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1.
Mol Autism ; 12(1): 57, 2021 08 14.
Article in English | MEDLINE | ID: mdl-34391468

ABSTRACT

BACKGROUND: Restricted and repetitive behavior (RRB) is one of the characteristic features of Autism Spectrum Disorder. This domain of symptoms includes a broad range of behaviors. There is a need to study each behavior individually to better understand the role of each in the development of autistic children. Moreover, there are currently no longitudinal studies investigating change in these behaviors over development. METHODS: The goal of the present study was to explore the association between age and non-verbal IQ (NVIQ) on 15 RRB symptoms included in the Autism Diagnostic Interview-Revised (ADI-R) over time. A total of 205 children with ASD were assessed using the ADI-R at time of diagnosis, at age 6 years, and at age 11 years, and with the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) at age 8 years. RESULTS: The proportion of children showing each RRB tended to diminish with increasing age, except for sensitivity to noise and circumscribed interests, where the proportion increased over time. Although there was no significant main effect of NVIQ, there was a significant interaction between age and NVIQ. This was mainly driven by Difficulties with change in routine, for which higher NVIQ was associated with the behavior remaining relatively stable with age, while lower NVIQ was associated with the behavior becoming more prevalent with age. LIMITATIONS: The study focused on the presence/absence of each RRB but did not account for potential changes in frequency or severity of the behaviors over development. Furthermore, some limitations are inherent to the measures used. The ADI-R relies on parent report and hence has some level of subjectivity, while the Wechsler intelligence scales can underestimate the intellectual abilities of some autistic children. CONCLUSIONS: These results confirm that specific RRB are differentially linked to age and NVIQ. Studying RRB individually is a promising approach to better understanding how RRB change over the development of autistic children and are linked to other developmental domains.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Autism Spectrum Disorder/diagnosis , Child , Cognition , Humans , Intelligence Tests , Longitudinal Studies
2.
Genet Med ; 22(1): 95-101, 2020 01.
Article in English | MEDLINE | ID: mdl-31363181

ABSTRACT

PURPOSE: Clinical utility describes a genetic test's value to patients, families, health-care providers, systems, or society. This study aims to define clinical utility from the perspective of clinicians and develop a novel outcome measure that operationalizes this concept. METHODS: Item selection for the Clinician-reported Genetic testing Utility InDEx (C-GUIDE) was informed by a scoping review of the literature. Item reduction was guided by qualitative and quantitative feedback from semistructured interviews and a cross-sectional survey of genetics and nongenetics specialists. Final item selection, index scoring, and structure were guided by feedback from an expert panel of genetics professionals. RESULTS: A review of 194 publications informed the selection of a preliminary set of 25 items. Feedback from 35 semistructured interviews, 113 surveys, and 11 expert panelists informed the content and wording of C-GUIDE's final set of 18 items that reflect on the utility of testing related to diagnosis, management, and familial/psychosocial impact. C-GUIDE achieves content and face validity for use in a range of diagnostic genetic testing settings. CONCLUSION: Work to establish reliability and construct validity is underway. C-GUIDE will be useful in comparative studies to generate policy-relevant evidence pertaining to the clinical utility of genetic testing across a range of settings.


Subject(s)
Evidence-Based Practice/methods , Genetic Testing/methods , Outcome Assessment, Health Care/methods , Cross-Sectional Studies , Female , Genetic Testing/legislation & jurisprudence , Humans , Male , Reproducibility of Results
3.
Genet Med ; 22(3): 667-668, 2020 03.
Article in English | MEDLINE | ID: mdl-31740736

Subject(s)
Genetic Testing
4.
J Autism Dev Disord ; 49(11): 4390-4399, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31372802

ABSTRACT

Preschool children with autism spectrum disorder (ASD) experience slower development of daily living skills (DLS) that are essential for independent functioning compared to typically developing children. Few studies have examined the trajectories of DLS in preschoolers with ASD and the existing literature has reported conflicting results. This study examined DLS trajectories and potential covariates for preschoolers with ASD from a multi-site longitudinal study following children from diagnosis to the end of grade 1. Multi-level modeling was conducted with DLS domain scores from the Vineland Adaptive Behavior Scales-2. The results demonstrated a positive trajectory of increasing scores over time, associations of age of diagnosis, developmental level, stereotypy, and language skills with the mean score at T4 or age 6 years, whereas rate of change was only associated with ASD symptom severity, such that an improvement in DLS trajectory was associated with lower and improving ASD symptom severity.


Subject(s)
Activities of Daily Living/psychology , Autism Spectrum Disorder/psychology , Child , Child Development , Child Language , Child, Preschool , Female , Humans , Longitudinal Studies , Male , Multilevel Analysis , Severity of Illness Index , Time Factors
5.
Pharmacogenomics J ; 18(3): 391-397, 2018 05 22.
Article in English | MEDLINE | ID: mdl-28696420

ABSTRACT

Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine. Pharmacogenetic testing may be a valuable tool to identify such mothers, but testing can be costly. The objective of the study was to determine the incremental costs of genotyping to avert neonatal adverse events during maternal pharmacotherapy. A cost-effectiveness analysis, using a decision model, was performed with a hypothetical cohort of prenatal subjects. Parameter estimates, costs and ranges for sensitivity analyses were ascertained from the literature and expert opinion. Sensitivity analyses were conducted to assess the robustness of the results. Probabilistic sensitivity analysis revealed an incremental cost-effectiveness (ICER) of $10 433 (Canadian dollars) for genotyping compared to no genotyping per adverse event averted. Results were sensitive to hospital admission costs. The ICER was lower when evaluating only subjects having caesarean deliveries or those from ethnic populations known to have a high prevalence of ultra-rapid metabolizers. Although genotyping to guide pharmacotherapy was not cost saving, the cost to avert an infant adverse event may represent good value for money in specific populations. With a growing demand for personalized medicine, these findings are relevant for decision makers, clinicians and patients.


Subject(s)
Cytochrome P-450 CYP2D6/genetics , Drug-Related Side Effects and Adverse Reactions/genetics , Pain/drug therapy , Postpartum Period/genetics , Breast Feeding/economics , Canada , Codeine/adverse effects , Cost-Benefit Analysis , Drug-Related Side Effects and Adverse Reactions/economics , Female , Genetic Testing/economics , Genotyping Techniques/economics , Humans , Infant , Morphine , Pain/economics , Pain/genetics , Pain/pathology , Postpartum Period/drug effects , Pregnancy
6.
Pharmacogenomics J ; 16(4): 305-11, 2016 08.
Article in English | MEDLINE | ID: mdl-27217052

ABSTRACT

Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3-87.0%) and 98.9% (96.3-100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1-99.4%) and 100.0% (99.9-100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4-95.5%) and 92.6% (86.5-96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6-97.5%) and 99.2% (98.4-99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.37.


Subject(s)
Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/genetics , Drug-Related Side Effects and Adverse Reactions/prevention & control , Methyltransferases/genetics , Pharmacogenomic Testing/methods , Pharmacogenomic Variants/genetics , Purine-Pyrimidine Metabolism, Inborn Errors/diagnosis , Purine-Pyrimidine Metabolism, Inborn Errors/genetics , Purines/adverse effects , Area Under Curve , Drug Hypersensitivity/enzymology , Drug-Related Side Effects and Adverse Reactions/enzymology , Drug-Related Side Effects and Adverse Reactions/genetics , Genetic Predisposition to Disease , Humans , Methyltransferases/metabolism , Phenotype , Predictive Value of Tests , Purine-Pyrimidine Metabolism, Inborn Errors/enzymology , Purines/metabolism , ROC Curve , Reproducibility of Results
7.
Pharmacogenomics J ; 14(6): 493-502, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25156214

ABSTRACT

A common pharmacogenomic test is for thiopurine S-methyltransferase (TPMT) status prior to treatment with thiopurine drugs, used to treat auto-immune conditions and pediatric cancer. Guidelines assist practitioners with decisions regarding testing and treatment. The objectives were to conduct a systematic review and critical appraisal of guidance documents with statements regarding TPMT testing and thiopurine dosing. Guidelines, clinical protocols and care pathways from all disciplines were eligible. A quality appraisal was carried out by three appraisers using the Appraisal of Guidelines for Research and Evaluation II. Of the 20 documents found, 5 recommended genotyping while 4 recommended phenotyping. Thirteen documents provided dosing recommendations based on TPMT status. The quality appraisal revealed wide variation across documents. The National Institute for Health and Clinical Excellence and Cincinnati Children's Hospital guidelines demonstrated the highest overall quality with scores of 79 and 76, respectively. Low-scoring documents failed to use systematic methods to develop recommendations or to provide evidence to support recommendations. Guidance documents that included dosing recommendations demonstrated higher quality.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/pharmacology , Mercaptopurine/administration & dosage , Mercaptopurine/therapeutic use , Methyltransferases/antagonists & inhibitors , Methyltransferases/genetics , Antimetabolites, Antineoplastic/therapeutic use , Humans , Mercaptopurine/pharmacology , Methyltransferases/metabolism
8.
Haemophilia ; 16(2): 322-32, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20028424

ABSTRACT

SUMMARY: Physiotherapy and radiography of the joints are standard diagnostic strategies for assessment of haemophilic arthropathy. The use of ultrasonography as an adjunct tool for early diagnosis of haemophilic arthropathy may optimize factor replacement therapy. The objective of this study was to compare costs and effectiveness of physiotherapy, radiography and ultrasonography (intervention strategy, IS) with physiotherapy and radiography alone (standard care strategy, SCS) for diagnosing soft tissue and osteocartilaginous changes in haemophilic joints. We retrospectively compared costs and effectiveness of IS vs. SCS in knees, ankles and elbows of 31 children (age range, 4-17 years) with haemophilia A (n = 30) or B (n = 1) (IS, n = 11; SS, N = 20). Direct health care costs were measured from the provincial health care perspective. Effectiveness was measured by false-negative (FN) rates in each study arm by comparing presence or absence of abnormalities of physiotherapy and imaging exams to the reference standard measure (MRI). In scenario 1, all diagnostic tests matched with MRI. In scenario 2, at least one diagnostic test matched with MRI. The IS was more costly [incremental cost/100 patients, Canadian (CND) $4987] and more effective (incremental effectiveness, FNs/100 patients for scenario 1, -4.09, and for scenario 2, -41) for both scenarios. The incremental cost-effectiveness ratios for scenario 1 and for scenario 2 were CND$1166 and CDN$116 per FN result averted per 100 patients, respectively. In conclusion, in the short-term, the incorporation of ultrasonography in a test set for diagnosis of haemophilic arthropathy substantially improved the diagnostic performance of this test set, however at an increased cost.


Subject(s)
Hemophilia A/complications , Joint Diseases/diagnosis , Joint Diseases/economics , Adolescent , Child , Child, Preschool , Cost-Benefit Analysis , Delivery of Health Care/economics , Health Care Costs , Humans , Joint Diseases/etiology , Joint Diseases/therapy , Magnetic Resonance Imaging , Male , Muscle, Skeletal/pathology , Physical Therapy Modalities , Retrospective Studies
9.
J Obstet Gynaecol ; 25(3): 241-4, 2005 Apr.
Article in English | MEDLINE | ID: mdl-16147725

ABSTRACT

The Pregnancy-Unique Quantification of Emesis (PUQE) is a scoring system to quantify the severity of nausea and vomiting of pregnancy (NVP). Based on quantification of the 3 physical symptoms of NVP (nausea, vomiting and retching), PUQE closely correlates with the validated but much more complex Rhodes' score. We examined the ability of PUQE to predict four independent aspects of NVP: (a) pregnant women's ability to take multivitamins. (b) rates of emergency room visits and hospitalisation for NVP. (c) health cost of NVP. (d) women's self scores of well-being in NVP. Using large prospective cohorts of women for each end point, severity of NVP measured by PUQE had significant predictive value for all 4 aspects sought. PUQE has been validated through 4 independent clinical outcomes of direct importance and relevance for NVP. The simplicity of PUQE and the ease of its execution make it a practical tool for both clinical follow-up and research.


Subject(s)
Morning Sickness/diagnosis , Severity of Illness Index , Emergency Service, Hospital/statistics & numerical data , Female , Health Care Costs , Health Status , Hospitalization , Humans , Pregnancy , Prenatal Care , Vitamins
10.
Haemophilia ; 10 Suppl 1: 50-7, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14987249

ABSTRACT

Prophylaxis is an expensive form of management in haemophilia but has demonstrated many advantages with respect to decreasing joint bleeds and potentially preventing joint damage. The valuation of prophylaxis and how the costs and benefits of this intervention compare with other interventions in the management of haemophiliacs can be evaluated through cost-utility analysis (CUA). CUA is an economic method of analysis where the benefits of a healthcare intervention are expressed as an overall utility or preference, usually in the form of quality-adjusted life years (QALYs). This is a composite measure, which takes into consideration both an individual's lifespan and quality of life (QoL). The most difficult aspect of performing a CUA is the measurement of health-related QoL (HRQoL). Much work is ongoing into evaluating HRQoL in haemophiliacs. This paper addresses some of the ways in which this can be achieved and some of the problems with evaluating HRQoL. Ultimately CUA may provide a tool to allow societies to decide if prophylaxis is worth the cost and how the costs and benefits of prophylaxis compare to other healthcare interventions for other disease entities.


Subject(s)
Health Status , Hemophilia A/economics , Quality of Life , Child , Cost of Illness , Costs and Cost Analysis , Drug Costs , Health Status Indicators , Hemophilia A/prevention & control , Humans , Quality-Adjusted Life Years , Treatment Outcome
11.
Arch Dis Child ; 89(1): 26-9, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14709497

ABSTRACT

BACKGROUND: Although standard methods for conducting economic evaluations have evolved, little attention has been paid to their application in paediatrics. The Paediatric Economic Database Evaluation (PEDE) Project was conceived to promote research into paediatric health economic methods. AIM: To examine trends in paediatric economic evaluation between 1980 and 1999. METHODS: A comprehensive literature database created for the PEDE project was the source of the data. Descriptive statistics were used to summarise trends. Publication volume, study outcome category, analytical technique, and journal type were examined over the study period. RESULTS: The literature search resulted in 787 full paediatric economic evaluations. The volume of publications increased from 61 to 440 citations per 5 year period. The most common health outcome category was cases of disease/condition/abnormality. Cost-effectiveness analysis (CEA) was the most common technique used, accounting for a majority of evaluations in all time periods. The proportion of studies using CEA increased by 23 percentage points, while the proportion using cost-benefit analysis decreased from 31% in 1980-84 to 12% in 1995-99. Cost-utility analysis was the least common analytical technique. Publication in journals of paediatrics/perinatal medicine was the most common venue for all intervals and increased as a proportion of the total over time. CONCLUSIONS: The growth in publication of paediatric economic evaluations suggests that increasing attention should be paid to the application of health economic methods to a paediatric population to ensure high quality allocation decisions.


Subject(s)
Child Health Services/economics , Pediatrics/economics , Child , Child Health Services/trends , Costs and Cost Analysis/trends , Health Policy/economics , Humans , Outcome Assessment, Health Care , Pediatrics/trends , Program Evaluation/economics
12.
Pediatr Pulmonol ; 32(2): 101-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11477726

ABSTRACT

Our objective was to assess the cost of asthma care at the patient level in children from the perspectives of society, the Ontario Ministry of Health, and the patient. In this longitudinal evaluation, health service use data and costs were collected during telephone interviews at 1, 3, and 6 months with parents of 339 Ontario children with asthma. Direct costs were respiratory-related visits to healthcare providers, emergency rooms, hospital admissions, pulmonary function tests, prescription medications, devices, and out-of-pocket expenses. Indirect costs were parents' absences from work/usual activities and travel and waiting time. Hospital admissions accounted for 43%, medications for 31%, and parent productivity losses for 12% of total costs from a societal perspective. Statistically significant predictors of higher total costs were worse symptoms, younger age group, and season of participation. Adjusted annual societal costs per patient in 1995 Canadian dollars varied from $1,122 in children aged 4-14 years to $1,386 in children under 4 years of age. From the Ministry of Health perspective, adjusted annual costs per patient were $663 in children over 4 years and $904 in younger children. Adjusted annual costs from the patient perspective were $132 in children over 4 years and $129 in children under 4 years. The rising incidence of pediatric asthma demands that greater attention be paid to the delivery of optimal care to this segment of the population. Appropriate methods must be used to analyze healthcare costs and the use of services in the midst of widespread healthcare reform. The quality of clinical and health policy decision-making may be enhanced by cost-of-illness estimates that are comprehensive, precise, and expressed from multiple perspectives.


Subject(s)
Asthma/economics , Asthma/therapy , Child Health Services/statistics & numerical data , Cost of Illness , Health Care Costs/statistics & numerical data , Adolescent , Age Factors , Canada , Child , Child, Preschool , Female , Health Policy , Humans , Male , Severity of Illness Index
13.
J Clin Densitom ; 3(3): 269-80, 2000.
Article in English | MEDLINE | ID: mdl-11090234

ABSTRACT

The Simple Calculated Osteoporosis Risk Estimation (SCORE) questionnaire is a tool to assist physicians to identify women who might require bone densitometry. The purpose of this study was to develop a Canadian SCORE and to assess validity and reliability. Twenty sites enrolled 307 postmenopausal women ages 50-70 yr. SCORE results were compared to hip and lumbar spine bone density assessed by dual X-ray absorptiometry. Sensitivity and specificity of a range of SCORE cut-points were assessed in a receiver operating characteristics analysis to determine the optimal cut-point for SCORE. With low bone density defined as a T-score < or = -2.0, a SCORE cut-point of 6 in women ages 50-59 yr displayed a sensitivity of 0. 96, 95% confidence interval (CI) (0.89, 1.00), a specificity of 0.51, 95% CI (0.43, 0.58). In women ages 60-70 yr, a SCORE cut-point of 8 displayed a sensitivity of 0.90, 95% CI (0.80, 0.97) and a specificity of 0.20, 95% CI (0.11, 0.29). The test-retest reliability (intraclass correlation coefficient) was 0.95. SCORE performed better in women in their fifties than women in ther sixties. Older women require higher SCORE cut-points. The use of SCORE as an initial measure for identifying those at risk for osteoporosis may reduce costs by limiting unnecessary tests.


Subject(s)
Absorptiometry, Photon , Bone Density , Osteoporosis, Postmenopausal/diagnostic imaging , Surveys and Questionnaires , Aged , Canada , Female , Humans , Middle Aged , Predictive Value of Tests , ROC Curve , Reproducibility of Results , Risk Factors , Sensitivity and Specificity
14.
Health Econ ; 9(1): 37-46, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10694758

ABSTRACT

In assessments of the cost of illness, productivity losses potentially constitute a large proportion. The present study objective was to develop a method to measure restricted days and to quantify total productivity loss days (PLDs) in adult asthma patients. Patient and disease characteristics, occupation, annual wage, work absences, restricted days, level of functioning on restricted days, and travel and waiting time were collected over 6 months in 892 adult asthma outpatients residing in southern Ontario. Annual PLDs varied from 12 in employed persons to 49 in disability pensioners. Homemakers reported 22 PLDs per year. Restricted days accounted for most PLDs and functional level during restricted days varied from 55% to 81%. Annual PLDs increased with increasing disease severity. Employed persons experienced the fewest PLDs and functioned at the highest level during restricted days, but also demonstrated a milder disease compared with other groups. Most productivity loss in asthma patients resulted from numerous restricted days, a category of PLD that is often ignored in economic assessments. The presentation of PLD results disaggregated by category of time loss and wage rate may provide valuable information to employers and health policy makers and may facilitate the application of multiple approaches to the calculation of indirect costs.


Subject(s)
Asthma/economics , Cost of Illness , Efficiency , Adult , Chi-Square Distribution , Data Collection , Employment/economics , Employment/statistics & numerical data , Female , Humans , Male , Middle Aged , Ontario , Statistics, Nonparametric
15.
J Clin Epidemiol ; 51(12): 1335-42, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10086828

ABSTRACT

Health services utilization information is important for outcomes research. This study assessed the reliability of self-reports of health services utilization in respiratory patients. Patients reported health services use and other information during three telephone interviews over 6 months. Reports of visits to general practitioners (GPs), specialists, emergency room (ER)/clinics, and hospital admissions were compared with corresponding fee service claims in the Ontario Health Insurance Plan administrative database in 83 subjects. Agreement between the two sources was calculated using observed agreement and estimated kappa. Substantial agreement was found for hospital admissions and visits to respiratory specialists. Agreement was moderate for GP visits and slight for ER/clinic visits. Patient self-report of ER use appeared unreliable and may be related to imprecise questionnaire wording and inadequately defined fee service codes. The findings emphasize the importance of the methods used to assess the reliability of patient self-reports used in outcomes research.


Subject(s)
Bronchial Diseases/drug therapy , Bronchodilator Agents/therapeutic use , Health Services/statistics & numerical data , Bronchial Diseases/epidemiology , Emergency Service, Hospital/statistics & numerical data , Family Practice/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Ontario/epidemiology , Outcome Assessment, Health Care , Quality of Life , Reproducibility of Results , Self Disclosure , Social Class
16.
Can Respir J ; 5(6): 463-71, 1998.
Article in English | MEDLINE | ID: mdl-10070174

ABSTRACT

OBJECTIVE: To assess the annual cost of asthma per adult patient from the perspectives of society, the Ontario Ministry of Health and the patient. DESIGN: Prospective cost of illness evaluation. SETTING: Ambulatory out-patients residing in southern central Ontario. POPULATION STUDIED: Nine hundred and forty patients with asthma over 15 years of age studied between May 1995 and April 1996. OUTCOME MEASURES: Direct costs, such as respiratory-related visits to general/family practitioners, respiratory specialists, emergency rooms, hospital admissions, laboratory tests, prescription medications, dispensing fees, devices and out-of-pocket expenses, were calculated. Indirect costs, such as absences from work or usual activities, and travel and waiting time, were studied. MAIN RESULTS: Unadjusted annual costs were $2,550 per patient. Hospitalizations and medications each accounted for 22% of the total cost and indirect costs 50% of the total costs. More severe disease, older age, smoking, drug plan availability and retirement were significant predictors of costs. Annual costs per patient varied from $1,255 (95% CI $1,061 to $1,485) in young nonsmokers with no drug plan and mild disease to $5,032 (95% CI $4,347 to $5,825) in older smokers with drug plans and severe disease. Clinically important reductions in the quality of life occurred with increasing severity. CONCLUSIONS: Interventions aimed at reducing productivity losses, admissions to hospital and medication costs may result in savings to society, the provincial government and the patient. The quality of policy and allocation decisions may be enhanced by cost of illness estimates that are comprehensive, precise and incorporate multiple perspectives.


Subject(s)
Asthma/economics , Financing, Personal , Absenteeism , Adolescent , Adult , Age Factors , Ambulatory Care/economics , Confidence Intervals , Cost of Illness , Drug Costs , Drug Prescriptions/economics , Emergency Service, Hospital/economics , Family Practice/economics , Female , Forecasting , Hospitalization/economics , Humans , Insurance, Pharmaceutical Services , Male , Middle Aged , Ontario , Prospective Studies , Respiratory Therapy/economics , Retirement , Smoking/adverse effects , Time Factors , Transportation of Patients/economics
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