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1.  Effects of a Pharmacy-Driven Perisplenectomy Vaccination Program on Vaccination Rates and Adherence to Guidelines 
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.
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.
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.
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.
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
2.  Bereavement-Related Regret Trajectories Among Widowed Older Adults 
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.
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.
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.
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.
PMCID: PMC3894125  PMID: 23766434
Continuing bonds; Death and dying; Marital quality; Regret; Unfinished business.
3.  The Unique Impact of Late-Life Bereavement and Prolonged Grief on Diurnal Cortisol 
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.
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 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.
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.
PMCID: PMC3894130  PMID: 23740094
Biomarkers; Death and dying; Widowhood; Salivary cortisol; Complicated grief.
4.  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
5.  Efficacy and Retention of the French-Canadian Version of the Wheelchair Skills Training Program for Manual Wheelchair Users: A Randomized Controlled Trial 
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.
Multi-center, single-blind randomized controlled trial (RCT).
39 manual wheelchair users, a sample of convenience.
3 rehabilitation centers in Montreal, Quebec, Canada.
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).
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).
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.
PMCID: PMC3708861  PMID: 22494946 CAMSID: cams3053
Wheelchair; Training; Rehabilitation; Motor skills
6.  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.
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.
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.
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 Registry (NCT00885456).
PMCID: PMC3004878  PMID: 21143864
7.  Application of the International Germ Cell Consensus Classification to the Nova Scotia population of patients with germ cell tumours 
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.
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.
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.
The IGCCC seems applicable to a population-based cohort, with similar distribution of categories and clear prognostic ability.
PMCID: PMC2666903  PMID: 19424465
8.  Dalteparin Vs Low-Dose Unfractionated Heparin for Prophylaxis Against Clinically Evident Venous Thromboembolism in Acute Traumatic Spinal Cord Injury: A Retrospective Cohort Study 
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.
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).
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.
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.
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
9.  The impact of warfarin use on clinical outcomes in atrial fibrillation: A population-based study 
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.
To determine the rates of thromboembolism and bleeding in an ambulatory cohort of patients with AF.
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.
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).
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
10.  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? 
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.
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.
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.
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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