Biomedical subjects

J L Hutton

Publications and source records attributed to J L Hutton.

At least 37 records · Page 2Linked to original sources

PubMed2000

Gabapentin for drug-resistant partial epilepsy.

BACKGROUND: The majority of epileptic patients have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarise the current evidence regarding a new antiepileptic drug, gabapentin, when used as an add-on treatment for drug-resistant partial epilepsy OBJECTIVES: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for patients with drug-resistant partial epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trial register, the Cochrane Controlled Trials Register of The Cochrane Library Issue 4, 1998. In addition, we contacted Parke Davis (manufacturers of gabapentin) and experts in the field to seek any ongoing studies or unpublished studies. SELECTION CRITERIA: Randomized placebo controlled double blind add-on trials of gabapentin in patients with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios were estimated for each outcome. Dose response was evaluated in regression models, and Number Needed to Treat (NNTs) were calculated for individual doses. MAIN RESULTS: Four trials were included representing 750 randomized patients. EFFICACY: Overall odds ratio (OR) (95% Confidence Interval (CI)) for 50% or greater reduction in seizure frequency compared to placebo 2.22 (1.49 - 3.32). Dose regression analysis shows increasing efficacy with increasing dose, with 28.5% (21.5 - 36.7) of patients responding to 1800mg of gabapentin compared to placebo, NNT 6.7 (3.0 - 10.5). Global effectiveness: treatment withdrawal OR (95% CI) compared to placebo 1.40 (0.76 - 2.55); Side effects: OR (99% CI) compared to placebo. dizziness 2.26 (1.28 - 3.99); fatigue 2.29 (1.11 - 4.74); somnolence 2.04 (1.21 - 3.45) were significanty associated with gabapentin. REVIEWER'S CONCLUSIONS: Gabapentin has efficacy as an add-on treatment in patients with drug-resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long term efficacy of gabapentin. Results cannot be extrapolated to monotherapy or patients with other epilepsy types.

Acetates↗

PubMed2000

Topiramate for drug-resistant partial epilepsy.

BACKGROUND: The majority of epileptic patients have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding a new antiepileptic drug, topiramate, when used as an add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of topiramate when used as an add-on treatment in patients with drug resistant partial epilepsy. SEARCH STRATEGY: (a) The Cochrane Library (1999 Issue 1); (b) The controlled trial register of the Cochrane Epilepsy Group; (c) Johnson and Johnson, makers of topiramate; (d) Experts in the field. SELECTION CRITERIA: Randomized placebo controlled add-on trials of topiramate in patients with drug resistant epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention to treat. Summary odds ratios (OR) were estimated for each outcome. Dose response was evaluated in regression models. MAIN RESULTS: Six trials were included representing 743 randomized patients. EFFICACY: Overall OR (95% CIs) for 50% or greater reduction in seizure frequency compared to placebo 4.06 (2.86-5.78). Dose regression analysis shows increasing efficacy with increasing dose, but found no advantage for doses over 400 mg per day. Global effectiveness: treatment withdrawal OR (95% CIs) compared to placebo 2.57 (1.65-4.00). Side effects: OR (99% CIs)compared to placebo, dizziness 1.99 (1.20-3.29); fatigue 2.52 (1. 47-4.32); nausea 2.84 (1.36-5.93); somnolence 2.89 (1.72-4.85) and 'thinking abnormally' 3.71 (2.02-6.80) were significantly associated with topiramate. REVIEWER'S CONCLUSIONS: Topiramate has efficacy as an add-on treatment in patients with drug resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long term efficacy of topiramate. Results cannot be extrapolated to monotherapy or patients with other epilepsy types.

Anticonvulsants↗

PubMed2000

Fraud in medical research: an international survey of biostatisticians. ISCB Subcommittee on Fraud.

The characteristics of scientific fraud and its impact on medical research are in general not well known. However, the interest in the phenomenon has increased steadily during the last decade. Biostatisticians routinely work closely with physicians and scientists in many branches of medical research and have therefore unique insight into data. In addition, they have methodological competence to detect fraud and could be expected to have a professional interest in valid results. Biostatisticians therefore are likely to provide reliable information on the characteristics of fraud in medical research. The objective of this survey of biostatisticians, who were members of the International Society for Clinical Biostatistics, was to assess the characteristics of fraud in medical research. The survey was performed between April and July 1998. The participation rate was only 37%. We report the results because a majority (51%) of the participants knew about fraudulent projects, and many did not know whether the organization they work for has a formal system for handling suspected fraud or not. Different forms of fraud (e.g., fabrication and falsification of data, deceptive reporting of results, suppression of data, and deceptive design or analysis) had been observed in fairly similar numbers. We conclude that fraud is not a negligible phenomenon in medical research, and that increased awareness of the forms in which it is expressed seems appropriate. Further research, however, is needed to assess the prevalence of different types of fraud, as well as its impact on the validity of results published in the medical literature.

Biometry↗

PubMed2000

Some popular versions of uninformed consent.

A patient's informed consent is required by the Nuremberg code, and its successors, before she can be entered into a clinical trial. However, concern has been expressed by both patients and professionals about the beneficial or detrimental effect on the patient of asking for her consent. We examine advantages and drawbacks of popular variations on consent, which might reduce the stress on patients at the point of illness. Both informed and uninformed responses to particular trials, and trials in general, are discussed. The selection by doctors of patients, to whom entry to trials will be offered, is explored. Alternative forms of consent require restrictions on patients' knowledge, personal responsibility and freedom of choice.

Clinical Trials as Topic↗

PubMed2000

Individual patient data meta-analysis of randomized anti-epileptic drug monotherapy trials.

Meta-analysis may be based on either aggregate data or individual patient data (IPD). Three reasons why IPD are desirable for the meta-analysis of anti-epileptic drug (AED) monotherapy trials are: (1) to undertake a more complete analysis of time-to-event outcomes; (2) to investigate the interaction between AED and type of epilepsy; and (3) to undertake re-analysis of the trial to obtain results for all relevant outcomes. We demonstrate that IPD meta-analysis is possible in AED research. Problems arose from missing data at four levels: (1) unknown trials; (2) known trials but no IPD supplied; (3) known trials but missing outcome data for some individuals within trials; and (4) known trials but missing covariate data for some individuals within trials. Empirical evidence of the reliability of meta-analyses based on aggregate rather than individual patient data is still lacking. Examples of other benefits such projects may bring include improvements to the design of a new trial in the area, in terms of the sample size considerations, the definition of outcomes and data collection.

Anticonvulsants↗

PubMed2000

Effect of severity of disability on survival in north east England cerebral palsy cohort.

AIMS: To investigate the effect of motor and cognitive disabilities on the survival of people on the North of England Collaborative Cerebral Palsy Survey, and compare this with other published results. METHODS: The cerebral palsy cohort consists of 1960-1990 births in Northumberland, Newcastle, and North Tyneside health districts. Survival and cause of death were analysed in relation to data on birth, disabilities, and a unique measure of the impact of disability. RESULTS: Disability strongly influences survival. More than a third of those with a severe disability die before age 30. Fewer than a third of deaths are attributed to cerebral palsy on death certificates. Of those with severe cognitive disability, 63% live to age 35 (58% with severe ambulatory disability and 53% with severe manual disability), whereas at least 98% without severe disabilities live to age 35. The Lifestyle Assessment Score (LAS) allows a finer categorisation of impact of disability, and is strongly associated with survival: a ten point increase in LAS is associated with a doubling of the hazard rate. People who had LAS of at least 70, and had survived to age 5 have a 39% chance of dying before age 35. CONCLUSIONS: The majority of people with cerebral palsy attain adulthood. There appears to be more variation in survival rates associated with severe disability between regions of England, than between north east England, British Columbia, and California. Instantaneous risks of dying vary widely between England and California. This variation is not obviously attributable to differing rates of severe disability.

Birth Weight↗

PubMed2000

Ethics of medical research in developing countries: the role of international codes of conduct.

Many statisticians work with informal codes of ethics, and are probably unaware of the existence or content of rules which have been drawn up to govern statistical practice. Medical statisticians will be aware of codes of conduct for medical research, and most codes of professional ethics have some dependence on evidence. Statisticians, therefore, have a valuable contribution to make to debates on ethics which concern scientific soundness, data and perceptions of risk. A lively debate on the revision of the widely respected Declaration of Helsinki, to reflect issues arising from research in developing countries, particularly HIV research, centres on questions of study design, data analysis and assessment of risk. Collectively owned multiprofessional work requires each of the various professions to take responsibility for the conduct of the research, and the impact that it might have. Statisticians share important responsibilities in maintaining ethical medical research in all countries.

Developing Countries↗

PubMed1999

Cause of death in cerebral palsy: a descriptive study.

BACKGROUND: Cause specific research on death certification in chronic disease has rarely involved cerebral palsy. AIMS: To evaluate cause of death information in people known to have cerebral palsy by: describing the cause of death distribution; determining case ascertainment using death certification as the data source; and analysing the choice of wording and its arrangement in the "cause of death statement". STUDY CASES AND SETTING: People with early or late impairment cerebral palsy who died by 30 June 1998, on the population based Mersey Cerebral Palsy Register born 1966-91 to mothers resident locally. STUDY DESIGN: Descriptive study of the multiply coded cause of death statements from National Health Service Central Register flagging. RESULTS: Death certificate copies were acquired for all 282 (13.4%) of the 2102 registered cases who died. Cerebral palsy was the most common "underlying cause of death" (95 of 282; 33.7%) and was mentioned in a further 61 cases. The underlying cause of death was more likely to be cerebral palsy with increasingly severe disability and was derived from Part II in 16 of 95 cases. CONCLUSIONS: The potential of death certification for case ascertainment of cerebral palsy is important, but limited, even with multiple cause coding. Mortality data need careful interpretation as a proxy source for examining trends and patterns in cerebral palsy.

Adolescent↗

PubMed1998

Magnocellular visual function and children's single word reading.

Recent research has shown that reading disabled children find it unusually difficult to detect flickering or moving visual stimuli, consistent with impaired processing in the magnocellular visual stream. Yet, it remains controversial to suggest that reduced visual sensitivity of this kind might affect children's reading. Here we suggest that when children read, impaired magnocellular function may degrade information about where letters are positioned with respect to each other, leading to reading errors which contain sounds not represented in the printed word. We call these orthographically inconsistent nonsense errors "letter" errors. To test this idea we assessed magnocellular function in a sample of 58 unselected children by using a coherent motion detection task. We then gave these children a single word reading task and found that their "letter" errors were best explained by independent contributions from motion detection (i.e., magnocellular function) and phonological awareness (assessed by a spoonerism task). This result held even when chronological age, reading ability, and IQ were controlled for. These findings suggest that impaired magnocellular visual function, as well as phonological deficits may affect how children read.

Child↗

PubMed1997

The new antiepileptic drugs: a systematic review of their efficacy and tolerability.

PURPOSE: Gabapentin (GBP), lamotrigine (LTG), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), and zonisamide (ZNS) are all in use as "add-on" treatment for patients with refractory epilepsy. There have been no comparative randomized controlled trials allowing an evidence-based choice between these drugs. We report a series of meta-analyses of randomized placebo-controlled add-on trials in which these drugs have been tested in patients with partial epilepsy. This work provides an estimate of each drug's efficacy and tolerability compared with placebo. These estimates are compared across drugs to give broad estimates of comparative efficacy and tolerability. METHODS: Trial reports were found by searching Medline, by searching through journals by hand, and by contacting the pharmaceutical industry. The outcomes chosen were the proportion of patients who (a) have a > or = 50% reduction in seizure frequency (50% responders); (b) withdrew from the study (any reason); or (c) reported the following side effects: ataxia, dizziness, fatigue, nausea, or somnolence. Overall odds ratio (OR) with 95% confidence intervals (CIs; 50% responders) or 99% CIs; side effects) were calculated. RESULTS: Twenty-nine trials were included, representing 4,091 randomized patients. The ORs for 50% response (95% CI) were GBP, 2.29 (1.53-3.43); LTG, 2.32 (1.47-3.68); TGB, 3.03 (2.01-4.58); TPM, 4.07 (2.87-5.78); VGB, 3.67 (2.44-5.51); and ZNS, 2.7 (1.36-4.47). ORs for discontinuation were GBP, 1.36 (0.75-2.49); LTG, 1.19 (0.79-1.79); TGB, 1.81 (1.21-2.70); TPM, 2.56 (1.64-4.00); VGB, 2.58 (126-5.27); and ZNS, 4.23 (1.71-10.49). CONCLUSIONS: We have clear evidence that each of these drugs is better than placebo at preventing seizures. When results are compared across drugs, the confidence intervals overlap, and we have no conclusive evidence of differences in efficacy or tolerability. Despite this, the agent that appears most effective may be twice as effective as the agent that appears least effective, and the agent that appears most likely to cause discontinuation may be 4 times more likely to do so than the treatment that appears least likely to do so. Comparative randomized studies are needed further to evaluate these drugs.

Acetates↗

PubMed1997

Differential effects of preterm birth and small gestational age on cognitive and motor development.

AIMS: To determine the differential effects of preterm birth and being small for gestational age on the cognitive and motor ability of the child. METHODS: A longitudinal cohort of all infants of gestational age < or = 32 weeks born to mothers resident in the counties of Cheshire and Merseyside in 1980-1 was studied. The children were assessed at the age of 8 to 9 years using the Wechsler Intelligence Scale for Children, the Neale analysis of reading ability, and the Stott-Moyes-Henderson test of motor impairment. Adequacy of fetal growth was determined by the birthweight ratio--that is, the ratio of the observed birthweight to the expected birthweight for a given gestational age. Children with clinically diagnosed motor, learning or sensory disabilities were excluded. Information on social variables was obtained by a questionnaire completed by the parents. Of the 182 children, 158 were assessed. RESULTS: IQ was positively correlated with birthweight ratio but not with birthweight or gestational age. Motor ability was associated with birthweight, gestational age, and birthweight ratio. Reading comprehension was associated with birthweight ratio, but reading rate and accuracy were best explained by social variables and sex. IQ remained associated with birthweight ratio, after adjusting for maternal education, housing status, and number of social service benefits received. Reading ability was related to these social variables but motor ability was not. CONCLUSIONS: The effects of SGA and preterm birth differed: SGA was associated with cognitive ability, as measured by IQ and reading comprehension; motor ability was additionally associated with preterm birth. Reading rate and accuracy were not associated with SGA or preterm birth but were socially determined.

Birth Weight↗

PubMed1997

Implications of socio-cultural contexts for the ethics of clinical trials.

BACKGROUND: Health technology assesment (HTA) requires scientifically rigorous experimentation involving patients as subjects. HTA itself is required so that treatment given to patients will be both effective and efficient; this requirement is itself ethical in nature. At the same time it is essential that the methods used in HTA are ethically sound. Most healthcare researchers agree that the most effective and soundest method for assessing treatments is the randomised controlled trial (RCT). However, some researchers believe that the RCT is unethical, either in essence, or for use in some forms of medical research and HTA. Furthermore, many patients seem unable to understand the principles and purposes of the RCT, a factor which is highly detrimental for the validity of informed consent. Informed consent is the key to the ethics of medical research, both in most theories and in all codes of research conduct. Many RCTs therefore risk being unethical in practice, even if ethical in principle. AIM OF REPORT: To survey the main objections to the RCT and its alternatives. To assess the philosophical and methodological basis of these objections, and of the methods recommended for addressing them. To identify areas where objections are founded in social or cultural factors normally overlooked in ethical argument about the RCT methodology. To identify alternative arguments or methods which might resolve ethical conflicts in this area. HOW THE RESEARCH WAS CONDUCTED: The methods used were adapted from systematic reviews in medicine. Systematic searches of Medline, Psychlit and Sociofile CD-ROM databases; hand-searches of the major journals in general medicine and surgery, medical ethics and philosophy; and searches of books were carried out. The literature survey was restricted to articles published or abstracted in English. A database of the most relevant and useful materials was compiled, and is accessible on the Internet (http://www.liv.ac.uk/sdthomps/page1.html). RESEARCH FINDINGS: UNDERSTANDING RCTS AND THEIR ALTERNATIVES: There is some evidence of difficulty in understanding the aims and methods of RCTs, and some disquiet about elements of the RCT methodologies. These objections are well known and much discussed, and concern the use of placebo, the continuation of trials after significant differentials in benefit or harm are apparent, and randomisation. CULTURAL OR RELIGIOUS OBJECTIONS: There was an absence of evidence of cultural or religious objections to randomisation, placebo or other kinds of controlled prospective trials. This most likely reflects an absence of research rather than absence of objections. (ABSTRACT TRUNCATED)

Cultural Diversity↗

PubMed1996

The ethics of randomised controlled trials: a matter of statistical belief?

This paper outlines the approaches of two apparently competing schools of statistics. The criticisms made by supporters of Bayesian statistics about conventional Frequentist statistics are explained, and the Bayesian claim that their method enables research into new treatments without the need for clinical trials is examined in detail. Several further important issues are considered, including: the use of historical controls and data routinely collected on patients; balance in randomised trials; the possibility of giving information to patients; patient choice and patient autonomy; and how widely the results of clinical trials can be used. It is concluded that good statistical techniques in the design and analysis of medical studies are essential, but the statistical school used in developing such techniques is relatively unimportant.

Bayes Theorem↗

PubMed1996

A randomized controlled trial of early physiotherapy for high-risk infants.

The aim of this study was to investigate the hypothesis that infants at high risk of cerebral palsy would benefit from early physiotherapy. In total, 105 infants with abnormal cranial ultrasound scans were randomized at around term to early physiotherapy or standard treatment (delaying physiotherapy until abnormal physical signs became apparent). At 12 and 30 months there were clinical and objective assessments. Nine infants died and nine were lost to follow-up by 12 months when 87 infants were assessed. One other child had died and three others were lost to follow-up by 30 months when 83 children were assessed. Cerebral palsy was only accurately predicted in 45 (54%) infants. There was no difference in outcome. The difficulty of predicting cerebral palsy reliably and the heterogeneity of the condition should be borne in mind when planning treatment and assessing its efficacy.

Cerebral Palsy↗

PubMed1995

Prospective evaluation of a prognostic index for intrinsic supratentorial tumours.

A prognostic index for patients with intrinsic supratentorial tumours based on prebiopsy findings was proposed on the basis of data bases of patients presenting between 1975 and 1989. The value of this index is confirmed from data on 76 patients who presented during 1991. Patients classified by the index as having a poor prognosis had a median survival of six months, and those classified as having a good prognosis had a median survival of five years. The expected duration of survival, allowing for this initial prognosis, also depended on whether a patient received resective surgery, radiotherapy, or steroids. Histological grade provided no additional information on survival.

Epilepsy↗

PubMed1994

Life expectancy in children with cerebral palsy.

OBJECTIVE: To determine life expectancy of children with cerebral palsy. DESIGN: Cohort analysis, by means of register compiled from multiple sources of ascertainment, of all children with cerebral palsy born during 1966-84 to mothers resident in Mersey region. Status of children was determined by flagging through NHS central register. SUBJECTS: 1258 subjects with idiopathic cerebral palsy, of whom 1251 were traced and included in analysis. MAIN OUTCOME MEASURES: Effect of functional ability (ambulation, manual dexterity, and mental ability), sex, birth weight, and gestational age on survival. RESULTS: 20 year survival for whole cohort was 89.3% for females and 86.9% for males. For subjects with no severe functional disabilities 20 year survival was 99% (95% confidence interval 98% to 100%), while subjects severely disabled in all three functional groups had 20 year survival of 50% (42% to 58%). Subjects with birth weight < or = 2500 g had 20 year survival of 92% (89% to 95%), while those with birth weight > 2500 g had survival of 87% (84% to 89%). Subjects with gestational age of > 37 weeks had 20 year survival of 93% (91% to 96%), while those with gestational age > or = 37 weeks had survival of 85% (83% to 88%). Birth weight and gestational age were less predictive of survival than functional disability. Best statistical model used gestational age and number of severe functional disabilities as predictors. CONCLUSIONS: Life expectancy of this cohort of children with cerebral palsy was greater than has been suggested in some previous studies. This has important implications for social, educational, and health services.

Birth Weight↗

PubMed1994

Nursing treatment of patients with chronic leg ulcers in the community.

A descriptive survey of current reported practice by 146 community nurses for their nursing treatment of leg ulcers was undertaken. Sixty-four per cent of nurses reported they would apply compression bandages to only venous ulcers; in only 23% of cases could the products described achieve an adequate level of compression. A variety of modern wound dressings were used by the nurses; 89% of nurses reported using a combination of different products layered over the ulcer. There is no evidence that this has any beneficial effect and could therefore be a potential waste of money, as well as contributing to allergic skin reactions. It would be useful if primary-health-care teams and Family Health Service Authority information pharmacists formulated protocols based upon effective treatments for patients with chronic leg ulcers.

Bandages↗

PubMed1994

The long-term stability in whole blood of 14 commonly-requested hormone analytes.

Concentrations of 14 commonly-requested plasma hormones were measured in octuplicate in each of six subjects to determine their stability when unseparated from red cells for periods up to 1 week. Most of the analytes were stable when stored in this way and although statistically significant changes were recorded, in the great majority of cases the changes seen would have no bearing on the clinical interpretation of the result. In the light of these findings, we would confidently report results of analyses for these hormones in plasma that had remained in contact with red cells at ambient temperature for long periods of time.

17-alpha-Hydroxyprogesterone↗