Raeburn B. Forbes

Frequency, timing and outcome of gastrostomy tubes for amyotrophic lateral sclerosis/motor neurone disease--a record linkage study from the Scottish Motor Neurone Disease Register.

Abstract.Aims:To describe the frequency, timing and outcome from gastrostomy in amyotrophic lateral sclerosis/motor neurone disease (ALS/MND).Methods:The Scottish MND Register, a population based disease register (1989–1998), with record linkage to the Scottish Morbidity 1 dataset of hospital discharges coded for gastrostomy procedure was used. Descriptive statistics of patients undergoing gastrostomy were extracted. Survival analysis used Kaplan Meier and Cox proportional hazards methods.Results:For patients diagnosed between 1989–98, 142 percutaneous endoscopic gastrostomy (PEG) insertion episodes were identified in 1226 patients, 130 of which occurred before the censoring date of 31 December 1999.Annually, on average, 5% of all revalent patients underwent gastrostomy, and this rate appeared to double between 1989–98. The cumulative incidence of gastrostomy was 11%.Mean age at PEG tube insertion was 66.8 years, with a mean disease duration of 24 months. Median survival from PEG tube insertion was 146 days. The 1 month mortality after gastrostomy was 25%. Gastrostomy did not confer a survival advantage compared with no gastrostomy.Conclusions:We found that gastrostomy feeding tubes are being inserted more frequently in people with ALS/MND. An unexpectedly high early mortality was detected which probably reflects a lack of selection bias compared with previously published data. It is possible that changes in the practice of gastrostomy placement since 1998 result in better outcomes for patients with ALS/MND. Prospective studies are required to assess the risks and benefits of enteral nutrition in ALS/MND.

Population based cost utility study of interferon beta-1b in secondary progressive multiple sclerosis

Abstract Objective: To evaluate the cost utility of interferon beta-1b in secondary progressive multiple sclerosis. Design: Population based cost utility model (healthcare perspective). Data on use of health services were obtained from case records and routine morbidity data and utility values from a EuroQol survey. Local and published costs were used. Effectiveness was modelled using data on relative risk reductions from a randomised trial of interferon beta-1b. Setting: Tayside region, 1993-5. Subjects: 132 ambulatory people with secondary progressive multiple sclerosis. Main outcome measures: Cost per quality adjusted life year (QALY) gained. Rate of relapse and proportion becoming wheelchair dependent over three years. Results: The number needed to treat for 30 months to delay time to wheelchair dependence in one person by nine months was 18 (95% confidence interval 5 to 26). For every 18 people treated for 30 months, six relapses would be prevented, gaining 0.397 discounted QALYs. The cost per QALY gained was £1 024 667 (£276 466 to £1 485 499). If treatment was restricted to patients attending neurology services, the number needed to treat was 14 (cost per QALY gained £833 514 (£161 358 to ∞)). The cost per QALY gained was not sensitive to changes in cost which took account of a societal perspective. Conclusions: The cost per QALY gained from interferon beta is high because of the high drug cost and modest clinical effect. Resources could be used more efficiently elsewhere. Key messages Secondary progressive multiple sclerosis is a potentially disabling disorder associated with low health related quality of life Interferon beta-1b may reduce rate of relapse The benefits of interferon beta-1b treatment are very low relative to its cost Cost utility analysis estimated a cost of over £1m per QALY gained Cost per QALY was not affected by taking into account the costs of care Money would be better spent on other ways of improving quality of life than on interferon beta

The incidence of motor nueron disease in Scotland

AbstractBetween 1989 and 1998, 1226 cases of ALS/MND were identified in Scotland, with mean age of onset 65.2 (SD 11.9) years for men and 67.2 (SD 11.0) for women. Annual standardized incidence was 2.40 per 100,000 (95% CI 2.22-2.58). Using capture recapture methods we confirm a high level of case ascertainment for each year of study. Incidence and ascertainment of ALS has remained stable in a large population over a prolonged period of time. Large population-based databases can be used to test aetiological hypotheses.

Unexpected decline in survival from amyotrophic lateral sclerosis/motor neurone disease

Objectives: To describe survival of 1226 Scottish adults with amyotrophic lateral sclerosis/motor neurone disease (ALS/MND). Methods: Ten year, prospective, population based disease register. Cox time dependent proportional hazards modelling for multivariate survival analyses. Results: Median survival from onset was 25 months (interquartile range 16–34 months). In multivariate models we found an increased hazard with more recently diagnosed cases—that is, there was an unexpected decline in survival over the 10 year period (hazard ratio (HR) 1.06 (95% CI 1.04 to 1.09). Positive effects on survival were demonstrated for longer time from onset to diagnosis (HR 0.38 (95% CI 0.33 to 0.42), assessment by a neurological specialist (HR 0.56 (95% CI 0.40 to 0.77), and treatment with riluzole (HR 0.24 (95% CI 0.14 to 0.42). Poor prognosis was associated with bulbar onset (HR 1.25 (95% CI 1.09 to 1.46) and a mixed lower and upper motor neurone syndrome (HR 1.23 (95% CI 1.01–1.49) and increasing age. Conclusions: We found an unexpected decline in survival over the 10 year period, despite controlling for potential confounding variables. We would be cautious about overinterpreting these observations and suggest that further research is required to confirm or refute these findings.

The prevalence of multiple sclerosis in Tayside, Scotland: do latitudinal gradients really exist?

Abstract To determine the prevalence of multiple sclerosis (MS) in the Tayside Health Board Area, Scotland, we carried out a population-based survey using four intersecting sources (Neurology Department records, a survey of general practitioners, Scottish Morbidity Records of discharges from hospitals and visual evoked response requests). A two-source capture-recapture model estimated survey coverage, and direct age-sex standardisation was used to take account of different population structures. Comparisons were made between the prevalence in Scotland and that in the rest of the United Kingdom. A total of 727 (definite and probable) and 880 cases (early, probable and possible) were identified using the criteria of Poser et al. and those of Allison and Millar in a population of 395,600 (1995 mid-year estimate). The prevalence of MS on 1 September 1996 was 184/100,000 (95% confidence interval 171–198) and 222/100,000 (95% confidence interval 210–240), respectively. The two-source capture-recapture model estimated that the survey was between 93% and 99% complete. Age-sex standardisation eliminated certain north-south differences in prevalence when comparisons were made with previous surveys. Diagnostic misclassification may also have influenced reported prevalence statistics. The prevalence is similar to that found in revised figures from the Grampian region in Scotland but significantly higher than recent estimates from England and Wales. Methodological differences may account for most of the reported differences between north and south, although there is still evidence to suggest that MS is more prevalent in northern Great Britain and Northern Ireland than in England and Wales.

Multiple sclerosis in Tayside, Scotland: detection of clusters using a spatial scan statistic

Debate continues over the relative importance of genetic factors over infectious agents in the aetiology of multiple sclerosis (MS). Detection of clusters of MS in space and time in the Tayside region of Scotland, UK would provide valuable evidence for the movement of infectious agents into a genetically susceptible population. A spatial scan statistic was used to detect, locate and provide a robust statistical test of any clusters found, without prior knowledge of their location or size. This was applied to a population-based MS register for the Tayside region of Scotland from 1970 to 1997, allowing for age at symptom onset, gender, population density and social deprivation. There were a total of 772 cases during the study period; an annual incidence of 7.2 per 100 000. The mean age of symptom onset was 35.7 (SD=10.5) and 73.8% of cases were women. There was a general increase in cases over time probably reflecting gradually better detection and diagnosis. There was a peak around the mid-1990s and some evidence of periodicity. There was a highly significant temporal cluster between 1982 and 1995 (p=0.002) for the whole region. Additionally, a significant spatial cluster for the time period 1993-1995 was found centred in the rural area south-west of Perth (p=0.016). Significant temporal and spatial-temporal clusters are consistent with exogenous factors contributing to the distribution of MS in Tayside, Scotland.

Are the El Escorial and Revised El Escorial criteria for ALS reproducible? A study of inter-observer agreement

INTRODUCTION: For accurate diagnosis, inter-observer agreement of criteria is important. METHODS: Using case records, the reproducibility of the original and revised El Escorial diagnostic criteria for amyotrophic lateral sclerosis were tested in a consecutive series of people referred to the Scottish Motor Neuron Disease Register. RESULTS: Agreement between independent observers was similar (weighted kappa: 0.783, 95% CI 0.656 to 0.911 (original criteria), 0.681, 95% CI 0.485 to 0.878 (revised)). CONCLUSIONS: Serious errors are unlikely, but the revised criteria may be less reproducible as they include more diagnostic categories. Revisions of diagnostic criteria should be tested for reproducibility and validity prior to widespread adoption.