Health trends in Canada 1990-2019: An analysis for the Global Burden of Disease Study.

OBJECTIVE: Monitoring trends in key population health indicators is important for informing health policies. The aim of this study was to examine population health trends in Canada over the past 30 years in relation to other countries. METHODS: We used data on disability-adjusted life years (DALYs), years of life lost (YLL), years lived with disability, life expectancy (LE), and child mortality for Canada and other countries between 1990 and 2019 provided by the Global Burden of Disease Study. RESULTS: Life expectancy, age-standardized YLL, and age-standardized DALYs all improved in Canada between 1990 and 2019, although the rate of improvement has leveled off since 2011. The top five causes of all-age DALYs in Canada in 2019 were neoplasms, cardiovascular diseases, musculoskeletal disorders, neurological disorders, and mental disorders. The greatest increases in all-age DALYs since 1990 were observed for substance use, diabetes and chronic kidney disease, and sense organ disorders. Age-standardized DALYs declined for most conditions, except for substance use, diabetes and chronic kidney disease, and musculoskeletal disorders, which increased by 94.6%, 14.6%, and 7.3% respectively since 1990. Canada's world ranking for age-standardized DALYs declined from 9th place in 1990 to 24th in 2019. CONCLUSION: Canadians are healthier today than in 1990, but progress has slowed in Canada in recent years in comparison with other high-income countries. The growing burden of substance abuse, diabetes/chronic kidney disease, and musculoskeletal diseases will require continued action to improve population health.

RéSUMé: OBJECTIF: La surveillance des tendances des indicateurs clés de la santé de la population est importante pour éclairer les politiques de santé. Dans cette étude, nous avons examiné les tendances de la santé de la population au Canada au cours des 30 dernières années par rapport à d'autres pays. MéTHODES: Nous avons utilisé des données sur les années de vie ajustées en fonction de l'incapacité (DALY), les années de vie perdues (YLL), les années vécues avec un handicap, l'espérance de vie (LE) et la mortalité infantile pour le Canada et d'autres pays entre 1990 et 2019, fournies par l'Étude mondiale sur le fardeau de la maladie. RéSULTATS: L'espérance de vie, les YLL ajustées selon l'âge et les DALY ajustées selon l'âge ont tous connu une amélioration au Canada entre 1990 et 2019, bien que le taux d'amélioration se soit stabilisé depuis 2011. Les cinq principales causes des DALY pour tous les âges au Canada en 2019 étaient les néoplasmes, les maladies cardiovasculaires, les affections musculosquelettiques, les affections neurologiques et les troubles mentaux. Les plus fortes augmentations des DALY pour tous les âges depuis 1990 ont été observées pour l'usage de substances, le diabète et les maladies rénales chroniques, ainsi que les troubles des organes sensoriels. Les DALY ajustées selon l'âge ont diminué pour la plupart des conditions, à l'exception de l'usage de substances, du diabète et des maladies rénales chroniques, ainsi que des troubles musculosquelettiques, qui ont augmenté de 94,6 %, 14,6 % et 7,3 % respectivement depuis 1990. Le classement mondial du Canada pour les DALY ajustées selon l'âge est diminué de la 9ième place en 1990 à la 24ième place en 2019. CONCLUSION: Les Canadiens sont en meilleure santé aujourd'hui qu'en 1990, mais les progrès se sont ralentis ces dernières années par rapport à d'autres pays à revenu élevé. La croissance du fardeau lié à l'abus de substances, au diabète/maladies rénales chroniques et aux affections musculosquelettiques exigera des actions continues pour améliorer la santé de la population.

Effect of Immunosuppressive or Immunomodulatory Agents on Severe COVID-19 Outcomes: A Population-Based Cohort Study.

OBJECTIVE: We estimated the association between immunosuppressive and immunomodulatory agent (IIA) exposure and severe COVID-19 outcomes in a population-based cohort study. METHODS: Participants were 18 years or older, tested positive for SARS-CoV-2 between February 6, 2020, and August 15, 2021, and were from administrative health data for the entire province of British Columbia, Canada. IIA use within 3 months prior to positive SARS-CoV-2 test included conventional disease-modifying antirheumatic drugs (antimalarials, methotrexate, leflunomide, sulfasalazine, individually), immunosuppressants (azathioprine, mycophenolate mofetil/mycophenolate sodium [MMF], cyclophosphamide, cyclosporine, individually and collectively), tumor necrosis factor inhibitor (TNFi) biologics (adalimumab, certolizumab, etanercept, golimumab, infliximab, collectively), non-TNFi biologics or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) (rituximab separately from abatacept, anakinra, secukinumab, tocilizumab, tofacitinib and ustekinumab collectively), and glucocorticoids. Severe COVID-19 outcomes were hospitalizations for COVID-19, ICU admissions, and deaths within 60 days of a positive test. Exposure score-overlap weighting was used to balance baseline characteristics of participants with IIA use compared with nonuse of that IIA. Logistic regression measured the association between IIA use and severe COVID-19 outcomes. RESULTS: From 147,301 participants, we identified 515 antimalarial, 573 methotrexate, 72 leflunomide, 180 sulfasalazine, 468 immunosuppressant, 378 TNFi biologic, 49 rituximab, 144 other non-TNFi biologic or tsDMARD, and 1348 glucocorticoid prescriptions. Risk of hospitalizations for COVID-19 was significantly greater for MMF (odds ratio [95% CI]): 2.82 [1.81-4.40], all immunosuppressants: 2.08 [1.51-2.87], and glucocorticoids: 1.63 [1.36-1.96], relative to nonuse. Similar outcomes were seen for ICU admission and MMF: 2.52 [1.34-4.74], immunosuppressants: 2.88 [1.73-4.78], and glucocorticoids: 1.86 [1.37-2.54]. Only glucocorticoids use was associated with a significant increase in 60-day mortality: 1.58 [1.21-2.06]. No other IIAs displayed statistically significant associations with severe COVID-19 outcomes. CONCLUSION: Current use of MMF and glucocorticoids were associated with an increased risk of severe COVID-19 outcomes compared with nonuse. These results emphasize the variety of circumstances of patients taking IIAs.

The Impact of 51 Risk Factors on Life Expectancy in Canada: Findings from a New Risk Prediction Model Based on Data from the Global Burden of Disease Study.

The aims of this study were (1) to develop a comprehensive risk-of-death and life expectancy (LE) model and (2) to provide data on the effects of multiple risk factors on LE. We used data for Canada from the Global Burden of Disease (GBD) Study. To create period life tables for males and females, we obtained age/sex-specific deaths rates for 270 diseases, population distributions for 51 risk factors, and relative risk functions for all disease-exposure pairs. We computed LE gains from eliminating each factor, LE values for different levels of exposure to each factor, and LE gains from simultaneous reductions in multiple risk factors at various ages. If all risk factors were eliminated, LE in Canada would increase by 6.26 years for males and 5.05 for females. The greatest benefit would come from eliminating smoking in males (2.45 years) and high blood pressure in females (1.42 years). For most risk factors, their dose-response relationships with LE were non-linear and depended on the presence of other factors. In individuals with high levels of risk, eliminating or reducing exposure to multiple factors could improve LE by several years, even at a relatively advanced age.

Distinguishing symptom patterns in adults newly diagnosed with cancer: a latent class analysis.

CONTEXT: Socio-demographic differences, including place of residence, socio-economic status, ethnicity, and gender, have been associated with various inequities in cancer care outcomes. OBJECTIVES: The aims were to distinguish subgroups of patients with different symptom patterns at the time of the initial oncology visit and determine which clinical and socio-demographic variables are associated the different symptom patterns. METHOD: Responses to the Edmonton Symptom Assessment Scale- revised and clinical and socio-demographic variables were obtained via the Ontario Cancer Registry and linked health data files. Latent class analyses were conducted to identify and compare the subgroups. RESULTS: The cohort (n = 216,110) with a mean age of 64.5 years consisted of 54.1% women. The analyses identified six latent classes (proportions ranging from 0.09 to 0.31) with distinct symptom patterns, including: 1) many severe symptoms, 2) many less severe symptoms, 3) predominantly mild symptoms, 4) severe psychosocial symptoms, 5) severe somatic symptoms, 6) few symptoms. The subgroups were associated not only with clinical differences (diagnoses and functional status), but also with various socio-demographic (age, sex) and community characteristics (neighborhood income, proportion of foreign born, rurality). CONCLUSION: The results indicated that there were substantial differences in symptom patterns at the time of the initial oncology visit, which were associated with both clinical diagnoses and socio-demographic differences. These results point to the importance of taking the social situation of patients into account, and not just diagnosis, to better understand differences in symptom patterns of people living with cancer.

A comparison of three strategies to reduce the burden of osteoarthritis: A population-based microsimulation study.

OBJECTIVES: The purpose of this study was to compare three strategies for reducing population health burden of osteoarthritis (OA): improved pharmacological treatment of OA-related pain, improved access to joint replacement surgery, and prevention of OA by reducing obesity and overweight. METHODS: We applied a validated computer microsimulation model of OA in Canada. The model simulated a Canadian-representative open population aged 20 years and older. Variables in the model included demographics, body mass index, OA diagnosis, OA treatment, mortality, and health-related quality of life. Model parameters were derived from analyses of national surveys, population-based administrative data, a hospital-based cohort study, and the literature. We compared 8 what-if intervention scenarios in terms of disability-adjusted life years (DALYs) relative to base-case, over a wide range of time horizons. RESULTS: Reductions in DALYs depended on the type of intervention, magnitude of the intervention, and the time horizon. Medical interventions (a targeted increase in the use of painkillers) tended to produce effects quickly and were, therefore, most effective over a short time horizon (a decade). Surgical interventions (increased access to joint replacement) were most effective over a medium time horizon (two decades or longer). Preventive interventions required a substantial change in BMI to generate a significant impact, but produced more reduction in DALYs than treatment strategies over a very long time horizon (several decades). CONCLUSIONS: In this population-based modeling study we assessed the potential impact of three different burden reduction strategies in OA. Data generated by our model may help inform the implementation of strategies to reduce the burden of OA in Canada and elsewhere.

Association of Knee Effusion Detected by Physical Examination With Bone Marrow Lesions: Cross-Sectional and Longitudinal Analyses of a Population-Based Cohort.

OBJECTIVE: To determine the association of effusion detected by physical examination with the prevalence of bone marrow lesions (BMLs) on magnetic resonance imaging (MRI), and the incidence/progression of BMLs over 3 years in subjects with knee osteoarthritis. METHODS: A population-based cohort with knee pain (n = 255) was assessed for effusion on physical examination. On MRI, BMLs were graded 0-3 (none, mild, moderate, severe), and incidence/progression was defined as a worsening of the sum of BML scores over 6 surfaces by ≥1 grade. We analyzed the full cohort and a mild disease subsample with a Kellgren/Lawrence (K/L) grade <3. Cross-sectional logistic and longitudinal exponential regression analyses were performed, adjusted for age, sex, body mass index (BMI) and pain. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for effusion detected by physical examination versus BMLs (prevalence and incidence/progression). RESULTS: The weighted mean age was 56.7 years, the mean BMI was 26.5, 56.3% were women, 20.1% had effusion on physical examination, and 80.7% had a K/L grade <3. Effusion on physical examination was significantly associated with prevalent BMLs in the full cohort (odds ratio [OR] 6.10 [95% confidence interval (95% CI) 2.77-13.44]) and in the K/L grade <3 cohort (OR 6.88 [95% CI 2.76-17.15]). In the full cohort, sensitivity, specificity, PPV, and NPV were 34.6, 92.5, 79.9, and 62.1%, respectively, and in the K/L <3 cohort 31.7, 94.0, 75.5, and 70.1%, respectively. Longitudinally, effusion on physical examination was not significantly associated with BML incidence/progression in the full cohort (hazard ratio [HR] 1.83 [95% CI 0.95-3.52]) or in the K/L grade <3 cohort (HR 1.73 [95% CI 0.69-4.33]). In the two cohorts, sensitivity, specificity, PPV, and NPV were 32.0, 82.2, 42.2, and 74.9%, respectively, and 21.2, 85.6, 30.1, and 78.8% respectively. CONCLUSION: BMLs on MRI can be predicted from physical examination effusion cross-sectionally, with a high PPV of 79.9%. Assessment for knee effusion on physical examination is useful for determining potential candidates with BMLs before costly MRI screening for recruitment into clinical trials.

Associations between MRI features versus knee pain severity and progression: Data from the Vancouver Longitudinal Study of Early Knee Osteoarthritis.

OBJECTIVE: To determine associations between features of osteoarthritis (OA) on MRI and knee pain severity and knee pain progression. DESIGN: Baseline, 3.3- and 7.5-year assessments were performed for 122 subjects with baseline knee pain (age 40-79), sample-weighted for population (with knee pain) representativeness. MRIs were scored for: osteophytes (0:absent to 3:large); cartilage (0:normal to 4:full thickness defect; 0/1 collapsed); subchondral sclerosis (0:none to 3:>50% of site), subchondral cyst (0:absent to 3:severe), bone marrow lesions (0:none to 3:≥50% of site); and meniscus (0:normal to 3:maceration/resection), in 6-8 regions each. Per feature, scores were averaged across regions. Effusion/synovitis (0:absent to 3:severe) was analyzed as ≥2 vs. <2. Linear models predicted WOMAC knee pain severity (0-100), and binary models predicted 10+ (minimum perceptible clinical improvement [MPCI]) and 20+ (minimum clinically important difference [MCID]) increases. Models were adjusted for age, sex, BMI (and follow-up time for longitudinal models). RESULTS: Pain severity was associated with osteophytes (7.17 per unit average; 95% CI = 3.19, 11.15) and subchondral sclerosis (11.03; 0.68, 21.39). MPCI-based pain increase was associated with osteophytes (odds ratio per unit average 3.20; 1.36, 7.55), subchondral sclerosis (5.69; 1.06, 30.44), meniscal damage (1.68; 1.08, 2.61) and effusion/synovitis ≥2 (2.25; 1.07, 4.71). MCID-based pain increase was associated with osteophytes (3.79; 1.41, 10.20) and cartilage defects (2.42; 1.24, 4.74). CONCLUSIONS: Of the features investigated, only osteophytes were consistently associated with pain cross-sectionally and longitudinally in all models. This suggests an important role of bone in early knee osteoarthritis.

Distribution and Drivers of Average Direct Cost of Osteoarthritis in Canada From 2003 to 2010.

OBJECTIVE: To estimate the distribution and drivers of the average direct cost of osteoarthritis (OA) in Canada using a population-based health microsimulation model of OA from 2003 to 2010. METHODS: We used a previously published microsimulation model to estimate the distribution of average cost of OA across different cost components and OA stages. OA stages were defined according to the patient flow within the health care system. Cost components associated with pharmacologic and nonpharmacologic treatments, physician visits, and hospitalization were included. Scenario analysis was performed to evaluate average cost drivers from 2003 to 2010. RESULTS: During the study period, the OA population size grew from 2.9 to 3.6 million, while the average cost increased from $577 to $811 (Canadian) per patient per year. The highest increase in share of cost components was for total joint replacement (TJR) surgery (24% to 32%). The highest average cost was incurred by patients in stage 4 (during and after revision surgery), while around 80% of OA patients were in stage 1 (OA diagnosed but has not visited an orthopedic surgeon). Increase in the proportion of OA patients receiving TJR surgeries (34%) and price inflation (29%) were the most significant drivers of average cost. CONCLUSION: The average cost of OA has been increasing during the study period mostly due to an increase in the proportion of patients receiving TJR surgeries and price inflation. The distribution of average cost of OA across disease stages needs to be considered when designing policies targeting specific aspects of OA care.

The effect of waiting time on pain intensity after elective surgical lumbar discectomy.

BACKGROUND CONTEXT: Waitlists are commonly used in Canada to manage access to surgical procedures such as elective surgical lumbar discectomy (ESLD). The timing of enrollment onto the waitlist is important as this is a proxy measure for the concordance of preferences for surgery between a patient and surgeon. After enrollment, the waiting time to actual surgery extends the duration of preoperative symptoms, which possibly affects the outcome of ESLD. Waiting time also specifically reflects the delay in service delivery imposed by the limited capacity of the health-care system. PURPOSE: To determine if a system-imposed delay in treatment, that is, longer waiting time, for ESLD is associated with a higher odds of experiencing residual postoperative pain. STUDY DESIGN/SETTING: Ambidirectional cohort study with 2-year retrospective and 3-year prospective components, conducted at a major tertiary care center serving a metropolitan area in Canada. PATIENT SAMPLE: Patients aged 16 years or older with sciatica because of herniated lumbar disc, confirmed on advanced imaging, were recruited at the time of waitlist enrollment for ESLD. Patients with significant comorbidity or emergency indications for surgery were excluded. Of 391 participants, 291 had complete follow-up information at 6 months postoperatively. OUTCOME MEASURE: Intensity of the predominant symptom (worse of either back or leg pain) was assessed on the 11-point numerical rating scale at waitlist enrollment and 6 months postoperatively. Pain scores were highly skewed and therefore categorized into four ordinal levels defined by quartiles. METHODS: For the primary analysis, time to surgery from waitlist enrollment was dichotomized based on a predetermined clinically meaningful cut-point of 12 weeks. Ordinal logistic regression was used to compare the odds of experiencing higher pain intensity between wait groups. Control of confounders was achieved using both propensity scores and conventional multivariable modeling. RESULTS: In unadjusted analyses, long-wait patients were 80% more likely than short-wait patients to experience higher ordinal pain intensity at 6 months; unadjusted proportional odds ratio (POR)=1.8 (95% confidence interval [CI], 1.2-2.8). The association held after controlling for all imbalances in measured confounders, with long-wait patients still being 70% more likely to report worse pain; adjusted POR=1.7 (95% CI, 1.0-2.8). CONCLUSIONS: A waiting time of 12 weeks or more after waitlist enrollment for ESLD is associated with a modest likelihood of experiencing worse pain at 6 months postoperatively. This result was not because of differences in measured confounders. Future studies are encouraged to identify other, as-of-yet unmeasured, variables that might be associated with both longer waiting times and worse outcomes among ESLD patients. Until then, in jurisdictions where highly constrained access to ESLD is managed through waitlists, the expected waiting time for the operation could be an informative deciding criterion for patients with otherwise unresolved preferences for operative treatment.

The relationship between osteoarthritis and cardiovascular disease in a population health survey: a cross-sectional study.

OBJECTIVES: Our objective was to determine the relationship between osteoarthritis (OA) and heart diseases (myocardial infarction (MI), angina, congestive heart failure (CHF)) and stroke using population-based survey data. DESIGN: Cross-sectional study. SETTING: Canadian Community Health Survey (CCHS). PARTICIPANTS: Adult participants in the CCHS cycles 1.1, 2.1 and 3.1 were included. CCHS provides nationally representative data on health determinants, health status and health system utilisation. We have identified 40 817 self-reported OA subjects and selected 1:1 matched non-OA respondents by age, sex and CCHS cycles. MAIN OUTCOME MEASURES: Self-reported heart disease was the primary outcome and MI, angina, CHF and stroke were considered as secondary outcomes. Multivariable logistic regression models were used to estimate the ORs after adjusting for sociodemographic status, obesity, physical activity, smoking status, fruit and vegetable consumption, medication use, diabetes, hypertension and chronic obstructive pulmonary disease. RESULTS: The mean age of OA cases was 66 years and 71.6% were women. OA exhibited increased odds of prevalent heart disease, and adjusted overall OR (95% CI) was 1.45 (1.36 to 1.54), 1.35 (1.21 to 1.50) among men and 1.51 (1.39 to 1.64) among women with OA. OA showed increased ORs for angina and CHF in both men and women, and for MI in women. ORs (95% CI) for men and women, respectively, were 1.08 (0.91 to 1.28) and 1.49 (1.28 to 1.75) for MI, 1.76 (1.43 to 2.17) and 1.84 (1.59 to 2.14) for angina, 1.50 (1.13 to 1.97) and 1.81 (1.49 to 2.21) for CHF, and 1.08 (0.83 to 1.40) and 1.13 (0.93 to 1.37) for stroke. CONCLUSIONS: Prevalent OA was associated with self-reported heart disease, particularly angina, and CHF in both men and women, after controlling for established risk factors for these conditions. This study provides a rationale for further investigation of the association between OA and heart disease in longitudinal studies for investigating possible biological and behavioural mechanisms.

Relationship between arm morbidity and patient-reported outcomes following surgery in women with node-negative breast cancer: NSABP protocol B-32.

BACKGROUND: The impact of arm morbidity following breast cancer surgery on patient-observed changes in daily functioning and health-related quality of life (HRQoL) has not been well-studied. OBJECTIVE: To examine the association of objective measures such as range of motion (ROM) and lymphedema, with patient-reported outcomes (PROs) in the arm and breast, upper extremity function, activities, and HRQoL. METHODS: The National Surgical Adjuvant Breast and Bowel Project Protocol B-32 was a randomized trial comparing sentinel node resection (SNR) with axillary dissection (AD) in women with node-negative breast cancer. ROM and arm volume were measured objectively. PROs included symptoms; arm function; limitations in social, recreational, occupational, and other regular activities; and a global index of HRQoL. Statistical methods included cross-tabulations and multivariable linear regression models. RESULTS: In all, 744 women provided at least 1 postsurgery assessment. About one-third of the patients experienced arm mobility restrictions. A similar number of patients avoided the use of the arm 6 months after surgery. Limitations in work and other regular activities were reported by about a quarter of the patients. In this multivariable analysis, arm mobility and sensory neuropathy were predictors of patient-reported arm function and overall HRQoL. Predictors for activity limitations also included side of surgery (dominant vs nondominant). Edema was not significant after adjustment for sensory neuropathy and ROM. LIMITATIONS: Arm mobility and edema were measured simultaneously only once during the follow-up (6 months). CONCLUSION: Clinical measures of sensory neuropathy and restrictions in arm mobility following breast cancer surgery are associated with self-reported limitations in activity and reductions in overall HRQoL.

Long-term neurotoxicity effects of oxaliplatin added to fluorouracil and leucovorin as adjuvant therapy for colon cancer: results from National Surgical Adjuvant Breast and Bowel Project trials C-07 and LTS-01.

BACKGROUND: Neurotoxicity from adjuvant treatment with oxaliplatin has been studied in patients with colorectal carcinoma in short-term studies, but, to the authors' knowledge, the current article is the first long-term assessment which reports the National Surgical Adjuvant Breast and Bowel Project (NSABP) investigation of whether excess neurotoxicity persists beyond 4 years. METHODS: As part of a colorectal cancer long-term survivor study (LTS-01), long-term neurotoxicity was assessed in 353 patients on NSABP Protocol C-07 (cross-sectional sample). Ninety-two of these patients from LTS-01 also had longitudinal data and were reassessed 5 to 8 years (median, 7 years) after random assignment (longitudinal sample). Contingency tables compared cohorts, a mixed model compared neurotoxicity between treatments over time, and a Wilcoxon rank-sum test compared neurotoxicity between treatments (cross-sectional sample). RESULTS: In the cross-sectional sample, the increase in mean total neurotoxicity scores of 1.8 with oxaliplatin was statistically significant (P = .005), but not clinically significant (a minimally important difference of 4 was reported at the long-term assessment). Patients who received oxaliplatin had increased odds of numbness and tingling in hands (odds ratio, 2.00; P = .015) and feet (odds ratio, 2.78; P < .001) versus patients who did not receive oxaliplatin. The magnitude of the oxaliplatin effect varied with time (P < .001) in the longitudinal sample, such that the oxaliplatin-treated group did not have significantly greater total neurotoxicity scores by 7 years. CONCLUSIONS: At the long-term endpoint, there was no clinically significant increase in total neurotoxicity scores for patients who received oxaliplatin, but the specific neurotoxicities of numbness and tingling of the hands and feet remained significantly elevated for oxaliplatin-treated patients.

Delayed recovery in patients with whiplash-associated disorders.

BACKGROUND: Prognosis of whiplash injury has been found to be related to a number of sociodemographic, treatment and clinical factors. In the current study, we attempt to identify several novel prognostic factors for delayed recovery in whiplash-associated disorders (WADs), using a validated and reliable measure of recovery. PATIENTS AND METHODS: Retrospective review of a large database of a national network of physiotherapy and rehabilitation service providers in Canada yielded 5581 individuals injured in motor vehicle collisions. Cases were grouped into 3 cohorts based on time lapsed between injury date and initial presentation. Acute (n=3075), early chronic (n=958) and chronic (n=1548) patient cohorts were compared regarding treatment outcome and relative distribution of 29 prognostic factors. Outcome was defined by a minimally important clinical change (10%) on a previously validated disability questionnaire between initial and discharge rehabilitation visits. RESULTS: Analysis demonstrated positive outcomes to be proportionally fewer in the chronic cohort (52.1%) relative to the early chronic (61.4%), which was in turn lower than the acute cohort (72.3%). Furthermore, individuals presenting with chronic pain were more likely to: (1) be female; (2) present with lower limb pain or nonorganic signs; (3) have returned to work; (4) have retained a lawyer; or (5) have undergone previous spinal surgery, and were less likely to: (1) present with neck or midback pain; (2) live in Ontario or Nova Scotia; or (3) have modified duties upon return to work. Acute, early chronic and chronic cohorts were also found to differ in the distribution of several other prognostic factors at initial clinical visit. CONCLUSIONS: Recovery in whiplash-associated disorder appears to be multifactorial with both medical and non-injury related factors influencing outcome. Further characterisation of these factors may prove invaluable in guiding future clinical treatment and referral practices.

Frequency of bone marrow lesions and association with pain severity: results from a population-based symptomatic knee cohort.

OBJECTIVE: To evaluate the prevalence of bone marrow lesions (BML) and their association with pain severity in a population-based cohort of symptomatic early knee osteoarthritis (OA). METHODS: Subjects with knee pain (n = 255), age 40-79 years, were evaluated by radiograph and magnetic resonance imaging (MRI) and classified into OA stages: no OA (NOA), preradiographic OA (PROA), and radiographic OA (ROA). BML were graded 0-3 (none, mild, moderate, severe) in 6 regions and defined as (1) BMLsum = the sum of 6 scores; and (2) BMLmax = the worst score at any region. Pain was assessed by the Western Ontario and McMaster Universities OA Index (WOMAC). Linear regression analysis was completed to assess the association of Total WOMAC Pain (primary outcome) versus BMLsum or BMLmax. Secondary outcomes were WOMAC Pain on Walking and WOMAC Pain on Climbing Stairs. All analyses were adjusted for age, sex, body mass index, OA stage, joint effusion, and meniscal damage. RESULTS: BML were present in 11% of NOA, 38% of PROA, and 71% of ROA subjects (p < 0.001). No association was seen for BMLsum or BMLmax versus Total WOMAC Pain or Pain on Walking. However, BMLsum was associated with Pain on Climbing Stairs [regression coefficients (RC) = 0.09, 95% CI 0.00-0.18]. BMLmax was associated with Pain on Climbing Stairs, with the strongest association for severe BML (RC 0.60, 95% CI 0.04-1.17). CONCLUSION: BML were present in 38% of PROA and 71% of ROA subjects in this symptomatic knee cohort. BML were significantly associated with Pain on Climbing Stairs but not Total WOMAC or Pain on Walking.

Patient-reported outcomes in sentinel node-negative adjuvant breast cancer patients receiving sentinel-node biopsy or axillary dissection: National Surgical Adjuvant Breast and Bowel Project phase III protocol B-32.

PURPOSE: Sentinel lymph node resection (SNR) may reduce morbidity while providing the same clinical utility as conventional axillary dissection (AD). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 is a randomized phase III trial comparing SNR immediately followed by AD (SNAD) to SNR and subsequent AD if SN is positive. We report the definitive patient-reported outcomes (PRO) comparisons. PATIENTS AND METHODS: Eligible patients had clinically node-negative, operable invasive breast cancer. The PRO substudy included all SN-negative participants enrolled May 2001 to February 2004 at community institutions in the United States (n = 749; 78% age > or = 50; 87% clinical tumor size < or = 2.0 cm; 84% lumpectomy; 87% white). They completed questionnaires presurgery, 1 and 2 to 3 weeks postoperatively, and every 6 months through year 3. Arm symptoms, arm use avoidance, activity limitations, and quality of life (QOL) were compared with intent-to-treat two-sample t-tests and repeated measures analyses. RESULTS: Arm symptoms were significantly more bothersome for SNAD compared with SNR patients at 6 months (mean, 4.8 v 3.0; P < .001) and at 12 months (3.6 v 2.5; P = .006). Longitudinally, SNAD patients were more likely to experience ipsilateral arm and breast symptoms, restricted work and social activity, and impaired QOL (P < or = .002 all items). From 12 to 36 months, fewer than 15% of either SNAD or SNR patients reported moderate or greater severity of any given symptom or activity limitation. CONCLUSION: Arm morbidity was greater with SNAD than with SNR. Despite considerable fears about complications from AD for breast cancer, this study demonstrates that initial problems with either surgery resolve over time.

The effect of compensation status on waiting time for elective surgical lumbar discectomy.

STUDY DESIGN: Prospective cohort study of patients registered for elective surgical lumbar discectomy (ESLD) between November 1999 and December 2003 at a major tertiary care center in Vancouver. OBJECTIVE: To determine whether compensation status was associated with longer waiting time for ESLD. SUMMARY OF BACKGROUND DATA: In Canada, access to publicly funded ESLD is managed through waitlists. Patients are prioritized according to case severity and clinical need. However, it is not known whether compensation status is associated with waiting times. METHODS: Patients with sciatica from herniated lumbar disc, confirmed on advanced imaging, were registered for surgery. Information was collected on 393 patients, 66 (17%) who were receiving workers' compensation or personal disability insurance. Waiting time was calculated from registration to surgery and back pain and leg pain intensities were assessed by surgeons, using an 11-point numerical rating scale. Weekly probabilities of remaining on the waitlist were estimated using Kaplan-Meier methods. Patients undergoing emergency surgery or waiting longer than 12 months were censored. Waiting times were compared using the log-rank test, and Cox regression was used to estimate the effect of compensation on waiting after controlling for confounders. RESULTS: Pain intensity, neurologic status, and symptom duration were associated with waiting time. Compensation status was associated with a lower, statistically nonsignificant, likelihood of undergoing ESLD; hazard ratio (HR) = 0.83 (95% CI: 0.63-1.11) and the effect was attenuated with adjustment; HR = 1.02 (95% CI: 0.76-1.38). The median adjusted waiting time for surgery was 7 weeks among noncompensated and compensated patients. CONCLUSION: These results provide evidence that, contrary to conventional wisdom, compensation status was not associated with longer waits for ESLD. While patients receiving compensation have elsewhere been observed to have worse outcomes after discectomy, our results suggest this is unlikely to be due to delays imposed by queuing.

Reliability of self-report versus chart-based prostate cancer, PSA, DRE and urinary symptoms.

INTRODUCTION: Medical chart-review and self-reported questionnaire are two common methods of determining cancer screening and symptoms. We investigate the validity of these methods and therefore of a class of clinical/epidemiological studies. We compare variables on prostate cancer, any prostate-specific antigen (PSA) test, asymptomatic screening PSA, any digital rectal exam (DRE), and urinary symptoms. We used data from a 2005 case control study of PSA and metastatic prostate cancer (253 cases and 496 controls). Data were collected from 1999 to 2002. METHODS: We calculated kappa, percent agreement (PPA) and prevalence adjusted bias adjusted kappa (PABAK). We compared percentage positive response (PPR) and sensitivities/specificities of questionnaire against chart and vice versa. We measured the degree of differential agreement between cases and controls using odds ratios. RESULTS: We found almost perfect agreement on prostate cancer, moderate agreement on any PSA and DRE, and slight agreement on asymptomatic screening PSA and urinary symptoms. PABAK ranged from 0.134 (urinary symptoms) to 0.879 (prostate cancer). Differences between cases/controls in PPR are similar according to chart or questionnaire, though PPR itself is usually higher on the questionnaire. Only for any PSA (including diagnostic), cases had better recall than controls. We found no evidence of differential agreement that might lead to bias in a case control study. CONCLUSIONS: Some variables are more reliable than others comparing medical chart review and self-report. Diagnosis of prostate cancer has near perfect agreement, but for less catastrophic events such as PSA (especially asymptomatic screening tests), DRE or urinary symptoms, agreement ranges from slight to moderate.

Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07.

PURPOSE: The randomized, multicenter, phase III protocol C-07 compared the efficacy of adjuvant bolus fluorouracil and leucovorin (FULV) versus FULV with oxaliplatin (FLOX) in stage II or III colon cancer. Definitive analysis revealed an increase in 4-year disease-free survival from 67.0% to 73.2% in favor of FLOX. This study compares neurotoxicity between the treatments. PATIENTS AND METHODS: Neurotoxicity was recorded for all patients using standard adverse event reporting. Patients at select institutions completed a neurotoxicity questionnaire through 18 months of follow-up. RESULTS: A total of 2,492 patients enrolled onto C-07 and 400 patients enrolled onto the patient-reported substudy. Mean patient-reported neurotoxicity was higher with oxaliplatin throughout the 18 months of study (P < .0001). During therapy, patients receiving oxaliplatin experienced significantly more hand/foot toxicity (eg, "quite a bit" of cold-induced hand/foot pain 26% FLOX v 2.6% FULV) and overall weakness (eg, moderate weakness in 27.4% FLOX v 16.2% FULV). At 18 months, hand neuropathy had diminished, but patients who received oxaliplatin experienced continued foot discomfort (eg, moderate foot numbness and tingling for 22.1% FLOX v 4.6% FULV). Observer-reported neurotoxicity was low grade and primarily neurosensory rather than neuromotor. Sixty-eight percent in the FLOX group v 8% in the FULV group had neurotoxicity at their first on-treatment assessment. Time to resolution was significantly longer for those receiving oxaliplatin, and continued beyond 2 years for more than 10% in the oxaliplatin group. CONCLUSION: Oxaliplatin causes significant neurotoxicity. It is experienced primarily in the hands during therapy and in the feet during follow-up. In a minority of patients the neurotoxicity is long lasting.

Quality of life in operable colon cancer patients receiving oral compared with intravenous chemotherapy: results from National Surgical Adjuvant Breast and Bowel Project Trial C-06.

PURPOSE: We compared health-related quality of life (HRQL), symptoms, and convenience of care (COC) in patients with stage II/III carcinoma of the colon who received either oral uracil/ftorafur (UFT) plus leucovorin (LV) or standard intravenous (IV) fluorouracil (FU) plus LV as adjuvant chemotherapy. PATIENTS AND METHODS: We measured HRQL with the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire, Short Form-36 Vitality Scale (SF-36), and a Quality of Life Rating Scale (QLRS) at baseline, once during chemotherapy, and at 1 year. We used the Symptom Distress Scale (SDS) and treatment-specific Symptom Checklist (SCL) to assess symptoms and a modified Burden of Care form to assess COC at baseline, on day 1 of each treatment cycle, and at 1 year. Repeated measures analyses controlling for demographic variables and baseline scores were used for statistical comparisons. RESULTS: The study accrued 1,608 patients, 803 to the FU arm and 805 to the UFT arm. There were no differences between the arms in overall FACT-C scores, FACT-C scores within the subscales of colon-specific, physical, emotional, social, and functional health, or QLRS scores. Patients taking UFT reported substantially higher COC. Statistically significant but small differences were observed for SF-36, favoring FU, and for SDS and SCL, both favoring UFT. CONCLUSION: Patients perceive adjuvant treatment with UFT + LV as more convenient than standard IV treatment with FU + LV. Both regimens are well tolerated and do not differ in their impact on HRQL.

Screening with prostate specific antigen and metastatic prostate cancer risk: a population based case-control study.

PURPOSE: Screening of asymptomatic men with prostate specific antigen (PSA) remains a controversial issue. There is limited evidence that screening is effective in reducing mortality from prostate cancer. In the current study we determined if screening with PSA reduces the risk of metastatic prostate cancer. MATERIALS AND METHODS: We conducted a population based case-control study among the residents of Metropolitan Toronto and 5 surrounding counties in Ontario, Canada. Data were obtained from 236 cases of metastatic prostate cancer and 462 controls randomly sampled from the source population and frequency matched to cases for age and area of residence. History of PSA testing, digital rectal examination, symptoms and other data were obtained from medical records and a self-administered questionnaire. The association between PSA screening and metastatic prostate cancer was measured by the Mantel-Haenszel odds ratio stratified by exposure observation time and other potential confounding factors. RESULTS: In asymptomatic men, the frequency of PSA screening as determined from medical records was significantly lower among the cases compared with the controls (odds ratio 0.65, 95% confidence interval 0.45 to 0.93). The odds ratio was 0.52 (0.28 to 0.98) in men 45 to 59 years old and 0.67 (0.41 to 1.09) in those 60 to 84 years old. CONCLUSIONS: In this case-control study screening of asymptomatic men with PSA was associated with a significantly reduced risk of metastatic prostate cancer. The results need to be confirmed in randomized controlled trials.