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Biomedical subjects

W Kennedy

Publications and source records attributed to W Kennedy.

At least 19 recordsLinked to original sources
PubMed2004

The cost-effectiveness of high-dose oral proton pump inhibition after endoscopy in the acute treatment of peptic ulcer bleeding.

BACKGROUND: Recent data suggest a role for high-dose oral proton pump inhibition in ulcer bleeding. AIM: To compare the cost-effectiveness of oral high-dose proton pump inhibition to both high-dose intravenous proton pump inhibition and placebo administration. METHODS: The model adopted a 30-day time horizon, and focused on patients with ulcer haemorrhage initially treated endoscopically for high-risk stigmata. Re-bleeding rates were set a priori based on non-head-to-head data from the literature, and charges and lengths of stay from a national American database. Sensitivity analyses were carried across a broad range of clinically relevant assumptions. RESULTS: Re-bleeding rates for patients receiving intravenous, oral, or placebo therapies were 5.9%, 11.8%, and 27%, respectively. The mean lengths of stay and costs for admitted patients with and without re-bleeding were 4.7 and 3 days; $11,802, and $7993, respectively. High-dose intravenous proton pump inhibition was more effective and less costly (dominant) than high-dose oral proton pump inhibition with incremental savings of $136.40 per patient treated. The oral high-dose strategy in turn dominated placebo administration. Results remained robust according to one- and two-way sensitivity analyses. CONCLUSION: In patients undergoing endoscopic haemostasis, subsequent high-dose intravenous proton pump inhibition is more cost-effective than high-dose oral proton pump inhibition, which in turn dominates placebo. The results from this exploratory-type cost analysis require confirmation by head-to-head prospective trials performed in Western populations.

Cost-Benefit Analysis↗
PubMed2004

High-dose intravenous proton pump inhibition following endoscopic therapy in the acute management of patients with bleeding peptic ulcers in the USA and Canada: a cost-effectiveness analysis.

BACKGROUND: The efficacy of high-dose intravenous proton pump inhibition has recently been shown, yet its cost-effectiveness remains poorly studied. AIM: To assess the cost-effectiveness of this approach separately for American and Canadian health care settings. METHODS: A validated decision model included patients with bleeding ulcers after successful endoscopic haemostasis. Probabilities were determined from the literature, and charges and lengths of stay from national databases. A third-party payer perspective was adopted over a 30-day time horizon. RESULTS: Re-bleeding rates were 5.9% for patients who received high-dose intravenous proton pump inhibition and 22.9% for those who did not. Hospitalization costs for patients with and without re-bleeding were 11,802 US dollars and 7993 US dollars, and 5220 Canadian dollars and 2696 Canadian dollars, respectively. High-dose intravenous proton pump inhibition was more effective and less costly than the alternative of not administering it. The cost-effectiveness ratios for high-dose and no high-dose intravenous proton pump inhibition were 9112 US dollars and 11,819 US dollars (3293 dollars and 4284 dollars for the Canadian case), respectively. Sensitivity and threshold analyses showed that the results were robust across a wide range of clinically relevant assumptions. CONCLUSION: In the USA and Canada, administering high-dose intravenous proton pump inhibition for 3 days is both more effective and less costly than not doing so for patients with bleeding ulcers after successful endoscopic haemostasis.

Anti-Ulcer Agents↗
PubMed2003

Adenovirus-mediated gene therapy for bladder cancer: efficient gene delivery to normal and malignant human urothelial cells in vitro and ex vivo.

Existing local therapies for superficial transitional cell carcinoma (TCC) of the bladder have limited success in preventing progression to life-threatening, muscle-invasive disease, and novel therapies are needed. Recent studies have raised doubts concerning the feasibility of adenovirus-mediated gene therapy for bladder cancer. We have therefore investigated adenoviral transduction of normal and malignant human urothelial cells, both as primary cultures and in intact epithelium. All 15 primary normal human urothelial cell lines tested were transduced in vitro by Adv-cmv-beta-gal at high efficiency, and better than most human TCC cell lines. Eight primary human TCC explants were also successfully transduced. In contrast, in intact normal urothelium, transduction efficiency was lower, and occurred only in superficial epithelial layers. Expression of the hCAR adenovirus receptor, however, occurred throughout the full thickness of urothelium. Transduction of human TCC biopsy specimens was at least as efficient as intact normal urothelium.We demonstrate for the first time that adenoviral transduction of both normal and malignant human urothelial cells is feasible. A physical barrier, rather than hCAR status, may be the main determinant of transduction of intact epithelium. Clinical trials of adenovirus-mediated gene therapy for superficial bladder cancer are warranted.

Adenoviruses, Human↗
PubMed2003

Effect of age on the conformity rate to short-acting beta-agonist use criteria in asthma.

STUDY OBJECTIVES: Assess compliance to asthma guidelines and influence of age concerning inhaled short-acting beta2-agonist (SABA) utilization in 5 to 45-year-old asthmatic subjects in the province of Quebec. DESIGN: Population-based retrospective drug utilization review using a computerized database of claims submitted to a private prescription drug insurance plan. PATIENTS: Subjects who received at least one outpatient prescription of SABA (age range, 5 to 45 years) for the treatment of asthma between January 1996 and December 1997. MEASUREMENTS: Percentages of patients whose use was appropriate according to the criteria regarding the average daily dose of SABA. Use was considered appropriate if the consumption rate corresponded to a maximum of two puffs per day (Salbutamol equivalent) in subjects who did or did not use inhaled corticosteroids (ICS) at an estimated maximum dose of 800 mcg/day of Beclomethasone (BDP) equivalent for the 5 to 11-year-olds and 1000 mcg/day for the 12 to 45-year-olds. RESULTS: In 1996, use was found to be appropriate for 74.4% of the 394 patients who received an SABA without ICS as compared with 70.7% for 593 patients in 1997. If we consider those who received an ICS at low to moderate doses, appropriate use was found for 51% of the 375 patients in 1996 and 57.6% for 254 patients in 1997. If we exclude patients who did not renew their SABA, appropriate use drops to 46.3% for 1996 and 34.3% for 1997 for the group who receive SABA without ICS (29.4% and 37.6%, respectively, for those with ICS). There is a relationship between age and appropriateness; the percentage of appropriateness was higher for the younger ones (5 to 14-year-old group; 83% in 1996 and 86% in 1997 for the patients who received a SABA without IS and 58.5% in 1996 and 73% in 1997 for the patients who received a SABA using ICS (p < 0.05). CONCLUSION: Our results indicate that adherence to asthma guidelines concerning SABA is poor. SABA are still overused, particularly among ICS users, which might be explained by undertreatment or poor compliance. Appropriate SABA use was significantly more common among younger groups (p < 0.05). This can be explained by better treatment in that age group, better compliance or less severe asthma.

Administration, Inhalation↗
PubMed2001

Negative regulation of G(1)/S transition by the candidate bladder tumour suppressor gene DBCCR1.

Deletion of all or part of chromosome 9q is the most common genetic alteration in all stages and grades of bladder cancer. DBCCR1 (deleted in bladder cancer chromosome region candidate 1) maps to the chromosome region 9q32-33, a candidate tumour suppressor locus for bladder cancer. Although no mutations of DBCCR1 have been detected in bladder tumours, expression of DBCCR1 is silenced by promoter hypermethylation in 50% of bladder cancer cell lines analysed. Here we sought to provide functional evidence to authenticate DBCCR1 as a tumour suppressor using gene-transfer methods. Exogenous expression of DBCCR1 protein or an HA epitope-tagged fusion protein, HA-DBCCR1 in NIH3T3 cells and human bladder tumour cell lines resulted in suppression of proliferation. Cell cycle analyses in NIH3T3 cells revealed that DBCCR1-mediated growth inhibition was due to an increase in the number of cells in the G(1) phase of the cell cycle. The levels of apoptosis were not altered. These results demonstrate a role for DBCCR1 in cell cycle control, thereby supporting the hypothesis that this is the tumour suppressor gene targeted by 9q32-33 deletion in bladder cancer.

3T3 Cells↗
PubMed2001

Magnetic resonance imaging detection of avascular necrosis of the bone in children receiving intensive prednisone therapy for acute lymphoblastic leukemia or non-Hodgkin lymphoma.

The purpose of this study was to determine the frequency with which magnetic resonance (MR) imaging detects avascular necrosis of the bone (AVNB) in children with acute lymphoblastic leukemia (ALL) or advanced-stage non-Hodgkin lymphoma (NHL) who receive prednisone during remission induction, reinduction, and maintenance chemotherapy; to assess the clinical significance of these findings; and to identify factors predictive of AVNB. We prospectively obtained MR imaging of the hips and knees of 116 children who had completed at least 1 year of treatment for ALL or advanced-stage NHL on identical prednisone-containing regimens between December 1991 and October 1994. MR imaging findings of AVNB were compared with clinical outcomes, and the effect of therapeutic and patient factors on the frequency of AVNB was analyzed. The MR imaging findings of 17 of the 116 participating patients were consistent with AVNB. The most common clinical manifestation was joint pain (11 patients). Only one patient had progressive joint deterioration that necessitated surgical replacement. Only age 10 years or more at the time of the primary diagnosis was significantly associated with the development of AVNB (P = 0.004). MR imaging showed changes consistent with AVNB in approximately 15% of this patient population. However, most patients in this study who had MR imaging signs of AVNB did not experience progressive joint destruction, even with continued prednisone therapy. Therefore, the clinical usefulness of MR imaging as a screening tool for AVNB in this set of patients remains uncertain.

Adolescent↗
PubMed2001

Climbing the ladder: a step by step approach to international guidelines for water recycling.

Given the pressures on the world's freshwater resources, recycled water is a valuable resource. Recycled water can increase the reliability of water supply because it is an independent source of water. Water recycling requires effective measures to protect public health and the environment. In the absence of comprehensive international guidelines, different countries have developed different approaches to managing water recycling depending on the understanding of the health risks, their individual economic circumstances, and affordability. Approaches vary between high technology/high cost/low risk and low technology/low cost/controlled risk. Furthermore, differences occur between countries and within individual countries. Inconsistencies can often be traced to lack of a unified scientific position on health effects. These inconsistencies increase public concerns about health risks and may give rise to conservative controls on responses to water recycling projects that some countries may be unable to afford. In this paper, an international panel of authors discusses how the different water recycling approaches might be linked together into international water recycling guidelines. These guidelines would incorporate a uniform approach to assessing hazards and risks while providing flexibility for individual countries to vary requirements to suit local circumstances of affordability and risk. The authors propose a framework of guidelines in which individual countries can progressively improve recycled water quality as lower risk levels become more affordable. The authors argue that a uniform international approach will result in a number of benefits including a better focus on risk management, better targeted research and development efforts and greater public confidence in water recycling. The authors invite discussion on the concepts put forward in the paper.

Animals↗
PubMed2000

Performance of the ImmunoCard STAT! E. coli O157:H7 test for detection of Escherichia coli O157:H7 in stools.

ImmunoCard STAT! E. coli O157:H7 (Meridian Diagnostics, Inc., Cincinnati, Ohio) is a novel rapid (10-min) test for the presence of Escherichia coli O157:H7 in stools. The test may be performed either directly on stool specimens or on an overnight broth culture of stool. In a multicenter prospective study, 14 of 14 specimens positive by culture for E. coli O157:H7 were positive by the ImmunoCard STAT! O157:H7 test, and there were no false positives from 263 culture-negative specimens. In a retrospective study, the test was positive in 339 (81%) of 417 stored culture-positive specimens and the specificity was 95% (98 of 103 specimens). No false positives were associated with alternate stool pathogens. The ImmunoCard STAT! O157:H7 test has high sensitivity and specificity.

Enzyme-Linked Immunosorbent Assay↗
PubMed1999

Risk scoring, fetal fibronectin, and bacterial vaginosis to predict preterm delivery.

OBJECTIVE: To determine the value of markers for predicting spontaneous preterm birth. METHODS: One hundred forty asymptomatic gravidas were recruited from 20-24 weeks' gestation. Risk score was assessed, vaginal swabs were analyzed for bacterial vaginosis, and cervical and vaginal swab were tested for fetal fibronectin FDC-6, X18A4, and CAF. Univariate analysis was used to determine potential predictors (and combinations of predictors) of outcome. Multiple logistic regression was done to identify independent predictors of spontaneous preterm birth. Sensitivity, specificity, positive and negative predictive values; and odds and likelihood ratios were calculated for significant predictors. RESULTS: Predictors significantly associated with the primary outcome were preterm birth-risk score and vaginal fetal fibronection FDC-6 (logistic regression odds ratio [OR] 16.9 [95% confidence interval (CI) 3.1, 92.8]) and 8.0 ([95% CI 1.6, 38.2], respectively). Bacterial vaginosis, fetal fibronectin X18A4, fibronectin CAF, and cervical fetal fibronectin FDC-6 were not associated with spontaneous preterm birth; however, the statistical power to assess these variables was limited. The combination of positive preterm birth-risk score and vaginal fetal fibronectin FDC-6 had a sensitivity of 44.4%, specificity of 97.7%, positive predictive value of 57.1%, negative predictive value of 96.2%, and a significant likelihood ratio for a positive test of 19.4 (95% CI 5.1, 73.8). CONCLUSION: The combination of preterm birth-risk score and vaginal fetal fibronectin FDC-6 predicted spontaneous preterm birth. Intervention trials are required to determine whether a combination of screening tests will reduce rates of spontaneous preterm birth.

Adult↗
PubMed1999

Cross-Canada spread of methicillin-resistant Staphylococcus aureus via transplant organs.

We report our investigation of the transmission of methicillin-resistant Staphylococcus aureus (MRSA) through transplantation. The kidneys, liver, and corneas were harvested from a child who died in Nova Scotia. Several days postmortem it was learned that culture of a premortem endotracheal tube aspirate from the donor yielded MRSA. Both kidneys were transplanted into a child in Nova Scotia and the liver into a child in Alberta. Both recipients subsequently became blood culture-positive for MRSA. One corneal ring from the donor was MRSA-positive. All four MRSA isolates were mecA-positive by polymerase chain reaction (PCR). The relatedness of the MRSA isolates was examined by restriction fragment length polymorphism (RFLP) analysis, a 16S-23S ribosomal PCR typing method, and comparison of antibiograms. Results were identical for all four MRSA isolates. These findings indicate that MRSA from the donor was transferred to recipients during implantation of harvested organs in Alberta and Nova Scotia, a cross-Canada spread.

Adolescent↗
PubMed1999

Immunophenotype of transitional metaplasia of the uterine cervix.

Transitional, glandular, and squamous epithelia show distinctive patterns of expression of cytokeratins 13, 17, 18, and 20. Furthermore, some markers, such as cytokeratin (CK) 20 and the asymmetric unit membrane, are related to terminal urothelial differentiation, their expression limited to superficial and occasional intermediate cells. In this study, seven cases fulfilling the morphologic criteria of transitional metaplasia of the uterine cervix were investigated with these markers to determine whether there was evidence of true urothelial-type differentiation in these lesions. Results were consistent and showed clear differences between the squamous, glandular, and metaplastic transitional areas of the cervix. In particular, the expression of CK13, CK17, and CK18 in the metaplastic areas was identical to the pattern observed in normal urothelium. However, full urothelial differentiation was not observed, as CK20 and asymmetric unit membrane were never expressed in the transitional metaplasia. Based on these findings, the term of immature transitional metaplasia would be a more accurate description of this entity.

Aged↗
PubMed1999

Rate and cost of hospitalizations for asthma in Quebec: An analysis of 1988/89, 1989/90 and 1994/95 data.

The objectives of this study were to evaluate recent trends in the frequency and length of stay of hospitalization for asthma in the province of Quebec and to estimate the costs of asthma hospitalizations. Data were extracted for persons hospitalized for 30 days or less with a primary diagnosis of asthma in all Quebec short-stay hospitals during the years 1988/89, 1989/90 and 1994/95. There were 1.76 asthma hospitalizations per 1000 persons in Quebec in 1988/89, down to 1.44 in 1989/90 and up again to 1.75 in 1994/95. There was a small decrease in mean length of stay when the three data years were compared. In all three years, the rate of hospitalization was particularly high among young boys. In 1994/95, more hospitalizations occurred during the fall months. We estimated the total cost for asthma hospitalization that year to be $18 to $21 million.

Adolescent↗
PubMed1997

Utilization of anti-asthma medications in two Quebec populations of anti-asthma medication users: a prescription database analysis.

This study describes the utilization of anti-asthma medications in two groups of users of such medications in the province of Quebec, Canada, during the year from June 1, 1990, to May 31, 1991. It is based on a secondary analysis of existing data banks recording the medications reimbursed by two government-funded ambulatory drug reimbursement programs that cover individuals aged 65 and over (seniors) and income security (welfare) recipients (ISRs). The study analyzed the use of the anti-asthma medications included in the list of medications eligible for reimbursement for program beneficiaries. Use was studied in two random samples of individuals who had at least one prescription filled for an anti-asthma medication (2566 seniors and 3695 ISRs). The most commonly used medication in both groups was inhaled salbutamol 100 mcg. Various forms of theophylline tablets were also used by a high proportion of the sample studied. Over 75% of the seniors and 68% of the ISR group used at least one form of theophylline during the course of the year. Inhaled corticosteroids were used by 43% of the seniors and by 36% of the ISR group, and sympathomimetics (beta 2-agonists), by 63% of seniors and 68% of ISRs.

Adolescent↗
PubMed1996

Canadian guidelines for economic evaluation of pharmaceuticals. Canadian Collaborative Workshop for Pharmacoeconomics.

In 1994, Canada became the second country to release national guidelines for the economic evaluation of pharmaceuticals. The guidelines were developed over a period of 18 months through an elaborate process of broad consultation with a wide variety of relevant stakeholders. The intent of the guidelines is to provide guidance to doers and users of studies, by laying out the general 'state of the art' regarding methods, and by providing specific methodological advice on many matters. The aim is to improve the scientific quality and integrity of studies, and to enhance consistency and comparability across studies. This article presents the Canadian guidelines, both in summary and in detail. Because the techniques of economic evaluation are widely applicable beyond pharmaceuticals, the guidelines will be of interest to researchers and decision makers in all fields of healthcare. Because the methods are not country specific, the guidelines will be of interest to those in other countries as well as in Canada.

Canada↗
PubMed1995

Category-specific brain activation in fMRI during picture naming.

Neuropsychological, computational, and psycholinguistic data suggest the existence of semantic maps, i.e. localized representations of semantic information in the brain. Using functional magnetic resonance imaging, this hypothesis was directly tested with a picture naming task involving items from four different semantic categories. Small left lateralized fronto-temporal cortical sites of category-specific activation were found when brain activation signals were averaged. Data suggest the existence of multiple maps coding high-level representations of objects, such that meaningful distinctions, at least in part, govern the physical distribution of cortical semantic storage.

Brain Mapping↗