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R J Swingler

Publications and source records attributed to R J Swingler.

At least 19 recordsLinked to original sources
PubMed2004

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 over-interpreting these observations and suggest that further research is required to confirm or refute these findings.

Aged↗
PubMed2002

Rapid mutation detection by the transgenomic wave analyser DHPLC identifies MYOC mutations in patients with ocular hypertension and/or open angle glaucoma.

AIMS: To rapidly screen Scottish patients with a family history of open angle glaucoma (OAG) or ocular hypertension (OHT) for mutations in the myocilin gene (MYOC) and develop a new rapid screening method for MYOC mutation detection. METHODS: All three exons of the MYOC gene were amplified by PCR from genomic DNA and subjected to direct DNA sequencing. Mutation detection methodology was also developed based on denaturing high performance liquid chromatography (DHPLC). A recurrent mutation was investigated by analysis of microsatellite haplotypes at the MYOC gene locus. RESULTS: Mutations were identified by DNA sequencing in four families. MYOC mutation Q368X was found in three kindreds and the fourth family carried the mutation G367R. The Q368X mutation was found to be associated with the same haplotype for markers closely flanking the MYOC gene. The mutations were identified by direct sequencing and were also readily detected by DHPLC analysis of PCR fragments, demonstrating that this is a robust method for MYOC analysis in future. CONCLUSIONS: Mutations in the MYOC gene were identified in patients presenting with highly variable phenotypes from normal through OHT to severe OAG. Haplotype analysis showed that mutation Q368X is likely to be an ancestral mutation in this population. DHPLC analysis is an accurate, rapid and cost effective method for MYOC mutation analysis in large population samples.

Adult↗
PubMed2001

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.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Motor neuron disease--a review.

It is now clear that patients with MND are best managed using a multi-disciplinary approach conforming to evidence-based guidelines. Whilst scientific advances into the aetiology of MND have been of great importance in both the understanding of this and other neurodegenerative disease, they have only recently led to therapy directed at disease progression. The management of patients with MND remains largely supportive but it is hoped that the future may hold better prospects for those with the disease.

Adult↗
PubMed1999

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

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 pounds sterling (276 466 pounds sterling to 485 499 pound sterling). If treatment was restricted to patients attending neurology services, the number needed to treat was 14 (cost per QALY gained 833 pounds sterling 514 (161 358 pounds sterling to infinity)). 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.

Activities of Daily Living↗
PubMed1999

Molecular genetic analysis of the APEX nuclease gene in amyotrophic lateral sclerosis.

We analyzed genomic DNA from ALS patients for mutations in the apurinic/apyrimidinic endonuclease (APEX nuclease) gene. We identified three rare polymorphisms in the untranslated region of the gene and one common two-allele polymorphism (D148E). The allelic frequency D148E was significantly different in sporadic ALS patients compared with controls. A conserved amino acid change and a 4-base pair deletion were also identified in sporadic ALS patients. These data suggest that APEX nuclease may contribute to the etiology of ALS.

Adult↗
PubMed1999

Estimating the prevalence of multiple sclerosis in the United Kingdom by using capture-recapture methodology.

The geographic distribution of multiple sclerosis is nonrandom, as the disease is more prevalent in temperate than in tropical regions. Surveys conducted between 1970 and 1996 suggest that multiple sclerosis is more prevalent in the northern part of the United Kingdom than in the southern part. This north-south gradient ("the latitudinal gradient") might be a methodological artifact, because high prevalence figures from serial surveys of the northern part of the United Kingdom might have been the result of better ascertainment. By using capture-recapture methods, the authors found that case ascertainment was similar in the northern and southern parts of the United Kingdom. When prevalence figures for multiple sclerosis in the southern United Kingdom were increased to account for the number of unobserved cases, the difference persisted: The prevalence of multiple sclerosis in the northern part of the United Kingdom appeared to be at least 180 cases per 100,000 persons, whereas the maximum prevalence in the southern part of the United Kingdom was less than 160 cases per 100,000 persons. The distribution of multiple sclerosis in the United Kingdom is not uniform and is consistent with the hypothesis that populations with a high prevalence of multiple sclerosis may be genetically predisposed to the disease.

Adult↗
PubMed1999

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

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.

Adolescent↗
PubMed1996

Avoiding false positive diagnoses of motor neuron disease: lessons from the Scottish Motor Neuron Disease Register.

OBJECTIVES: To describe the frequency and characteristics of those patients initially registered with the Scottish Motor Neuron Disease Register (SMNDR) but who subsequently had a diagnosis other than MND made (false positives), to analyse the features which led to a revised diagnosis, and to draw conclusions which might improve routine neurological practice. METHODS: The Scottish Motor Neuron Disease Register is a community based, prospective disease register to identify and follow up all incident cases of motor neuron disease in Scotland. Fifty three patients out of a total of 552 registered are presented, who, after initial registration, were later excluded because they failed to satisfy the register's diagnostic criteria. RESULTS: Seven of these patients were labelled as "MND plus" syndromes and may represent a distinct subset of MND. The remaining 46 patients had an alternative diagnosis made (false positive group), accounting for 8% of the total. In half of these cases, potentially beneficial therapies are available. The predominant reasons which lead to a diagnostic revision were: failure of symptom progression, development of atypical clinical features for MND, and investigation results. CONCLUSIONS: Patients with MND should undergo thorough and relevant investigations at presentation with the emphasis on neuroradiological imaging and neurophysiology; all patients should be followed up by an experienced neurologist, particularly those in whom symptoms and signs are restricted to either the bulbar or spinal muscles; failure of symptom progression or development of atypical features should lead to an early reassessment; finally, patients should be informed of the diagnosis only when it is secure.

False Positive Reactions↗
PubMed1995

Superoxide dismutase mutations in an unselected cohort of Scottish amyotrophic lateral sclerosis patients.

Mutations in the Cu/Zn superoxide dismutase (SOD1) gene are responsible for some cases of familial amyotrophic lateral sclerosis (ALS). We have shown that SOD1 mutations can also occur in apparently sporadic ALS. To establish how often this happens we have undertaken a study of the prevalence of SOD1 mutations in an unselected cohort of Scottish ALS patients, with both sporadic (n = 57) and familial (n = 10) disease. Single strand conformation polymorphism analysis was used to scan for new mutations, and selective restriction enzyme digestion to screen for 11 of the 20 SOD1 mutations published to date. We detected mutations in five (50%) of the familial ALS patients and also in four (7%) of the sporadic patients. One mutation, ile113thr, seems to be particularly prevalent in the Scottish population since it was detected in a total of 6/67 (9%) unrelated cases.

Aged↗