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1.
Int J Paediatr Dent ; 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37969051

RESUMO

BACKGROUND: Molar-incisor hypomineralisation (MIH) is a prevalent condition, and how it is managed varies greatly between professional groups. AIM: To explore, and compare, the UK and Australian general dental practitioners' management of MIH in children. DESIGN: Face-to-face (remote) semistructured interviews were undertaken, using country-specific topic guides. Participants were purposively sampled and recruited through national conferences and research networks (eviDent Foundation and Northern Dental Practice Based Research Network). Interviews (from each country) were audio-recorded, transcribed verbatim and independently analysed using thematic analysis. RESULTS: Two major themes arose from the UK interviews: (i) decision-making complexities and understanding of treatment options and (ii) need for specialist input. The main Australian themes were (i) multidisciplinary approach to management supporting decision-making complexities and (ii) economic implications for care. Several difficulties, such as financial implications, multidisciplinary care and clinical decision-making, were identified as barriers to effectively managing MIH by GDPs in primary care. CONCLUSION: There are similarities and differences in the knowledge and management of MIH amongst UK and Australian nonspecialists. The different healthcare systems played a significant role in shaping how GDPs manage MIH with barriers relating to affordability, multidisciplinary care and clinical decision-making.

2.
Environ Toxicol Chem ; 42(8): 1791-1805, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37283216

RESUMO

Early life stages are commonly thought to be highly sensitive to environmental contaminants and may offer insight into the future health of a population. Despite the importance of studying early life stages, very few standard protocols for benthic invertebrates commonly used in ecotoxicological assessments measure developmental endpoints. The goal of the present study was to develop and optimize a robust standard protocol for studying embryonic endpoints in freshwater gastropods. The developed method was then used to characterize the sensitivity of four embryonic endpoints (viability, hatching, deformities, and biomass production), in conjunction with juvenile and adult mortality, for the snail Planorbella pilsbryi exposed to three metals (copper [Cu], cadmium [Cd], and nickel [Ni]). Biomass production was typically the most sensitive endpoint but was relatively variable, while embryo hatching was slightly less sensitive but highly consistent for all three metals. However, no single embryonic endpoint was consistently the most sensitive, which demonstrates the importance of assessing a broad range of endpoints and life stages in ecotoxicological risk assessment. Interestingly, the embryonic life stage of P. pilsbryi was considerably less sensitive to Cu exposure compared with juvenile and adult mortality. However, for Cd exposure, embryonic endpoints were the most sensitive, and for Ni exposure, embryonic endpoints were similar in sensitivity to juvenile and adult mortality. The present study has valuable applications in conducting developmental toxicity research with organisms lacking standardized testing protocol as well as future applications in multigenerational and in silico toxicity research. Environ Toxicol Chem 2023;42:1791-1805. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Assuntos
Gastrópodes , Metais , Testes de Toxicidade , Poluentes Químicos da Água , Embrião não Mamífero , Água Doce , Metais/toxicidade , Animais , Cádmio , Cobre/toxicidade , Níquel/toxicidade
3.
J Sci Med Sport ; 25(4): 287-292, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35016820

RESUMO

OBJECTIVES: We assessed the diagnostic yield and costs of an electrocardiogram-based national screening programme in elite cricket players and the incremental value of transthoracic echocardiography and periodic evaluation. DESIGN: Cross-sectional study. METHODS: Between 2008 and 2019, 1208 cricketers underwent screening with a health questionnaire, 12-lead electrocardiogram and cardiology consultation. Athletes with concerning findings underwent on-site transthoracic echocardiography and further investigations as necessary. In addition, despite a normal health questionnaire and electrocardiogram, 342 (28.3%) athletes had a transthoracic echocardiogram and 493 (40.8%) underwent repeat evaluations. RESULTS: After initial evaluation, 47 (3.9%) athletes underwent on-site transthoracic echocardiography of whom 35 (2.8%) were referred for further evaluation. Four athletes (0.3%) were diagnosed with major cardiac conditions; hypertrophic cardiomyopathy (n = 1), arrhythmogenic cardiomyopathy (n = 1) and Wolff-Parkinson-White pattern (n = 2). Two athletes were identified with minor valvular abnormalities. Repeat evaluation of 493 athletes identified hypertrophic cardiomyopathy in a 22-year-old athlete, two years after his initial normal screening. During a follow-up of 5.8 ±â€¯2.9 years no additional diagnoses or adverse cardiac events were reported. The cost of the electrocardiogram-based programme was £127,844, translating to £106 per athlete and £25,569 per major cardiac condition identified.Routine transthoracic echocardiography in 342 athletes identified two athletes with major cardiac conditions (bicuspid aortic valve with severe aortopathy and aortic regurgitation and an atrial septal defect associated with right ventricular volume overload) and 10 athletes with minor abnormalities. CONCLUSIONS: An electrocardiogram-based national screening programme identified a major cardiac condition in 0.3% of athletes. Routine transthoracic echocardiography and periodic evaluation increased the diagnostic yield to 0.6%, at an incremental cost.


Assuntos
Morte Súbita Cardíaca , Cardiopatias , Adulto , Atletas , Estudos Transversais , Morte Súbita Cardíaca/prevenção & controle , Eletrocardiografia/métodos , Cardiopatias/diagnóstico , Humanos , País de Gales , Adulto Jovem
4.
J. obstet. gynaecol. Can ; 43(1): 91-105, Jan. 1, 2021.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1146603

RESUMO

This guideline reviews the clinical evaluation and management of gestational trophoblastic diseases, including surgical and medical management of benign, premalignant, and malignant entities. The objective of this guideline is to assist health care providers in promptly diagnosing gestational trophoblastic diseases, to standardize treatment and follow-up, and to ensure early specialized care of patients with malignant or metastatic disease. General gynaecologists, obstetricians, family physicians, midwives, emergency department physicians, anaesthesiologists, radiologists, pathologists, registered nurses, nurse practitioners, residents, gynaecologic oncologists, medical oncologists, radiation oncologists, surgeons, general practitioners in oncology, oncology nurses, pharmacists, physician assistants, and other health care providers who treat patients with gestational trophoblastic diseases. This guideline is also intended to provide information for interested parties who provide follow-up care for these patients following treatment. Women of reproductive age with gestational trophoblastic diseases. Women diagnosed with a gestational trophoblastic disease should be referred to a gynaecologist for initial evaluation and consideration for primary surgery (uterine evacuation or hysterectomy) and follow-up. Women diagnosed with gestational trophoblastic neoplasia should be referred to a gynaecologic oncologist for staging, risk scoring, and consideration for primary surgery or systemic therapy (single- or multi-agent chemotherapy) with the potential need for additional therapies. All cases of gestational trophoblastic neoplasia should be discussed at a multidisciplinary cancer case conference and registered in a centralized (regional and/or national) database. Relevant studies from 2002 onwards were searched in Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and Cochrane Systematic Reviews using the following terms, either alone or in combination: trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome, and remission. The initial search was performed in April 2017 and updated in May 2019. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 673, with 79 studies cited in this review. The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of Directors of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of Directors for the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. See the online appendix tables for key to grading and interpretation of recommendations. These guidelines will assist physicians in promptly diagnosing gestational trophoblastic diseases and urgently referring patients diagnosed with gestational trophoblastic neoplasia to gynaecologic oncology for specialized management. Treating gestational trophoblastic neoplasia in specialized centres with the use of centralized databases allows for capturing and comparing data on treatment outcomes of patients with these rare tumours and for optimizing patient care.


Assuntos
Humanos , Feminino , Gravidez , Biomarcadores Tumorais/sangue , Doença Trofoblástica Gestacional/diagnóstico , Doença Trofoblástica Gestacional/terapia , Gonadotropina Coriônica/sangue , Mola Hidatiforme/terapia
5.
Br J Dermatol ; 180(6): 1506-1516, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30597532

RESUMO

BACKGROUND: Health literacy (HL) - the ability to seek, understand and utilize health information - is important for good health. Suboptimal HL has been associated with poorer health outcomes in other chronic conditions, although this has not previously been studied in patients with psoriasis. OBJECTIVES: To investigate the HL strengths and weaknesses of a cohort of patients with moderate-to-severe psoriasis. Another aim was to examine possible associations between patients' quality of life, their demographic, clinical and self-management characteristics, and dimensions of HL. METHODS: A cross-sectional study was conducted. Data were collected from a cohort of patients with psoriasis who had received climate helio therapy from 2011 to 2016 (n = 825). HL was assessed by the Health Literacy Questionnaire (HLQ). The association between HL domains, demographic, clinical and self-management variables were analysed using bivariate correlation and a four-step linear multiple regression model. RESULTS: The scores on all HLQ dimensions indicated lower health literacy than other populations. The linear regression models showed a significant association between HL, quality of life and self-management variables, with higher HL predicting higher quality of life, self-efficacy and psoriasis knowledge. Sex, educational attainment, age and disease severity had less influence on health literacy. CONCLUSIONS: Improving HL may be a useful strategy for reducing disparities in self-management skills for patients with psoriasis. Interventions that aim to reduce disease severity and increase psoriasis knowledge, self-efficacy and quality of life may positively increase HL.


Assuntos
Letramento em Saúde , Educação de Pacientes como Assunto , Psoríase/terapia , Autogestão , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica/terapia , Estudos de Coortes , Estudos Transversais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Qualidade de Vida , Índice de Gravidade de Doença , Adulto Jovem
7.
Environ Pollut ; 218: 428-435, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27450416

RESUMO

Neonicotinoid insecticides can be transported from agricultural fields, where they are used as foliar sprays or seed treatments, to surface waters by surface or sub-surface runoff. Few studies have investigated the toxicity of neonicotinoid or the related butenolide insecticides to freshwater mollusk species. The current study examined the effect of neonicotinoid and butenolide exposures to the early-life stages of the ramshorn snail, Planorbella pilsbryi, and the wavy-rayed lampmussel, Lampsilis fasciola. Juvenile P. pilsbryi were exposed to imidacloprid, clothianidin, or thiamethoxam for 7 or 28 d and mortality, growth, and biomass production were measured. The viability of larval (glochidia) L. fasciola was monitored during a 48 h exposure to six neonicotinoids (imidacloprid, thiamethoxam, clothianidin, acetamiprid, thiacloprid, or dinotefuran), or a butenolide (flupyradifurone). The 7-d LC50s of P. pilsbryi for imidacloprid, clothianidin, and thiamethoxam were ≥4000 µg/L and the 28-d LC50s were ≥182 µg/L. Growth and biomass production were considerably more sensitive endpoints than mortality with EC50s ranging from 33.2 to 122.0 µg/L. The 48-h LC50s for the viability of glochidia were ≥456 µg/L for all seven insecticides tested. Our data indicate that neonicotinoid and butenolide insecticides pose less of a hazard with respect to mortality of the two species of mollusk compared to the potential hazard to other non-target aquatic insects.


Assuntos
4-Butirolactona/análogos & derivados , Monitoramento Ambiental/métodos , Água Doce/química , Inseticidas/toxicidade , Piridinas/toxicidade , Unionidae/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , 4-Butirolactona/química , 4-Butirolactona/toxicidade , Animais , Guanidinas/química , Guanidinas/toxicidade , Imidazóis/química , Imidazóis/toxicidade , Inseticidas/química , Neonicotinoides , Nitrocompostos/química , Nitrocompostos/toxicidade , Oxazinas/química , Oxazinas/toxicidade , Piridinas/química , Tiametoxam , Tiazinas/química , Tiazinas/toxicidade , Tiazóis/química , Tiazóis/toxicidade , Unionidae/crescimento & desenvolvimento , Poluentes Químicos da Água/química
8.
Osteoarthritis Cartilage ; 24(8): 1357-66, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27038491

RESUMO

OBJECTIVE: This study reports the development of the OsteoArthritis Questionnaire (OA-Quest) - a new measure designed to comprehensively capture the potentially modifiable burden of osteoarthritis. DESIGN: Item development was guided by the a priori conceptual framework of the Personal Burden of Osteoarthritis (PBO) which captures 8 dimensions of osteoarthritis burden (Physical distress, Fatigue, Physical limitations, Psychosocial distress, Physical de-conditioning, Financial hardship, Sleep disturbances, Lost productivity). One hundred and twenty three candidate items were pretested in a clinical sample of 18 osteoarthritis patients. The measurement properties of the OA-Quest were assessed with exploratory factor analysis (EFA), Rasch modelling, and confirmatory factor analysis (CFA) in a community-based sample (n = 792). RESULTS: EFA replicated 7 of the 8 PBO domains. An exception was PBO Fatigue domain, with items merging into the Physical distress subscale in the OA-Quest. Following item analysis, a 42-item 7-subscale questionnaire was constructed, measuring Physical distress (seven items, Cronbach's α = 0.93), Physical limitations (11 items, α = 0.95), Psychosocial distress (seven items, α = 0.93), Physical de-conditioning (four items, α = 0.87), Financial hardship (four items, α = 0.93), Sleep disturbances (five items, α = 0.96), and Lost productivity (four items α = 0.90). A highly restricted 7-factor CFA model had excellent fit with the data (χ(2)(113) = 316.36, P < 0.001; chi-square/degrees of freedom = 2.8; comparative fit index [CFI] = 0.97; root mean square error of approximation [RMSEA] = 0.07), supporting construct validity of the new measure. CONCLUSIONS: The OA-Quest is a new measure of osteoarthritis burden that is founded on a comprehensive conceptual model. It has strong evidence of construct validity and provides reliable measurement across a broad range of osteoarthritis burden.


Assuntos
Osteoartrite , Eficiência , Análise Fatorial , Humanos , Psicometria , Inquéritos e Questionários
9.
Public Health ; 132: 3-12, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26872738

RESUMO

The concept of 'health literacy' refers to the personal and relational factors that affect a person's ability to acquire, understand and use information about health and health services. For many years, efforts in the development of the concept of health literacy exceeded the development of measurement tools and interventions. Furthermore, the discourse about and development of health literacy in public health and in clinical settings were often substantially different. This paper provides an update about recently developed approaches to measurement that assess health literacy strengths and limitations of individuals and of groups across multiple aspects of health literacy. This advancement in measurement now allows diagnostic and problem-solving approaches to developing responses to identified strengths and limitations. In this paper, we consider how such an approach can be applied across the diverse range of settings in which health literacy has been applied. In particular, we consider some approaches to applying health literacy in the daily practice of health-service providers in many settings, and how new insights and tools--including approaches based on an understanding of diversity of health literacy needs in a target community--can contribute to improvements in practice. Finally, we present a model that attempts to integrate the concept of health literacy with concepts that are often considered to overlap with it. With careful consideration of the distinctions between prevailing concepts, health literacy can be used to complement many fields from individual patient care to community-level development, and from improving compliance to empowering individuals and communities.


Assuntos
Atenção à Saúde/organização & administração , Letramento em Saúde , Disparidades em Assistência à Saúde , Humanos
10.
Clin Exp Dermatol ; 41(2): 148-51, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25703642

RESUMO

We present a rare condition, hyperkeratosis of the areola, induced by vemurafenib. Only a few papers have described an association of BRAF inhibitors with hyperkeratosis of the areola and/or nipple. Vemurafenib is a selective BRAF inhibitor used in patients with unresectable or metastatic melanoma who are positive for the V600 mutation. This drug has been associated with numerous cutaneous side effects, both benign and malignant. We report a male patient with vemurafenib-induced hyperkeratosis of the areola managed successfully with a topical retinoid, and describe for the first time a treatment for this side effect.


Assuntos
Adapaleno/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Antineoplásicos/efeitos adversos , Fármacos Dermatológicos/administração & dosagem , Indóis/efeitos adversos , Ceratose/tratamento farmacológico , Mamilos , Sulfonamidas/efeitos adversos , Humanos , Ceratose/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vemurafenib
11.
Arch Osteoporos ; 10: 229, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26272712

RESUMO

UNLABELLED: A randomised controlled trial of vertebroplasty (VP) versus placebo assessed the effect of VP on the risk of further vertebral fractures. While no statistically significant between-group differences for new or progressed fracture risk at 12 and 24 months were observed, we observed a consistent trend towards higher risk of any type of fracture in the group undergoing VP. Our analysis was underpowered, and further adequately powered studies are needed to be able to draw firm conclusions about further vertebral risk with vertebroplasty. PURPOSE: This study seeks to assess the effect of VP on the risk of further radiologically apparent vertebral fracture within two years of the procedure. METHODS: We conducted a randomised placebo-controlled trial of VP in people with acute osteoporotic vertebral fracture. Eligible participants were randomly assigned to VP (n = 38) or placebo (n = 40). Cement volume and leakage were recorded for the VP group. Plain thoracolumbar radiographs were taken at baseline, 12 and 24 months. Two independent radiologists assessed these for new and progressed fractures at the same, adjacent and non-adjacent levels. RESULTS: At 12 and 24 months, radiographs were available for 45 (58 %) and 47 (60 %) participants, respectively. There were no between-group differences for new or progressed fractures: 32 and 40 in the VP group after 12 and 24 months compared with 21 and 33 in the placebo group (hazard ratio (HR) 1.80, 95 % confidence interval (CI) 0.82 to 3.94). Similar results were seen when considering only adjacent (HR (95 % CI) 2.30 (0.57 to 9.29)) and non-adjacent (HR (95 % CI) 1.45 (0.55 to 3.81) levels. In all comparisons, there was a consistent trend towards higher risk of any type of fracture in the group undergoing VP. Within the VP group, fracture risk was unrelated to total (HR (95 % CI) 0.91 (0.71 to 1.17)) or relative (HR (95 % CI) 1.31 (0.15 to 11.48)) cement volume or cement leakage (HR (95 % CI) 1.20 (0.63 to 2.31)). CONCLUSION: For patients undergoing VP, our study did not demonstrate significant increases in subsequent fracture risk beyond that experienced by those with vertebral fractures who did not undergo the procedure. However, because of the non-significant numerical increases observed, studies with adequate power are needed to draw definite conclusions about fracture risk.


Assuntos
Fraturas por Osteoporose/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Vertebroplastia/efeitos adversos , Idoso , Cimentos Ósseos , Feminino , Fraturas por Compressão/epidemiologia , Fraturas por Compressão/etiologia , Fraturas por Compressão/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/cirurgia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/cirurgia
12.
Eur J Cancer ; 51(14): 2049-57, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26208461

RESUMO

AIMS: The aims of this analysis were to examine levels of unmet needs and depression among carers of people newly diagnosed with cancer and to identify groups who may be at higher risk, by examining relationships with demographic characteristics. METHODS: One hundred and fifty dyads of people newly diagnosed with cancer and their carers, aged 18 years and older, were recruited from four Australian hospitals. People with cancer receiving adjuvant cancer treatment with curative intent, were eligible to participate. Carers completed the Supportive Care Needs Survey-Partners & Caregivers (SCNS-P&C45), and both carers and patients completed the Centre of Epidemiologic-Depression Scale (CES-D). RESULTS: Overall, 57% of carers reported at least one, 37% at least three, 31% at least five, and 15% at least 10 unmet needs; the most commonly endorsed unmet needs were in the domains of information and health care service needs. Thirty percent of carers and 36% of patients were at risk of clinical depression. A weak to moderate positive relationship was observed between unmet needs and carer depression (r=0.30, p<0.001). Carer levels of unmet needs were significantly associated with carer age, hospital type, treatment type, cancer type, living situation, relationship status (in both uni- and multi-factor analysis); person with cancer age and carer level of education (in unifactor analysis only); but not with carer gender or patient gender (in both uni- and multi-factor analyses). CONCLUSION: Findings highlight the importance of developing tailored programmes to systematically assist carers who are supporting patients through the early stages of cancer treatment.


Assuntos
Cuidadores/psicologia , Depressão/psicologia , Necessidades e Demandas de Serviços de Saúde , Avaliação das Necessidades , Neoplasias/psicologia , Neoplasias/terapia , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Efeitos Psicossociais da Doença , Depressão/diagnóstico , Depressão/prevenção & controle , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Vitória , Adulto Jovem
13.
Qual Life Res ; 23(9): 2531-43, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24777867

RESUMO

PURPOSE: To assess stable effects of self-management programs, measurement instruments should primarily capture the attributes of interest, for example, the self-management skills of the measured persons. However, measurements of psychological constructs are always influenced by both aspects of the situation (states) and aspects of the person (traits). This study tests whether the Health Education Impact Questionnaire (heiQ™), an instrument assessing a wide range of proximal outcomes of self-management programs, is primarily influenced by person factors instead of situational factors. Furthermore, measurement invariance over time, changes in traits and predictors of change for each heiQ™ scale were examined. METHODS: Subjects were N = 580 patients with rheumatism, asthma, orthopedic conditions or inflammatory bowel disease, who filled out the heiQ™ at the beginning, the end of and 3 months after a disease-specific inpatient rehabilitation program in Germany. Structural equation modeling techniques were used to estimate latent trait-change models and test for measurement invariance in each heiQ™ scale. Coefficients of consistency, occasion specificity and reliability were computed. RESULTS: All scales showed scalar invariance over time. Reliability coefficients were high (0.80-0.94), and consistency coefficients (0.49-0.79) were always substantially higher than occasion specificity coefficients (0.14-0.38), indicating that the heiQ™ scales primarily capture person factors. Trait-changes with small to medium effect sizes were shown in five scales and were affected by sex, age and diagnostic group. CONCLUSION: The heiQ™ can be used to assess stable effects in important outcomes of self-management programs over time, e.g., changes in self-management skills or emotional well-being.


Assuntos
Doença Crônica/reabilitação , Educação em Saúde , Autocuidado/métodos , Inquéritos e Questionários , Adulto , Feminino , Alemanha , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Teoria Psicológica , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes
14.
J Autoimmun ; 52: 130-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24378287

RESUMO

Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T cell responses in patients with MuSK MG. Intracellular production of IFN-gamma, TNF-alpha, IL-2, IL-17, and IL-21 by CD4+ and CD8+ T cells was measured by polychromatic flow cytometry in peripheral blood samples from 11 Musk MG patients and 10 healthy controls. Only one MuSK MG patient was not receiving immunosuppressive therapy. Regulatory T cells (Treg) were also included in our analysis to determine if changes in T cell function were due to altered Treg frequencies. CD8+ T cells from MuSK MG patients had higher frequencies of polyfunctional responses than controls, and CD4+ T cells had higher IL-2, TNF-alpha, and IL-17. MuSK MG patients had a higher percentage of CD4+ T cells producing combinations of IFN-gamma/IL-2/TNF-gamma, TNF-alpha/IL-2, and IFN-gamma/TNF-alpha. Interestingly, Treg numbers and CD39 expression were not different from control values. MuSK MG patients had increased frequencies of Th1 and Th17 cytokines and were primed for polyfunctional proinflammatory responses that cannot be explained by a defect in CD39 expression or Treg number.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Citocinas/metabolismo , Miastenia Gravis/imunologia , Células Th1/imunologia , Células Th17/imunologia , Adulto , Idoso , Separação Celular , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina G/sangue , Imunofenotipagem , Pessoa de Meia-Idade , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Fatores Sexuais , Adulto Jovem
15.
Br J Dermatol ; 170(1): 87-95, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23855404

RESUMO

BACKGROUND: Advanced melanoma is an aggressive disease with a poor prognosis. Approved therapy is limited in the U.K. and, until recently, no treatment had improved survival over best supportive care. A deeper understanding of current clinical practice will help new agents find a place in future treatment pathways. OBJECTIVES: To document U.K. clinical practice for the treatment of patients with unresectable stage III/IV (advanced) melanoma. METHODS: MELODY (melanoma treatment patterns and outcomes among patients with unresectable stage III/IV disease: a retrospective longitudinal survey) compiled registries of consecutive patients with malignant melanoma (any stage) between 1 July 2005 and 30 June 2006 from France, Italy and the U.K. Patients with advanced melanoma and ≥ 2 months of follow-up were eligible for analysis. RESULTS: There were 220 eligible patients identified in the U.K., of whom 117 (53.2%) received systemic therapy outside of clinical trials. Over half of these patients received dacarbazine as first- or second-line therapy. Healthcare-resource utilization was extensive and patients had short survival times: 1- and 2-year survival rates after first-line systemic treatment were 45.5% [95% confidence interval (CI) 37.1-53.6] and 24.7% (95% CI 17.7-32.3), respectively. CONCLUSIONS: Systemic and palliative treatments used to manage advanced melanoma in the U.K. are associated with considerable healthcare resource utilization and poor short-term survival.


Assuntos
Antineoplásicos/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Feminino , Recursos em Saúde/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Resultado do Tratamento , Reino Unido/epidemiologia
16.
Drugs Today (Barc) ; 49(11): 739-44, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24308019

RESUMO

The sixth Annual International Partnering Conference, Biopharm America 2013, took full advantage of its setting in Boston, Massachusetts, home of perhaps the greatest concentration of academic institutions in the U.S., if not the world. With a keynote address from a systems biologist from Harvard University, a networking reception at the Boston Museum of Science and a spirited 'Academic Innovators Showcase', the EBD Group's gathering paid homage to the links between a steady flow of new scientific ideas and a healthy biopharmaceutical pipeline.


Assuntos
Biotecnologia/organização & administração , Indústria Farmacêutica/organização & administração , Cooperação Internacional , Desenho de Fármacos , Humanos , Produção de Droga sem Interesse Comercial , Medicina Regenerativa/organização & administração
17.
Br J Dermatol ; 169 Suppl 2: 32-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23786618

RESUMO

In human skin fibroblasts in vitro, procollagen-1 and NAD(+)/NADH were reduced in three strains of adult fibroblasts compared with neonatal fibroblasts. The levels of both procollagen-1 and NAD(+)/NADH were increased in the adult fibroblasts by treatment for 24 (NAD energy) or 48 h (procollagen-1) with a complex containing niacinamide, Pal-KTTKS peptide and an olive oil fatty acid derivative (Olivem(®)), especially in combination with a natural extract from dill (Lys'lastine V(®)). In one of the adult fibroblast strains evaluated, these changes in procollagen-1 and NAD(+)/NADH in response to the complex of bioactives were in parallel with increased expression of mRNA biomarkers related primarily to dermal matrix and basement membrane structure, including COL1A1, COL3A1, COL5A1, COL14A1, ELN and LOXL2, in addition to SOD2, NAMPT and TGFBR3; MMP1 was decreased in expression. In general, these mRNA biomarker effects were maintained or boosted by the addition of Lys'lastine V, particularly at 1%, and were similar to the fold changes in mRNA expression in neonatal compared with adult fibroblasts. These results indicate that the complex of niacinamide, Pal-KTTKS and Olivem, especially with addition of Lys'lastine V, increases the NAD(+)/NADH bioenergy level of adult skin fibroblasts in parallel with increased expression of skin structure biomarkers in vitro to levels similar to those in younger fibroblasts. Thus, niacinamide, Pal-KTTKS, Olivem and Lys'lastine V are promising bioactive candidates for inclusion in cosmetic formulations.


Assuntos
Metabolismo Energético/fisiologia , Niacinamida/farmacologia , Oligopeptídeos/farmacologia , Óleos de Plantas/farmacologia , Envelhecimento da Pele/fisiologia , Pele/efeitos dos fármacos , Adulto , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , NAD/genética , NAD/metabolismo , Azeite de Oliva , Extratos Vegetais/farmacologia , RNA Mensageiro/metabolismo , Pele/citologia , Pele/metabolismo
18.
Br J Dermatol ; 166 Suppl 2: 1-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22670612

RESUMO

The skin has an amazing array of complex interacting biological processes. Recent advances in investigational techniques now allow evaluation of these processes at the level of the gene, protein and metabolite. Sometimes collectively known as the omics, these fields of inquiry, known as genomics, proteomics and metabolomics, respectively, are yielding new and important insights into skin structure and processes, its responses to injury and age, and the mechanisms by which new interventions and compounds may work to improve the health and integrity of this crucial organ.


Assuntos
Genômica/tendências , Metabolômica/tendências , Fenômenos Fisiológicos da Pele/genética , Cromatografia/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Previsões , Expressão Gênica/genética , Genômica/métodos , Humanos , Metabolômica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Proteômica/métodos , Proteômica/tendências , Análise Espectral/métodos
19.
Br J Dermatol ; 166 Suppl 2: 16-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22670614

RESUMO

The use of global gene expression profiling, also known as transcriptomics or genomics, provides a means to identify key pathways affected in ageing skin that can be improved with appropriate cosmetic compounds. Aspects of skin ageing that can be addressed include matrix production, barrier, lipid synthesis, antioxidant capacity and hyperpigmentation. Gene expression profiling together with in vitro human skin cell cultures for compound screening and verification have led to the identification of cosmetic compounds and an understanding of the biological effects of compounds such as niacinamide, Pal-KTTKS, hexamidine, retinyl propionate and sodium dehydroacetate. In addition, understanding of the decreased antioxidant capacity of aged skin has led to the identification of new antiageing ingredients, olive-derived fatty acid ethoxylates, which have been shown to restore antioxidant enzymes in skin keratinocytes and fibroblasts. Gene expression profiling of age spots has also provided an understanding of the role of undecylenoyl phenylalanine in reducing melanin production by an adrenergic receptor mechanism in melanocytes. The use of these compounds in cosmetic formulations for skin care can aid improvements in the appearance of aged skin, including the improved appearance of fine lines, wrinkles and age spots.


Assuntos
Cosméticos/farmacologia , Genômica/métodos , Transtornos da Pigmentação/tratamento farmacológico , Envelhecimento da Pele/genética , Antioxidantes/farmacologia , Cosméticos/química , Ácidos Graxos/farmacologia , Humanos , Azeite de Oliva , Óleos de Plantas/farmacologia , Receptores Adrenérgicos beta/fisiologia , Envelhecimento da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/genética , Transcrição Gênica/genética , Regulação para Cima
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