Exploring the experiences of transgender adolescents using the creative arts and a participatory approach to research.

Research investigating the emotional wellbeing of transgender children and young people (CYP) has explored the impact of their experiences on their mental health and education (Bradlow, Bartram, Guasp & Jadva, 2017). In particular, adolescence has been identified as a challenging time for CYP questioning their gender identity (Lee, 2004 cited in Hellen, 2009). The presented research aimed to explore the experiences of transgender CYP in order to identify ways in which schools and educational professionals can offer support. Taking a participatory approach using the creative arts, the individual stories of four transgender adolescents were explored. Co-researchers aged between 14-22 detailed their experiences of being transgender through the use of a visual method, supported by text generated through discussion. In line with participatory approaches, the co-researchers worked with the researcher to conduct the analysis and interpretation of the data. Thematic analysis was chosen as the method of analysis as it allowed for the interpretation of both visual and textual data while being aligned to no specific research method. The findings from this research aim to deepen the understanding of the lives of transgender adolescents through exploring similarities and differences within their stories of their formative years. Themes are identified including mental health, identity, stereotypes and knowledge. Through identifying these themes recommendations are made regarding how schools and educational professionals may be able to support transgender CYP during their education by considering the multiple systems within which they are located

Are physiotherapists walking the walk? : a global survey of physiotherapists' physical activity levels

Background: Insufficient physical activity (PA) is 1 of the 10 leading risk factors for non-communicable diseases and early death worldwide (WHO 2010). PA counselling by physicians and other healthcare professionals has been shown to be effective in increasing PA levels, at least in the short-term (Orrow et al 2012). It has also been shown to increase years lived free from disease (Gulliford et al 2013) and has been shown to be cost-effective (Murphey et al 2012). Conveying information about PA to patients in a way that will facilitate behaviour change is a complex intervention and is influenced by many factors. One factor that has been identified in the literature as having a strong influence over this interaction is the PA habits of the healthcare professionals. There is compelling evidence that the PA habits of healthcare professionals influence the amount that they promote PA in their clinical practice (Lobelo 2014). There is a need to better understand Physiotherapists´ own PA levels in order to understand this important variable that influences PA promotion in clinical practice. Purpose: To record the physical activity levels of physiotherapists around the globe. Methods: Survey data was collected from participants of a global online physiotherapy and physical activity course. A validated, single-item question was used to assess the number of days on which respondents had been active for at least 30 minutes in the last week. Responses were collated and preliminary descriptive statistics were performed. Further data analysis is planned. Results: 2498 responses were collected from 120 countries. The mean number of days on which respondents had been active in the week prior to completion was 3. The proportion of respondents who had been active on 5 or more days was 26% (n=647). The guideline of 5 x 30 minutes of moderate PA on 5 or more days per week was not achieved by 74% (n=1851) of respondents and 11% (n=287) respondents had not achieved 30 minutes moderate PA on any day in the previous week. Conclusion(s): These are preliminary findings only and further analysis (including analysis by country) is planned. Self-report of PA is known to have limitations and the measurement tool used may not capture all relevant PA. However, the results suggest the levels of PA amongst Physiotherapists around the globe may be surprisingly low. Implications: It is essential that the limitations of a single-item question are kept in mind when considering implications. The preliminary results suggest that PA levels of Physiotherapists may be low, this has important implications firstly for Physiotherapists as promoters of PA, this may be an important issue in increasing PA promotion in clinical practice. Secondly there may be important implications for workforce health. Key-Words: physical activity; physiotherapy; health promotion Funding acknowledgements: No funding was sought for this project. Acknowledgements to Sheffield Hallam University and Physiopedia. Ethics approval: Ethical Approval was granted by Sheffield Hallam University Faculty of Health & Wellbeing Ethics Board. Presentation Type: Platform presentatio

“It Makes You Feel Alive and Younger…but It’s Stressful …My Back and Legs Ache”: A Focus Group Study Encouraging Resistance Training Around Retirement

Muscle weakness is a key component of age-related conditions such as sarcopenia and frailty. Resistance training is highly effective at preventing and treating muscle weakness; however, few adults meet recommended levels. Retirement may be a key life-stage to promote resistance training. We carried out a virtual focus group study to explore motivators and barriers to resistance training around the time of retirement, with the aim of determining strategies and messages to increase its uptake. The five focus groups (n = 30) were recorded, transcribed and thematically analysed. We found that resistance training was positively viewed when associated with immediate and long-term health and wellbeing benefits and had a social dimension; but there was a lack of understanding as to what constitutes resistance training, the required intensity level for effects; the role of pain; and the consequences of muscle weakness

Ocrelizumab B cell depletion has no effect on HERV RNA expression in PBMC in MS patients

Background: Epstein barr virus (EBV) infection of B cells is now understood to be one of the triggering events for the development of Multiple Sclerosis (MS), a progressive immune-mediated disease of the central nervous system. EBV infection is also linked to expression of human endogenous retroviruses (HERVs) of the HERV-W group, a further risk factor for the development of MS. Ocrelizumab is a high-potency disease-modifying treatment (DMT) for MS, which depletes B cells by targeting CD20. Objectives: We studied the effects of ocrelizumab on gene expression in peripheral blood mononuclear cells (PBMC) from paired samples from 20 patients taken prior to and 6 months after beginning ocrelizumab therapy. We hypothesised that EBV and HERV-W loads would be lower in post-treatment samples.Methods: Samples were collected in Paxgene tubes, subject to RNA extraction and Illumina paired end short read mRNA sequencing with mapping of sequence reads to the human genome using Salmon and differential gene expression compared with DeSeq2. Mapping was also performed separately to the HERV-D database of HERV sequences and the EBV reference sequence.Results: Patient samples were more strongly clustered by individual rather than disease type (relapsing/remitting or primary progressive), treatment (pre and post), age, or sex. Fourteen genes, all clearly linked to B cell function were significantly down regulated in the post treatment samples. Interestingly only one pre-treatment sample had detectable EBV RNA and there were no significant differences in HERV expression (of any group) between pre- and post-treatment samples.Conclusions: While EBV and HERV expression are clearly linked to triggering MS pathogenesis, it does not appear that high level expression of these viruses is a part of the ongoing disease process or that changes in virus load are associated with ocrelizumab treatment

"It makes you feel alive and younger…but it's stressful …my back and legs ache": A focus group study encouraging resistance training around retirement.

Muscle weakness is a key component of age-related conditions such as sarcopenia and frailty. Resistance training is highly effective at preventing and treating muscle weakness; however, few adults meet recommended levels. Retirement may be a key life-stage to promote resistance training. We carried out a virtual focus group study to explore motivators and barriers to resistance training around the time of retirement, with the aim of determining strategies and messages to increase its uptake. The five focus groups (n = 30) were recorded, transcribed and thematically analysed. We found that resistance training was positively viewed when associated with immediate and long-term health and wellbeing benefits and had a social dimension; but there was a lack of understanding as to what constitutes resistance training, the required intensity level for effects; the role of pain; and the consequences of muscle weakness

Evaluation of Kilifi epilepsy education programme: a randomized controlled trial

Objectives: The epilepsy treatment gap is largest in resource-poor countries.Weevaluated the efficacy of a 1-day health education program in a rural area of Kenya. The primary outcome was adherence to antiepileptic drugs (AEDs) as measured by drug levels in the blood, and the secondary outcomes were seizure frequency and Kilifi Epilepsy Beliefs and Attitudes Scores (KEBAS). Methods: Seven hundred thirty-eight people with epilepsy (PWE) and their designated supporter were randomized to either the intervention (education) or nonintervention group. Data were collected at baseline and 1 year after the education intervention was administered to the intervention group. There were 581 PWE assessed at both time points. At the end of the study, 105 PWE from the intervention group and 86 from the nonintervention group gave blood samples, which were assayed for the most commonly used AEDs (phenobarbital, phenytoin, and carbamazepine). The proportions of PWE with detectable AED levels were determined using a standard blood assay method. The laboratory technicians conducting the assays were blinded to the randomization. Secondary outcomes were evaluated using questionnaires administered by trained field staff. Modified Poisson regression was used to investigate the factors associated with improved adherence (transition from nonoptimal AED level in blood at baseline to optimal levels at follow-up), reduced seizures, and improved KEBAS, which was done as a post hoc analysis. This trial is registered in ISRCTN register under ISRCTN35680481. Results: There was no significant difference in adherence to AEDs based on detectable drug levels (odds ratio [OR] 1.46, 95% confidence interval [95% CI] 0.74–2.90, p = 0.28) or by self-reports (OR 1.00, 95% CI 0.71–1.40, p = 1.00) between the intervention and nonintervention group. The intervention group had significantly fewer beliefs about traditional causes of epilepsy, cultural treatment, and negative stereotypes than the nonintervention group. There was no difference in seizure frequency. A comparison of the baseline and follow-up data showed a significant increase in adherence—intervention group (36–81% [p \u3c 0.001]) and nonintervention group (38–74% [p \u3c 0.001])—using detectable blood levels. The number of patients with less frequent seizures (≤3 seizures in the last 3 months) increased in the intervention group (62–80% [p = 0.002]) and in the nonintervention group (67–75% [p = 0.04]). Improved therapeutic adherence (observed in both groups combined) was positively associated with positive change in beliefs about risks of epilepsy (relative risk [RR] 2.00, 95% CI 1.03–3.95) and having nontraditional religious beliefs (RR 2.01, 95% CI 1.01–3.99). Reduced seizure frequency was associated with improved adherence (RR 1.72, 95% CI 1.19–2.47). Positive changes in KEBAS were associated with having tertiary education as compared to none (RR 1.09, 95% CI 1.05–1.14). Significance: Health education improves knowledge about epilepsy, but once only contact does not improve adherence. However, sustained education may improve adherence in future studies

Why asthma still kills: The national review of asthma deaths (NRAD)

Advancements in drug treatments, applied research and the development of evidence-based clinical guidelines have contributed to the reduction of deaths from asthma over the past 50 years.Previous confidential enquiries have suggested that avoidable factors play a part in as many as threequarters of cases of asthma death. These studies have often been small, conducted locally and undertaken at a considerable time after death. The National Review of Asthma Deaths (NRAD), reported here, is the first national investigation of asthma deaths in the UK and the largest study worldwide to date. Work on the NRAD was undertaken over a 3-year period and was one element of the Department of Health inEngland’s Respiratory Programme. The primary aim of the NRAD was to understand the circumstances surrounding asthma deaths in the UK in order to identify avoidable factors and make recommendations to improve care and reduce the number of deaths.Asthma deaths occurring between February 2012 and January 2013 were identified through the Office for National Statistics (ONS) for England and Wales, the Northern Ireland Statistics and Research Agency(NISRA) and the National Records of Scotland (NRS). Extensive information about each death was sought from multiple sources, including primary, secondary and tertiary care, as well as ambulance, paramedic and out-of-hours care providers. 374 local coordinators were appointed in 297 hospitals across the NHS to collect and submit information to the project team, and 174 expert clinical assessors were recruited from primary, secondary and tertiary care throughout the UK to join expert panels that reviewed data. Each assessor participated in one or more expert panels, during which all information gathered on each death, including post-mortem reports, was reviewed by two assessors in detail, and this was followed by discussion and a consensus agreement of avoidable factors and recommendations by the whole panel.Data were available for analysis on 195 people who were thought to have died from asthma during the review period and the key findings relate to this group. Denominators vary according to where data were missing

Longitudinal evaluation of proton magnetic resonance spectroscopy metabolites as biomarkers in Huntington’s disease

Proton Magnetic resonance spectroscopy (1H-MRS) is a non-invasive method of exploring cerebral metabolism. In Huntington’s disease, altered 1H-MRS-determined concentrations of several metabolites have been described; however, findings are often discrepant and longitudinal studies are lacking. 1H-MRS metabolites may represent a source of biomarkers, thus their relationship with established markers of disease progression require further exploration to assess prognostic value and elucidate pathways associated with neurodegeneration. In a prospective single-site controlled cohort study with standardised collection of CSF, blood, phenotypic and volumetric imaging data, we used 3T 1H-MRS in conjunction with the linear combination of model spectra method to quantify seven metabolites (total n-acetylaspartate, total creatine, total choline, myo-inositol, GABA, glutamate and glutathione) in the putamen of 59 participants at baseline (15 healthy controls, 15 premanifest and 29 manifest Huntington’s disease gene expansion carriers) and 48 participants at 2-year follow-up (12 healthy controls, 13 premanifest and 23 manifest Huntington’s disease gene expansion carriers). Intergroup differences in concentration and associations with CSF and plasma biomarkers; including neurofilament light chain and mutant Huntingtin, volumetric imaging markers; namely whole brain, caudate, grey matter and white matter volume, measures of disease progression and cognitive decline, were assessed cross-sectionally using generalized linear models and partial correlation. We report no significant groupwise differences in metabolite concentration at baseline but found total creatine and total n-acetylaspartate to be significantly reduced in manifest compared with premanifest participants at follow-up. Additionally, total creatine and myo-inositol displayed significant associations with reduced caudate volume across both time points in gene expansion carriers. Although relationships were observed between 1H-MRS metabolites and biofluid measures, these were not consistent across time points. To further assess prognostic value, we examined whether baseline 1H-MRS values, or rate of change, predicted subsequent change in established measures of disease progression. Several associations were found but were inconsistent across known indicators of disease progression. Finally, longitudinal mixed effects models revealed glutamine + glutamate to display a slow linear decrease over time in gene expansion carriers. Altogether, our findings show some evidence of reduced total n-acetylaspartate and total creatine as the disease progresses and cross-sectional associations between select metabolites, namely total creatine and myo-inositol, and markers of disease progression, potentially highlighting the proposed roles of neuroinflammation and metabolic dysfunction in disease pathogenesis. However, the absence of consistent group differences, inconsistency between baseline and follow-up, and lack of clear longitudinal change suggests that 1H-MRS metabolites have limited potential as Huntington’s disease biomarkers

Fronto-striatal circuits for cognitive flexibility in far from onset Huntington's disease: evidence from the Young Adult Study.

OBJECTIVES: Cognitive flexibility, which is key for adaptive decision-making, engages prefrontal cortex (PFC)-striatal circuitry and is impaired in both manifest and premanifest Huntington's disease (pre-HD). The aim of this study was to examine cognitive flexibility in a far from onset pre-HD cohort to determine whether an early impairment exists and if so, whether fronto-striatal circuits were associated with this deficit. METHODS: In the present study, we examined performance of 51 pre-HD participants (mean age=29.22 (SD=5.71) years) from the HD Young Adult Study cohort and 53 controls matched for age, sex and IQ, on the Cambridge Neuropsychological Test Automated Battery (CANTAB) Intra-Extra Dimensional Set-Shift (IED) task. This cohort is unique as it is the furthest from disease onset comprehensively studied to date (mean years=23.89 (SD=5.96) years). The IED task measures visual discrimination learning, cognitive flexibility and specifically attentional set-shifting. We used resting-state functional MRI to examine whether the functional connectivity between specific fronto-striatal circuits was dysfunctional in pre-HD, compared with controls, and whether these circuits were associated with performance on the critical extradimensional shift stage. RESULTS: Our results demonstrated that the CANTAB IED task detects a mild early impairment in cognitive flexibility in a pre-HD group far from onset. Attentional set-shifting was significantly related to functional connectivity between the ventrolateral PFC and ventral striatum in healthy controls and to functional connectivity between the dorsolateral PFC and caudate in pre-HD participants. CONCLUSION: We postulate that this incipient impairment of cognitive flexibility may be associated with intrinsically abnormal functional connectivity of fronto-striatal circuitry in pre-HD

Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial

Background Previous prospective cohort studies have shown that angiogenic factors have a high diagnostic accuracy in women with suspected pre-eclampsia, but we remain uncertain of the effectiveness of these tests in a real-world setting. We therefore aimed to determine whether knowledge of the circulating concentration of placental growth factor (PlGF), an angiogenic factor, integrated with a clinical management algorithm, decreased the time for clinicians to make a diagnosis in women with suspected pre-eclampsia, and whether this approach reduced subsequent maternal or perinatal adverse outcomes. Methods We did a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial in 11 maternity units in the UK, which were each responsible for 3000–9000 deliveries per year. Women aged 18 years and older who presented with suspected pre-eclampsia between 20 weeks and 0 days of gestation and 36 weeks and 6 days of gestation, with a live, singleton fetus were invited to participate by the clinical research team. Suspected pre-eclampsia was defined as new-onset or worsening of existing hypertension, dipstick proteinuria, epigastric or right upper-quadrant pain, headache with visual disturbances, fetal growth restriction, or abnormal maternal blood tests that were suggestive of disease (such as thrombocytopenia or hepatic or renal dysfunction). Women were approached individually, they consented for study inclusion, and they were asked to give blood samples. We randomly allocated the maternity units, representing the clusters, to blocks. Blocks represented an intervention initiation time, which occurred at equally spaced 6-week intervals throughout the trial. At the start of the trial, all units had usual care (in which PlGF measurements were also taken but were concealed from clinicians and women). At the initiation time of each successive block, a site began to use the intervention (in which the circulating PlGF measurement was revealed and a clinical management algorithm was used). Enrolment of women continued for the duration of the blocks either to concealed PlGF testing, or after implementation, to revealed PlGF testing. The primary outcome was the time from presentation with suspected pre-eclampsia to documented pre-eclampsia in women enrolled in the trial who received a diagnosis of pre-eclampsia by their treating clinicians. This trial is registered with ISRCTN, number 16842031. Findings Between June 13, 2016, and Oct 27, 2017, we enrolled and assessed 1035 women with suspected pre-eclampsia. 12 (1%) women were found to be ineligible. Of the 1023 eligible women, 576 (56%) women were assigned to the intervention (revealed testing) group, and 447 (44%) women were assigned to receive usual care with additional concealed testing (concealed testing group). Three (1%) women in the revealed testing group were lost to follow-up, so 573 (99%) women in this group were included in the analyses. One (99%) women in this group were included in the analyses. The median time to pre-eclampsia diagnosis was 4·1 days with concealed testing versus 1·9 days with revealed testing (time ratio 0·36, 95% CI 0·15–0·87; p=0·027). Maternal severe adverse outcomes were reported in 24 (5%) of 447 women in the concealed testing group versus 22 (4%) of 573 women in the revealed testing group (adjusted odds ratio 0·32, 95% CI 0·11–0·96; p=0·043), but there was no evidence of a difference in perinatal adverse outcomes (15% vs 14%, 1·45, 0·73–2·90) or gestation at delivery (36·6 weeks vs 36·8 weeks; mean difference −0·52, 95% CI −0·63 to 0·73). Interpretation We found that the availability of PlGF test results substantially reduced the time to clinical confirmation of pre-eclampsia. Where PlGF was implemented, we found a lower incidence of maternal adverse outcomes, consistent with adoption of targeted, enhanced surveillance, as recommended in the clinical management algorithm for clinicians. Adoption of PlGF testing in women with suspected pre-eclampsia is supported by the results of this study