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Biomedical subjects

D M Goodridge

Publications and source records attributed to D M Goodridge.

14 recordsLinked to original sources
PubMed2004

Assign 2.0: software for the analysis of Phred quality values for quality control of HLA sequencing-based typing.

As improvements to DNA sequencing technology have resulted in increasing the throughput of DNA sequencing, the bottleneck for high throughput DNA sequencing-based typing (SBT) has shifted to sequence analysis, genotyping and quality control (QC). Consistent high-quality DNA sequence is required in order to reduce manual verification and editing of sequence electropherograms. However, identifying systematic changes in quality is difficult to achieve without the aid of sophisticated sequence analysis programs dedicated to this purpose. We describe a computer software program called Assign 2.0, which integrates sequence QC analysis and genotyping in order to facilitate high-throughput SBT. Assign 2.0 performs an analysis of Phred quality values in order to produce quality scores for a sample and a sequencing run. This enables sample-to-sample and run-to-run QC monitoring and provides a mechanism for the comparison of sequence quality between various genes, various reagents and various protocols with the aim of improving the overall quality of DNA sequence data. This, in turn, will result in reducing sequence analysis as a bottleneck for high-throughput SBT.

Alleles↗
PubMed2001

Mortality in epilepsy in the first 11 to 14 years after diagnosis: multivariate analysis of a long-term, prospective, population-based cohort.

The United Kingdom National General Practice Study of Epilepsy is a prospective, population-based study of newly diagnosed epilepsy. A cohort of 792 patients has now been followed for up to 14 years (median follow-up [25th, 75th percentiles] 11.8 years, range 10.6-11.7 years), a total of 11,400 person-years. These data are sufficient for a detailed analysis of mortality in this early phase of epilepsy. Over 70% of patients in this cohort have developed lasting remission from seizures, although the mortality rate in the long term was still twice that of the general population. The standardized mortality ratio (SMR), the number of observed deaths per number of expected deaths, was 2.1 (95% confidence interval [CI] = 1.8, 2.4). Patients with acute symptomatic epilepsy (SMR 3.0; 95% CI = 2.0, 4.3), remote symptomatic epilepsy (SMR 3.7; 95% CI = 2.9, 4.6), and epilepsy due to congenital neurological deficits (SMR 25; 95% CI = 5.1, 73.1) had significantly increased long-term mortality rates, whereas patients with idiopathic epilepsy did not (SMR 1.3; 95% CI = 0.9, 1.9). This increase in mortality rate was noted particularly in the first few years after diagnosis. Multivariate Cox regression and time-dependent co-variate analyses were utilized for the first time in a prospective study of mortality in epilepsy. The former showed that patients with generalized tonic-clonic seizures had an increased risk of mortality. The hazard ratio (HR), or risk of mortality in a particular group with a particular risk factor compared to another group without that particular risk factor, was 6.2 (95% CI = 1.4, 27.7; p = 0.049). Cerebrovascular disease (HR 2.4; 95% CI = 1.7, 3.4; p < 0.0001), central nervous system tumor (HR 12.0; 95% CI = 7.9, 18.2; p < 0.0001), alcohol (HR 2.9; 95% CI = 1.5, 5.7; p = 0.004), and congenital neurological deficits (HR 10.9; 95% CI = 3.2, 36.1; p = 0.003) as causes for epilepsy and older age at index seizure (HR 1.9; 95% CI = 1.7,2.0; p < 0.0001) were also associated with significantly increased mortality rates. These hazard ratios suggest that epilepsy due to congenital neurological deficits may carry almost the same risk of mortality as epilepsy due to central nervous system tumors and that epileptic seizures subsequent to alcohol abuse may carry almost the same risk of mortality as epilepsy due to cerebrovascular disease. The occurrence of one or more seizures before the index seizure (the seizure that led to the diagnosis of epilepsy and enrolment in the study) was associated with a significantly reduced mortality rate (HR 0.57; 95% CI = 0.42, 0.76; p = 0.00001). Time-dependent co-variate analysis was used to examine the influence of ongoing factors, such as seizure recurrence, remission, and antiepileptic drug use, on mortality rates in the cohort. Seizure recurrence (HR 1.30; 95% CI = 0.84, 2.01) and antiepileptic drug treatment (HR 0.97; 95% CI = 0.67, 1.38) did not influence mortality rate. There were only 5 epilepsy-related deaths (1 each of sudden unexpected death in epilepsy, status epilepticus, burns, drowning, and cervical fracture), suggesting that death directly due to epileptic seizures is uncommon in a population-based cohort with epilepsy.

Adolescent↗
PubMed2000

Factors predicting prognosis of epilepsy after presentation with seizures.

The objective of this study was to identify the factors, at the time of diagnosis, that determine the prognosis for remission of epilepsy. A prospective community-based cohort study of 792 patients recruited at the time of their first diagnosis of epileptic seizures was undertaken; in those classified 6 months after presentation, the median follow-up period was 7.2 years (quartiles at 6.2 and 8.2 years) after presentation. We analyzed data from 6 months after the first identified seizure, which prompted the diagnosis of epilepsy, to allow us to factor in those aspects contingent on a diagnostic assessment Baseline clinical and demographic data were analyzed using the Cox proportional hazards regression model with remission of epilepsy for 1, 2, 3, and 5 years as outcome measures. The dominant clinical feature predicting remission was the number of seizures in the 6-month diagnostic assessment period. Thus, the chance of entering 1 year of remission by 6 years for a patient who had 2 seizures during this initial 6 months was 95%; for 5 years of remission, it was 47% as opposed to 75% for 1 year of remission and 24% for 5 years of remission if there had been 10 or more seizures during this period. The number of seizures in the early phase of epilepsy (here, taken as the first 6 months after presentation) is the single most important predictive factor for both early and long-term remission of seizures.

Child↗
PubMed1999

Assessing the psychosocial consequences of epilepsy: a community-based study.

BACKGROUND: Few studies have measured, using validated scales, the psychosocial handicap of epilepsy in a general practice setting. AIM: To assess the prevalence of psychosocial problems associated with epilepsy. METHOD: A survey was undertaken of 309 subjects, with one or more non-febrile epileptic seizures, drawn from two general practices in the United Kingdom (UK). The outcome measures were the Subjective Handicap of Epilepsy Scale (SHE), the SF-36, and the Hospital Anxiety and Depression scale (HAD). RESULTS: One-third of persons with active epilepsy were significantly handicapped by their condition. The severity of subjective handicap was related to seizure frequency and to the duration of remission of seizures. Between one-third and one-half of subjects scored as 'cases' on the HAD scale and on the mental health subscale of the SF-36. Only one-third of the psychiatric morbidity revealed by the questionnaires had been recognized by the general practitioner (GP). Scores on the SF-36 indicated that people with active seizures perceived themselves as significantly less healthy than those in remission, and that, for persons in remission, drug treatment had a detrimental effect on certain aspects of well-being. CONCLUSIONS: The occurrence of seizures, even at low frequencies, is associated with psychosocial handicap, and this may remain covert in general practice.

Adolescent↗
PubMed1998

Risk-assessment scores, prevention strategies, and the incidence of pressure ulcers among the elderly in four Canadian health-care facilities.

The accurate prediction of pressure ulcer (PU) development among hospitalized elderly patients is a complex endeavour. A prospective, longitudinal, cohort study of 330 patients over age 65 in 2 Canadian tertiary-care teaching hospitals and 2 long-term-care facilities examined the association between risk-assessment scores, prevention strategies, and PU incidence. The overall PU incidence rate was 9.7%, with half of the subjects who developed a PU doing so in the first week of hospitalization. The incidence rate for "at risk" patients (10.1%) was similar to the rate for "not at risk" patients (9.3%). The number of prevention strategies used was related to risk-assessment scores and to PU development. Paradoxically, the incidence rate increased with the number of prevention strategies employed. The total risk-assessment score that appeared to have the best balance of sensitivity (69%) and specificity (55%) was 19. Four of the 6 risk-assessment subscales were associated with PU development. Logistic regression modelling confirmed the univariate results that the number of prevention strategies used was the best single predictor of PU development. The data confirm that predicting PU development for individual patients is difficult at best. Results suggest that use of a risk-assessment scale alone is not sufficient to accurately predict PU development. The clinical judgement and experience of nurses are required in providing supplementary information to standard measurement instruments.

Aged↗
PubMed1996

Neurological disease in a defined population: the results of a pilot study in two general practices.

A pilot study was set up to ascertain incident neurological disorders occurring in 25,000 people attending two general-practice surgeries for a period of 1 year. To achieve completeness of ascertainment and diagnostic validity poses considerable logistical and theoretical difficulties, and these are discussed. The commonest disorders (incidence in parentheses) were headaches (210/100,000), back syndromes (319/100,000), acute cerebrovascular disease (128/100,000), and migraine (64/100,000), with non-specific symptoms the most common problem overall (514/100,000). The incidence of Parkinson's disease was 26/100,000 and that of epilepsy 23/100,000. The pilot study will form the basis for a more comprehensive linkage scheme between the National Hospital for Neurology and Neurosurgery in London and surrounding general practices with a total base population of 100,000.

Brain↗
PubMed1995

Epilepsy in a population of 6000 re-examined: secular trends in first attendance rates, prevalence, and prognosis.

It is important to document changes in the vital statistics of epilepsy in the general population so that the success or failure of prevention and treatment can be assessed and health provisions planned. A population of 6000 persons was studied 10 years apart to determine secular trends in the prevalence and prognosis of epilepsy. The lifetime prevalence of all patients with one or more afebrile seizures was 20.3/1000 (95% CI 16.9-24.3) in 1983 and 21.0/1000 (95% CI 17.6-25.1) in 1993. The prevalence of active epilepsy was 5.3/1000 (95% CI 3.6-7.5) in 1983 and 4.3 (95% CI 2.8-6.3) in 1993. To assess trends in incidence rates the annual first attendance rates were measured from 1964 to 1993. Annual first attendance rates in children (age < 20 years) have declined from 152.4/100,000 (90% CI 106.0-212.9) in the years 1974-83, to 60.9/100,000 (90% CI 33.0-103.3) in the years from 1984-93, suggesting that the incidence of epilepsy in children is falling. Also noteworthy was the first attendance rates for epilepsy in elderly people (61-80 years) in the years 1984-93, of 82.0 (90% CI 38.5-154.0), higher than in any other age group. This increase in the number of elderly patients with epilepsy is important, and has health planning implications, especially with the overall increase in the total elderly population. There was, however, no evidence that prognosis has significantly altered in the past 40 years.

Adolescent↗
PubMed1994

Mortality from epilepsy: results from a prospective population-based study.

Patients with epilepsy may be subject to an increased risk of premature death from the underlying cause, or from the epilepsy itself. The extent and nature of this risk has been insufficiently investigated. Standard mortality ratios (SMRs) of patients with newly diagnosed epilepsy were determined in a prospective national population-based study. 1091 patients with newly diagnosed or suspected epilepsy were ascertained who were attending one of 275 UK general practices from 1984-1987. 1091 patients were classified after 6 months as definite epilepsy (564), possible epilepsy (228), febrile seizures (220), or not epilepsy (79). Over a median follow up of 6.9 years the SMR for patients with definite or possible epilepsy was 2.5 (95% CI 2.1-2.9), and 3.0 (2.5-3.7) for definite epilepsy. The SMR was highest during the first year after diagnosis 5.1 (3.8-6.5), declined to 2.5 (1.5-3.9) at 3 years, and 1.3 (0.7-2.0) at 5 years. The commonest causes of death were pneumonia (SMR 7.2), cancer (3.5), and stroke (3.7). The SMR for patients with idiopathic epilepsy was 1.6 (1.0-2.4), remote symptomatic epilepsy 4.3 (3.3-5.5), and acute symptomatic epilepsy 2.9 (1.7-4.5). Mortality in patients with newly-diagnosed epilepsy was high, mainly due to the underlying cause. The SMR for idiopathic epilepsy was also raised, suggesting that epilepsy per se may carry a small risk of death.

Adolescent↗
PubMed1994

The chemoenzymatic synthesis of neoglycolipids and lipid-linked oligosaccharides using glycosyltransferases.

The application of glycosyltransferases to the chemoenzymatic synthesis of neoglycosphingolipids and lipid-linked oligosaccharides allows the regio- and stereoselective formation of glycosidic bonds. In our laboratory galactosyl-, sialyl-, and fucosyltransferases have been used to assemble oligosaccharide headgroups directly on a sphingosine derivative without the need for any protection group strategies, including the Lewisx antigen. In complementary studies on N-linked oligosaccharide biosynthesis, chemically phosphorylated dolichol analogues have been tested as substrates for Dol-P-Man synthetase. Also, the substrate recognition of the core beta-1,4-mannosyltransferase from yeast has been investigated using a range of chitobiose derivatives as potential substrates.

Carbohydrate Sequence↗
PubMed1993

Pressure ulcer risk assessment tools. What's new for gerontological nurses.

Impaired skin integrity is one of the most common and most costly problems facing the institutionalized elderly. Risk assessment tools provide the nurse with an efficient and systematic means of identifying those clients at high risk for pressure ulcer development. Pressure ulcer risk assessment tools are usually based on a combination of the following variables: mobility, continence, mental status, activity, nutrition, or physical status. Further testing and comparison of the various pressure ulcer risk assessment tools in the elderly population is needed to establish relative scientific and practical merit.

Aged↗
PubMed1983

Epileptic seizures in a population of 6000. I: Demography, diagnosis and classification, and role of the hospital services.

A total of 122 patients with a history of non-febrile epileptic seizures were identified in a survey of 6000 persons from a single general practice. The lifetime prevalence was 20.3/1000 including single seizures and 17.0/1000 excluding single seizures; 5.3/1000 had active epilepsy. Diagnosis and classification of seizures in such a survey were difficult. Most patients were seen by a hospital specialist at some point, but hospital follow up was sporadic. Overall patient assessment and monitoring was poor. There is a place for specialised epilepsy clinics that could be organised along the lines of the clinics for diabetes. These provide facilities for initial diagnosis and assessment, for planning long term management, for the selected follow up of difficult cases, and for referral for specific problems. Such a system would improve the long term care of patients with epilepsy.

Adolescent↗
PubMed1983

Epileptic seizures in a population of 6000. II: Treatment and prognosis.

Treatment and prognosis were studied in 122 patients with non-febrile seizures in a population of 6000. Phenytoin and phenobarbitone were the most commonly prescribed drugs, although the popularity of phenobarbitone had declined over time. The average duration of treatment was relatively short, and most patients received single drug treatment. Treatment patterns were erratic, and the surveillance and audit of treatment generally poor. Recurrence after a first attack was found in four fifths of the patients. Generally the total number of seizures suffered by each patient was small, the period of active epilepsy short, and remission when it occurred was usually permanent. The cumulative probability of continuing activity fell and the proportion of patients in remission rose over time. Patients with partial or mixed seizure types had a poorer overall prognosis. The course of the epilepsy in the early years of treatment proved to be a useful guide to the long term prognosis, and the possibility that effective treatment might influence long term prognosis is raised.

Adolescent↗
PubMed1982

An analysis of fat folders.

A review of patients with fat folders showed that a high proportion of them had evidence of organic disease and were frequent attenders. Many of them had also changed their allegiance between doctors and there was often evidence of past or present marital disharmony. A high percentage were on psychotropic medication.

Adult↗