Qualitative study exploring general dental practitioners' views of MIH and its management in the UK and Australia.

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.

Health literacy: a new piece of the puzzle in psoriasis care? A cross-sectional study.

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.

Development and preliminary evaluation of the OsteoArthritis Questionnaire (OA-Quest): a psychometric study.

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.

Vemurafenib-induced hyperkeratosis of the areola treated with topical adapelene.

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.

Health literacy: applying current concepts to improve health services and reduce health inequalities.

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.

Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis.

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.

Treatment patterns, outcomes, and resource utilization of patients with metastatic melanoma in the U.K.: the MELODY study.

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.

Measurement of stable changes of self-management skills after rehabilitation: a latent state-trait analysis of the Health Education Impact Questionnaire (heiQ™).

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.

Practical application of cellular bioenergetics to the care of aged skin.

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.

Development of an Embryo Toxicity Test to Assess the Comparative Toxicity of Metal Exposure on Different Life Stages of Freshwater Gastropods.

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.

Cancer of unknown primary: progress in the search for improved and rapid diagnosis leading toward superior patient outcomes.

This paper explores the enigma of cancer of unknown primary (CUP) in relation to rapidly improving molecular diagnostic approaches. It is based on the first global collaboration meeting on improving research and clinical outcomes in CUP organized by the CUP Foundation. We review the difficulties of classifying this widely heterogeneous disease and the available diagnostic and pathological evaluative techniques, focusing on molecular profiling. Retrospective studies in CUP patients are shown to provide indirect validation of the accuracy of several platforms of gene expression profiling assays that may identify CUP subsets that respond favorably to active chemotherapy regimens. This review concludes that the recent major improvements in pathologic and molecular diagnostics, coupled with new improved therapies for several specific advanced solid tumors, need to be harmonized with more evidence from clinical-translational trials. All patients with CUP could thus be appropriately managed without the constant uncertainty that has previously severely hampered patient care and optimal outcomes. The longer-term objective is to understand the biology of highly metastatic disease, leading to the development of future global therapeutic programs. Current clinical studies, such as CUP-ONE, will address some of these issues.

Application of genomics to breakthroughs in the cosmetic treatment of skin ageing and discoloration.

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.

Beyond the blot: cutting edge tools for genomics, proteomics and metabolomics analyses and previous successes.

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.

Results of a nationally implemented cardiac screening programme in elite cricket players in England and Wales.

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.

Phase II trial of combretastatin A4 phosphate, carboplatin, and paclitaxel in patients with platinum-resistant ovarian cancer.

BACKGROUND: A previous dose-escalation trial of the vascular disrupting agent combretastatin A4 phosphate (CA4P) given before carboplatin, paclitaxel, or both showed responses in 7 of 18 patients with relapsed ovarian cancer. PATIENTS AND METHODS: Patients with ovarian cancer that had relapsed and who could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63 mg/m(2) minimum 18 h before paclitaxel 175 mg/m(2) and carboplatin AUC (area under the concentration curve) 5, repeated every 3 weeks. RESULTS: Five of the first 18 patients' disease responded, so the study was extended and closed after 44 patients were recruited. Grade ≥2 toxic effects were neutropenia in 75% and thrombocytopenia in 9% of patients (weekly blood counts), tumour pain, fatigue, and neuropathy, with one patient with rapidly reversible ataxia. Hypertension (23% of patients) was controlled by glyceryl trinitrate or prophylactic amlodipine. The response rate by RECIST was 13.5% and by Gynecologic Cancer InterGroup CA 125 criteria 34%. CONCLUSIONS: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will test this hypothesis.

Gemcitabine alone or in combination with cisplatin in patients with advanced or metastatic cholangiocarcinomas or other biliary tract tumours: a multicentre randomised phase II study - The UK ABC-01 Study.

BACKGROUND: We assessed the activity of gemcitabine (G) and cisplatin/gemcitabine (C/G) in patients with locally advanced (LA) or metastatic (M) (advanced) biliary cancers (ABC) for whom there is no standard chemotherapy. METHODS: Patients, aged > or =18 years, with pathologically confirmed ABC, Karnofsky performance (KP) > or =60, and adequate haematological, hepatic and renal function were randomised to G 1000 mg m(-2) on D1, 8, 15 q28d (Arm A) or C 25 mg m(-2) followed by G 1000 mg m(-2) D1, 8 q21d (Arm B) for up to 6 months or disease progression. RESULTS: In total, 86 patients (A/B, n=44/42) were randomised between February 2002 and May 2004. Median age (64/62.5 years), KP, primary tumour site, earlier surgery, indwelling biliary stent and disease stage (LA: 25/38%) are comparable between treatment arms. Grade 3-4 toxicity included (A/B, % patients) anaemia (4.5/2.4), leukopenia (6.8/4.8), neutropenia (13.6/14.3), thrombocytopenia (9.1/11.9), lethargy (9.1/28.6), nausea/vomiting (0/7.1) and anorexia (2.3/4.8). Responses (WHO criteria, % of evaluable patients: A n=31 vs B n=36): no CRs; PR 22.6 vs 27.8%; SD 35.5 vs 47.1% for a tumour control rate (CR+PR+SD) of 58.0 vs 75.0%. The median TTP and 6-month progression-free survival (PFS) (the primary end point) were greater in the C/G arm (4.0 vs 8.0 months and 45.5 vs 57.1% in arms A and B, respectively). CONCLUSION: Both regimens seem active in ABC. C/G is associated with an improved tumour control rate, TTP and 6-month PFS. The study has been extended (ABC-02 study) and powered to determine the effect on overall survival and the quality of life.

Effectiveness of a community-based osteoporosis education and self-management course: a wait list controlled trial.

UNLABELLED: Osteoporosis is an increasing burden on individuals and health resources. The Osteoporosis Prevention and Self-Management Course (OPSMC) was designed to assist individuals to prevent and manage osteoporosis; however, it had not been evaluated in an Australian setting. This randomised controlled trial showed that the course increased osteoporosis knowledge. INTRODUCTION AND HYPOTHESIS: Osteoporosis is a major and growing public health concern. An OPSMC was designed to provide individuals with information and skills to prevent or manage osteoporosis, but its effectiveness has not previously been evaluated. This study aimed to determine whether OPSMC attendance improved osteoporosis knowledge, self-efficacy, self-management skills or behaviour. MATERIALS AND METHODS: Using a wait list randomised controlled trial design, 198 people (92% female) recruited from the community and aged over 40 (mean age = 63) were randomised into control (n = 95) and intervention (n = 103) groups. The OPSMC consists of four weekly sessions which run for 2 h and are led by two facilitators. The primary outcome were osteoporosis knowledge, health-directed behaviour, self-monitoring and insight and self-efficacy. RESULTS: The groups were comparable at baseline. At 6-week follow-up, the intervention group showed a significant increase in osteoporosis knowledge compared with the control group; mean change 3.5 (p < 0.001) on a measure of 0-20. The intervention group also demonstrated a larger increase in health-directed behaviour, mean change 0.16 (p < 0.05), on a measure of 0-6. CONCLUSION: The results indicate that the OPSMC is an effective intervention for improving understanding of osteoporosis and some aspects of behaviour in the short term.

Holocene sea-level curves for santa monica shelf, california continental borderland.

A curve is constructed showing changes in sea level at the Santa Monica shelf over the past 18,000 years. The curve is based on radiocarbon dates, sedimentologic data, and high-resolution seismic stratigraphic analysis of late Quaternary terrace deposits. Sea level was 117 meters below its present position about 18,000 years ago. During the first 8000 years of the Flandrian transgression, sea level rose to at least 24 meters, fell to about 46 meters, and then rose to 20 meters, all below present sea level. Subsequently, sea level rose more slowly and without discernible interruption to its present position.

Functional human corneal equivalents constructed from cell lines.

Human corneal equivalents comprising the three main layers of the cornea (epithelium, stroma, and endothelium) were constructed. Each cellular layer was fabricated from immortalized human corneal cells that were screened for use on the basis of morphological, biochemical, and electrophysiological similarity to their natural counterparts. The resulting corneal equivalents mimicked human corneas in key physical and physiological functions, including morphology, biochemical marker expression, transparency, ion and fluid transport, and gene expression. Morphological and functional equivalents to human corneas that can be produced in vitro have immediate applications in toxicity and drug efficacy testing, and form the basis for future development of implantable tissues.