Utilisation of specialist epilepsy services and antiseizure medication adherence rates in a cohort of people with epilepsy (PWE) accessing emergency care.

BACKGROUND: An epilepsy-related attendance at A&E is associated an increased risk of subsequent death within 6 months. Although further work is required to provide a definitive explanation to account for these findings, in the interim it would seem reasonable that services are designed to ensure timely access and provide support at a time of greatest risk. We aim to determine the frequency of patients accessing specialist neurology services following an epilepsy-related admission/unscheduled care episode and consider ASM adherence at the point of attendance. METHODS: Patients were identified retrospectively via the NHS Greater Glasgow and Clyde live integrated epilepsy Dashboard following an unscheduled epilepsy-related admission or A&E attendance between 1st January 2022 and 30th June 2022. We calculated adherence to anti-seizure medication for a period of 6 months prior to admission and defined poor medication adherence as a medication possession ratio of less than 80 %. We evaluated the rate of any outpatient neurology clinic attendance in the subsequent 3, 6 and 12 months following an epilepsy-related unscheduled care episode. Additional clinical information was identified via the electronic patient records. RESULTS: Between 1st Jan 2022 and 30th June 2022, there were 266 emergency care seizure-related attendances. The mean age at attendance was 46 years (range: 16-91). Most of PWE were males (63 %) and 37 % were females. Epilepsy classification-29.3 % had GGE, 41.7% had focal epilepsy, and in 29 % of cases the epilepsy was unclassified. Of the admissions, 107/ 266 (40.2 %) generated follow-up within 6 months of attendance. Poor medication adherence was noted in 54/266 (20.3 %). 28.2 % of cases had input from on-call neurology service during admission/ED attendance, and of those 60 % had ASM adjusted. 18 % of attendances had a background diagnosis of learning disability. One-third of attendances of PWE had a history of mental health disorder 35 % (93/266). 25 % of ED attendances noted an active history of alcohol consumption misuse or/and recreational drug use. 14 (5.5 %) of PWE died during the period of interest (12 months following the last ED visit). In 6/14 (42.3 %) death was associated with poor medication adherence. CONCLUSION: This study demonstrates that a significant proportion of patients who experienced seizure-related admissions/ attendance did not access specialist neurology services in a timely manner. In addition, poor medication adherence remains a problem for a substantial number of people living with epilepsy. Early access to specialist services may go some way to improving care and reducing excessive mortality in PWE by allowing anti-seizure medication to be titrated and poor medication adherence to be addressed in those at greatest risk.

Specialist epilepsy service input following an epilepsy related unscheduled care episode.

BACKGROUND: Emergency and unplanned epilepsy-related attendances are associated with an increased risk of subsequent death within 6 months. Although further work is required to provide a definitive explanation to account for these findings, in the interim it would seem reasonable that services are designed to ensure timely access and provide support at a time of greatest risk. We aim to determine the frequency of patients with epilepsy (PWE) accessing specialist neurology services following an epilepsy-related admission/unscheduled care episode. METHODS: Patients were included in the cohort if they had at least 1 prescription for an anti-seizure medication and at least one epilepsy-related admission, emergency department attendance, or outpatient neurology clinic attendance between January 2011 and November 2021. We evaluated the rate of any outpatient neurology clinic attendance in the subsequent 6 months following an epilepsy related unscheduled care episode. RESULTS: Of the 6,449 PWE included in the cohort, 4,465 were included for analysis. At the end of the follow up period less than 40% were accessing specialist services within 6 months of an episode of admission/ unscheduled care episode. Around a third (31.1%) of deaths occurred within 6 months of an epilepsy-related admission, and in the majority of cases patients were not seen by an epilepsy specialist in the period between discharge and death. The frequency of mental health comorbidity in PWE accessing unscheduled care remains very high with almost 80% having a diagnosis of either depression or anxiety. CONCLUSION: A significant proportion of PWE are not accessing specialist services in a timely manner following an episode of unscheduled care. Such provision may potentially provide an opportunity to reduce epilepsy related mortality by altering antiseizure medication doses and considering reversible factors associated with poor outcomes in PWE, such as poor medication adherence.

The impact of the COVID-19 pandemic on a cohort of adults with epilepsy.

OBJECTIVES: The aim of this study was to assess the direct and indirect impacts of the COVID-19 pandemic on adults with epilepsy in Glasgow. METHODS: We used routinely collected data for a previously identified cohort of patients with epilepsy to evaluate access to scheduled and unscheduled care with quarterly rates of inpatient admissions, outpatient attendance and accident & emergency attendance calculated. Anti-seizure medication prescribing and persistence, incidence of anxiety and depression and deaths for a cohort of patients with epilepsy was evaluated prior to the pandemic in comparison to during the pandemic, from 2015 to 2021. RESULTS: All-cause mortality and epilepsy related mortality showed a statistically significant reduction during the pandemic. Although overall rates of out-patient hospital attendance dropped during the early stages of the pandemic (and had not returned to pre-pandemic levels by the end of 2021) epilepsy-related services saw maintenance of patient contact as a result of a rapid adoption of telephone clinics. A significant decrease in overall mortality was observed in PWE during the pandemic compared to the pre-pandemic period. COVID-19 was the single commonest cause of death in PWE during the pandemic (61/453) and 160 patients (3.7%) had at least 1 admission to hospital for COVID-19. Anti-seizure medication (ASM) prescribing remained rates remained stable during the pandemic. During the pandemic an average of 38.8% of cohort patients were treated for depression and 16.3% for anxiety per quarter, 8.2% and 12.4% of whom had not been previously treated for these conditions respectively. CONCLUSION: We have shown that during a national lockdown, in the context of a pandemic, mortality in patients with epilepsy has reduced, while out-patient services were delivered remotely, primarily via the telephone. The reasons for this remain unclear but suggest that some of the excess mortality in people with epilepsy may be potentially avoidable by changes in lifestyle.

The influence of demographics and comorbidity on persistence with anti-seizure medication.

PURPOSE: To examine the rate of persistence with anti-seizure medications (ASMs) in a cohort of patients with epilepsy, and to investigate the impact of a range of clinical and demographic factors on persistence METHODS: Patients receiving ASMs for epilepsy were identified from linked, routinely collected data within the NHS Greater Glasgow and Clyde health board area between January 2011 and August 2019. Persistence with individual ASMs at 365-days after initiation was assessed using a 90-day allowable gap between individual prescriptions. Univariate logistic regression was used to estimate the association between 1-year persistence with ASM and demographic characteristics, comorbidities, and medication characteristics. RESULTS: In total, 6,449 patients with epilepsy were identified - 1,631 were new users of ASMs at baseline and 4,818 had been prescribed at least one ASM prior to baseline. Persistence with individual ASMs ranged 11.8% to 78.6%. Persistence was significantly lower in younger patients and patients who had previously been non-persistent to ASMs. Persistence was higher amongst those with cardiac comorbidities, previous stroke, or higher overall comorbidity, as well as those prescribed newer ASMs. CONCLUSION: Persistence varied widely. Demographic factors, previous non-persistence and overall number of comorbidities were more important determinants of persistence to anti-seizure medications than specific individual comorbidities. Interventions to improve persistence should be targeted at younger patients from more deprived backgrounds and those who have previously been non-persistent with ASMs.

A review of medication adherence in people with epilepsy.

People with epilepsy (PWE) have a higher risk of mortality in comparison with the general population. This in part reflects intrinsic factors or associated comorbidities, but poor adherence to anti-epileptic drugs (AED) has also been shown to contribute to increased risk of death and increased utilization of unscheduled care. The aim of this review was to determine the prevalence of non-adherence to AED in PWE, evaluate whether specific clinical and demographic features can allow clinicians to identify those at highest risk and identify the methods and techniques that can be used to improve adherence in clinical settings. We identified relevant studies for the prevalence of medication non-adherence in PWE by searching MEDLINE (1946-7 Dec 2015), EMBASE (1947-7 Dec 2015) and Cochrane Library (1946-7 Dec 2015) as per predefined inclusion and exclusion criteria. We included 17 research studies from our review of the medical literature to determine the prevalence of medication non-adherence in epilepsy. The prevalence of significant medication non-adherence in epilepsy has been reported to vary between 26% and 79%. This variation partly reflects the differences in defining what clinically significant medication adherence is, the methods used to estimate the scale of the problem and the underlying population heterogeneity. A number of clinical and demographic features have been associated with poor adherence allowing clinicians to identify those at greatest risk. Educating patients and their carers about the risks associated with poor adherence, certain behavioural interventions and simplifying their drug regimens have been shown to improve adherence.

Sequential sampling: a novel method in farm animal welfare assessment.

Lameness in dairy cows is an important welfare issue. As part of a welfare assessment, herd level lameness prevalence can be estimated from scoring a sample of animals, where higher levels of accuracy are associated with larger sample sizes. As the financial cost is related to the number of cows sampled, smaller samples are preferred. Sequential sampling schemes have been used for informing decision making in clinical trials. Sequential sampling involves taking samples in stages, where sampling can stop early depending on the estimated lameness prevalence. When welfare assessment is used for a pass/fail decision, a similar approach could be applied to reduce the overall sample size. The sampling schemes proposed here apply the principles of sequential sampling within a diagnostic testing framework. This study develops three sequential sampling schemes of increasing complexity to classify 80 fully assessed UK dairy farms, each with known lameness prevalence. Using the Welfare Quality herd-size-based sampling scheme, the first 'basic' scheme involves two sampling events. At the first sampling event half the Welfare Quality sample size is drawn, and then depending on the outcome, sampling either stops or is continued and the same number of animals is sampled again. In the second 'cautious' scheme, an adaptation is made to ensure that correctly classifying a farm as 'bad' is done with greater certainty. The third scheme is the only scheme to go beyond lameness as a binary measure and investigates the potential for increasing accuracy by incorporating the number of severely lame cows into the decision. The three schemes are evaluated with respect to accuracy and average sample size by running 100 000 simulations for each scheme, and a comparison is made with the fixed size Welfare Quality herd-size-based sampling scheme. All three schemes performed almost as well as the fixed size scheme but with much smaller average sample sizes. For the third scheme, an overall association between lameness prevalence and the proportion of lame cows that were severely lame on a farm was found. However, as this association was found to not be consistent across all farms, the sampling scheme did not prove to be as useful as expected. The preferred scheme was therefore the 'cautious' scheme for which a sampling protocol has also been developed.

Vascular comorbidities in younger people with dementia: a cross-sectional population-based study of 616†245 middle-aged people in Scotland.

INTRODUCTION: There is growing evidence of an aetiological relationship between vascular risk factors and the development of dementia in later life. Dementia in the under-65s has historically been considered to be more driven by genetic factors, but previous epidemiological studies in the young have been relatively small. This study aims to determine the prevalence of vascular comorbidity in people aged <65 with dementia in comparison to the general population. METHODS: Analysis of routine clinical data from 314 (30%) general medical practices in Scotland. RESULTS: From an overall population of 616 245 individuals, 1061 cases of 'all-cause' dementia were identified (prevalence 172/100 000 population, 95% CI 161 to 182). The prevalence of dementia was higher in people with vascular morbidities, and prevalence progressively increased from 129/100 000 in people with no vascular comorbidity to 999/100 000 in people with four or more (p=0.01). The strength of association was greatest with a previous transient ischaemic attack (TIA) or stroke and chronic kidney disease (adjusted OR=3.1 and 2.9, respectively). Statistically significant, but smaller associations were seen with the presence of hypertension, diabetes, ischaemic heart disease and peripheral vascular disease (adjusted OR=1.4, 2.0, 1.9 and 2.2, respectively). DISCUSSIONS: Vascular comorbid diseases were more commonly recorded in people aged 40-64 with dementia than those without. This finding indicates that vascular disease may be more important in the aetiology of young-onset dementia than previously believed, and is of concern given the continuing rise in obesity and diabetes internationally.

Navigating the iceberg: reducing the number of parameters within the Welfare Quality(®) assessment protocol for dairy cows.

The Welfare Quality(®) protocols provide a multidimensional assessment of welfare, which is lengthy, and hence limited in terms of practicality. The aim of this study was to investigate potential 'iceberg indicators' which could reliably predict the overall classification as a means of reducing the length of time for an assessment and so increase the feasibility of the Welfare Quality(®) protocol as a multidimensional assessment of welfare. Full Welfare Quality(®) assessments were carried out on 92 dairy farms in England and Wales. The farms were all classified as Acceptable or Enhanced. Logistic regression models with cross validation were used to compare model fit for the overall classification on farms. 'Absence of prolonged thirst', on its own, was found to correctly classify farms 88% of the time. More generally, the inclusion of more measures in the models was not associated with greater predictive ability for the overall classification. Absence of prolonged thirst could thus, in theory, be considered to be an iceberg indicator for the Welfare Quality(®) protocol, and could reduce the length of time for a farm assessment to 15 min. Previous work has shown that the parameters within the Welfare Quality(®) protocol are important and relevant for welfare assessment. However, it is argued that the credibility of the published aggregation system is compromised by the finding that one resource measure (Absence of prolonged thirst) is a major driver for the overall classification. It is therefore suggested that the prominence of Absence of prolonged thirst in this role may be better understood as an unintended consequence of the published measure aggregation system rather than as reflecting a realistic iceberg indicator.

Are we discussing SUDEP?--A retrospective case note analysis.

PURPOSE: Sudden unexplained death in epilepsy (SUDEP) is uncommon. Discussing the risk of SUDEP can be difficult, particularly in those where the risk is considered low, and previous studies have suggested that clinical practice varies widely. The Scottish Intercollegiate Guidelines Network (SIGN) suggest information on SUDEP is "essential" and National Institute of Clinical Excellence (NICE) recommend that "tailored information on the person's relative risk of SUDEP should be part of the counselling process…". The study aimed to evaluate if discussion of SUDEP risk is being documented in clinical records and to determine if there is an association between documented discussion and risk factors for SUDEP. METHODS: A retrospective case note review was undertaken in those with an established diagnosis of epilepsy attending clinic between 1st January 2009 and 30th June 2009. RESULTS: Overall, a documented SUDEP discussion was noted in 14/345 (4%) cases. Patients were statistically more likely to have a documented SUDEP discussion if they had ongoing generalised tonic-clonic seizures, with a trend also towards informing those non-compliant with medication. CONCLUSION: Patients were more likely to be informed of SUDEP if they had potentially modifiable risk factors identified. There was, however, no documented evidence to suggest that SUDEP is being discussed in the majority of cases.

Diagnosing variant Creutzfeldt-Jakob disease: a retrospective analysis of the first 150 cases in the UK.

INTRODUCTION: Establishing an early clinical diagnosis in variant Creutzfeldt-Jakob disease (vCJD) can be difficult, resulting in extended periods of uncertainty for many families and sometimes a view that patients have been subjected to unnecessary investigations. This issue is accentuated by the progressive nature of vCJD and by the difficulty in achieving a confident clinical diagnosis before an advanced stage of illness. Although diagnostic delay may be a result of the non-specific early clinical features, a systematic analysis of the process of diagnosis was undertaken, with the aim of trying to achieve earlier diagnosis of vCJD. METHODS: Retrospective case file analysis was undertaken of the first 150 definite and clinically probable cases of vCJD identified by the UK surveillance system. RESULTS: There is a significant interval between illness onset and presentation to a primary care physician, which is influenced by the nature of the initial clinical features. Neurological review is invariably sought following the development of clinical signs and a diagnosis is then established relatively quickly. Despite the progressive clinical course, a confident clinical diagnosis is not usually achieved until a relatively advanced stage of illness (mean time to diagnosis 10.5 months) with a more rapid clinical progression accounting for those cases diagnosed earlier after symptom onset. CONCLUSIONS: Early clinical diagnosis in vCJD is not possible in the great majority of cases because of non-specific initial symptoms. Once neurological signs develop, a diagnosis is usually made promptly but this is often at a relatively advanced stage of illness. The inherent delays in the diagnosis of vCJD have implications for those involved in both public health and therapeutics.

Sporadic Creutzfeldt-Jakob disease with cerebellar ataxia at onset in the UK.

OBJECTIVE: To determine the frequency, in the UK, of sporadic Creutzfeldt-Jakob Disease (sCJD) with a cerebellar ataxic onset, and to describe the clinical features of the syndrome. METHODS: A retrospective review of autopsy-proved cases of sCJD cases in the UK, 1990-2005, identifying those presenting with cerebellar features without early cognitive decline. RESULTS: 29 of 618 (5%) patients with sCJD had an isolated cerebellar onset. Mean illness duration was 9 months. Subsequently, 21 (72%) developed myoclonus and 23 (79%) developed pyramidal features. Magnetic resonance imaging showed high signal in the basal ganglia in 11 of 14 (79%) patients. 7 of 15 (47%) patients were valine homozygotic at prion protein gene (PRNP)-129. Only 8 (28%) cases were referred to the surveillance unit after death. CONCLUSION: A better definition of sCJD presenting with an isolated cerebellar syndrome might improve future case recognition and contribute to the determination of its cause.

Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK.

Between 1970 and 2003, seven cases of human dura mater-associated Creutzfeldt-Jakob disease (CJD) were identified in the UK. Furthermore, we identified a case of CJD in a porcine dura graft recipient. The mean incubation period of the human dura mater cases was 93 (range 45-177) months. The clinico-pathological features of the cases are described and compared with cases previously reported in the world literature.

Isolated visual symptoms at onset in sporadic Creutzfeldt-Jakob disease: the clinical phenotype of the "Heidenhain variant".

BACKGROUND: The Heidenhain variant of sporadic Creutzfeldt-Jakob disease (sCJD) is commonly understood to represent cases with early, prominent visual complaints. The term is clarified to represent those who present with isolated visual symptoms. This group may pose diagnostic difficulties and often present to ophthalmologists where they may undergo needless invasive procedures. METHOD: A retrospective review of 594 pathologically proved sCJD cases referred to the UK National CJD Surveillance Unit over a 15 year period to identify Heidenhain cases. RESULTS: 22 cases had isolated visual symptoms at onset with a mean illness duration of 4 months. The mean age at disease onset was 67 years. Most displayed myoclonus, pyramidal signs, and a delay in the onset of dementia for some weeks. 17 (77%) were referred initially to ophthalmology. Two underwent cataract extraction before diagnosis. All tested cases were homozygous for methionine at codon 129 of the prion protein gene. CONCLUSIONS: This rare, but clinically distinct, group of patients with sCJD may cause diagnostic difficulties. Because ocular intervention carries with it the risk of onward transmission awareness of this condition among ophthalmologists is important.

Cells for tissue engineering.

Recent advances in stem-cell technology have improved the prognosis for tissue engineering. The use of cultured stem and/or progenitor cells has the potential to improve the extent of regeneration, and also increases the likelihood that the transplanted tissue will integrate with the surrounding tissue. It could eventually even reduce or eliminate the need for immunosuppressive drugs.

Influence of intermittent pressure, fluid flow, and mixing on the regenerative properties of articular chondrocytes.

Equine articular chondrocytes, embedded within a polyglycolic acid nonwoven mesh, were cultured with various combinations of intermittent pressure, fluid flow, and mixing to examine the effects of different physical stimuli on neochondrogenesis from young cells. The cell/polymer constructs were cultured first in 125 ml spinner flasks for 1, 2, or 4 weeks and then in a perfusion system with intermittent pressure for a total of up to 6 weeks. Additional constructs were either cultured for all 6 weeks in the spinner flasks or for 1 week in spinners followed by 5 weeks in the perfusion system without intermittent pressure. Tissue constructs cultivated for 2 or 4 weeks in spinner flasks followed by perfusion with intermittent pressure had significantly higher concentrations of both sulfated glycosaminoglycan and collagen than constructs cultured entirely in spinners or almost entirely in the pressure/perfusion system. Initial cultivation in the spinner flasks, with turbulent mixing, enhanced both cell attachment and early development of the extracellular matrix. Subsequent culture with perfusion and intermittent pressure appeared to accelerate matrix formation. While the correlation was much stronger in the pressurized constructs, the compressive modulus was directly proportional to the concentration of sulfated glycosaminoglycan in all physically stressed constructs. Constructs that were not stressed beyond the 1-week seeding period lost mechanical integrity upon harvest, suggesting that physical stimulation, particularly with intermittent pressure, of immature tissue constructs during their development may contribute to their ultimate biomechanical functionality.

Semi-continuous perfusion system for delivering intermittent physiological pressure to regenerating cartilage.

A semi-continuous compression/perfusion system has been custom made to allow the application of intermittent hydrostatic pressure, at physiological levels, to regenerating tissues over the long term. To test the system, isolated foal chondrocytes were seeded in resorbable polyglycolic acid meshes and cultured in the system for 5 weeks. The cell/polymer constructs were subjected to an intermittent hydrostatic pressure of 500 psi and were fed semi-continuously. Assays of the resulting tissue constructs indicate that the reactor supports cartilage development and that physiological intermittent compression enhances the production of extracellular matrix by the chondrocytes. The concentrations of sulfated glycosaminoglycan were found to be at least twice as high as those in control (unpressurized) samples. A correlation between the sulfated glycosaminoglycan content and the compressive modulus in pressurized, but not control, samples suggests that physiological intermittent pressurization not only enhances the production of extracellular matrix but may also influence matrix organization resulting in a stronger construct.

Increasing extracellular matrix production in regenerating cartilage with intermittent physiological pressure.

Isolated equine chondrocytes, from juveniles and adults, were cultured in resorbable polyglycolic acid meshes for up to 5 weeks with semicontinuous feeding using a custom-made system to intermittently compress the regenerating tissue. Assays of the tissue constructs indicate that intermittent compression at 500 and 1000 psi (3.44 and 6.87 MPa, respectively) stimulated the production of extracellular matrix, enhancing the rate of de novo chondrogenesis. Constructs derived from juvenile cells contained concentrations of extracellular matrix components at levels more like that of native tissue than did constructs derived from adult cells. With intermittent pressurization, however, even adult cells were induced to increase the production of extracellular matrix. At both levels of intermittent pressure, the concentration of sulfated glycosaminoglycan in constructs from juvenile cells was found to be up to ten times greater than concentrations in control (nonpressurized) and adult cell-derived constructs. Whereas collagen concentrations in the 500 psi and control constructs were not significantly different for either juvenile or adult cell-derived constructs, intermittent pressurization at 1000 psi enhanced the production of collagen, suggesting that there may be a minimum level of pressure necessary to stimulate collagen formation.