Measuring aspects of self in dementia and investigating the validity of a self-compassion scale

This portfolio thesis consists of three parts. Part one is a systematic literature review, part two is an empirical paper and part three forms the accompanying appendices. Overall, they aim to evaluate and to add to the existing literature in relation to measuring specific aspects of self with people living with dementia.Part One: A systematic literature review that investigated what aspects of self have been measured using self-report instruments in evaluating psychosocial interventions for people with dementia. A narrative synthesis was conducted with 24 studies and included a variety of psychosocial interventions. The review identified seven aspects of self, which were measured using a range of self-report instruments, however the effectiveness of the interventions for these aspects of self were mixed. Limitations and methodological quality of the studies are discussed, alongside clinical implications and future considerations for research.Part Two: An empirical study that investigated the validity, reliability, and factor structure of the SCS-SF for people with dementia, as well as exploring correlations with well-being and demographic differences in self-compassion. The SCS-SF subscale intercorrelations and correlational analyses with measures of well-being, self-esteem and depression were investigated to assess convergent and discriminant validity of the SCS-SF in dementia. Exploratory Factor Analysis was conducted to determine the factor structure of the SCS-SF in dementia and to further assess construct validity. Differences in self-compassion based on participant age, gender, dementia subtype and time since diagnosis were also analysed. The study findings, implications and future recommendations are discussed.Part Three: Appendices for the systematic literature review and empirical paper

Self-report instruments measuring aspects of self for people living with dementia: A systematic literature review of psychosocial interventions

Objective: A positive sense of self may be a key domain of psychological well-being for people living with dementia and therefore a legitimate target for psychosocial interventions in dementia care. Determining the effectiveness of such interventions often requires valid self-report instruments. This review aimed to investigate what aspects of self have been measured using self-report instruments in evaluating psychosocial interventions for people living with dementia and to explore the effectiveness of these interventions in terms of positive outcomes related to aspects of self. Method: A systematic search of the literature using five electronic databases and one register (CENTRAL) was conducted. A narrative synthesis and methodological quality assessment was completed for the included studies. Results: A total of 24 studies were included in the review. Seven aspects of self were measured using a range of self-report instruments, many of which have not been validated for dementia. Aspects of self were; self-esteem, self-efficacy, self-compassion, self-growth, self-acceptance, self-management, and self-identity. Studies included a variety of interventions; however, the effectiveness of these interventions for these aspects of self was mixed

Feasibility trial of an early therapy in perinatal stroke (eTIPS)

Background: Perinatal stroke (PS) affects up to 1/2300 infants and frequently leads to unilateral cerebral palsy (UCP). Preterm-born infants affected by unilateral haemorrhagic parenchymal infarction (HPI) are also at risk of UCP. To date no standardised early therapy approach exists, yet early intervention could be highly effective, by positively influencing processes of activity-dependent plasticity within the developing nervous system including the corticospinal tract. Our aim was to test feasibility and acceptability of an "early Therapy In Perinatal Stroke" (eTIPS) intervention, aiming ultimately to improve motor outcome. Methods: Design: Feasibility trial, North-East England, August 2015-September 2017. Participants were infants with PS or HPI, their carers and therapists. The intervention consisted of a parent-delivered lateralised therapy approach starting from term equivalent age and continuing until 6 months corrected age. The outcome measures were feasibility (recruitment and retention rates) and acceptability of the intervention (parental questionnaires including the Warwick-Edinburgh Mental Wellbeing Scale (WEBWMS), qualitative observations and in-depth interviews with parents and therapists). We also reviewed clinical imaging data and undertook assessments of motor function, including the Hand Assessment for Infants (HAI). Assessments were also piloted in typically developing (TD) infants, to provide further information on their ease of use and acceptability. Results: Over a period of 18 months we screened 20 infants referred as PS/HPI: 14 met the inclusion criteria and 13 took part. At 6 months, 11 (85%) of those enrolled had completed the final assessment. Parents valued the intervention and found it acceptable and workable. There were no adverse events related to the intervention. We recruited 14 TD infants, one of whom died prior to undertaking any assessments and one of whom was subsequently found to have a condition affecting neurodevelopmental progress: thus, data for 12 TD infants was analysed to 6 months. The HAI was well tolerated by infants and highly valued by parents. Completion rates for the WEBWMS were high and did not suggest any adverse effect of engagement in eTIPS on parental mental wellbeing. Conclusion: The eTIPS intervention was feasible to deliver and acceptable to families. We plan to investigate efficacy in a multicentre randomised controlled trial

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Participatory design in the development of an early therapy intervention for perinatal stroke

Abstract Background Perinatal stroke is the leading cause of unilateral (hemiparetic) cerebral palsy, with life-long personal, social and financial consequences. Translational research findings indicate that early therapy intervention has the potential for significant improvements in long-term outcome in terms of motor function. By involving families and health professionals in the development and design stage, we aimed to produce a therapy intervention which they would engage with. Methods Nine parents of children with hemiparesis and fourteen health professionals involved in the care of infants with perinatal stroke took part in peer review and focus groups to discuss evolving therapy materials, with revisions made iteratively. The materials and approach were also discussed at a meeting of the London Child Stroke Research Reference Group. Focus group data were coded using Normalisation Process Theory constructs to explore potential barriers and facilitators to routine uptake of the intervention. Results We developed the Early Therapy in Perinatal Stroke (eTIPS) program - a parent-delivered, home-based complex intervention addressing a current gap in practice for infants in the first 6\ua0months of life after unilateral perinatal stroke and with the aim of improving motor outcome. Parents and health professionals saw the intervention as different from usual practice, and valuable (high coherence). They were keen to engage (high cognitive participation). They considered the tasks for parents to be achievable (high collective action). They demonstrated trust in the approach and felt that parents would undertake the recommended activities (high collective action). They saw the approach as flexible and adaptable (high reflexive monitoring). Following suggestions made, we added a section on involving the extended family, and obtained funding for a website and videos to supplement written materials. Conclusions Focus groups with parents and health professionals provided meaningful feedback to iteratively improve the intervention materials prior to embarking on a pilot study. The intervention has a high potential to normalize and become a routine part of parents\u2019 interactions with their child following unilateral perinatal stroke

Towards Reliable, Automated General Movement Assessment for Perinatal Stroke Screening in Infants Using Wearable Accelerometers

Perinatal stroke (PS) is a serious condition that, if undetected and thus untreated, often leads to life-long disability, in particular Cerebral Palsy (CP). In clinical settings, Prechtl's General Movement Assessment (GMA) can be used to classify infant movements using a Gestalt approach, identifying infants at high risk of developing PS. Training and maintenance of assessment skills are essential and expensive for the correct use of GMA, yet many practitioners lack these skills, preventing larger-scale screening and leading to significant risks of missing opportunities for early detection and intervention for affected infants. We present an automated approach to GMA, based on body-worn accelerometers and a novel sensor data analysis method--Discriminative Pattern Discovery (DPD)--that is designed to cope with scenarios where only coarse annotations of data are available for model training. We demonstrate the effectiveness of our approach in a study with 34 newborns (21 typically developing infants and 13 PS infants with abnormal movements). Our method is able to correctly recognise the trials with abnormal movements with at least the accuracy that is required by newly trained human annotators (75%), which is encouraging towards our ultimate goal of an automated PS screening system that can be used population-wide

Feasibility trial of an early therapy in perinatal stroke (eTIPS).

BACKGROUND: Perinatal stroke (PS) affects up to 1/2300 infants and frequently leads to unilateral cerebral palsy (UCP). Preterm-born infants affected by unilateral haemorrhagic parenchymal infarction (HPI) are also at risk of UCP. To date no standardised early therapy approach exists, yet early intervention could be highly effective, by positively influencing processes of activity-dependent plasticity within the developing nervous system including the corticospinal tract. Our aim was to test feasibility and acceptability of an "early Therapy In Perinatal Stroke" (eTIPS) intervention, aiming ultimately to improve motor outcome. METHODS: Design: Feasibility trial, North-East England, August 2015-September 2017. Participants were infants with PS or HPI, their carers and therapists. The intervention consisted of a parent-delivered lateralised therapy approach starting from term equivalent age and continuing until 6 months corrected age. The outcome measures were feasibility (recruitment and retention rates) and acceptability of the intervention (parental questionnaires including the Warwick-Edinburgh Mental Wellbeing Scale (WEBWMS), qualitative observations and in-depth interviews with parents and therapists). We also reviewed clinical imaging data and undertook assessments of motor function, including the Hand Assessment for Infants (HAI). Assessments were also piloted in typically developing (TD) infants, to provide further information on their ease of use and acceptability. RESULTS: Over a period of 18 months we screened 20 infants referred as PS/HPI: 14 met the inclusion criteria and 13 took part. At 6 months, 11 (85%) of those enrolled had completed the final assessment. Parents valued the intervention and found it acceptable and workable. There were no adverse events related to the intervention. We recruited 14 TD infants, one of whom died prior to undertaking any assessments and one of whom was subsequently found to have a condition affecting neurodevelopmental progress: thus, data for 12 TD infants was analysed to 6 months. The HAI was well tolerated by infants and highly valued by parents. Completion rates for the WEBWMS were high and did not suggest any adverse effect of engagement in eTIPS on parental mental wellbeing. CONCLUSION: The eTIPS intervention was feasible to deliver and acceptable to families. We plan to investigate efficacy in a multicentre randomised controlled trial. TRIAL REGISTRATION: ISRCTN12547427 (registration request submitted 28/05/2015; retrospectively registered, 30/09/2015)

Emerging evidence from a systematic review of safety of pre-exposure prophylaxis for pregnant and postpartum women: where are we now and where are we heading?

IntroductionHIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre-exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout.MethodsWe used a standard Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)-based oral PrEP safety in pregnant and breastfeeding HIV-uninfected women.Results and discussionWe identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP-exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV-uninfected women who use PrEP during pregnancy and/or lactation.ConclusionsExpanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy

Emerging evidence from a systematic review of safety of pre‐exposure prophylaxis for pregnant and postpartum women: where are we now and where are we heading?

IntroductionHIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre-exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout.MethodsWe used a standard Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)-based oral PrEP safety in pregnant and breastfeeding HIV-uninfected women.Results and discussionWe identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP-exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV-uninfected women who use PrEP during pregnancy and/or lactation.ConclusionsExpanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy

Defining gaps in pre-exposure prophylaxis delivery for pregnant and post-partum women in high-burden settings using an implementation science framework

Pregnancy is a high-risk period for HIV acquisition in African women, and pregnant women who become acutely infected with HIV account for up to a third of vertical HIV transmission cases in African settings. To protect women and eliminate vertical transmission, WHO recommends offering oral pre-exposure prophylaxis (PrEP) based on tenofovir to HIV-negative pregnant and post-partum women with a substantial risk of HIV acquisition. PrEP implementation for pregnant and post-partum women lags behind implementation for other high-risk populations. Unique considerations for PrEP implementation arise during pregnancy and post partum, including the integration of provider training with clinical delivery and monitoring of PrEP exposure and outcomes within existing maternal health systems, yet scarce implementation data are available to generate evidence in this context