact of hip fracture on the people who sustain these injuries. METHODS: Five databases were searched for qualitative studies reporting on the psychosocial impact of hip fracture, supplemented by reference list checking and citation tracking. Data were synthesised inductively and confidence in findings reported using the Confidence in the Evidence from Reviews of Qualitative research approach, taking account of methodological quality, coherence, relevance and adequacy. RESULTS: Fifty-seven studies were included. Data were collected during the peri-operative period to >12 months post fracture from 919 participants with hip fracture (median age > 70 years in all but 3 studies), 130 carers and 297 clinicians. Hip fracture is a life altering event characterised by a sense of loss, prolonged negative emotions and fear of the future, exacerbated by negative attitudes of family, friends and clinicians. For some people after hip fracture there is, with time, acceptance of a new reality of not being able to do all the things they used to do. There was moderate to high confidence in these findings. CONCLUSIONS: Hip fracture is a life altering event. Many people experience profound and prolonged psychosocial distress following a hip fracture, within a context of negative societal attitudes. Assessment and management of psychosocial distress during rehabilitation may improve outcomes for people after hip fracture.


Assuntos
Fraturas do Quadril , Pesquisa Qualitativa , Humanos , Fraturas do Quadril/psicologia , Fraturas do Quadril/reabilitação , Idoso , Feminino , Masculino , Idoso de 80 Anos ou mais , Qualidade de Vida , Acontecimentos que Mudam a Vida
3.
Artigo em Inglês | MEDLINE | ID: mdl-39343707

RESUMO

BACKGROUND: Hip-related pain (HRP) affects young to middle-aged active adults and impacts physical activity, finances and quality of life. HRP includes conditions like femoroacetabular impingement syndrome and labral tears. Lateral hip muscle dysfunction and atrophy in HRP are more pronounced in advanced hip pathology, with limited evidence in younger populations. While MRI use for assessing hip muscle morphology is increasing, with automated deep-learning techniques showing promise, studies assessing their accuracy are limited. Therefore, we aimed to compare hip intramuscular fat infiltrate (MFI) and muscle volume, in individuals with and without HRP as well as assess the reliability and accuracy of automated machine-learning segmentations compared with human-generated segmentation. METHODS: This cross-sectional study included sub-elite/amateur football players (Australian football and soccer) with a greater than 6-month history of HRP [n = 180, average age 28.32, (standard deviation 5.88) years, 19% female] and a control group of sub-elite/amateur football players without pain [n = 48, 28.89 (6.22) years, 29% female]. Muscle volume and MFI of gluteus maximus, medius, minimis and tensor fascia latae were assessed using MRI. Associations between muscle volume and group were explored using linear regression models, controlling for body mass index, age, sport and sex. A convolutional neural network (CNN) machine-learning approach was compared with human-performed muscle segmentations in a subset of participants (n = 52) using intraclass correlation coefficients and Sorensen-Dice index. RESULTS: When considering adjusted estimates of muscle volume, there were significant differences observed between groups for gluteus medius (adjusted mean difference 23 858 mm3 [95% confidence interval 7563, 40 137]; p = 0.004) and tensor fascia latae (6660 mm3 [2440, 13 075]; p = 0.042). No differences were observed between groups for gluteus maximus (18 265 mm3 [-21 209, 50 782]; p = 0.419) or minimus (3893 mm3 [-2209, 9996]; p = 0.21). The CNN was trained for 30 000 iterations and assessed its accuracy and reliability on an independent testing dataset, achieving high segmentation accuracy (mean Sorenson-Dice index >0.900) and excellent muscle volume and MFI reliability (ICC2,1 > 0.900). The CNN outperformed manual raters, who had slightly lower interrater accuracy (Sorensen-Dice index >0.800) and reliability (ICC2,1 > 0.800). CONCLUSIONS: The increased muscle volumes in the symptomatic group compared with controls could be associated with increased myofibrillar size, sarcoplasmic hypertrophy or both. These changes may facilitate greater muscular efficiency for a given load, enabling the athlete to maintain their normal level of function. In addition, the CNNs for muscle segmentation was more efficient and demonstrated excellent reliability in comparison to manual segmentations.

4.
bioRxiv ; 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39345541

RESUMO

Pre-cancerous lung lesions are commonly initiated by activating mutations in the RAS pathway, but do not transition to lung adenocarcinomas (LUAD) without additional oncogenic signals. Here, we show that expression of the extracellular matrix protein Tenascin-C (TNC) is increased in and promotes the earliest stages of LUAD development in oncogenic KRAS-driven lung cancer mouse models and in human LUAD. TNC is initially expressed by fibroblasts and its expression extends to tumor cells as the tumor becomes invasive. Genetic deletion of TNC in the mouse models reduces early tumor burden and high-grade pathology and diminishes tumor cell proliferation, invasion, and focal adhesion kinase (FAK) activity. TNC stimulates cultured LUAD tumor cell proliferation and migration through engagement of αv-containing integrins and subsequent FAK activation. Intringuingly, lung injury causes sustained TNC accumulation in mouse lungs, suggesting injury can induce additional TNC signaling for early tumor cell transition to invasive LUAD. Biospecimens from patients with stage I/II LUAD show TNC in regions of FAK activation and an association of TNC with tumor recurrence after primary tumor resection. These results suggest that exogenous insults that elevate TNC in the lung parenchyma interact with tumor-initiating mutations to drive early LUAD progression and local recurrence.

5.
Physiother Res Int ; 29(4): e2118, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39132922

RESUMO

BACKGROUND: Hip osteoarthritis (OA) is a prevalent and burdensome condition that leads to impaired quality of life and a substantial economic burden. Encouraging physical activity, particularly walking, is crucial for OA management, but many individuals with hip OA fail to meet recommended activity levels. Prefabricated contoured foot orthoses have shown promise in improving hip muscle efficiency during walking in laboratory settings, but their real-world feasibility and efficacy remain uncertain. OBJECTIVE: The aim of this study was to assess the feasibility of conducting a fully powered randomised controlled trial (RCT) to evaluate the effectiveness of prefabricated contoured foot orthoses, prescribed via telehealth, in people with hip OA. METHODS: This feasibility trial randomised 27 participants with hip OA into two groups: prefabricated contoured foot orthoses or flat shoe inserts. Feasibility outcomes were assessed, including recruitment rate, adherence, logbook completion, and dropout rate. Patient-reported outcomes and accelerometer-measured physical activity were collected as secondary outcomes. RESULTS: While the recruitment rate was low (0.88 people/week), adherence to the intervention (59%), logbook completion (93%), and dropout rates (7%) met or exceeded our predefined feasibility parameters. Participants found the intervention acceptable, and practicality was demonstrated with minor adverse events. Preliminary efficacy testing indicated that prefabricated contoured foot orthoses positively affected physical activity (adjusted mean difference = 2590 [260 to 4920] steps/day), with comparable outcomes for hip-related quality of life and pain. CONCLUSION: This trial supports proceeding to a fully powered RCT to assess the effect of teleheath prescribed prefabricated contoured foot orthoses on physical activity in people with hip OA. STUDY REGISTRATION NUMBER: National Institutes of Health Trial Registry (NCT05138380).


Assuntos
Estudos de Viabilidade , Órtoses do Pé , Osteoartrite do Quadril , Humanos , Osteoartrite do Quadril/reabilitação , Osteoartrite do Quadril/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Qualidade de Vida , Exercício Físico/fisiologia , Medidas de Resultados Relatados pelo Paciente , Desenho de Equipamento , Caminhada/fisiologia , Cooperação do Paciente , Manejo da Dor/métodos , Resultado do Tratamento , Telemedicina
6.
Cancer Res ; 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39207369

RESUMO

The acquisition of invasive properties is a prerequisite for tumor progression and metastasis. Molecular subtypes of KRAS-driven lung cancer exhibit distinct modes of invasion that contribute to unique growth properties and therapeutic susceptibilities. Despite this, pre-clinical strategies designed to exploit growth within the context of invasion are lacking. To address this, we designed an experimental system to screen for targetable signaling pathways linked to active early 3D invasion phenotypes in different molecular subtypes of KRAS-driven lung adenocarcinoma (LUAD). Combined live-cell imaging of human bronchial epithelial cells in a 3D invasion matrix and transcriptomic profiling identified mutant LKB1-specific upregulation of BMP6. LKB1 loss increased BMP6 signaling, which induced the canonical iron regulatory hormone hepcidin. Intact LKB1 was necessary to maintain BMP6 signaling homeostasis and restrict ALK2/BMP6-fueled growth. Pre-clinical studies in a Kras/Lkb1-mutant syngeneic mouse model and in a xenograft model showed potent growth suppression by inhibiting the ALK2/BMP6 signaling axis with single agent inhibitors that are currently in clinical trials. Lastly, BMP6 expression was elevated in LKB1-mutant early-stage lung cancer patient tumors. These results are consistent with a model where LKB1 acts as a 'brake' to iron regulated growth and suggest that ALK2 inhibition can be used for patients with LKB1-mutant tumors.

7.
Health Expect ; 27(4): e14182, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-39152538

RESUMO

BACKGROUND: Back pain is a huge global problem. For some people, the pain is so severe that they feel the need to present to an emergency department (ED). Our aim was to explore patient and staff perspectives for the development of a digital care pathway (DCP) for people with back pain who have presented to ED, including acceptability, barriers and facilitators. METHODS: We used a descriptive phenomenology approach using semi-structured interviews with patient and staff participants at a tertiary hospital. Interviews were transcribed and data codes were developed using inductive thematic analysis. Themes were discussed between researchers until consensus was achieved. RESULTS: A total of 16 interviews were carried out, half of which involved patient participants. We identified three major themes: (i) expectations and experiences of staff and patients with low back pain in ED; (ii) a digital care pathway can empower patients and support clinicians in providing care; and (iii) acceptability, barriers, facilitators and recommendations of engaging with a DCP to track the trajectory of back pain. Each theme was further categorised into subthemes. CONCLUSION: Introducing a DCP was perceived as acceptable and beneficial by patients and staff. Both groups were aware of the potential participant burden if surveys were too long. Introducing a DCP could be a valuable adjunct to current management care models, providing a standardised source of education with the potential for individualised tracking and monitoring. The design and development of a DCP will need to consider reported facilitators and address perceived barriers for engagement. PATIENT OR PUBLIC CONTRIBUTION: This project sought insights from patients and staff about a digital care pathway. This forms the first step of patient and consumer consultation before implementing a digital care pathway. All consumers were offered the opportunity to review their responses and our interpretation.


Assuntos
Serviço Hospitalar de Emergência , Entrevistas como Assunto , Dor Lombar , Pesquisa Qualitativa , Humanos , Dor Lombar/terapia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Procedimentos Clínicos , Atitude do Pessoal de Saúde , Idoso
8.
Sci Adv ; 10(31): eadn9815, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093976

RESUMO

Memories of events are linked to the contexts in which they were encoded. This contextual linking ensures enhanced access to those memories that are most relevant to the context at hand, including specific associations that were previously learned in that context. This principle, referred to as encoding specificity, predicts that context-specific neural states should bias retrieval of particular associations over others, potentially allowing for the disambiguation of retrieval cues that may have multiple associations or meanings. Using a context-odor paired associate learning paradigm in mice, here, we show that chemogenetic manipulation of dentate gyrus ensembles corresponding to specific contexts reinstates context-specific neural states in downstream CA1 and biases retrieval toward context-specific associations.


Assuntos
Giro Denteado , Animais , Giro Denteado/fisiologia , Camundongos , Memória/fisiologia , Masculino , Rememoração Mental/fisiologia , Neurônios/fisiologia , Camundongos Endogâmicos C57BL
9.
Endocr Relat Cancer ; 31(10)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39133175

RESUMO

Phaeochromocytomas and paragangliomas (collectively termed PPGL) are rare yet highly heritable neuroendocrine tumours, with over one-third of cases associated with germline pathogenic variants (PVs) in numerous genes. PVs in the succinate dehydrogenase subunit-A gene (SDHA) were initially implicated in hereditary PPGL in 2010, and SDHA has since become an important susceptibility gene accounting for up to 2.8% of cases. However, it remains poorly understood, particularly regarding the clinical nature of SDHA PPGL, rates of recurrence and metastasis, and the nature of metastatic disease. We present a narrative review of SDHA-related PPGL, covering pathophysiology, relevance to current clinical practice, and considerations for clinical genetics. We analyse a pool of 107 previously reported cases of SDHA-associated PPGL to highlight the spectrum of SDHA-related PPGL. Our analysis demonstrates that SDHA PPGL occurs across a wide age range (11-81 years) and affects men and women equally. SDHA PPGL typically presents as single tumours (91%), usually occurring in the head and neck (46%) or abdomen (43%, including 15% with phaeochromocytomas). Metastatic disease was reported in 25.5% of cases, with bone (82%) and lymph nodes (71%) being the most common sites of metastasis, often identified many years after the initial diagnosis. A family history of SDHA-related neoplasia was rare, reported in only 4% of cases. Understanding the clinical nature and risks associated with SDHA PVs is essential for facilitating the optimal management of patients and their families.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/genética , Feocromocitoma/terapia , Feocromocitoma/patologia , Paraganglioma/genética , Paraganglioma/terapia , Paraganglioma/patologia , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/terapia , Neoplasias das Glândulas Suprarrenais/patologia , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Idoso , Adolescente , Criança , Adulto Jovem , Complexo II de Transporte de Elétrons/genética , Idoso de 80 Anos ou mais
10.
Cureus ; 16(6): e62376, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39006647

RESUMO

Background Recent research has suggested a role for mindfulness-based therapy for patients with chronic medical conditions, but there is limited data on pelvic pain. We aim to determine if mindfulness improves patient-reported outcomes in pelvic pain and to determine the feasibility of implementation of this program. Methodology This is a pilot feasibility trial consisting of women with chronic pelvic pain at a single academic tertiary referral clinic. A convenience sample of 15 subjects was enrolled. Subjects were scheduled for three 60-minute virtual mind-body sessions with a certified counselor. Baseline scores were obtained using the Patient-Reported Outcomes Measurement Information System-Computer Adaptive Testing (PROMIS-CAT) platform. They were repeated three months and six months after enrollment. Descriptive statistics were performed. Results A total of 15 patients were enrolled in the study. Among the 13 patients who completed the three-month PROMIS-CAT scores, seven had a clinically significant 5-point improvement in sleep disturbance T-score. At least a 5-point improvement in fatigue, pain interference, and ability to participate in social roles and activities T-scores were observed in six patients each. There was a 40% dropout rate. Conclusions A formal mind-body counseling program can support patients with chronic pelvic pain. Our trial demonstrated the feasibility of establishing a program and modest improvement in patient-reported quality of life.

11.
Anesth Analg ; 139(2): 375-384, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39008977

RESUMO

BACKGROUND: Burnout, depression, and anxiety are increasingly recognized as common among health care providers. Risks for these conditions are exacerbated in low-resource settings by excessive workload, high disease burden, resource shortage, and stigma against mental health issues. Based on discussions and requests to learn more about burnout during the Vital Anaesthesia Simulation Training (VAST), our team developed VAST Wellbeing, a 1-day course for health care providers in low-resource settings to recognize and mitigate burnout and to promote personal and professional well-being. METHODS: This mixed-methods study used quantitative pre- and postcourse surveys using validated mental health measures and qualitative semistructured interviews to explore participants' experience of VAST Wellbeing during and after the course. Quantitative outcomes included burnout and professional fulfillment as measured by the Professional Fulfillment Index and general well-being as measured by the Warwick-Edinburgh Mental Wellbeing Scale. RESULTS: Twenty-six participants from 9 countries completed the study. In the immediate postcourse survey, study participants rated the course overall as "very good" (60.7%) and "excellent" (28.6%). Quantitative analysis showed no statistical differences in levels of work exhaustion, interpersonal disengagement, burnout, professional fulfillment, or general mental well-being 2 months after the course. Five themes on the impact of VAST Wellbeing were identified during qualitative analysis: (1) raising awareness, breaking taboos; (2) not feeling alone; (3) permission and capacity for personal well-being; (4) workplace empowerment; and (5) VAST Wellbeing was relevant, authentic, and needed. CONCLUSIONS: Causes of burnout are complex and multidimensional. VAST Wellbeing did not change measures of burnout and fulfillment 2 months postcourse but did have a meaningful impact by raising awareness, reducing stigma, fostering connection, providing skills to prioritize personal well-being, and empowering people to seek workplace change.


Assuntos
Esgotamento Profissional , Saúde Mental , Humanos , Esgotamento Profissional/psicologia , Esgotamento Profissional/prevenção & controle , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Países em Desenvolvimento , Recursos em Saúde , Anestesiologistas/psicologia , Estudos de Coortes , Anestesiologia/educação , Saúde Ocupacional , Carga de Trabalho/psicologia , Inquéritos e Questionários , Satisfação no Emprego
12.
J Emerg Nurs ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980247

RESUMO

OBJECTIVES: Back pain is a prevalent condition that affects 1 in 6 Australians at any time, with high associated health care costs. To date, there is limited information relating to symptom severity and recovery trajectory in people with back pain who present to the emergency department for care. A digital care pathway (DCP) can track patient outcomes following presentation with back pain. The primary aim of this protocol is to outline the co-development, implementation, and evaluation of a DCP for back pain patients who present to the emergency department. METHODS: The primary aim will be addressed in 3 overlapping phases: Phase 1 (co-design) will include interviews with back pain patients and health care professionals from the Northern Hospital Emergency Department. Interview findings will inform education resources featured on the DCP and establish questionnaire content and frequency acceptability. Phase 2 (implementation) will include the rollout of the DCP and tracking of patient-reported outcome measures, which will be collected over 12 weeks. Phase 3 (evaluation) will include interviews with a subset of back pain patients who have participated in Phase 2 to evaluate the acceptability of the DCP and the barriers and facilitators of using the DCP. ETHICS AND DISSEMINATION: This project has been approved via the National Health and Medical Research Council of Australia's National Mutual Acceptance Scheme by St Vincent's Hospital Human Ethics Committee (2022/PID06476), La Trobe University Research Governance (HEC#206/22), and Northern Health Research Governance (NH-2023-372687). We plan to publish the findings in a peer-reviewed journal and present them at conferences.

13.
J Cardiovasc Dev Dis ; 11(7)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39057647

RESUMO

BACKGROUND: The choice of prosthesis for aortic valve replacement (AVR) remains challenging. The risk of anticoagulation complications vs. the risk of aortic valve reintervention should be weighed. This study compared the outcomes of bioprosthetic vs. mechanical AVR in patients older and younger than 50. METHODS: This retrospective study was conducted from 2009 to 2019 and involved 292 adult patients who underwent isolated AVR. The patients were divided according to their age (above 50 years or 50 years and younger) and the type of valves used in each age group. The outcomes of bioprosthetic valves (Groups 1a (>50 years) and 1b (≤50 years)) were compared with those of mechanical valves (Groups 2a (>50 years) and 2b (≤50 years)) in each age group. RESULTS: The groups had nearly equal rates of preexisting comorbidities except for Group 1b, in which the rate of hypertension was greater (32.6% vs. 14.7%; p = 0.025). This group also had higher rates of old stroke (8.7% vs. 0%, p = 0.011) and higher creatinine clearance (127.62 (108.82-150.23) vs. 110.02 (84.87-144.49) mL/min; p = 0.026) than Group 1b. Patients in Group 1a were significantly older than Group 2a (64 (58-71) vs. 58 (54-67) years; p = 0.002). There was no significant difference in the NYHA class between the groups. The preoperative ejection fraction and other echocardiographic parameters did not differ significantly between the groups. Re-exploration for bleeding was more common in patients older than 50 years who underwent mechanical valve replacement (p = 0.021). There was no difference in other postoperative complications between the groups. The groups had no differences in survival, stroke, or bleeding rates. Aortic valve reintervention was significantly greater in patients ≤ 50 years old with bioprosthetic valves. There were no differences between groups in the changes in left ventricular mass, ejection fraction, or peak aortic valve pressure during the 5-year follow-up. CONCLUSIONS: The outcomes of mechanical and bioprosthetic valve replacement were comparable in patients older than 50 years. Using bioprosthetic valves in patients younger than 50 years was associated with a greater rate of valve reintervention, with no beneficial effect on the risk of bleeding or stroke.

14.
Nat Neurosci ; 27(9): 1794-1804, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39030342

RESUMO

Across systems, higher-order interactions between components govern emergent dynamics. Here we tested whether contextual threat memory retrieval in mice relies on higher-order interactions between dorsal CA1 hippocampal neurons requiring learning-induced dendritic spine plasticity. We compared population-level Ca2+ transients as wild-type mice (with intact learning-induced spine plasticity and memory) and amnestic mice (TgCRND8 mice with high levels of amyloid-ß and deficits in learning-induced spine plasticity and memory) were tested for memory. Using machine-learning classifiers with different capacities to use input data with complex interactions, our findings indicate complex neuronal interactions in the memory representation of wild-type, but not amnestic, mice. Moreover, a peptide that partially restored learning-induced spine plasticity also restored the statistical complexity of the memory representation and memory behavior in Tg mice. These findings provide a previously missing bridge between levels of analysis in memory research, linking receptors, spines, higher-order neuronal dynamics and behavior.


Assuntos
Amnésia , Região CA1 Hipocampal , Camundongos Transgênicos , Plasticidade Neuronal , Animais , Camundongos , Plasticidade Neuronal/fisiologia , Amnésia/fisiopatologia , Espinhas Dendríticas/fisiologia , Neurônios/fisiologia , Neurônios/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Memória/fisiologia , Peptídeos beta-Amiloides/metabolismo
15.
J Am Coll Emerg Physicians Open ; 5(4): e13231, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39056087

RESUMO

Emergency department (ED) overcrowding remains a persistent challenge in global public health, leading to detrimental outcomes for patients and healthcare professionals. Traditional approaches to improve this issue have been insufficient, prompting exploration of novel strategies such as virtual care interventions. Our team developed the first comprehensive statewide virtual ED in Australia, the Victorian Virtual Emergency Department, offering an alternative to in-person care for non-life-threatening emergencies. Here, we present the development and ongoing refinement of this pioneering virtual care service, aiming to provide insights for hospital administrators and policymakers seeking to implement patient-centric care solutions worldwide. By sharing our model of care, we hope to guide further work toward addressing the global problem of over crowded EDs.

16.
Health Econ ; 33(11): 2558-2574, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39030850

RESUMO

Estimates of the impact of body mass index and obesity on health and labor market outcomes often use instrumental variables estimation (IV) to mitigate bias due to endogeneity. When these studies rely on survey data that include self- or proxy-reported height and weight, there is non-classical measurement error due to the tendency of individuals to under-report their own weight. Mean reverting errors in weight do not cause IV to be asymptotically biased per se, but may result in bias if instruments are correlated with additive error in weight. We demonstrate the conditions under which IV is biased when there is non-classical measurement error and derive bounds for this bias conditional on instrument strength and the severity of mean-reverting error. We show that improvements in instrument relevance alone cannot eliminate IV bias, but reducing the correlation between weight and reporting error mitigates the bias. A solution we consider is regression calibration (RC) of endogenous variables with external validation data. In simulations, we find IV estimation paired with RC can produce consistent estimates when correctly specified. Even when RC fails to match the covariance structure of reporting error, there is still a reduction in asymptotic bias.


Assuntos
Viés , Índice de Massa Corporal , Obesidade , Humanos , Custos de Cuidados de Saúde , Análise de Regressão
17.
Sci Signal ; 17(844): eadn6052, 2024 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980922

RESUMO

Inhibitors of the transforming growth factor-ß (TGF-ß) pathway are potentially promising antifibrotic therapies, but nonselective simultaneous inhibition of all three TGF-ß homologs has safety liabilities. TGF-ß1 is noncovalently bound to a latency-associated peptide that is, in turn, covalently bound to different presenting molecules within large latent complexes. The latent TGF-ß-binding proteins (LTBPs) present TGF-ß1 in the extracellular matrix, and TGF-ß1 is presented on immune cells by two transmembrane proteins, glycoprotein A repetitions predominant (GARP) and leucine-rich repeat protein 33 (LRRC33). Here, we describe LTBP-49247, an antibody that selectively bound to and inhibited the activation of TGF-ß1 presented by LTBPs but did not bind to TGF-ß1 presented by GARP or LRRC33. Structural studies demonstrated that LTBP-49247 recognized an epitope on LTBP-presented TGF-ß1 that is not accessible on GARP- or LRRC33-presented TGF-ß1, explaining the antibody's selectivity for LTBP-complexed TGF-ß1. In two rodent models of kidney fibrosis of different etiologies, LTBP-49247 attenuated fibrotic progression, indicating the central role of LTBP-presented TGF-ß1 in renal fibrosis. In mice, LTBP-49247 did not have the toxic effects associated with less selective TGF-ß inhibitors. These results establish the feasibility of selectively targeting LTBP-bound TGF-ß1 as an approach for treating fibrosis.


Assuntos
Matriz Extracelular , Fibrose , Proteínas de Ligação a TGF-beta Latente , Fator de Crescimento Transformador beta1 , Fator de Crescimento Transformador beta1/metabolismo , Animais , Humanos , Proteínas de Ligação a TGF-beta Latente/metabolismo , Proteínas de Ligação a TGF-beta Latente/antagonistas & inibidores , Matriz Extracelular/metabolismo , Camundongos , Masculino , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/tratamento farmacológico , Progressão da Doença , Rim/patologia , Rim/metabolismo , Rim/efeitos dos fármacos , Camundongos Endogâmicos C57BL
18.
Ochsner J ; 24(2): 157-161, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912178

RESUMO

Background: Male breast cancer remains relatively underexplored in the medical literature. At present, male patients with breast cancer follow the same treatment guidelines as female patients with breast cancer, principally because of similar outcomes with treatment. However, this practice should not preclude generating evidence for male breast cancer surveillance, diagnosis, and management. BRCA2 gene mutations are associated with an increased risk of male breast cancer, along with lesser-known gene mutations that could also increase this risk, such as mutations of the BRIP1 gene. This case report presents a male patient with dual BRCA2 and BRIP1 deleterious gene mutations. To our knowledge, this combination has not been reported in the medical literature to date. Case Report: A 53-year-old male presented with a palpable symptomatic mass underneath the right nipple-areolar complex. Biopsies confirmed a poorly differentiated, infiltrating ductal carcinoma that was estrogen and progesterone receptor positive and human epidermal growth factor receptor-2 negative. The patient underwent a left modified radical mastectomy, with a right prophylactic simple mastectomy. Postoperatively, he underwent adjuvant chemotherapy and endocrine therapy. Conclusion: This novel case of genetically based male breast cancer with dual deleterious gene mutations provides insight into current treatment recommendations and the subtle differences between male breast cancer and female breast cancer. Engaging in discussions surrounding such rare cases not only raises awareness of male breast cancer but also indicates the need for further research aimed at establishing evidence-based management strategies for male patients with breast cancer.

19.
J Arthroplasty ; 39(9S2): S158-S162, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38750833

RESUMO

BACKGROUND: Achieving a minimal clinically important difference (MCID) in patient-reported outcomes following total knee arthroplasty (TKA) is common, yet up to 20% patient dissatisfaction persists. Unmet expectations may explain post-TKA dissatisfaction. No prior studies have quantified patient expectations using the same patient-reported outcome metric as used for MCID to allow direct comparison. METHODS: This was a prospective study of patients undergoing TKA with 5 fellowship-trained arthroplasty surgeons at one academic center. Baseline Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) and Pain Interference (PI) domains were assessed. Expected PROMIS scores were determined by asking patients to indicate the outcomes they were expecting at 12 months postoperatively. Predicted scores were generated from a predictive model validated in the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) dataset. T-tests were used to compare baseline, expected, and predicted PROMIS scores. Expected scores were compared to PROMIS MCID values obtained from the literature. Regression models were used to identify patient characteristics associated with high expectations. RESULTS: There were 93 patients included. Mean age was 67 years (range, 30 to 85) and 55% were women. Mean baseline PROMIS PF and PI was 34.4 ± 6.7 and 62.2 ± 6.4, respectively. Patients expected significant improvement for PF of 1.9 times the MCID (MCID = 11.3; mean expected improvement = 21.6, 95% confidence interval [CI] 19.6 to 23.5, P < .001) and for PI of 2.3 times the MCID (MCID = 8.9; mean expected improvement = 20.6, 95% CI 19.1-22.2, P < .001). Predicted scores were significantly lower than expected scores (mean difference = 9.5, 95% CI 7.7 to 11.3, P < .001). No unique patient characteristics were associated with high expectations (P > .05). CONCLUSIONS: To our knowledge, this study is the first to quantify preoperative patient expectations using the same metric as MCID to allow for direct comparison. Patient expectations for improvement following TKA are ∼2× greater than MCID and are significantly greater than predicted outcome scores. This discrepancy challenges currently accepted standards of success after TKA and indicates a need for improved expectation setting prior to surgery.


Assuntos
Artroplastia do Joelho , Diferença Mínima Clinicamente Importante , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Humanos , Feminino , Idoso , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso de 80 Anos ou mais , Adulto , Resultado do Tratamento
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