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Biomedical subjects

R F Logan

Publications and source records attributed to R F Logan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Aspirin, NSAIDs and colorectal cancer--what do the epidemiological studies show and what do they tell us about the modus operandi?

A large number of observational epidemiological studies show that regular use of aspirin and other NSAID's is associated with a reduction in the risk of developing both colorectal adenomas and cancer. Furthermore, the prodrug sulindac appears clinically to be able to reduce and reverse the growth of existing polyps in familial adenomatous polyposis (FAP). For aspirin and NSAID's the dose, duration of effect and length of protection seen after cessation remain to be fully established. The available data for aspirin suggest that doses higher than those needed for heart disease prevention are required. It is also likely that the drug needs to be taken continuously for a number of years. With regards to randomised controlled trials to evaluate chemopreventive strategies there are so far only limited data available. The only trial reported to date found no effect but employed a relatively low dose of 325 mg of aspirin every other day and the randomised intervention period was relatively short (5 years). Further trials of intermediate endpoints (adenomas) are currently underway in the UK and USA and are employing higher doses of aspirin. Randomised clinical studies of sulindac have been more encouraging demonstrating that it is a useful drug for therapeutic applications in FAP patients. Its relatively greater side effects, however, prevent its consideration for primary chemoprevention. The mechanisms by which NSAID's act are still sought. Strategies for possible primary and secondary chemoprevention in humans also require evaluation.

Journal Article↗
PubMed1999

Immunosuppressive therapy for ulcerative colitis: results of a nation-wide survey among consultant physician members of the British Society of Gastroenterology.

BACKGROUND: The role of immunosuppressive therapy in ulcerative colitis remains controversial. There is little information available on how frequently immunosuppressives are used, the circumstances, dose and duration of use and perceived benefit. METHODS: A postal survey was sent to consultant gastroenterologist members of the British Society of Gastroenterology. RESULTS: Questionnaires were returned by 81% of the 496 UK consultants approached. Azathioprine use was frequent, with 93% reporting previous use and 86% use within the past year. Although 95% usually prescribed a < or =2 mg/kg dose, only 39% were prepared to prescribe higher doses. There was marked variation in duration of use, with 46% using azathioprine for <2 years and 17% continuing it for 4 years or longer. Consultants with more experience of azathioprine in ulcerative colitis used it at higher maintenance doses for longer periods, and in patients with less extensive disease. Cyclosporin use was reported by 47% of those caring for ulcerative colitis patients, with 36% having used it at least once in the past year. However, 65% of users estimated that fewer than 50% of patients subsequently avoided colectomy. On stopping cyclosporin only 21% always introduced an alternative immunosuppressive, while 23% never did so. Potentially serious side-effects attributable to azathioprine and cyclosporin were reported by 36% and 45% of users of each drug, respectively. CONCLUSIONS: This survey reveals considerable variation in the amount and pattern of immunosuppressive use in ulcerative colitis, with serious side-effects commonly seen. There is a pressing need for further randomized controlled trials to provide reliable evidence as to how immunosuppressive therapy should be used in ulcerative colitis.

Azathioprine↗
PubMed1999

Contribution of the MHC region to the familial risk of coeliac disease.

Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.

Celiac Disease↗
PubMed1998

Varying efficacy of Helicobacter pylori eradication regimens: cost effectiveness study using a decision analysis model.

OBJECTIVE: To determine how small differences in the efficacy and cost of two antibiotic regimens to eradicate Helicobacter pylori can affect the overall cost effectiveness of H pylori eradication in duodenal ulcer disease. DESIGN: A decision analysis to examine the cost effectiveness of eight H pylori eradication strategies for duodenal ulcer disease with and without 13C-urea breath testing to confirm eradication. MAIN OUTCOME MEASURES: Cumulative direct treatment costs per 100 patients with duodenal ulcer disease who were positive for H pylori. RESULTS: In model 1 the strategy of omeprazole, clarithromycin, and metronidazole alone was the most cost effective of the four strategies assessed. The addition of the 13C-urea breath test and a second course of omeprazole, clarithromycin, and metronidazole achieved the highest eradication rate (97%) but was the most expensive (62.63 pounds per patient). The cost of each additional effective eradication was 589.00 pounds (incremental cost per case) when compared with the cost of treating once only with omeprazole, clarithromycin, and metronidazole; equivalent to the cost of a patient receiving ranitidine for duodenal ulcer relapse for more than 15 years. Eradication strategies of omeprazole, amoxycillin, and metronidazole were less cost effective than omeprazole, clarithromycin, and metronidazole alone. In model 2 the addition of the 13C-urea breath test after treatment, and maintenance treatment, increased the cost of all the strategies and reduced the cost advantage of omeprazole, clarithromycin, and metronidazole alone. CONCLUSION: Small differences in efficacy can influence the comparative cost effectiveness of strategies for eradicating H pylori. Of the strategies tested the most cost effective (omeprazole, clarithromycin, and metronidazole alone) was neither the least expensive (omeprazole, amoxycillin, and metronidazole alone) nor the most effective (omeprazole, clarithromycin, and metronidazole with further treatment for patients found positive for H pylori on 13C-urea breath testing). Cost effectiveness should be an important part of choosing an eradication strategy for H pylori.

Breath Tests↗
PubMed1998

Postmarketing surveillance of the safety of cimetidine: 15-year mortality report.

The pattern of mortality after 15 years of observation is reported among almost 10,000 patients who were taking cimetidine when they were first recruited between 1977 and 1980. Many took the drug for a number of years, some switching to other antisecretory agents as the study progressed. The findings are reassuring and provide no evidence of any long-term adverse effects of cimetidine which might be detected by monitoring mortality rates. The data have also been used to examine the possible positive relationships between aluminium ingestion and Alzheimer's disease and H. pylori infection and ischaemic heart disease. No significant evidence was obtained in support of the existence of these relationships.

Journal Article↗
PubMed1998

Inflammatory bowel disease: is there any relation between smoking status and disease presentation? European Collaborative IBD Study Group.

Smoking is associated with Crohn's disease and nonsmoking with ulcerative colitis. The aim of this study was to compare the clinical features at diagnosis and during the first year of follow-up in smokers and nonsmokers with inflammatory bowel disease (IBD). In 19 centers across Europe, a prospective study was performed of 457 newly diagnosed patients with Crohn's disease and 930 with ulcerative colitis. The characteristics of the disease were recorded by the treating physician by using a standard protocol at the time of diagnosis. Treatment characteristics were assessed after 1 year of follow-up. Weight loss occurred significantly more often in smoking patients with Crohn's disease, as well as in smokers with ulcerative colitis (p < 0.02), and diarrhea was more frequent in smoking patients with Crohn's disease compared with non-smoking individuals (p < 0.01). Patients with Crohn's disease who smoke were less likely to have colonic involvement (p < 0.01) and were more often prescribed immunosuppressive medication (p < 0.02). The study suggests that (a) smoking protects the colon from inflammation and (b) is associated with more active disease in Crohn's disease. The association between weight loss and smoking in both diseases is probably due to a general effect of smoking. The reported relation between smoking and the course of Crohn's disease is a strong argument for encouraging patients to give up smoking.

Adolescent↗
PubMed1998

Appendicectomy, childhood hygiene, Helicobacter pylori status, and risk of inflammatory bowel disease: a case control study.

AIMS: To examine the relation between inflammatory bowel disease and appendicectomy, childhood domestic hygiene, and Helicobacter pylori infection. METHODS: Case control study involving 213 patients with ulcerative colitis, 110 with Crohn's disease, and 337 controls having elective surgery. RESULTS: Nine patients with ulcerative colitis (4.5%) reported a previous appendicectomy compared with 57 controls (19%) (odds ratio (OR) 0.20, 95% confidence interval (CI) 0. 1-0.4, p<0.0001). The inverse association was unaffected by excluding operations performed after the age of onset of ulcerative colitis and was stronger for appendicectomy performed before age 20 (OR 0.14). No association with appendicectomy was found for Crohn's disease and no associations with tonsillectomy for either disease. The availability of a fixed hot water supply in early childhood (before age 11) was associated with Crohn's disease (OR for hot water not always versus always available 0.56, 95% CI 0.3-0.9, p=0. 02) but not with ulcerative colitis. No other aspect of domestic hygiene before or after age 11 was associated with either Crohn's disease or ulcerative colitis. Although H pylori seroprevalence was positively associated with overcrowding (p<0.001) and the absence of running hot water in childhood it was not associated with the presence of either Crohn's disease or ulcerative colitis. H pylori seroprevalence was no lower in patients who had been exposed to sulphasalazine than in controls or those not exposed. CONCLUSIONS: Our findings confirm the strong inverse association between previous appendicectomy and the development of ulcerative colitis and suggest that the protective effect is greater for appendicectomy performed in childhood.

Adolescent↗
PubMed1997

Continued inadequacies in data sources for the evaluation of cancer services.

There is a need to evaluate cancer services and provide a baseline on current treatment success and organization. This study shows that this process may be severely hindered by case note destruction or inaccessibility and incomplete information. This is an ongoing problem that needs to be addressed now.

Breast Neoplasms↗
PubMed1997

Prescribing of nonsteroidal anti-inflammatory drugs in general practice: determinants and consequences.

AIM: To use Prescribing Analysis and Costs data to investigate factors associated with differences in rates of nonsteroidal anti-inflammatory drug prescribing in Nottingham general practices. RESULTS: Poisson regression analysis revealed that the Age. Sex and Temporary Resident Prescribing Unit Index was the largest identifiable influence; larger practice size and a higher index of deprivation were also significantly associated with lower prescribing, whilst the number of partners was associated with higher levels of prescribing. However, even after correcting for the influence of age, sex and temporary residents, there was an 5.9-fold variation in rates of prescribing. A similar Poisson regression analysis to identify factors associated with admission to hospital with ulcer bleeding in the elderly over the preceding 57 months identified the rate of nonsteroidal anti-inflammatory drug (NSAID) prescribing as the only significant influence. CONCLUSION: The data are compatible with 1 hospital admission per 2823 NSAID prescriptions (95% confidence intervals 2098-8110) and they emphasize the need for strategies to reduce levels of NSAID prescribing.

Aged↗
PubMed1997

Linkage analysis of candidate regions for coeliac disease genes.

A strong HLA association is seen in coeliac disease [specifically to the DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. One or more genes at HLA-unlinked loci also predispose to coeliac disease and are probably stronger determinants of disease susceptibility than HLA. A recent study has proposed a number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked susceptibility gene. We have examined these regions in 28 coeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus telomeric to HLA. No significant evidence in favour of linkage to coeliac disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing close to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chromosome 15q26 is not strong, the well established association between coeliac disease and insulin dependent diabetes mellitus, together with the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring susceptibility to coeliac disease in some families.

Celiac Disease↗
PubMed1997

Peptic ulcer bleeding in the elderly: relative roles of Helicobacter pylori and non-steroidal anti-inflammatory drugs.

BACKGROUND: Most ulcers are caused, one can deduce, by Helicobacter pylori or by use of non-steroidal anti-inflammatory drugs (NSAIDs). Whether both together are worse than one alone is something that is quite unknown. AIM: To study both factors in order to see wither they interact together positively. METHOD: A case control study of ulcer bleeding in elderly patients chosen without weeding. RESULTS: NSAID usage increased risk substantially. So did H pylori infection (but relative risk less than three). Neither seemed to interact. Their actions were discretely intact. CONCLUSION: H pylori effects ulcer bleeding in an adverse manner but does not make the risk of NSAIDs worse.

Aged↗
PubMed1997

Influencing the practice and outcome in acute upper gastrointestinal haemorrhage. Steering Committee of the National Audit of Acute Upper Gastrointestinal Haemorrhage.

AIMS: To assess changes in practice and outcome in acute upper gastrointestinal haemorrhage following the feedback of data, the reemphasis of national guidelines, and specific recommendations following an initial survey. DESIGN: A prospective, multicentre, audit cycle. Forty five hospitals from three health regions participated in two phases of the audit cycle. PATIENTS: Phase I: 2332 patients with acute upper gastrointestinal haemorrhage; phase II: 1625 patients with upper gastrointestinal haemorrhage. METHODS: Patients were evaluated with respect to management (with reference to the recommendations in the national guidelines), mortality, and length of hospital stay. RESULTS: Following the distribution of data from the first phase of the National Audit and the formulation of specific recommendations for improving practice, the proportion of hospitals with local guidelines or protocols for the management of upper gastrointestinal haemorrhage rose from 71% (32/45) to 91% (41/45); 12 of the 32 hospitals with guidelines during the first phase revised their guidelines following the initial survey. There was a small but significant increase in the proportion of all patients who underwent endoscopy (from 81% to 86%), the proportion who underwent endoscopy within 24 hours of admission (from 50% to 56%), and the use of central venous pressure monitoring in patients with organ failure requiring blood transfusion or those with profound shock (from 30% to 43%). There was, however, no change in the use of high dependency beds or joint medical/surgical management in high risk cases. There was no significant change in crude or risk standardised mortality (13.4% in the first phase and 14.4% in the second phase). CONCLUSIONS: Although many of the participating hospitals have made efforts to improve practice by producing or updating guidelines or protocols, there has been only a small demonstrable change in some areas of practice during the National Audit. The failure to detect any improvement in mortality may reflect this lack of change of practice, but may also reflect the fact that a large proportion of the deaths in this unselected study are not preventable; only a very large study could hope to demonstrate a significant change out of the context of a clinical trial.

Acute Disease↗
PubMed1996

Selection of patients for early discharge or outpatient care after acute upper gastrointestinal haemorrhage. National Audit of Acute Upper Gastrointestinal Haemorrhage.

BACKGROUND: Acute upper gastrointestinal haemorrhage is a common medical emergency and hospital admission has usually been regarded as obligatory until the risk of further haemorrhage has receded. This policy means that some patients at low risk stay in hospital for longer than is necessary especially when diagnostic endoscopy is delayed. We attempted to identify patients who had negligible risk of further bleeding or death and for whom early discharge or even outpatient management would be possible with no adverse effect on standards of care. METHODS: We used a validated risk scoring system based on age (score 0-2), presence of shock (0-2), comorbidity (0-3), diagnosis (0-2), and endoscopic stigmata of recent haemorrhage (0-2); the maximum possible score was 11. We studied patients identified through the UK national Audit of acute upper gastrointestinal haemorrhage; they had been admitted with upper gastrointestinal haemorrhage to hospitals in the UK during 4 months of 1993. This analysis was based on the 2531 patients from the national audit who underwent endoscopy after an acute admission. FINDINGS: 744 (29.4%) of the 2531 patients scored 2 or less on the risk score. Of these patients only 32 (4.3% [95% Cl 3.0-6.0] rebled and only one (0.1% [0.006-0.75] died). Thus, the risk score identifies patients at low risk of rebleeding or death. The median hospital stay increased with risk score. Within risk score categories of 5 or less, there was a trend of increasing hospital stay as the time between admission and endoscopy increased. INTERPRETATION: Our risk score identifies a large proportion of patients with acute upper gastrointestinal haemorrhage who are at low risk of further bleeding or death. Early endoscopy and discharge of such patients could allow substantial resource savings.

Acute Disease↗