Supporting Families Affected by Adversity: An Open Feasibility Trial of Family Life Skills Triple P.

This pilot feasibility study examined the effects of a new trauma-informed parenting program, Family Life Skills Triple P (FLSTP), in an open uncontrolled trial conducted in a regular service delivery context via video conferencing. FLSTP was trialed as a group-delivered 10-session intervention. Program modules target positive parenting skills (4 sessions) and adult life skills including coping with emotions, taking care of relationships, self-care, dealing with the past, healthy living, and planning for the future. Participants were 50 parents with multiple vulnerabilities, due to social disadvantage or adverse childhood experiences, who had children aged 3-9 with early onset behavior problems. Outcomes were assessed across four data collection points: baseline, mid-intervention (after Session 4), post-intervention, and 3-month follow up. Findings show moderate to large intra-group effect sizes for changes in child behavior problems, parenting practices and risk of child maltreatment, and medium effect sizes for parental distress, emotion regulation and self-compassion. Parents and practitioners reported high levels of consumer satisfaction with the program. Parents with lower levels of parental self-efficacy, lower personal agency and higher baseline scores on a measure of child abuse potential were at greater risk of not completing the program. The strength of these preliminary findings indicates that a more rigorous evaluation using a randomized clinical trial is warranted.

Knowledge of vitamin D and practices of vitamin D supplementation in a Scottish adult population: A cross-sectional study.

Background: Vitamin D supplementation practices (dose and frequency) are relatively unknown in the Scottish population, with no recent up-to-date data available. Reassessing current knowledge, practices, and awareness of vitamin D supplementation following a national health campaign in 2020 by Food Standards Scotland on vitamin D is warranted. Aim: This article aims to present the knowledge and awareness of vitamin D, and current vitamin D supplementation practices in adults living in Scotland. Methods: A cross-sectional study was performed between June and July 2022 using an online survey adapted from previous work on assessing knowledge of vitamin D in adults. Participants aged 18+, living in Scotland for ≥6 months were eligible to participate. Scores for knowledge were calculated as a percentage. Univariate associations between demographic and supplement use were established by χ2-test and logistic regression performed to predict factors associated with daily vitamin D intake. Results: Four hundred and three participants (72.7% female), mean age 36.4 (±14.2 years), completed the study. Awareness of vitamin D was very high (99.5%) but the mean overall knowledge score was poor (31.4 ± 15.3%), with those with a university degree more likely to have knowledge scores at/above the mean compared with those with lower levels of education, χ2(1, N = 393) 10.7, p = 0.001, odds ratio (OR) = 2.1 (95% confidence interval (CI) 1.7-2.7). Finally, 64.3% took vitamin D supplements, of which 37.5% took them daily during winter months, with only 7.4% taking the recommended daily dose. Conclusion: The current study highlights the need to improve both knowledge of vitamin D and practices of vitamin D supplementation during the autumn and winter months in Scotland.

Exploring Indigenous Community Conceptions of Parent Wellbeing: A Qualitative Analysis.

Using non-Indigenous perspectives of parental social and emotional wellbeing in the design and application of parent support programs can undermine program effectiveness as it may not account for Indigenous family structures and community values. With a clearer understanding of Indigenous parent wellbeing and its determinants, parenting interventions can be more appropriately designed and tailored to provide support for Indigenous families. This study utilised a community-based participatory action research approach involving collaboration between the research team, participants, and community advisory groups to explore Indigenous parents' and carers' conceptions of wellbeing. Participants' cultural perspectives on parent wellbeing were collected through semi-structured focus groups and in-depth interviews (N = 20). Thematic analysis was undertaken using theory-driven and interpretative phenomenological analysis. Eleven themes emerged as risk and protective factors across three domains: child domain (i.e., school attendance and education, respect, routine, development), parent domain (i.e., role modelling, self-regulation of body, self-regulation of mind and emotions, parenting strategies), and context domain (i.e., connections to family and kinship, community, access to services). It is noteworthy that parents reported three super-ordinate intersecting themes across all domains: connection to culture, Country, and spirituality. In addition, Indigenous parents' and carers' conception of their own wellbeing is closely linked to their children's wellbeing, their lived community context, and expected personal indicators. In recognising and working with this holistic view of Indigenous parent wellbeing, parent support programs can be optimally designed and implemented in Indigenous communities.

Pakistani orphanage caregivers' perspectives regarding their caregiving abilities, personal and orphan children's psychological wellbeing.

BACKGROUND: Pakistan is home to 4.6 million children who have been orphaned. Limited data on caregiving in orphanages suggests that caregivers do not have specialized training and experience heavy workloads and high-stress levels. Supporting these caregivers to provide responsive and consistent caregiving can improve their well-being along with the psychological and physical development of children who have been orphaned. This research explored the main caregiving-related challenges faced by caregivers in orphanage settings, their professional and personal needs and perceived emotional and behavioural problems manifesting in children under their care. METHOD: This research adopted a qualitative research design with a thematic analysis approach. Semi-structured interviews were conducted with 14 caregivers who were currently caring for four to 12-year-old children in Pakistani orphanages. RESULTS: Five main themes: (1) religiosity, (2) economic relief, (3) caregivers' needs and well-being, (4) caring for children who have been orphaned and (5) need for context specific training, emerged from the data, which included several subthemes. Findings revealed the presence of positive religious views regarding the upbringing and care of children who have been orphaned. Work-provided accommodation was an important economic relief. Caregivers' psychological, physiological and personal lives were affected by job-related stress and demands. Many helpful and unhelpful parenting practices were documented, and challenges such as children's verbal and physical aggression, stealing, non-cooperation and poor social skills were reported. The main professional issues included low salary, high numbers of children in care and lack of context specific professional caregiving training provided. CONCLUSION: This study established the need for a tailored programme that suits the context specific caregiving needs in Pakistani orphanages to support the training and professional growth of caregivers and promote their wellbeing along with positive developmental outcomes in the children under their care.

Asking the Question 'What Matters to You?' in a London Intensive Care Unit.

Purpose: At the heart of the paradigm shift in approach to patient care from paternalism toward shared decision-making lies the international "What Matters To You?" (WMTY) movement. However, WMTY principles are not frequently applied to the critical care setting. The aim of this quality improvement project work was to design and integrate a tool for all patients admitted to the intensive care unit (ICU) that helped answer WMTY. Methods: Using Plan-Do-Study-Act (PDSA) methodology across 8 cycles, a multidisciplinary team designed and integrated a bedside poster into the ICU. Quantitative and qualitative data were collected via a bedside audit process on a regular basis during each of the study phases comprising PDSA cycles. Results: Project results confirmed that the introduction of this poster/tool, alongside resource- and staff engagement-focused interventions, enabled the ICU to offer more than 50% of patients a WMTY conversation, as compared to zero at the start of the project. Consistently, 100% of staff surveyed (n=46 over all cycles) felt the posters were a useful addition to the ICU and confirmed they learned something new about their patients that they didn't know already. Conclusions: This novel poster design successfully summarized patients' responses to the question "What matters to you?" for ICU staff and would be transferable to other ICUs.

A review of Australian Government funding of parenting intervention research.

OBJECTIVES: Parenting is central to children's optimal development and accounts for a substantial proportion of the variance in child outcomes, including up to 40% of child mental health. Parenting is also one of the most modifiable, proximal, and direct factors for preventing and treating a range of children's problems and enhancing wellbeing. To determine the effectiveness of new approaches to parenting intervention, and to evaluate how to optimise reach and uptake, sufficient funding must be allocated for high quality research. METHOD: We reviewed funding awarded by the National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) for parenting intervention research during 2011-2020. RESULTS: Parenting intervention research received 0.25% of the NHMRC and ARC research budgets. CONCLUSIONS: There is a substantial mismatch between the funding of parenting intervention research and the impact of improved parenting on short- and long-term child outcomes. To rectify this, it is critical that Australian Government funding schemes include parenting interventions as priority areas for funding. IMPLICATIONS FOR PUBLIC HEALTH: Changes in allocation of funding to parenting research will support the establishment of evidence for the effective development, implementation and dissemination of parenting interventions to maximise health outcomes for children and their families.

Scaling Up Parenting Interventions is Critical for Attaining the Sustainable Development Goals.

Of all the potentially modifiable influences affecting children's development and mental health across the life course, none is more important than the quality of parenting and family life. In this position paper, we argue that parenting is fundamentally linked to the development of life skills that children need in order to achieve the United Nations Sustainable Development Goals. We discuss key principles that should inform the development of a global research and implementation agenda related to scaling up evidence-based parenting support programs. Research over the past 50 years has shown that parenting support programs of varied intensity and delivery modality can improve a wide range of developmental, emotional, behavioral and health outcomes for parents and their children. Such findings have been replicated across culturally and socioeconomically diverse samples, albeit primarily in studies from Western countries. We highlight the evidence for the relevance of parenting interventions for attaining the SDGs globally, and identify the barriers to and strategies for achieving their scale-up. The implications of the global COVID-19 pandemic for the delivery of evidence-based parenting support are also discussed.

Predicting positive outcomes and successful completion in an online parenting program for parents of children with disruptive behavior: An integrated data analysis.

Online delivery of parenting support is steadily increasing, yet the factors that influence program engagement and efficacy are still understudied. This study used an integrated data analysis approach to identify family and program-related factors that influence outcomes. We combined individual data from seven published efficacy trials of the web-based version of the Triple P-Positive Parenting Program. Data were analyzed for 985 families with children aged between 2 and 12 years (M = 4.87; SD = 2.14) using a Latent Change Score approach. At post-intervention, sociodemographic factors were not predictive of changes in child behavior problems, while parents of boys and those with higher education showed greater improvements in dysfunctional parenting. Parents who were initially more confident in their parenting showed more overall gains while parents with more initial adjustment difficulties showed less improvement. Only the effect of baseline child behavior problems on changes in dysfunctional parenting was moderated by treatment condition. At follow-up, program variant and completion were the primary outcome predictors, with completion found to be related to initial parenting confidence, internet usage and program variant. The implications of these findings for reaching and retaining parents in online programs across all phases of the engagement process are discussed.

Paradoxical bronchospasm in U.S. military veterans with COPD or asthma at a tertiary VA medical center in Chicago, Illinois.

Inhaled short-acting ß2-adrenergic agonists can rarely elicit paradoxical bronchospasm (PB), which may be fatal. The purpose to this study was to determine whether post-bronchodilator PB is reported in spirometry test results of veterans with Chronic Obstructive Pulmonary Disease (COPD) or asthma followed at the Jesse Brown Veterans Affairs (VA) Medical Center in Chicago between 2017-2020. Eighteen of 1,150 test reports reviewed were identified with post-bronchodilator PB (1.5%).12 out of the 18 identified patients with PB had COPD, 4 hadasthma and 2 had asthma/COPD. No report alluded to post-bronchodilator PB. Among the identified PB patients, there were 17 males and one female, 14 African Americans, 3 Caucasian and one Latinx, aged 67±8 years (mean±SD) with BMI 28±5 kg/m2. Thirteen were ex-tobacco smokers, 4 current smokers and one never smoked. Most recent chest CT revealed emphysema in 8 veterans with COPD and bronchial wall thickening in 3. Chest radiographs of 4 veterans with asthma were unremarkable. All veterans were treated with inhaled ß2-adrenergic agonists. Five were treated with cardio selective beta1 blockers and 10 for gastroesophageal reflux disease. Eleven veterans were diagnosed with obstructive sleep apnea. In 12 veterans, inhaled albuterol (4 actuations)-induced decrease in FEV1 was 22±8% and 367±167 mL from baseline. In 6 veterans, only FVC decreased significantly from baseline (14±3% and 448±179 mL). No veteran reported respiratory symptoms during or after spirometry testing. Two veterans died during follow-up. Based on spirometry test reports, inhaled ß2-adrenergic agonists were discontinued in 2 veterans with COPD and asthma. We propose that post-bronchodilator PB observed during spirometry testing of veterans should be recognized and reported, and its possible clinical implications addressed accordingly.

Patient-oriented research: A qualitative study of research involvement of parents of children with neurodevelopmental disabilities.

Patient-oriented research engages patients and caregivers as partners contributing to all phases of the research process. This was the goal of the Strongest Families Institute Neurodevelopmental research, in Halifax, Nova Scotia, when they included a parent advisory committee, made up of parents and caregivers of children and adolescents with a neurodevelopmental condition, to complete their research project. The purpose of this qualitative research was to examine the experiences of researchers and parents of children with a neurodevelopmental condition who participated on a research study advisory committee for the Strongest Families Neurodevelopment research project. From interviews with both parents/caregivers and researchers that played a role on the advisory committee, four major themes emerged on how to negotiate and navigate their time on the committee and what worked well and what did not. This led to recommendations for future researchers and patients who may create or be a part of an advisory committee.

Rescue In Vitro Maturation in Polycystic Ovarian Syndrome Patients Undergoing In Vitro Fertilization Treatment who Overrespond or Underrespond to Ovarian Stimulation: Is It A Viable Option? A Case Series Study.

BACKGROUND: This study intends to present the role of rescue in vitro maturation (IVM) in polycystic ovarian syndrome (PCOS) patients undergoing in vitro fertilization (IVF) treatment who have inappropriate responses to ovarian stimulation. MATERIALS AND METHODS: This was a retrospective case series study of five PCOS patients undergoing IVF treatment considered for cycle cancellation due to increased risk of ovarian hyperstimulation syndrome (OHSS) as group A or poor response to ovarian stimulation as group B. Patients in group A had high oestradiol levels and recruitment of high numbers of small/intermediate sized follicles that did not meet the criteria for human chorionic gonadotropin (hCG) triggering. Patients in group B responded inadequately to hormonal stimulation despite high gonadotropin dosage. Treatment was changed to rescue IVM cycles after the patients provided consent. RESULTS: In group A, three IVF patients deemed to have high chances of developing OHSS as evidenced by high oestradiol levels were converted to IVM. A total of the 58/68 oocytes retrieved were mature or matured in vitro. There were 26 cleaving embryos obtained. Two patients had live births and one patient suffered a miscarriage. In group B, rescue IVM was implemented in two patients due to poor ovarian response (POR). A total of 22/26 oocytes retrieved were mature or matured in vitro. There were 13 cleaving embryos obtained. One patient had a live birth, whilst the other suffered a miscarriage. CONCLUSION: Rescue IVM could be a viable option in PCOS patients undergoing IVF treatment who are unable to safely meet the criteria for hCG triggering due to overresponse to ovarian stimulation or ovarian resistance to high doses of stimulation. Conversion to IVM can still result in reasonable oocyte retrieval and lead to clinical pregnancy and live births without the risks of OHSS.

Use of phospholipase C zeta analysis to identify candidates for artificial oocyte activation: a case series of clinical pregnancies and a proposed algorithm for patient management.

OBJECTIVE: To investigate the applicability of phospholipase C zeta (PLCζ) analysis in assisting the clinical decision-making process when considering artificial oocyte activation (AOA) for infertile males in assisted reproductive technology. DESIGN: Fifty-six males (43 infertile/13 fertile) were screened using our PLCζ assay. SETTING: Fertility unit/university laboratory. PATIENT(S): Infertile males with abnormal sperm morphology or total fertilization failure, low fertilization rate (<50%), or repeated fertilization failure in assisted reproductive technology. INTERVENTION(S): We analyzed PLCζ levels in sperm from fertile and infertile males. Eligible patients subsequently underwent intracytoplasmic sperm injection (ICSI)/artificial oocyte activation (AOA) with calcimycin (GM508). MAIN OUTCOME MEASURE(S): PLCζ localization and level and the proportion of sperm expressing PLCζ. Thresholds of PLCζ deficiency, fertilization rates, pregnancy rates, and live birth rates of AOA and non-AOA cycles. RESULT(S): Compared with 13 fertile controls, 34 of the 43 infertile males had significantly lower levels of PLCζ and/or a significantly lower proportion of sperm exhibiting PLCζ. Of these 34 patients, 15 showed a significant PLCζ reduction in both parameters, which we termed "PLCζ deficiency." Five PLCζ-deficient patients opted for AOA; all five achieved fertilization, and four achieved clinical pregnancies and live births. The fertilization rate improved significantly from 18.6% (ICSI) to 56.8% (ICSI/AOA). The clinical pregnancy rate and live birth rate with AOA were both 40% per initiated cycle. Youden index analysis revealed that the cutoffs below which infertile males were likely to benefit from AOA were 71% for the proportion of sperm expressing PLCζ and 15.57 arbitrary units for mean PLCζ level. CONCLUSION(S): PLCζ analysis is a useful diagnostic tool to determine patient eligibility for subsequent AOA treatment.

Jandu Yani U 'For All Families' Triple P-positive parenting program in remote Australian Aboriginal communities: a study protocol for a community intervention trial.

INTRODUCTION: The population-based (Lililwan) study of fetal alcohol spectrum disorder (FASD) revealed a high prevalence of FASD in the remote communities of the Fitzroy Valley, Western Australia (WA) and confirmed anecdotal reports from families and teachers that challenging child behaviours were a significant concern. In response, Marninwarntikura Women's Resource Centre initiated a partnership with researchers from The University of Sydney to bring the positive parenting program (Triple P) to the Valley. Triple P has been effective in increasing parenting skills and confidence, and improving child behaviour in various Indigenous communities. METHODS AND ANALYSIS: Extensive consultation with community leaders, service providers, Aboriginal health networks and academic institutions was undertaken and is ongoing. Based on community consultations, the intervention was adapted to acknowledge local cultural, social and language complexities. Carers of children born after 1 January 2002 and living in the Fitzroy Valley are invited to participate in Group Triple P, including additional Stepping Stones strategies for children with complex needs. Programme are delivered by local community service workers, trained and accredited as Triple P providers or 'parent coaches'. Assessments for parent coach pretraining and post-training includes their perceived ability to deliver the intervention and the cultural appropriateness of the programme. Carers complete preintervention and postintervention and 6-month follow-up assessments of parenting practices, self-efficacy and child behaviour. ETHICS AND DISSEMINATION: Approval was granted by the University of Sydney Human Ethics Committee, WA Aboriginal Health Ethics Committee, WA Country Health Services Ethics Committee and Kimberley Aboriginal Health Planning Forum. Consultation with community is imperative for efficacy, engagement, community ownership and sustainability of the programme, and will be ongoing until findings are disseminated. Anonymous findings will be disseminated through peer-reviewed journals, community feedback sessions and scientific forums.

Comparing apples and pears: misleading conclusions about the population mental health impact of a parenting programme, a commentary on Marryat, Thompson and Wilson (2017).

BACKGROUND: The article by Marryat, Thompson and Wilson (2017) in BMC Pediatrics presents an evaluation of the implementation of the Triple P system as a public health intervention conducted by the Glasgow City Council and NHS Greater Glasgow and Clyde. DISCUSSION: Unfortunately, the conclusions drawn are questionable for multiple reasons. The lack of a controlled design precludes defensible conclusions about intervention effects free from routine threats to internal validity. There was a substantial mismatch between the intervention sample and the population sample assessed. The article's title and abstract leave readers with the mistaken impression that the children assessed for outcome were suitably representative of intervention families, when in fact many of the children in the intervention families were missing from the teacher-report outcome assessment (a single questionnaire), and many or most of the children in the teacher-report outcome assessment belonged to families who had never received the intervention. Although Triple P targets parent-child relations and child behavioural and emotional problems at home, Marryat et al. narrowly defined mental health impact as child difficulties in nursery or preschool, while not reporting data from practitioners and parents in the same evaluation that did not support the authors' conclusion. The paper was further diminished by a number of misleading statements and factual errors related for example to other research on Triple P. Studying the extent to which child mental health functioning at home can generalise to school settings is an important topic of inquiry in relation to parenting support interventions, but unfortunately the Marryat et al. article did not move this area forward.

Skin Complications Associated With Pediatric Central Venous Access Devices: Prevalence, Incidence, and Risk.

Central venous access devices (CVADs) are vital to enable treatment for children with cancer and other complex health conditions. However, complications effecting the CVAD wound are commonly reported. This study aimed to identify the incidence and prevalence of CVAD-associated skin complications current management, and characteristics associated with complication development, in pediatrics. A prospective observational study performed across medical, oncology, and hematology departments at a tertiary pediatric hospital in Australia, between April and July 2017. Children admitted with CVADs were assessed twice weekly for CVAD-associated skin complications and associated signs and symptoms. The data were analyzed using descriptive statistics (i.e., proportions, frequency) and time-to-event multivariable regression (i.e., hazard ratios [HRs]). Two hundred and seventy-one CVADs were reviewed over 43,787 catheter days, with over one eighth of participants (14%; n = 37) having a CVAD-associated skin complication during their admission (0.95 per 1,000 catheter days, 95% confidence interval [CI; 0.61, 1.17]), most commonly contact dermatitis (11%; n = 29; 0.72 per 1,000 catheter days 95% CI [0.50, 1.04]). Within biweekly checks the median point prevalence of complications varied between 0.4% and 11% and clinical management was wide-ranging. A primary diagnosis of oncology (HR 2.89, 95% CI [1.10, 7.62]) or medical/surgical (HR 2.55, 95% CI [1.04, 6.22]) conditions; plain, nonbordered polyurethane dressings (HR 4.92, 95% CI [2.00, 12.13]); and poor dressing integrity (HR 2.64, 95% CI [1.18, 5.92]) were significantly associated with contact dermatitis. In conclusion, substantial numbers of pediatric patients experience CVAD-associated skin complications, and innovations are necessary to identify, prevent, and treat these health care-associated injuries.

Facebook ads to the rescue? Recruiting a hard to reach population into an Internet-based behavioral health intervention trial.

OBJECTIVE: Facebook (FB) ads are touted as a way to facilitate recruitment of hard to reach participants into digital health research but the evidence has been mixed. This study aimed to empirically evaluate the impact and cost-effectiveness of paid ads for recruitment into a national trial testing an Internet-based, coached intervention for parents of children with Fetal Alcohol Spectrum Disorders. METHODS: Post hoc analysis of FB ad data and Google analytics on the online trial consent site (myStudies) were conducted on 11 campaigns employing static image/text ads. Standard metrics (e.g., click through rate, cost per 1000 impressions, cost per consent) were calculated and descriptive statistics comparing FB ad engagement and enrolled participants over time were conducted. RESULTS: Ad campaigns were active for a combined 115 days over 58 weeks resulting in 1533 links to the online recruitment site. During the ad campaigns, the mean rate of enrolment was 1 participant every 2 days. The first 3 ad campaigns were the most cost-effective. Mean cost per enrolment was $19.27 (Canadian dollars). CONCLUSIONS: FB ads were efficient and cost-effective in broad dissemination of trial information, but more research is needed to explore the impact of saturation (how often ads are posted), design (what is in the ad), and individual determinants (who is likely to respond to an ad) on converting FB ad engagement into enrolment. Avoiding a reductionist approach to analytics will help ensure appropriate and targeted strategies remain the priority for digital health research recruitment through social media.

Applying Self-Regulation Principles in the Delivery of Parenting Interventions.

An individual's capacity to self-regulate their cognitions, emotions and actions is an important life skill and emergent developmental competency for both children and parents. Individuals with better self-regulation achieve more positive life course outcomes and are less likely to develop significant mental health, social, and relationship problems. Parenting support programs that promote positive, nurturing parent-child relationships provide a unique multigenerational context to promote the self-regulatory capacity of both parents and children. Such programs provide a meaningful context and many opportunities for parents to enhance their self-regulation capacities, including skills such as goal setting, self-monitoring, self-evaluation, self-efficacy, personal agency, and thought and emotion regulation that, in turn, enable independent problem solving and responsive parenting. Parenting programs based on social learning theory, cognitive behavioral principles, and developmental theory typically include structured session activities and homework tasks that can be optimized to promote parental self-regulation. These include enhancing executive functions such as anticipating, planning ahead, following a plan, and problem solving, so that parents acquire greater cognitive flexibility, better impulse control, and are better able to generalize and apply learned parenting principles and skills beyond their immediate concerns to a broader range of child problems and challenging parenting and family situations. We illustrate how positive parenting principles and strategies can promote enhanced self-regulation, and discuss implications for research and practice.

In vitro decidualisation of human endometrial stromal cells is enhanced by seminal fluid extracellular vesicles.

Extracellular vesicles are highly abundant in seminal fluids and have a known role enhancing sperm function. Clinical pregnancy rates after IVF treatment are improved after female exposure to seminal fluid. Seminal fluid extracellular vesicles (SF-EVs) are candidate enhancers, however, whether SF-EVs interact with cells from the endometrium and modulate the implantation processes is unknown. Here, we investigated whether SF-EVs interact with endometrial stromal cells (ESCs) and enhance decidualisation, a requisite for implantation. SF-EVs, isolated from human seminal fluid (n = 11) by ultracentrifugation, were characterised by nanoparticle tracking analysis and Western blotting, and purified using size exclusion chromatography. Non-decidualised and decidualised primary ESCs (n = 5) were then treated with SF-EVs. Binding of bio-maleimide-labelled SF-EVs was detected by flow cytometry and fluorescence microscopy. Prolactin and IGFBP-1 protein levels in culture media were also analysed after single and multiple SF-EV exposure. SF-EVs size ranged from 50 to 300 nm, and they expressed exosomal markers (ALIX, SYNTENIN-1, CD9 and CD81). SF-EVs bound to non-decidualised and decidualised ESCs at similar levels. ESCs prolactin secretion was increased after single (p = 0.0044) and multiple (p = 0.0021) SF-EV exposure. No differences were found in IGFBP-1 protein levels. In conclusion, SF-EVs enhance in vitro ESC decidualisation and increase secretion of prolactin, an essential hormone in implantation. This elucidates a novel role of SF-EVs on endometrial receptivity. Abbreviations: ECACC: European Collection of Authenticated Cell Cultures; ESCs: endometrial stromal cells; EVs: extracellular vesicles; FCS: foetal calf serum; HRP: horse-radish peroxidase; IFNγ: interferon-gamma; IGF: insulin-like growth factor; IGFBP-1: insulin-like growth factor binding protein 1; IVF: in vitro fertilisation; MVB: multivesicular bodies; NTA: nanoparticle tracking analysis; PRLR-/-: homozygous prolactin receptor knockout; RT: room temperature; SF-EVs: seminal fluid extracellular vesicles; STR: short tandem repeat; TGFß: transforming growth factor ß; uNK: uterine natural killer.

Pressure garment to prevent abnormal scarring after burn injury in adults and children: the PEGASUS feasibility RCT and mixed-methods study.

BACKGROUND: Eleven million people suffer a fire-related injury worldwide every year, and 71% have significant scarring. Pressure garment therapy (PGT) is a standard part of burn scar management, but there is little evidence of its clinical effectiveness or cost-effectiveness. OBJECTIVE: To identify the barriers to, and the facilitators of, conducting a randomised controlled trial (RCT) of burn scar management with and without PGT and test whether or not such a trial is feasible. DESIGN: Web-based surveys, semistructured individual interviews, a pilot RCT including a health economic evaluation and embedded process evaluation. SETTING: UK NHS burns services. Interviews and the pilot trial were run in seven burns services. PARTICIPANTS: Thirty NHS burns services and 245 staff provided survey responses and 15 staff participated in individual interviews. Face-to-face interviews were held with 24 adult patients and 16 parents of paediatric patients who had undergone PGT. The pilot trial recruited 88 participants (57 adults and 31 children) who were at risk of hypertrophic scarring and were considered suitable for scar management therapy. Interviews were held with 34 participants soon after recruitment, with 23 participants at 12 months and with eight staff from six sites at the end of the trial. INTERVENTIONS: The intervention was standard care with pressure garments. The control was standard care comprising scar management techniques involving demonstration and recommendations to undertake massage three or four times per day with moisturiser, silicone treatment, stretching and other exercises. MAIN OUTCOME MEASURES: Feasibility was assessed by eligibility rates, consent rates, retention in allocated arms, adherence with treatment and follow-up and completion of outcome assessments. The outcomes from interview-based studies were core outcome domains and barriers to, and facilitators of, trial participation and delivery. RESULTS: NHS burns services treat 2845 patients per annum (1476 paediatric and 1369 adult) and use pressure garments for 6-18 months, costing £2,171,184. The majority of staff perceived a need for a RCT of PGT, but often lacked equipoise around the research question and PGT as a treatment. Strong views about the use of PGT have the potential to influence the conduct of a full-scale RCT. A range of outcome domains was identified as important via the qualitative research: perceptions of appearance, specific scar characteristics, function, pain and itch, broader psychosocial outcomes and treatment burden. The outcome tools evaluated in the pilot trial did not cover all of these domains. The planned 88 participants were recruited: the eligibility rate was 88% [95% confidence interval (CI) 83% to 92%], the consent rate was 47% (95% CI 40% to 55%). Five (6%) participants withdrew, 14 (16%) were lost to follow-up and 8 (9%) crossed over. Adherence was as in clinical practice. Completion of outcomes was high for adult patients but poorer from parents of paediatric patients, particularly for quality of life. Sections on range of movement and willingness to pay were found to be challenging and poorly completed. LIMITATIONS: The Brisbane Burn Scar Impact Profile appears more suitable in terms of conceptual coverage than the outcome scales that were used in the trial but was not available at the time of the study. CONCLUSIONS: A definitive RCT of PGT in burn scar management appears feasible. However, staff attitudes to the use of pressure garments may lead to biases, and the provision of training and support to sites and an ongoing assessment of trial processes are required. FUTURE WORK: We recommend that any future trial include an in-depth mixed-methods recruitment investigation and a process evaluation to account for this. TRIAL REGISTRATION: Current Controlled Trials ISRCTN34483199. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 36. See the NIHR Journals Library website for further project information.