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1.
JAMA Dermatol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717780

RESUMO

Importance: The HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia. Objective: To evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy. Design, Setting, and Participants: A model with components of decision analysis and Markov simulation was developed to simulate clinical trajectories of adult Asian Australian patients with newly diagnosed epilepsy being considered for carbamazepine treatment. Cost-effectiveness and cost-utility analyses over a lifetime time horizon were conducted from the perspective of the Australian health care sector. The study was conducted in May 2023 and data analysis was performed from August 2023 to November 2023. Intervention: No HLA-B*15:02 genotyping and the empirical initiation of treatment with carbamazepine vs HLA-B*15:02 genotyping and the initiation of treatment with valproate in allele carriers. Main Outcomes and Measures: Life-years (LYs), quality-adjusted life-years (QALYs), and costs in 2023 Australian dollars (A$); incremental cost-effectiveness ratios. Results: HLA-B*15:02 screening was associated with an additional mean cost of A$114 (95% CI, -A$83 to A$374; US$76; 95% CI, -US$55 to US$248) and a reduction in 0.0152 LYs (95% CI, 0.0045 to 0.0287 LYs) but improvement by 0.00722 QALYs (95% CI, -0.0247 to -0.01210) compared with no screening, resulting in an incremental cost-effectiveness ratio of A$15 839 per QALY gained (US$10 523 per QALY). Therefore, universal genotyping for Asian Australian individuals was cost-effective compared with current standards of practice at the A$50 000 per QALY willingness-to-pay threshold. Sensitivity analyses demonstrated that the intervention remained cost-effective across a range of costs, utilities, transition probabilities, and willingness-to-pay thresholds. At the A$50 000 per QALY willingness-to-pay threshold, universal screening was the preferred strategy in 88.60% of simulations. Conclusions and Relevance: The results of this economic evaluation suggest that HLA-B*15:02 screening represents a cost-effective choice for Asian Australian patients with epilepsy who are being considered for treatment with carbamazepine.

2.
J Prim Care Community Health ; 15: 21501319241241188, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577788

RESUMO

INTRODUCTION/OBJECTIVES: A non-laboratory-based pre-diabetes/diabetes mellitus (pre-DM/DM) risk prediction model developed from the Hong Kong Chinese population showed good external discrimination in a primary care (PC) population, but the estimated risk level was significantly lower than the observed incidence, indicating poor calibration. This study explored whether recalibrating/updating methods could improve the model's accuracy in estimating individuals' risks in PC. METHODS: We performed a secondary analysis on the model's predictors and blood test results of 919 Chinese adults with no prior DM diagnosis recruited from PC clinics from April 2021 to January 2022 in HK. The dataset was randomly split in half into a training set and a test set. The model was recalibrated/updated based on a seven-step methodology, including model recalibrating, revising and extending methods. The primary outcome was the calibration of the recalibrated/updated models, indicated by calibration plots. The models' discrimination, indicated by the area under the receiver operating characteristic curves (AUC-ROC), was also evaluated. RESULTS: Recalibrating the model's regression constant, with no change to the predictors' coefficients, improved the model's accuracy (calibration plot intercept: -0.01, slope: 0.69). More extensive methods could not improve any further. All recalibrated/updated models had similar AUC-ROCs to the original model. CONCLUSION: The simple recalibration method can adapt the HK Chinese pre-DM/DM model to PC populations with different pre-test probabilities. The recalibrated model can be used as a first-step screening tool and as a measure to monitor changes in pre-DM/DM risks over time or after interventions.


Assuntos
Diabetes Mellitus , Estado Pré-Diabético , Adulto , Humanos , Hong Kong/epidemiologia , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Diabetes Mellitus/epidemiologia , Atenção Primária à Saúde
3.
Med Educ Online ; 29(1): 2330257, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38493489

RESUMO

Enhancing health professional students' effective learning and collaborative practice requires a deep understanding of strategies for facilitating interprofessional learning. While faculty members and clinical preceptors are recognized as facilitators in interprofessional education (IPE), there is limited knowledge about the impact of student facilitators' engagement in IPE. Accordingly, this study aims to explore the perceptions and experiences of student facilitators in IPE. Thirteen student facilitators were recruited to lead an interprofessional learning program, and they were subsequently invited to participate in one-on-one interviews. An interview guide was developed to explore their motivations, expectations, engagement, effectiveness, and achievements in IPE facilitation. Thematic analysis was conducted using MAXQDA software to analyze the student facilitators' experiences and perceptions. Eight interviewees from various disciplines, including Medicine, Nursing, Pharmacy, Speech and Hearing Sciences, and Social Work, took part in the study. The findings revealed that student facilitators highly valued their IPE facilitation experience, which aligned with their expectations and led to the creation of social networks, increased confidence, improved understanding of other professions, and the development of lifelong skills. Furthermore, the student facilitators demonstrated cognitive and social congruence by establishing a relaxed learning environment, displaying empathetic and supportive behaviors, and using inclusive language to engage IPE learners in group discussions. This study provides a comprehensive understanding of the role of student facilitators in IPE, contributing to the evolving literature on IPE. A conceptual framework was developed to explore the entire facilitation experience, encompassing the motivations and expectations of student facilitators, their engagement and effectiveness, and the observed achievements. These findings can inform the development of peer teaching training in IPE and stimulate further research in identifying relevant facilitator competencies for optimal delivery of IPE.


Assuntos
Relações Interprofissionais , Estudantes de Ciências da Saúde , Humanos , Educação Interprofissional , Pesquisa Qualitativa , Aprendizagem , Estudantes de Ciências da Saúde/psicologia
4.
Int J Mol Sci ; 24(16)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37629070

RESUMO

Phagocytosis is one of the key functions of retinal pigment epithelium (RPE) cells, which maintain photoreceptor health by removing photoreceptor outer segments (POSs) that are regularly shed. A deficiency in RPE function to phagocytose POSs may lead to vision loss in inherited retinal diseases and eventually to age-related macular degeneration (AMD) with geographic atrophy. Significant progress has been made in the field of cell replacement therapy for AMD using stem-cell-derived RPE. To test their function, RPE cells are incubated with purified bovine POSs for the demonstration of efficient binding, internalization, and digestion of POSs. Here, we present an image-based method to measure phagocytosis activity by using POSs labeled with a pH-sensitive fluorescent dye, which has low fluorescence at neutral pH outside of the cell and high fluorescence at low pH inside the phagosome. Further, we introduce a unique flow-cytometry-based method for the characterization of POSs by measuring specific markers for POSs such as rhodopsin and opsin. Using this method, we demonstrated a comparable quality of several bovine POS isolation batches and a reliable assessment of POS quality on RPE phagocytosis assay performance when subjected to different stress conditions. This work provides new tools to characterize POSs and insight into RPE phagocytosis assay development for the functional evaluation of RPE cells in the field of cell replacement therapy.


Assuntos
Degeneração Macular , Epitélio Pigmentado da Retina , Animais , Bovinos , Citometria de Fluxo , Neuritos , Neurônios , Fagocitose
5.
BMC Med Educ ; 23(1): 457, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37340427

RESUMO

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.


Assuntos
Educação Interprofissional , Estudantes de Ciências da Saúde , Humanos , Aprendizagem , Resolução de Problemas , Universidades , Relações Interprofissionais , Atitude do Pessoal de Saúde
6.
Ann Med ; 55(1): 2210842, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37166406

RESUMO

BACKGROUND: Interprofessional education (IPE) has been promoted as a breakthrough in healthcare because of the impact when professionals work as a team. However, despite its inception dating back to the 1960s, its science has taken a long time to advance. There is a need to theorize IPE to cultivate creative insights for a nuanced understanding of IPE. This study aims to propose a research agenda on social interaction by understanding the measurement scales used and guiding researchers to contribute to the discussion of social processes in IPE. METHOD: This quantitative research was undertaken in a cross-institutional IPE involving 925 healthcare students (Medicine, Nursing, Social Work, Chinese Medicine, Pharmacy, Speech Language Pathology, Clinical Psychology, Food and Nutritional Science and Physiotherapy) from two institutions in Hong Kong. Participants completed the Social Interaction Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6). We applied a construct validation approach: within-network and between-network validation. We performed confirmatory factors analysis, t-test, analysis of variance and regression analysis. RESULTS: CFA results indicated that current data fit the a priori model providing support to within-network validity [RMSEA=.08, NFI=.959, CFI=.965, IFI=.965, TLI=.955]. The criteria for acceptable fit were met. The scales were invariant between genders, across year levels and disciplines. Results indicated that social interaction anxiety and social phobia negatively predicted behavioural engagement (F = 25.093, p<.001, R2=.065) and positively predicted behavioural disaffection (F = 22.169, p<.001, R2=.057) to IPE, suggesting between-network validity. CONCLUSIONS: Our data provided support for the validity of the scales when used among healthcare students in Hong Kong. SIAS-6 and SPS-6 have sound psychometric properties based on students' data in Hong Kong. We identified quantitative, qualitative and mixed methods research designs to guide researchers in getting involved in the discussion of students' social interactions in IPE.Key MessagesThe Social Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6) scales have sound psychometric properties based on the large-scale healthcare students' data in IPE in Hong Kong.Social interaction anxiety and social phobia negatively predicted students' behavioural engagement with IPE and positively predicted behavioural disaffection. The scales are invariant in terms of gender, year level and discipline.Quantitative, qualitative and mixed methods studies are proposed to aid researchers to contribute in healthcare education literature using the SIAS-6 and SPS-6.


Assuntos
Fobia Social , Humanos , Masculino , Feminino , Hong Kong , Educação Interprofissional , Relações Interprofissionais , Ansiedade , Estudantes
7.
J Clin Pharmacol ; 63(1): 126-134, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36063443

RESUMO

Through examining the incidence of cardiovascular diseases (CVDs) among nonsteroidal anti-inflammatory drug (NSAID) users and nonusers, this study aims to compare the risks contributed by different NSAIDs in a Chinese population. The retrospective cohort including 4 298 368 adults without CVD from electronic health records between 2008 and 2017 in Hong Kong was adopted. A total of 4.5% of individuals received NSAIDs including celecoxib, etoricoxib, diclofenac, ibuprofen, indomethacin, mefenamic acid, or naproxen for ≥4 consecutive weeks at baseline. Cox regression, including NSAID use as a time-dependent covariate and adjusted with patient's characteristics, was conducted to examine the association between NSAID exposure and incident CVD. After a median follow-up of 6.9 years (30 million person-years), a total of 258 601 cases of incident CVD was recorded. NSAID use was shown to be associated with a significantly higher risk of CVD (hazard ratio [HR], 1.32 [95%CI, 1.28-1.37]) compared to non-NSAID use. Similar results in coronary heart disease (HR, 1.37 [95%CI, 1.31-1.43]), stroke (HR, 1.27 [95%CI, 1.21-1.33]), and heart failure (HR, 1.25 [95%CI, 1.16-1.34]) were obtained. Overall, similar CVD risk was observed across users of NSAIDs except for etoricoxib, which showed a higher risk (HR, 2.01 [95%CI, 1.63-2.48]). Considering that a higher CVD risk was consistently displayed among NSAID users, NSAIDs should be used cautiously, and the usage of etoricoxib in the Chinese population should be reviewed.


Assuntos
Doenças Cardiovasculares , Adulto , Humanos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Estudos Retrospectivos , Estudos de Coortes , Etoricoxib/efeitos adversos , Fatores de Risco , Anti-Inflamatórios não Esteroides/efeitos adversos
8.
BMC Med Educ ; 22(1): 820, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36447247

RESUMO

BACKGROUND: Team cohesiveness and collective efficacy have been construed as important characteristics of a high-functioning team. However, the psychological mechanism through which they promote positive outcomes remains unknown. Understanding this psychological process is important to teachers and programme implementers to yield actionable interventions that can be used to craft effective practices for optimizing team outcomes. This is especially true in interprofessional education (IPE) in medical education, where a team-based approach to patient management is promoted. Drawing from the social-cognitive theory, we examined a hypothesized model where team cohesiveness predicts collaboration outcomes (teamwork satisfaction, overall satisfaction with the team experience, and IPE goal attainment) via collective efficacy. METHODS: We used data from Chinese medicine, medicine, nursing, and social work students in Hong Kong (n = 285) who were enrolled in IPE. They were invited to respond to scales in two time points. We performed mediation analysis using structural equations modelling to test the indirect effect model: team cohesiveness → collective efficacy → outcomes. RESULTS: Results of structural equation modelling revealed that collective efficacy fully mediated the relationships between team cohesiveness and all three team outcomes, providing support for the hypothesised model [RMSEA = 0.08, NFI = 0.90, CFI = 0.93, IFI = 0.93, TLI = 0.93]. Team cohesiveness predicted the achievement of collaboration outcomes via collective efficacy. CONCLUSION: The findings demonstrated the important roles of team cohesiveness and collective efficacy in promoting successful team collaboration. Team cohesiveness predicted collective efficacy, and collective efficacy, in turn, predicted collaboration outcomes. This study contributed to theorising the pathways towards successful team collaboration outcomes.


Assuntos
Educação Médica , Pessoal de Educação , Medicina , Humanos , Educação Interprofissional , Hong Kong
9.
Nurse Educ Today ; 119: 105549, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36182789

RESUMO

OBJECTIVES: Despite the popularity of interprofessional education, the empirical and theoretical development of its scholarship and science is just emerging. This may be caused in part by the non-availability of measures that can be used by researchers in this field. This study aimed to contribute to the psychological theorizing of interprofessional education by uncovering the psychometric properties of Perceived Locus of Causality adapted to Interprofessional Education (PLOC-IPE) in healthcare education and provide a comprehensive guide on how this can be used to advance the IPE research agenda. METHODS: Confirmatory factor analysis (quantitative design) was used to examine the acceptability of psychometric properties of PLOC-IPE. Data were collected through questionnaires administered at two different time points. The participants consisted of 345 students from Chinese Medicine, Clinical Psychology, Medicine, Nursing, Pharmacy, and Social Work from a university in Hong Kong. RESULTS: Based on confirmatory factor analysis, results of within-network construct validity showed good psychometric properties of PLOC-IPE while between-network validity indicated that the scale can predict IPE-related outcomes. Students' intrinsic motivation in IPE positively predicted emotional engagement and negatively predicted emotional disaffection, demonstrating the applicability of the newly validated PLOC-IPE. Amotivation was a negative predictor of emotional engagement and a positive predictor of emotional disaffection. CONCLUSIONS: Findings support the acceptability of PLOC when adapted to IPE. PLOC-IPE obtained acceptable psychometric properties as a measure of students' academic motivation in IPE. It is an adapted scale that can be used to understand self-determined motivation in the context of IPE in health and social care education. A guide on how PLOC-IPE can be a means by which researchers can contribute to the advancement of scholarship of IPE was provided.


Assuntos
Educação Interprofissional , Motivação , Humanos , Relações Interprofissionais , Estudantes/psicologia , Psicometria , Atitude do Pessoal de Saúde
10.
BMJ Case Rep ; 15(4)2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379684

RESUMO

Neutrophilic eccrine hidradenitis (NEH) is a rare neutrophilic dermatosis involving the eccrine glands. It is commonly associated with haematological malignancy and administration of chemotherapy. An infective aetiology for NEH is termed infectious eccrine hidradenitis (IEH). Pathogens that have been associated with IEH include Nocardia, Serratia, Enterobacter sp., Staphylococcus aureus and Mycobacterium chelonae We describe a case of IEH in a patient with prolonged use of a compression sleeve for their upper limb lymphoedema. The histopathological findings of NEH and IEH are almost identical. Skin tissue culture and rapid clinical improvement with antibiotic therapy are keys in delineating the two subtypes.


Assuntos
Hidradenite , Mycobacterium chelonae , Nocardia , Celulite (Flegmão)/complicações , Celulite (Flegmão)/tratamento farmacológico , Hidradenite/tratamento farmacológico , Hidradenite/etiologia , Hidradenite/patologia , Humanos , Glândulas Sudoríparas/patologia
11.
Can Fam Physician ; 68(3): e107-e117, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35292475

RESUMO

OBJECTIVE: To identify barriers to and facilitators of primary care provider (PCP) referral for bariatric surgery in patients with obesity. DATA SOURCES: MEDLINE, EMBASE, and PsycINFO databases were searched and reference lists of included articles were screened to identify additional relevant articles. Two reviewers independently reviewed citations and full-text articles, and appraised the quality of the included articles using the Critical Appraisal Skills Programme Tool Qualitative Checklist and the Appraisal Tool for Cross-Sectional Studies. They extracted data on the study characteristics and the barriers to and facilitators of PCP referral for bariatric surgery. Appraisal discrepancies were resolved through consensus among authors. STUDY SELECTION: Overall, 882 citations were identified and 18 articles were then selected for this review. SYNTHESIS: Barriers included fear of surgery complications and side effects, cost, lack of availability, perception that surgery is a quick fix or a last resort, and prior negative experiences. Facilitators included direct requests from patients, patient motivation, previously failed weight-loss interventions, and obesity-related comorbidities. Those PCPs who were knowledgeable about the risks and benefits of bariatric surgery were more likely to refer their patients. CONCLUSION: Education and continuing professional development programs regarding bariatric surgery are needed to improve PCP knowledge and capacity to manage patients with obesity. Also, educating the general public on obesity, weight management, and available treatment options can empower patients and families to manage their weight and pursue evidence-informed treatments.


Assuntos
Cirurgia Bariátrica , Estudos Transversais , Humanos , Obesidade , Atenção Primária à Saúde , Encaminhamento e Consulta
12.
Nurse Educ Today ; 112: 105321, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35303541

RESUMO

OBJECTIVES: Calls to promote team-based interprofessional collaborative practice in managing patients with complex health problems are ubiquitous. However, the literature remains silent on what characterises successful teams in interprofessional education (IPE) and on profiling successful teams. To help conceptualise successful teams, this study investigated the differences in attitudes and achievement between high- and low-performing teams in an online asynchronous and synchronous IPE programme, and the role of autonomous motivation in determining team membership. METHODS: Using extreme case sampling involving health and social care students, we identified ten high-performing teams and seven low-performing teams based on their team composite scores on three interprofessional collaborative outcomes: team effectiveness, goal achievement, and scores on the readiness assurance test. Each team had five to seven members of diverse backgrounds. Independent t-tests were performed to identify differences in interprofessional collaborative outcomes, namely teamwork and collaboration, patient-centredness, diversity and ethics, community-centeredness, and interprofessional biases for the affective domain and application exercise for the cognitive domain. We employed logistic regression in which autonomous motivation was used to predict group membership. RESULTS: High-performing teams were characterised as those whose members endorsed or valued "teamwork and collaboration" in IPE simulations. Compared with the low-performing groups, they better recognised and endorsed diversity and ethics, patient-centeredness, and community-centeredness. Membership to high- and low-performing teams was linked to autonomous motivation. CONCLUSIONS: High-performing teams have higher favourable valuing of important interprofessional collaborative competencies, and membership to which is predicted by autonomous motivation. The results suggest the need to pay special attention to struggling teams to facilitate desirable collaborative competencies, especially in terms of members' motivation. Theoretical, methodological, and practical implications are discussed.


Assuntos
Educação Interprofissional , Relações Interprofissionais , Comportamento Cooperativo , Humanos , Motivação , Equipe de Assistência ao Paciente
13.
Med Educ Online ; 27(1): 2044635, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35275804

RESUMO

BACKGROUND: The COVID-19 pandemic has exacerbated the pre-existing global crisis of physician burnout. Physician and particularly medical educator well-being, has come into focus as educators can influence their own and learners' well-being. Measuring this construct is one important step towards promoting well-being in the work and learning environments. The 5-item World Health Organization Well-Being Index (WHO-5) has been validated in different populations worldwide for assessing well-being. Yet, its psychometric acceptability remains unexplored among medical educators in Asia including Hong Kong (HK). This study evaluates the validity of the WHO-5 when used among HK medical educators. METHOD: Using data from 435 medical educators, we employed combined within-network (confirmatory factor analysis; CFA) and between-network approaches (correlation and regression) to scale validation. RESULTS: CFA results indicated that our data fit the a priori WHO-5 model, suggesting structural validity. Results of comparison of means indicated no gender differences, but there were significant differences when participants were compared by age and professional backgrounds. Resilience predicted well-being as measured by the WHO-5, suggesting construct criterion validity. CONCLUSIONS: Our findings extend the validity evidence for the WHO-5 to HK medical educators examined in this study. This enables their well-being to be assessed when evaluating the impact of future well-being programmes.


Assuntos
Docentes de Medicina , Saúde Mental , Inquéritos e Questionários , COVID-19/epidemiologia , Análise Fatorial , Docentes de Medicina/psicologia , Hong Kong/epidemiologia , Humanos , Pandemias , Reprodutibilidade dos Testes , Organização Mundial da Saúde
14.
Australas J Dermatol ; 63(2): e159-e161, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35133665

RESUMO

Anticoagulant-induced skin necrosis is a rare and potentially life-threatening complication of anticoagulant therapy. The majority of cases of anticoagulant-induced skin necrosis have been attributed to warfarin, known as warfarin-induced skin necrosis (WISN). The use of anticoagulation reversal agents such as Prothrombinex-VF in the development of WISN is not a commonly documented phenomenon. The authors present a case of WISN post-recommencement of warfarin and the use of Prothrombinex-VF.


Assuntos
Toxidermias , Lesões dos Tecidos Moles , Anticoagulantes/efeitos adversos , Reversão da Anticoagulação , Toxidermias/etiologia , Humanos , Necrose/induzido quimicamente , Pele , Varfarina/efeitos adversos
15.
Int J Pharm ; 608: 121075, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34481889

RESUMO

PEGylation is the standard approach for prolonging the plasma exposure of protein therapeutics but has limitations. We explored whether polymers prepared by Reversible Addition-Fragmentation chain-Transfer (RAFT) may provide better alternatives to polyethylene glycol (PEG). Four RAFT polymers were synthesised with varying compositions, molar mass (Mn), and structures, including a homopolymer of N-(2-hydroxypropyl)methacrylamide, (pHPMA) and statistical copolymers of HPMA with poly(ethylene glycol methyl ether acrylate) p(HPMA-co-PEGA); HPMA and N-acryloylmorpholine, p(HPMA-co-NAM); and HPMA and N-isopropylacrylamide, p(HPMA-co-NIPAM). The intravenous pharmacokinetics of the polymers were then evaluated in rats. The in vitro activity and in vivo pharmacokinetics of p(HPMA-co-NIPAM)-conjugated trastuzumab Fab' and full length mAb were then evaluated. p(HPMA-co-NIPAM) prolonged plasma exposure more avidly compared to the other p(HPMA) polymers or PEG, irrespective of molecular weight. When conjugated to trastuzumab-Fab', p(HPMA-co-NIPAM) prolonged plasma exposure of the Fab' similar to PEG-Fab'. The generation of anti-PEG IgM in rats 7 days after intravenous and subcutaneous dosing of p(HPMA-co-NIPAM) conjugated trastuzumab mAb was also examined and was shown to exhibit lower immunogenicity than the PEGylated construct. These data suggest that p(HPMA-co-NIPAM) has potential as a promising copolymer for use as an alternative conjugation strategy to PEG, to prolong the plasma exposure of therapeutic proteins.


Assuntos
Polietilenoglicóis , Polímeros , Animais , Metacrilatos , Ratos , Trastuzumab
16.
Clin J Am Soc Nephrol ; 16(6): 898-907, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33910887

RESUMO

BACKGROUND AND OBJECTIVES: There have been doubts about the association between nonsteroidal anti-inflammatory drug use and worsening kidney function, and whether there is a difference between risks of individual nonsteroidal anti-inflammatory drugs is presently unclear. Therefore, this study aimed to evaluate the association between nonsteroidal anti-inflammatory drug exposure and the risk of incident eGFR <60 ml/min per 1.73 m2 and compare the risks between nonsteroidal anti-inflammatory drug subtypes in the Chinese population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From 2008 to 2017, a total of 1,982,488 subjects aged 18 years or older with baseline eGFR ≥60 ml/min per 1.73 m2 were enrolled in this retrospective cohort study. Multivariable Cox proportional hazards regression adjusted for each patient's baseline characteristics was adopted to examine the association between nonsteroidal anti-inflammatory drug and incident eGFR <60 ml/min per 1.73 m2 or eGFR decline ≥30% with reference to baseline. RESULTS: After a median follow-up duration of 6.3 (interquartile range, 3.3-9.4) years, 271,848 cases (14%) of incident eGFR <60 ml/min per 1.73 m2 and 388,386 (21%) events of eGFR decline ≥30% were recorded. After adjusting for each patient's baseline characteristics, nonsteroidal anti-inflammatory drug treatment was shown to be associated with a significantly higher risk of incident eGFR <60 ml/min per 1.73 m2 (hazard ratio, 1.71; 95% confidence interval, 1.67 to 1.75) and eGFR decline ≥30% (hazard ratio, 1.93; 95% confidence interval, 1.89 to 1.96) when compared with no nonsteroidal anti-inflammatory drug, with etoricoxib exhibiting the highest risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio, 3.12; 95% confidence interval, 2.69 to 3.62) and eGFR decline ≥30% (hazard ratio, 3.11; 95% confidence interval, 2.78 to 3.48) and ibuprofen displaying the lowest risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio, 1.12; 95% confidence interval, 1.02 to 1.23) and eGFR decline ≥30% (hazard ratio, 1.32; 95% confidence interval, 1.23 to 1.41). CONCLUSIONS: Nonsteroidal anti-inflammatory drug exposure was associated with higher risks of incident eGFR <60 ml/min per 1.73 m2 and eGFR decline ≥30%. Highest risk was observed in etoricoxib users, and lowest risk was with ibuprofen. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_04_28_CJN18501120.mp3.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Renal Crônica/fisiopatologia , Adulto , Idoso , China , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco
17.
BMC Fam Pract ; 22(1): 14, 2021 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422014

RESUMO

BACKGROUND: Primary care providers (PCPs) are typically the primary contact for patients with obesity seeking medical and surgical weight loss interventions; however, previous studies suggest that fewer than 7% of eligible adult patients are referred to publically funded medical and surgical weight loss interventions (MSWLI). METHODS: We performed an anonymous survey study between October 2017 and June 2018 to explore the knowledge, experiences, perceptions, and educational needs of PCPs in Southeastern Ontario in managing patients with class II and III obesity. RESULTS: Surveys were distributed to 591 PCPs (n = 538 family physicians; n = 53 nurse practitioners) identified as practicing in the Southeastern Ontario and 92 (15.6%) participated. PCPs serving a rural population estimated that 14.2 ± 10.9% of patients would qualify for MSWLI compared to 9.9 ± 8.5% of patients of PCPs serving an urban population (p = .049). Overall, 57.5% of respondents did not feel competent prescribing MSWLI to patients with class II/III obesity, while 69.8% stated they had 'good' knowledge of the referral criteria for MSWLI. 22.2% of respondents were hesitant to refer patients for bariatric surgery (BS) due to concerns about postoperative surgical complications and risks associated with surgery. Only 25% of respondents were comfortable providing long-term follow up after BS, and only 39.1% had participated in continuing education on management of patients with class II/III obesity in the past 5 years. CONCLUSION: The majority of PCPs believe there is a need for additional education about MSWLI for patients with class II/III obesity. Future studies are needed to develop and compare the effectiveness of additional education and professional development around risks of contemporary BS, indications to consider referral for MSWLI, management and long-term follow-up of patients after BS.


Assuntos
Médicos de Atenção Primária , Adulto , Humanos , Obesidade/epidemiologia , Obesidade/terapia , Ontário/epidemiologia , Percepção , Atenção Primária à Saúde , Inquéritos e Questionários
19.
J Am Acad Dermatol ; 82(2): 311-316, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31233857

RESUMO

BACKGROUND: The treatment response to new immunotherapy in advanced melanoma patients remains varied between individuals. Immune-related cutaneous side effects might have prognostic value. OBJECTIVE: To determine whether development of ≥1 of the 3 immune-mediated cutaneous events (eczema, lichenoid reaction, or vitiligo-like depigmentation) is associated with improved progression-free survival. METHODS: A cohort study of adults with stage IIIC-IV melanoma treated with pembrolizumab or nivolumab during May 1, 2012-February 1, 2018, at Westmead Hospital, Sydney, Australia. Treatment response was based on iRECIST version 1.1. RESULTS: In total, 82 patients of an average age of 59.9 years were included. Median follow-up was 40.7 months; 33 patients had ≥1 target skin reaction. Skin reactions developed in one-third of individuals by 6 months. At any given time, the instantaneous risk of disease progression and death was lower for individuals who had ≥1 cutaneous adverse event (CAE) develop. Compared with individuals with no CAE, the hazard ratio for disease progression and death for individuals who had ≥1 CAE develop was 0.46 (95% confidence interval 0.23-0.91; P = .025) by the time-dependent Cox proportional hazards model. LIMITATIONS: Single-center study. CONCLUSION: This study demonstrates an association between the development of ≥1 of 3 CAEs and improved progression-free survival in this cohort of patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Pele/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Austrália/epidemiologia , Eczema/induzido quimicamente , Eczema/epidemiologia , Eczema/imunologia , Feminino , Seguimentos , Humanos , Hipopigmentação/induzido quimicamente , Hipopigmentação/epidemiologia , Hipopigmentação/imunologia , Incidência , Erupções Liquenoides/induzido quimicamente , Erupções Liquenoides/epidemiologia , Erupções Liquenoides/imunologia , Masculino , Melanoma/imunologia , Melanoma/mortalidade , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Estudos Prospectivos , Pele/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Adulto Jovem
20.
Clin Teach ; 16(4): 384-389, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31397101

RESUMO

BACKGROUND: Educators have unique opportunities to cultivate resilience in themselves and in their learners across the medical education continuum through the formal, informal and hidden curricula. Yet, there is a dearth of research exploring how medical educators conceptualise resilience, and how they foster learner resilience in medical education. METHODS: Thematic framework analysis was conducted on data collected through an online questionnaire, which was part of a larger study exploring resilience in medical educators. Open-ended questions examined educators' conceptualisations of resilience and how they reported supporting resilience in their learners. Sociodemographic characteristics were also collected to describe the sample of participants. FINDINGS: A total of 244 medical educators participated from across the UK. They predominantly conceptualised resilience as an individual process. Participants mostly reported approaches to fostering learner resilience that aligned with the formal and informal curricula. Approaches addressing the hidden curriculum were seldom mentioned. DISCUSSION: Opportunities exist for faculty development around multidimensional conceptualisations of resilience, and for medical educators to critically reflect on how their concepts of resilience may be influencing their approach to fostering learner resilience. Furthermore, the hidden curriculum could be featured as one of the multifaceted strategies to support resilience in learners


Assuntos
Docentes de Medicina/psicologia , Resiliência Psicológica , Adulto , Estudos Transversais , Currículo , Educação Médica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Reino Unido , Adulto Jovem
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