PubMed Health⌕ Search

Biomedical subjects

S J Edwards

Publications and source records attributed to S J Edwards.

At least 19 recordsLinked to original sources
PubMed2006

Systematic review: proton pump inhibitors (PPIs) for the healing of reflux oesophagitis - a comparison of esomeprazole with other PPIs.

BACKGROUND: No randomized controlled trial has compared all the licensed standard dose proton pump inhibitors in the healing of reflux oesophagitis. AIM: To compare the effectiveness of esomeprazole with licensed standard dose proton pump inhibitors for healing of reflux oesophagitis (i.e. lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg). METHODS: Systematic review of CENTRAL, BIOSIS, EMBASE and MEDLINE for randomized controlled trials in patients with reflux oesophagitis. Searching was completed in February 2005. Data on endoscopic healing rates at 4 and 8 weeks were extracted and re-analysed if not analysed by intention-to-treat. Meta-analysis was conducted using a fixed effects model. RESULTS: Of 133 papers identified in the literature search, six were of sufficient quality to be included in the analysis. No studies were identified comparing rabeprazole with esomeprazole. A meta-analysis of healing rates of esomeprazole 40 mg compared with standard dose proton pump inhibitors gave the following results: at 4 weeks [relative risk (RR) 0.92; 95% CI: 0.90, 0.94; P < 0.00001], and 8 weeks (RR 0.95; 95% CI: 0.94, 0.97; P < 0.00001). Publication bias did not have a significant impact on the results. The results were robust to changes in the inclusion/exclusion criteria and using a random effects model. CONCLUSION: Esomeprazole consistently demonstrates higher healing rates when compared with standard dose proton pump inhibitors.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

The effects of early syphilis on CD4 counts and HIV-1 RNA viral loads in blood and semen.

OBJECTIVE: To examine the effect of early syphilis on blood and semen plasma HIV-1 viral loads and CD4 counts. METHODS: In a retrospective case-control study, blood plasma HIV-1 viral loads and CD4 counts in cases during early syphilis (n = 63, 27 receiving antiretroviral therapy) were compared to those before and after syphilis and with controls with non-systemic acute sexually transmitted infections (STI) (n = 104, 39 receiving antiretroviral therapy). In a prospective substudy in those not receiving antiretroviral therapy, semen plasma viral loads during early syphilis (n = 13) were compared with those 1 month, 3 months, and 6 months after treatment for syphilis and with controls with no STIs (n = 20). RESULTS: Retrospective study: CD4 counts were similar in cases (median 410, n = 139 counts) during early syphilis compared to before (485, n = 80) and after (475, n = 88). In a secondary analysis, a drop in CD4 count (21%) among those with early latent syphilis was observed compared with controls. Blood plasma viral loads did not change significantly overall or in those with primary, secondary, or early latent syphilis. Effects were similar on or off antiretroviral therapy. Prospective study: blood and semen viral loads were slightly higher in cases compared with controls but treatment of early syphilis did not reduce either. CONCLUSIONS: We detected no association between early syphilis and changes in blood or semen viral load or CD4 count. Increased HIV-1 infectivity associated with early syphilis is unlikely to be associated with increased levels of HIV-1 RNA in blood or semen.

CD4 Lymphocyte Count↗
PubMed2005

Lay public's understanding of equipoise and randomisation in randomised controlled trials.

OBJECTIVES: To research the lay public's understanding of equipoise and randomisation in randomised controlled trials (RCTs) and to look at why information on this may not be not taken in or remembered, as well as the effects of providing information designed to overcome barriers. DESIGN: Investigations were informed by an update of systematic review on patients' understanding of consent information in clinical trials, and by relevant theory and evidence from experimental psychology. Nine investigations were conducted with nine participants. SETTING: Access (return to education), leisure and vocational courses at Further Education Colleges in the Midlands, UK. PARTICIPANTS: Healthy adults with a wide range of educational backgrounds and ages. INVESTIGATIONS: Participants read hypothetical scenarios and wrote brief answers to subsequent questions. Sub-samples of participants were interviewed individually to elaborate on their written answers. Participants' background assumptions concerning equipoise and randomisation were examined and ways of helping participants recognise the scientific benefits of randomisation were explored. MAIN OUTCOME MEASURES: Judgments on allocation methods; treatment preferences; the acceptability of random allocation; whether or not individual doctors could be completely unsure about the best treatment; whether or not doctors should reveal treatment preferences under conditions of collective equipoise; and how sure experts would be about the best treatment following random allocation vs doctor/patient choice. Assessments of understanding hypothetical trial information. RESULTS: Recent literature continues to report trial participants' failure to understand or remember information about randomisation and equipoise, despite the provision of clear and readable trial information leaflets. In current best practice, written trial information describes what will happen without offering accessible explanations. As a consequence, patients may create their own incorrect interpretations and consent or refusal may be inadequately informed. In six investigations, most participants identified which methods of allocation were random, but judged the random allocation methods to be unacceptable in a trial context; the mere description of a treatment as new was insufficient to engender a preference for it over a standard treatment; around half of the participants denied that a doctor could be completely unsure about the best treatment. A majority of participants judged it unacceptable for a doctor to suggest letting chance decide when uncertain of the best treatment, and, in the absence of a justification for random allocation, participants did not recognise scientific benefits of random allocation over normal treatment allocation methods. The pattern of results across three intervention studies suggests that merely supplementing written trial information with an explanation is unlikely to be helpful. However, when people manage to focus on the trial's aim of increasing knowledge (as opposed to making treatment decisions about individuals), and process an explanation actively, they may be helped to understand the scientific reasons for random allocation. CONCLUSIONS: This research was not carried out in real healthcare settings. However, participants who could correctly identify random allocation methods, yet judged random allocation unacceptable, doubted the possibility of individual equipoise and saw no scientific benefits of random allocation over doctor/patient choice, are unlikely to draw upon contrasting views if invited to enter a real clinical trial. This suggests that many potential trial participants may have difficulty understanding and remembering trial information that conforms to current best practice in its descriptions of randomisation and equipoise. Given the extent of the disparity between the assumptions underlying trial design and the assumptions held by the lay public, the solution is unlikely to be simple. Nevertheless, the results suggest that including an accessible explanation of the scientific benefits of randomisation may be beneficial provided potential participants are also enabled to reflect on the trial's aim of advancing knowledge, and to think actively about the information presented. Further areas for consideration include: the identification of effective combinations of written and oral information; helping participants to reflect on the aim of advancing knowledge; and an evidence-based approach to leaflet construction.

Adolescent↗
PubMed2004

The effect of temperature on food poisoning: a time-series analysis of salmonellosis in ten European countries.

We investigated the relationship between environmental temperature and reported Salmonella infections in 10 European populations. Poisson regression adapted for time-series data was used to estimate the percentage change in the number of cases associated with a 1 degree C increase in average temperature above an identified threshold value. We found, on average, a linear association between temperature and the number of reported cases of salmonellosis above a threshold of 6 degrees C. The relationships were very similar in The Netherlands, England and Wales, Switzerland, Spain and the Czech Republic. The greatest effect was apparent for temperature 1 week before the onset of illness. The strongest associations were observed in adults in the 15-64 years age group and infection with Salmonella Enteritidis (a serotype of Salmonella). Our findings indicate that higher temperatures around the time of consumption are important and reinforce the need for further education on food-handling behaviour.

Adolescent↗
PubMed2002

Structural basis for the spotted appearance of amphibian neuromuscular junctions stained for synaptic vesicles.

We have compared the distribution of vesicles in amphibian motor nerve terminals determined by electron microscopy and by functional labeling with the styryl dye, FM2-10. Our aim was to resolve apparent discrepancies in the literature on the distribution of vesicles determined by the two procedures. Electron photomicrographs of non-serial cross sections of terminal branches were analyzed by stereological procedures to obtain indices of the terminal and vesicle areas. Terminal cross sectional area varied 3-fold on average along terminal branches and was largest particularly when active zone was present in the section. The vesicle area index (a measure of vesicle abundance) was highly correlated with the terminal area index, suggesting that the average density of vesicles is constant throughout the branches. When the data were separated according to whether active zone was present or not in a section, we found a small (26%) but significant increase in the average density of vesicles in active zone compared with non-active zone regions in the terminal. The distribution of spots along terminal branches following vesicle staining with FM2-10, as well as with antibodies to vesicle proteins, suggested that vesicles were distributed in highly concentrated clusters. However, the degree of variation between spot and inter-spot staining intensities found with the FM-dye was similar in magnitude to that for terminal cross sectional area determined from the electron microscopy. We conclude that the spotty pattern of stained vesicles seen with the optical microscope results primarily from vesicle accumulations associated with terminal varicosities.

Animals↗
PubMed2002

Antibody responses to HPV6b E polyproteins and production of monoclonal antibodies.

A range of fusion constructs (expressed in Escherichia coli) were produced that contained two or more HPV6b E proteins, producing a single continuous amino acid sequence corresponding to the sequences of the individual E proteins. The constructs also included a C-terminal hexahistidine tag fused in-frame to aid purification. The fusion proteins (polyproteins) were semipurified by Ni(++) metal affinity chromatography under denaturing conditions. Immunization of BALB/c mice with these polyproteins resulted in the production of specific E protein antibodies. The draining lymph nodes from these mice were used to produce monoclonal antibodies (MAbs). The specificity of the polyclonal and MAbs was confirmed by immunoblotting and by screening for reaction with a series of synthetic peptides of E proteins. HPV E polyproteins were found to be immunogenic and immunization with the polyproteins resulted in specific antibody responses to the component E proteins.

Amino Acids↗
PubMed2001

Are randomized clinical trials good for us (in the short term)? Evidence for a "trial effect".

OBJECTIVE: To assess whether there is evidence that randomized controlled trials are systematically beneficial, or harmful, for patients. In other words, is there a "trial effect"? If so, to examine whether the evidence sheds light on the likely sources of the difference in outcomes. METHODS: Systematic review of the literature. RESULTS: We set out in some detail potential sources of a "trial effect" and potential biases. We found only 14 research articles (covering more than 21 trials) with relevant primary data. We extracted, with difficulty, quantitative data-sets from the articles, and classified these according to likely source of any apparent trial effect. The categories used were: differences in prognosis; superior treatment in the trial; and "protocol/Hawthorne effect" (benefit from improved routine care within a trial). ANALYSIS: The evidence available is limited in breadth (coming largely from cancer trials) and quality, as well as quantity. There is weak evidence to suggest that clinical trials have a positive effect on the outcome of participants. This does not appear to depend strongly on the trial demonstrating that an experimental treatment is superior. However, benefit to participants is less evident where scope for a "protocol/Hawthorne effect" was apparently limited (because there was no effective routine treatment or because the comparison group also received protocol care). A form of bias, arising if clinicians who tend to recruit to trials also tend to be better clinicians, could also explain these results. CONCLUSION: While the evidence is not conclusive, it is more likely that clinical trials have a positive rather than a negative effect on the outcome of patients. In the limited data available, the effect seems to be larger in trials where an effective treatment already exists and is included in the trial protocol. RECOMMENDATION: That carefully researched treatment protocols, and monitoring of outcomes, be used for all patients, not just those in trials.

Bias↗
PubMed2001

Systematic review of proton pump inhibitors for the acute treatment of reflux oesophagitis.

BACKGROUND: Esomeprazole is a new proton pump inhibitor, which has been compared to omeprazole for the treatment of reflux oesophagitis in clinical trials. AIM: To compare the effectiveness of esomeprazole with the recommended dose of proton pump inhibitors in the healing of reflux oesophagitis, using omeprazole as a common comparator. METHODS: Systematic review of randomized controlled trials. Extraction and re-analysis of data to provide 'intention-to-treat' results. Meta-analysis using a Fixed Effects model. RESULTS: A meta-analysis of healing rates of esomeprazole 40 mg compared to omeprazole 20 mg gave the following results: at 4 weeks (relative risk 1.14; 95% CI: 1.10, 1.18) and 8 weeks (RR 1.08; 95%CI: 1.05, 1.10). Other proton pump inhibitors compared to omeprazole 20 mg are as follows: lansoprazole 30 mg at 4 weeks (RR 1.02; 95%CI: 0.97, 1.08) and 8 weeks (RR 1.01; 95%CI: 0.97, 1.06); pantoprazole 40 mg at 4 weeks (RR 0.99; 95%CI: 0.91, 1.07) and 8 weeks (RR 0.98; 95%CI: 0.93, 1.04); rabeprazole 20 mg at 4 weeks (RR 1.00; 95%CI: 0.87, 1.14) and 8 weeks (RR 0.98; 95%CI: 0.91, 1.05). CONCLUSIONS: Esomeprazole has demonstrated higher healing rates than omeprazole at 4 and 8 weeks. Other proton pump inhibitors (lansoprazole, pantoprazole and rabeprazole) have not shown higher healing rates when compared with omeprazole.

Administration, Oral↗
PubMed2001

IL-1 genotype and adult periodontitis among young New Zealanders.

Several recent studies have investigated the association between interleukin-1 genotype and periodontitis in clinical samples, where generalizability is an issue. The aim of this study was to investigate the association between adult periodontitis and IL-1 genotype in a population-based sample of 26-year-olds. Based on probing depth (PD) measurements, participants were divided into three disease groups: "Severe" (1+ teeth with 5+mm PD; N = 25), "Moderate" (2+ teeth with 4+mm PD; N = 36), and "Controls" (the remainder; N = 800). The "periodontitis-associated genotype" (PAG; Kornman et al., 1997) was present in 20.0% of the "Severe" group and in 34.8% of "Controls", whereas the IL-1A(+4845) [1,1]/IL-1B(+3953) [2,2] genotype was present in 12.0% and 0.9%, respectively. After controlling for sex, smoking status, and plaque levels, we found that those with IL-1B(+3953) [1,1]/IL-1A(+4845) [2,2] had 12.3 times the odds of being in the "Severe" group. Analysis of these data suggests that the IL-1A(+4845) [1,1]/IL-1B(+3953) [2,2] genotype is associated with periodontal disease in this young population. Future periodontal data collections as this cohort ages are required to confirm the predictive value of that genotype.

Adult↗
PubMed2000

Efficient induction of cell death by adenoviruses requires binding of E1B55k and p53.

The use of an Elb55k-deficient adenovirus, ONYX-015, to selectively target tumor cells containing a mutated p53 gene has produced promising results. However, recent reports have questioned the selectivity of this virus, showing that ONYX-015 can replicate in cells containing a wild-type p53 and that p53 may actually be required for cell death. To address these apparent contradictions in the literature, we infected a number of mutant and wild-type p53-containing cell lines with ONYX-015 and wild-type adenovirus and observed their death profiles up to 10 days postinfection. We demonstrate that two distinct cell death phenotypes exist, one of which is rapid and dependent on the presence of p53 and one of which is p53 independent. Using adenoviruses expressing E1b55k proteins deficient in their ability to bind p53, we show that formation of a complex between p53 and the adenoviral Elb55k protein is necessary for the activation of the rapid cell death pathway. In the absence of p53 or the absence of complex formation between p53 and Elb55k, cell death is delayed considerably. These data suggest three things: that the selectivity of killing appears to be dependent on the presence of the E1b55k/p53 complex; that viruses lacking Elb55k (such as ONYX-015) kill cells in a delayed manner independent of p53; and that binding of E1b55k to p53 does not merely serve to inactivate p53, but rather is required for the induction of rapid cell death. The components of this complex that lead to rapid cell death remain to be determined.

Adenoviridae↗
PubMed2000

Clinical trials. A place for randomization in the interval between the end of recruitment and availability of results.

There is a time delay between the final recruitment of patients to a randomized controlled trial and the publication of results. The practical options available to decision makers during this gap can be listed according to whether all treatments are already widely available or whether at least one has been restricted to the trial. When the treatments are already in widespread use, the options are simply either to stop randomizing or to continue. When one trial treatment is restricted, there are further options: a) withdraw the restricted treatment altogether, pending the final analysis; b) continue to offer randomization, with a view to providing further data should these be needed; or c) make the intervention widely available to patients who would have previously been eligible for the trial. In this paper, we discuss the relative advantages and disadvantages of each option and discuss their attendant ethical implications. In particular, we suggest that continuing randomization is an option worthy of serious consideration. Randomizing patients acts as a "hedge" against the need for more data, given that sample size calculation is an inexact science. However, patients must be made aware of the basis on which randomization is offered.

Decision Making↗
PubMed2000

Can unequal be more fair? A response to Andrew Avins.

In this paper, we respond to Andrew Avins's recent review of methods whose use he advocates in clinical trials, to make them more ethical. He recommends in particular, "unbalanced randomisation". However, we argue that, before such a recommendation can be made, it is important to establish why unequal randomisation might offer ethical advantages over equal randomisation, other things being equal. It is important to make a pragmatic distinction between trials of treatments that are already routinely available and trials of restricted treatments. We conclude that unequal randomisation could, indeed, be an ethical compromise between protecting the interests of participants and those of society.

England↗
PubMed2000

Measurement of gastric residual volume: state of the science.

This literature review substantiates that there is confusion regarding what constitutes excessive gastric residual volume in adult tube-fed patients. Only one research study regarding gastric residuals was located; it indicated that 200 ml for a nasogastric tube and 100 ml for a gastrostomy tube should cause concern. The implications of these findings for adult-health nurses are discussed.

Adult↗