AEDAntiepilpetic drugs CHI Community Health Index AIM To measure the adherence to antiepileptic drugs (AED) in a population cohort of children with epilepsy and to study the relationship between adherence and a series of clinical variables.METHOD A population-based study of children (<16y) with epilepsy on AED treatment from the Tayside region of Scotland during two epochs of 12 months each. A clinical database was constructed using hospital records and linked to a community dispensing pharmacy database to calculate an Adherence Index. The principal outcome measure was the measurement of population-based adherence to AEDs. Secondary outcome measures were the association of adherence with the clinical characteristics of the population. RESULTSThe median age of study group was 10 years and the median duration of epilepsy was 4 years. Only 30.9% of the total 320 children adhered to recommended AED treatment (Adherence Index >90%) across a year of treatment. Twenty-five percent of children had an Adherence Index of less than 50%. Adherence declined with increasing age. There was no significant correlation between adherence and other clinical characteristics studied (sex, duration of epilepsy, other comorbid health problems, other regular medications, and seizure frequency).INTERPRETATION Our data shows adherence to AED treatment is poor in children with epilepsy.

During vertebrate eye morphogenesis, a transient fissure forms at its inferior part, known as the optic fissure. This will gradually close, giving rise to a healthy, spherical optic cup. Failure of the optic fissure to close gives rise to an ocular disorder known as coloboma. During this developmental process, Foxg1 is expressed in the optic neuroepithelium, with highest levels of expression in the nasal optic stalk. Foxg1−/− mutant mice have microphthalmic eyes with a large ventral coloboma. We found Wnt8b expression upregulated in the Foxg1−/− optic stalk and hypothesized that, similar to what is observed in telencephalic development, Foxg1 directs development of the optic neuroepithelium through transcriptional suppression of Wnt8b. To test this, we generated Foxg1−/−;Wnt8b−/− double mutants of either sex and found that the morphology of the optic cup and stalk and the closure of the optic fissure were substantially rescued in these embryos. This rescue correlates with restored Pax2 expression in the anterior tip of the optic fissure. In addition, although we do not find evidence implicating altered proliferation in the rescue, we observe a significant increase in apoptotic cell density in Foxg1−/−;Wnt8b−/− double mutants compared with the Foxg1−/− single mutant. Upregulation of Wnt/β-catenin target molecules in the optic cup and stalk may underlie the molecular and morphological defects in the Foxg1−/− mutant. Our results show that proper optic fissure closure relies on Wnt8b suppression by Foxg1 in the nasal optic stalk to maintain balanced apoptosis and Pax2 expression in the nasal and temporal edges of the fissure.SIGNIFICANCE STATEMENT Coloboma is an ocular disorder that may result in a loss of visual acuity and accounts for ∼10% of childhood blindness. It results from errors in the sealing of the optic fissure (OF), a transient structure at the bottom of the eye. Here, we investigate the colobomatous phenotype of the Foxg1−/− mutant mouse. We identify upregulated expression of Wnt8b in the optic stalk of Foxg1−/− mutants before OF closure initiates. Foxg1−/−;Wnt8b−/− double mutants show a substantial rescue of the Foxg1−/− coloboma phenotype, which correlates with a rescue in molecular and cellular defects of Foxg1−/− mutants. Our results unravel a new role of Foxg1 in promoting OF closure providing additional knowledge about the molecules and cellular mechanisms underlying coloboma formation.

BackgroundCause-specific mortality trends are routinely reported for Scotland. However, ill-defined deaths are not routinely redistributed to more precise and internationally comparable categories nor is the mortality reported in terms of years of life lost to facilitate the calculation of the burden of disease. This study describes trends in Years of Life Lost (YLL) for specific causes of death in Scotland from 2000 to 2015.MethodsWe obtained records of all deaths in Scotland by age, sex, area and underlying cause of death between 2000 and 2015. We redistributed Ill-Defined Deaths (IDDs) to more exact and meaningful causes using internationally accepted methods. Years of Life Lost (YLL) using remaining life expectancy by sex and single year of age from the 2013 Scottish life table were calculated for each death. These data were then used to calculate the crude and age-standardised trends in YLL by age, sex, cause, health board area, and area deprivation decile.ResultsBetween 2000 and 2015, the annual percentage of deaths that were ill-defined varied between 10% and 12%. The proportion of deaths that were IDDs increased over time and were more common: in women; amongst those aged 1–4 years, 25–34 years and >80 years; in more deprived areas; and in the island health boards. The total YLL fell from around 17,800 years per 100,000 population in 2000 to around 13,500 years by 2015. The largest individual contributors to YLL were Ischaemic Heart Disease (IHD), respiratory cancers, Chronic Obstructive Pulmonary Disease (COPD), cerebrovascular disease and Alzheimer’s/dementia. The proportion of total YLL due to IHD and stroke declined over time, but increased for Alzheimer’s/dementia and drug use disorders. There were marked absolute inequalities in YLL by area deprivation, with a mean Slope Index of Inequality (SII) for all causes of 15,344 YLL between 2001 and 2015, with IHD and COPD the greatest contributors. The Relative Index of Inequality (RII) for YLL was highest for self-harm and lower respiratory infections.ConclusionThe total YLL per 100,000 population in Scotland has declined over time. The YLL in Scotland is predominantly due to a wide range of chronic diseases, substance misuse, self-harm and increasingly Alzheimer’s disease and dementia. Inequalities in YLL, in both relative and absolute terms, are stark.

Aim To describe the epidemiology and outcomes of convulsive status epilepticus (CSE) since the introduction of buccal midazolam and the change in International League Against Epilepsy definition of CSE to include seizures of at least 5 minutes. Method All children presenting to paediatric emergency departments with CSE (2011–2017) in Lothian, Scotland, were identified. Data, collated from electronic health records, included patient demographics, clinical characteristics, acute seizure management, and adverse outcomes (for example admission to intensive care). Results Six hundred and sixty‐five children were admitted with CSE who had 1228 seizure episodes (381 males, 284 females; median age 3y 8mo; age range 0–20y 11mo). CSE accounted for 0.38% (95% confidence interval 0.34–0.42) of annual attendances at emergency departments. Annual prevalence was 0.8 per 1000 children aged 0 to 14 years. Thirty‐four per cent of children had recurrent CSE. Sixty‐nine per cent of seizures lasted 5 to 29 minutes (median duration 10min). Buccal midazolam was given to 30% of children with CSE and had no effect on need for ventilatory support. Seventy per cent of children with CSE required hospital admission. Four per cent resulted in adverse outcome and there were only two deaths. Recurrent seizures, longer duration, and unprovoked seizures increased the odds of adverse outcome. Interpretation Adverse outcomes have decreased and the use of buccal midazolam is promising. Identifying high‐risk groups provides an opportunity for early intervention. These data form the basis for an extensive evaluation of acute seizure management and monitoring long‐term outcomes. The annual prevalence of convulsive status epilepticus in Lothian, Scotland, was 0.8 per 1000 children. There was a decrease in case‐fatality proportion from 3–9% to 0.2%. Use of buccal midazolam has increased, with no increase in adverse outcomes.

Background The availability of robust evidence to inform effective public health decision making is becoming increasingly important, particularly in a time of competing health demands and limited resources. Comparative Risk Assessments (CRA) are useful in this regard as they quantify the contribution of modifiable exposures to the disease burden in a population. The aim of this study is to assess the contribution of a range of modifiable exposures to the burden of disease due to stroke, an important public health problem in Scotland. Methods We used individual-level response data from eight waves (1995–2012) of the Scottish Health Survey linked to acute hospital discharge records from the Scottish Morbidity Record 01 (SMR01) and cause of death records from the death register. Stroke was defined using the International Classification of Disease (ICD) 9 codes 430–431, 433–4 and 436; and the ICD10 codes I60-61 and I63-64 and stroke incidence was defined as a composite of an individual’s first hospitalisation or death from stroke. A literature review identified exposures causally linked to stroke. Exposures were mapped to the layers of the Dahlgren & Whitehead model of the determinants of health and Population Attributable Fractions were calculated for each exposure deemed a significant causal risk of stroke from a Cox Proportional Hazards Regression model. Population Attributable Fractions were not summed as they may add to more than 100% due to the possibility of a person being exposed to more than one exposure simultaneously. Results Overall, the results suggest that socioeconomic factors explain the largest proportion of incident stroke hospitalisations and deaths, after adjustment for confounding. After DAG adjustment, low education explained 38.8% (95% Confidence Interval 26.0% to 49.4%, area deprivation (as measured by the Scottish Index of Multiple Deprivation) 34.9% (95% CI 26.4 to 42.4%), occupational social class differences 30.3% (95% CI 19.4% to 39.8%), high systolic blood pressure 29.6% (95% CI 20.6% to 37.6%), smoking 25.6% (95% CI 17.9% to 32.6%) and area deprivation (as measured by the Carstairs area deprivation Index) 23.5% (95% CI 14.4% to 31.7%), of incident strokes in Scotland after adjustment. Conclusion This study provides evidence for prioritising interventions that tackle socioeconomic inequalities as a means of achieving the greatest reduction in avoidable strokes in Scotland. Future work to disentangle the proportion of the effect of deprivation transmitted through intermediate mediators on the pathway between socioeconomic inequalities and stroke may offer additional opportunities to reduce the incidence of stroke in Scotland.

BackgroundSBOD2015 was the first endeavour to produce burden of disease estimates in Scotland using linkage of routine health records. In 2017, the study highlighted disparities in burden due to morbidity and mortality with respect to age and gender for 132 conditions, diseases and injuries. ObjectivesThe aim of SBOD2016 is to report on socioeconomic inequalities to provide further evidence to support preventable public health. MethodsMorbidity estimates were estimated using an extensive range of administrative datasets to provide a transparent and systematic approach to describe non-fatal population health loss. Combining these estimates with the Global Burden of Disease 2016 study’s relative assessment of severity and disability for each condition, we were able to calculate the Years Lived with Disability (YLD). Death registrations were used alongside life expectancy data to calculate the Years of Life Lost to premature mortality (YLL) as a measure of fatal burden. FindingsPreliminary findings show a three-fold increase in the burden of disease between individuals living in the most deprived areas compared to the least deprived areas. The profile of diseases contributing the largest burden also varies between the most and least deprived areas. ConclusionsBy combining information on fatal burden with the burden of living in less than ideal health (non-fatal burden), planners and policymakers have a better idea of the contribution that different diseases, conditions and injuries make to the total burden of disease and how this varies by levels of deprivation. This in turn provides information to support decisions about where prevention and service activity should be focused. It also provides a way of looking at the proportion of the burden that can be explained by a range of exposures in the population such as poverty or smoking.

ObjectivesThe gap between a population's actual and ideal health can be quantified by Disability-Adjusted Life Years (DALY). This metric combines the Years Lived with Disability (YLD) and Years of Life Lost (YLL). When supplemented by a Comparative Risk Assessment (CRA) it can depict the magnitude of disease burden and the effect that modifiable exposures contribute. We aim to utilise routine healthcare records to quantify the burden and potential reduction in DALY caused by stroke. ApproachHospital stays involving a stroke diagnosis 436; were identified through secondary care primary diagnoses from 1981-2013 and used to derive the incidence of acute stroke and the point-prevalence of chronic stroke. Disability weights for each health state of stroke sequelae were sourced from the Global Burden of Disease 2013 study and used to derive YLD. YLL for each death was calculated using Scotland-specific life tables for deaths where stroke was the underlying cause.Eight waves of the Scottish Health Survey (SHES) from 1995-2012 were linked to secondary care and mortality records. Risk factors were identified from SHES then mapped to levels in the Dahlgren and Whitehead model and Population Attributable Fractions (PAFs) were calculated for each risk factor that was a significant casual risk of stroke from a Cox-proportional hazard regression model.