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Biomedical subjects

John K Marshall

Publications and source records attributed to John K Marshall.

At least 19 recordsLinked to original sources
PubMed2006

The incidence of irritable bowel syndrome among community subjects with previous acute enteric infection.

The purpose of this study was to determine the incidence of postinfectious irritable bowel syndrome (IBS) among community subjects with positive stool studies. This was a prospective cohort study whereby all individuals with stool-positive acute enteric infection (AEI) were recruited from 3 health regions in Ontario, Canada. Each person completed questionnaires regarding preinfectious bowel habit and their bowel habit 3 months postinfection. Manning and Rome I criteria were used to diagnose irritable bowel syndrome. Two hundred thirty-one patients participated. Forty had preexisting IBS and were excluded. Of the remaining 191 patients, 7 developed irritable bowel syndrome, for an incidence of 3.7% (95% confidence interval: 1.0-6.3%). Fever during AEI was the only identifiable risk factor for developing postinfectious IBS (odds ratio, 11.96; P = .02). The incidence of postinfectious IBS in community subjects is 3.7%. Fever during the AEI may be an important risk factor for this condition.

Acute Disease↗
PubMed2006

Randomized active and placebo-controlled endoscopy study of a novel protected formulation of oral alendronate.

Although generally well tolerated, oral aminobisphosphonates have been associated with sporadic cases of severe esophageal injury attributed to pill contact. A novel protected formulation of oral alendronate uses an inert cylindrical shell to prevent mucosal contact with intact tablets. An active and placebo-controlled endoscopy study was undertaken to assess mucosal injury associated with this protected formulation. Healthy volunteers with normal baseline endoscopy were randomly assigned to receive protected alendronate 70 mg/day, standard alendronate 70 mg/day, or placebo for 14 days. Endoscopy was repeated on days 8 and 15. Of 78 subjects, 30 received protected alendronate, 28 received standard alendronate, and 20 received placebo. Mean gastric injury scores did not differ significantly among treatment groups. However, subjects on standard alendronate were more likely than those on protected alendronate to develop severe gastric injury, defined as Lanza score 3 or 4 (67.9% versus 33.3%, P=.009), and more likely to develop a gastric ulcer (21.4% versus 3.3%, P=.015). No differences in symptoms or adverse events were observed. In conclusion, a novel protected formulation of oral alendronate is less likely than standard alendronate to induce severe mucosal injury to the upper gastrointestinal tract.

Administration, Oral↗
PubMed2006

Incidence and epidemiology of irritable bowel syndrome after a large waterborne outbreak of bacterial dysentery.

BACKGROUND & AIMS: Postinfectious irritable bowel syndrome (PI-IBS) is a common clinical phenomenon. To better define its incidence and epidemiology, a large cohort study was initiated after the contamination of a municipal water supply led to a large outbreak of acute Escherichia coli 0157:H7 and Campylobacter jejuni gastroenteritis. METHODS: Local residents were invited to undergo structured assessments at research clinics established 2 years after the outbreak. Permanent adult residents with no prior history of inflammatory bowel disease or IBS were eligible. Standardized questionnaires defined past and current health. The cohort was divided into controls without gastroenteritis, subjects with clinically suspected gastroenteritis, and subjects with only self-reported gastroenteritis that could not be substantiated by another source. A modified Bowel Disease Questionnaire identified IBS according to Rome criteria. The incidence and epidemiology of PI-IBS was characterized. Risk factors were assessed using multiple logistic regression. RESULTS: There were 2069 eligible study participants. Rome I criteria were met by 71 of 701 controls (10.1%) vs 249 of 904 subjects with self-reported gastroenteritis (27.5%) and 168 of 464 subjects with clinically suspected gastroenteritis (36.2%) (all comparisons, P < 001). Independent risk factors for PI-IBS included younger age, female sex, bloody stools, abdominal cramps, weight loss, and prolonged diarrhea. PI-IBS was more likely than sporadic IBS to show diarrhea-predominant features. CONCLUSIONS: PI-IBS is common after gastroenteritis from water contamination and often is diarrhea-predominant. Characteristics of the acute illness identify patients at increased risk for PI-IBS.

Campylobacter Infections↗
PubMed2006

Functional gastrointestinal disorders and mood disorders in patients with inactive inflammatory bowel disease: prevalence and impact on health.

BACKGROUND: Symptoms of functional gastrointestinal disorders (FGID) associated with mood disorders (MD), such as depression and anxiety, occur in some patients with quiescent inflammatory bowel disease (IBD) and could be caused by changes in gut motility, visceral hypersensitivity, or psychological dysfunction. We assessed the prevalence of FGID symptoms and mood disorders in ambulatory patients with quiescent IBD and examined their impact on health-related quality of life (HRQOL) and use of health resources. METHODS: Consecutive ambulatory patients with IBD completed a survey of Rome II criteria for FGID, the Hospital Anxiety and Depression Survey, HRQOL indices, and health resource utilization. Logistic and linear regression analyses tested for predictors of FGID and HRQOL. RESULTS: Of 361 patients surveyed, 149 (44 ulcerative colitis [UC] and 105 Crohn's disease [CD]) had inactive IBD during the previous 12 months. Symptoms of at least 1 FGID occurred in 81.9%. Functional anorectal disorders were the most prevalent (53.7%) followed by functional bowel disorders (51.7%), and both were of greater prevalence than in the Canadian population (41.6% and 22.6%, respectively). Irritable bowel syndrome symptoms were more common in inactive CD than in UC (26% versus 9.1%, P = .01) and functional constipation was more common in inactive UC than in CD (26.2% versus 5.8%, P < .01). MD occurred in 27.3% of UC and 31.3% of CD patients. Age > or =40 years and anxiety independently predicted an FGID. Both FGID symptoms and MD were associated with impaired HRQOL and increased use of health services. CONCLUSIONS: Many patients with inactive IBD have symptoms compatible with FGID. Both FGID-like symptoms and MD are associated with impaired HRQOL and increased health resource utilization. Recognition and treatment of FGID and MD could potentially improve daily functioning of IBD patients.

Adult↗
PubMed2005

CD23-mediated IgE transport across human intestinal epithelium: inhibition by blocking sites of translation or binding.

BACKGROUND & AIMS: In previous studies in rodent models of food allergy, we identified that sensitization induces expression of CD23 on intestinal epithelial cells and results in enhanced IgE-dependent transepithelial antigen uptake; further studies in CD23-/- mice provided evidence that CD23 is involved in protected transport of antigen into the body. Little information exists in humans on receptor-mediated immunoglobulin (Ig)E transport across epithelia. The present study was designed to examine expression of CD23 by human epithelial cells, determine its isoform and regulation by interleukin (IL) 4, and identify the role of CD23 in transepithelial IgE transport. METHODS: Epithelial expression of CD23 was studied in cell lines, ileal biopsy specimens, and explanted fetal intestine. Bidirectional transport of IgE was measured across filter-grown cells, either normal cells or those transfected with antisense CD23 oligonucleotides, or in the presence of blocking antibody. RESULTS: Expression of the low-affinity IgE receptor was demonstrated in cultured epithelial cells as well as in situ cells in human intestine. CD23b was the isoform expressed by HT29, T84, and Caco-2 cells. IL-4 up-regulated the expression of epithelial CD23. IgE was transported in both the basal-to-apical direction and the apical-to-basal direction across filter-grown epithelial cells, a process that was inhibited by transfection of cells with CD23 antisense oligonucleotides or pretreatment with nonspecific IgE or anti-CD23 antibody. CONCLUSIONS: These findings provide evidence that CD23 encodes a functional IgE receptor on human intestinal epithelial cells and that this epithelial receptor is likely to play an important role in food allergies.

Antigens, CD↗
PubMed2005

The impact of reference pricing of nonsteroidal anti-inflammatory agents on the use and costs of analgesic drugs.

OBJECTIVE: To estimate the effect of reference pricing (RP) of nonsteroidal anti-inflammatory drugs (NSAIDs) on drug subsidy program and beneficiary expenditures on analgesic drugs. DATA SOURCES/STUDY SETTING: Monthly claims data from Pharmacare, the public drug subsidy program for seniors in British Columbia, Canada, over the period of February 1993 to June 2001. STUDY DESIGN: RP limits drug plan reimbursement of interchangeable medicines to a reference price, which is typically equal to the price of the lowest cost interchangeable drug; any cost above that is borne by the patient. Pharmacare introduced two different forms of RP to the NSAIDs, Type 1 in April 1994 and Type 2 in November 1995. Under Type 1 RP, generic and brand versions of the same NSAID are considered interchangeable, whereas under Type 2 RP different NSAIDs are considered interchangeable. We extrapolated average reimbursement per day of NSAID therapy over the months before RP to estimate what expenditures would have been without the policies. These counterfactual predictions were compared with actual values to estimate the impact of the policies; the estimated impacts on reimbursement rates were multiplied by the postpolicy volume of NSAIDS dispensed, which appeared unaffected by the policies, to estimate expenditure changes. PRINCIPAL FINDINGS: After Type 2 RP, program expenditures declined by $22.7 million (CAN), or $4 million (CAN), annually cutting expenditure by about half. Most savings accrued from the substitution of low-cost NSAIDs for more costly alternatives. About 20 percent of savings represented expenditures by seniors who elected to pay for partially reimbursed drugs. Type 1 RP produced one-quarter the savings of type 2 RP. CONCLUSIONS: Type 2 RP of NSAIDs achieved its goal of reducing drug expenditures and was more effective than Type 1 RP. The effects of RP on patient health and associated health care costs remain to be investigated.

Aged↗
PubMed2005

Canadian Consensus Conference on the management of gastroesophageal reflux disease in adults - update 2004.

BACKGROUND: Gastroesophageal reflux disease (GERD) is the most prevalent acid-related disorder in Canada and is associated with significant impairment of health-related quality of life. Since the last Canadian Consensus Conference in 1996, GERD management has evolved substantially. OBJECTIVE: To develop up-to-date evidence-based recommendations relevant to the needs of Canadian health care providers for the management of the esophageal manifestations of GERD. CONSENSUS PROCESS: A multidisciplinary group of 23 voting participants developed recommendation statements using a Delphi approach; after presentation of relevant data at the meeting, the quality of the evidence, strength of recommendation and level of consensus were graded by participants according to accepted principles. OUTCOMES: GERD applies to individuals who reflux gastric contents into the esophagus causing symptoms sufficient to reduce quality of life, injury or both; endoscopy-negative reflux disease applies to individuals who have GERD and a normal endoscopy. Uninvestigated heartburn-dominant dyspepsia - characterised by heartburn or acid regurgitation - includes erosive esophagitis or endoscopy-negative reflux disease, and may be treated empirically as GERD without further investigation provided there are no alarm features. Lifestyle modifications are ineffective for frequent or severe GERD symptoms; over-the-counter antacids or histamine H2-receptor antagonists are effective for some patients with mild or infrequent GERD symptoms. Proton pump inhibitors are more effective for healing and symptom relief than histamine H2-receptor antagonists; their efficacy is proportional to their ability to reduce intragastric acidity. Response to initial therapy - a once-daily proton pump inhibitor unless symptoms are mild and infrequent (fewer than three times per week) - should be assessed at four to eight weeks. Maintenance medical therapy should be at the lowest dose and frequency necessary to maintain symptom relief; antireflux surgery is an alternative for a small proportion of selected patients. Routine testing for Helicobacter pylori infection is unnecessary before starting GERD therapy. GERD is associated with Barrett's epithelium and esophageal adenocarcinoma but the risk of malignancy is very low. Endoscopic screening for Barrett's epithelium may be considered in adults with GERD symptoms for more than 10 years; Barrett's epithelium and low-grade dysplasia generally warrant surveillance; endoscopic or surgical management should be considered for confirmed high-grade dysplasia or malignancy. CONCLUSION: Prospective studies are needed to investigate clinically relevant risk factors for the development of GERD and its complications; GERD progression, on and off therapy; optimal management strategies for typical GERD symptoms in primary care patients; and optimal management strategies for atypical GERD symptoms, Barrett's epithelium and esophageal adenocarcinoma.

Adult↗
PubMed2004

Prospective comparison of small bowel meal with pneumocolon versus ileo-colonoscopy for the diagnosis of ileal Crohn's disease.

BACKGROUND AND AIMS: Both endoscopy and barium radiography are used routinely to diagnose terminal ileal (TI) Crohn's disease (CD). A prospective study was undertaken to compare ileoscopy with biopsy to small bowel meal with pneumocolon (SBMP) in patients with suspected TI CD. METHODS: A cohort of outpatients investigated for diarrhea with features of TI disease underwent SBMP followed by colonoscopy with ileal intubation and biopsy within 21 days. All results were reported in a standardized, sequential format to assign SBMP TI diagnoses by the duty radiologist and by dual reading with consensus, ileoscopy by the attending endoscopist, and ileoscopy with biopsy by a blinded panel of endoscopists and pathologists. Reference standard TI diagnoses were determined by a consensus panel with full access to medical records. RESULTS: Among 120 subjects, the reference standard TI diagnosis was normal in 47 (39.1%), lymphoid nodular hyperplasia (LNH) in 24 (20.0%), CD in 48 (40.0%), and NSAID enteropathy in 1 (0.9%). Colonoscopy provided TI images and/or biopsies in 97 cases (80.8%), while SBMP provided TI images in 119 (99.1%). When ileoscopy with biopsy succeeded, its accuracy was similar to SBMP with dual reading (89.7%vs 89.9%, p = NS) but superior to SBMP if interpreted only by the duty radiologist (80.0%, p < 0.05). Biopsy improved the accuracy of ileoscopy, while dual reading improved that of SBMP. Both ileoscopy with biopsy and SBMP with dual reading are highly accurate for diagnosing TI CD. Choice of initial test should reflect local expertise and availability, and the likelihood of associated disease in the proximal small bowel or colon.

Adolescent↗
PubMed2003

Consensus recommendations for managing patients with nonvariceal upper gastrointestinal bleeding.

BACKGROUND: The management of patients with acute nonvariceal upper gastrointestinal bleeding has evolved substantially over the past 10 years amid a paucity of published consensus guidelines. PURPOSE: To provide evidence-based management recommendations that address clinically relevant issues. REVIEW AND CONSENSUS PROCESSES: A multidisciplinary consensus group of 25 voting participants representing 11 national societies used a 7-step approach to develop recommendation statements according to accepted standards. Sources of data included narrative and systematic reviews as well as published and new meta-analyses. The quality of the evidence, the strength of the recommendation, and the level of consensus were graded according to recognized classifications. MAIN FINDINGS: Recommendations emphasize appropriate initial resuscitation of the patient and a multidisciplinary approach to clinical risk stratification that determines the need for early endoscopy. Early endoscopy allows safe and prompt discharge of selected patients classified as low risk. Endoscopic hemostasis is reserved for patients with high-risk endoscopic lesions. Although monotherapy with injection or thermal coagulation is effective, the combination is superior to either treatment alone. The placement of endoscopic clips for endoscopic hemostasis appears promising. High-dose intravenous proton-pump inhibition is recommended in patients who have undergone successful endoscopic therapy. Routine second-look endoscopy is not recommended. Patients with upper gastrointestinal bleeding should be tested for Helicobacter pylori infection and receive eradication therapy if infection is present. FUTURE DIRECTIONS: The efficacy of newer endoscopic therapeutic technologies, the optimal regimen of proton-pump inhibition, and the roles of other pharmacologic agents require further research.

Endoscopy, Gastrointestinal↗
PubMed2002

Impact of reference-based pricing for histamine-2 receptor antagonists and restricted access for proton pump inhibitors in British Columbia.

BACKGROUND: Two programs to reduce expenditures for common gastrointestinal drugs were introduced simultaneously by British Columbia (BC) Pharmacare in 1995. Reference-based pricing restricted reimbursement for all histamine-2 receptor antagonists (H2RAs) to the cost of the least expensive H2RA available, generic cimetidine. Special authority restricted reimbursement for proton pump inhibitors (PPIs) to patients who met certain eligibility criteria. We evaluated the effect of reference-based pricing for H2RAs and special authority for PPIs on dispensing and reimbursement for senior citizen beneficiaries of BC Pharmacare. METHODS: Itemized monthly claims data for upper gastrointestinal drugs were obtained from BC Pharmacare for all beneficiaries 65 years of age or older. Periods before and after implementation of reference-based pricing and special authority were compared with respect to defined daily doses dispensed per 100,000 beneficiaries, BC Pharmacare reimbursement per 100,000 beneficiaries, BC Pharmacare reimbursement per defined daily dose and beneficiary contributions per defined daily dose. We used regression models to project forward trends in expenditures observed before implementation of the new policies and hence to estimate accrued cost savings. RESULTS: Before reference-based pricing and special authority, the numbers of defined daily doses that were dispensed and total BC Pharmacare reimbursements for H2RAs appeared to be declining gradually, whereas those for PPIs were rising. With reference-based pricing, the monthly defined daily dose of cimetidine dispensed increased more than 4-fold, to 116,257 per 100,000 beneficiaries, while those of other restricted H2RAs decreased by more than half, to 50,927 per 100,000 beneficiaries. Special authority immediately reduced the dispensed volumes of PPIs by one-fourth, but growth in volume then appeared to resume at its previous rate. The estimated annualized cost savings achieved by reference-based pricing and special authority were $1.8 million to $3.2 million for H2RAs (depending on the estimation method used) and $5.5 million for PPIs. However, beneficiary contributions for H2RAs increased from negligible amounts to approximately 16% of total drug expenditures. INTERPRETATION: Reference-based pricing and special authority appear to have been successful in altering prescribing habits and reducing provincial expenditures for upper gastrointestinal drugs, but they have increased the financial burden on senior citizen beneficiaries.

Aged↗
PubMed2002

Minimizing postcolonoscopy abdominal pain by using CO(2) insufflation: a prospective, randomized, double blind, controlled trial evaluating a new commercially available CO(2) delivery system.

BACKGROUND: Abdominal pain after colonoscopy is a common, distressing symptom resulting from bowel distension by insufflated gas. CO(2), unlike air, is rapidly cleared from the colon by passive absorption. A commercially available CO(2) delivery system has only recently become available. The effects of CO(2) and air insufflation on residual bowel gas and postprocedure pain were compared. METHODS: One hundred patients were randomized to undergo colonoscopy with insufflation of air (n = 51) or CO(2) (n = 49) by means of a regulator; 97 patients completed the study. Patients with active GI bleeding, inflammatory bowel disease, or previous colectomy were excluded. Pain scores (ordinal scale: 0 = none, to 5 = extreme) were recorded immediately after colonoscopy and at 1, 6, and 24 hours. Residual colonic gas was evaluated on abdominal radiographs at 1 hour. RESULTS: Residual colonic gas and postprocedural pain at 1 and 6 hours were significantly less in the CO(2) group. 71% of patients insufflated with room air had colonic distension in excess of 6 cm versus 4% for those in the CO(2) group. 94% of patients insufflated with CO(2) had minimal colonic gas versus 2% in whom air was used (p < 0.0001). Of patients insufflated with air, 45% and 31% had pain at, respectively, 1 hour and 6 hours, versus 7% and 9%, respectively, for those insufflated with CO(2) (respectively, p < 0.0001 and p < O.02). No complications resulted from use of the CO(2) delivery system. CONCLUSIONS: Insufflation of CO(2) rather than air significantly reduces abdominal pain and bowel distension after colonoscopy. CO(2) may be insufflated safely and effectively with the new CO(2) delivery system.

Abdominal Pain↗
PubMed2002

Use and misuse of cost-effectiveness terminology in the gastroenterology literature: a systematic review.

OBJECTIVES: The increased popularity of economic analyses for evaluating medical interventions has given rise to concern about the rigor with which economic constructs and terminology are used. True cost-effectiveness analysis considers both the costs and outcomes of alternative interventions. A systematic review of the gastroenterology literature was undertaken to evaluate how appropriately cost-effectiveness is assessed. METHODS: A structured MEDLINE search identified all studies published in major gastroenterology journals between 1980 and 1998 that claimed in their abstracts to have assessed the cost-effectiveness of an intervention. Blinded copies of eligible studies were assessed by two independent reviewers who used standard criteria to evaluate the use of economic terminology and key economic constructs. Discrepancies were resolved by consensus. Studies met a "broad criterion" for appropriateness by evaluating both costs and effects and a "strict criterion" by demonstrating dominance of one strategy or considering both incremental costs and incremental effects. RESULTS: Of 110 eligible studies, 77 (70.0%) met the broad criterion and 62 (56.4%) met the strict criterion for appropriateness. This did not seem to vary with either journal impact factor or publication year. Only eight of 18 studies reporting an incremental cost-effectiveness ratio compared its value to an external standard. Few studies explicitly stated their analytic perspective, and a minority of those with time horizons longer than 1 yr had discounted future costs or effects. CONCLUSIONS: Although most studies seem to use cost-effectiveness terminology well, there remains room to improve the rigor with which economic terminology and constructs are applied.

Canada↗
PubMed2002

Resource utilization for acute lower gastrointestinal hemorrhage: the Ontario GI bleed study.

OBJECTIVES: Acute lower gastrointestinal hemorrhage (LGIH) is a common indication for hospitalization. However, there are few published studies of related health care resource utilization. Resource utilization, length of stay (LOS) and direct medical costs were characterized in a cohort of patients admitted for nonmalignant LGIH to centres in Ontario. METHODS: Consecutive admissions for LGIH were identified at four Ontario hospitals. Profiles of resource utilization, LOS and estimates of direct medical costs were compiled through detailed chart review and adaptation of an administrative database. All centres were participants in the Ontario Case Cost Project. Linear regression models of log-transformed data were constructed to identify demographic variables predictive of LOS and case cost. RESULTS: Among 124 patients enrolled (mean age 58.8 years) the average case cost was dollars 4832 (SD dollars 7187) for 7.5 days in hospital (SD 12.0). Diverticular disease was the bleeding source most often identified (34.6%), followed by hemorrhoids (13.7%) and ischemic colitis (9.7%). Older age and comorbid illness, specifically coronary artery disease (CAD), were associated with both increased LOS and higher case cost in univariate regression analyses. Age persisted as the lone independent predictor of LOS in the multivariate model (P<0.05, R2=0.076), and age and CAD were both independent predictors of cost (P<0.05, R2=0.109) in a stepwise multiple linear regression analysis. Neither sex nor nonsteroidal anti-inflammatory drug use predicted LOS or cost. CONCLUSIONS: Admissions for acute LGIH are associated with significant resource utilization, particularly among elderly patients with CAD.

Acute Disease↗
PubMed2002

The gastrointestinal tolerability and safety of oral bisphosphonates.

Oral bisphosphonates are effective for osteoporosis and other hyperresorptive bone disorders. Although well-tolerated in efficacy trials, some oral aminobisphosphonates have been associated with upper gastrointestinal intolerance and injury in postmarketing experience. Clinical trials often underestimate the rate of adverse events in clinical practice, and ethics prohibit direct evaluation of toxicity in high-risk patients. Accordingly, animal models and endoscopy studies of oral bisphosphonates provide valuable insight. It is unclear whether variation in ulcerogenic potential reflects differences in dosing, formulation or chemical structure. Furthermore, the clinical relevance of endoscopic lesions is uncertain. Ongoing postmarketing review will determine whether differences in endoscopic damage predict tolerability and safety in clinical practice. However, physicians and patients should consider risk factors for oesophageal injury when initiating therapy.

Administration, Oral↗