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2.
Oncogene ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877132

RESUMO

Treatment-induced neuroendocrine prostate cancer (t-NEPC) often arises from adenocarcinoma via lineage plasticity in response to androgen receptor signaling inhibitors, such as enzalutamide. However, the specific regulators and targets involved in the transition to NEPC are not well understood. Plexin D1 (PLXND1) is a cellular receptor of the semaphorin (SEMA) family that plays important roles in modulating the cytoskeleton and cell adhesion. Here, we found that PLXND1 was highly expressed and positively correlated with neuroendocrine markers in patients with NEPC. High PLXND1 expression was associated with poorer prognosis in prostate cancer patients. Additionally, PLXND1 was upregulated and negatively regulated by androgen receptor signaling in enzalutamide-resistant cells. Knockdown or knockout of PLXND1 inhibited neural lineage pathways, thereby suppressing NEPC cell proliferation, patient derived xenograft (PDX) tumor organoid viability, and xenograft tumor growth. Mechanistically, the heat shock protein 70 (HSP70) regulated PLXND1 protein stability through degradation, and inhibition of HSP70 decreased PLXND1 expression and NEPC organoid growth. In summary, our findings indicate that PLXND1 could serve as a promising therapeutic target and molecular marker for NEPC.

3.
New Phytol ; 243(3): 1034-1049, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38853453

RESUMO

Processing by proteases irreversibly regulates the fate of plant proteins and hampers the production of recombinant proteins in plants, yet only few processing events have been described in agroinfiltrated Nicotiana benthamiana, which has emerged as the main transient protein expression platform in plant science and molecular pharming. Here, we used in-gel digests and mass spectrometry to monitor the migration and topography of 5040 plant proteins within a protein gel. By plotting the peptides over the gel slices, we generated peptographs that reveal where which part of each protein was detected within the protein gel. These data uncovered that 60% of the detected proteins have proteoforms that migrate at lower than predicted molecular weights, implicating extensive proteolytic processing. This analysis confirms the proteolytic removal and degradation of autoinhibitory prodomains of most but not all proteases, and revealed differential processing within pectinemethylesterase and lipase families. This analysis also uncovered intricate processing of glycosidases and uncovered that ectodomain shedding might be common for a diverse range of receptor-like kinases. Transient expression of double-tagged candidate proteins confirmed processing events in vivo. This large proteomic dataset implicates an elaborate proteolytic machinery shaping the proteome of N. benthamiana.


Assuntos
Nicotiana , Proteínas de Plantas , Proteólise , Proteoma , Nicotiana/genética , Nicotiana/metabolismo , Proteoma/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Proteômica , Hidrolases de Éster Carboxílico/metabolismo , Hidrolases de Éster Carboxílico/genética , Lipase/metabolismo , Lipase/genética , Peptídeo Hidrolases/metabolismo , Glicosídeo Hidrolases/metabolismo , Glicosídeo Hidrolases/genética
4.
J Hand Surg Am ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38934999

RESUMO

PURPOSE: The purpose of this study was to assess the content, construct, and discriminative validity and responsiveness of the Patient-Specific Functional Scale (PSFS) in patients with thumb carpometacarpal arthritis. METHODS: Data were collected at Xpert Clinics, comprising 34 outpatient hand surgery and hand therapy clinics in the Netherlands. We included 267 patients for content validity and 323 patients for construct validity and responsiveness. The PSFS items were classified into the International Classification of Function Core Set for Hand Conditions to assess content validity. We used hypothesis testing to investigate the construct validity and responsiveness. The Michigan Hand Outcomes Questionnaire was used as a comparator instrument. The standardized response mean was calculated to evaluate the magnitude of change. For discriminative validity, we used independent t tests to discriminate between satisfied and dissatisfied patients. RESULTS: We classified 98% of the PSFS items in the International Classification of Function "activities" and "participation" domains, indicating good content validity. Two of six hypotheses for construct validity and three of six hypotheses for responsiveness were confirmed. The standardized response mean for the PSFS was 0.57 (0.46-0.68) and 0.47 (0.35-0.58) for the Michigan Hand Outcomes Questionnaire total score. The mean PSFS score showed good discriminative validity because it could distinguish between satisfied and dissatisfied patients at the 3-month follow-up. CONCLUSIONS: The PSFS scores showed good content and discriminative validity in patients with first carpometacarpal arthritis. Hypothesis testing for responsiveness and construct validity indicates that the PSFS measures a unique construct different from the Michigan Hand Outcomes Questionnaire. CLINICAL RELEVANCE: The PSFS may be a useful scale for measuring the patient-specific status of individuals with thumb carpometacarpal arthritis.

5.
Rheumatol Ther ; 11(3): 755-771, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38662148

RESUMO

INTRODUCTION: Transforming growth factor beta (TGFß) cytokines (TGFß1, TGFß2, and TGFß3) play critical roles in tissue fibrosis. However, treatment with systemic pan-TGFß inhibitors have demonstrated unacceptable toxicities. In this study, we evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7303509, a high-affinity, TGFß3-specific, humanized immunoglobulin G1 monoclonal antibody, in healthy adult volunteers (HVs). METHODS: This phase 1a, randomized, double-blind trial included six cohorts for evaluation, with each cohort receiving single doses of placebo or RO7303509, administered intravenously (IV; 50 mg, 150 mg, 240 mg) or subcutaneously (SC; 240 mg, 675 mg, 1200 mg). The frequency and severity of adverse events (AEs) and RO7303509 serum concentrations were monitored throughout the study. We also measured serum periostin and cartilage oligomeric matrix protein (COMP) by immunoassay and developed a population pharmacokinetics model to characterize RO7303509 serum concentrations. RESULTS: The study enrolled 49 HVs, with a median age of 39 (range 18-73) years. Ten (27.8%) RO7303509-treated subjects reported 24 AEs, and six (30.8%) placebo-treated subjects reported six AEs. The most frequent AEs related to the study drug were injection site reactions and infusion-related reactions. Maximum serum concentrations (Cmax) and area under the concentration-time curve from time 0 to infinity (AUC0-inf) values for RO7303509 appeared to increase dose-proportionally across all doses tested. Serum concentrations across cohorts were best characterized by a two-compartment model plus a depot compartment with first-order SC absorption kinetics. No subjects tested positive for anti-drug antibodies (ADAs) at baseline; one subject (2.8%; 50 mg IV) tested positive for ADAs at a single time point (day 15). No clear pharmacodynamic effects were observed for periostin or COMP upon TGFß3 inhibition. CONCLUSION: RO7303509 was well tolerated at single SC doses up to 1200 mg in HVs with favorable pharmacokinetic data that appeared to increase dose-proportionally. TGFß3-specific inhibition may be suitable for development as a chronic antifibrotic therapy. TRIAL REGISTRATION: ISRCTN13175485.

6.
J Pain ; : 104517, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38609027

RESUMO

The purpose of this study was to identify meaningful response patterns in self-report survey data collected from Canadian military veterans with chronic pain and to create an algorithm intended to facilitate triage and prioritization of veterans to the most appropriate interventions. An online survey was presented to former members of the Canadian military who self-identified as having chronic pain. Variables collected were related to pain, physical and mental interference, prior traumatic experiences, and indicators from each of the 7 potential drivers of the pain experience. Maximum likelihood estimation-based latent profile analysis was used to identify clinically and statistically meaningful profiles using the 7-axis variables, and classification and regression tree (CRT) analysis was then conducted to identify the most parsimonious set of indicators that could be used to accurately classify respondents into the most relevant profile group. Data from N = 322 veterans were available for analysis. The results of maximum likelihood estimation-based latent profile analysis indicated a 5-profile structure was optimal for explaining the patterns of responses within the data. These were: Mood-Dominant (13%), Localized Physical (24%), Neurosensory-Dominant (33%), Central-Dominant with complex mood and neurosensory symptoms (16%), and Trauma- and mood-dominant (14%). From CRT analysis, an algorithm requiring only 3 self-report tools (central symptoms, mood screening, bodily coherence) achieved 83% classification accuracy across the 5 profiles. The new classification algorithm requiring 16 total items may be helpful for clinicians and veterans in pain to identify the most dominant drivers of their pain experience that may be useful for prioritizing intervention strategies, targets, and relevant health care disciplines. PERSPECTIVE: This article presents the results of latent profile (cluster) analysis of responses to standardized self-report questionnaires by Canadian military veterans with chronic pain. It identified 5 clusters that appear to represent different drivers of the pain experience. The results could be useful for triaging veterans to the most appropriate pain care providers.

7.
Clin Pharmacol Drug Dev ; 13(6): 655-664, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38651245

RESUMO

Zinpentraxin alfa is a recombinant form of the human pentraxin-2 that was studied in idiopathic pulmonary fibrosis (IPF). To improve the purity and yield of the drug material, a 2nd-generation drug product was developed. To characterize and compare the pharmacokinetic (PK) properties of the 1st- and 2nd-generation zinpentraxin alfa, PK studies were conducted in healthy volunteers (HVs). In a phase 1 randomized, double-blind, 2-sequence crossover, sequential 2-stage study (ISRCTN59409907), single intravenous (IV) doses of 1st- and 2nd-generation zinpentraxin alfa at 10 mg/kg were studied with a blinded interim analysis (IA) at the end of stage 1. Bioequivalence (BE) was achieved for the maximum observed plasma concentration (Cmax), but the overall exposure was higher for the 2nd- compared to the 1st-generation zinpentraxin alfa. The study was stopped after stage 1 as the gating criteria were met based on the result of the blinded IA. Safety profiles were similar for the 1st- and 2nd-generation drug products, and antidrug antibody (ADA) was not observed in this study.


Assuntos
Estudos Cross-Over , Voluntários Saudáveis , Componente Amiloide P Sérico , Equivalência Terapêutica , Humanos , Masculino , Método Duplo-Cego , Adulto , Componente Amiloide P Sérico/metabolismo , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Área Sob a Curva , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Administração Intravenosa
8.
ACS Omega ; 9(11): 13100-13111, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38524426

RESUMO

Agricultural rice straw (RS), often discarded as waste in farmlands, represents a vast and underutilized resource. This study explores the valorization of RS as a potential feedstock for rigid polyurethane/polyisocyanurate foam (RPUF) production. The process begins with the liquefaction of RS to create an RS-based polyol, which is then used in a modified foam formulation to prepare RPUFs. The resulting RPUF samples were comprehensively characterized according to their physical, mechanical, and thermal properties. The results demonstrated that up to 50% by weight of petroleum-based polyol can be substituted with RS-based polyol to produce a highly functional RPUF. The obtained foams exhibited a notably low apparent density of 18-24 kg/m3, exceptional thermal conductivity ranging from 0.031-0.041 W/m-K, and a high compressive strength exceeding 250 kPa. This study underlines the potential of the undervalued agricultural RS as a green alternative to petroleum-based feedstocks to produce a high-value RPUF. Additionally, the findings contribute to the sustainable utilization of abundant agricultural waste while offering an eco-friendly option for various applications, including construction materials and insulation.

9.
PLoS One ; 19(3): e0299288, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478486

RESUMO

Gender expression may be associated with exercise self-efficacy and outcome expectations for exercise in the general population. Exercising for challenge and enjoyment are associated with the instrumental traits typically held by individuals with masculine gender expressions. Conversely, exercising for weight loss to receive validation from others are in line with the expressive traits most commonly held by individuals with feminine gender expressions. Moreover, possessing neither dominant nor expressive traits (undifferentiated gender expressions) have been linked to poorer psychological outcomes. Exercise is important after stroke, but gender differences in psychosocial factors for exercise in this population were unknown. The purpose of this study was to explore whether gender expression differences exist in exercise self-efficacy and outcome expectations for exercise post-stroke. Gender expression (masculine, feminine, androgynous, undifferentiated) was assessed using the Bem Sex-Role Inventory-12 (BSRI-12) in 67 individuals with stroke. Self-efficacy and outcomes expectations for exercise were assessed using the Self-Efficacy for Physical Activity Scale and Short Outcome Expectations for Exercise Scale, respectively. One-way analysis of covariance models were conducted, adjusting for biological sex, age, and time post-stroke. There were differences in exercise self-efficacy across the four gender expression groups (F(3,60) = 4.28, p<0.01), where individuals with masculine gender expressions had higher self-efficacy than those with undifferentiated gender expressions (adjusted mean: 3.56 [SE: 0.17] vs. 2.72 [SE:0.18], p<0.01). There were no differences in outcome expectations for exercise (F(3,57) = 1.08, p = 0.36) between gender expressions. In our pairwise comparisons, we found that individuals with masculine gender expressions had higher exercise self-efficacy than individuals possessing undifferentiated gender expressions. Strategies to enhance exercise self-efficacy after stroke are needed, particularly for individuals with undifferentiated gender expression. There were no associations between gender expression and outcome expectations for exercise after stroke. Clinicians may continue reinforcing the positive expectations towards exercise across all gender expressions.


Assuntos
Identidade de Gênero , Autoeficácia , Humanos , Masculino , Feminino , Motivação , Masculinidade , Feminilidade , Exercício Físico
10.
Adv Radiat Oncol ; 9(2): 101354, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38405322

RESUMO

Purpose: As global cancer incidence continues to rise, low- to middle-income countries like the Philippines are projected to experience a disproportionate increase in cancer burden, further straining already limited resources. Radiation therapy (RT) is an essential and cost-effective modality in cancer care, both in the curative and palliative settings. In this article, we provide a brief narrative on the history of the field of radiation oncology in the Philippines and review the current challenges to effective and equitable RT service delivery in the country. Methods and Materials: We gathered data from the official websites of the Philippine government's health and statistics agencies, the Philippine Radiation Oncology Society, and the Directory of Radiotherapy Centers of the International Atomic Energy Agency, to review available human and infrastructure resources related to RT delivery in the country. Using the 6 health care dimensions of the World Health Organization's Building Blocks of Health Systems framework, we identified barriers to access and proposed possible initiatives for development. Results: Despite the remarkable growth of radiation oncology in the country in the past 2 decades, many challenges remain in the areas of human resources, infrastructure, policymaking, health economics, education, and service delivery. Radiation health workers and facilities are concentrated in the National Capital Region, limiting accessibility in rural areas. Out-of-pocket spending on RT-related expenditures remains high. The proper allocation of resources according to varying regional needs is impeded by the lack of a robust national cancer registry. Legislative reforms have been initiated but have yet to be fully implemented. Conclusions: Addressing these gaps in RT access will require in-depth study and multi-sectoral commitment aimed at establishing and implementing a nationwide framework for RT service delivery that can be readily adapted to varying regional needs. Despite many complex geographic, social, and economic obstacles, efforts by private and public sectors of society to provide ready access to RT services for all Filipinos continue to gain momentum.

11.
J Aging Phys Act ; : 1-8, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38417423

RESUMO

Research indicates a positive relationship between physical literacy and healthy aging; however, there is no consensus on the components required to become a physically literate adult. The objective of this study was to understand how physical literacy for adults with chronic conditions is characterized from the perspective of healthcare professionals. Physiotherapy leaders and physical literacy researchers within North America were invited to an online consensus panel and presented with questions related to physical literacy and rehabilitation. A nominal group technique was used for idea generation, clarification, and ranking. Confidence and safety with movements, motivation and commitment to physical activity, the ability to self-monitor changes in function, and understanding the benefits of physical activity were key components when defining physical literacy. There is a need to reconceptualize physical literacy to include the rehabilitation needs of adults living with chronic conditions, and to design programs that promote physical literacy to enhance function and mobility.

12.
J Orthop Sports Phys Ther ; 54(6): 1-16, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38406873

RESUMO

OBJECTIVE: To evaluate the effectiveness of remote rehabilitation interventions for people living with chronic musculoskeletal pain and depression. DESIGN: A systematic review with network meta-analysis (NMA) of randomized controlled trials. LITERATURE SEARCH: We searched the Cochrane Central Register of Controlled Trials, CINAHL, EMBASE, LILACS MEDLINE, PSYNDEX, and PsycINFO databases from inception to May 2023. STUDY SELECTION CRITERIA: Randomized controlled trials that evaluated the effectiveness of remote rehabilitation interventions in people with chronic musculoskeletal pain and depression. DATA SYNTHESIS: We used Bayesian random-effects models for the NMA. Effect estimates were comparisons between rehabilitation interventions and waitlist. We performed a sensitivity analysis based on bias in the randomization process, large trials (>100 patients per arm) and musculoskeletal condition. RESULTS: Fifty-eight randomized controlled trials involving 10 278 participants (median sample size: 137; interquartile range [IQR]: 77-236) were included. Interactive voice response cognitive behavioral therapy (CBT; standardized mean difference [SMD] -0.66, 95% credible interval [CrI] -1.17 to -0.16), CBT in person (SMD -0.50, 95% CrI -0.97 to -0.04), and mobile app CBT plus exercise (SMD -0.37, 95% CrI -0.69 to -0.02) were superior to waitlist at 12-week follow-up for reducing pain (> 98% probability of superiority). For depression outcomes, Internet-delivered CBT and telecare were superior to waitlist at 12-week follow-up (SMD -0.51, 95% CrI -0.87 to -0.13) (> 99% probability of superiority). For pain outcomes, the certainty of evidence ranged from low to moderate. For depression outcomes, the certainty of evidence ranged from very low to moderate. The proportion of dropouts attributed to adverse events was unclear. No intervention was associated with higher odds of dropout. CONCLUSION: Interactive voice response CBT and mobile app CBT plus exercise showed similar treatment effects with in-person CBT on pain reduction among people living with chronic musculoskeletal pain and depression had over 98% probability of superiority than waitlist control at 12-week follow-up. Internet-delivered CBT and telecare had over 99% probability of superiority than waitlist control for improving depression outcomes at 12-week follow-up. J Orthop Sports Phys Ther 2024;54(6):1-16. Epub 26 February 2024. doi:10.2519/jospt.2024.12216.


Assuntos
Teorema de Bayes , Dor Crônica , Terapia Cognitivo-Comportamental , Depressão , Dor Musculoesquelética , Metanálise em Rede , Telerreabilitação , Humanos , Dor Musculoesquelética/reabilitação , Dor Crônica/reabilitação , Terapia Cognitivo-Comportamental/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Exercício/métodos
13.
Vaccine ; 42(3): 455-463, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38184392

RESUMO

BACKGROUND: Misinformation presents a critical concern for academic and public health discourse, particularly around vaccine response. Before the COVID-19 pandemic, vaccine hesitancy was responsible for decreased immunization uptake for vaccine-preventable diseases. Misinformation connected to the novel COVID-19 vaccine has further fueled vaccine hesitancy in Colorado and the United States. Our study brings together three different perspectives - physicians, public health professionals, and parents - to understand the impact of misinformation on vaccine uptake in Colorado. Our study proposes a framework for combining the Health Belief Model with the Socio-Ecological model to account for societal factors in healthcare decision making. METHODS: Semi-structured interviews and focus groups with public health professionals, physicians, and parents (n = 31) were conducted in late spring and summer 2022. Data were coded inductively using thematic analysis. Identified themes were deductively categorized according to the Socio-Ecological Model and Health Belief Model. RESULTS: Using a theoretical framework that combined the Health Belief Model and the Socio-Ecological Model, we identified seven factors that influenced vaccine hesitancy in Colorado. Intrapersonal factors included routine vaccine hesitancy connected to perceptions of severity and susceptibility, efficacy, and benefits and barriers to vaccine uptake; interpersonal factors included social networks; institutional factors included mass mediated platforms, portrayals of uncertainty, distrust in institutional sources of information, and political influences in vaccine decision making; and structural factors included economic barriers behind vaccine hesitancy. CONCLUSIONS: Our study provides a unique, triangulated, post-positivist perspective on the role of misinformation in vaccine hesitancy in Colorado. The findings provide evidence that misinformation is an important barrier to vaccination uptake and can permeate multiple socio-ecological determinants/characteristics to influence vaccination behaviors including intrapersonal, interpersonal, institutional, and structural levels. We introduce the Social Ecology of Health Beliefs and Misinformation Framework to account for how misinformation may interrupt vaccine uptake.


Assuntos
Vacinas contra COVID-19 , Vacinas , Humanos , Pandemias , Fatores Sociológicos , Vacinação , Rede Social , Meio Social
15.
Clin Pharmacol Ther ; 115(4): 786-794, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38140747

RESUMO

Natural language processing (NLP) is a branch of artificial intelligence, which combines computational linguistics, machine learning, and deep learning models to process human language. Although there is a surge in NLP usage across various industries in recent years, NLP has not been widely evaluated and utilized to support drug development. To demonstrate how advanced NLP can expedite the extraction and analyses of information to help address clinical pharmacology questions, inform clinical trial designs, and support drug development, three use cases are described in this article: (1) dose optimization strategy in oncology, (2) common covariates on pharmacokinetic (PK) parameters in oncology, and (3) physiologically-based PK (PBPK) analyses for regulatory review and product label. The NLP workflow includes (1) preparation of source files, (2) NLP model building, and (3) automation of data extraction. The Clinical Pharmacology and Biopharmaceutics Summary Basis of Approval (SBA) documents, US package inserts (USPI), and approval letters from the US Food and Drug Administration (FDA) were used as our source data. As demonstrated in the three example use cases, advanced NLP can expedite the extraction and analyses of large amounts of information from regulatory review documents to help address important clinical pharmacology questions. Although this has not been adopted widely, integrating advanced NLP into the clinical pharmacology workflow can increase efficiency in extracting impactful information to advance drug development.


Assuntos
Processamento de Linguagem Natural , Farmacologia Clínica , Humanos , Inteligência Artificial , Registros Eletrônicos de Saúde , Aprendizado de Máquina
16.
Artigo em Inglês | MEDLINE | ID: mdl-38076224

RESUMO

Background: Arthritis leads to disabilities impacting patients' physical and mental health. Objective: To synthesize the evidence on measurement properties of the patient-reported outcome measures (PROMs) for people with upper extremity arthritis. Design: Overview of systematic reviews (SRs). Methods: We performed an electronic search of 6 databases to retrieve SRs looking at any measurement property related to PROMs for people with upper extremity arthritis. Two authors rated the risk of bias (ROB) of the included SRs using AMSTAR. We extracted data on measurement properties from each SR. Results: From 6 included SRs, 6 PROMs (Arthritis Impact Measurement Scale [AIMS], AIMS-2, AIMS-Short Form, Cedars-Sinai Health-Related Quality of Life for Rheumatoid Arthritis (CSHQ-RA), Revised CSHQ-RA, and Influence of Rheumatic Disease on General Health and Lifestyle) were evaluated in 2 or more SRs. The ROB of the included SRs ranged from moderate to high. Low- to moderate-quality evidence was found of good construct and criterion validity, acceptable content validity, and good responsiveness of the AIMS. We found low- to moderate-quality evidence of good internal consistency, test-retest reliability, and construct validity of the CSHQ-RA. Conclusion: We found a moderate to high ROB in the included SRs on the upper extremity PROMs for patients with arthritis. More evidence was specific to upper extremity arthritis in measures not in common use versus well-validated measures used in upper extremity conditions and recommended in current core sets. These factors suggest an urgent need for additional research to improve the scope and quality of evidence before recommendations can be made specific to patients with arthritis. Registration Number: on PROSPERO CRD 42019137491.

17.
Plast Reconstr Surg ; 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-38085953

RESUMO

BACKGROUND: No patient-reported instrument assesses patient-specific information needs, treatment goals, and Personal Meaningful Gain (PMG, a novel construct evaluating individualized, clinically relevant improvement). This study reports the development of the Patient-Specific Needs Evaluation (PSN) and examines its discriminative validity (i.e., its ability to distinguish satisfied from dissatisfied patients) and test-retest reliability in patients with hand or wrist conditions. METHODS: A mixed-methods approach was used to develop and validate the PSN, following COSMIN guidelines, including pilot testing, a survey (pilot: n=223, final PSN: n=275), cognitive debriefing (n=16), expert input, and validation. Discriminative validity was assessed by comparing the satisfaction level of patients who did or did not achieve their PMG (n=1,985) and test-retest reliability using absolute agreement, Cohen's kappa, and ICCs (n=102). We used a sample of 2,860 patients to describe responses to the final PSN. RESULTS: The PSN has only five questions (completion time ±3 minutes) and is freely accessible online. The items and response options were considered understandable by 90-92% and complete by 84-89% of the end-users. The PSN had excellent discriminative validity (Cramer's V: 0.48, p<0.001) and moderate to high test-retest reliability (Kappa: 0.46-0.68, ICCs: 0.53-0.73). CONCLUSIONS: The PSN is a freely available patient-centered decision-support tool that helps clinicians tailor their consultations to the patient's individual needs and goals. It contains the PMG, a novel construct evaluating individualized, clinically relevant treatment outcomes. The PSN may function as a conversation starter, facilitate expectation management, and aid shared decision-making. The PSN is implementation-ready and can be readily adapted to other patient populations. LEVEL OF EVIDENCE: I.

18.
PLoS One ; 18(12): e0290515, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38060584

RESUMO

BACKGROUND: Movement-related behaviours, including prolonged sedentary behaviour, physical inactivity, and poor sleep, are associated with worse functional outcomes poststroke. Addressing these co-dependent behaviours early after stroke may help to optimize recovery and improve overall quality of life for individuals with stroke. OBJECTIVE: This study aims to determine the feasibility and effect of a 'sit less, move more, sleep better' program early after stroke on functional mobility and global disability outcomes, while also exploring imaging and behavioural markers that may influence walking recovery. METHODS: The study is an assessor-blinded, single-center, parallel-group, randomized controlled trial to be completed within 24 months from July 12, 2023 to June 30, 2025. We will enroll 50 patients with acute ischemic stroke within 7 days from symptom onset, aged 18 years or older, and with ongoing walking goals. Demographic and stroke characteristics, including stroke risk factors, neuroimaging, and acute stroke treatments, will be determined and documented. All participants will wear an accelerometer for one week at three different time-points (baseline, 6, and 12 weeks) to assess movement-related behaviours. Following randomization, participants in the intervention arm will receive a 'sit less, move more, sleep better' program for up to 1 hour/day, 5 days/week, for 6 weeks to enhance self-efficacy for change. Participants in the control arm will receive usual inpatient and early supported stroke discharge care. The feasibility outcomes will include reach (enrolled/eligible), retention (completed/enrolled), adverse events, and program adherence. Other outcomes at 6 and 12 weeks include the modified Rankin Scale, Timed-Up and Go, movement-related behaviours, walking endurance, gait speed, cognition, stroke severity and quality of life. Mixed-effects models will assess changes in outcomes over time. Compositional associations between movement-related behaviours and outcomes will consider covariates such as imaging markers. DISCUSSION: Adopting a whole-day approach to poststroke rehabilitation will provide valuable insights into the relationship between optimizing movement-related behaviours early after stroke and their impact on functional outcomes. Through exploring person-specific behavioural and imaging markers, this study may inform precision rehabilitation strategies, and guide clinical decision making for more tailored interventions. TRIAL REGISTRATION: Clinical Trial registration (ClinicalTrials.gov Identifier: NCT05753761, March 3, 2023).


Assuntos
AVC Isquêmico , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Reabilitação do Acidente Vascular Cerebral/métodos , Qualidade de Vida , Resultado do Tratamento , Sono , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
PLoS One ; 18(11): e0294552, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38011205

RESUMO

Single motherhood is associated with higher demands in home and family responsibilities that may exist in similar sized households with grandparents. These demands can compete with opportunities and resources for maintenance of healthy behaviours. This may have been exacerbated during the COVID-19 pandemic since supports outside the home may have been restricted by public health measures. A qualitative narrative study was conducted to explore these issues with 12 single mothers in Canada. Semi-structured interviews provided an in-depth understanding of the challenges and facilitators to maintaining healthy eating habits, physical activity levels, and mental health. Theory-driven content and structural analysis were applied through a descriptive thematic approach. Challenges to maintaining healthy eating behaviours included stay-at-home orders, limited budget, unhealthy food/cravings, and lack of motivation. In contrast, living with grandparents who provide help or having an understanding of healthy food were factors that facilitated engagement in healthy eating. Challenges to maintaining physical activity levels included lack of willpower, lack of time, and low energy. Whereas time on one's own, weighing scales or outdoor gear, and weather conditions promoted physical activity. Spirituality and gratitude were the main coping mechanisms used to deal with loneliness, unemployment, and depressive symptoms. Further research into the utility of gratitude as a coping mechanism could inform public health interventions that aim to increase levels of well-being among single mothers.


Assuntos
Dieta Saudável , Saúde Mental , Humanos , Feminino , Dieta Saudável/psicologia , Pandemias , Exercício Físico , Pesquisa Qualitativa , Canadá , Mães/psicologia
20.
Workplace Health Saf ; 71(12): 606-616, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37997916

RESUMO

BACKGROUND: Posture mechanics during fire suppression tasks are associated with musculoskeletal injuries in firefighters. METHODS: This study uses the Ovako Working Posture Analyzing System (OWAS) ergonomics tool to describe and evaluate the postures of 48 firefighters during 3 simulated tasks: (a) hose drag, (b) hose pull, and (c) high-rise pack lift. Ergonomics intervention prioritizations based on the OWAS action classification (AC) scores were identified using Wilcoxon signed-rank tests. Chi-square analyses identified associations between firefighter characteristics and OWAS AC scores. FINDINGS: The initial hose pick-up phase of each task was identified as a high priority for ergonomics intervention (OWAS AC = 4) in 45.8%, 54.2%, and 45.8% of cases for Tasks 1, 2, and 3, respectively. Lower BMI was associated with higher AC scores for the initial hose pick-up during Task 3 (likelihood ratio = 9.20, p value = .01). CONCLUSION: The results inform ergonomics priorities for firefighter training based on the tasks analyzed. Application to Practice: This study evaluates the posture mechanics of three commonly performed firefighting tasks. The results help inform an ergonomics training intervention focused on posture mechanics during occupational activities for firefighters.


Assuntos
Bombeiros , Doenças Musculoesqueléticas , Humanos , Ergonomia , Postura
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