Glucose tolerance in children and adolescents with cystic fibrosis.

Cystic Fibrosis (CF) is the most common fatal inherited disease in Caucasians. Mean survival for this condition has increased significantly in recent decades such that extra- pulmonary complications of CF have become more apparent (1). The most important complication is abnormal glucose tolerance (AGT) as it is known to have a negative impact on important CF outcomes such as lung function and nutrition (2). Despite this, AGT in CF remains poorly understood. The overall aim of this thesis was to increase understanding of how AGT affects children and adolescents with CF. This thesis is comprised of 3 studies. The first is a cross sectional study that examined the impact of AGT on a group of children and adolescents attending the CF unit at the Royal Children’s Hospital in Melbourne. This study identified that AGT has a significantly negative impact on children and adolescents with CF including significantly worse lung function, increased admissions and infection with Pseudomonas aeruginosa. This effect was most pronounced in patients with Cystic Fibrosis Related Diabetes (CFRD) but was also present to a lesser extent in those with Impaired Glucose Tolerance (IGT). The second study examined the impact of AGT on structural lung disease in CF. In a retrospective review, spirometry and CT findings were compared in patients with Normal Glucose Tolerance (NGT), IGT and CFRD. Despite stable lung function over 2 years in all 3 groups, CT scores progressed in proportion to worsening glucose tolerance status. Finally, the impact of CF pulmonary exacerbations on glucose tolerance was studied prospectively. An oral glucose tolerance test and continuous glucose monitoring were performed during exacerbations and repeated at follow up. Contrary to a previous study, it was found that glucose tolerance status did not change significantly during exacerbations. These findings of the first two studies confirm the importance of early diagnosis and treatment of AGT in CF. Structural lung disease progressed more rapidly in patients with AGT despite stable lung function. Glucose tolerance is therefore important as it is strongly associated with progression of lung structural damage. Conventional lung function is not a surrogate for either assessing glucose status or lung structure. Finally, hyperglycaemia found during CF pulmonary exacerbations is unlikely to resolve and consideration should be given to starting those patients on insulin. Abstract references 1. Reid DW, Blizzard CL, Shugg DM, Flowers C, Cash C, Greville HM.Changes in cystic fibrosis mortality in Australia, 1979-2005. Med J Aust. 2011 Oct 3;195(7):392-5. 2. Moran A, Becker D, Casella SJ, Gottlieb PA, Kirkman MS, Marshall BC, et al. Epidemiology, pathophysiology, and prognostic implications of cystic fibrosis-related diabetes: a technical review. Diabetes Care. 2010 Dec;33(12):2677-83

Cystic Fibrosis–Related Diabetes

Cystic fibrosis–related diabetes (CFRD) results in significant morbidity and mortality for patients with cystic fibrosis (CF). It is the endpoint of a spectrum of progressive insulin deficiency with resulting abnormalities of glucose tolerance. The consequence of glycaemic abnormalities in CF is poorer nutritional status, an increase in respiratory exacerbations with decline in lung function and ultimately greater morbidity and mortality. CFRD can be diagnosed by the standard oral glucose tolerance test (OGTT) usually performed from 10 years of age. However, this may miss early glycaemic abnormalities which appear to be clinically important. Early recognition of CFRD and treatment have been shown to improve outcomes in CF. Novel diagnostic methods such as 30-min sampled OGTT and continuous glucose monitoring (CGM) may prove to be useful in screening for this disorder and in the early identification of glycaemic abnormalities

Using multiple routine data sources linked to a trial cohort to establish the longer-term effectiveness of specialist home visiting in England: main results of the BB:2-6 study of the Family Nurse Partnership.

Objectives The Family Nurse Partnership (FNP) is a specialist home-visiting programme for first-time teenage mothers. Developed in the US, short-term outcomes (by age 2 years) were established in England in the Building Blocks trial. We used routine data (health, education, social care) linked to our trial cohort to assess longer-term impact. Approach Mothers recruited to the trial and their first-born children were linked to health (Hospital Episode Statistics/HES: NHS Digital; Abortion statistics: Department of Health and Social Care), education/social care (National Pupil Database/NPD: Department for Education) data in England up to age 7-years. Analysis of data within in a trusted-research environment assessed programme impact upon child maltreatment, child development/educational and maternal life course outcomes when compared to usually provided health and social care support alone. Our primary outcome was child in need registration. Planned sub-group analysis included differential effects by maternal age, deprivation level, care experience and for child outcomes, sex. Results Match rates for 1547 children were 97.4% (NPD) and 98.3% (HES). We found no difference between trial arms in proportion of children assessed as in need (adjusted odds ratio (aOR) OR:0.98, 95% confidence interval (CI): 0.74 to 1.31). Aside from a longer duration in care for children in the usual care arm (two months), there were no other differences in maltreatment outcomes. Children in the FNP arm were more likely to achieve a good level of development at reception age at age 4-5 years (aOR:1.24, 95%CI: 1.01 to 1.52) and, after adjusting for month of birth, to reach the expected standard in reading at Key Stage 1 at age around 7 years (aOR:1.26, 95%CI: 1.02 to 1.57). Conclusions We found programme improvements for child development/educational achievement but not for child maltreatment outcomes. Additional sub-group analysis revealed some evidence of the programme benefiting mothers with greater baseline vulnerability and boys, consistent with previous trials. The study benefits from the linkage of administrative data to a previously randomised trial cohort

Assessing the impact of specialist home visiting upon maltreatment in England: a feasibility study of data linkage from a public health trial to routine health and social care data

Background Follow-up for public health trials may benefit from greater use of routine data. Our trial of a home-visiting intervention for first-time teenage mothers assessed outcomes to the child’s second birthday. To examine its medium-term impact, particularly upon maltreatment outcomes, we designed a study using routine records. Methods We aimed to establish the feasibility of our study design, which combines trial data with routine health, social care and education data using a dissent-based linkage model. Trial participant identifiers were linked to routine health, social care and education data if women did not dissent. Data were forwarded to a safe haven and further linked to de-identified trial outcome data. The feasibility study aimed first to establish the acceptability of data linkage through a discussion group of young mothers and by levels of dissent received by the research team. Second, we assessed levels of accurate linkage to both health (via NHS Digital) and education and social care (both via National Pupil Database, NPD). Third, we assessed the availability of data and levels of missingness for key outcomes received for a sample of target study years. Results Of 1545 mother-child dyads contacted, eight women opted out. The engagement exercise with stakeholders found support for the principle of data linkage, including in the context of maltreatment. Some contributors preferred opt-in consent. Most (99.9%) health records were matched on either three or all four identifiers. Fifty participants were not matched to any health data. Primary outcome data from NPD are derived from any one of three fields, all of which were satisfactorily returned and provided an indication of cases for analysis. Missing data for secondary outcomes varied from 0% (Child looked after status) to 70% (Anatomical Area A&E diagnosis) however when combined with other variables the levels of missingness for outcome decrease. Conclusions Through study set-up and in this pilot, we provide evidence that the main study is feasible, satisfies governance requirements and is likely to generate data of sufficient quality to address our main research questions. Observed levels of missingness or low event rates are likely to affect some secondary analysis (e.g. state transition modelling) although overall were satisfactory

Evaluating the Family Nurse Partnership Programme in Scotland: a natural experiment approach

Peer reviewedPublisher PD

Assessing the impact of a family nurse-led intervention on young mothers’ references to internal states

A mother's propensity to refer to internal states during mother–child interactions is important for her child's developing social understanding. However, adolescent mothers are less likely to reference internal states when interacting with their children. We investigated whether young mothers’ references to internal states are promoted by the Family Nurse Partnership (FNP) intervention, an intensive home‐visiting programme designed to support adolescent mothers in England. We also investigated family, maternal, and child factors associated with young mothers’ references to inner states during interactions with their children. Adolescent mothers (n = 483, aged ≤ 19 years when recruited in pregnancy) and their children participated in an observational substudy of a randomized controlled trial investigating the impact of FNP compared to usual care. Mother–child dyads were video‐recorded during free play, and mothers’ speech was coded for use of internal state language (references to cognitions, desires, emotions, intentions, preferences, physiology, and perception). We found no differences in mothers’ use of internal state language between the FNP and usual care groups. A sample‐wide investigation identified that other features of mothers’ language and relationship status with the child's father were associated with internal state language use. Findings are discussed with reference to targeted interventions and implications for future research

Lessons learned from using linked administrative data to evaluate the Family Nurse Partnership in England and Scotland

Introduction “Big data” – including linked administrative data – can be exploited to evaluate interventions for maternal and child health, providing time- and cost-effective alternatives to randomised controlled trials. However, using these data to evaluate population-level interventions can be challenging. Objectives We aimed to inform future evaluations of complex interventions by describing sources of bias, lessons learned, and suggestions for improvements, based on two observational studies using linked administrative data from health, education and social care sectors to evaluate the Family Nurse Partnership (FNP) in England and Scotland. Methods We first considered how different sources of potential bias within the administrative data could affect results of the evaluations. We explored how each study design addressed these sources of bias using maternal confounders captured in the data. We then determined what additional information could be captured at each step of the complex intervention to enable analysts to minimise bias and maximise comparability between intervention and usual care groups, so that any observed differences can be attributed to the intervention. Results Lessons learned include the need for i) detailed data on intervention activity (dates/geography) and usual care; ii) improved information on data linkage quality to accurately characterise control groups; iii) more efficient provision of linked data to ensure timeliness of results; iv) better measurement of confounding characteristics affecting who is eligible, approached and enrolled. Conclusions Linked administrative data are a valuable resource for evaluations of the FNP national programme and other complex population-level interventions. However, information on local programme delivery and usual care are required to account for biases that characterise those who receive the intervention, and to inform understanding of mechanisms of effect. National, ongoing, robust evaluations of complex public health evaluations would be more achievable if programme implementation was integrated with improved national and local data collection, and robust quasi-experimental designs

Evaluation of the effectiveness of the Family Nurse Partnership home visiting programme in first time young mothers in Scotland : a protocol for a natural experiment

This project was funded by the Scottish Government Children and Families Directorate [project reference CASE/290185].Peer reviewedPublisher PD

What are the risks for Domiciliary Care Workers in Wales from COVID-19?

Objectives Domiciliary care workers (DCWs) continued to provide social care to vulnerable adults in their own homes throughout the COVID-19 pandemic. However, evidence of pandemic impact upon DCWs’ health is mixed. The OSCAR study aimed to quantify the impact of COVID-19 upon health outcomes of DCWs in Wales, and explore causes of variation. Approach Data for all registered DCWs in Wales are newly available via the SAIL Databank using a secured, privacy-protecting encrypted anonymisation process. Occupational registration data for DCWs working during the pandemic was combined with electronic health records data to describe health outcomes within the first two years of the pandemic. Rates of confirmed COVID-19 infections and health outcomes including mental health contacts, fit notes, respiratory infections, and mortality will be reported and explore variation (by factors such as age, sex, ethnicity, deprivation quintile, employer). We will also explore changes over time (pre- and post- onset of COVID-19 pandemic) in outcomes. Results The OSCAR study used anonymised health records for 15,727 registered DCWs in Wales. PCR-confirmed infection rates in the first full year of the pandemic (March20-February21) were 12% although lower in males (9%) than for females (12%). However, 28% of care workers received care for mental health with large differences observed between males (20%) and females (29%), and between workers from different health board regions (range 22% to 33%). The extent to which these represent pre-pandemic rates overall and how they compare to the broader community will be explored in our remaining work. A qualitative sub-study involving interviews with DCWs has informed our approach to modelling and to interpretation of findings. Conclusion Using novel anonymised occupational records at a national level and existing linked EHR data and qualitative interviews, the OSCAR study will quantify the risk of COVID-19 on DCWs' health and explore sources of variation. This will provide a secure base for informing public health policy and occupational guidance