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Biomedical subjects

S Dixon

Publications and source records attributed to S Dixon.

At least 37 records · Page 2Linked to original sources

False positive results do not have a negative effect on reattendance for subsequent breast screening.

OBJECTIVES: To find out whether a false positive breast screening result has a negative effect on subsequent screening attendance. Also considered was the proportion of women who had ever failed to reattend for screening, having previously attended routinely. DESIGN: The study was a retrospective cohort design. SETTING: Data from the call and recall records of the Central and East London Breast Screening Service (CELBSS) were used. PARTICIPANTS: Women who had been invited to attend for breast screening by the CELBSS during 1997. MAIN OUTCOME MEASURES: Subsequent attendance or non-attendance for the next routine breast screen, after a false positive screening result. RESULTS: A substantial number of women failed to reattend for a breast screen during their screening history, having attended for their previous routine breast screen. No differences in the rates of reattendance were found between those who had previously received a false positive result and those who had not. CONCLUSION: From the results obtained in the present study it would seem that the experience of a false positive breast screen does not deter women from reattending in the future. However, many women living in inner city areas who attend for an initial breast screen are failing to attend for subsequent routine mammograms. This may have a deleterious effect for these women in terms of the benefits of attendance for regular screening.

Breast Neoplasms↗

The prevalence of Chlamydia trachomatis infection in male undergraduates: a postal survey.

OBJECTIVES: To determine the prevalence of Chlamydia trachomatis infection in male undergraduates and to investigate whether prevalence increases with time spent at university. To investigate the feasibility of screening men for C trachomatis by self sampling and posting of urine specimens. METHODS: The study design was a postal survey undertaken by the Department of Genito-Urinary Medicine (GUM) and Student University Health Service (SUHS) in SHEFFIELD: 2607 male undergraduates from the SUHS patient list were invited to participate in the study by providing a first void urine specimen and posting it to the laboratory. The main outcome measure was the detection of C trachomatis infection. RESULTS: 758 students participated in the study, a response rate of 29.1%. Nine students (1.2%) tested positive for C trachomatis. The prevalence of infection in the first, second, and third year of study was 0.7%, 1.5%, and 1.6% of participants respectively. There was no statistically significant difference in prevalence of infection between first and third year students (chi(2) test, p = 0.32). However, students with chlamydia had a higher median age (Mann-Whitney U test, p < or = 0.05). Contact tracing identified four further cases of C trachomatis infection. CONCLUSION: Screening for C trachomatis infection by postal survey is feasible. However, the response rate in this study was poor and the estimated sample size was not reached. Therefore, it has not been possible to determine the true prevalence of infection in this population or to accurately assess changes in prevalence with time spent at university.

Adolescent↗

Geriatric assessment in primary care: formulating best practice.

Comprehensive geriatric assessment (CGA) is a structured approach to measuring physical, mental and social functioning of older people to identify needs and to plan care. Meta-analysis of trials of CGA suggest that it is cost-effective, but there is no agreed approach to its implementation in primary care. Our aim was to develop a best-practice model for geriatric assessment in primary care. We took an iterative approach to development, combining expert and local stakeholder opinion, and using semi-structured interviews to assess patient and practitioner experience in nine general practices in Sheffield. Patients were aged 75 and over, living at home. The best-practice model was the use of a standardized instrument (EASY-Care) to unselected patients aged 75 years and over living at home or in residential care, administered by a practice nurse in the context of an over-75s health check. There was high patient and practitioner acceptability, and significant cost savings were noted. Key beneficial features were the assessment of mental health and sources of support; goal-setting; generation of a disability score; and high patient satisfaction from contact with nursing staff. We conclude that geriatric assessment in primary care is feasible, economical and beneficial to patients and practitioners. Nursing staff are central to successful implementation of geriatric assessment in primary care.

Aged↗

What will be the costs of a quality emergency service?

The Clinical Standards Advisory Group report on urgent and emergency admissions to hospital identified several important issues regarding emergency care. This paper examines what we know about the costs of a quality emergency service. Estimating the cost of a quality emergency service is not yet possible, but ongoing and future research should be capable of highlighting the costs of important service improvements. It must, however, be recognized that such work by itself will not automatically lead to increased funding within emergency care. Further consideration must be given to the funding arrangements for emergency care if long-term improvements are to be secured.

Emergency Medical Services↗

A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer.

PURPOSE: Thalidomide is a potent teratogen that causes dysmelia in humans. Recently, in vitro data suggested that it inhibits angiogenesis. Prostate cancer is dependent on the recruitment of new blood vessels to grow and metastasize. Based on those data, we initiated a Phase II trial of thalidomide in patients with metastatic androgen-independent prostate cancer. EXPERIMENTAL DESIGN: This was an open-label, randomized Phase II study. Thalidomide was administered either at a dose of 200 mg/day (low-dose arm) or at an initial dose of 200 mg/day that escalated to 1200 mg/day (high-dose arm). RESULTS: A total of 63 patients were enrolled onto the study (50 patients on the low-dose arm and 13 patients on the high-dose arm). Serum prostate-specific antigen (PSA) decline of > or = 50% was noted in 18% of patients on the low-dose arm and in none of the patients on the high-dose arm. Four patients were maintained for > 150 days. The most prevalent complications were constipation, fatigue, neurocortical, and neurosensory. CONCLUSION: Thalidomide, an antiangiogenesis agent, has some activity in patients with metastatic prostate cancer who have failed multiple therapies. A total of 27% of all patients had a decline in PSA of > or = 40%, often associated with an improvement of clinical symptoms. Because our preclinical studies had shown that thalidomide increases PSA secretion, we believe that the magnitude of PSA decline seen in our trial justifies further study.

Aged↗

The cost of diabetes: time for a different approach?

We argue that studies estimating the treatment cost of diabetes and other economic issues have progressed dramatically over recent years. This has undoubtedly improved our understanding of diabetes. However, attention needs to now shift to more detailed studies that require prospective bespoke data collection from epidemiologists as well as economists. This is not to say that investigation of costs using routine data is of no value--such work will continue to provide new data and methods to those evaluating new interventions, as well as by helping to identify important research areas. However, it may be time for a new paradigm to help in our understanding of this challenging disease. Such an approach must be capable of supporting the complex evaluation of new technologies, and subsequently, can not rely solely on routine data.

Diabetes Mellitus↗

Smooth muscle myosin light chain kinase expression in cardiac and skeletal muscle.

The purpose of this study was to characterize myosin light chain kinase (MLCK) expression in cardiac and skeletal muscle. The only classic MLCK detected in cardiac tissue, purified cardiac myocytes, and in a cardiac myocyte cell line (AT1) was identical to the 130-kDa smooth muscle MLCK (smMLCK). A complex pattern of MLCK expression was observed during differentiation of skeletal muscle in which the 220-kDa-long or "nonmuscle" form of MLCK is expressed in undifferentiated myoblasts. Subsequently, during myoblast differentiation, expression of the 220-kDa MLCK declines and expression of this form is replaced by the 130-kDa smMLCK and a skeletal muscle-specific isoform, skMLCK in adult skeletal muscle. These results demonstrate that the skMLCK is the only tissue-specific MLCK, being expressed in adult skeletal muscle but not in cardiac, smooth, or nonmuscle tissues. In contrast, the 130-kDa smMLCK is ubiquitous in all adult tissues, including skeletal and cardiac muscle, demonstrating that, although the 130-kDa smMLCK is expressed at highest levels in smooth muscle tissues, it is not a smooth muscle-specific protein.

Amino Acid Sequence↗

A pilot study examining changes in dust lead loading on walls and ceilings after lead hazard control interventions.

The U.S. Department of Housing and Urban Development (HUD) guidelines on lead hazard control instruct contractors to clean floors, windows, walls, ceilings, and other horizontal surfaces to remove lead-contaminated dust and debris after lead interventions are conducted. This dust removal activity adds costs to each project. The need to clean floors and windows is well documented in the HUD guidelines. However, there is substantially less documentation to support the recommendation to clean walls and ceilings. We examined whether it is necessary to clean walls and ceilings after lead hazard control (LHC) interventions by comparing dust lead loadings measured on these surfaces before an LHC intervention to dust lead loadings after the intervention. Twenty-two dwelling units undergoing substantial LHC measures consistent with the HUD guidelines were enrolled in the study. There was a significant increase in dust lead loading on walls and ceilings between the pre- and postintervention. The change in wall dust lead loading was substantial and created potentially harmful lead exposures. Although statistically significant, the change in ceiling dust lead loading was minimal and the postintervention dust lead loadings were far below the existing federal floor dust lead clearance standard. These results strongly support the recommendations in the HUD guidelines to clean walls after LHC interventions and do not provide sufficient justification to alter the current recommendation to clean ceilings after lead work.

Child↗

Testing the validity of cost-effectiveness models.

A growing body of recent work has identified several problems with economic evaluations undertaken alongside controlled trials that can have potentially serious impacts on the ability of decision makers to draw valid conclusions. At the same time, the use of cost-effectiveness models has been drawn into question, due to the alleged arbitrary nature of their construction. This has led researchers to try and identify ways of improving the quality of cost-effectiveness models through identifying 'best practice', producing guidelines for peer review and identifying tests of validity. This paper investigates the issue of testing the validity of cost-effectiveness models or, perhaps more appropriately, whether it is possible to objectively measure the quality of a cost-effectiveness model. A review of the literature shows that there is much confusion over the different aspects of modelling that should be assessed in respect to model quality, and how this should be done. We develop a framework for assessing model quality in terms of: (i) the structure of the model; (ii) the inputs of the model; (iii) the results of the model; and (iv) the value of the model to the decision maker. Quality assessment is investigated within this framework, and it is argued that it is doubtful that a set of objective tests of validity will ever be produced, or indeed that such an approach would be desirable. The lack of any clearly definable and objective tests of validity means that the other parts of the evaluation process need to be given greater emphasis. Quality assurance forms a small part of a broader process and is best implemented in the form of good practice guidelines. A set of key guidelines are presented.

Cost-Benefit Analysis↗

A randomised controlled trial of prehospital intravenous fluid replacement therapy in serious trauma.

RESULTS: In total 1309 patients were entered in the study: 699 (53.4%) were treated by paramedics operating protocol A and 610 (46.6%) were treated by paramedics operating protocol B. The randomisation worked well and there were no significant differences between treatment groups in incident characteristics, ambulance performance times, or patient or injury characteristics, apart from slightly more moderate or severe head injuries in the protocol A group (25.3% versus 20.3%). Protocol compliance was poor, with only 31% of protocol A patients receiving prehospital fluids and only 80% of protocol B patients not given fluids. The estimated odds ratio for being given prehospital fluids when treated by protocol A compared to protocol B was 2.09 (95% confidence interval (CI), 1.53 to 2.81). MORTALITY: There were 73 deaths within 6 months in the 699 patients in the protocol A group (10.4%), and 60/610 (9.8%) in the protocol B group. Thus the crude odds ratio for deaths when managed by protocol A was 1.07 (95% CI, 0.73 to 1.54). Excluding 26 patients whose cause of death may not have been trauma related, the odds ratio was 1.04 (95% CI, 0.69 to 1.55). Excluding 17 patients who may have been dead on arrival of the ambulance at the scene the odds ratio was 1.04 (95% CI, 0.70 to 1.53). Adjustment for age, injury severity and whether the patient was unconscious at the scene did not significantly alter these odds ratios. COMPLICATIONS: A total of 106 patients were identified from hospital notes as having at least one of eight major complications (adult respiratory distress syndrome, sepsis, acute renal failure, coagulopathy, wound infection, pneumonia, fat embolism or pulmonary embolism). The proportions with recorded complications were similar in the two groups: 60/699 (8.5%) in the protocol A group versus 46/610 (7.5%) in the protocol B group. HEALTH STATUS: A total of 878 questionnaires were sent to patients, and 559 (64%) usable replies were received. The response rate was similar in the two groups (62.9% versus 64.6%). In all eight dimensions of the SF-36 health status measure patients who had been managed by paramedics operating protocol A reported better average health than did patients in the protocol B group. However, none of the differences were at a level considered clinically important and only for one of the eight dimensions was the difference statistically significant. COMPOSITE OUTCOMES: No significant differences in outcome were found between the two protocol groups in terms of patients who either died or had serious complications, nor for patients who either died or had known poor health. SUBGROUPS: Subgroups of patients were defined on eight characteristics (ambulance service area, whether a doctor was on scene, paramedic-patient contact time, injury severity, whether taken to theatre for emergency surgery, type of injuries, type of area, and whether the patient was treated before or after protocol cross-over). There was no evidence of any difference in mortality rates or composite outcomes between any subgroups, or between protocols within any subgroup. Time to A&E department The analysis suggests that patients given fluids spent 12-13 minutes longer at the accident scene than did patients not given fluids. However, because only one-quarter of patients were given fluids, and the specific protocol used made little difference to this, average on-scene times were largely unaffected by protocols. COSTS: In the prehospital and immediate-care phase (including A&E treatment), the mean costs of the protocol A and protocol B groups were ¿419 and ¿416, respectively. This small difference reflects two small and offsetting effects of protocol B: reduced on-scene time (p = 0.08) and increased use of blood in the A&E department (p = 0.03). There were no other statistically significant differences in costs, with the mean total costs being ¿2706 and ¿2678 in the protocol A and protocol B groups, respectively (p = 0.52). (ABSTRACT TRUNCA

Adolescent↗

Crystal structure of the bifunctional N-acetylglucosamine 1-phosphate uridyltransferase from Escherichia coli: a paradigm for the related pyrophosphorylase superfamily.

N-acetylglucosamine 1-phosphate uridyltransferase (GlmU) is a cytoplasmic bifunctional enzyme involved in the biosynthesis of the nucleotide-activated UDP-GlcNAc, which is an essential precursor for the biosynthetic pathways of peptidoglycan and other components in bacteria. The crystal structure of a truncated form of GlmU has been solved at 2.25 A resolution using the multiwavelength anomalous dispersion technique and its function tested with mutagenesis studies. The molecule is composed of two distinct domains connected by a long alpha-helical arm: (i) an N-terminal domain which resembles the dinucleotide-binding Rossmann fold; and (ii) a C-terminal domain which adopts a left-handed parallel beta-helix structure (LbetaH) as found in homologous bacterial acetyltransferases. Three GlmU molecules assemble into a trimeric arrangement with tightly packed parallel LbetaH domains, the long alpha-helical linkers being seated on top of the arrangement and the N-terminal domains projected away from the 3-fold axis. In addition, the 2.3 A resolution structure of the GlmU-UDP-GlcNAc complex reveals the structural bases required for the uridyltransferase activity. These structures exemplify a three-dimensional template for the development of new antibacterial agents and for studying other members of the large family of XDP-sugar bacterial pyrophosphorylases.

Acetyltransferases↗

Measuring health-related quality of life in patients with venous leg ulcers.

INTRODUCTION: The effect on quality of life by healing leg ulcers is not known and no validated disease-specific tool is available for measuring health-related quality of life (HRQoL) for people with venous leg ulcers. The objective of this paper was to compare four generic instruments [MOS 36-Item Short-Form Health Survey (SF-36); EuroQol (EQ); McGill Short Form Pain Questionnaire (SF-MPQ) and the Frenchay Activities Index (FAI)] used for measuring HRQoL in people with venous leg ulcers, and to offer guidance on the most appropriate tool for researchers. METHODS: Two hundred and thirty-three patients with venous leg ulcers were recruited as part of a randomised controlled trial of the cost-effectiveness of community leg ulcer clinics. Subjects completed questionnaires containing the four instruments on three occasions (initial assessment, 3 and 12 months). The discriminative and evaluative properties of the four instruments were compared. RESULTS: All four instruments were acceptable to patients, taking a mean of 19.3 (SD 6.3) min to complete. At initial assessment, the SF-MPQ had poorer discriminative properties than the other three instruments and was not able to distinguish between the different patient groups in relation to age and ulcer duration. The FAI was good at discriminating between the different patient groups (at initial assessment) in relation to age, mobility and ulcer size. At the three-month follow-up, the SF-MPQ was more responsive than the other measures and detected changes in HRQoL, whereas the EQ and SF-36 did not. At 12 months, the SF-MPQ still identified differences and the SF-36 and EQ also did at this stage. CONCLUSION: In the absence of a validated condition-specific tool for measuring changes in general health status for patients with venous leg ulcers, we make the following recommendations. For evaluating the outcome of interventions with a short-term follow-up (three months) in a clinical study we recommend the SF-MPQ and for 12-month follow-up in a clinical study the SF-36, with or without the SF-MPQ.

Aged↗

Achieving dust lead clearance standards after lead hazard control projects: an evaluation of the HUD-recommended cleaning procedure and an abbreviated alternative.

The U.S. Department of Housing and Urban Development's (HUD's) Guidelines for the Evaluation and Control of Lead-Based Paint Hazards in Housing strongly recommend that after lead hazard control interventions all walls, ceilings, floors, and other horizontal surfaces be cleaned using a three-step process to reduce lead-contaminated dust and debris. The three steps are: an initial vacuuming using a machine equipped with a high-efficiency particulate air (HEPA) filter (HEPA vacuum), wet wash with a lead cleaner, and a final HEPA vacuum. This study evaluated the effectiveness of two cleaning protocols: (1) the HUD-recommended three-step procedure, and (2) an abbreviated two-step cleaning procedure that omits the final HEPA vacuum. Cleaning procedures were evaluated in 27 dwelling units that had undergone significant lead hazard control interventions likely to produce lead dust. Dust lead samples were collected on floors and in window sills and troughs prior to the lead control hazard intervention, after the wet wash step of the cleaning procedure, and after completion of the second HEPA vacuuming. The results of the study demonstrate that dust lead surface loading on smooth and cleanable surfaces following the three-step and two-step cleaning procedures can achieve 1995 federal guidance dust clearance levels and levels substantially lower. Although the dust lead clearance rates before and after the second HEPA vacuum were the same, the time saved by omitting the second HEPA is small relative to the other elements of the cleaning process.

Air Pollution, Indoor↗