International cross-cultural validation study of the Canadian haemophilia outcomes: kids' life assessment tool.

Health-related quality of life (HRQoL) assessment is recognized as an important outcome in the evaluation of different therapeutic regimens for persons with haemophilia. The Canadian Haemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT) is a disease-specific measure of HRQoL for 4 to 18-year-old boys with haemophilia. The purpose of this study was to extend this disease-specific, child-centric, outcome measure for use in international clinical trials. We adapted the North American English CHO-KLAT version for use in five countries: France, Germany, the Netherlands, Spain and the United Kingdom (UK). The process included four stages: (i) translation; (ii) cognitive debriefing; (iii) validity assessment relative to the PedsQL (generic) and the Haemo-QoL (disease-specific) and (iv) assessment of inter and intra-rater reliability. Cognitive debriefing was performed in 57 boys (mean age 11.4 years), validation was performed in 144 boys (mean age 11.0 years) and reliability was assessed for a subgroup of 64 boys (mean age 12.0 years). Parents also participated. The mean scores reported by the boys were high: CHO-KLAT 77.0 (SD = 11.2); PedsQL 83.8 (SD = 11.9) and Haemo-QoL 79.6 (SD = 11.5). Correlations between the CHO-KLAT and PedsQL ranged from 0.63 in Germany to 0.39 in the Netherlands and Spain. Test-retest reliability (concordance) for child self-report was 0.67. Child-parent concordance was slightly lower at 0.57. The CHO-KLAT has been fully culturally adapted and validated for use in five different languages and cultures (in England, the Netherlands, France, Germany and Spain) where treatment is readily available either on demand or as prophylaxis.

Process and experience of cross-cultural adaptation of a quality of life measure (CHO-KLAT) for boys with haemophilia in Brazil.

Health-related quality of life (HRQoL) is an important outcome from the perspective of boys with haemophilia and their parents. Few studies have captured the HRQoL of boys with haemophilia in developing countries. This article reports on the cross-cultural adaptation of the Canadian Haemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT) for use in São Paulo, Brazil. The CHO-KLAT(2.0) was translated into Portuguese, and then translated back into English. The original English and back-translation versions were compared by a group of three clinicians, whose first language was Portuguese. The resulting Portuguese version was assessed through a series of cognitive debriefing interviews with children and their parents. This process identified concepts that were not clear and revised items to ensure appropriate understanding through an iterative process. The initial back-translation was not discrepant from the original English version. We made changes to 66% of the CHO-KLAT(2.0) items based on clinical expert review and 26% of the items based on cognitive debriefings. In addition, two new items were added to the final Portuguese version to reflect the local cultural context. The final result had good face validity. This process was found to be extremely valuable in ensuring the items were accurately interpreted by the boys/parents in São Paulo Brazil. The results suggest that professional translators, clinical experts and cognitive debriefing are all required to achieve a culturally appropriate instrument. The Portuguese CHO-KLAT(2.0) is well understood by Sao Paulo boys/parents. The next step will be to test its validity and reliability locally.

Health care services utilization stratified by virological and immunological markers of HIV: evidence from a universal health care setting.

OBJECTIVE: The aim of the study was to determine rates of utilization of in-patient, out-patient and laboratory services stratified by virological and immunological markers of HIV disease among patients on antiretroviral treatment in British Columbia, Canada. METHODS: We estimated resource utilization for in-patient visits, out-patient visits, and laboratory tests among patients initiating antiretroviral treatment between 1 April 1994 and 31 December 2000, with follow-up to 31 March 2001. Resource use was stratified by CD4 cell count and plasma HIV viral load (pVL) at the time of utilization and rates per 100 patient-years were calculated for each health care resource. RESULTS: A total of 2718 patients were included in our analyses. The overall rates of in-patient visits, out-patient visits, and laboratory tests were 902, 3001 and 840 per 100 patient-years, respectively. Utilization was higher for patients with low CD4 cell counts and high pVLs when compared with patients with high CD4 cell counts and low pVLs. CONCLUSIONS: Patients with low CD4 cell counts and high pVLs had the highest use of health care services. Regular follow-up with health care providers in an out-patient setting, allowing for proper monitoring and maintenance of HIV care, is important in minimizing unnecessary and potentially costly in-patient care.

Cost-effectiveness of losartan-based therapy in patients with hypertension and left ventricular hypertrophy: a UK-based economic evaluation of the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study.

The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study demonstrated the clinical benefit of losartan-based therapy in hypertensive patients with left ventricular hypertrophy (LVH), mainly due to a highly significant 25% reduction in the relative risk of stroke compared with an atenolol-based regimen, for a similar reduction in blood pressure. The aim of this economic evaluation was to estimate the cost-effectiveness of losartan compared with atenolol from a UK national health system perspective. Quality-adjusted survival and direct medical costs were modelled beyond the trial using the within-trial incidence of stroke. Survival with stroke, study medication use and quality of life by stroke status were taken directly from the LIFE trial. The LIFE data were supplemented with UK data on lifetime direct medical costs of stroke and life expectancy in individuals without stroke. No additional stroke events or use of study treatment were assumed beyond the trial. Costs and benefits were discounted using current UK Treasury rates. In the base-case analysis, the reduction in stroke-related costs (by 968 sterling pound) offset 86% of the increase in study medication costs (1128 sterling pound) among losartan-treated patients. The incremental cost-effectiveness ratio (ICER) for losartan versus atenolol in hypertensive patients with LVH was 2130 sterling pound per quality-adjusted life year (QALY) gained (3195 Euro/QALY), and this increased to 11,352 sterling pound per QALY gained (16,450 Euro/QALY) when the costs of stroke beyond the first 5 years were excluded. Thus, the clinical benefit of losartan was achieved at a cost well within reported thresholds for cost-effectiveness.

A test of worker policing theory in an advanced eusocial wasp, Vespula rufa.

Mutual policing is an important mechanism for maintaining social harmony in group-living organisms. In some ants, bees, and wasps, workers police male eggs laid by other workers in order to maintain the reproductive primacy of the queen. Kin selection theory predicts that multiple mating by the queen is one factor that can selectively favor worker policing. This is because when the queen is mated to multiple males, workers are more closely related to queen's sons than to the sons of other workers. Here we provide an additional test of worker policing theory in Vespinae wasps. We show that the yellowjacket Vespula rufa is characterized by low mating frequency, and that a significant percentage of the males are workers' sons. This supports theoretical predictions for paternities below 2, and contrasts with other Vespula species, in which paternities are higher and few or no adult males are worker produced, probably due to worker policing, which has been shown in one species, Vespula vulgaris. Behavioral observations support the hypothesis that V. rufa has much reduced worker policing compared to other Vespula. In addition, a significant proportion of worker-laid eggs were policed by the queen.

Application of a propensity score to adjust for channelling bias with NSAIDs.

PURPOSE: To compare the relative risks of upper GI haemorrhage (UGIH) in users of Newer versus Older, non-specific NSAIDs when adjusted for channelling bias by regression on individual covariates, a propensity score and both. METHODS: Cohort study of patients prescribed NSAIDs between June 1987 and January 2000. Exposure to Newer and Older non-specific NSAIDs was identified, and risk factors evaluated for each patient. Results of multiple covariate analyses and the propensity scoring technique to assess potential channelling bias in comparisons between Newer and Older non-specific NSAIDs were compared. RESULTS: This study included 7.1 thousand patient years (tpy) exposure to meloxicam, 1.6 tpy exposure to coxibs, and 628 tpy exposure to Older non-specific NSAIDs. Patients receiving Newer NSAIDs were older, more likely to have a history of GI symptoms, and at higher risk for GI complications. Adjusting for these risk factors reduced the relative risks of UGIH on meloxicam and coxibs versus Older non-specific NSAIDs to 0.84 (95%CI 0.60, 1.17) and 0.36 (0.14, 0.97) respectively. CONCLUSIONS: Channelling towards high GI risk patients occurred in the prescribing of Newer NSAIDs. Propensity scores highlighted the markedly different risk profiles of users of Newer and Older non-specific NSAID. Correcting for channelling bias, coxib exposure, but not meloxicam exposure, was associated with less UGIH than Older non-specific NSAID exposure. In the present study, corrections made by regression on a propensity score and on individual covariates were similar.

Population impact of losartan use on stroke in the European Union (EU): projections from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study.

The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study was designed to compare losartan- vs atenolol-based antihypertensive treatment on cardiovascular morbidity and mortality in a population of 9193 hypertensive patients with left ventricular hypertrophy (LVH). In LIFE, the losartan-based treatment further reduced the primary composite end point (cardiovascular death, myocardial infarction, or stroke) by 13% (risk reduction (RR) 0.87, 95% confidence interval (CI) 0.77-0.98, P=0.021). The further reduction in stroke with losartan (RR 0.75, 95% CI 0.63-0.89, P=0.001) was the major contributing factor to the reduction in the primary end point. Our objective was to project the reduction in stroke observed with a losartan- vs an atenolol-based antihypertensive treatment regimen in the LIFE study to the European Union (EU) population. The number of stroke events averted was estimated by identifying the number of persons in the EU expected to meet the LIFE inclusion criteria, and multiplying this figure by the cumulative incidence risk difference in stroke from LIFE at 5.5 years. The age- and gender-specific prevalence of hypertension, electrocardiographically (ECG)-diagnosed LVH among those with hypertension (inclusion criteria), and heart failure among those with LVH and hypertension (exclusion criteria) were applied to the EU census estimates. We conservatively projected that an estimated 7.8 million individuals aged 55-80 years in the EU are affected by hypertension and ECG-diagnosed LVH. Use of a losartan-based antihypertensive treatment in this population is projected to prevent approximately 125 000 first strokes over a 5.5-year period. A population-wide prevention strategy of using losartan in patients with LVH and hypertension has the potential to have a major public health impact by reducing the morbidity and mortality of stroke in the EU.

Adherence to proton pump inhibitors or H2-receptor antagonists during the use of non-steroidal anti-inflammatory drugs.

BACKGROUND: The efficacy of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) prescribed as prophylaxis for NSAID-related upper gastrointestinal (UGI) toxicity is dependent upon patient adherence. AIM: To describe patient adherence to prophylactically prescribed PPIs and H2RAs in the clinical setting. METHODS: We conducted a retrospective observational cohort study using the Integrated Primary Care Information Project database. The study population consisted of incident non-specific NSAID users prescribed a PPI or H2RA specifically as prophylaxis for NSAID-related UGI toxicity. Patients were classified as non-adherent if < 75% of days of NSAID use were covered by one of these agents, and as continuing users after discontinuation of NSAID use if they had a renewed prescription for these agents after their last NSAID prescription. RESULTS: The study cohort comprised 784 patients: 374 with H2RAs, 405 with PPIs, and 5 with both PPI and H2RA. Eighty-five percent of H2RA users and 7% of PPI users were prescribed these drugs at doses below the minimum recommended/effective dose for NSAID-associated gastroduodenal ulcer prophylaxis. Thirty-seven percent of patients were non-adherent. The lowest rate of non-adherence was associated with the first NSAID prescription (9%), increasing to 61% for patients with >/= 3 prescriptions. In a cohort of subjects who stopped their NSAID and were followed for up to 2 years (n = 711), there was significant persistent use of acid suppressive agents; 40% of patients had at least one additional prescription for the acid suppressive agent after stopping NSAIDs, and> 30% received enough drug to cover a period longer than 2 months after stopping their NSAID. CONCLUSIONS: The pattern of PPI and H2RA prescriptions, when prescribed as prophylactic strategy, does not correspond with the pattern of NSAID use. Physicians should consider the medical impact of non-adherence with dual therapies and the impact of prolonged use of GPAs on treatment cost.

Underutilization of preventive strategies in patients receiving NSAIDs.

BACKGROUND: Multiple treatment guidelines for non-steroidal anti-inflammatory drugs (NSAIDs) suggest that patients with one or more risk factors for NSAID-associated upper gastrointestinal (UGI) ulcer complications should be prescribed preventive strategies such as acid-suppressive drugs, misoprostol or cyclooxygenase (COX)-2-specific inhibitors to reduce their risk of serious ulcer complications. The purpose of the present study was to evaluate the extent to which new NSAID users receive recommended preventive strategies and to assess the association between risk factors and a prescription of acid suppressive drugs or misoprostol. METHOD: A retrospective observational cohort study was conducted using the Integrated Primary Care Information (IPCI) database, a longitudinal database of electronic general practitioner patient records in The Netherlands. The study population comprised all new NSAID users, defined as users of non-specific NSAIDs, COX-2-preferential NSAIDs and COX-2-specific inhibitors, during the period from January 1996 to April 2002. Subjects were excluded if they had an H2-receptor antagonist (H2RA), proton pump inhibitor (PPI) or misoprostol prescription in the 3 months prior to the first NSAID prescription. Preventive use of acid-suppressive drugs or misoprostol was identified by the coprescription for these drugs on the same day (+/-2 days) as the NSAID prescription. The drug use for each patient was validated as having a preventive indication by reviewing the physician-recorded symptoms and diagnoses. Risk factors for UGI ulcer events were defined as age >65 yr, UGI history (gastroduodenal ulcer, UGI bleeding, dyspepsia) and concomitant medications (anticoagulants, aspirin, oral corticosteroids). The study population comprised 69 648 new NSAID users. RESULTS: Overall, 7.9% of NSAID users received a preventive strategy (6.6% received a gastroprotective agent and an additional 1.3% received COX-2-specific inhibitors). Patients using preventive drugs had higher odds of having one or more UGI risk factors than patients without preventive drugs [adjusted odds ratio (OR) 1.78, 95% confidence interval 1.66-1.92]. Despite the greater rate of preventive drug prescriptions in patients who may have been at higher risk, 86.6% of patients with one risk factor and 81.2% with two or more risk factors received no preventive strategies. In contrast to non-specific NSAIDs, patients who received a prescription for a COX-2-specific inhibitor had significantly lower adjusted odds (OR = 0.22) of having H2RA/PPI or misoprostol coprescribed. CONCLUSIONS: Although patients who are treated with preventive strategies have higher odds of having gastrointestinal risk factors than those not prescribed preventive therapies, the majority (>80%) of patients with one or more gastrointestinal risk factors do not receive the recommended NSAID treatment regimen of a COX-2-specific inhibitor or NSAID + H2RA/PPI or misoprostol and are therefore undertreated.

Channelling bias and the incidence of gastrointestinal haemorrhage in users of meloxicam, coxibs, and older, non-specific non-steroidal anti-inflammatory drugs.

BACKGROUND: Although clinical trial results suggest that meloxicam has less gastrointestinal toxicity than most other non-steroidal anti-inflammatory drugs (NSAIDs), in practice it has been associated with a large number of yellow card reports of gastrointestinal complications. AIMS: To estimate whether meloxicam and the coxibs, rofecoxib and celecoxib, have been channelled towards high risk patients, and to estimate the risk of hospitalisation for gastrointestinal haemorrhage associated with the use of these drugs, allowing for the effects of channelling. PATIENTS: Using the UK General Practice Research Database, this study included 7.1 thousand patient years (tpy) exposure to meloxicam, 1.6 tpy exposure to coxibs, and 628 tpy exposure to older non-specific NSAIDs. METHODS: Cohort study of patients who received a prescription for an NSAID between June 1987 and January 2001. Exposure to newer NSAIDs (meloxicam, rofecoxib, celecoxib) and to older non-specific NSAIDs was identified. Channelling was assessed on factors including: demographic variables; diagnosis of arthritis; history of NSAID use or gastrointestinal events, including gastrointestinal haemorrhage; and use of ulcer healing drugs. RESULTS: Most risk factors for gastrointestinal haemorrhage were more prevalent among patients prescribed the newer NSAIDs. Adjusting for these risk factors reduced the relative risks of gastrointestinal haemorrhage on meloxicam and coxibs versus older non-specific NSAIDs to 0.84 (95% confidence interval 0.60, 1.17) and 0.36 (0.14, 0.97), respectively. CONCLUSIONS: Channelling towards high risk gastrointestinal patients occurred in the prescribing of newer NSAIDs. After attempting to correct for channelling bias, coxib exposure, but not meloxicam exposure, was associated with a significantly lower risk of gastrointestinal haemorrhage than older non-specific NSAID exposure.

Dyspepsia tolerability from the patients' perspective: a comparison of celecoxib with diclofenac.

AIM: To compare celecoxib (800 mg/day, n=1997) with diclofenac (150 mg/day, n=1996) on dyspepsia-related tolerability. METHODS: In one of the two protocols comprising the Celecoxib Long-Term Arthritis Safety Study, a randomized double-blind trial, patients completed the Severity of Dyspepsia Assessment Questionnaire at baseline and at weeks 4, 13, 26 and 52 for the following three scales: Pain Intensity, Non-Pain Symptoms and Satisfaction with Dyspepsia-Related Health. RESULTS: For the Pain Intensity scale, patients given diclofenac had significantly higher (worsening dyspepsia) mean changes, defined as follow-up minus baseline, than patients given celecoxib (P < 0.001, at all assessments). The mean changes in the Pain Intensity scale (scale, 2-47; higher score is higher pain intensity) were 0.99 (95% confidence interval (CI): 0.50, 1.48) for celecoxib and 2.76 (95% CI: 2.28, 3.25) for diclofenac at 4 weeks. Satisfaction was superior with celecoxib at all assessments (P < 0.001). At 4 weeks, the mean changes in the Satisfaction scale (scale, 7-35; higher score is higher satisfaction) were 0.02 (95% CI: - 0.26, 0.29) for celecoxib and - 0.72 (95% CI: - 1.00, - 0.45) for diclofenac. Diclofenac patients had significantly higher Non-Pain Symptoms at 4 weeks (P=0.005). CONCLUSIONS: Celecoxib, at two to four times the recommended dose, demonstrated a superior dyspepsia-related tolerability and satisfaction compared with standard dosages of diclofenac.

Turning science into junk: the tobacco industry and passive smoking.

In this issue, Glantz and Ong offer a powerful analysis of the tobacco industry's attempt to discredit the scientific evidence on passive smoking, particularly the industry's use of the label "junk science." Environmental epidemiologic studies in other arenas have also been targets for the "junk science" label. Lessons for researchers involved in high-stakes issues in the public policy arena include a need for awareness of competing interests, for transparency concerning funding, and for adherence to rigorous quality assurance and peer review practices. The goal of "sound science" seems an admirable one; it should not, however, be used to dismiss available but uncertain evidence in order to delay action.

A framework for evaluating the clinical consequences of initial therapy with NSAIDs, NSAIDs plus gastroprotective agents, or celecoxib in the treatment of arthritis.

OBJECTIVE: The purpose of this study is to provide a framework for estimating the economic efficiency of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), concomitant gastroprotective agents (GPAs) to reduce the risk of NSAID toxicity, and celecoxib, a specific cyclo-oxygenase-2 inhibitor. Concomitant GPA therapies considered include one of the following: proton pump inhibitors (PPIs) plus NSAIDs, histamine H2 receptor antagonists (H2RAs) plus NSAIDs, misoprostol plus NSAIDs, and a single tablet formulation of diclofenac/misoprostol. DESIGN: The study employs a decision-tree framework to establish probabilities of upper gastrointestinal (GI) adverse events occurring over a 6-month time frame. Celecoxib clinical trial data are used to establish probabilities of upper GI events for celecoxib and NSAIDs, and published literature is used to predict upper GI events for the other concomitant therapies. Upper GI adverse events included in the decision-tree are as follows: GI discomfort, symptomatic ulcer, serious GI complications (with and without death), and anaemia with occult bleeding. MAIN OUTCOME MEASURES AND RESULTS: Clinical probabilities indicate celecoxib has significant tolerability and safety advantages compared with nonselective NSAIDs. Celecoxib also reduces the risk of GI adverse events to a similar or superior degree when compared with reductions observed with NSAIDs with concomitant GPAs. CONCLUSION: Use of celecoxib is expected to significantly reduce the economic costs of GI toxicity and its associated morbidity.

An economic model for determining the costs and consequences of using various treatment alternatives for the management of arthritis in Canada.

OBJECTIVE: To construct a decision analytical model to compare the costs and clinical consequences of treating patients with celecoxib or various nonsteroidal anti-inflammatory drug (NSAID)/gastrointestinal (GI) co-therapy regimens for the management of osteoarthritis and rheumatoid arthritis. The model quantified the number of patients expected to experience any GI complication commonly associated with NSAID therapy. DESIGN: Resource use for the treatment of each GI complication in the model was estimated after consulting Canadian experts. Standard unit costs from Ontario were applied to resources to calculate the cost of each complication. MAIN OUTCOME MEASURES AND RESULTS: The model revealed that the NSAID-alone regimen was associated with the lowest cost [$262 Canadian dollars ($Can) per patient per 6 months] followed by the celecoxib regimen ($Can273), diclofenac/misoprostol ($Can365), NSAID + histamine H2 receptor antagonist ($Can413), NSAID + misoprostol ($Can421), and NSAID + proton pump inhibitor ($Can731). A break-even analysis showed that up to 80% of the study cohort could be treated with celecoxib instead of the NSAID-alone regimen without increasing the health system's overall budget. Celecoxib was associated with the fewest GI-related deaths, hospitalised events; symptomatic ulcers, and cases of anaemia. The celecoxib regimen was also associated with the fewest cases of upper GI distress. Sensitivity analyses revealed that the model was most sensitive to the distribution of GI risk in the population and to the ingredient costs of the treatment alternatives. CONCLUSIONS: This model indicates that the use of celecoxib could lead to the avoidance of a significant number of NSAID-attributable GI adverse events, and the incremental cost of using celecoxib for arthritis patients > or = 65 years of age in place of current treatment alternatives would not impose an excessive incremental impact on a Canadian provincial healthcare budget.

Regulation of plasminogen binding to neutrophils.

Plasminogen plays an integral role in the inflammatory response, and this participation is likely to depend on its interaction with cell surfaces. It has previously been reported that isolation of human neutrophils from blood leads to a spontaneous increase in their plasminogen-binding capacity, and the basis for this up-regulation has been explored as a model for mechanisms for modulation of plasminogen receptor expression. Freshly isolated human peripheral blood neutrophils exhibited relatively low plasminogen binding, but when cultured for 20 hours, they increased this capacity dramatically, up to 50-fold. This increase was abolished by soybean trypsin inhibitor and was susceptible to carboxypeptidase B treatment, implicating proteolysis and exposure of carboxy-terminal lysines in the enhanced interaction. In support of this hypothesis, treatment of neutrophils with elastase, cathepsin G, or plasmin increased their plasminogen binding, and specific inhibitors of elastase and cathepsin G suppressed the up-regulation that occurred during neutrophil culture. When neutrophils were stimulated with phorbol ester, their plasminogen binding increased rapidly, but this increase was insensitive to the protease inhibitors. These results indicate that plasminogen binding to neutrophils can be up-regulated by 2 distinct pathways. A major pathway with the propensity to markedly up-regulate plasminogen binding depends upon the proteolytic remodeling of the cell surface. In response to thioglycollate, neutrophils recruited into the peritoneum of mice were shown to bind more plasminogen than those in peripheral blood, suggesting that modulation of plasminogen binding by these or other pathways may also occur in vivo.

Upper gastrointestinal tolerability of celecoxib, a COX-2 specific inhibitor, compared to naproxen and placebo.

OBJECTIVE: To determine the upper gastrointestinal (GI) tolerability of celecoxib, naproxen, and placebo in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: An analysis of 5, 12-week, randomized, double blind, parallel group, placebo controlled clinical trials was conducted. In these trials, patients were randomized to: naproxen 500 mg bid (n = 1,099), placebo (n = 1,136), celecoxib 50 mg bid (n = 690) (subtherapeutic dose), celecoxib 100 mg (n = 1,131) or 200 mg bid (n = 1,125) (therapeutic dose), or celecoxib 400 mg bid (n = 434) (supratherapeutic dosage). The incidence and time until moderate to severe abdominal pain, dyspepsia, nausea, and any of the aforementioned 3 upper GI symptoms (composite endpoint) were determined using time-to-event analysis. RESULTS: The cumulative incidences of moderate to severe abdominal pain, dyspepsia, or nausea (composite endpoint) were: naproxen 500 mg (12.0%; 95% CI 9.9%-14.0%), celecoxib 50 mg bid (7.1%; 95% CI 5.0%-9.2%), celecoxib 100 mg bid (7.8%; 95% CI 6.0%-9.5%), celecoxib 200 mg bid (8.1%; 95% CI 6.4%-9.9%), celecoxib 400 mg bid (6.0%; 95% CI 3.6%-8.4%), and placebo (8.5%; 95% CI 6.5%-10.8%). After controlling for independent predictors of the composite endpoint, relative risks (RR) for the various treatments relative to naproxen 500 mg bid were: celecoxib 50 mg (RR 0.54; 95% CI 0.37-0.77; p < 0.001), celecoxib 100 mg (RR 0.60; 95% CI 0.45-0.80; p < 0.001), celecoxib 200 mg bid (RR 0.63; 95% CI 0.47-0.83; p = 0.001), celecoxib 400 mg bid (RR 0.56; 95% CI 0.35-0.89; p = 0.015), and placebo (RR 0.63; 95% CI 0.47-0.85; p = 0.002). After controlling for independent predictors of the composite endpoint, celecoxib treatment group patients did not differ from placebo patients when reporting the composite endpoint, with p values ranging from 0.40 to 0.96. CONCLUSION: The upper GI tolerability of celecoxib is superior to naproxen. A dose-response relationship between celecoxib and upper GI symptoms was not apparent.

Chemical and radiation environmental risk management: differences, commonalities, and challenges.

Driven by differing statutory mandates and programmatic separation of regulatory responsibilities between federal, state, and tribal agencies, distinct chemical and radiation risk management strategies have evolved. In the field this separation poses real challenges since many of the major environmental risk management decisions we face today require the evaluation of both types of risks. Over the last decade, federal, state, and tribal agencies have continued to discuss their different approaches and explore areas where their activities could be harmonized. The current framework for managing public exposures to chemical carcinogens has been referred to as a "bottom up approach." Risk between 10(-4) and 10(-6) is established as an upper bound goal. In contrast, a "top down" approach that sets an upper bound dose limit and couples with site specific As Low As Reasonably Achievable Principle (ALARA), is in place to manage individual exposure to radiation. While radiation risk are typically managed on a cumulative basis, exposure to chemicals is generally managed on a chemical-by-chemical, medium-by-medium basis. There are also differences in the nature and size of sites where chemical and radiation contamination is found. Such differences result in divergent management concerns. In spite of these differences, there are several common and practical concerns among radiation and chemical risk managers. They include 1) the issue of cost for site redevelopment and long-term stewardship, 2) public acceptance and involvement, and 3) the need for flexible risk management framework to address the first two issues. This article attempts to synthesize key differences, opportunities for harmonization, and challenges ahead.

A comparison of time-and-motion and self-reporting methods of work measurement.

OBJECTIVE: To compare results obtained from a time-and-motion study with those obtained using self-reporting. SUMMARY BACKGROUND DATA: Nurse executives are often required to provide additional patient care services with limited personnel resources. As a result, nurse executives must evaluate the appropriate allocation of nursing personnel resources. Work measurement may be used to evaluate personnel allocation. Multiple measurement approaches are available, but few studies have compared these methods. METHODS AND SUBJECTS: Eight nurses were observed by a single observer during five shifts (or approximately 40 hours per nurse). After completion of the time-and-motion study, participants were to self-report their work activities during their ensuing five shifts. Mixed-effects analysis of variance was used to determine the significance of the work measurement method on percentage of total time, number of activities, and mean time per activity by activity category. RESULTS: Two hundred ninety hours of time-and-motion study observations and 338 hours of self-report data were available for analysis. Comparable amounts of total time were reported within the various activity categories using time-and-motion and self-reporting methods. In terms of number of activities reported, a significantly higher number of activities were reported using time-and-motion. As a result, mean activity times were significantly longer using the self-reporting method compared with time-and-motion. CONCLUSIONS: Nurse executives should consider continuous self-reporting as a low-cost means of quantifying allocation of time among nursing personnel. Self-reporting, however, is not recommended for estimating the total number of activities or the mean time per activity because of perceptual differences between participants of what constitutes an activity.

Linking public health and the health of the Chesapeake Bay.

The Chesapeake Bay has a profound impact on the lives of all who reside in the 64,000 square miles of its watershed. From crab cakes to sail-boats, drinking water to naval ships, the Bay touches virtually every aspect of life in the region. The Bay has inspired literature, driven the regional economy, and shaped political decision making and development patterns for homes, industry, agriculture, and transportation. As population demands increase and urban boundaries expand into pristine landscapes, the sustainability of the Chesapeake Bay and its resources face unprecedented pressures. Consequently, the public's health also is vulnerable to Bay pollution and other stresses stemming from development activities and widespread growth occurring throughout the Chesapeake Bay watershed. This paper will examine the linkages between the environmental quality of the Bay and the population health status, recommend ways to bridge ecological and human health concerns in the context of the Bay, and finally present a framework for developing a public health report card for the Bay.