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Biomedical subjects

J K Marshall

Publications and source records attributed to J K Marshall.

At least 19 recordsLinked to original sources
PubMed2001

Epidemiological aspects of irritable bowel syndrome in Europe and North America.

The epidemiology of irritable bowel syndrome (IBS) in Europe and North America was analyzed from published material. The percentage of the population of Western civilisation with IBS symptoms is between 10 and 15% in most studies. The proportion of a Western population visiting a doctor for IBS symptoms is around 5%. The prevalence of IBS and the proportion of consulters do not seem to depend on age in an adult population. The female-to-male ratio of IBS in the population is close to 2. It is higher in IBS consulters in primary care and may be as high as 3 or 4 in tertiary referral centers. At least in patients from these centers, the number of physician visits and colonoscopies is considerable. Most of the consulters get a drug prescription.

Colonic Diseases, Functional↗
PubMed2001

Incremental cost-effectiveness analysis comparing rofecoxib with nonselective NSAIDs in osteoarthritis: Ontario Ministry of Health perspective.

BACKGROUND: Clinical trials have shown rofecoxib, a selective inhibitor of cyclo-oxygenase-2, to be associated with fewer gastrointestinal complications than non-selective nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVE: To evaluate the potential clinical and economic consequences of rofecoxib prescription in Ontario, Canada, for patients with osteoarthritis (OA) aged >65 years who did not respond to paracetamol (acetaminophen) therapy. DESIGN: Decision analytic modelling study. METHODS: A model was constructed to compare rofecoxib and nonselective NSAIDs with respect to their gastrointestinal complications in patients with OA. The model had a 1-year horizon and considered direct medical costs from the perspective of the Ontario Ministry of Health. Event rates were estimated from a pooled analysis of 8 phase IIb/Ill clinical trials. The number of perforations, ulcers and bleeds (PUBs) with each strategy was used as the primary measure of effectiveness. RESULTS: In the base-case scenario, the expected total cost per patient-day on nonselective NSAIDs was 1.60 Canadian dollars (Can dollars) versus 1.67 Can dollars on rofecoxib (1999 values). Rofecoxib was associated with 0.0109 fewer PUBs per patient per year. The incremental cost to avoid 1 additional PUB by substituting rofecoxib for nonselective NSAIDs was 2247 Can dollars. The rofecoxib strategy became dominant if a gastroprotective agent was prescribed to more than 27.5% of the patients receiving nonselective NSAIDs. CONCLUSION: For patients with OA aged >65 years in whom paracetamol therapy has failed, rofecoxib may represent a cost-effective alternative to nonselective NSAIDs. Increased costs for drug acquisition are offset, in part. by avoidance of gastrointestinal complications and reduced use of gastroprotective agents. Rofecoxib may offer increased benefit among patients at a higher risk of serious gastrointestinal events.

Aged↗
PubMed2001

LDP-02 (Millenium).

Millennium (formerly LeukoSite) and Genentech are developing LDP-02, a humanized monoclonal antibody to the alpha4beta7 integrin receptor on leukocytes, for potential use in the treatment of inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis [274580]. LeukoSite intended to develop iv and sc formulations of LDP-02 for acute IBD [315156]. In December 1997, Genentech entered into a collaboration with LeukoSite to develop and commercialize LDP-02 for the treatment of IBD [275395], [279420]. A phase II SBIR grant was awarded to LeukoSite in September 1996. The US $750,000 grant was used to develop LDP-02 and to conduct preclinical tests on the antibody for the treatment of IBD [218689]. In February 1999, Lehman Brothers predicted the drug had a 10% probability of reaching market. Assuming a successful launch, Lehman Brothers analysts estimated peak sales would occur in 2011 with sales at that time of US $250 million [319225].

Animals↗
PubMed2000

A randomized controlled trial to assess alendronate-associated injury of the upper gastrointestinal tract.

BACKGROUND: Aminobisphosphonates are recommended for postmenopausal osteoporosis but have been associated with injury to the upper gastrointestinal tract. AIM: To conduct a randomized controlled trial, to assess the endoscopic damage caused by alendronate and its effect on gastric mucosal prostaglandin synthesis. METHODS: Seventy-six healthy volunteers age 40-60 years, with normal baseline endoscopy were randomly assigned to treatment with: (A) ASA 650 mg q. d.s.; (B) alendronate 10 mg o.d.; or (C) placebo o.d. for 14 days. Mucosal injury scores on day 14 of treatment were reported by a blinded endoscopist. Gastric biopsies were analysed for prostaglandin E2 (PGE2) concentration by radioimmunoassay. RESULTS: Oesophageal injury did not differ among treatment groups. Gastric ulcers developed in five out of 26 subjects given ASA, two out of 25 given alendronate, and none of 25 given placebo. The mucosal damage scores for the alendronate group exceeded those for the placebo group in the gastric body but not at other sites. Injury scores for ASA exceeded those for placebo in the duodenum, antrum, body, and fundus. The mean change in log10[PGE2] (ng/mg protein) was - 0.07 for placebo, - 0.80 for ASA, and + 0.62 for alendronate (differences not significant). CONCLUSIONS: Alendronate is associated with injury and ulceration of the gastric mucosa. This effect was not associated with any significant change in gastric mucosal PGE2 levels.

Adult↗
PubMed2000

Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk.

Increased intestinal permeability to several specific molecular probes has been observed in patients with Crohn's disease and their first-degree relatives. A positive family history is also a potent risk factor for inflammatory bowel disease. Although it has been argued that increased permeability in relatives may confer an increased future risk of developing Crohn's disease, long-term follow-up of such family members has been lacking. We describe a 24-year-old woman with a positive family history of Crohn's disease who had an elevated gut permeability to (51)Cr-EDTA at age 13, as part of a cross-sectional cohort study in patients and their first-degree relatives. She was asymptomatic at the time, and extensive investigation found no evidence of microscopic or macroscopic Crohn's disease. Repeat investigation because of symptom onset at age 21 revealed ileocolonic Crohn's disease, which required treatment with systemic corticosteroids to induce a clinical remission. In this case, a permeability defect was clearly identified to precede the onset of Crohn's disease in a subject at increased risk. This observation provides support for the hypothesis that increased gut permeability to macromolecules is an early step in the pathogenesis of this disorder.

Adolescent↗
PubMed2000

Putting rectal 5-aminosalicylic acid in its place: the role in distal ulcerative colitis.

Oral aminosalicylates such as sulfasalazine and mesalamine are widely prescribed for the treatment of mild or moderately active distal ulcerative colitis. However, a critical review of the literature demonstrates that rectal 5-aminosalicylic acid (5-ASA) is the optimal therapy for this disease. Meta-analyses of published trials show that rectally delivered 5-ASA is superior to placebo and to conventional rectal corticosteroids in inducing remission of distal ulcerative colitis, whereas the combination of rectal 5-ASA with a rectal corticosteroid or oral aminosalicylate is superior to rectal 5-ASA alone. For maintaining remission of distal ulcerative colitis, rectal 5-ASA is significantly better than placebo and at least as effective as oral 5-ASA. The dosage forms available for rectal delivery include suppositories, foams, and liquid enemas, and selection among these preparations should be guided by the proximal extent of disease and patient preference. The efficacy of rectal 5-ASA is complemented by its low rate of reported adverse effects, which may reflect its reduced potential for systemic absorption. This review summarizes the evidence supporting the role of rectal 5-ASA as a first-line therapy for mild or moderately active distal ulcerative colitis, and offers guidelines for its use.

Administration, Oral↗
PubMed2000

A critical approach to clinical practice guidelines.

The rate of publication of clinical practice guidelines for the management of common medical illnesses continues to accelerate. The appropriate dissemination and uptake of high quality practice guidelines can synthesize evidence, improve patient outcomes and enhance the efficiency of health care delivery. However, the methodological rigour and relevance of the growing number of publications labelled 'clinical practice guidelines' vary widely. Health care payers, providers and advocates must learn to appraise and interpret guideline recommendations critically. A simple and practical nine-question approach to evaluating the quality, relevance and effectiveness of clinical practice guidelines is presented.

Practice Guidelines as Topic↗
PubMed2000

Obscure gastrointestinal bleeding: an approach to management.

Obscure gastrointestinal bleeding provides an uncommon but frustrating and resource-intensive challenge for clinicians. Such patients hemorrhage recurrently from sites within the gastrointestinal tract that are not detected by routine endoscopy or radiography, and require a special diagnostic approach to localize or exclude less common bleeding sources such as small bowel angioectasia or neoplasia. The differential diagnosis of obscure gastrointestinal hemorrhage is discussed, and the performance of available endoscopic, radiological and surgical diagnostic tools including enteroscopy are examined critically. A stepwise management algorithm that progresses from the history and physical examination to surgical exploration is offered to facilitate early and efficient diagnosis.

Angiography↗
PubMed2000

Test and treat strategies for Helicobacter pylori in uninvestigated dyspepsia: a Canadian economic analysis.

BACKGROUND: Recognition of the pivotal role of Helicobacter pylori in the pathogenesis of peptic ulcer disease has revolutionized primary care approaches to dyspepsia. Decision analysis was used to compare the cost effectiveness of empirical ranitidine with a test and treat strategy using either H pylori serology or the 13carbon-urea breath test (13C-UBT). PATIENTS AND METHODS: A cohort of patients under age 50 years presenting with uninvestigated dyspepsia was evaluated. Three initial strategies were compared with respect to direct medical costs and effectiveness in curing H pylori-related ulcers - empirical ranitidine, H pylori serology and UBT. A one-year time horizon and third-party payer perspective were adopted in a Canadian health care setting. RESULTS: UBT was more costly than either serology or ranitidine but was the most effective strategy and required the fewest endoscopies. No strategy demonstrated dominance over another in the base case. The incremental cost effectiveness ratio (ICER) of serology versus ranitidine was $118/cure, and sensitivity analysis induced dominance of serology in several plausible scenarios. The baseline ICER of UBT versus serology was $885/cure but showed substantial variation in sensitivity analysis. Each ICER was highly sensitive to variation in the cost of the tests themselves. At a serology cost of $25, UBT became dominant when its cost fell to $39. CONCLUSIONS: In low risk patients with uninvestigated dyspepsia, testing for H pylori using serology appears to be economically attractive. 13C-UBT may be a cost effective alternative to serology if local conditions closely approximate the model parameters. Future changes in the costs of serology and 13C-UBT may determine the optimal approach.

Anti-Ulcer Agents↗
PubMed1999

Demographic predictors of resource utilization for bleeding peptic ulcer disease: the Ontario GI Bleed Study.

Peptic ulcer disease (PUD) and its complications impose a substantial burden on health care resources. To help identify subpopulations in which preventative measures might achieve maximal cost savings, the authors studied the variation in resource utilization and cost for management of bleeding PUD among demographic subgroups. Resource utilization profiles and direct medical cost estimates were generated for consecutive admissions for bleeding PUD at four hospitals in southern Ontario via chart review and adaptation of an administrative cost database. Multiple linear regression models were developed to identify independent demographic predictors of direct medical case cost and hospital length of stay (LOS). Among 158 admissions, the average LOS and case costs were 5.73 days and $2,953 (Canadian) respectively. Age, comorbid illness, nonsteroidal anti-inflammatory drug use, and the absence of prior PUD or upper gastrointestinal hemorrhage were associated with higher cost in univariate analysis, whereas increasing age and comorbidity predicted LOS. Only age and absence of prior PUD persisted as independent predictors of direct medical cost and LOS in a stepwise multiple linear regression. Costs for managing bleeding PUD vary substantially among demographic subgroups. More careful stratification of treatment costs is needed when economic models of interventions to prevent or to treat PUD are applied to specific subpopulations.

Adult↗
PubMed1999

Prediction of resource utilization and case cost for acute nonvariceal upper gastrointestinal hemorrhage at a Canadian community hospital.

OBJECTIVE: Upper gastrointestinal hemorrhage (UGIH) is common, and thus imposes a substantial burden on health care resources. We describe resource utilization and cost for management of acute nonvariceal UGIH, and studied their variation among population subgroups. METHODS: Resource utilization and direct medical case costs were extracted for consecutive admissions for nonvariceal UGIH at a large community hospital in southern Ontario through chart review and adaptation of an administrative case cost database. Univariate and multiple regression models were then developed to identify independent demographic predictors of case cost and length of stay. RESULTS: Among 116 eligible admissions the average length of stay and case cost were 4.26 days and Can$2690, respectively (Can$1 = US$0.70). Both cost and length of stay demonstrated significant univariate relationships with age, comorbid illness, prior peptic ulcer disease (PUD), and prior UGIH. Age and prior PUD persisted as independent predictors in multiple regression models. An inverse transformation of total case cost allowed these variables to explain 26% of the total variance. CONCLUSIONS: Resource utilization for management of acute nonvariceal UGIH at a Canadian community hospital varies substantially among population subgroups, but correlates independently with age and prior ulcer history. Careful attention must be paid to practice environments and demographic profiles before economic models of strategies to prevent or treat UGIH are applied to specific subpopulations.

Acute Disease↗
PubMed1998

Terminal ileal imaging with ileoscopy versus small-bowel meal with pneumocolon.

Disease of the terminal ileum can be diagnosed by ileocolonoscopy or barium radiography. We compared the diagnostic accuracy in the terminal ileum of ileocolonoscopy and small-bowel meal with pneumocolon. Consecutive patients during an 18-month period who had both ileocolonoscopy and small bowel meal with pneumocolon were identified and their colonoscopy reports, radiographs, and ileal biopsies reviewed blindly by paired gastroenterologists, radiologists, and pathologists, respectively. A gold-standard diagnosis was determined for each patient by consensus. Of 48 study subjects, 14 (29.2%) had Crohn's disease, 5 (10.4%) had lymphoid nodular hyperplasia, and 29 (60.4%) were normal. The sensitivity for a diagnosis of Crohn's ileitis was 92.9% for ileocolonoscopy and 100% for small-bowel meal, while their specificities were 100% and 97.1% respectively. The gold standard diagnosis confirmed ileocolonoscopic findings in 45 patients (93.8%) and radiographic findings in 42 patients (87.5%). Agreement between ileocolonoscopy and small bowel meal occurred in 39 cases (81.2%). By combining histology with ileocolonoscopy, the sensitivity and specificity could be increased to 100% for all diagnoses. Ileocolonoscopy and small-bowel meal with pneumocolon are complementary techniques for imaging the terminal ileum. A prospective comparative trial is now needed to more objectively assess their accuracy, cost effectiveness, and adverse effects.

Adolescent↗
PubMed1998

Omeprazole for refractory gastroesophageal reflux disease during pregnancy and lactation.

Symptomatic gastroesophageal reflux is a common complication of pregnancy and lactation. However, the safety of many effective medical therapies, including oral proton pump inhibitors, has not been well defined. The administration of oral omeprazole to a 41-year-old female during the third trimester of pregnancy, after ranitidine and cisapride failed to control her refractory gastroesophageal reflux, is reported. No adverse fetal effects were apparent, and the patient elected to continue omeprazole therapy (20 mg/day) while breastfeeding. Peak omeprazole concentrations in breast milk (58 nM, 3 h after ingestion) were less than 7% of the peak serum concentration (950 nM at 4 h), indicating minimal secretion. Although omeprazole is a potentially useful therapy for refractory gastroesophageal reflux during pregnancy and lactation, further data are needed to define better its safety and efficacy.

Adult↗
PubMed1997

Hormonal therapy for bleeding gastrointestinal mucosal vascular abnormalities: a promising alternative.

Recurrent bleeding from an obscure gastrointestinal source is a common but often frustrating clinical challenge. Frequently these bleeds can be attributed to vascular anomalies in the upper or lower gastrointestinal tract. Traditional management has included surgical resection and endoscopic fulguration. However, these methods are often ineffective when vascular lesions are diffuse, difficult to identify, or endoscopically inaccessible. Hormone therapy with a combination of oestrogen and progesterone represents a promising alternative. Since initial reports of success in patients with epistaxis from hereditary haemorrhagic telangiectasia, growing evidence supports its role in reducing bleeding from gastrointestinal vascular anomalies. Existing literature is critically reviewed and management strategies incorporating hormone therapy are suggested.

Arteriovenous Malformations↗
PubMed1997

Rectal corticosteroids versus alternative treatments in ulcerative colitis: a meta-analysis.

BACKGROUND: Clear strategies to optimise the use of corticosteroids in ulcerative colitis are lacking. AIM: A meta-analysis was undertaken to examine critically the role of rectal corticosteroids in the management of active distal ulcerative colitis. METHODS: All reported randomised controlled trials were retrieved by searching the Medline and EMBASE databases and the bibliographies of relevant studies. Trials which met inclusion criteria were assessed for scientific rigour. Data were extracted by two independent observers according to predetermined criteria. RESULTS: Of 83 trials retrieved, 33 met inclusion criteria. Pooled odds ratios (POR) showed conventional rectal corticosteroids and rectal budesonide to be clearly superior to placebo. In seven trials, rectal 5-aminosalicylic acid (5-ASA) was significantly better than conventional rectal corticosteroids for inducing remission of symptoms, endoscopy, and histology with POR of 2.42 (95% confidence interval (CI) 1.72-3.41), 1.89 (95% CI 1.29-2.76), and 2.03 (95% CI 1.28-3.20), respectively. Rectal budesonide was of comparable efficacy to conventional corticosteroids but produced less endogenous cortisol suppression. Side effects, although inconsistently reported, were generally minor. A cost comparison of rectal preparations showed 5-ASA to be less expensive than corticosteroids. CONCLUSIONS: Rectal 5-ASA is superior to rectal corticosteroids in the management of distal ulcerative colitis.

Administration, Oral↗
PubMed1997

Successful therapy of refractory erythema nodosum associated with Crohn's disease using potassium iodide.

Erythema nodosum is a common extraintestinal manifestation of Crohn's disease. While mild skin involvement often responds to conservative management, severe or refractory cases may require systemic corticosteroid or immunosuppressive therapy. This report describes successful treatment of severe, refractory erythema nodosum associated with Crohn's colitis using oral potassium iodide. While the mechanism of action of this agent is poorly understood, it appears to be an effective and nontoxic therapy for Crohn's-related erythema nodosum and warrants further evaluation in a placebo controlled trial.

Administration, Oral↗