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Biomedical subjects

S Knight

Publications and source records attributed to S Knight.

At least 55 records · Page 3Linked to original sources
PubMed1998

Clinical trials of antibacterial agents: a practical guide to design and analysis. Statisticians in the Pharmaceutical Industry Working Party.

Guidelines on the conduct of clinical trials of antibacterial agents produced by the US Food and Drug Administration, the British Society for Antimicrobial Chemotherapy, the Infectious Diseases Society of America and a European Working Party have been reviewed. Although very informative, these guidelines provide limited practical guidance on the design and statistical aspects of phase III studies of antimicrobial agents. This paper describes the differences between antibacterial trials and clinical studies in other therapeutic areas with regard to subjective endpoints, dual clinical and bacteriological endpoints, frequent protocol violations and difficulty of using placebo controls. The importance of a detailed protocol and planned analysis strategy is emphasized. The choice of comparator agents, practical issues with the blinding of trial materials and the documentation of patients excluded from study entry are discussed. The use of different patient groups and different endpoints in analyses are described. The principles of equivalence and their application to trials of antibacterial agents are discussed, together with an approach to calculating sample size. A variety of statistical analyses of results are compared for different situations indicating some of the problems that can arise. Different methods of presentation of study data are included with emphasis on regulatory submissions rather than scientific publications. Some graphical presentations are recommended and issues regarding data across different studies are discussed.

Anti-Infective Agents↗
PubMed1998

Beneficial impact of the homelands movement on health outcomes in central Australian aborigines.

OBJECTIVE: This study compares prevalence of obesity, hypertension and diabetes in two groups of Aboriginal adults: those living in homelands versus centralised communities in central Australia. It also compares weight gain, incidence of diabetes, mortality and hospitalisation rates between the groups over a seven-year period. METHODS: Baseline survey of 826 Aboriginal adults in rural central Australian communities in 1987-88 with a follow-up survey of 416 (56% response rate, excluding deaths). Each time, they had a 75 g oral glucose tolerance test (OGTT), and blood pressure and anthropometry measurement. Deaths and hospitalisations for all of the original cohort were recorded for the seven-year period. RESULTS: Homelands residents had a lower baseline prevalence of diabetes (risk ratio [RR] = 0.77, 0.59-1.00), hypertension (RR = 0.66, 0.54-0.80) and overweight/obesity (RR = 0.70, 0.59-0.83). The incidence of diabetes was lower among homelands residents (RR = 0.70, 0.46-1.06). They were less likely to die than those living in centralised communities (RR = 0.56, 0.37-0.85) and less likely to be hospitalised for any cause (RR = 0.79, 0.71-0.87), particularly infections (RR = 0.70, 0.61-0.80), injury involving alcohol (RR = 0.61, 0.47-0.79) and other injury (RR = 0.75, 0.60-0.93). Mean age at death was 58 and 48 years for residents of homelands and centralised communities respectively. CONCLUSION: Aboriginal people who live in homelands communities appear to have more favourable health outcomes with respect to mortality, hospitalisation, hypertension, diabetes and injury, than those living in more centralised settlements in Central Australia. These effects are most marked among younger adults.

Adult↗
PubMed1998

Phase II study of dexverapamil plus anthracycline in patients with metastatic breast cancer who have progressed on the same anthracycline regimen.

The purpose of this study is to evaluate whether metastatic breast cancer that has progressed on an anthracycline-containing drug regimen will subsequently respond to that identical regimen if dexverapamil, a modulator of P-glycoprotein-mediated drug resistance, is given concomitantly. Eligible patients received 180 mg/m2 dexverapamil every 6 h for 15 doses with the anthracycline administered 30 min after the seventh dose. Blood for dexverapamil levels was drawn before and 30 min after this dose. When possible, biopsies were obtained to measure mdr-1 expression by reverse transcription-PCR and by image cytometry. Of the 21 patients entered onto the trial, 20 were evaluable for response. There were two partial responses (10%) that both lasted for 6 months, and two additional patients had stable disease. Seven patients had asymptomatic cardiotoxicity consisting of hypotension (24%), bradycardia (5%), or prolongation of the P-R interval (14%). Two patients developed acute congestive heart failure, one on dexverapamil and one 10 days after stopping it. Dexverapamil did not seem to increase anthracycline toxicity. The median trough dexverapamil plus norverapamil level on day 3 was 1110 ng/ml (range, 186-3385 ng/ml), and the median peak level was 2164 ng/ml (range, 964-8382 ng/ml). There was poor correlation between reverse transcription-PCR and image cytometry for the level of mdr-1 expression. Because dexverapamil has been shown to affect doxorubicin pharmacokinetics subsequent to the initiation of this trial, it cannot be concluded that the responses seen were necessarily due to P-glycoprotein inhibition. Additional studies are necessary to determine whether mdr-1 modulators can reverse clinical drug resistance in breast cancer patients. The intrinsic cardiotoxicity of dexverapamil makes it less suitable for such studies than several other available agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Practice-led education and development project: developing styles in clinical supervision.

This paper is the second installment which reports a study conducted by the authors following successful application to the Yorkshire Regional Health Authority in response to a call for proposals for studies into practice-led education and development. The aim of the project is to pilot and evaluate an approach to leadership development based upon a conceptual model of reflectivity within a learning organization whilst developing and evaluating a model of supervised practice.

Education, Nursing, Baccalaureate↗
PubMed1997

Hemodynamic evaluation of foot venous compression devices.

PURPOSE: Venous compression devices effectively prevent deep venous thrombosis. Recently, because traumatic injury of the limb often precludes application of calf devices, newer methods have been developed that are only applied to the foot. This study was designed to evaluate the venous hemodynamic effects produced by four different compressive devices compared with calf-only intermittent pneumatic compression (IPC). METHODS: Twenty-seven healthy volunteers had application of each device followed by duplex scanning determination of the venous hemodynamics at the popliteal vein (PV) and the common femoral vein (CFV). Endpoints included (1) resting (peak) systolic velocity (RSV); (2) maximum venous velocity (MVV) during device activation; (3) acceleration, the slope of the line from RSV to MVV; and (4) return time (RT) from MVV back to RSV. The devices evaluated included two commercially available mechanical foot devices, (1) foot compressive device (FCD1), and (2) FCD2; (3) an experimental mechanical foot device (FCD3); (4) an experimental pneumatic foot device (FCD4); and (5) a calf-only IPC device (IPC). RESULTS: The RSV was higher in the CFV than the PV. The initial RSV was not statistically significant between the five experimental groups (p = 0.37) at either the PV or CFV, although the RSV was higher in the CFV than in the calf (CFV, 24.3 +/- 6.7 cm/sec; PV, 12.5 +/- 3.7 cm/sec; p < 0.0001). MVV was significantly higher with FCD2 and the IPC (p = 0.0002) at the PV level, but this difference decreased at the CFV. Acceleration was greatest with the two available foot devices, FCD1 and FCD2, compared with the other three devices (p < 0.0001) at both levels. On the other hand, the RT was significantly longer only with the IPC; RT was four to 10 times slower at the PV and three to five times slower at the CFV compared with the other four devices. CONCLUSIONS: The two commercially available foot devices, FCD1 and FCD2, and the IPC produced significant alterations in venous hemodynamics. Changes produced at the PV level by both foot and calf devices were seen proximally at the CFV, although the changes were usually less. The mechanical devices produced rapid acceleration of venous flow to an elevated MVV, whereas the IPC produced an elevated peak with a sustained period of flow above baseline (RT). Further clinical comparison should be completed before widespread adaptation of these devices as an equivalent to existing IPC devices.

Adult↗
PubMed1997

Molecular-cytogenetic detection of a deletion of 1p36.3.

We report a deletion of 1p36.3 in a child with microcephaly, mental retardation, broad forehead, deep set eyes, depressed nasal bridge, flat midface, relative prognathism, and abnormal ears. The phenotype is consistent with that described for partial monosomy for 1p36.3. Reverse chromosome painting and microsatellite and Southern blot analyses were used to map the extent of the deletion. Fluorescence in situ hybridisation (FISH) analysis using probes from every telomere indicates that the rearrangement is likely to be a chromosomal truncation or rearrangement involving subtelomeric repetitive DNA. The deletion was identified by screening a sample of children and adults with idiopathic mental retardation. In conjunction with previous work on this sample, we estimate that 7.4% of the group have subtelomeric rearrangements.

Adolescent↗
PubMed1997

Psychiatric complications of homozygous sickle cell disease among young adults in the Jamaican Cohort Study.

BACKGROUND: This study aimed to determine the prevalence of psychiatric disorder in young adults with homzygous sickle cell (SS) disease and in controls with normal haemoglobin, and to examine factors associated with psychiatric disorder. METHOD: The study design was cross-sectional. Subjects were aged 18-20 years: 63 with SS disease and 89 controls. The Psychiatric Assessment Schedule was used to determine psychiatric disorder at index of Definition level 5. RESULTS: Psychiatric disorder was identified in 18 (29%) SS disease patients and in 22 (25%) controls. In SS patients, psychiatric disorder was not related to illness severity but was associated with leaving school early, difficulties in social adjustment, impaired cognitive function and having previous psychiatric difficulties. Male SS patients with psychiatric disorder all had low body mass index (BMI < 17.60). In controls, psychiatric disorder was associated with female gender, unemployment and difficulties in social adjustment. CONCLUSIONS: The prevalence of psychiatric disorder was similar in patients and controls, although associated factors tended to be different. The association with low BMI in SS men merits further study.

Adolescent↗
PubMed1996

Defining a model for team leader development.

This paper will provide details of a study conducted jointly by the authors following successful application to the Yorkshire Regional Health Authority in response to a call for proposals for studies into 'Practice-Led Education and Development'. The aim of the project was to pilot and evaluate an approach to leadership development based upon a conceptual model of reflectivity within a learning organization whilst developing and evaluating a model of supervised practice.

Education, Nursing, Continuing↗
PubMed1996

Fostering multidisciplinary research and approaches to rural health issues: the concept of an International Summer Institute.

The challenge of how best to provide equitable, accessible and affordable health care in rural and remote settings is an international concern. It has been acknowledged that a multidisciplinary approach to current rural health issues involving social scientists and health practitioners may be crucial in developing appropriate responses. One initiative designed to facilitate multidisciplinary research and greater collaboration between researchers and practitioners was an International Summer Institute sponsored by the Social Science and Humanities Research Council of Canada. This article outlines an Australian perspective on the rationale for, background to, and structure of this initiative, and evaluates it as one option for promoting multidisciplinary approaches to rural health research.

Allied Health Personnel↗
PubMed1996

Effect of an immunisation campaign in Natal and KwaZulu on vaccinaton coverage rates, 1990-1991.

In 1990 the Department of National Health and Population Development of South Africa launched a nationwide immunisation campaign targeted mainly at measles. In order to measure the effect of the campaign on vaccination coverage rates for children, pre- and post- campaign vaccination coverage surveys were undertaken using a modified Expanded Programme for Immunisation technique, stratified for race and urban/rural residence. The results in KwaZulu-Natal showed no significant increase in measles vaccination coverage for any race rates after the campaign (as documented by Road-to-Health cards). There was a decrease in coverage of the black population. However, when a history of measles vaccination was accepted, the results showed an increase in coverage. The results call into question the effectiveness of immunisation campaigns as a strategy for raising vaccination coverage levels, as well as their having a sustained impact on the incidence of measles. Alternative strategies, such as the strengthening and expansion of existing primary health care services, should be considered.

Child, Preschool↗
PubMed1995

Factors associated with lowered intelligence in homozygous sickle cell disease.

The intelligence quotient (IQ) of 60 patients with homozygous sickle cell (SS) disease and 60 age and sex matched controls with a normal haemoglobin (AA) genotype aged 15-18 years, followed up in a cohort study from birth, was assessed by the Wechsler intelligence scales for children or for adults. IQ appeared to be normally distributed in both genotypes but mean values in SS disease were 5.6 points (95% confidence interval (CI) 1.0 to 10.2) lower than in AA controls (p = 0.016). The difference occurred in both verbal (5.5 points, p = 0.017) and performance (5.0 points, p = 0.044) subscales of the IQ score and the IQ defect in SS disease was associated with a significantly lower attention factor score (p = 0.005) but not with other factor scores. The genotype difference in IQ was not accounted for by differences in parental occupational level, school absenteeism, or school drop out, or reported activity level. In SS disease, IQ was not related to mean steady state haemoglobin, fetal haemoglobin, or mean cell haemoglobin concentration, or clinical severity as judged by the frequency of painful crises, hospital admission, or sick visits. IQ, at age 15-18 years, correlated with the patients' height at all ages from 1 to 10 years (partial correlations increasing from 0.14 (p = 0.15) at age 1 to 0.27 (p = 0.004) at age 10). Adjusting for height reduced the mean genotype difference in IQ to 5.5 (95% CI 0.6 to 10.3) points at age 1 and to 2.6 points (95% CI to -2.3, 7.5) at age 10. Prepubertal height therefore accounted for much of the genotype difference in IQ. It is speculated that early factors, possible nutritional, contribute to both impaired growth and mental development in sickle cell disease.

Adolescent↗
PubMed1994

2.2 A resolution structure of the amino-terminal half of HIV-1 reverse transcriptase (fingers and palm subdomains).

BACKGROUND: HIV-1 reverse transcriptase (RT) catalyzes the transformation of single-stranded viral RNA into double-stranded DNA, which is integrated into host cell chromosomes. The molecule is a heterodimer of two subunits, p51 and p66. The amino acid sequence of p51 is identical to the sequence of the amino-terminal subdomains of p66. Earlier crystallographic studies indicate that the RT molecule is flexible, which may explain the difficulty in obtaining high-resolution data for the intact protein. We have therefore determined the structure of a fragment of RT (RT216), which contains only the amino-terminal half of the RT molecule ('finger' and 'palm' subdomains). RESULTS: The crystal structure of RT216 has been refined at 2.2 A resolution to a crystallographic R-value of 20.8%. The structure is very similar to that of the corresponding part of the p66 subunit in the p66/p51 heterodimer, although there is a small difference in the relative orientation of the two subdomains compared with the structure of an RT-DNA-antibody fragment complex. There are a large number of stabilizing contacts (mainly hydrogen bonds and hydrophobic interactions) between the subdomains. The locations of conserved amino acids and the position of some important drug-resistant mutations are described. CONCLUSIONS: The RT216 structure provides detailed three-dimensional information of one important part of HIV-1 RT (including the critical active site residues). We propose a model to explain the inhibitory effect of non-nucleoside inhibitors, which partially accounts for their effect in terms of conformational changes of active site residues.

Binding Sites↗
PubMed1994

Food-purchasing behaviour in an Aboriginal community. 1. Results of a survey.

Attempts to improve the nutritional status of Aboriginal people through nutritional education programs should be informed by an understanding of contemporary patterns of food procurement, preparation and distribution. This paper describes the results of a survey of food-purchasing behaviour in a central-Australian Aboriginal community. Every transaction occurring in each food outlet in the community over a two-week period was recorded and the data analysed. The results show that women play a much greater role than men in food purchasing, that there is a significant recourse to takeaway foods, that there is a cycle of expenditure determined by distribution of pension and Community Development Employment Project cheques, and that children have sufficient disposable income to be able to provision themselves from the food outlets, so that much of their food consumption is not determined by adult members of their family.

Adolescent↗
PubMed1994

Food-purchasing behaviour in an Aboriginal community. 2. Evaluation of an intervention aimed at children.

The previously described survey of food-purchasing behaviour in a central-Australian Aboriginal community demonstrated that children have sufficient disposable income to provision themselves directly from food outlets. Subsequently, a community-based intervention project developed strategies to provide healthier choices for these children. Two years after the initial survey, a follow-up survey was conducted in which all food purchases by children under the age of 15 in the community were recorded over a two-week period. The results demonstrate an improvement in the quality of foods and beverages purchased by children at the time of the second survey.

Adolescent↗