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1.  Mood Disorders in Systemic Lupus Erythematosus 
Objective
To determine the frequency, clinical and autoantibody associations and outcome of mood disorders in a multi-ethnic/racial, prospective, inception cohort of SLE patients.
Methods
Patients were assessed annually for mood disorders (4 types as per DSM-IV) and 18 other neuropsychiatric (NP) events. Global disease activity (SLEDAI-2K), SLICC/ACR damage index (SDI) and SF-36 subscale, mental (MCS) and physical (PCS) component summary scores were collected. Time to event, linear and ordinal regressions and multi-state models were used as appropriate.
Results
Of 1,827 SLE patients, 88.9% were female, 48.9% Caucasian, mean ± SD age 35.1±13.3 years, disease duration 5.6±4.8 months and follow-up 4.73±3.45 years. Over the study 863 (47.2%) patients had 1,627 NP events. Mood disorders occurred in 232/1827 (12.7%) patients and 98/256 (38.3%) events were attributed to SLE. The estimated cumulative incidence of any mood disorder after 10 years was 17.7% (95%CI=[15.1%,20.2%]). There was a greater risk of mood disorder in patients with concurrent NP events (p ≤ 0.01) and lower risk with Asian race/ethnicity (p=0.01) and immunosuppressive drugs (p=0.003). Mood disorders were associated with lower mental health subscale and MCS scores but not with SLEDAI-2K, SDI scores or lupus autoantibodies. Antidepressants were used in 168/232 (72.4%) patients with depression. 126/256 (49.2%) mood disorders resolved in 117/232 (50.4%) patients.
Conclusion
Mood disorders, the second most frequent NP event in SLE patients, have a negative impact on HRQoL and improve over time. The lack of association with global SLE disease activity, cumulative organ damage and lupus autoantibodies emphasize their multifactorial etiology and a role for non-lupus specific therapies.
doi:10.1002/art.39111
PMCID: PMC4485527  PMID: 25778456
Systemic lupus erythematosus; Mood disorders; Inception cohort; Outcomes research
2.  Association among different measures of alcohol use across adolescence and emerging adulthood 
Addiction (Abingdon, England)  2014;109(6):894-903.
Background and Aims
The use of alterative alcohol indices in developmental research may generate conflicting findings in the literature. This study examined the longitudinal associations among four indices of alcohol involvement from ages 15 to 25 years and examined their concurrent associations with alcohol-related problems in emerging adulthood.
Design
Data are from the Victoria Healthy Youth Survey, a five-wave multi-cohort study conducted biennially in Victoria, Canada between 2003 and 2011.
Setting and Participants
This study included a subsample of 637 randomly recruited Canadian adolescents, aged 15–25 years.
Measurements
Four indices of alcohol use were compared using multivariate piecewise growth modeling: frequency, usual quantity, heavy episodic drinking and volume.
Findings
All indices increased on average from ages 15 to 21, peaked at approximately age 21, and gradually declined from ages 21 to 25. Levels of use at age 21 were highly correlated across indices (r = 0.63–0.94, P < 0.001), but correlations among rates of change varied between pairs of indices. Heavy episodic drinking and volume had the strongest correlations over time (r = 0.64–0.81, P < 0.001) and accounted for the greatest variance in alcohol use disorder symptoms (R2 = 0.35) and social and health consequences (R2 = 16) in emerging adulthood. Frequency and quantity had the weakest associations during adolescence (r = 0.49, P = 0.001) and were uncorrelated during emerging adulthood (r = 0.23, P = 0.09).
Conclusions
Among Canadian youth aged 15–25 years, measures of heavy episodic drinking and volume are the most strongly correlated over time and account for greater variance in alcohol-related problems in emerging adulthood than either frequency or quantity alone.
doi:10.1111/add.12499
PMCID: PMC4905750  PMID: 24467265 CAMSID: cams5728
Adolescence; alcohol; development; latent growth modeling; measurement; young adult
3.  The Effect of Types of Postsecondary Education on Drinking: Does Age of Enrollment Matter? 
Emerging adulthood (Print)  2014;3(3):154-165.
Using longitudinal data from early adolescence through young adulthood, this study examined the association between different types of postsecondary education (PSE), age of enrollment in PSE, and the trajectory of alcohol use for Canadian young adults (N = 521). Trajectories of alcohol use were compared across young adults at 2-year colleges, 4-year universities, transfer programs (started at a 2-year college and transferred to a 4-year university), and terminal high school graduates. While initial findings revealed significant differences in the drinking trajectories of 2-year college students and 4-year university students, all differences were accounted for by variability in the age of enrollment. Overall, there were few differences in heavy drinking across types of institutions, but younger students increased their alcohol use more than older students following enrollment. However, young adults who do not attend PSE may be at greatest risk for heavy drinking over time.
doi:10.1177/2167696814561999
PMCID: PMC4905749  PMID: 27308184 CAMSID: cams5729
alcohol use; emerging adulthood; postsecondary education; college; growth curve modeling
4.  It gets better or does it? Peer victimization and internalizing problems in the transition to young adulthood 
Development and psychopathology  2014;26(3):675-688.
Consistent research shows that peer victimization predicts internalizing symptoms in childhood and adolescence, but the extent to which peer victimization and its harmful effects on mental health persists into young adulthood is unclear. The current study describes patterns of physical and relational victimization during and after high school, and examines concurrent and prospective associations between internalizing symptoms (depressive and anxious symptoms) and peer victimization (physical and relational) from adolescence to young adulthood (ages 12–27). Data were collected from the Victoria Healthy Youth Survey, a five-wave multicohort study conducted biennially between 2003 and 2011 (N = 662). Physical victimization was consistently low and stable over time. Relational victimization increased for males after high school. Both types of victimization were associated concurrently with internalizing symptoms across young adulthood for males and for females. Although sex differences were important, victimization in high school also predicted increases in internalizing problems over time.
doi:10.1017/S0954579414000315
PMCID: PMC4905753  PMID: 25047291 CAMSID: cams5726
5.  The Relationship of Higher Education to Substance Use Trajectories: Variations as a Function of Timing of Enrollment 
Objective
This study examined the association between time to enrollment into postsecondary education and trajectories of heavy episodic drinking (HED) and marijuana use using a prospective longitudinal study.
Method
Participants included 391 postsecondary students (55% female) drawn from the Victoria Healthy Youth Survey, a five-wave, multi-cohort sample interviewed biennially between 2003 and 2011. Using piecewise latent growth modeling, we compared changes in the trajectories of HED and marijuana use before and after postsecondary enrollment across three groups of young adults: (a) direct entrants (enrolled directly out of high school), (b) gap entrants (took a year off), and (c) delayed entrants (took longer than a year off).
Results
Heavy drinking increased after enrollment for direct entrants and gap entrants and decreased for delayed entrants. Marijuana use increased after enrollment for direct entrants, and decreased for gap entrants and delayed entrants. Yet, overall levels of marijuana use were significantly higher among the gap and delay entrants over time compared with direct entrants. Group differences in heavy drinking appeared to reflect age-related changes in drinking patterns. However, differences in marijuana use may reflect pre-existing inequities in access to higher education across groups.
Conclusions
The association between postsecondary education and increased substance use may be limited to students who enroll at a postsecondary institution directly out of high school. However, students who delay enrollment have higher levels of substance use before enrollment, as well as lower high school grades and socioeconomic status compared with direct entrants, and may be particularly vulnerable to long-term substance use problems and degree noncompletion.
PMCID: PMC4905754  PMID: 25486398 CAMSID: cams5730
6.  Co-occurring Trajectories of Symptoms of Anxiety, Depression, and Oppositional Defiance From Adolescence to Young Adulthood 
This study uses a cohort-sequential longitudinal design to examine the patterns of change and codevelopment of anxiety, depression, and oppositional defiant symptoms (ODS) from late adolescence to young adulthood. Four waves of data were collected biennially by individual interview with a random, community-based sample of 662 youth ages 12 to 18 years at Time 1 (18–26 years at Time 4). Using latent growth curve modeling, we examined co-occurring changes in the levels, rates of change, and variability in symptoms of anxiety, depression, and oppositional defiance. Sex differences were also assessed. Levels of anxiety, depression, and ODS were correlated at each time point. Moreover, adolescents with high initial levels in one domain tended to have high initial levels in the other domains. In addition, increases in depressive symptoms were significantly correlated with increases in anxiety and in ODS, but adolescent levels of symptoms did not predict increases over time. Symptoms of anxiety (for female and male individuals) and depression (for male individuals) continue to increase in young adulthood, whereas ODS stabilize or decline. Adolescent levels of these problems have a significant impact on later levels, suggesting that preventive interventions may be needed in adolescence to defer negative consequences of mental health problems in young adults.
doi:10.1080/15374416.2012.694608
PMCID: PMC4905756  PMID: 22742519 CAMSID: cams5725
7.  Trajectories of Marijuana Use in Youth Ages 15–25: Implications for Postsecondary Education Experiences 
Objective
This study examined associations between longitudinal trajectories of marijuana use from adolescence to young adulthood and postsecondary education (PSE) experiences. Outcomes examined included the type of PSE undertaken, the timing of enrollment, and the likelihood of dropping out.
Method
Participants (N = 632; 332 females) were from the Victoria Healthy Youth Survey, a five-wave multicohort study of young people interviewed biennially between 2003 and 2011. Latent class growth analysis was used to identify distinct trajectories of the frequency of marijuana use from ages 15 to 25. Logistic regression analyses evaluated class membership as a predictor of the three PSE outcomes, with sex, maternal education, family structure, high school grades, and conduct problems controlled for.
Results
Three trajectory groups of marijuana use were identified: abstainers (31%), occasional users (44%), and frequent users (25%). Compared with abstainers, frequent users had the lowest high school grades and the most conduct problems and were least likely to enroll in PSE, especially in a university. Occasional users did not differ from abstainers on high school grades or conduct problems and were no less likely than abstainers to enroll in PSE. However, they delayed enrollment longer and were more likely to drop out of PSE.
Conclusions
Frequent marijuana use from adolescence to young adulthood may close off opportunities for entering PSE, whereas occasional use may create delays in starting and finishing PSE among less at-risk young people. The mechanisms underlying associations between marijuana use and educational difficulties during emerging adulthood as well as adolescence need to be better understood.
PMCID: PMC4905757  PMID: 24988266 CAMSID: cams5727
8.  Reciprocal Effects of Internalizing and Oppositional Defiance Symptoms on Heavy Drinking and Alcohol-Related Harms in Young Adulthood 
There is a need for longitudinal research to understand how psychopathology relates to the onset and maintenance of substance use from adolescence into young adulthood. Hence, we investigate the longitudinal, reciprocal influences of internalizing (anxiety and depression) and externalizing (oppositional defiance) symptoms on heavy episodic drinking (HED; ≥5 drinks per occasion) and alcohol-related harms in a community-based sample of youth aged 12–27 years. Participants were chosen from the Victoria Healthy Youth Survey, followed six times, biennially between 2003 and 2013 (N = 662). Analyses used cross-lagged panel models to examine reciprocal relations over time. Differences across age and sex were also tested. Defiance symptoms predicted increases in HED, which reciprocally predicted increases in defiance symptoms for females. Internalizing symptoms were related to HED within time for females. Alcohol-related harms had reciprocal positive associations with internalizing and defiance symptoms for both males and females. Associations were largely invariant across age groups, suggesting that the presence and strength of associations persisted across development. While psychopathology preceded the onset of HED and harms, the overall findings suggest that these risk processes are mutually reinforcing across development and that youth may become entrenched in an interdependent cycle that significantly increases their risk of comorbid disorders in adulthood.
doi:10.4137/SART.S33928
PMCID: PMC4723048  PMID: 26819553
internalizing symptoms; externalizing symptoms; heavy drinking; alcohol; harm; adolescence; young adulthood; longitudinal
9.  Effectiveness of a Wheelchair Skills Training Program for Powered Wheelchair Users: A Randomized Controlled Trial 
Objectives
To test the hypothesis that powered wheelchair users who receive the Wheelchair Skills Training Program (WSTP) improve their wheelchair skills in comparison with a Control group that receives standard care. Our secondary objectives were to assess goal achievement, satisfaction with training, retention, injury rate, confidence with wheelchair use and participation.
Design
Randomized controlled trial (RCT).
Setting
Rehabilitation centers and communities.
Participants
116 powered wheelchair users.
Intervention
Five 30-minute WSTP training sessions.
Main Outcome Measures
Assessments were done at baseline (T1), post-training (T2) and 3 months post-training (T3) using the Wheelchair Skills Test Questionnaire (WST-Q 4.1), Goal Attainment Score (GAS), Satisfaction Questionnaire, Injury Rate, Wheelchair Use Confidence Scale for Power Wheelchair Users (WheelCon) and Life Space Assessment (LSA).
Results
There was no significant T2-T1 difference between the groups for WST-Q capacity scores (p = 0.600) but the difference for WST-Q performance scores was significant (p = 0.016) with a relative (T2/T1 x 100%) improvement of the median score for the Intervention group of 10.8%. The mean (SD) GAS for the Intervention group after training was 92.8% (11.4) and satisfaction with training was high. The WST-Q gain was not retained at T3. There was no clinically significant difference between the groups in injury rate and no statistically significant differences in WheelCon or LSA scores at T3.
Conclusions
Powered wheelchair users who receive formal wheelchair skills training demonstrate modest transient post-training improvements in their WST-Q performance scores, they have substantial improvements on individualized goals and they are positive about training.
doi:10.1016/j.apmr.2015.07.009
PMCID: PMC4674291  PMID: 26232684 CAMSID: cams5021
Wheelchair; rehabilitation; training; motor skills; RCT
10.  Seizure disorders in Systemic Lupus Erythematosus 
Annals of the rheumatic diseases  2012;71(9):1502-1509.
Objective
To describe the frequency, attribution, outcome and predictors of seizures in SLE
Methods
The Systemic Lupus International Collaborating Clinics (SLICC) performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLEDAI-2K), cumulative organ damage (SLICC/ACR Damage Index (SDI)) and neuropsychiatric events were recorded at enrollment and annually. Lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrollment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 mental (MCS) and physical (PCS) component summary scores. Statistical analyses included Cox and linear regressions.
Results
The cohort was 89.4% female with a mean follow up of 3.5±2.9 years. 75/1631 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR(CI):1.97 (1.07–3.63); p=0.03) and lower education status (1.97 (1.21–3.19); p<0.01). Higher damage scores (without NP variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46–10.55)); SDI=2 or 3:1.57 (0.32–7.65); SDI≥4:7.86 (0.89–69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78(76%)) in the absence of anti-seizure drugs. There was no significant impact on the MCS or PCS scores. Anti-malarial drugs in absence of immunosuppressive agents were associated with reduced seizure risk (0.07(0.01–0.66); p=0.03).
Conclusion
Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Anti-malarial drugs were associated with a protective effect.
doi:10.1136/annrheumdis-2011-201089
PMCID: PMC4656036  PMID: 22492779 CAMSID: cams5144
Systemic lupus erythematosus; Neuropsychiatric; Seizures; Inception cohort
11.  The use of administrative health care databases to identify patients with rheumatoid arthritis 
Objective
To validate and compare the decision rules to identify rheumatoid arthritis (RA) in administrative databases.
Methods
A study was performed using administrative health care data from a population of 1 million people who had access to universal health care. Information was available on hospital discharge abstracts and physician billings. RA cases in health administrative databases were matched 1:4 by age and sex to randomly selected controls without inflammatory arthritis. Seven case definitions were applied to identify RA cases in the health administrative data, and their performance was compared with the diagnosis by a rheumatologist. The validation study was conducted on a sample of individuals with administrative data who received a rheumatologist consultation at the Arthritis Center of Nova Scotia.
Results
We identified 535 RA cases and 2,140 non-RA, noninflammatory arthritis controls. Using the rheumatologist’s diagnosis as the gold standard, the overall accuracy of the case definitions for RA cases varied between 68.9% and 82.9% with a kappa statistic between 0.26 and 0.53. The sensitivity and specificity varied from 20.7% to 94.8% and 62.5% to 98.5%, respectively. In a reference population of 1 million, the estimated annual number of incident cases of RA was between 176 and 1,610 and the annual number of prevalent cases was between 1,384 and 5,722.
Conclusion
The accuracy of case definitions for the identification of RA cases from rheumatology clinics using administrative health care databases is variable when compared to a rheumatologist’s assessment. This should be considered when comparing results across studies. This variability may also be used as an advantage in different study designs, depending on the relative importance of sensitivity and specificity for identifying the population of interest to the research question.
doi:10.2147/OARRR.S92630
PMCID: PMC5045118  PMID: 27790047
inflammatory arthritis; case definitions; incidence; prevalence; population health
12.  A different entity: a population based study of characteristics and recurrence patterns in oropharyngeal squamous cell carcinomas 
Background
Cases of squamous cell carcinoma (SCC) of the oropharynx were compared with other head and neck cancer (HNC) anatomic subsites in patients treated at the provincial referral centre for HNC, the Nova Scotia Cancer Centre (NSCC).
Methods
A retrospective chart review was performed on HNC patients assessed at the NSCC between 2010 and 2011. Patient demographics, disease characteristics, treatment details and outcomes, including recurrence rates and survival were collected. Data was collected on new and recurrent cases of HNC. This data was compared between the two types of HNC using chi-square tests for dichotomous categorical variables or Fishers exact test where appropriate. Wald test was used to compare categorical variables with 3 categories. Continuous variables were compared using the non-parametric Wilcoxon test.
Results
318 charts were included in the analysis. 122 (38 %) were oropharyngeal squamous cell carcinomas (OPSCCs). In terms of disease characteristics, OPSCCs were more likely to be poorly differentiated/undifferentiated (n = 267, 49(40 %) vs 42(21 %), p < 0.001), non-keratinizing (n = 169, 25(20 %) vs 17(9 %), p < 0.001), greater than 2 cm (n = 253, 72(59 %) vs 78(40 %), p = 0.0061), stage 4 (n = 313, 55(45 %) vs 64(33 %), p = 0.0315) and have had locoregional nodal spread (n = 315, 103(84 %) vs 55(28 %), p < 0.001). In the subset of 57 patients that had p16 testing, OPSCCs were more likely to be p16(+) (37(30 %) vs 1(1 %), p < .001). There were no significant differences in terms of Charlson probability of 10 year survival, smoking or alcohol consumption although OPSCC patients were significantly less likely to have COPD as a co-morbidity (n = 318, 19(16 %) vs 53(27 %), p = 0.0175). Finally, OPSCCs had less chance for relapse than non-OPSCCs in both univariate (2.119 times less, p=0.0034) and multivariate (1.899 times less, p=0.0505) analyses along with a 1.822 times less overall mortality in a multivariae analysis (p=0.0408). 
Conclusions
This analysis suggests that Nova Scotian OPSCCs should be considered distinct from other HNC lesions, most notably in terms of disease characteristics and prognosis. Specifically, despite a higher association with disease factors traditionally considered to be linked to poor prognosis, outcomes were actually superior in terms of relapse and overall mortality.
doi:10.1186/s40463-015-0082-6
PMCID: PMC4551366  PMID: 26310237
Oropharyngeal squamous cell carcinoma; Human papillomavirus; p16; Head and neck cancer; Staging
13.  Effects of a Pharmacy-Driven Perisplenectomy Vaccination Program on Vaccination Rates and Adherence to Guidelines 
Background
Overwhelming postsplenectomy infection is a serious potential outcome for patients who have undergone resection of the spleen and is associated with a high mortality rate. The most common bacterial causes are the encapsulated organisms Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae type B, all of which are vaccine-preventable. Current guidelines recommend vaccination against these 3 bacteria, but adherence to these guidelines is less than ideal. In 2007, a “perisplenectomy vaccination kit” was introduced at the authors’ institution to improve compliance with immunization guidelines by making the vaccines and necessary information for patients and providers more readily available.
Objective:
To evaluate and compare vaccination rates for patients who underwent splenectomy before and after introduction of the perisplenectomy vaccination kit and, secondarily, to identify any characteristics unique to those who did not receive appropriate perisplenectomy vaccinations.
Methods:
In this observational study, performed at the QEII Health Sciences Centre of Capital Health in Halifax, Nova Scotia, data were reviewed for patients who underwent splenectomy between 2008 and 2011. Vaccination rates and other descriptive statistics were calculated and compared with data for a 3-year period before implementation of the program.
Results:
Vaccination rates in the 3-year period following implementation of the perisplenectomy vaccination kit were 100% against S. pneumoniae, 97% against N. meningitidis, and 93% against H. influenzae type B. The corresponding rates in the 3 years before introduction of the kit were 91%, 75%, and 68%, respectively. No characteristics predicting inadequate immunization were identified in univariate or multivariate analysis.
Conclusion:
Introduction of a pharmacy-driven perisplenectomy vaccination kit program improved rates of appropriate vaccination for patients who underwent splenectomy.
PMCID: PMC4152964  PMID: 25214656
splenectomy; vaccination; immunization; overwhelming postsplenectomy infection; splénectomie; vaccination; immunisation; infection fulminante post-splénectomie
14.  Bereavement-Related Regret Trajectories Among Widowed Older Adults 
Objectives.
Although regrets and unfinished business with a deceased spouse are frequently discussed as crucial determinants of one’s postloss adjustment, there have been few empirical investigations of bereavement-related regrets. This present study aimed to investigate the longitudinal course of these regrets and their correlates among widowed older adults.
Methods.
Drawing upon information from 201 widowed older adults in the Changing Lives of Older Couples study, this present study used latent class growth analysis to identify unique longitudinal trajectories of regret from 6 to 48 months postloss and examine differences between these trajectories with regard to grief and depressive symptomatology.
Results.
Three distinct bereavement-related regret trajectories were identified, characterized by Stable Low Regret, Stable High Regret, and Worsening High Regret. Results revealed that those in the Worsening High Regret group, whose bereavement-related regrets were exacerbated during the study, had the poorest grief outcomes. No differences were observed between these groups with regard to depressive symptoms, indicating that regret may be a unique marker of difficulties in the grieving process.
Discussion.
These findings highlight the importance of periodically reassessing bereavement-related regrets (and perhaps other aspects of the continued relationship with the deceased) over time and support the rationale behind interventions designed to facilitate resolution of these issues.
doi:10.1093/geronb/gbt050
PMCID: PMC3894125  PMID: 23766434
Continuing bonds; Death and dying; Marital quality; Regret; Unfinished business.
15.  The Unique Impact of Late-Life Bereavement and Prolonged Grief on Diurnal Cortisol 
Objectives.
This study expands on previous research by examining the effects of prolonged grief disorder (PGD) symptoms and bereavement on diurnal cortisol patterns above and beyond depressive symptomatology.
Methods.
Drawing on information from 56 depressed older adults, 3 groups were compared: (1) a depressed nonbereaved group, (2) a depressed bereaved without elevated PGD symptoms group, and (3) a depressed bereaved with elevated PGD symptoms group. Multilevel modeling was used to examine differences in diurnal cortisol profiles between these 3 groups, controlling for demographic factors and depressive symptoms.
Results.
Results revealed that those who were bereaved had more dysregulated cortisol patterns, but PGD symptomatology seemed to have little effect. Subsidiary analysis with just the bereaved participants suggests that those who were recently widowed may have had greater cortisol dysregulation compared with other bereaved individuals in the sample.
Discussion.
These findings suggest that the circumstance of being bereaved may be associated with more dysregulated cortisol, regardless of PGD symptomatology. This pattern of results might reflect greater disturbance in daily routines among bereaved individuals and acute stress in the case of those experiencing the recent loss of a spouse, which leads to disruption in circadian rhythms and the diurnal cycle of cortisol.
doi:10.1093/geronb/gbt051
PMCID: PMC3894130  PMID: 23740094
Biomarkers; Death and dying; Widowhood; Salivary cortisol; Complicated grief.
16.  Ephrin B2 Receptor and Microsatellite Status in Lymph Node-Positive Colon Cancer Survival1 
Translational Oncology  2013;6(5):520-527.
BACKGROUND: Ephrin B2 receptor (EphB2) is a target of the canonical wnt pathway implicated in colorectal carcinogenesis, and its down-regulation may be associated with adverse prognosis. We evaluated its prognostic value in resected colon cancer stratified by microsatellite status and other clinicopathologic characteristics. METHODS: We identified all cases of resected stage III colon cancer from 1995 to 2009 managed in the Capital Health district of Nova Scotia. Tissue microarrays were constructed and immunohistochemistry (IHC) for tumor EphB2 staining assigned into quartiles. Microsatellite status was evaluated by IHC for MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2). Microsatellite stable tumors were defined as both MLH1/MSH2 (+/+); tumors staining otherwise were classified with microsatellite instability (MSI-H). Primary and secondary outcomes were disease-free survival (DFS) and overall survival (OS), respectively. RESULTS: We identified 159 cases with sufficient tissue for microarray analysis having a median follow-up of 3.47 years (range, 0.14–14). Median age was 61, 52% were male, 40% had an event, and 29% died. MSI-H was present in 18 (13%). Univariate analysis of EphB2 expression on DFS and OS showed a hazard ratio (HR) of 2.00 (P = .01) and 2.14 (P = .03), respectively. Multivariate analysis of EphB2 expression on DFS and OS showed an HR of 2.24 and 2.23, respectively, with tumor IHC ≤ 50%. CONCLUSIONS: In this cohort, decreased EphB2 expression was an independent prognostic factor for recurrence and death and may have prognostic relevance in tumors with MSI-H. However, this would require prospective validation in a larger study.
PMCID: PMC3799194  PMID: 24151532
17.  Efficacy and Retention of the French-Canadian Version of the Wheelchair Skills Training Program for Manual Wheelchair Users: A Randomized Controlled Trial 
Objectives
To test the hypotheses that, in comparison with a Control group that received standard care, users of manual wheelchairs who also received the French-Canadian version of the Wheelchair Skills Training Program (WSTP) would significantly improve their wheelchair-skills capacity and that these improvements would be retained at 3 months.
Design
Multi-center, single-blind randomized controlled trial (RCT).
Participants
39 manual wheelchair users, a sample of convenience.
Setting
3 rehabilitation centers in Montreal, Quebec, Canada.
Intervention
Participants were randomly allocated to the WSTP or Control groups. Participants in both groups received standard care. Participants in the WSTP group also received a mean of 5.9 training sessions (mean total duration of 5 hours and 36 minutes).
Main Outcome Measures
The French-Canadian version of the Wheelchair Skills Test (WST) (Version 3.2) was administered at baseline (T1), post-training (T2, a mean of 47 days after T1) and at follow-up (T3, a mean of 101 days after T2).
Results
At T2, the mean ± SD total percentage WST capacity scores were 77.4 ± 13.8% for the WSTP group and 69.8 ± 18.4% for the Control group (p = 0.0296). Most of this difference was due to the Community-level skills (p=0.0018). The total and subtotal WST scores at T3 decreased by ≤ 0.5% from the T2 values, but differences between groups at T3, adjusting for T1, did not reach statistical significance (p ≥ 0.017 at a Bonferroni-adjusted α level of 0.005).
Conclusion
WSTP training improves wheelchair skills immediately after training, particularly at the Community-skills level, but this study did not show statistically significant differences between the groups at 3 months.
doi:10.1016/j.apmr.2012.01.017
PMCID: PMC3708861  PMID: 22494946 CAMSID: cams3053
Wheelchair; Training; Rehabilitation; Motor skills
18.  Program of rehabilitative exercise and education to avert vascular events after non-disabling stroke or transient ischemic attack (PREVENT Trial): a multi-centred, randomised controlled trial 
BMC Neurology  2010;10:122.
Background
Despite lack of outward signs, most individuals after non-disabling stroke (NDS) and transient ischemic attack (TIA) have significant cardiovascular and cerebrovascular disease and are at high risk of a major stroke, hospitalization for other vascular events, or death. Most have multiple modifiable risk factors (e.g., hypertension, physical inactivity, hyperlipidaemia, diabetes, tobacco consumption, psychological stress). In addition, accelerated rates of depression, cognitive decline, and poor quality of sleep have been reported following TIA, which correlate with poor functional outcomes and reduced quality of life. Thus, NSD and TIA are important warning signs that should not be overlooked. The challenge is not unlike that facing other 'silent' conditions - to identify a model of care that is effective in changing people's current behaviors in order to avert further morbidity.
Methods/Design
A single blind, randomized controlled trial will be conducted at two sites to compare the effectiveness of a program of rehabilitative exercise and education versus usual care in modifying vascular risk factors in adults after NDS/TIA. 250 adults within 90 days of being diagnosed with NDS/TIA will be randomly allocated to a 12-week program of exercise and education (PREVENT) or to an outpatient clinic assessment and discussion of secondary prevention recommendations with return clinic visits as indicated (USUAL CARE). Primary outcome measures will include blood pressure, waist circumference, 12-hour fasting lipid profile, and 12-hour fasting glucose/hemoglobin A1c. Secondary measures will include exercise capacity, walking endurance, physical activity, cognitive function, depression, goal attainment and health-related quality of life. Outcome assessment will be conducted at baseline, post-intervention, and 6- and 12-month follow-ups. Direct health care costs incurred over one year by PREVENT versus USUAL CARE participants will also be compared. Ethical approval for the trial has been obtained from the relevant Human Research Ethics Boards.
Discussion
Whether timely delivery of an adapted cardiac rehabilitation model is effective in attaining and maintaining vascular risk reduction targets in adults after NDS/TIA is not yet known. We anticipate that the findings of this trial will make a meaningful contribution to the knowledge base regarding secondary stroke prevention.
Trial registration
This trial is registered with the Clinical Trials.gov Registry (NCT00885456).
doi:10.1186/1471-2377-10-122
PMCID: PMC3004878  PMID: 21143864
19.  Application of the International Germ Cell Consensus Classification to the Nova Scotia population of patients with germ cell tumours 
Background
The International Germ Cell Consensus Classification (IGCCC) is the internationally accepted, clinically based prognostic classification used to assist in the management and research of metastatic germ cell tumours (GCTs). The goal of this study was to determine whether the IGCCC is applicable to a population-based cohort.
Methods
We completed a retrospective chart review of patients who received diagnoses of GCT in Nova Scotia between 1984 and 2004 and who received treatment with platin-based chemotherapy for metastatic disease. We assigned the IGCCC to each patient based on the site of the primary lesion, the presence or absence of nonpulmonary visceral metastases and prechemotherapy tumour marker values. We calculated Kaplan–Meier estimates of 5-year progression-free survival (PFS) and overall survival for each IGCCC group.
Results
The study cohort comprised 129 patients. The distribution and outcomes in each group of patients in Nova Scotia was similar to that published in the IGCCC. Among patients with nonseminoma GCTs (NSGCT) 61% had good, 22% had intermediate and 17% had poor prognoses. Among those with seminomas, 85% had good and 15% had intermediate prognoses. Among patients with NSGCTs, the 5-year PFS was 90%, 69% and 55%, and the 5-year overall survival was 94%, 84%, 61% in the good, intermediate, and poor prognostic categories respectively. Among patients with seminomas, the 5-year PFS was 95% and 50% and the 5-year overall survival was 94% and 50% in the good and intermediate prognostic categories, respectively.
Conclusion
The IGCCC seems applicable to a population-based cohort, with similar distribution of categories and clear prognostic ability.
PMCID: PMC2666903  PMID: 19424465
20.  Dalteparin Vs Low-Dose Unfractionated Heparin for Prophylaxis Against Clinically Evident Venous Thromboembolism in Acute Traumatic Spinal Cord Injury: A Retrospective Cohort Study 
Background:
When venous thromboembolism (VTE) includes deep-vein thrombosis (DVT) and pulmonary embolism (PE), patients with acute traumatic spinal cord injury (SCI) have the highest incidence of VTE among all hospitalized groups, with PE the third most common cause of death. Although low–molecular-weight heparin (LMWH) outperforms low-dose unfractionated heparin (LDUH) in other patient populations, the evidence in SCI remains less robust.
Objective:
To determine whether the efficacy for LMWH shown in previous SCI surveillance studies (eg, routine Doppler ultrasound) would translate into real-world effectiveness in which only clinically evident VTE is investigated (ie, after symptoms or signs present).
Methods:
A retrospective cohort study was conducted of 90 patients receiving LMWH dalteparin (5,000 U daily) or LDUH (5,000 U twice daily) for VTE prophylaxis after acute traumatic SCI. The incidence of radiographically confirmed VTE was primarily analyzed, and secondary outcomes included complications of bleeding and heparin-induced thrombocytopenia.
Results:
There was no statistically significant association (p = 0.7054) between the incidence of VTE (7.78% overall) and the type of prophylaxis received (LDUH 3/47 vs dalteparin 4/43). There was no significant differences in complications, location of VTE, and incidence of fatal PE. Paraplegia (as opposed to tetraplegia) was the only risk factor identified for VTE.
Conclusions:
There continues to be an absence of definitive evidence for dalteparin (or other LMWH) over LDUH as the choice for VTE prophylaxis in patients with SCI. Novel approaches to VTE prophylaxis are urgently required for this population, whose risk of fatal PE has not decreased over the last 25 years.
PMCID: PMC2582433  PMID: 18959355
Dalteparin; Heparin, low–molecular-weight; Pulmonary embolism; Rehabilitation; Spinal cord injuries; Venous thrombosis; Tetraplegia; Paraplegia
21.  The impact of warfarin use on clinical outcomes in atrial fibrillation: A population-based study 
BACKGROUND:
Atrial fibrillation (AF) is the most common adult arrhythmia, and significantly increases the risk of ischemic stroke. Oral anticoagulation may be underused and may be less effective in community settings than clinical trial settings.
OBJECTIVES:
To determine the rates of thromboembolism and bleeding in an ambulatory cohort of patients with AF.
METHODS:
Observational study of Nova Scotian residents with AF identified by electrocardiogram in ambulatory settings between November 1999 and January 2001. Main outcome measures were rates of thromboembolism and bleeding over two years.
RESULTS:
Four hundred twenty-five patients were included in the study. The mean (±SD) age was 70.6±11.1 years, and 40% were women. Warfarin therapy was used by 68% of patients. Sixty-two per cent of patients had hypertension, 21% had a previous stroke or transient ischemic attack, 44% had congestive heart failure and 20% were diabetic. The overall rate of thromboembolic events was 2.7% in warfarin users and 8.5% in nonwarfarin users over two years, with an RR reduction of 68% (OR 0.31, 95% CI 0.09 to 0.91; P=0.047). The annual rate of ischemic stroke was 1.2% and 3.1% in warfarin and nonwarfarin users, respectively, with an RR reduction of 62% (OR 0.29, 95% CI 0.08 to 1.04; P=0.057). The overall rate of major bleeding was 2.6% in warfarin users and 1.4% in nonwarfarin users (P=0.667). The annual mortality rate was 7.79% in warfarin users and 9.93% in nonwarfarin users (P=0.192).
CONCLUSIONS:
Warfarin use was found to significantly reduce the rate of thromboembolic events without a concomitant increase in hemorrhagic events. The present study confirms the effectiveness of warfarin therapy in a population-based cohort.
PMCID: PMC2650665  PMID: 17487290
Atrial fibrillation; Hemorrhage; Mortality; Stroke
22.  Serum creatinine in patients with advanced liver disease is of limited value for identification of moderate renal dysfunction: Are the equations for estimating renal function better? 
BACKGROUND:
The Cockcroft-Gault formula (CGF) is used to estimate the glomerular filtration rate (GFR) based on serum creatinine (Cr) levels, age and sex. A new formula developed by the Modification of Diet in Renal Disease (MDRD) Study Group, based on the patient’s Cr levels, age, sex, race and serum urea nitrogen and serum albumin levels, has shown to be more accurate. However, the best formula to identify patients with advanced liver disease (ALD) and moderate renal dysfunction (GFR 60 mL/min/1.73 m2 or less) is not known. The aim of the present study was to compare calculations of GFR, using published formulas (excluding those requiring urine collections) with standard radionuclide measurement of GFR in patients with ALD.
METHODS:
Fifty-seven consecutive subjects (40% women) with a mean age of 50 years (range 16 to 67 years) underwent 99m-technetium-diethylenetriamine pentaacetic acid (99mTc-DTPA) (single injection) radionuclide measurement of GFR. To calculate GFR, three formulas were used: the reciprocal of Cr multiplied by 100 (100/Cr), the CGF and the MDRD formulas. Pearson’s correlation coefficient (r) and Bland-Altman analyses of agreement were used to analyze the association between 99mTc-DTPA clearance and the three equations for GFR.
RESULTS:
The mean 99mTc-DTPA clearance was 83 mL/min/1.73 m2 (range 28 mL/min/1.73 m2 to 173 mL/min/1.73 m2). Mean calculated GFRs by 100/Cr, the CGF and the MDRD formula were 106 mL/min/1.73 m2, 98 mL/min/1.73 m2 and 86 mL/min/1.73 m2, respectively. Regression analysis showed good correlation between radionuclide GFR and calculated GFR with r(100/Cr)=0.74, r(CGF)=0.80, r(MDRD)=0.87, all at P≤0.0001. The MDRD formula provided the least bias. The Bland-Altman plot showed best agreement between GFR calculated by the MDRD formula and 99mTc-DTPA clearance, with only 3 mL/min/1.73 m2 overestimation. There was higher variability between radionuclide GFR and calculated GFR by the CGF and by 100/Cr. Although there was no difference in precision, GFR calculated by the MDRD formula had the best overall accuracy. The sensitivity and specificity for detection of moderate renal dysfunction by the MDRD formulas were 73% and 87%, respectively.
CONCLUSIONS:
Among the Cr-based GFR formulas, the MDRD formula showed a larger proportion of agreement with radionuclide GFR in patients with ALD. In clinical practice, the MDRD is the best formula for detection of moderate renal dysfunction among those with ALD.
PMCID: PMC2659934  PMID: 16955148
Cirrhosis; Cockcroft-Gault formula; Creatinine; Glomerular filtration rate; Liver disease

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