Communicating, Networking: Interacting: The International Year of Global Understanding - IYGU

Communication Studies; Sustainable Development; Communications Engineering, Networks; Computer Systems Organization and Communication Network

Communicating, Networking: Interacting: The International Year of Global Understanding - IYGU

Communication Studies; Sustainable Development; Communications Engineering, Networks; Computer Systems Organization and Communication Network

Evaluation of the effectiveness and cost-effectiveness of Families for Health V2 for the treatment of childhood obesity : study protocol for a randomized controlled trial

Background: Effective programs to help children manage their weight are required. Families for Health focuses on a parenting approach, designed to help parents develop their parenting skills to support lifestyle change within the family. Families for Health V1 showed sustained reductions in overweight after 2 years in a pilot evaluation, but lacks a randomized controlled trial (RCT) evidence base. Methods/design: This is a multi-center, investigator-blind RCT, with parallel economic evaluation, with a 12-month follow-up. The trial will recruit 120 families with at least one child aged 6 to 11 years who is overweight (≥91st centile BMI) or obese (≥98th centile BMI) from three localities and assigned randomly to Families for Health V2 (60 families) or the usual care control (60 families) groups. Randomization will be stratified by locality (Coventry, Warwickshire, Wolverhampton). Families for Health V2 is a family-based intervention run in a community venue. Parents/carers and children attend parallel groups for 2.5 hours weekly for 10 weeks. The usual care arm will be the usual support provided within each NHS locality. A mixed-methods evaluation will be carried out. Child and parent participants will be assessed at home visits at baseline, 3-month (post-treatment) and 12-month follow-up. The primary outcome measure is the change in the children’s BMI z-scores at 12 months from the baseline. Secondary outcome measures include changes in the children’s waist circumference, percentage body fat, physical activity, fruit/vegetable consumption and quality of life. The parents’ BMI and mental well-being, family eating/activity, parent–child relationships and parenting style will also be assessed. Economic components will encompass the measurement and valuation of service utilization, including the costs of running Families for Health and usual care, and the EuroQol EQ-5D health outcomes. Cost-effectiveness will be expressed in terms of incremental cost per quality-adjusted life year gained. A de novo decision-analytic model will estimate the lifetime cost-effectiveness of the Families for Health program. Process evaluation will document recruitment, attendance and drop-out rates, and the fidelity of Families for Health delivery. Interviews with up to 24 parents and children from each arm will investigate perceptions and changes made. Discussion: This paper describes our protocol to assess the effectiveness and cost-effectiveness of a parenting approach for managing childhood obesity and presents challenges to implementation. Trial registration: Current Controlled Trials ISRCTN4503220

Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline

<b>Objective</b>: MicroRNAs (miRNAs) are small noncoding RNAs that have the capacity to control protein production through binding "seed" sequences within a target mRNA. Each miRNA is capable of potentially controlling hundreds of genes. The regulation of miRNAs in the lung during the development of pulmonary arterial hypertension (PAH) is unknown.<p></p> <b>Methods and Results</b>: We screened lung miRNA profiles in a longitudinal and crossover design during the development of PAH caused by chronic hypoxia or monocrotaline in rats. We identified reduced expression of Dicer, involved in miRNA processing, during the onset of PAH after hypoxia. MiR-22, miR-30, and let-7f were downregulated, whereas miR-322 and miR-451 were upregulated significantly during the development of PAH in both models. Differences were observed between monocrotaline and chronic hypoxia. For example, miR-21 and let-7a were significantly reduced only in monocrotaline-treated rats. MiRNAs that were significantly regulated were validated by quantitative polymerase chain reaction. By using in vitro studies, we demonstrated that hypoxia and growth factors implicated in PAH induced similar changes in miRNA expression. Furthermore, we confirmed miR-21 downregulation in human lung tissue and serum from patients with idiopathic PAH.<p></p> <b>Conclusion</b>: Defined miRNAs are regulated during the development of PAH in rats. Therefore, miRNAs may contribute to the pathogenesis of PAH and represent a novel opportunity for therapeutic intervention.<p></p&gt

Changes in HPV prevalence following a national bivalent HPV vaccination programme in Scotland: a 7-year cross-sectional study

Background: On Sept 1, 2008, Scotland launched routine vaccination for human papillomavirus (HPV) types 16 and 18, targeted at 12–13-year-old girls, of whom 92·4% were fully vaccinated in 2008–09. In this study, we report on vaccine effectiveness of the bivalent vaccine in these vaccinated women who attended for routine cervical screening at age 20–21 years. Methods: In this 7-year cross-sectional study (covering birth cohorts 1988–1995), we sampled approximately 1000 samples per year from those attending cervical screening at age 20–21 years and tested each for HPV. By linkage to vaccination records we ascertained prevalence by birth cohort and vaccination status. Estimates of vaccine effectiveness for HPV types 16 and 18, HPV types 31, 33, and 45, other high-risk types, and any HPV were calculated using logistic regression. Findings: In total, 8584 samples were HPV genotyped. Prevalence of HPV types 16 and 18 reduced substantially from 30·0% (95% CI 26·9–33·1) in the 1988 cohort to 4·5% (3·5–5·7) in the 1995 cohort, giving a vaccine effectiveness of 89·1% (85·1–92·3) for those vaccinated at age 12–13 years. All cross-protective types showed significant vaccine effectiveness (HPV type 31, 93·8% [95% CI 83·8–98·5]; HPV type 33, 79·1% [64·2–89·0]; HPV type 45, 82·6% [61·5–93·9]). Unvaccinated individuals born in 1995 had a reduced odds of HPV types 16 and 18 infection compared with those born in 1988 (adjusted odds ratio 0·13 [95% CI 0·06–0·28]) and reduced odds of HPV types 31, 33, and 45 (odds ratio 0·45 [0·23–0·89]). Interpretation: Bivalent vaccination has led to a startling reduction in vaccine and cross-protective HPV types 7 years after vaccination. There is also evidence of herd protection against the vaccine-specific and cross-protective types in unvaccinated individuals born in 1995. These findings should be considered in cost-effectiveness models informing vaccine choice and models to shape the future of cervical screening programmes

Pilot randomized trial of therapeutic hypothermia with serial cranial ultrasound and 18-22 month follow-up for neonatal encephalopathy in a low resource hospital setting in Uganda: study protocol

Background: There is now convincing evidence that in industrialized countries therapeutic hypothermia for perinatal asphyxial encephalopathy increases survival with normal neurological function. However, the greatest burden of perinatal asphyxia falls in low and mid-resource settings where it is unclear whether therapeutic hypothermia is safe and effective.Aims: Under the UCL Uganda Women's Health Initiative, a pilot randomized controlled trial in infants with perinatal asphyxia was set up in the special care baby unit in Mulago Hospital, a large public hospital with similar to 20,000 births in Kampala, Uganda to determine:(i) The feasibility of achieving consent, neurological assessment, randomization and whole body cooling to a core temperature 33-34 degrees C using water bottles(ii) The temperature profile of encephalopathic infants with standard care(iii) The pattern, severity and evolution of brain tissue injury as seen on cranial ultrasound and relation with outcome(iv) The feasibility of neurodevelopmental follow-up at 18-22 months of ageMethods/Design: Ethical approval was obtained from Makerere University and Mulago Hospital. All infants were in-born. Parental consent for entry into the trial was obtained. Thirty-six infants were randomized either to standard care plus cooling (target rectal temperature of 33-34 degrees C for 72 hrs, started within 3 h of birth) or standard care alone. All other aspects of management were the same. Cooling was performed using water bottles filled with tepid tap water (25 degrees C). Rectal, axillary, ambient and surface water bottle temperatures were monitored continuously for the first 80 h. Encephalopathy scoring was performed on days 1-4, a structured, scorable neurological examination and head circumference were performed on days 7 and 17. Cranial ultrasound was performed on days 1, 3 and 7 and scored. Griffiths developmental quotient, head circumference, neurological examination and assessment of gross motor function were obtained at 18-22 months.Discussion: We will highlight differences in neonatal care and infrastructure that need to be taken into account when considering a large safety and efficacy RCT of therapeutic hypothermia in low and mid resource settings in the future

Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction.

AIMS: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide linked to vascular diseases through a common intronic gene enhancer [(rs9349379-G allele), chromosome 6 (PHACTR1/EDN1)]. We performed a multimodality investigation into the role of ET-1 and this gene variant in the pathogenesis of coronary microvascular dysfunction (CMD) in patients with symptoms and/or signs of ischaemia but no obstructive coronary artery disease (CAD). METHODS AND RESULTS: Three hundred and ninety-one patients with angina were enrolled. Of these, 206 (53%) with obstructive CAD were excluded leaving 185 (47%) eligible. One hundred and nine (72%) of 151 subjects who underwent invasive testing had objective evidence of CMD (COVADIS criteria). rs9349379-G allele frequency was greater than in contemporary reference genome bank control subjects [allele frequency 46% (129/280 alleles) vs. 39% (5551/14380); P = 0.013]. The G allele was associated with higher plasma serum ET-1 [least squares mean 1.59 pg/mL vs. 1.28 pg/mL; 95% confidence interval (CI) 0.10-0.53; P = 0.005]. Patients with rs9349379-G allele had over double the odds of CMD [odds ratio (OR) 2.33, 95% CI 1.10-4.96; P = 0.027]. Multimodality non-invasive testing confirmed the G allele was associated with linked impairments in myocardial perfusion on stress cardiac magnetic resonance imaging at 1.5 T (N = 107; GG 56%, AG 43%, AA 31%, P = 0.042) and exercise testing (N = 87; -3.0 units in Duke Exercise Treadmill Score; -5.8 to -0.1; P = 0.045). Endothelin-1 related vascular mechanisms were assessed ex vivo using wire myography with endothelin A receptor (ETA) antagonists including zibotentan. Subjects with rs9349379-G allele had preserved peripheral small vessel reactivity to ET-1 with high affinity of ETA antagonists. Zibotentan reversed ET-1-induced vasoconstriction independently of G allele status. CONCLUSION: We identify a novel genetic risk locus for CMD. These findings implicate ET-1 dysregulation and support the possibility of precision medicine using genetics to target oral ETA antagonist therapy in patients with microvascular angina. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03193294.The Wellcome Trust 107715/Z/15/Z