Prevalence and burden of COPD misclassification in the Canadian Longitudinal Study on Aging (CLSA).

INTRODUCTION: To examine the prevalence of chronic obstructive pulmonary disease (COPD) misclassification and the associated burden of symptoms, healthcare utilisation and physical performance status in the Canadian general population. This information is presently lacking from large population-based studies with high-quality spirometry data that can be generalised to the general population. METHODS: The prevalence of self-reported physician-diagnosed COPD and the concordance with spirometry airflow obstruction (AO) were assessed in a cross-sectional cohort of Canadian older adults. The associations between confirmed COPD, under-diagnosis and over-diagnosis with self-reported respiratory symptoms, healthcare utilisation and physical performance (timed up and go, handgrip strength and 4 metres walk test) were assessed, adjusting for baseline characteristics using multivariable linear and logistic models. RESULTS: A total of 21 242 participants (mean age 64 (SD 10) years; 42% men) with high quality spirometry were included. Physician-diagnosed COPD was reported in (n=973) 5% of the participants. Only (n=217) 1% of the entire cohort had confirmed COPD supported by spirometry AO. Discordance between self-reported COPD and spirometry findings was observed in (n=1565) 8%: with 4% representing under-diagnosis cases (no self-reported COPD but AO) and 4% representing over-diagnosis cases (self-reported COPD but no AO). Compared with normals (no self-reported COPD and normal spirometry), those with confirmed, under-diagnosed or over-diagnosed COPD showed higher risks for respiratory symptoms (adjusted OR (aOR) 2.1 (95% CI: 1.6 to 2.7); aOR 1.8 (95% CI: 1.6 to 2.1]; aOR 1.6 (95% CI: 1.4 to 1.9)); healthcare utilisation in the prior 12 months (ß coefficient 0.8 (95% CI: 0.2 to 2.6); ß 0.9 (95% CI: 0.5 to 1.5); ß 1.6 (95% CI: 0.7 to 4.0)). Mood disorders were higher in confirmed and over-diagnosed COPD (aOR 1.7 (95% CI: 1.3 to 2.4); 1.7 (95% CI: 1.4 to 2.0), respectively). Physical performance was lower for COPD groups. CONCLUSIONS: The prevalence of COPD misclassification is high in the general population of older adults. These were associated with significantly high burden of respiratory symptoms, healthcare utilisation and low physical performance compared with the general population with normal spirometry and no self-reported COPD. These findings highlight the high burden of COPD misclassification, which may be substantially reduced with greater accessibility to spirometry measurements in the community.

The Canadian longitudinal study on aging (CLSA).

ABSTRACTCanadians are living longer, and older persons are making up a larger share of the population (14% in 2006, projected to rise to 20% by 2021). The Canadian Longitudinal Study on Aging (CLSA) is a national longitudinal study of adult development and aging that will recruit 50,000 Canadians aged 45 to 85 years of age and follow them for at least 20 years. All participants will provide a common set of information concerning many aspects of health and aging, and 30,000 will undergo an additional in-depth examination coupled with the donation of biological specimens (blood and urine). The CLSA will become a rich data source for the study of the complex interrelationship among the biological, physical, psychosocial, and societal factors that affect healthy aging.

Exploring the acceptability and feasibility of conducting a large longitudinal population-based study in Canada.

ABSTRACTSuccessful recruitment and retention for population-based longitudinal studies requires understanding facilitators and barriers to participation. This study explored Canadians' views regarding one such study, the proposed Canadian Longitudinal Study on Aging (CLSA). Focus groups of participants > or =40 years of age were held in six proposed CLSA data collection sites (Halifax, Montreal, Hamilton, Winnipeg, Calgary, and Vancouver) to discuss participating in a long-term study of healthy aging. There was fundamental support for longitudinal research on health and aging. Altruism was a key motivation to participation, and universities were viewed as credible parties to conduct such studies. Participants had few worries about providing biological samples but expressed concern about potential misuse of genetic materials, commercialization of participant data, and privacy issues. These findings have already informed current, and will inform future, work on the CLSA, and will also provide useful information to researchers who undertake other population-based longitudinal studies.

The Canadian community health survey as a potential recruitment vehicle for the Canadian longitudinal study on aging.

ABSTRACTThe goal of the Canadian Longitudinal Study on Aging (CLSA) is to recruit 50,000 participants aged 45 to 85 years of age and follow them for at least 20 years. The sampling and recruitment processes for a study of this scope and magnitude present important challenges. Statistics Canada was approached to collaborate with the CLSA with the goal of determining whether the Canadian Community Health Survey (CCHS) could be used as a recruitment vehicle for the CLSA. In this pilot study conducted in 2004, it was determined that 63.8 per cent and 75.8 per cent of the respondents agreed to share their contact information and their survey responses with the CLSA, respectively. The most commonly reported concerns were confidentiality/privacy issues, lack of interest, and commitment issues. This pilot study identified some challenges to the use of the CCHS as a recruitment vehicle for the CLSA.

Telephone-administered cognitive tests as tools for the identification of eligible study participants for population-based research in aging.

ABSTRACTAs part of its recruitment process, the Canadian Longitudinal Study on Aging (CLSA) will face the challenge of screening out individuals who are sufficiently impaired in their ability to provide informed consent. In the process of developing the design of the CLSA, a review of the literature was performed with the goal of identifying currently existing telephone cognitive screening tools that can be used to identify eligible study participants for population-based research on aging. We identified 12 telephone screening tools, four of which were based on the Mini-Mental State Exam (MMSE) and eight that were based on other face-to-face screening tools. Characteristics - including the constructs measured, the length of time for administration, the scoring/classification scheme, and any information regarding the validation of each tool - were extracted and summarized.

Feasibility of biological specimen collection for the Canadian longitudinal study on aging (CLSA) biorepository.

ABSTRACTBiological specimen collection is an integral part of many longitudinal epidemiological studies. It is important to achieve high participant satisfaction for continuing involvement, and high sample quality for accurate biomarker measurement. We conducted a study to evaluate these issues on the sample collection proposed for the Canadian Longitudinal Study on Aging (CLSA). There were 85 participants recruited, and 65 attended either a hospital laboratory or private laboratory. Approximately 100 mL of blood and a random urine specimen were collected from each participant for a total of 2,108 sample aliquots. Quality standards were met for more than 90 per cent of samples and were similar for samples collected in both laboratories. More than 90 per cent of participants rated satisfaction with the collection as being good or excellent, and 84 per cent would be willing to repeat the collection in one to three years.

Ascertainment of chronic diseases in the Canadian longitudinal study on aging (CLSA), systematic review.

ABSTRACTStandard clinical diagnostic procedures are often inappropriate and frequently not feasible to apply in population-based studies, yet ascertaining accurate disease status is essential. We conducted a systematic review to identify algorithms, criteria, and tools used to ascertain 17 chronic diseases, and assessed the feasibility of developing algorithms for the CLSA. Of the 29,616 citations screened, 668 papers met all inclusion criteria. We determined that the information included in a disease algorithm will differ by condition type. The diagnosis of some symptomatic conditions, such as osteoarthritis and arthritis, will require substantiation by clinical criteria (e.g., x-rays, bone density measurement) while other conditions, such as depression, will rely solely on self-report. Asymptomatic conditions, such as hypertension, are more difficult to ascertain by self-report and will require additional physiologic measures (e.g., blood pressure) as well as laboratory measures (e.g., glucose). This pilot study identified the tools necessary to develop disease ascertainment algorithms.

Accessing health care utilization databases for health research: a Canadian longitudinal study on aging feasibility study.

ABSTRACTOne of the keys to the success of the Canadian Longitudinal Study on Aging (CLSA) will be the leveraging of secondary data sources, particularly health care utilization (HCU) data. To examine the practical, methodological, and ethical aspects of accessing HCU data, one-on-one qualitative interviews were conducted with 53 data stewards and privacy commissioners/ombudsmen from across Canada. Study participants indicated that obtaining permission to access HCU data is generally possible; however, they noted that this will be a complex and lengthy process requiring considerable and meticulous preparatory work to ensure proper documentation and compliance with jurisdictional variations along legislative and policy lines.

Evidence for the use of B-type natriuretic peptides for screening asymptomatic populations and for diagnosis in primary care.

OBJECTIVES: To determine the screening and diagnostic properties of BNP and NT-proBNP for heart failure in primary care. DESIGN AND METHODS: We conducted a systematic review of randomized control trials and observational (cohort or case-control) studies of heart failure detection using B-type natriuretic peptides published in English from January 1989 to February 2005. We extracted or calculated sensitivity, specificity, positive and negative likelihood ratios, area under the receiver-operator characteristic curve and diagnostic odds ratio (DOR). RESULTS: We included 17 studies (7 screening, 9 diagnosis in primary care or specialised clinic, 1 both). There was considerable heterogeneity within the study populations, reference standard for diagnosis, and B-type natriuretic peptide decision point. Sensitivity ranged from 26% to 98%; and specificity from 44% to 88%. For screening, the Diagnostic Odds Ratio (DOR) ranged from 2.7 to 29, and for diagnosis from 2.8 to 137. CONCLUSIONS: The performance characteristics of B-type natriuretic peptides measurement are not suitable for screening asymptomatic patients. For diagnosis in primary care, low B-type natriuretic peptide values may be used to rule-out heart failure but, due to poor specificity, high values cannot be used to rule-in the condition.

A systematic review of BNP as a predictor of prognosis in persons with coronary artery disease.

OBJECTIVE: This systematic review was conducted to examine whether B-type natriuretic peptide (BNP) can predict mortality and other cardiac endpoints in persons diagnosed with coronary artery disease (CAD). DESIGN AND METHODS: Databases were searched from 1989 to February 2005 for primary studies that measured BNP for the purpose of diagnosis, prognosis, and monitoring treatment. RESULTS: In 18 studies, concentrations of BNP were found to have consistent positive associations with poorer prognoses for persons with CAD. The overall range of effect (95% confidence interval) was 2.31 to 5.02, measured via a random effects meta-analysis on studies reporting an odds ratio. Prognostic ability was similar for mortality and non-fatal outcomes. Ranges of estimated measures of effect (i.e., odds ratio, relative risk, hazard ratio) were concentrated between 1.33 to 2.94 for mortality and 1.01 to 3.03 for non-fatal outcomes. CONCLUSIONS: Further research is needed to assess whether prognostic ability differs by comorbidity or concomitant treatment. As well, the importance and selection of cut points remains unresolved. Until greater clarity is given to these matters, it would be prudent for clinicians to employ caution when using concentrations of BNP to predict the prognosis of persons with CAD.

Physiological, pathological, pharmacological, biochemical and hematological factors affecting BNP and NT-proBNP.

OBJECTIVES: To gain a better understanding of the scope and breadth of factors associated with the B-type natriuretic peptides. DESIGN AND METHODS: Databases were searched from 1989 to February 2005 for primary studies that measured BNP or NT-proBNP for the purpose of diagnosis, prognosis and monitoring treatment. RESULTS: There were 103 factors identified in 72 studies. Most of the cardiac diseases were positively associated with BNP and NT-proBNP concentrations and of the non-cardiac conditions, dyspnea, diabetic nephropathy, and stroke were all associated with higher concentrations. Most biochemical and hematological markers showed positive associations. Factors that assessed heart function showed both positive and negative associations and drug therapy was either negatively associated or had no effect on BNP or BNT-proBNP concentrations. Few studies reported independent associations and of those that did age, female gender, and creatinine concentrations were positively associated with BNP and NT-proBNP. CONCLUSIONS: Various factors were found to be associated with BNP and NT-proBNP.

Diagnostic accuracy of BNP and NT-proBNP in patients presenting to acute care settings with dyspnea: a systematic review.

OBJECTIVE: We sought to compare the diagnostic performance of B-type natriuretic peptide (BNP) and N-terminal proBNP measurements in patients presenting to acute care settings with dyspnea, a common presenting symptom of heart failure. DESIGN AND METHODS: We conducted a systematic review of the literature. For all included studies, we applied the QUADAS 14-question quality assessment tool for systematic reviews of diagnostic accuracy and abstracted the data for every published cut point. RESULTS: We screened 4338 studies and included nine in the meta-analysis. All 9 studies scored positively on at least 50% of the QUADAS questions. The pooled estimates of sensitivity and specificity were the same for the BNP studies (0.97 (95% CI: 0.96, 0.98) and 0.70 (95% CI: 0.56, 0.85)) as for the NT-proBNP studies (0.95 (95% CI: 0.90, 1.01) and 0.72 (95% CI: 0.53, 0.90)). Tests for heterogeneity were significant in both subgroups: BNP (I(2)=97.9%, p<0.001) and NT-proBNP (I(2)=87.5%, p<0.001). Similar overall results were found for the likelihood and diagnostic odds ratios. CONCLUSIONS: BNP and NT-proBNP have very similar diagnostic performance characteristics and can be used to rule out heart failure as a cause of dyspnea in the acute clinical setting. However, there is no easily identifiable optimum cut point value for each peptide.

Brain type carnosinase in dementia: a pilot study.

BACKGROUND: The pathological processes underlying dementia are poorly understood and so are the markers which identify them. Carnosinase is a dipeptidase found almost exclusively in brain and serum. Carnosinase and its substrate carnosine have been linked to neuropathophysiological processes. METHODS: Carnosinase activity was measured by a flourometric method in 37 patients attending a Geriatric Outpatient Clinic. There were 17 patients without dementia, 13 had Alzheimer's disease (AD) and 7 had mixed dementia (MD). RESULTS: The range of serum carnosinase activity for patients without dementia was 14.5 - 78.5 micromol/ml/h. There was no difference in carnosinase activity between patients without dementia (40.3 +/- 15.2 micromol/ml/h) and patients with AD (44.4 +/- 12.4 micromol/ml/h) or MD (26.6 +/- 15 micromol/ml/h). However, levels in the MD group were significantly lower than the AD group (p = 0.01). This difference remained significant after adjusting for gender, MMSE score, exercise, but not age, one at a time and all combined. The effect of other medical conditions did not remove the significance between the AD and MD groups. The MD group, but not the AD group, demonstrated a significant trend with carnosinase activity decreasing with duration of disease (from first recorded date of diagnosis to date of blood collection) (r = -0.76, p = 0.049). There was no association with carnosinase activity and MMSE score in the AD or MD group. Both AD and MD patients on any dementia medication (donepezil, galantamine, memantine) had higher carnosinase activity compared to those not taking a dementia medication. Carnosinase activity was higher in patients who regularly exercised (n = 20) compared to those who did not exercise regularly (n = 17)(p = 0.006). CONCLUSION: This exploratory study has shown altered activities of the enzyme carnosinase in patients with dementia.

Reproducibility of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) classification: a systematic review.

BACKGROUND: The classifications of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) represent glucose levels above normal, but below the decision threshold for diabetes. We sought to determine what the reproducibility of these classifications was when repeat tests were performed by conducting a systematic review of the literature. METHODS: All primary studies published in English of any study design were included. Studies were excluded if they did not follow the World Health Organization or American Diabetes Association diagnostic criteria, used whole blood as the specimen type, a glucose meter for analysis, or performed repeat testing greater than 8 weeks apart. RESULTS: Five papers had reproducibility data for IGT or IFG, two of which where from the same population but sampled differently. The kappa coefficients, indicating agreement between repeat tests that exceeded chance, indicated poor to fair agreement for IGT (0.04, 0.22, 0.38, 0.42) and moderate agreement for IFG (0.44 and 0.56). Similarly, the observed reproducibility was slightly lower for IGT (33%, 44%, 47%, 48%) compared to IFG (51%, 64%). In two studies for which data were available for both IGT and IFG, the average reproducibility was lower (49%) for the prediabetes group compared to the diabetes group (73%) or the normal group (93%). CONCLUSIONS: Poor reproducibility of IGT and IFG classification suggests caution should be exercised when interpreting a single test result.

Is There a Tension between Clinical Practice and Reimbursement Policy? The Case of Osteoarthritis Prescribing Practices in Ontario.

BACKGROUND: Reimbursement policies, such as those used to manage the public drug program for senior citizens in Ontario, focus on providing access to cost-effective drug therapies. These policies may create a dilemma for physicians who want to prescribe a particular drug to a patient, but must factor reimbursement restrictions affecting patient-level access into the prescribing decision. METHODS: Information was collected from 102 physicians about prescriptions given to osteoarthritis patients (n=2,147) aged 65 years or older. Patients' access to prescribed drugs was determined from their insurance coverage and the reimbursement criteria set out in the formulary of the public Ontario Drug Benefit Program (ODBP). Starting from the assumption that physicians would follow published consensus guidelines respecting gastroprotection when prescribing NSAIDs in these at-risk elderly patients, three groups of physicians were identified from the record of their actual prescriptions. Group A physicians (n=14) prescribed non-selective NSAIDs alone to >60% of their patients. Group B physicians (n=26) prescribed an NSAID + gastroprotective agent or a Cox-2 selective NSAID to >70% of their patients. Group C physicians (n=62) were those that fit into neither category. An open-ended question was included in the study questionnaire to elicit physicians' own interpretation of what impact drug coverage had on their prescribing behaviour. RESULTS: No significant differences were found across groups with respect to years or type of practice, or to patient characteristics (LR=3.00, p>.2). Group C physicians were most likely to change their treatment choice in favour of restricted (limited use) drugs when patients met the criteria for reimbursement or had private insurance and therefore did not have to bear the additional cost out-of-pocket (LR=58.5; p<.0001). INTERPRETATION: Most elderly at-risk patients are prescribed NSAIDs according to the prevailing guidelines. We found, however, that 40% of physicians have prescribing behaviour that favours non-evidence-based (Group A) or evidence-based (Group B) prescribing in this clinical setting irrespective of drug coverage. The remaining 60% of physicians appeared to be more responsive in their prescribing behaviour to financial constraints on patients' access to drugs. They also self-identified as most likely to change treatment if drug coverage had been different. These results have important implications for equity and quality of patient care. They also confirm that physicians' knowledge, values and self-efficacy are key determinants of prescribing behaviour and require further study to better understand how medical education and third-party policies and programs that govern pharmaceutical care are integrated into physicans' decision-making.

The role of evidence in public health policy: an example of linkage and exchange in the prevention of scald burns.

Is sound evidence sufficient to change public health practice and policy? In this paper, we describe a campaign to reduce scald burns among children based on compelling evidence of the effectiveness of an intervention to reduce hot tap water temperature. We provide an overview of the problem and the evidence to support our efforts, the context for addressing the scald problem and the lessons learned about why the relationship between evidence and change in practice is not straightforward.

The influence of display and statistical factors on the interpretation of metaanalysis results by physicians.

OBJECTIVE: The objective of this study was to determine the extent to which various factors affect the interpretation of metaanalytic results by physicians. STUDY DESIGN: A sample of 120 physicians, selected from The Royal College of Physicians and Surgeons of Canada (RCPSC), was randomly assigned to 1 of 6 groups (n = 20) created from a combination of 3 summary measures and 2 levels of disease severity. The intervention consisted of a written scenario and 4 individual displays of metaanalyses (M-A), each followed by questions related to the interpretation of results of M-A. Two final questions examined statistical familiarity/proficiency with the summary measures used. DATA ANALYSIS: Analyses of variance examined main effects and interactions among 4 factors: summary measure, disease severity, effect size, and statistical consistency of the studies comprising the metaanalysis. Two outcomes were examined: interpretation of the treatment effect and confidence in the interpretation of the treatment effect. PRINCIPAL FINDINGS: Physicians were more likely to favor treatment when the results of the primary randomized, controlled trials (RCTs) were statistically homogeneous (P = 0.001) and when the overall effect size was large (P = 0.001). Also, physicians were more likely to be confident when the results were homogeneous (P = 0.001) and when effect size was large (P = 0.000). Interactions also revealed that the effect of statistical consistency of contributing to RCTs was greatest when data were presented as risk difference for treatment outcome (P = 0.026) and when effect size was small (P = 0.000). CONCLUSIONS: The interpretation of metaanalytic displays is influenced by the overall effect size of M-A, the statistical consistency of the contributing RCTs, and interactions of these factors with display factors.

Rasch analysis of the Gross Motor Function Measure: validating the assumptions of the Rasch model to create an interval-level measure.

OBJECTIVES: To describe the Rasch analysis of the Gross Motor Function Measure (GMFM-88) and to demonstrate how the assumptions of unidimensionality, sample-free measurement, and test-free measurement were validated to create an interval level measure. DESIGN: Cross-sectional and longitudinal (12-mo) data from a prospective study of motor development in children with cerebral palsy (CP) were used for the analysis. SETTING: Motor assessments were completed at 18 children's ambulatory rehabilitation centers in Ontario, Canada, by pediatric physical therapists trained in the use of the GMFM-88. PARTICIPANTS: The first 537 of 682 children enrolled into a longitudinal study of motor development in children with CP. Children had a mean age of 6.43+/-2.75 years (range, 11mo-12y) with varying types and severity of CP. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The GMFM-88. RESULTS: The Rasch analysis, in conjunction with clinical decisions, identified 66 items from the GMFM-88 that formed a unidimensional measure (GMFM-66). Assumptions of sample-free and test-free measurement were confirmed, and a user-friendly scoring program was developed. CONCLUSIONS: The GMFM-66 is an interval-level measure of gross motor function for children with CP; it should improve the scoring, interpretation, and overall clinical and research utility over the original GMFM.