Arron Lacey

Weight change associated with antiepileptic drugs

Aim To investigate antiepileptic drug (AED)-related weight changes in patients with epilepsy through a retrospective observational study. Method We analysed the anonymised electronic primary care records of 1.1 million adult patients in Wales. We included patients aged 18 years and over with a diagnosis of epilepsy, whose body weight had been measured up to 12 months before starting, and between 3 and 12 months after starting, one of five AEDs. We calculated the weight difference after starting the AED for each patient. Results 1423 patients were identified in total. The mean difference between body weight after and before starting each AED (together with 95% CI and p values for no difference) were: carbamazepine (CBZ) 0.43 (−0.19 to 1.05) p=0.17; lamotrigine (LTG) 0.31 (−0.38 to 1.00) p=0.38; levetiracetam (LEV) 1.00 (0.16 to 1.84) p=0.02; sodium valproate (VPA) 0.74 (0.10 to 1.38) p=0.02; topiramate (TPM) −2.30 (−4.27 to −0.33) p=0.02. Conclusions LEV and VPA were associated with significant weight gain, TPM was associated with significant weight loss, and LTG and CBZ were not associated with significant weight change.

Trends in the first antiepileptic drug prescribed for epilepsy between 2000 and 2010

PURPOSE To investigate changes in the choice of first anti-epileptic drug (AED) and co-prescription of folic acid after a new diagnosis of epilepsy. METHODS We searched anonymised electronic primary care records dating between 2000 and 2010 for patients with a new diagnosis of epilepsy and recorded the first AED prescribed and whether folic acid was co-prescribed. RESULTS From 13.3 million patient years of primary care records, we identified 3714 patients with a new diagnosis of epilepsy (925 children and 649 women aged 14-45 years). Comparing first time AED prescriptions in 2000 and 2001 to those in 2009 and 2010 showed a significant decrease in the proportion of carbamazepine and phenytoin prescribed and a significant increase in the proportion of lamotrigine and levetiracetam prescribed. In women aged 14-45 years, and girls aged <18 there was a significant decrease in the proportion of sodium valproate prescribed. Women aged 14-45 years were significantly more likely to be co-prescribed folic acid with their first AED compared to all other patients (20% vs 3%, p-value<0.001). The proportion of folic acid co-prescribed with the first AED did not change significantly between 2000 and 2010. CONCLUSION The changing trends in the first AED prescribed over the last decade, particularly in women of childbearing age, reflect published evidence in terms of AED efficacy, tolerability and safety.

Epilepsy and deprivation, a data linkage study

To investigate whether the link between epilepsy and deprivation is due to factors associated with deprivation (social causation) or factors associated with a diagnosis of epilepsy (social drift).

Cohort Profile: The Housing Regeneration and Health Study

A cohort comprising residents of a housing regeneration and health programme was created from routinely collected data using a system which allows us to anonymously link housing data to individuals and their health. The regeneration programme incorporating four rolling work packages runs from 2009 to 2014. The main intervention cohort we describe here contains the 18 312 residents of 9051 residences at baseline. The cohort will be followed continuously through routine health data (demographics, mortality, hospital admissions and general practitioner records including prescriptions) with periodic updates of housing regeneration intervention data. Here, we describe the baseline data for the primary health outcomes of emergency hospital admissions for cardiovascular and respiratory conditions and injuries for those aged ≥60 years. We will compare the health of residents within the homes before and after the housing regeneration work has taken place, and we will calculate the change in health service costs with use of hospital and General Practitioners (GP) services. We will also use a difference in differences approach to assess changes in comparison with comparator cohorts. These data will be accessible at the end of the study period in 2016. Further information about this study can be obtained from Ronan Lyons; r.a.lyons@swansea.ac.uk.

Validating epilepsy diagnoses in routinely collected data

Highlights • Cases with and without epilepsy were linked with anonymised primary care data.• Primary care diagnosis and drug codes accurately identify the cases with epilepsy.• Drug codes alone can be used to identify children with epilepsy.• Combining drug and diagnosis codes for adults and children increases accuracy.

Severe symptomatic aortic stenosis: medical therapy and transcatheter aortic valve implantation (TAVI)—a real-world retrospective cohort analysis of outcomes and cost-effectiveness using national data

Objectives Determine the real-world difference between 2 groups of patients with severe aortic stenosis and similar baseline comorbidities: surgical turn down (STD) patients, who were managed medically prior to the availability of transcatheter aortic valve implantation (TAVI) following formal surgical outpatient assessment, and patients managed with a TAVI implant. Design Retrospective cohort study from real-world data. Setting Electronic patient letters were searched for patients with a diagnosis of severe aortic stenosis and a formal outpatient STD prior to the availability of TAVI (1999–2009). The second group comprised the first 90 cases of TAVI in South Wales (2009 onwards). 2 years prior to and 5 years following TAVI/STD were assessed. Patient data were pseudoanonymised, using the Secure Anonymized Information Linkage (SAIL) databank, and extracted from Office National Statistics (ONS), Patient-Episode Database for Wales (PEDW) and general practitioner databases. Population 90 patients who had undergone TAVI in South Wales, and 65 STD patients who were medically managed. Main outcome measures Survival, hospital admission frequency and length of stay, primary care visits, and cost-effectiveness. Results TAVI patients were significantly older (81.8 vs 79.2), more likely to be male (59.1% vs 49.3%), baseline comorbidities were balanced. Mortality in TAVI versus STD was 28% vs 70% at 1000 days follow-up. There were significantly more hospital admissions per year in the TAVI group prior to TAVI/STD (1.5 (IQR 1.0–2.4) vs 1.0 IQR (0.5–1.5)). Post TAVI/STD, the TAVI group had significantly lower hospital admissions (0.3 (IQR 0.0–1.0) vs 1.2 (IQR 0.7–3.0)) and lengths of stay (0.4 (IQR 0.0–13.8) vs 11.0 (IQR 2.5–28.5), p<0.05). The incremental cost-effectiveness ratio (ICER) for TAVI was £10 533 per quality-adjusted life year (QALY). Conclusions TAVI patients were more likely to survive and avoid hospital admissions compared with the medically managed STD group. The ICER for TAVI was £10 533 per QALY, making it a cost-effective procedure.

Protein classification using Hidden Markov models and randomised decision trees

Since the introduction of next generation sequencing there is a demand for sophisticated methods to classify proteins based on sequence data. Two main approaches for this task are to use the raw sequence data and align them against other sequences, or to extract discrete high level features from the protein sequences and compare the features. Two machine learning methods are demonstrated to show each approach. Profile Hidden Markov Models are built from multiple alignment of raw sequence data and learn amino acid emission and transition parameters for a given alignment and effectively harness the power of aligning a test protein to a model built form many proteins. Random Forests on the other hand are used to discriminate between two sets of proteins based on features such as functional amino acid groups and physiochemical properties extracted from the raw sequences. The strengths and limitations of each method are presented and discussed, focussing on the individual merits and how they could work possibly compliment each other rather than just being compared by their classification accuracy.

Educational attainment of children born to mothers with epilepsy

Objective Small prospective studies have identified that children exposed to valproate in utero have poorer scores on cognitive testing. We wanted to identify whether children exposed to antiepileptic drugs (AEDs) in utero have poorer school performance. Methods We used anonymised, linked, routinely collected healthcare records to identify children born to mothers with epilepsy. We linked these children to their national attainment Key Stage 1 (KS1) tests in mathematics, language and science at the age of 7 and compared them with matched children born to mothers without epilepsy, and with the national KS1 results. We used the core subject indicator (CSI) as an outcome measure (the proportion of children achieving a minimum standard in all subjects) and the results in individual subjects. Results We identified 440 children born to mothers with epilepsy with available KS1 results. Compared with a matched control group, fewer children with mothers being prescribed sodium valproate during pregnancy achieved the national minimum standard in CSI (−12.7% less than the control group), mathematics (−12.1%), language (−10.4%) and in science (−12.2%). Even fewer children with mothers being prescribed multiple AEDs during pregnancy achieved a national minimum standard: CSI (by −20.7% less than the control group), mathematics (−21.9%), language (−19.3%) and science (−19.4%). We did not observe any significant difference in children whose mothers were prescribed carbamazepine or were not taking an AED when compared with the control group. Conclusions In utero exposure to AEDs in combination, or sodium valproate alone, is associated with a significant decrease in attainment in national educational tests for 7-year-old children compared with both a matched control group and the all-Wales national average. These results give further support to the cognitive and developmental effects of in utero exposure to sodium valproate as well as multiple AEDs, which should be balanced against the need for effective seizure control for women during pregnancy.

Meeting abstracts from the 64th British Thyroid Association Annual Meeting

• Users may freely distribute the URL that is used to identify this publication. • Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. • User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) • Users may not further distribute the material nor use it for the purposes of commercial gain.Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease. When fully expressed, it is characterized by inflammatory soft tissue changes, exophthalmos, ocular dysmotility causing diplopia, and, rarely, sight-threatening dysthyroid optic neuropathy (DON). The prevalence of GO among Graves’ patients seems lately declining, probably due to early diagnosis, early intervention on risk factors associated with its occurrence or progression (smoking, uncontrolled thyroid dysfunction), early correction of hyper and hypothyroidism. Only about 25–30% of newly diagnosed Graves’ hyperthyroids are affected with GO, which is usually mild and rarely progressive. Assessment of activity and severity of GO according to standardized criteria is fundamental to plan management. The European Thyroid Association and the European Group on Graves’ Orbitopathy (EUGOGO) have recently published the first guideline on management of GO. Mild GO usually requires only a watchful strategy, in addition to local measures (eye drops, ointments) and removal of risk factors. Intravenous glucocorticoids (ivGCs) are the first-line treatment for moderate-to-severe and active GO, as demonstrated by randomized clinical trials. When ivGCs fail or GO recurs after treatment withdrawal, options include a second course of ivGCs, oral GCs combined with orbital radiotherapy or cyclosporine, rituximab. Evidence that the any of the above treatment be effective in the context of a poor response to a first course of ivGCs is limited and should be investigated in larger studies. In addition to rituximab, ongoing investigations are exploring the role of other biologics targeting, e.g., the IGF-1 receptor or the IL-6 receptor, and results will probably available in 1–2 years. When GO has been treated medically and is inactive, rehabilitative surgery (orbital decompression, squint surgery, eyelid surgery) is often needed.

Equity in healthcare for coronary heart disease, Wales (UK) 2004–2010: A population-based electronic cohort study

Background Despite substantial falls in coronary heart disease (CHD) mortality in the United Kingdom (UK), marked socioeconomic inequalities in CHD risk factors and CHD mortality persist. We investigated whether inequity in CHD healthcare in Wales (UK) could contribute to the observed social gradient in CHD mortality. Methods and findings Linking data from primary and secondary care we constructed an electronic cohort of individuals (n = 1199342) with six year follow-up, 2004–2010. We identified indications for recommended CHD interventions, measured time to their delivery, and estimated risk of receiving the interventions for each of five ordered deprivation groups using a time-to-event approach with Cox regression frailty models. Interventions in primary and secondary prevention included risk-factor measurement, smoking management, statins and antihypertensive therapy, and in established CHD included medication and revascularization. For primary prevention, five of the 11 models favoured the more deprived and one favoured the less deprived. For medication in secondary prevention and established CHD, one of the 15 models favoured the more deprived and one the less deprived. In relation to revascularization, six of the 12 models favoured the less deprived and none favoured the more deprived–this evidence of inequity exemplified by a hazard ratio for revascularization in stable angina of 0.79 (95% confidence interval 0.68, 0.92). The main study limitation is the possibility of under-ascertainment or misclassification of clinical indications and treatment from variability in coding. Conclusions Primary care components of CHD healthcare were equitably delivered. Evidence of inequity was found for revascularization procedures, although this inequity is likely to have only a modest effect on social gradients in CHD mortality. Policymakers should focus on reducing inequalities in CHD risk factors, particularly smoking, as these, rather than inequity in healthcare, are likely to be key drivers of inequalities in CHD mortality.