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1.
BMC Public Health ; 24(1): 1806, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971784

RESUMO

BACKGROUND: Throughout history, vaccines have proven effective in addressing and preventing widespread outbreaks, leading to a decrease in the spread and fatality rates of infectious diseases. In a time where vaccine hesitancy poses a significant challenge to public health, it is important to identify the intricate interplay of factors exemplified at the individual and societal levels which influence vaccination behaviours. Through this analysis, we aim to shed new light on the dynamics of vaccine hesitancy among religious groups, contributing to the broader effort to promote vaccine uptake, dispel misunderstandings, and encourage constructive dialogue with these groups. METHODS: We used the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) using the 20-point checklist to guide this review. The inclusion criteria for our study were that the literature should be in English, concerned with vaccine hesitancy as the focus of study, study the impact religiosity or religious beliefs as either an outcome or control variable, concerning population levels, and be peer-reviewed. RESULTS: We analysed 14 peer-reviewed articles that included components related to religiosity or religious beliefs and their impact on vaccine hesitancy published until September 2023. All the articles were published in approximately the last decade between 2012 and 2023, with only 4 of the articles published before 2020. Out of the 14 studies included in our review, twelve utilized quantitative methods, while the remaining two employed qualitative approaches. Among the studies included in our analysis, we found various approaches to categorizing religious belief and identity. In most studies when religion is uniformly regarded as the sole determinant of vaccine hesitancy, it consistently emerges as a significant factor in contributing to vaccine hesitancy. All studies in our review reported sociodemographic factors to some degree related to vaccine hesitancy within their sample populations. Our analysis underscored the need for nuanced approaches to addressing vaccine hesitancy among religious groups. CONCLUSION: Vaccine hesitancy is a complex issue and driven by a myriad of individual and societal factors among which religious beliefs is commonly associated to be a driver of higher levels among populations.


Assuntos
Religião , Hesitação Vacinal , Humanos , Hesitação Vacinal/psicologia , Hesitação Vacinal/estatística & dados numéricos , Vacinação/psicologia , Vacinação/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde
2.
Musculoskeletal Care ; 22(2): e1908, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38898572

RESUMO

BACKGROUND: First Contact Physiotherapy Practitioners (FCPPs) provide expert care for patients with musculoskeletal (MSK) conditions in General Practice. Access to FCPPs can facilitate timely care and efficient use of health services. However, there is little evidence about patient experiences of accessing FCPP appointments. OBJECTIVE: To explore the experiences of patients with MSK conditions who have accessed an FCPP appointment in a General Practice setting in the UK. DESIGN: Exploratory qualitative design. METHODS: Patients with MSK conditions who had experience of accessing FCPP appointments were recruited via social media. Semi-structured interviews were conducted and recorded via MS Teams. Data were analysed using thematic analysis. RESULTS: Of 13 patients interviewed, there were 10 females and three males, with an age range between 20 and 80 years. The main themes identified were: (1) Awareness of FCPP, (2) Access routes, (3) Facilitators to access, (4) Barriers to access, (5) Likelihood of re-accessing FCPP. Awareness of FCPP was generally low amongst participants. There were a variety of routes to access FCPP appointments; some were felt to be sub-optimal by participants. Facilitators included quick/easy access to FCPP. Barriers included difficulty contacting General Practitioner (GP) surgeries and public perception of needing to see a GP initially. The likelihood of re-consultation with a FCPP was low when participants had disappointing care experiences. CONCLUSION: This study provides new evidence about patient experiences of accessing FCPP. It explores positive and negative aspects of access from patients' perspectives. It also highlights areas for improvement in terms of GP staff/patient awareness and understanding of FCPP.


Assuntos
Medicina Geral , Acessibilidade aos Serviços de Saúde , Doenças Musculoesqueléticas , Pesquisa Qualitativa , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Doenças Musculoesqueléticas/terapia , Doenças Musculoesqueléticas/reabilitação , Reino Unido , Idoso de 80 Anos ou mais , Agendamento de Consultas , Adulto Jovem , Modalidades de Fisioterapia
3.
Langmuir ; 40(20): 10623-10633, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38726951

RESUMO

Mixed A/B polyelectrolyte (PE) brushes of opposite charges are grown from a Y-shaped initiator-bearing coating to facilitate intimate mixing of the A and B polyelectrolytes in a 1:1 grafting ratio. The design of the Y-shaped inimer includes both ATRP and NMP initiators attached to a common Y-junction. A copolymer of a Y-shaped inimer with glycidyl methacrylate is cross-linked to the substrate resulting in a stable ultrathin coating decorated with Y-shaped initiators. Weak PE A/B mixed brushes based on poly(methacrylic acid)/poly(2-vinylpyridine) (PMAA/P2VP) with a high grafting density of ∼1 chain/nm2 are grown by surface-initiated ATRP and NMP, respectively. Detailed morphological characterization of the PMAA/P2VP brushes in response to pH changes reveals a nanoporous morphology under conditions that maximize complex coacervate formation between oppositely charged brushes. The charge ratio between the A and B brushes is varied via the composition of the brushes to further study the morphology evolution. The effect of intimate contact between the A and B brushes on the morphology is probed by comparing with a mixed A/B PE system with random fluctuations in grafting composition. A quantitative and qualitative study of the pore evolution with pH as well as charge composition is presented using a combination of atomic force microscopy, water contact angle measurement, and image analysis using Gwyddion software. These studies demonstrate that the porous morphology is enhanced and most uniform when the brushes are grown from the Y-inimer, indicating that a 1:1 grafting ratio and intimate contact between A and B brushes are essential.

4.
J Appl Psychol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780551

RESUMO

Organizations are increasingly expecting individuals to engage in task proactivity, that is, to find better ways of doing their job. While prior research has demonstrated the benefits of task proactivity, little is known about its cognitive costs. To investigate this issue, we build theory on how task proactivity affects end-of-day cognitive performance. We propose that task proactivity involves deviating from established ways of working and engaging in cognitively demanding activities requiring high levels of mental effort, which manifest as an erosion of end-of-day cognitive performance. In two daily diary studies, we found that individuals engaging in task proactivity experience lower end-of-day cognitive performance (Study 1 over five consecutive workdays: n = 163, k = 701; Study 2 with multiple daily assessments over seven consecutive workdays: n = 93, k = 471), even when controlling for task performance (Study 1) and beginning-of-day cognitive performance (Study 2). In two experiments, we then show that simulating task proactivity results in greater mental effort and lower routineness but not in greater ego depletion (Study 3: N = 318 and Study 4: N = 319) or increased self-control demands, -effort, or -motivation (Study 4). This provides support for our proposed cognitive pathway. Our findings enhance our understanding of the cognitively demanding nature of task proactivity and provide empirical support for its cognitive costs using a mental fatigue lens. They also suggest that the impact of a cognitively demanding activity like task proactivity may persist throughout the day and carry over to other tasks involving cognitive performance. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

5.
Pers Soc Psychol Bull ; : 1461672241247083, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38665035

RESUMO

People attend more to disadvantages in their lives than to advantages, a phenomenon known as the Headwinds/Tailwinds Asymmetry. In seven studies (N = 1,526), we present an important caveat to this pattern: When people do notice and acknowledge their advantages, they mostly focus on the benefits they receive from other people (i.e., interpersonal benefits), as opposed to benefits they receive because of their demographics, personal traits, and life circumstances (i.e., circumstantial benefits). We demonstrate that people notice and remember others who helped them rather than hurt them and that they notice the help they receive from people more than from favorable, non-interpersonal factors. Finally, we find that the tendency to notice interpersonal advantages is related to a social norm requiring people to acknowledge helpful others (but not other advantages) and that changing the salience of this norm affects people's likelihood of acknowledging the support they have received from others.

6.
Prev Vet Med ; 227: 106193, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38626594

RESUMO

Animal disease outbreaks, such as the recent outbreak of African Swine Fever in 2018, are a major concern for stakeholders across the food supply chain due to their potential to disrupt global food security, cause economic losses, and threaten animal welfare. As a result of their transboundary nature, discussions have shifted to preventive measures aimed at protecting livestock while ensuring food security and safety. Emergency assistance has been a critical response option during pandemics. However, this may not be sustainable in the long run because the expectation of government bailout may encourage risk taking behaviours. Our hypothesis is that an indemnity policy that is conditioned on showing biosecurity practices would increase compliance and reduce government expenditure during disease outbreaks. We developed and launched a survey from March to July 2022 targeted at swine producers across the US. From the survey, we examined livestock farmers' attitudes and intentions regarding biosecurity investment and assessed their attitudes towards the purchase of livestock insurance and reporting suspected infected livestock on their farm. We used a partial proportion odds model analysis to examine the model. Our analysis revealed that intention to call a veterinarian, trust in government agencies and risk perception of farmers were instrumental in the willingness to self-invest in biosecurity, purchase livestock insurance, and promptly report infected livestock on their farms. This provides evidence that biosecurity compliance would increase if indemnification was tied to a demonstration of effort to adopt biosecurity practices. We also show that individuals who have been in the industry for a longer period may become complacent and less likely to report outbreaks. Farmers with a higher share of income from their production operations bear a greater risk from their operational income and are more willing to report any suspected infections on their farms. The data suggest that motivating the willingness of farmers to invest in biosecurity while overcoming cost concerns is achievable.


Assuntos
Febre Suína Africana , Surtos de Doenças , Fazendeiros , Animais , Febre Suína Africana/prevenção & controle , Febre Suína Africana/epidemiologia , Febre Suína Africana/psicologia , Estados Unidos/epidemiologia , Surtos de Doenças/veterinária , Surtos de Doenças/prevenção & controle , Suínos , Fazendeiros/psicologia , Criação de Animais Domésticos/métodos , Biosseguridade , Humanos , Conhecimentos, Atitudes e Prática em Saúde , Masculino , Feminino , Inquéritos e Questionários
8.
J Lipid Res ; 65(3): 100514, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38309418

RESUMO

Human genetic evidence suggests a protective role of loss-of-function variants in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) for liver fibrotic diseases. Although there is limited preclinical experimental data on Hsd17b13 antisense oligonucleotide (ASO) or siRNA in a fibrosis model, several ASO and siRNA approaches are being tested clinically as potential therapies for nonalcoholic steatohepatitis (NASH). The aim of this study was to assess the therapeutic potential of Hsd17b13 ASO in a preclinical advanced NASH-like hepatic fibrosis in vivo model. In vitro testing on primary hepatocytes demonstrated that Hsd17b13 ASO exhibited strong efficacy and specificity for knockdown of the Hsd17b13 gene. In choline-deficient, L-amino acid-defined, HFD (CDAHFD)-induced steatotic and fibrotic mice, therapeutic administration of Hsd17b13 ASO resulted in a significant and dose-dependent reduction of hepatic Hsd17b13 gene expression. The CDAHFD group exhibited considerably elevated liver enzyme levels, hepatic steatosis score, hepatic fibrosis, and increased fibrotic and inflammatory gene expression, indicating an advanced NASH-like hepatic fibrosis phenotype. Although Hsd17b13 ASO therapy significantly affected hepatic steatosis, it had no effect on hepatic fibrosis. Our findings demonstrate, for the first time, that Hsd17b13 ASO effectively suppressed Hsd17b13 gene expression both in vitro and in vivo, and had a modulatory effect on hepatic steatosis in mice, but did not affect fibrosis in the CDAHFD mouse model of NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Modelos Animais de Doenças , Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/farmacologia , Oligonucleotídeos Antissenso/uso terapêutico , RNA Interferente Pequeno/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-38197703

RESUMO

BACKGROUND: Geographic location is a barrier to providing specialized care to pediatric traumas. In 2019, we instituted a pediatric teletrauma program in collaboration with the Statewide Pediatric Trauma Network at our level 1 pediatric trauma center (PTC). Triage guidelines were provided to partnering hospitals (PH) to aid in evaluation of pediatric traumas. Our pediatric trauma team was available for phone/video trauma consultation to provide recommendations on disposition and management. We hypothesized that this program would improve access and timely assessment of pediatric traumas while limiting patient transfers to our PTC. METHODS: A retrospective cohort study was conducted at the PTC between January 2019 to May 2023. All pediatric trauma patients age < 18 years who had teletrauma consults (TC) were included. We also evaluated all avoidable transfers without TC defined as admission for less than 36 hours without an intervention or imaging as a comparison group. RESULTS: A total of 151 TCs were identified: 62% male and median age of 8 years [IQR:4-12]. TC increased from 12 in 2019 to 100 in 2022-2023 and the number of partnering hospitals increased from 2 to 32. PH were 15-554 miles from the pediatric trauma center, with a median distance of 34 miles [IQR:28-119]. Following consultation, we recommended discharge 34%, admission 29%, or transfer to PTC 35%. Of those that were not transferred, 3% (3/97) required subsequent treatment at the PTC. Non-transferred TC had a higher percentage of TBI (61% vs 31%;p < 0.001) and were from farther, (40 miles[IQR:28-150] vs 30 miles[IQR:28-50];p < 0.001) compared to avoidable transferred patients without a TC. CONCLUSIONS: TC is a safe and viable addition to a pediatric trauma program faced with providing care to a large geographical catchment area. The pediatric teletrauma program provided management recommendations to 32 partnering hospitals and avoided transfer in approximately 63% of cases. LEVEL OF EVIDENCE: IV Treatment study.

10.
J Adv Nurs ; 80(4): 1283-1298, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37849045

RESUMO

AIM: To inform efforts to integrate gender and race into moral distress research, the review investigates if and how gender and racial analyses have been incorporated in such research. DESIGN: Scoping review. METHODS: The PRISMA (Preferred Reporting Items for Systematic and Meta-Analysis) Extension for Scoping Reviews was adopted. DATA SOURCES: Systematic literature search was conducted through PubMed, CINAHL and Web of Science databases. Boolean operators were used to identify moral distress literature which included gender and/or race data and published between 2012 and 2022. RESULTS: After screening and full-text review, 73 articles reporting on original moral distress research were included. Analysis was conducted on how gender and race were incorporated in research and interpretation of moral distress experiences among healthcare professionals. IMPACT: This study found that while there is an upward trend in including gender and race-disaggregated data in moral distress research, over half of such research did not conduct in-depth analysis of such data. Others only highlighted differential experiences such as moral distress levels of women vis-à-vis men. Only about 20% of publications interrogated how experiences of moral distress differed and/or explored factors behind their findings. CONCLUSION: There is a need to not only collect disaggregated data in moral distress research but also engage this data through gender and race-based analysis. Particularly, we highlight the need for intersectional analysis, which can elucidate how social identities and categories (such as gender and race) and structural inequalities (such as those sustained by sexism and racism) interact to influence moral experiences. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Moral distress as experienced by healthcare professionals is increasingly recognized as an important area of research with significant policy implications in the healthcare sector. This study offers insights for nuanced and targeted policy approaches. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.


Assuntos
Identidade de Gênero , Pessoal de Saúde , Masculino , Humanos , Feminino , Princípios Morais , Estresse Psicológico
11.
Vaccine ; 42(3): 522-528, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38154991

RESUMO

BACKGROUND: Myocarditis and myopericarditis are well described adverse events of special interest (AESI) following COVID-19 vaccinations. Although reports are reassuring regarding initial clinical outcomes, information about longer term outcomes remains limited. We aimed to further this knowledge and report outcomes to 6 months post diagnosis from a single population cohort. METHODS: Reports of myocarditis following COVID-19 vaccination were followed up by SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community), the state-wide vaccine safety service for Victoria, Australia. Confirmed myocarditis cases (Brighton Collaboration Criteria levels 1-3) were followed up via surveys at 1, 3 and 6 months post symptom onset. Responses received between 22 February 2021 and 30 September 2022 were analysed. RESULTS: 87.5 % (N = 182) of eligible participants completed at least 1 survey report. 377 reports were analysed. 76.9 % of completed reports were from male patients. The median age of patients was 21 years [IQR: 16 to 32]. 54.8 % (n = 74) of survey reports at 6 months, reported ongoing symptoms. At all follow-up time points, females were significantly more likely to have ongoing symptoms. At 6 months, 51.9 % of male respondents reported symptom resolution compared to 22.6 % of female patients (p = 0.002). Females were also more likely to continue medication and have ongoing exercise restrictions. However, males were significantly more likely to have higher initial peak troponin results and abnormal initial cardiac imaging investigations. CONCLUSIONS: There appears to be a significant proportion of patients who experience ongoing symptoms to 6 months post onset amongst patients that experience these AESI. Male patients were more likely to report earlier and more complete symptom recovery, despite significantly higher average initial peak troponin. This difference in phenotypic presentation in females compared to males warrants further investigation and there is a need for longer term follow up data.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Miocardite , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Seguimentos , Miocardite/induzido quimicamente , Miocardite/epidemiologia , Troponina , Vacinação/efeitos adversos , Vitória/epidemiologia
12.
Chemosphere ; 349: 140957, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128742

RESUMO

Microplastics and microfibres are found ubiquitously in global oceans as well as marine organisms from different trophic levels. However, little is known about the presence of microplastics and microfibres in marine megafauna, such as sharks. This study provided the first investigation of the presence of microplastics and other anthropogenic fibres (i.e., cellulose based fibres) in intestine and muscle samples of four large apex shark species in Australian coastal waters. Microplastics and other anthropogenic fibres were found in 82% of the analysed intestine samples. The mean abundance in intestine samples was 3.1 ± 2.6 particles/individual, which corresponded to 0.03 ± 0.02 particles/g of intestine, across all shark species. The size of particles ranged from 190 to 4860 µm in length with 92% being fibrous in shape and the rest fragments. FTIR spectroscopy identified that 70% of fibres were cellulose-based followed by polyethylene terephthalate (PET), while the fragments were polyethylene and polypropylene. In shark muscles, 60% of samples contained microplastics and other anthropogenic fibres, again with the majority being cellulose-based fibres followed by PET fibres. Methodological differences hinder a more comprehensive assessment of microplastic contamination across studies. Additionally, we identified some challenges which should be factored in for future studies looking at the presence of microplastics as well as other anthropogenic fibres in these large marine organisms. Overall, the findings provide first evidence of microplastics and other anthropogenic fibres not only in the intestines, but also in muscle tissues of large apex shark species.


Assuntos
Microplásticos , Poluentes Químicos da Água , Microplásticos/análise , Plásticos/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Austrália , Celulose , Polietilenotereftalatos
13.
BMC Public Health ; 23(1): 2497, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093212

RESUMO

The COVID-19 pandemic disproportionately affected those who face historical and ongoing marginalization. In centering pandemic experience of recent immigrant women in the accommodation and food services sector in Canada, we examine how their precarious work translated to experiences of work precarity and wellbeing. This paper illuminates how pre-existing and ongoing marginalization are reproduced during a health crisis for those at the intersection of gender, race, migration, and labour inequities. Using semi-structured interviews and systematic analysis using the Work Precarity Framework, we found that the pandemic exacerbated pre-existing socio-economic marginalization and resulted in unique experiences of work precarity. The latter was experienced as precarity of work (unpredictable work hours and job or employment insecurity), precarity from work (inadequate incomes), and precarity at work (physical, psychological, and relational unsafety). Work precarity stood out as a social determinant of health in relation to its outcome of degraded mental health and wellbeing. Recognizing the role of policies in producing, reproducing, and distributing precarity, we recommend policy directions to reduce social inequities in pandemic recovery.


Assuntos
Emigrantes e Imigrantes , Pandemias , Humanos , Feminino , Canadá/epidemiologia , Renda , Saúde Mental
14.
J Aging Health ; : 8982643231212981, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37943505

RESUMO

Objectives: In this study, we aimed to explore the relationship between intersectional inequities and moral distress among those working in Long-Term Care (LTC) in British Columbia, Canada. Methods: This was a cross-sectional and retrospective study. We assessed moral distress, of 1678 respondents, using a modified Moral Distress Scale, and an equivalent distress mitigation score, at the intersections of gender and racial/ethnic identity. Then, we explored which worker attributes were more predictive of intention to leave work. Results: We found notable difference in experiences of moral distress across intersecting identities, including high moral distress scores among Indigenous men and women, and white women. Significant differences in mitigation scores were also found by intersectional identities. Discussion: Moral distress was the most important predictor of intention to leave work. The differences across racial and gender identity groups suggest the need for tailored interventions to address moral distress among LTC providers.

15.
Glob Public Health ; 18(1): 2264946, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-37801724

RESUMO

The health burden due to mental health has historically been underestimated with focus on communicable diseases and deaths and little consideration of disability and comorbidity effects of poor mental health. Recent data show increasing trends of mental health disorders as a share of global health burdens and vulnerability of adolescents. This paper aims to explore social determinants of mental health as experienced by adolescent girls, drawing attention to gendered risks during the COVID-19 pandemic. Semi-structured interviews with twenty-two adolescent girls in urban informal settlements in Kenya and Nigeria reveal unique environmental, socio-cultural, economic and educational factors that threatened their mental wellbeing. The pandemic exacerbated these determinants. An equitable recovery will require a consideration of not only disproportional mental health outcomes, but also social determinants that contribute to these outcomes. As more than half of the urban population in sub-Saharan Africa reside in informal settlements, this study has implications for youth-focused mental health interventions in these and similar settings.


Assuntos
COVID-19 , Feminino , Adolescente , Humanos , Quênia/epidemiologia , COVID-19/epidemiologia , Nigéria/epidemiologia , Pandemias , Saúde Mental , Determinantes Sociais da Saúde
16.
Ann Rheum Dis ; 82(12): 1516-1526, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37699654

RESUMO

OBJECTIVES: To investigate the efficacy and safety of otilimab, an antigranulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis. METHODS: Two phase 3, double-blind randomised controlled trials including patients with inadequate responses to methotrexate (contRAst 1) or conventional synthetic/biologic disease-modifying antirheumatic drugs (cs/bDMARDs; contRAst 2). Patients received background csDMARDs. Through a testing hierarchy, subcutaneous otilimab (90/150 mg once weekly) was compared with placebo for week 12 endpoints (after which, patients receiving placebo switched to active interventions) or oral tofacitinib (5 mg two times per day) for week 24 endpoints. PRIMARY ENDPOINT: proportion of patients achieving an American College of Rheumatology response ≥20% (ACR20) at week 12. RESULTS: The intention-to-treat populations comprised 1537 (contRAst 1) and 1625 (contRAst 2) patients. PRIMARY ENDPOINT: proportions of ACR20 responders were statistically significantly greater with otilimab 90 mg and 150 mg vs placebo in contRAst 1 (54.7% (p=0.0023) and 50.9% (p=0.0362) vs 41.7%) and contRAst 2 (54.9% (p<0.0001) and 54.5% (p<0.0001) vs 32.5%). Secondary endpoints: in both trials, compared with placebo, otilimab increased the proportion of Clinical Disease Activity Index (CDAI) low disease activity (LDA) responders (not significant for otilimab 150 mg in contRAst 1), and reduced Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. Benefits with tofacitinib were consistently greater than with otilimab across multiple endpoints. Safety outcomes were similar across treatment groups. CONCLUSIONS: Although otilimab demonstrated superiority to placebo in ACR20, CDAI LDA and HAQ-DI, improved symptoms, and had an acceptable safety profile, it was inferior to tofacitinib. TRIAL REGISTRATION NUMBERS: NCT03980483, NCT03970837.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Humanos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Metotrexato/uso terapêutico , Produtos Biológicos/uso terapêutico , Resultado do Tratamento , Método Duplo-Cego , Pirróis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Ann Rheum Dis ; 82(12): 1527-1537, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37696589

RESUMO

OBJECTIVES: To investigate the efficacy and safety of otilimab, an anti-granulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis and an inadequate response to conventional synthetic (cs) and biologic disease-modifying antirheumatic drugs (DMARDs) and/or Janus kinase inhibitors. METHODS: ContRAst 3 was a 24-week, phase III, multicentre, randomised controlled trial. Patients received subcutaneous otilimab (90/150 mg once weekly), subcutaneous sarilumab (200 mg every 2 weeks) or placebo for 12 weeks, in addition to csDMARDs. Patients receiving placebo were switched to active interventions at week 12 and treatment continued to week 24. The primary end point was the proportion of patients achieving an American College of Rheumatology ≥20% response (ACR20) at week 12. RESULTS: Overall, 549 patients received treatment. At week 12, there was no significant difference in the proportion of ACR20 responders with otilimab 90 mg and 150 mg versus placebo (45% (p=0.2868) and 51% (p=0.0596) vs 38%, respectively). There were no significant differences in Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index, pain Visual Analogue Scale or Functional Assessment of Chronic Illness Therapy-Fatigue scores with otilimab versus placebo at week 12. Sarilumab demonstrated superiority to otilimab in ACR20 response and secondary end points. The incidence of adverse or serious adverse events was similar across treatment groups. CONCLUSIONS: Otilimab demonstrated an acceptable safety profile but failed to achieve the primary end point of ACR20 and improve secondary end points versus placebo or demonstrate non-inferiority to sarilumab in this patient population. TRIAL REGISTRATION NUMBER: NCT04134728.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Antirreumáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento , Método Duplo-Cego , Metotrexato/uso terapêutico
19.
IJID Reg ; 8: 19-27, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37317681

RESUMO

Background: Healthcare workers have experienced high rates of morbidity and mortality from coronavirus disease 2019 (COVID-19). Methods: A prospective cohort study was conducted in three Albanian hospitals between 19 February and 14 December 2021. All participants underwent polymerase chain reaction (PCR) and serological testing at enrolment, regular serology throughout, and PCR testing when symptomatic.Vaccine effectiveness (VE) against COVID-19 and against all severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections (symptomatic or asymptomatic) was estimated. VE was estimated using a Cox regression model, with vaccination status as a time-varying variable. Findings: In total, 1504 HCWs were enrolled in this study; 70% had evidence of prior SARS-CoV-2 infection. VE was 65.1% [95% confidence interval (CI) 37.7-80.5] against COVID-19, 58.2% (95% CI 15.7-79.3) among participants without prior SARS-CoV-2 infection, and 73.6% (95% CI 24.3-90.8) among participants with prior SARS-CoV-2 infection. For BNT162b2 alone, VE was 69.5% (95% CI 44.5-83.2). During the period when the Delta variant was predominant, VE was 67.1% (95% CI 38.3-82.5). VE against SARS-CoV-2 infection for the full study period was 36.9% (95% CI 15.8-52.7). Interpretation: This study found moderate primary series VE against COVID-19 among healthcare workers in Albania. These results support the continued promotion of COVID-19 vaccination in Albania, and highlight the benefits of vaccination in populations with high levels of prior infection.

20.
Langmuir ; 39(23): 8267-8278, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37253273

RESUMO

Polymer brushes with controllable grafting density are grown on an inimer coating bearing Reversible Addition-Fragmentation Chain Transfer polymerization (RAFT) chain transfer agents (CTAs). The inimer coating is cross-linked on the substrate to provide an initiator layer that is stable during exposure to organic solvents at high temperatures. Surface-initiated RAFT is conducted to grow poly(2-vinylpyridine) (P2VP) brushes on the coating at grafting densities approaching the theoretical limits. This methodology allows facile end-group functionalization using an efficient thiol-ene click chemistry. Chain ends were functionalized with low surface energy groups to modulate the location of the untethered chain ends by thermal annealing. At lower grafting densities, the low surface energy groups segregate to the surface upon annealing. This effect is less pronounced at higher grafting densities. Detailed characterization of the brushes at varying grafting densities using X-ray photoelectron spectroscopy (XPS) is presented. In tandem with experiments, Monte Carlo simulations examine the effect of the chain-end group size and selectivity on the conformation of the polymer brush, providing numerical evidence of laterally non-uniform distributions of functional groups at different locations in the brush. Simulations further predict the existence of morphologies with an interlayer formed by spherical micelles rich in functional end groups, demonstrating the possibility of end-group functionalization for synthetic modulation of both brush conformation and chain-end location.

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