Severity of Dementia and Survival in Patients Diagnosed with Colorectal Cancer: A National Cohort Study in England and Wales

AIMS: There is little evidence about the survival of patients with colorectal cancer (CRC) also diagnosed with dementia. We quantified dementia severity and estimated how it is associated with 2-year overall survival. MATERIALS AND METHODS: Records of patients aged 65 years or older diagnosed with CRC in England and Wales were identified. A novel proxy for dementia severity combined dementia diagnosis in administrative hospital data with Eastern Cooperative Oncology Group performance status. Cox regression was used to estimate hazard ratios with and without risk adjustment. RESULTS: In total, 4033 of 105 250 CRC patients (3.8%) had dementia recorded. Two-year survival decreased with increasing dementia severity from 65.4% without dementia, 53.5% with mild dementia, 33.0% with moderate dementia to 16.5% with severe dementia (hazard ratio comparing severe with no dementia: 2.97; 95% confidence interval 2.79, 3.16). Risk adjustment for comorbidity and cancer stage reduced this association slightly (hazard ratio 2.52; 95% confidence interval 2.37, 2.68) and additional adjustment for treatment factors reduced it further (hazard ratio 1.60; 95% confidence interval 1.50, 1.70). CONCLUSIONS: Survival of CRC patients varied strongly according to dementia severity, suggesting that a 'one-size-fits-all' policy for the care of CRC patients with dementia is not appropriate. Comprehensive assessment of cancer patients with dementia that considers dementia severity is essential in a shared decision-making process that ensures patients receive the most appropriate treatment for their individual needs and preferences

A multi-centre quality improvement project to reduce the incidence of obstetric anal sphincter injury (OASI): study protocol.

BACKGROUND: Third and fourth degree perineal tears, or obstetric anal sphincter injuries (OASI), sustained during childbirth can result in anal incontinence and psychosocial problems which require ongoing treatment. Within the English National Health System (NHS) reported rates of OASI have gradually increased. In response, a care bundle was developed incorporating four elements: 1) antenatal information to women, 2) manual perineal protection during all vaginal births, 3) episiotomy to be performed with a 60° mediolateral angle at crowning (when clinically indicated) and 4) perineal examination (including per rectum) after childbirth. Implementation of the OASI Care Bundle is aided by a skills development module and an awareness campaign. The project is a collaboration between two national professional bodies, an NHS hospital trust and an academic institution. METHODS: Implementation of the OASI Care Bundle will be evaluated using a stepped-wedge design. From January 2017 sixteen maternity units across England, Wales and Scotland will participate in the study over a 15-month period, with sequential roll-out of the intervention in four blocks (regions) of four units. The primary clinical outcome is OASI rate. Regression analysis will adjust for differences in organisational characteristics and obstetric risk factors in women who gave birth before and after implementation of the care bundle. Focus group discussions and in-depth interviews with clinicians will evaluate the feasibility of integrating the care bundle into routine practice. Interviews with women will explore the acceptability of the intervention. DISCUSSION: This protocol outlines the evaluation of our quality improvement project which aims to prevent OASI using a bundle of evidence-based interventions that are each widely used in practice. The OASI project aims to 1) standardise practice to prevent OASI in a way that is acceptable to clinicians and women and 2) identify the barriers and enablers associated with upscaling interventions within maternity units. If found to be effective, feasible and acceptable, the OASI Care Bundle will be shared with a range of audiences using the communication channels available to the professional bodies. TRIAL REGISTRATION: The OASI Project was retrospectively registered on the ISCTRN12143325 database date assigned 03/10/2017

Secreted and tumour targeted human carboxylesterase for activation of irinotecan

Irinotecan (CPT-11) is an anticancer agent for the treatment of colon cancer. CPT-11 can be considered as a prodrug, since it needs to be activated into the toxic drug SN-38 by the enzyme carboxylesterase. An approach to achieve tumour specific activation of CPT-11 is to transduce the cDNA encoding carboxylesterase into tumour cells. A secreted form of carboxylesterase may diffuse through a tumour mass and may activate CPT-11 extracellularly. This could enhance the antitumour efficacy by exerting a bystander effect on untransduced cells. In addition a secreted tumour-targeted form of carboxylesterase should prevent leakage of the enzyme from the site of the tumour into the circulation. We have constructed a secreted form of human liver carboxylesterase-2 by deletion of the cellular retention signal and by cloning the cDNA downstream of an Ig kappa leader sequence. The protein was secreted by transfected cells and showed both enzyme activity and efficient CPT-11 activation. To obtain a secreted, tumour-targeted form of carboxylesterase-2 the cDNA encoding the human scFv antibody C28 directed against the epithelial cell adhesion molecule EpCAM, was inserted between the leader sequence and carboxylesterase-2. This fusion protein showed CPT-11 activation and specific binding to EpCAM expressing cells. Importantly, in combination with CPT-11 both recombinant carboxylesterase proteins exerted strong antiproliferative effects on human colon cancer cells. They are, therefore, promising new tools for gene directed enzyme prodrug therapy approaches for the treatment of colon carcinoma with CPT-11

The Pathogenesis of Extraintestinal Manifestations: Implications for IBD Research, Diagnosis, and Therapy.

This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Crohn's and Colitis following peer review. The version of record Hedin, C. R. H., et al. (2018). "The Pathogenesis of Extraintestinal Manifestations: Implications for IBD research, diagnosis and therapy." Journal of Crohn's and Colitis: jjy191-jjy191.] is available online at:https://doi.org/10.1093/ecco-jcc/jjy191This article reports on the sixth scientific workshop of the European Crohn's and Colitis Organisation [ECCO] on the pathogenesis of extraintestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. This paper has been drafted by 15 ECCO members and 6 external experts [in rheumatology, dermatology, ophthalmology, and immunology] from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search, the supporting text was finalized under the leadership of the heads of the working groups before being integrated by the group consensus leaders

Establishing Zebrafish as a Novel Exercise Model: Swimming Economy, Swimming-Enhanced Growth and Muscle Growth Marker Gene Expression

Zebrafish has been largely accepted as a vertebrate multidisciplinary model but its usefulness as a model for exercise physiology has been hampered by the scarce knowledge on its swimming economy, optimal swimming speeds and cost of transport. Therefore, we have performed individual and group-wise swimming experiments to quantify swimming economy and to demonstrate the exercise effects on growth in adult zebrafish

Making effective use of healthcare data using data-to-text technology

Healthcare organizations are in a continuous effort to improve health outcomes, reduce costs and enhance patient experience of care. Data is essential to measure and help achieving these improvements in healthcare delivery. Consequently, a data influx from various clinical, financial and operational sources is now overtaking healthcare organizations and their patients. The effective use of this data, however, is a major challenge. Clearly, text is an important medium to make data accessible. Financial reports are produced to assess healthcare organizations on some key performance indicators to steer their healthcare delivery. Similarly, at a clinical level, data on patient status is conveyed by means of textual descriptions to facilitate patient review, shift handover and care transitions. Likewise, patients are informed about data on their health status and treatments via text, in the form of reports or via ehealth platforms by their doctors. Unfortunately, such text is the outcome of a highly labour-intensive process if it is done by healthcare professionals. It is also prone to incompleteness, subjectivity and hard to scale up to different domains, wider audiences and varying communication purposes. Data-to-text is a recent breakthrough technology in artificial intelligence which automatically generates natural language in the form of text or speech from data. This chapter provides a survey of data-to-text technology, with a focus on how it can be deployed in a healthcare setting. It will (1) give an up-to-date synthesis of data-to-text approaches, (2) give a categorized overview of use cases in healthcare, (3) seek to make a strong case for evaluating and implementing data-to-text in a healthcare setting, and (4) highlight recent research challenges.Comment: 27 pages, 2 figures, book chapte

Comorbidities and the referral pathway to access joint replacement surgery: an exploratory qualitative study

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The research was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care North Thames (CLAHRC) at Barts Health NHS Trust

First description of a fossil chamaeleonid from Greece and its relevance for the European biogeographic history of the group

The fossil record of Chamaeleonidae is very scarce and any new specimen is therefore considered important for our understanding of the evolutionary and biogeographic history of the group. New specimens from the early Miocene of Aliveri (Evia Island), Greece constitute the only fossils of these lizards from southeastern Europe. Skull roofing material is tentatively attributed to the Czech species Chamaeleo cf. andrusovi, revealing a range extension for this taxon, whereas tooth-bearing elements are described as indeterminate chamaeleonids. The Aliveri fossils rank well among the oldest known reptiles from Greece, provide evidence for the dispersal routes of chameleons out of Africa towards the European continent and, additionally, imply strong affinities with coeval chamaeleonids from Central Europe

Sexual dimorphism in cancer.

The incidence of many types of cancer arising in organs with non-reproductive functions is significantly higher in male populations than in female populations, with associated differences in survival. Occupational and/or behavioural factors are well-known underlying determinants. However, cellular and molecular differences between the two sexes are also likely to be important. In this Opinion article, we focus on the complex interplay that sex hormones and sex chromosomes can have in intrinsic control of cancer-initiating cell populations, the tumour microenvironment and systemic determinants of cancer development, such as the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment

Evaluating the Psychometric Quality of Social Skills Measures: A Systematic Review

Introduction - Impairments in social functioning are associated with an array of adverse outcomes. Social skills measures are commonly used by health professionals to assess and plan the treatment of social skills difficulties. There is a need to comprehensively evaluate the quality of psychometric properties reported across these measures to guide assessment and treatment planning. Objective - To conduct a systematic review of the literature on the psychometric properties of social skills and behaviours measures for both children and adults. Methods - A systematic search was performed using four electronic databases: CINAHL, PsycINFO, Embase and Pubmed; the Health and Psychosocial Instruments database; and grey literature using PsycExtra and Google Scholar. The psychometric properties of the social skills measures were evaluated against the COSMIN taxonomy of measurement properties using pre-set psychometric criteria. Results - Thirty-Six studies and nine manuals were included to assess the psychometric properties of thirteen social skills measures that met the inclusion criteria. Most measures obtained excellent overall methodological quality scores for internal consistency and reliability. However, eight measures did not report measurement error, nine measures did not report cross-cultural validity and eleven measures did not report criterion validity. Conclusions - The overall quality of the psychometric properties of most measures was satisfactory. The SSBS-2, HCSBS and PKBS-2 were the three measures with the most robust evidence of sound psychometric quality in at least seven of the eight psychometric properties that were appraised. A universal working definition of social functioning as an overarching construct is recommended. There is a need for ongoing research in the area of the psychometric properties of social skills and behaviours instruments