Kanggibbons5015

Background Cathepsin-D (CatD), owing to its dual role as a proteolytic enzyme and as a ligand, has been implicated in cancer progression. The role of CatD in pancreatic ductal adenocarcinoma is unknown. Methods CatD expression quantified by immunohistochemistry of tumor-tissue microarrays of 403 resected pancreatic cancer patients from the ESPAC-Tplus trial, a translational study within the ESPAC (European Study Group for Pancreatic Cancer) trials, was dichotomously distributed to low and high H scores (cut off 22.35) for survival and multivariable analysis. The validation cohort (n = 69) was recruited based on the hazard ratio of CatD from ESPAC-Tplus. 5-fluorouracil-, and gemcitabine-resistant pancreatic cancer cell lines were employed for mechanistic experiments. All statistical tests were two-sided. Results Median overall survival was 23.75 months and median overall survival for patients with high CatD expression was 21.09 (95% confidence interval [CI] = 17.31 to 24.80) months vs 27.20 (95% CI = 23.75 to 31.90) months for low CatD expression (χ2 LR, 1DF = 4.00; P = .04). Multivariable analysis revealed CatD expression as a predictive marker in gemcitabine-treated (z stat = 2.33; P = .02) but not in 5-fluorouracil-treated (z stat = 0.21; P = .82) patients. An independent validation cohort confirmed CatD as a negative predictive marker for survival (χ2 LR, 1DF = 6.80; P = .009) and as an independent predictive marker in gemcitabine-treated patients with a hazard ratio of 3.38 (95% CI = 1.36 to 8.38, P = .008). Overexpression of CatD was associated with a concomitant suppression of the acid sphingomyelinase, and silencing of CatD resulted in upregulation of acid sphingomyelinase with rescue of gemcitabine resistance. Conclusions Adjuvant gemcitabine is less effective in pancreatic ductal adenocarcinoma with high CatD expression, and thus CatD could serve as a marker for biomarker-driven therapy. © The Author(s) 2020. Published by Oxford University Press.Background Depression, anxiety and related disorders, including obsessive-compulsive disorders and trauma/stressor related disorders, have high prevalence, chronic courses and cause significant impairment. These disorders are also highly co-morbid, and appear to share etiology and maintenance factors. Recent developments have seen the emergence of transdiagnostic approaches that systematically address the common/shared features of these disorders. A key advantage of transdiagnostic approaches is that they can reduce the pressure on mental health professionals to be proficient in a plethora of single-disorder focused treatments. Currently almost all transdiagnostic approaches come from cognitive-behavioural therapy (CBT). However, not all clients prefer or benefit from CBT. Emotion-focused therapy (EFT) represents an evidence-based alternative to CBT. This study aims to examine a transdiagnostic adaptation of EFT (EFT-T) as a treatment for depression, anxiety and related disorders. Infigratinib Method The current study is ng EFT-T to a standard transdiagnostic treatment, CBT. Registration ISRCTN11430110; registered on 07 January 2019. Copyright © 2020 Timulak L et al.This Open Letter discusses the theme of 'diversity in brain health' in research, practice and policy for older LGBT+ people. It is written by a multidisciplinary group of Atlantic Fellows for Equity in Brain Health at the Global Brain Health Institute in Trinity College Dublin (TCD), from a variety of disciplines (health economics, human geography, anthropology, psychology, gerontology) and professions (researcher, clinicians, writers, practicing artists). The group developed a workshop to explore the theme of 'Diversity and Brain Health' through the lens of non-normative gender identities and sexualities. Guided by two advisors (Prof Agnes Higgins, TCD; Mr Ciaran McKinney, Age and Opportunity), we invited older LGBT+ people and those interested in the topic of LGBT+ and ageing, healthcare providers, policy makers and interested members of the research community. We partnered with colleagues in the School of Law to include socio-legal perspectives. Following the workshop, Roe and Walrath wrote an opinion editorial, published in the Irish Times during the 2019 PRIDE festival, and were subsequently invited by HRB Open Access to provide a more detailed expansion of that work. In this Open Letter we describe the theme of 'diversity and brain health' and some of the lessons we learned from listening to the lived experience of older LGBT+ people in Ireland today. We illustrate why it's important to understand the lived experience of older LGBT+ people and highlight the failure of the State to evaluate the experience of LGBT+ people in policy implementation. We call on researchers, clinicians, service planners and policy makers, to recognize and address diversity as an important way to address health inequities in Ireland. Copyright © 2020 Roe L et al.Background Neurogenic lower urinary tract dysfunction (NLUTD) is defined as a lower urinary tract dysfunction secondary to confirmed pathology of the nervous system. NLUTD is common in people with multiple sclerosis (MS), with prevalence estimates ranging from 49% to 92%. Managing NLUTD is complex and can be comprised of pharmacological and non-pharmacological interventions. Qualitative research exploring perspectives of people with MS and healthcare professionals on living with and managing NLUTD symptoms is sparse. This study aims to explore the perspectives of people with MS and healthcare professionals on managing NLUTD symptoms. Methods A qualitative descriptive approach will be applied in this study using audio-recorded semi structured interviews for people with MS and healthcare professionals. The Consolidated Criteria for Reporting Qualitative Studies (COREQ) guidelines will be used to standardize the conduct and reporting of the research. People with MS will be recruited through a gatekeeper at MS Ireland. Healthcare professionals will be recruited through gatekeepers at Irish Practice Nurses Association, Continence Foundation of Ireland, Irish Society of Chartered Physiotherapists, and Physiotherapists Interested in MS Group. Interviews will be transcribed and exported to NVivo software package (Version 12) for analysis. Data will be collectively synthesised using thematic analysis. Conclusion It is anticipated that exploring perspectives of people with MS and healthcare professionals on managing symptoms (including current practice) of NLUTD in MS will assist in the development of an evidence-based and stakeholder informed intervention for NLUTD in people with MS. Copyright © 2019 Al Dandan HB et al.Introduction Patients with multimorbidity are expected to adhere to complex medication regimens in order to manage their multiple chronic conditions. It has been reported the likelihood of adherence decreases as patients are prescribed more medications. Much medication adherence research to date is dominated by a single-disease focus, which is at odds with the rising prevalence of multimorbidity and may artificially underestimate the complexity of managing chronic illness. This review aims to describe the prevalence of medication non-adherence among patients with multimorbidity, and to identify potential predictors of non-adherence in this population. Methods A systematic review will be conducted and reported according to PRISMA guidelines. PubMed, EMBASE, CINAHL and PsycINFO will be searched using a predefined search strategy from 2009-2019. Quantitative studies will be considered eligible for review if prevalence of medication non-adherence among adults with two or more chronic conditions is reported. Studies will be included in the review if available in English full text. Titles and abstracts will be screened by single review, with 20% of screening cross-checked by a second reviewer. Full-text articles will be screened by two independent reviewers, noting reasons for exclusions. Data extraction will be performed using a predefined extraction form. Quality and risk of bias assessment will be conducted using criteria for observational studies outlined by Sanderson et al. (2007). A narrative synthesis and, if feasible, meta-analysis will be conducted. Discussion By exploring medication non-adherence from a multimorbidity perspective, the review aims to inform an evidence base for intervention development which accounts for the rising prevalence of patients with multiple chronic conditions.  Study registration The systematic review is prospectively registered in PROSPERO ( CRD42019133849); registered on 12 June 2019. Copyright © 2019 Foley L et al.Introduction The C9orf72 hexanucleotide repeat expansion is causal in amyotrophic lateral sclerosis (ALS) and has a negative effect on prognosis. The C9orf72 repeat expansion has been associated with an accelerated deterioration of respiratory function and survival in a cohort of 372 Portuguese patients. Methods Cases presenting to the Irish ALS clinic with both longitudinal occluded sniff nasal inspiratory pressure (SNIP) and C9orf72 testing were including in the study. Clinical variables and survival characteristics of these patients were collected. Joint longitudinal and time to event models were constructed to explore the longitudinal characteristics of the cohort by C9orf72 status. Results In total, 630 cases were included, of which 58 (9.2%) carried the C9orf72 repeat expansion. Plots of the longitudinal trend after joint modelling revealed that those carrying the expansion had worse respiratory function throughout the course of their disease than those without. The ALS Functional Rating Scale-revised (ALSFRS-R) respiratory sub-score did not distinguish C9orf72 normal from expanded cases. Furthermore, modelling by site of onset and gender sub-groups revealed that this difference was greatest in male spinal onset cases. Joint models further indicated that occluded SNIP values were of prognostic importance. Conclusions Our results confirm findings from Portugal that the C9orf72 repeat expansion is associated with accelerated respiratory function decline. Analysis via joint models indicate that respiratory function is of prognostic importance and may explain previous observations of poorer prognosis in male spinal onset patients carrying the C9orf72 expansion. Copyright © 2019 Rooney J et al.Background Current thinking in health recognises the influence of early life experiences (health and otherwise) on later life outcomes. The life course approach has been embedded in the work of the World Health Organisation since the Ageing and Health programme was established in 1995. Yet there has been limited debate on the relevancy of a life course lens to understanding health service utilisation. Aim The aim of the review was twofold. Firstly, identify existing healthcare utilisation frameworks other than the dominant Andersen's behavioural model currently in use. Secondly, to identify if current frameworks incorporate the advocated life course perspective in understanding health service utilisation.     Methods A scoping review of PubMed, Cinahl Plus, Emerald, PsycINFO, Web of Knowledge and Scopus was conducted. Data extraction used a framework approach with meta-synthesis guided by the four domains of the life course proposed by Elder (1979) human agency, location, temporality and relationships, and interdependencies.