A protocol for a cluster randomised feasibility study of an adolescent incentive intervention to increase uptake of HPV vaccination among girls

Background Uptake of the human papillomavirus (HPV) vaccine in the UK is good, but there are pockets of the community who remain unprotected. Immunisation teams usually require written parental consent for a girl to receive the vaccine. Evidence suggests that uptake of the vaccine might be improved by promoting consent form return (if returned, forms are likely to grant consent). Incentivising girls to return consent forms is a promising approach to promoting consent form return. Before testing the efficacy of an incentive intervention in a randomised controlled trial (RCT), we must first establish whether the RCT is feasible. In this randomised feasibility study, we aim to establish the feasibility of conducting a cluster RCT of an adolescent incentive intervention to increase uptake of HPV vaccination. Methods At least six schools will be randomised to either an incentive intervention arm or a standard invitation arm. Girls in standard invitation arm schools will receive the usual HPV vaccine programme invitation materials. Girls attending schools in the incentive intervention arm will receive the standard invitation and will also be told that they will receive an incentive if they return their consent form (regardless of whether consent is granted or denied). The incentive is being entered into a prize draw to win a retail voucher. Feasibility objectives include estimating the schools’ and parents’ willingness to participate in the study and be randomised; response rates to questionnaires; the extent of missing data; the girls’ and parents’ attitudes towards the incentive offered; school staff experiences of participating, fidelity to the trial procedures, data on any unintended consequences and the possible mechanisms of action, and proof-of-concept evidence of the effect of the intervention on consent form return rates and uptake of the vaccine. Analysis of feasibility outcomes will primarily be descriptive. Consent form return rates and uptake of the vaccine will be presented by trial arm without comparison. Discussion Incentivising HPV vaccine consent form return may promote HPV vaccine uptake. This study will provide the evidence needed to establish whether testing this incentive intervention using a RCT design in the future is feasible

COPe-support - a multi-component digital intervention for family carers for people affected by psychosis: study protocol for a randomized controlled trial.

BACKGROUND: Psychosis often causes significant distress and impacts not only in the individuals, but also those close to them. Many relatives and friends ('carers') provide long-term support and need resources to assist them. We have co-produced a digital mental health intervention called COPe-support (Carers fOr People with Psychosis e-support) to provide carers with flexible access to high quality psychoeducation and interactive support from experts and peers. This study evaluates the effectiveness of COPe-support to promote mental wellbeing and caregiving experiences in carers. METHODS: This study is a single-blind, parallel arm, individually randomized controlled trial (RCT) comparing COPe-support, with attention control. Both groups continue to receive usual care. COPe-support provides interactive web-based psychoeducation on psychosis-related issues, wellbeing-promotion and network support through forums. The attention-control is a non-interactive online information resource pack. Carers living in England are eligible if they provide at least weekly support to a family member or close friend affected by psychosis, and use internet communication (including emails) daily. All trial procedures are run online, including collection of outcome measurements which participants will directly input into our secure platform. Following baseline assessment, a web-based randomization system will be used to allocate 360 carers to either arm. Participants have unlimited access to the allocated condition for 40 weeks. Data collection is at three time points (10, 20, and 40 weeks after randomization). Analyses will be conducted by trial statisticians blinded to allocation. The primary outcome is mental wellbeing measured by Warwick Edinburgh Mental Wellbeing Scale (WEMWBS), at 20 weeks. As well as an intention-to-treat analysis, a complier average causal effect (CACE) analysis will be conducted to estimate the intervention effect in participants who have accessed COPe-support content twice or more. The secondary objectives and analysis will examine other health and caregiving-related outcomes and explore mechanisms. In a process evaluation, we will interview 20% of the intervention arm participants regarding the acceptability of COPe-support. We will explore in detail participants' usage patterns. DISCUSSION: The results of this trial will provide valuable information about the effectiveness of COPe-support in promoting wellbeing and caregiving experiences in carers. TRIAL REGISTRATION: The RCT is registered with the Current Controlled Trials registration (ISRCTN 89563420, registration date: 02/03/2018)

Evidence of oxidative stress and mitochondrial dysfunction in spinocerebellar ataxia type 2 (SCA2) patient fibroblasts: Effect of coenzyme Q10 supplementation on these parameters

Spinocerebellar ataxia type 2 (SCA2) is a rare neurodegenerative disorder caused by a CAG repeat expansion in the ataxin-2 gene. We show increased oxidative stress, abnormalities in the antioxidant system, changes in complexes involved in oxidative phosphorylation and changes in mitochondrial morphology in SCA2 patient fibroblasts compared to controls, and we show that treatment with CoQ10 can partially reverse these changes. Together, our results suggest that oxidative stress and mitochondrial dysfunction may be contributory factors to the pathophysiology of SCA2 and that therapeutic strategies involving manipulation of the antioxidant system could prove to be of clinical benefit

Practical approaches to Bayesian sample size determination in non-inferiority trials with binary outcomes.

Bayesian analysis of a non-inferiority trial is advantageous in allowing direct probability statements to be made about the relative treatment difference rather than relying on an arbitrary and often poorly justified non-inferiority margin. When the primary analysis will be Bayesian, a Bayesian approach to sample size determination will often be appropriate for consistency with the analysis. We demonstrate three Bayesian approaches to choosing sample size for non-inferiority trials with binary outcomes and review their advantages and disadvantages. First, we present a predictive power approach for determining sample size using the probability that the trial will produce a convincing result in the final analysis. Next, we determine sample size by considering the expected posterior probability of non-inferiority in the trial. Finally, we demonstrate a precision-based approach. We apply these methods to a non-inferiority trial in antiretroviral therapy for treatment of HIV-infected children. A predictive power approach would be most accessible in practical settings, because it is analogous to the standard frequentist approach. Sample sizes are larger than with frequentist calculations unless an informative analysis prior is specified, because appropriate allowance is made for uncertainty in the assumed design parameters, ignored in frequentist calculations. An expected posterior probability approach will lead to a smaller sample size and is appropriate when the focus is on estimating posterior probability rather than on testing. A precision-based approach would be useful when sample size is restricted by limits on recruitment or costs, but it would be difficult to decide on sample size using this approach alone

Alveolar soft part sarcoma: clinicopathological findings in a series of 11 cases

<p>Abstract</p> <p>Background</p> <p>Alveolar sarcoma of the soft parts (ASPS) represents a very rare entity of soft tissue sarcoma with special features such as young peak age incidence and frequent metastasis to the brain. The aim of this study was a clinicopathological analysis with special reference to treatment and outcome.</p> <p>Methods</p> <p>From the database of the BG-University Hospital Bergmannsheil, 1597 soft tissue sarcoma (STS) cases were reviewed and 11 consecutive patients with ASPS were isolated. Data was acquired from patients' charts and contact to patients, their relatives or general practitioners, with special reference to treatment and clinical course. The average follow up time from the time of the definite operation for the primary tumor was 6.5 years. Kaplan-Meier method was used to calculate survival.</p> <p>Results</p> <p>Patients with localized disease who received complete resection and adjuvant radiation and who did not develop recurrence or metastatic disease within 2 years after surgery had a positive outcome. The size of the tumor, its localization, and the time of untreated growth before treatment did not influence the long-term results. All patients who developed recurrent disease also suffered from distant metastasis, reflecting the aggressive biology of the tumor. All patients with distant metastasis had the lungs and the brain affected.</p> <p>Conclusion</p> <p>Due to the limited number of patients with ASPS, prospective studies would have to span decades to gather a significant collective of patients; therefore, it is not possible to comment meaningfully on a possible benefit of neoadjuvant or adjuvant therapy.</p> <p>We recommend wide surgical excision and, in the absence of data telling otherwise, adjuvant radiation. In cases with recurrent disease or metastasis, the prognosis is bad and further treatment will be restricted to palliation in most cases.</p

Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action

Introduction The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA). Methods KPL-1 cell growth was assessed by colorimetric 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21Cip1/Waf1, cyclin D1, Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet. Results CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G0/G1 arrest, which involved increased expression of p53 and p21Cip1/Waf1, and decreased expression of cyclin D1. CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner. Conclusion CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system.</p

A cluster randomised feasibility study of an adolescent incentive intervention to increase uptake of HPV vaccination.

BACKGROUND: Uptake of human papillomavirus (HPV) vaccination is suboptimal among some groups. We aimed to determine the feasibility of undertaking a cluster randomised controlled trial (RCT) of incentives to improve HPV vaccination uptake by increasing consent form return. METHODS: An equal-allocation, two-arm cluster RCT design was used. We invited 60 London schools to participate. Those agreeing were randomised to either a standard invitation or incentive intervention arm, in which Year 8 girls had the chance to win a £50 shopping voucher if they returned a vaccination consent form, regardless of whether consent was provided. We collected data on school and parent participation rates and questionnaire response rates. Analyses were descriptive. RESULTS: Six schools completed the trial and only 3% of parents opted out. The response rate was 70% for the girls' questionnaire and 17% for the parents'. In the intervention arm, 87% of girls returned a consent form compared with 67% in the standard invitation arm. The proportion of girls whose parents gave consent for vaccination was higher in the intervention arm (76%) than the standard invitation arm (61%). CONCLUSIONS: An RCT of an incentive intervention is feasible. The intervention may improve vaccination uptake but a fully powered RCT is needed.British Journal of Cancer advance online publication: 22 August 2017; doi:10.1038/bjc.2017.284 www.bjcancer.com

Effects of maternal and paternal smoking on attentional control in children with and without ADHD

Maternal smoking during pregnancy is a risk factor for attention-deficit/hyperactivity disorder (ADHD), but data on its adverse effects on cognitive functioning are sparse and inconsistent. Since the effect of maternal smoking during pregnancy may be due to correlated genetic risk factors rather than being a pure environmental effect, we examined the effect of prenatal exposure to smoking on attentional control, taking into account the effects of both maternal and paternal smoking, and examined whether these effects were genetically mediated by parental genotypes. We further examined whether the effect of prenatal exposure to smoking on attentional control interacted with genotypes of the child. Participants were 79 children with ADHD, ascertained for the International Multi-centre ADHD Gene project (IMAGE), and 105 normal controls. Attentional control was assessed by a visual continuous performance task. Three genetic risk factors for ADHD (DRD4 7-repeat allele of the exon 3 variable number of tandem repeats (VNTR), DAT1 10/10 genotype of the VNTR located in the 3′ untranslated region, and the DAT1 6/6 genotype of the intron 8 VNTR) were included in the analyses. Paternal smoking had a negative effect on attentional control in children with ADHD and this effect appeared to be mediated by genetic risk factors. The prenatal smoking effect did not interact with genotypes of the child. Maternal smoking had no main effect on attentional control, which may be due to lower smoking rates. This study suggests that the effects of paternal smoking on attentional control in children with ADHD should be considered a proxy for ADHD and/or smoking risk genes. Future studies should examine if the results can be generalized to other cognitive domains