Generalised and abdominal obesity and risk of diabetes, hypertension and hypertension–diabetes co-morbidity in England

Objectives To look at trends in generalised (body mass index (BMI) ≥30 kg m–2) and abdominal (waist circumference (WC) >102 cm in men, >88 cm in women) obesity among adults between 1993 and 2003, and to evaluate their association with diabetes, hypertension and hypertension–diabetes co-morbidity (HDC) in England. Design Analyses of nationally representative cross-sectional population surveys, the Health Survey for England (HSE). Subjects Non-institutionalised men and women aged ≥35 years. Measurements Interviewer-administered questionnaire (sociodemographic information, risk factors, doctor-diagnosed diabetes), measurements of height and weight to calculate BMI. WC and blood pressure measurements were taken by trained nurses. Results Generalised obesity increased among men from 15.8% in 1993 to 26.3% in 2003, and among women from 19.3% to 25.8%. Abdominal obesity also increased in both sexes (men: 26.2% in 1993 to 39.0% in 2003; women: 32.4% to 47.0%). In 1994, 1998 and 2003, generalised and abdominal obesity were independently associated with risk of hypertension, diabetes and HDC. The odds of diabetes associated with generalised obesity in 1994, 1998 and 2003 were 1.62, 2.26 and 2.62, respectively, in women and 1.24, 1.82 and 2.10, respectively, in men. Similar differences were observed for hypertension and HDC. Men and women with abdominal obesity also showed a higher risk for diabetes, hypertension and HDC than those with a normal WC. Conclusions If current trends in obesity continue then the risk of related morbidities may also increase. This will impact on cardiovascular disease morbidity and mortality, with cost implications for the health service. Therefore there is an urgent need to control the epidemic of obesity

Nutritional and Post-Transplantation Outcomes of Enteral versus Parenteral Nutrition in Pediatric Hematopoietic Stem Cell Transplantation: A Systematic Review of Randomized and Nonrandomized Studies

Hematopoietic stem cell transplantation (HSCT) involves the administration of chemotherapy followed by the infusion of donor stem cells. After treatment, children can consequently experience nausea, vomiting, diarrhea, anorexia, and mucositis, which negatively impact oral intake, leading to rapid deterioration in nutritional status and risk of malnutrition. Nutrition support therefore becomes necessary to circumvent these adverse effects. This has traditionally been provided via parenteral nutrition (PN), but pediatric evidence is increasingly advocating enteral nutrition (EN) as a preferential alternative. The objective of this review is to determine the efficacy of any forms of EN versus PN provided during admission to children aged ≤ 18 years undergoing HSCT. Primary outcomes considered efficacy in relation to various nutritional parameters, and secondary outcomes included a range of post-transplantation parameters. Data sources included English and non-English articles from the start date of MEDLINE, EMBASE, AMED, CINAHL and Cochrane Controlled Trials register, up to July 2018. Key journals were also hand searched, reference lists scanned, clinical experts contacted, and gray literature searched using EThOS and Open Grey. Randomized and observational studies comparing any forms of EN versus PN in children aged ≤ 18 years undergoing HSCT investigating nutritional or post-transplantation outcomes were eligible. Data were extracted from included studies using a custom extraction form that had previously been piloted. Because included studies were observational, risk of bias was assessed using Risk of Bias in Non-randomised Studies of Interventions. Because only a small number of heterogenous studies reporting a wide range of differently defined outcomes were included, meta-analyses were not performed and data were presented in narrative form. Conflicting results in favor of either method of nutrition support or no difference between methods were seen for duration of interventions, nutritional intakes, biochemical and anthropometric changes, mortality, infections, length of admission, and neutrophil engraftment. EN may provide favorable benefits over PN regarding acute graft-versus-host-disease (aGVHD) and platelet engraftment. A paucity of studies was found investigating the question posed by this review. Included studies were clinically heterogenous regarding populations, interventions, and outcomes, at moderate to serious risk of bias due to the absence of randomization, confounding parameters, statistical control, retrospective designs, and participant selection. Some studies were more than 15 years old. Despite the limited number and poor quality of identified studies, results support the growing body of pediatric evidence that EN is feasible during HSCT. Similar differences regarding many nutritional and post-transplantation outcomes were seen in both forms of nutrition support, but EN could provide benefits above PN including reduced incidence of aGVHD and faster platelet engraftment

Challenges in Patient Recruitment, Implementation, and Fidelity in a Mobile Telehealth Study

Introduction: Mobile telehealth (MTH) evaluations in diabetes have been conducted, but few report details and issues related to recruitment, implementation (intervention delivery), fidelity, and context. These have important implications on the interpretation of the findings and effectiveness of the intervention. This article reports these data from an MTH study and describes the challenges experienced in running an intervention such as this in an active clinical environment. Materials and Methods: We conducted a mixed-methods MTH study that included a 9-month randomized controlled trial in people with poorly controlled diabetes. Detailed recruitment data were recorded during the study. Data on contacts between MTH participants and the MTH team were collected and used to report on intervention delivery and fidelity. Meeting and field notes, as well as communications between research team members during the study, were used to report on the contextual factors that affected recruitment, implementation, and fidelity. Results: The recruited sample size represented 6% of the total clinic population (n = 1,360) and 10.7% of the number of potentially eligible people at the clinic (n = 802) identified at the beginning of the study. Contextual factors related to patients, healthcare providers, the institution, or the recruitment protocol contributed to influence access to study participants and the number of participants randomized (n = 81). Technical and device-related aspects of the MTH intervention were delivered successfully, but the expected education and clinical feedback by the MTH nurse were not delivered according to the protocol. Although 92.5% of introductory calls were made by the MTH nurses, only 13.3% of expected educational calls were performed. Changes to the MTH nursing staff affected intervention participants differently and contributed to the low fidelity of intervention delivery. Conclusions: The current article presents data on the influence of contextual factors on the conduct of this MTH study and underlines the need for these processes to be assessed and reported adequately in future MTH research

A randomised, controlled trial of the effects of a mobile telehealth intervention on clinical and patient-reported outcomes in people with poorly controlled diabetes

Objective The objective of this research is to determine the effects of mobile telehealth (MTH) on glycosylated haemoglobin (HbA1c) and other clinical and patient-reported outcomes in insulin-requiring people with diabetes. Methods A nine-month randomised, controlled trial compared standard care to standard care supplemented with MTH (self-monitoring, mobile-phone data transmissions, graphical and nurse-initiated feedback, and educational calls). Clinical (HbA1c, blood pressure, daily insulin dose, diabetes outpatient appointments (DOAs)) and questionnaire data (health-related quality of life, depression, anxiety) were collected. Mean group changes over time were compared using hierarchical linear models and Mann-Whitney tests. Results Eighty-one participants with a baseline HbA1c of 8.98% ± 1.82 were randomised to the intervention ( n = 45) and standard care ( n = 36). The Group by Time effect revealed MTH did not significantly influence HbA1c ( p = 0.228), but p values were borderline significant for blood pressure ( p = 0.054) and mental-health related quality of life ( p = 0.057). Examination of effect sizes and 95% confidence intervals for mean group differences at nine months supported the existence of a protective effect of MTH on mental health-related quality of life as well as depression. None of the other measured outcomes were found to be affected by the MTH intervention. Conclusions Findings from this study must be interpreted with caution given the small sample size, but they do not support the widespread adoption of MTH to achieve clinically significant changes in HbA1c. MTH may, however, have positive effects on blood pressure and protective effects on some aspects of mental health

Investigating the role of versican in immune exclusion in triple negative breast cancer

Triple negative breast cancer has the highest T cell infiltrate in comparison to other subtypes of breast cancer. To try to improve the anti-tumour response of these T cells, immunotherapy has been trialled, however clinical trials showed poor results. The response to immunotherapy in solid tumours is limited and this has been attributed to the presence of the extracellular matrix (ECM). The ECM can interact with T cells biochemically or physically, affecting their trafficking in the tumour. This can cause the restriction of T cells in the stroma limiting their contact with the tumour epithelial cells, leading to an immune excluded phenotype. Identifying key components of the ECM that are associated with the restriction of immune cells can provide potential targets that could be degraded to improve anti-tumour immunity. From previous work in the lab a signature of molecules were identified which were associated with immunosuppression. In the initial analysis of these molecules in a subset of TNBC tissues, versican (VCAN) was identified as an ECM component that associates with immune cell infiltration into the tumour epithelium. VCAN is a proteoglycan which has the glycosaminoglycan chondroitin sulphate (CS) attached to the peptide backbone. Through its multiple domains and glycan post-translational modifications, VCAN has been shown to have a role in inflammation and cancer progression. To study how VCAN may affect the trafficking of T cells, I first looked at how VCAN expression associated with immune excluded tissues. It was observed that VCAN levels were higher in the epithelial zone of excluded tissues compared to inflamed tissues. CS levels were then explored within the tissues where the sulphation patterns on CS in the stroma led to the discovery of CS-C being higher in excluded tissues and CS-A being higher in inflamed tissues. To observe this effect in-vitro, VCAN was enriched from TNBC and fibroblast cell line secretions. The effect of CS was tested through chondroitinase (CSase) treatment of VCAN enriched protein in a transwell model. An increase in invasion was observed following CSase treatment of protein with high levels of CS-C. To conclude, from the study I identified that within TNBC tissues the excluded immune phenotype associates with epithelial zone expressed VCAN which has a different CS sulphation pattern compared to inflamed tissues, and this difference in sulphation inhibits T-cell trafficking in in vitro models, which can be overcome through enzymatic digestion of the CS. Therefore, targeting VCAN by degrading CS may provide a way to drive excluded tumours into an inflamed and therapy responsive phenotype. Such an approach could be coupled with immunotherapy such as cell-based T-cell therapies

Knowledge, attitudes and practices of medical staff towards obesity management in patients with spinal cord injuries: an International survey of four western European countries

Objective: To (1) examine the opinions of medical staff working in spinal cord injury (SCI) centres (SCICs); (2) evaluate their knowledge, attitudes and practices towards obesity prevention and management; (3) report the number of beds and dietitians available at each SCIC. Methods: A 37-item questionnaire was sent to 23 SCICs in the UK, the Netherlands, Belgium and the Republic of Ireland between September 2012 and January 2013. Results: Eighteen SCICs returned the questionnaires for analysis. All respondents stated that they had an interest in obesity treatment but only 2.3% of the respondents received training in obesity management. Sixty-one percent of staff did not consider body mass index (BMI) to be appropriate for use in SCI patients and subsequently less than half of the respondents use BMI routinely. The majority of respondents reported that they are confident in dealing with overweight (74.5%) and obese (66.1%) SCI adults, less than half (44.1%) are confident in treating overweight and obese SCI children. Respondents also indicated the need for nationally adopted guidelines and a lack of physical activity provision. There were 17.5 whole-time equivalent (WTE) dietitians recorded in 22 SCICs, equivalent to 47.8 beds per WTE dietitians (range 10–420). Non-UK SCIC dietitians are significantly better resourced than in UK SCICs (beds per WTE dietitian: 36 vs 124, P=0.035). Conclusion: Medical staff expressed the need to participate in obesity prevention and management. Appropriate training should be considered for all medical staff and the development of specific weight management guidelines and dietetic provision should be considered

Targeting Versican as a Potential Immunotherapeutic Strategy in the Treatment of Cancer.

A growing body of literature links events associated with the progression and severity of immunity and inflammatory disease with the composition of the tissue extracellular matrix as defined by the matrisome. One protein in the matrisome that is common to many inflammatory diseases is the large proteoglycan versican, whose varied function is achieved through multiple isoforms and post-translational modifications of glycosaminoglycan structures. In cancer, increased levels of versican are associated with immune cell phenotype, disease prognosis and failure to respond to treatment. Whether these associations between versican expression and tumour immunity are the result of a direct role in the pathogenesis of tumours is not clear. In this review, we have focused on the role of versican in the immune response as it relates to tumour progression, with the aim of determining whether our current understanding of the immunobiology of versican warrants further study as a cancer immunotherapy target

Investigating the behavioural effects of a mobile-phone based home telehealth intervention in people with insulin-requiring diabetes: Results of a randomized controlled trial with patient interviews

INTRODUCTION: Evidence supporting home telehealth effects on clinical outcomes in diabetes is available, yet mechanisms of action for these improvements remain poorly understood. Behavioural change is one plausible explanation. This study investigated the behavioural effects of a mobile-phone based home telehealth (MTH) intervention in people with diabetes. It was hypothesized that MTH would improve self-efficacy, illness beliefs, and diabetes self-care. METHODS: A randomized controlled trial compared standard care to standard care supplemented with MTH (self-monitoring, data transmission, graphical and nurse-initiated feedback, educational calls). Self-report measures of self-efficacy, illness beliefs, and self-care were repeated at baseline, three months, and nine months. MTH effects were based on the group by time interactions in hierarchical linear models and effect sizes with 95% confidence intervals (CIs). Interviews with MTH participants explored the perceived effects of MTH on diabetes self-management. RESULTS: Eighty-one participants were randomized to the intervention (n = 45) and standard care (n = 36). Significant group by time effects were observed for five out of seven self-efficacy subscales. Effect sizes were large, particularly at nine months. Interaction effects for illness beliefs and self-care were non-significant, but effect sizes and confidence intervals suggested MTH may positively affect diet and exercise. In interviews, MTH was associated with increased awareness, motivation, and a greater sense of security. Improved self-monitoring and diet were reported by some participants. DISCUSSION: MTH empowers people with diabetes to manage their condition and may influence self-care. Future MTH research would benefit from investigating behavioural mechanisms and determining patient profiles predictive of greater behavioural effectiveness