Prevention of neural tube defects (NTDs) in ethnic communities in the UK: NTD epidemiology and pre-pregnancy knowledge, attitudes and health behaviour

Neural tube defects (NTD) are severe congenital abnormalities, caused by failed closure of the embryonic neural tube, that affect approximately 1 in 1,000 pregnancies worldwide. There is a paucity of epidemiological and qualitative research on NTDs within different ethnic communities in the UK. This thesis reports the findings of a mixed methods study conducted to explore NTD prevalence, pregnancy outcomes and attitudes towards prevention in different ethnic communities. For the quantitative study, congenital anomaly data supplemented with Department of Health termination data were used to explore the NTD prevalence and pregnancy decisions by maternal ethnicity. Semi-structured interviews, combined with grounded theory methodology, explored women’s pre-pregnancy knowledge, attitudes and health behaviours with regard to folic acid supplementation, and subsequent pregnancy decisions. After adjustment for maternal deprivation and age, NTD prevalence was found to be nearly twice as high in Indian mothers and almost three times as high in Bangladeshi mothers, as in mothers of White ethnicity. The excess was particularly marked in Indian mothers for non-isolated NTDs. Through qualitative interviews, women detailed how more information on why folic acid should be taken needs to be given and that health professionals (HPs), such as GPs, are the preferred information source. It was also indicated that HPs who rarely see children with spina bifida are less likely to give a balanced view of the condition, in relation to a decision on possible pregnancy termination. An ethnic discrepancy in prevalence being more marked for non-isolated NTDs is indicative of the involvement of genetic factors. Increasing folic acid use among all population groups is essential and targeting a culturally sensitive education campaign at HPs is a crucial first stage in increasing supplementation among South Asian mothers. It is also of critical importance that those counselling mothers when spina bifida is detected, are fully informed of the condition themselves

Maternal ethnicity and the prevalence of British pregnancies affected by neural tube defects

Background: Few data are available on the prevalence of neural tube defects (NTDs) within different ethnic communities of the United Kingdom. This study aimed to calculate prevalence estimates for NTD‐affected pregnancies, classified by maternal ethnicity, and to explore why variations in prevalence might exist. / Methods: A cross‐sectional study was performed with data from regional congenital anomaly registers in England and Wales, for NTD‐affected pregnancies between 2006 and 2011. Using binomial regression models, we examined NTD‐affected pregnancy prevalence estimates and rate ratios (PRRs), by maternal ethnicity. / Results: The prevalence of NTDs was 12.14 per 10,000 births, with no differences between study years. Anencephaly, encephalocele and spina bifida occurred at 4.98, 1.37 and 5.80 per 10,000 births respectively. Mothers of Indian ethnicity were 1.84 times more likely (95% CI: 1.24, 2.73) and Bangladeshi mothers 2.86 times more likely (95% CI: 1.48, 5.53) than White mothers to have an NTD‐affected pregnancy, after adjusting for maternal deprivation and maternal age. The excess prevalence in Indian mothers was specifically for anencephaly (PRR 2.57; 95% CI: 1.52, 4.34), and in Bangladeshi mothers the trend was for increased spina bifida (PRR 3.86; 95% CI: 0.72, 8.69). Anencephaly in Indian mothers was especially associated with other congenital anomalies (non‐isolated NTDs). / Conclusions: Different British ethnic groups vary in NTD prevalence. The excess prevalence of anencephaly as a non‐isolated NTD in pregnancies of Indian mothers could indicate involvement of genetic or other unmeasured behavioral factors. Future work is needed to seek etiological explanations for the ethnicity differences and to develop improved methods for primary prevention

Research barriers in children and young people with life-limiting conditions: a survey

Studies indicate research ethics committee (REC) approval and clinician gatekeeping are two key barriers in recruiting children and young people (CYP) with life-limiting conditions (LLCs) and life-threatening illnesses (LTIs) and their families to research. OBJECTIVES: To explore the reported experiences, difficulties and proposed solutions of chief investigators (CIs) recruiting CYP with LLCs/LTIs and families in the UK. METHODS: 61 CIs conducting studies with CYP with LLCs/LTIs and their families, identified from the UK National Institute of Health Research portfolio, completed an anonymous, web-based questionnaire, including both closed and open-ended questions. Descriptive statistics and inductive and deductive coding were used to analyse responses. RESULTS: UK CIs cited limitations on funding, governance procedures including Research and Development, Site-Specific and REC approval processes, and clinician gatekeeping as challenges to research. CIs offered some solutions to overcome identified barriers such as working with CYP and their families to ensure their needs are adequately considered in study design and communicated to ethics committees; and designing studies with broad inclusion criteria and developing effective relationships with clinicians in order to overcome clinician gatekeeping. CONCLUSIONS: Many of the challenges and solutions reported by UK CIs have applicability beyond the UK setting. The involvement of clinicians, patients and their families at the inception of and throughout paediatric palliative care research studies is essential. Other important strategies include having clinician research champions and increasing the visibility of research. Further research on the perspectives of all stakeholders, leading to mutually agreed guidance, is required if care and treatment are to improve

Using simulation to interpret a discrete time survival model in a complex biological system: fertility and lameness in dairy cows

The ever-growing volume of data routinely collected and stored in everyday life presents researchers with a number of opportunities to gain insight and make predictions. This study aimed to demonstrate the usefulness in a specific clinical context of a simulation-based technique called probabilistic sensitivity analysis (PSA) in interpreting the results of a discrete time survival model based on a large dataset of routinely collected dairy herd management data. Data from 12,515 dairy cows (from 39 herds) were used to construct a multilevel discrete time survival model in which the outcome was the probability of a cow becoming pregnant during a given two day period of risk, and presence or absence of a recorded lameness event during various time frames relative to the risk period amongst the potential explanatory variables. A separate simulation model was then constructed to evaluate the wider clinical implications of the model results (i.e. the potential for a herd’s incidence rate of lameness to influence its overall reproductive performance) using PSA. Although the discrete time survival analysis revealed some relatively large associations between lameness events and risk of pregnancy (for example, occurrence of a lameness case within 14 days of a risk period was associated with a 25% reduction in the risk of the cow becoming pregnant during that risk period), PSA revealed that, when viewed in the context of a realistic clinical situation, a herd’s lameness incidence rate is highly unlikely to influence its overall reproductive performance to a meaningful extent in the vast majority of situations. Construction of a simulation model within a PSA framework proved to be a very useful additional step to aid contextualisation of the results from a discrete time survival model, especially where the research is designed to guide on-farm management decisions at population (i.e. herd) rather than individual level

Effects on muscle performance of NSAID treatment with Piroxicam versus placebo in geriatric patients with acute infection-induced inflammation. a double blind randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp) with respect to muscle performance. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp.</p> <p>Methods</p> <p>Consecutive admissions to the geriatric ward were screened. 30 Caucasian patients, median age 84.5 years, with acute infection-induced inflammation and serum levels of CRP > 10 mg/L were included and randomized to active treatment with 10 mg piroxicam daily or placebo. Assessment comprised general clinical and biochemical parameters, 25 cytokines in serum, intra-and extracellular Hsp27 and Hsp70, Elderly Mobility Scale (EMS) scores, grip strength (GS), fatigue resistance (FR) and lean body mass (LBM). Patients were evaluated until discharge with a maximum of 3 weeks after treatment allocation.</p> <p>Results</p> <p>EMS scores, FR and grip work (GW), a measure taking into account GS and FR, significantly improved with piroxicam, but not with placebo. Early decreases in IL-6 serum levels with piroxicam correlated with better muscle performance at week 2. Basal expression of Hsp27 in monocytes without heat challenge (WHC) was positively correlated with FR at baseline and significantly increased by treatment with piroxicam compared to placebo. Profound modifications in the relationships between cytokines or Hsp and changes in muscle parameters were observed in the piroxicam group.</p> <p>Conclusions</p> <p>Piroxicam improves clinically relevant measures of muscle performance and mobility in geriatric patients hospitalized with acute infection-induced inflammation. Underlying mechanisms may include modifications in the cytokine network and increases in monocytic expression of cytoprotective Hsp27.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN96340690">ISRCTN96340690</a></p

Exercise and functional foods

Appropriate nutrition is an essential prerequisite for effective improvement of athletic performance, conditioning, recovery from fatigue after exercise, and avoidance of injury. Nutritional supplements containing carbohydrates, proteins, vitamins, and minerals have been widely used in various sporting fields to provide a boost to the recommended daily allowance. In addition, several natural food components have been found to show physiological effects, and some of them are considered to be useful for promoting exercise performance or for prevention of injury. However, these foods should only be used when there is clear scientific evidence and with understanding of the physiological changes caused by exercise. This article describes various "functional foods" that have been reported to be effective for improving exercise performance or health promotion, along with the relevant physiological changes that occur during exercise

CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis

The complement system is important for the host defence against infection as well as for the development of inflammatory diseases. Here we show that C1q/TNF-related protein 6 (CTRP6; gene symbol C1qtnf6) expression is elevated in mouse rheumatoid arthritis (RA) models. C1qtnf6 -/- mice are highly susceptible to induced arthritis due to enhanced complement activation, whereas C1qtnf6-transgenic mice are refractory. The Arthus reaction and the development of experimental autoimmune encephalomyelitis are also enhanced in C1qtnf6 -/- mice and C1qtnf6 -/- embryos are semi-lethal. We find that CTRP6 specifically suppresses the alternative pathway of the complement system by competing with factor B for C3(H 2 O) binding. Furthermore, treatment of arthritis-induced mice with intra-articular injection of recombinant human CTRP6 cures the arthritis. CTRP6 is expressed in human synoviocytes, and CTRP6 levels are increased in RA patients. These results indicate that CTRP6 is an endogenous complement regulator and could be used for the treatment of complement-mediated diseases