Directional cell movements downstream of Gbx2 and Otx2 control the assembly of sensory placodes

Cranial placodes contribute to sensory structures including the inner ear, the lens and olfactory epithelium and the neurons of the cranial sensory ganglia. At neurula stages, placode precursors are interspersed in the ectoderm surrounding the anterior neural plate before segregating into distinct placodes by as yet unknown mechanisms. Here, we perform live imaging to follow placode progenitors as they aggregate to form the lens and otic placodes. We find that while placode progenitors move with the same speed as their non-placodal neighbours, they exhibit increased persistence and directionality and these properties are required to assemble morphological placodes. Furthermore, we demonstrate that these factors are components of the transcriptional networks that coordinate placode cell behaviour including their directional movements. Together with previous work, our results support a dual role for Otx and Gbx transcription factors in both the early patterning of the neural plate border and the later segregation of its derivatives into distinct placodes

Evaluating complex interventions using routinely collected data: Methods to improve the validity of randomised controlled trials and observational studies

This thesis addresses the evaluation of complex interventions using routinely collected data, specifically the internal validity of observational studies and the generalisability of Randomised Controlled Trials (RCTs). Following a literature review, this thesis has four main objectives: to estimate the effect of telephone health coaching on hospital utilisation in an observational study; to assess optimal choices of control area in observational studies; to estimate the effect of telehealth within a large RCT; and to develop methods to assess aspects of the generalisability of RCTs empirically. The first paper compares health-coached patients with matched controls. Controls were selected from areas of England that were first matched to the characteristics of the intervention area. Health coaching did not reduce hospital admissions in this study. A second paper uses simulations to assess the relative bias and statistical precision in the treatment effects estimated under alternative approaches to selecting control areas. Lower bias is reported when using local controls than when selecting controls from matched areas, except when there is little unexplained area-level variation in outcomes, when the opposite is true. The third paper reports that, in the RCT, telehealth patients had fewer hospital admissions than controls, but admissions increased unexpectedly among controls after recruitment, leading to concerns about generalisability. Placebo tests find that control patients in the RCT experienced more admissions than matched non-participants receiving usual care. To address the concern that the control group did not receive ‘usual care’, sensitivity analyses are presented that contrast outcomes between the telehealth patients in the RCT and matched non-participants. In this comparison, telehealth is associated with a trend towards more admissions than usual care. The thesis concludes that careful control matching and placebo tests can address important aspects of the validity of observational studies and RCTs, but that further development of evaluation methods is warranted

National trends in emergency readmission rates: A longitudinal analysis of administrative data for England between 2006 and 2016

Objective To assess trends in 30-day emergency readmission rates across England over one decade. Design Retrospective study design. Setting 150 non-specialist hospital trusts in England. Participants 23 069 134 patients above 18 years of age who were readmitted following an initial admission (n=62 584 297) between April 2006 and February 2016. Primary and secondary outcomes We examined emergency admissions that occurred within 30 days of discharge from hospital (‘emergency readmissions’) as a measure of healthcare quality. Presented are overall readmission rates, and disaggregated by the nature of the indexed admission, including whether it was elective or emergency, and by clinical health condition recorded. All rates were risk-adjusted for patient age, gender, ethnicity, socioeconomic status, comorbidities and length of stay. Results The average risk-adjusted, 30-day readmission rate increased from 6.56% in 2006/2007 to 6.76% (P<0.01) in 2012/2013, followed by a small decrease to 6.64% (P<0.01) in 2015/2016. Emergency readmissions for patients discharged following elective procedures decreased by 0.13% (P<0.05), whereas those following emergency admission increased by 1.27% (P<0.001). Readmission rates for hip or knee replacements decreased (−1.29%; P<0.001); for acute myocardial infarction (−0.04%; P<0.49), stroke (+0.62%; P<0.05), chronic obstructive pulmonary disease (+0.41%; P<0.05) and heart failure (+0.15%; P<0.05) remained stable; and for pneumonia (+2.72%; P<0.001), diabetes (+7.09%; P<0.001), cholecystectomy (+1.86%; P<0.001) and hysterectomy (+2.54%; P<0.001) increased. Conclusions Overall, emergency readmission rates in England remained relatively stable across the observation period, with trends of slight increases contained post 2012/2013. However, there were large variations in trends across clinical areas, with some experiencing marked increases in readmission rates. This highlights the need to better understand variations in outcomes across clinical subgroups to allow for targeted interventions that will ensure highest standards of care provided for all patients

Designing assisted living technologies 'in the wild' : preliminary experiences with cultural probe methodology

Background There is growing interest in assisted living technologies to support independence at home. Such technologies should ideally be designed ‘in the wild’ i.e. taking account of how real people live in real homes and communities. The ATHENE (Assistive Technologies for Healthy Living in Elders: Needs Assessment by Ethnography) project seeks to illuminate the living needs of older people and facilitate the co-production with older people of technologies and services. This paper describes the development of a cultural probe tool produced as part of the ATHENE project and how it was used to support home visit interviews with elders with a range of ethnic and social backgrounds, family circumstances, health conditions and assisted living needs. Method Thirty one people aged 60 to 98 were visited in their homes on three occasions. Following an initial interview, participants were given a set of cultural probe materials, including a digital camera and the ‘Home and Life Scrapbook’ to complete in their own time for one week. Activities within the Home and Life Scrapbook included maps (indicating their relationships to people, places and objects), lists (e.g. likes, dislikes, things they were concerned about, things they were comfortable with), wishes (things they wanted to change or improve), body outline (indicating symptoms or impairments), home plan (room layouts of their homes to indicate spaces and objects used) and a diary. After one week, the researcher and participant reviewed any digital photos taken and the content of the Home and Life Scrapbook as part of the home visit interview. Findings The cultural probe facilitated collection of visual, narrative and material data by older people, and appeared to generate high levels of engagement from some participants. However, others used the probe minimally or not at all for various reasons including limited literacy, physical problems (e.g. holding a pen), lack of time or energy, limited emotional or psychological resources, life events, and acute illness. Discussions between researchers and participants about the materials collected (and sometimes about what had prevented them completing the tasks) helped elicit further information relevant to assisted living technology design. The probe materials were particularly helpful when having conversations with non-English speaking participants through an interpreter. Conclusions Cultural probe methods can help build a rich picture of the lives and experiences of older people to facilitate the co-production of assisted living technologies. But their application may be constrained by the participant’s physical, mental and emotional capacity. They are most effective when used as a tool to facilitate communication and development of a deeper understanding of older people’s needs

Protocol for the OCAY study: a cohort study of orphanhood and caregiver loss in the COVID-19 era to explore the impact on children and adolescents

INTRODUCTION: Globally, no person has been untouched by the COVID-19 pandemic. Yet, little attention has been given to children and adolescents in policy, provision and services. Moreover, there is a dearth of knowledge regarding the impact of COVID-19-associated orphanhood and caregiver loss on children. This study aims to provide early insights into the mental health and well-being of children and adolescents experiencing orphanhood or caregiver loss in South Africa. METHODS AND ANALYSIS: Data will be drawn from a quantitative longitudinal study in Cape Town, South Africa. A sample of children and adolescents between the ages of 9 and 18 years, experiencing parental or caregiver loss from COVID-19, will be recruited together with a comparison group of children in similar environments who did not experience loss. The study aims to recruit 500 children in both groups. Mental health and well-being among children will be explored through the use of validated and study-specific measures. Participants will be interviewed at two time points, with follow-up data being collected 12-18 months after baseline. A combination of analytical techniques (including descriptive statistics, regression modelling and structural equation modelling) will be used to understand the experience and inform future policy and service provision. ETHICS AND DISSEMINATION: This study received ethical approval from the Health Research Ethics Committee at Stellenbosch University (N 22/04/040). Results will be disseminated via academic and policy publications, as well as national and international presentations including high-level meetings with technical experts. Findings will also be disseminated at a community level via various platforms

Key normative, legal, and policy considerations for supporting pregnant and postpartum adolescents in high HIV-burden settings: a critical analysis

Rates of adolescent pregnancy within sub-Saharan Africa are increasing. Adolescent mothers ages 10-19 years face a distinct set of risks to their own and their children's health, compounded by many economic, social, and epidemiological challenges, such as living with HIV. In navigating this complex developmental period, many adolescent mothers face structural barriers impeding safe transitions to adulthood and motherhood. Drawing on existing literature and emerging data, we outline three normative, legal, and policy issues - violence and gender inequity, access to sexual and reproductive health services, and access to social and structural supports - which affect the health, wellbeing and development of adolescent mothers and their children. We also highlight emergent evidence about programming and policy changes that can better support adolescent mothers and their children. These key proposed responses include removing barriers to SRH and HIV service integration; ensuring implementation of return-to-school policies; and extending social protection systems to cater for adolescent mothers. Despite ongoing global crises and shifts in funding priorities, these normative, legal, and policy considerations remain critical to safeguard the health and wellbeing of adolescent mothers and their children

Does pre-COVID impulsive behaviour predict adherence to hygiene and social distancing measures in youths following the COVID-19 pandemic onset? Evidence from a South African longitudinal study

BACKGROUND: Engagement in protective behaviours relating to the COVID-19 pandemic has been proposed to be key to infection control. This is particularly the case for youths as key drivers of infections. A range of factors influencing adherence have been identified, including impulsivity and risk taking. We assessed the association between pre-COVID impulsivity levels and engagement in preventative measures during the COVID-19 pandemic in a longitudinal South African sample, in order to inform future pandemic planning. METHODS: Data were collected from N = 214 youths (mean age at baseline: M = 17.81 (SD = .71), 55.6% female) living in a South African peri-urban settlement characterised by high poverty and deprivation. Baseline assessments were taken in 2018/19 and the COVID follow-up was conducted in June–October 2020 via remote data collection. Impulsivity was assessed using the Balloon Analogue Task (BART), while hygiene and social distancing behaviours were captured through self-report. Stepwise hierarchical regression analyses were performed to estimate effects of impulsivity on measure adherence. RESULTS: Self-rated engagement in hygiene behaviours was high (67.1–86.1% “most of the time”, except for “coughing/sneezing into one’s elbow” at 33.3%), while engagement in social distancing behaviours varied (22.4–57.8% “most of the time”). Higher impulsivity predicted lower levels of hygiene (β = .14, p = .041) but not social distancing behaviours (β = −.02, p = .82). This association was retained when controlling for a range of demographic and COVID-related factors (β = .14, p = .047) and was slightly reduced when including the effects of a life-skills interventions on hygiene behaviour (β = −.13, p = .073). CONCLUSIONS: Our data indicate that impulsivity may predict adolescent engagement in hygiene behaviours post COVID-19 pandemic onset in a high risk, sub-Saharan African setting, albeit with a small effect size. For future pandemics, it is important to understand predictors of engagement, particularly in the context of adversity, where adherence may be challenging. Limitations include a small sample size and potential measure shortcomings

Are people with chronic diseases interested in using telehealth?: a cross-sectional postal survey

Background There is growing interest in telehealth—the use of technology to support the remote delivery of health care and promote self-management—as a potential alternative to face-to-face care for patients with chronic diseases. However, little is known about what precipitates interest in the use of telehealth among these patients. Objective This survey forms part of a research program to develop and evaluate a telehealth intervention for patients with two exemplar chronic diseases: depression and raised cardiovascular disease (CVD) risk. The survey was designed to explore the key factors that influence interest in using telehealth in these patient groups. Methods Thirty-four general practices were recruited from two different regions within England. Practice records were searched for patients with (1) depression (aged 18+ years) or (2) 10-year risk of CVD ≥20% and at least one modifiable risk factor (aged 40-74 years). Within each general practice, 54 patients in each chronic disease group were randomly selected to receive a postal questionnaire. Questions assessed five key constructs: sociodemographics, health needs, difficulties accessing health care, technology-related factors (availability, confidence using technology, perceived benefits and drawbacks of telehealth), and satisfaction with prior use of telehealth. Respondents also rated their interest in using different technologies for telehealth (phone, email and Internet, or social media). Relationships between the key constructs and interest in using the three mediums of telehealth were examined using multivariable regression models. Results Of the 3329 patients who were sent a study questionnaire, 44.40% completed it (872/1740, 50.11% CVD risk; 606/1589, 38.14% depression). Overall, there was moderate interest in using phone-based (854/1423, 60.01%) and email/Internet-based (816/1425, 57.26%) telehealth, but very little interest in social media (243/1430, 16.99%). After adjusting for health needs, access difficulties, technology-related factors, and prior use of telehealth, interest in telehealth had largely no association with sociodemographic variables. For both patient groups and for each of the three technology mediums, the most important constructs related to interest in telehealth were having the confidence to use the associated technology, as well as perceiving greater advantages and fewer disadvantages from using telehealth. To illustrate, greater confidence using phone technologies (b=.16, 95% CI 0.002-0.33), while also perceiving more benefits (b=.31, 95% CI 0.21-0.40) and fewer drawbacks (b=-.23, 95% CI -0.28 to -0.17) to using telehealth were associated with more interest in using phone-based telehealth technologies for patients with depression. Conclusions There is widespread interest in using phone-based and email/Internet-based telehealth among patients with chronic diseases, regardless of their health status, access difficulties, age, or many other sociodemographic factors. This interest could be increased by helping patients gain confidence using technologies and through highlighting benefits and addressing concerns about telehealth. While the same pattern exists for social media telehealth, interest in using these technologies is minimal