An exploration of the statutory Healthy Start vitamin supplementation scheme in North West England.

BACKGROUND: Government nutritional welfare support from the English 'Healthy Start' scheme is targeted at low-income pregnant women and preschool children, but take-up of its free food vouchers is much better than its free vitamin vouchers. While universal implementation probably requires a more extensive scheme to be cost-effective, the everyday experience of different ways of receiving or facilitating Healthy Start, especially via children's centres, also requires further evidence. This study therefore aimed to explore (in the context of low take-up levels) perceptions of mothers, health professionals, and commissioners about Healthy Start vitamin and food voucher take-up and compare experiences in a targeted and a universal implementation-area for those vitamins. METHODS: Informed by quantitative analysis of take-up data, qualitative analysis focused on 42 semi-structured interviews with potentially eligible mothers and healthcare staff (and commissioners), purposively sampled via children's centres in a similarly deprived universal and a targeted implementation-area of North West England. RESULTS: While good food voucher take-up appeared to relate to clear presentation, messaging, practicality, and monetary (albeit low) value, poor vitamin take-up appeared to relate to overcomplicated procedures and overreliance on underfunded centres, organizational goodwill, and families' resilience. CONCLUSION: Higher 'universal' vitamin take-up may well have reflected fewer barriers when it became everyone's business to be vitamin-aware. Substantive Healthy Start reform in England (not just cosmetic tinkering) is long overdue. Our study highlights that 'policy, politics, and problem' should be aligned to reach considerable unmet need

An exploration of the statutory Healthy Start vitamin supplementation scheme in North West England

Background Government nutritional welfare support from the English ‘Healthy Start’ scheme is targeted at low-income pregnant women and preschool children, but take-up of its free food vouchers is much better than its free vitamin vouchers. While universal implementation probably requires a more extensive scheme to be cost-effective, the everyday experience of different ways of receiving or facilitating Healthy Start, especially via children’s centres, also requires further evidence. This study therefore aimed to explore (in the context of low take-up levels) perceptions of mothers, health professionals, and commissioners about Healthy Start vitamin and food voucher take-up and compare experiences in a targeted and a universal implementation-area for those vitamins. Methods Informed by quantitative analysis of take-up data, qualitative analysis focused on 42 semi-structured interviews with potentially eligible mothers and healthcare staff (and commissioners), purposively sampled via children’s centres in a similarly deprived universal and a targeted implementation-area of North West England. Results While good food voucher take-up appeared to relate to clear presentation, messaging, practicality, and monetary (albeit low) value, poor vitamin take-up appeared to relate to overcomplicated procedures and overreliance on underfunded centres, organizational goodwill, and families’ resilience. Conclusion Higher ‘universal’ vitamin take-up may well have reflected fewer barriers when it became everyone’s business to be vitamin-aware. Substantive Healthy Start reform in England (not just cosmetic tinkering) is long overdue. Our study highlights that ‘policy, politics, and problem’ should be aligned to reach considerable unmet need

Measuring older people’s socioeconomic position: a scoping review of studies of self-rated health, health service and social care use

Background The challenges of measuring socioeconomic position in older populations were first set out two decades ago. However, the question of how best to measure older people’s socioeconomic position remains pertinent as populations age and health inequalities widen. Methods A scoping review aimed to identify and appraise measures of socioeconomic position used in studies of health inequalities in older populations in high-income countries. Medline, Scopus, EMBASE, HMIC and references lists of systematic reviews were searched for observational studies of socioeconomic health inequalities in adults aged 60 years and over, published between 2000 and 2020. A narrative synthesis was conducted. Findings One-hundred and thirty-eight studies were included; 20 approaches to measuring socioeconomic position were identified. Few studies considered which pathways the chosen measures of socioeconomic position intended to capture. The validity of subjective socioeconomic position measures, and measures that assume shared income and educational capital, should be verified in older populations. Incomplete financial data risk under-representation of some older groups when missing data are socially patterned. Older study samples were largely homogeneous on measures of housing tenure, and to a lesser extent, measures of educational attainment. Measures that use only two response categories risk missing subtle differences in older people’s socioeconomic circumstances. Conclusion Poor choice of measures of socioeconomic position risk underestimating the size of health inequalities in older populations. Choice of measures should be shaped by considerations of theory, context and response categories that detect subtle, yet important, inequalities. Further evidence is required to ascertain the validity of some measures identified in this review

Formulation and evaluation of floating mucoadhesive alginate beads for targetingHelicobacter pylori

Objectives: There are various obstacles in the eradication of Helicobacter.pylori (H. pylori) infections, including low antibiotic levels and poor accessibility of the drug at the site of the infection. This study describes the preparation and characterisation of novel floating-mucoadhesive alginate beads loaded with clarithromycin (CMN) for delivery to the gastric mucosa to improve the eradication of this micro-organism. Methods: Calcium alginate beads were prepared by ionotropic gelation. The formulation was modified through addition of oil and coating with chitosan in order to improve floating, mucoadhesion and modify drug release. Key findings: SEM confirmed the sphericity of the beads with X-ray microtomography (XμMT) showing the 3D structure of the beads with the layered internal structure of the bead and the even distribution of the drug within the bead. This formulation combined two gastro-retentive strategies and these formulations produced excellent in vitro floating, mucoadhesive and drug release characteristics. Enhanced stability of the beads in phosphate buffer raises a potential for the modified formulations to be targeted to regions of higher pH within the gastrointestinal tract with a higher pH. Drug release from these beads was sustained through an unstirred mucin layer simulating in vivo conditions under which the H. pylori resides in the gastric mucosa. Conclusions: This novel formulation will ensure retention for a longer period in the stomach than conventional formulations and control drug release, ensuring high local drug concentrations, leading to improved eradication of the bacteria

Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation

While the catalog of mammalian transcripts and their expression levels in different cell types and disease states is rapidly expanding, our understanding of transcript function lags behind. We present a robust technology enabling systematic investigation of the cellular consequences of repressing or inducing individual transcripts. We identify rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%–99% knockdown with minimal off-target effects, and activators (CRISPRa) to endogenous genes via endonuclease-deficient Cas9. Together they enable modulation of gene expression over a ∼1,000-fold range. Using these rules, we construct genome-scale CRISPRi and CRISPRa libraries, each of which we validate with two pooled screens. Growth-based screens identify essential genes, tumor suppressors, and regulators of differentiation. Screens for sensitivity to a cholera-diphtheria toxin provide broad insights into the mechanisms of pathogen entry, retrotranslocation and toxicity. Our results establish CRISPRi and CRISPRa as powerful tools that provide rich and complementary information for mapping complex pathways

Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): a multicentre, parallel-group, randomised placebo-controlled trial

BackgroundDiarrhoea-predominant irritable bowel syndrome (IBS-D) is a common outcome after inflammation due to bacterial gastroenteritis. Several studies have shown ongoing immune activation in the mucosa of patients with IBS-D and a number of studies have suggested that mesalazine slow-release granule formulation (2?g; PENTASA®, Ferring Pharmaceuticals Ltd) may provide benefit including a reduction in stool frequency.ObjectivesOur primary aim was to compare the effect of mesalazine with placebo on stool frequency. Our secondary aims were to assess the effect of mesalazine on abdominal pain, stool consistency, urgency and satisfactory relief of irritable bowel syndrome (IBS) symptoms.Design/participants/interventionWe performed a double-blind, randomised placebo-controlled trial of 2?g mesalazine twice daily compared with placebo for 3 months in Rome III criteria patients with IBS-D.SettingsParticipants were recruited from the primary care research network and secondary care hospitals. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘satisfactory relief of IBS symptoms’. Those recruited in Nottingham had sigmoid biopsies and/or magnetic resonance imaging of the abdomen at the start and end of the trial.ResultsA total of 136 patients with IBS-D (82 female, 54 male) were randomised; 10 patients withdrew from each group. Analysis by intention to treat showed that the mean daily average stool frequency during weeks 11 and 12 was 2.8 [standard deviation (SD) 1.2] in the mesalazine group and 2.7 (SD 1.9) in the placebo group, with a group difference of 0.1 (95% confidence interval –0.33 to 0.53); p?=?0.66.ConclusionsMesalazine did not improve abdominal pain, stool consistency or percentage with satisfactory relief compared with placebo during the last 2 weeks’ follow-up. A post hoc analysis in 13 postinfectious patients with IBS appeared to show benefit but this needs confirmation in a larger group. More precise subtyping based on underlying disease mechanisms may allow more effective targeting of treatment in IBS.Trial registrationCurrent Controlled Trials ISRCTN76612274.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.<br/

TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis

Although tumor necrosis factor (α) (TNF) exerts proinflammatory activities in a variety of diseases, including inflammatory bowel disease, there is increasing evidence for antiinflammatory actions of TNF. In contrast, glucocorticoids (GCs) are steroid hormones that suppress inflammation, at least in part by regulating the expression and action of TNF. We report that TNF induces extraadrenal production of immunoregulatory GCs in the intestinal mucosa during acute intestinal inflammation. The absence of TNF results in a lack of colonic GC synthesis and exacerbation of dextran sodium sulfate–induced colitis. TNF seems to promote local steroidogenesis by directly inducing steroidogenic enzymes in intestinal epithelial cells. Therapeutic administration of TNF induces GC synthesis in oxazolone-induced colitis and ameliorates intestinal inflammation, whereas inhibition of intestinal GC synthesis abrogates the therapeutic effect of TNF. These data show that TNF suppresses the pathogenesis of acute intestinal inflammation by promoting local steroidogenesis

The cancer care experiences of gay, lesbian and bisexual patients: A secondary analysis of data from the UK Cancer Patient Experience Survey

Understanding the effects of population diversity on cancer-related experiences is a priority in oncology care. Previous research demonstrates inequalities arising from variation in age, gender and ethnicity. Inequalities and sexual orientation remain underexplored. Here, we report, for the first time in the UK, a quantitative secondary analysis of the 2013 UK National Cancer Patient Experience Survey which contains 70 questions on specific aspects of care, and six on overall care experiences. 68,737 individuals responded, of whom 0.8% identified as lesbian, gay or bisexual. Controlling for age, gender and concurrent mental health comorbidity, logistic regression models applying post-estimate probability Wald tests explored response differences between heterosexual, bisexual and lesbian/gay respondents. Significant differences were found for 16 questions relating to: (1) a lack of patient-centred care and involvement in decision-making, (2) a need for health professional training and revision of information resources to negate the effects of heteronormativity and (3) evidence of substantial social isolation through cancer. These findings suggest a pattern of inequality, with less positive cancer experiences reported by lesbian, gay and (especially) bisexual respondents. Poor patient–professional communication and heteronormativity in the healthcare setting potentially explain many of the differences found. Social isolation is problematic for this group and warrants further exploration

Roles of allostatic load, lifestyle and clinical risk factors in mediating the association between education and coronary heart disease risk in Europe

Background Previous studies have shown that differential exposure to lifestyle factors may mediate the association between education and coronary heart diseases (CHD). However, few studies have examined the potential roles of allostatic load (AL) or differential susceptibility. Methods 25 310 men and 26 018 women aged 35\u201374 and CHD free at baseline were identified from 21 European cohorts and followed for a median of 10 years, to investigate the mediating role of AL, as well as of smoking, alcohol use and body mass index (BMI), on educational differences in CHD incidence, applying marginal structural models and three-way decomposition. Results AL is a mediator of the association between educational status and CHD incidence, with the highest proportion mediated observed among women and largely attributable to differential exposure, (28% (95% CI 19% to 44%)), with 8% (95% CI 0% to 16%) attributable to differential susceptibility. The mediating effects of smoking, alcohol and BMI, compared with AL, were relatively small for both men and women. Conclusion Overall, the educational inequalities in CHD incidence were partially mediated through differential exposure to AL. By contrast, the mediation of the educational gradient in CHD by investigated lifestyle risk factors was limited. As differential susceptibility in men was found to have a predominant role in the accumulation of AL in low educational classes, the investigation of AL-related risk factors is warranted