Short link N acts as a disease modifying osteoarthritis drug.

Osteoarthritis (OA) is a degenerative joint disease characterised by a progressive degradation of articular cartilage and underlaying bone and is associated with pain and disability. Currently, there is no medical treatment to reverse or even retard OA. Based on our previous reports, where we establish the repair potential of short Link N (sLN) in the intervertebral disc, a cartilage-like tissue, we hypothesise that sLN may hold similar promises in the repair of articular cartilage. This study aimed to determine if sLN, could prevent OA disease progression. Skeletally mature New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT) of their left femorotibial joints to induce joint degeneration typical of OA. Beginning 3 weeks post-operatively, and every three weeks thereafter for 12 weeks, either saline (1 mL) or sLN (100 µg in 1 mL saline) was injected intraarticularly into the operated knee. Six additional rabbits underwent sham surgery but without ACLT or post-operative injections. The effects on gross joint morphology and cartilage histologic changes were evaluated. In the Saline group, prominent erosion of articular cartilage occurred in both femoral condyle compartments and the lateral compartment of the tibial plateau while, sLN treatment reduced the severity of the cartilage damage in these compartments of the knee showing erosion. Furthermore, statistically significant differences were detected between the joint OA score of the saline and sLN treated groups (p = 0.0118). Therefore, periodic intraarticular injection of sLN is a promising nonsurgical treatment for preventing or retarding OA progression, by reducing cartilage degradation.

Impact of government health coverage for ART: The results of a 5-year experience in Quebec.

An analysis of national registry data for 5 years of in-vitro fertilization (IVF) funding in Quebec, Canada was compared with the previous complete year of non-funded IVF cycles, as well as the first complete year following the end of funding. The number of cycles, livebirth rates, age group of patients treated, use of donor gametes, multiple pregnancy rates and cycle cancellation rates were assessed. The total number of IVF cycles performed increased dramatically during the funded period, averaging over 10,000 cycles per year. There was no change in the age group distribution of patients treated, but less egg donation was performed. Interestingly, funding was also associated with an increase in the IVF cycle cancellation rate (17.0% versus 34.4%, P < 0.001), a dramatic decline in the multiple pregnancy rate (25.6% versus 4.9%, P < 0.001), and a decline in the livebirth rate per fresh embryo transfer in stimulated IVF cycles (32.3% versus 25.5%, P < 0.001). Although the livebirth rate for stimulated IVF declined, over 9000 babies were born as a result of the coverage. Lessons learned from this experience could help develop a more fiscally responsible programme that still facilitates access to IVF care.

Clinical Benefits of Tramiprosate in Alzheimer's Disease Are Associated with Higher Number of APOE4 Alleles: The "APOE4 Gene-Dose Effect".

BACKGROUND: Tramiprosate is an oral amyloid anti-aggregation agent that reduces amyloid oligomer toxicity in preclinical studies and was evaluated in two 78-week trials in North America and Western Europe that enrolled 2,025 patients with Mild to Moderate Alzheimer's Disease. The completed North American study did not achieve its efficacy objectives, but a pre-specified subgroup analysis suggested potential efficacy in apolipoprotein E4 (APOE4) carriers. To further explore this observation, we analyzed tramiprosate Phase 3 clinical data based on the number of APOE4 alleles. OBJECTIVES: To analyze tramiprosate efficacy, safety, and occurrence of vasogenic edema in the three APOE4 subgroups: homozygous, heterozygous and non-carriers. DESIGN: Randomized, double-blind, placebo-controlled parallel-arm multi-center studies. SETTING: Academic Alzheimer's disease and dementia centers, community-based dementia and memory clinics, and neuropsychiatric clinical research sites. PARTICIPANTS: Subjects included 2,025 patients, 50 years of age or older, with approximately 60% having APOE4 carrier status (10-15% homozygotes and 45-50% heterozygotes), and mild to moderate disease. All subjects were on stable symptomatic drugs. INTERVENTION: Randomized subjects received placebo, 100 mg BID, or 150 mg BID of tramiprosate. MEASUREMENTS: Co-primary outcomes in both studies were change from baseline in the ADAS-cog11 and CDR-SB assessment scales. RESULTS: Highest efficacy was observed in APOE4/4 homozygotes receiving 150 mg BID of tramiprosate, showing statistically significant effects on ADAS-cog and positive trends on CDR-SB (respectively, 40-66% and 25-45% benefit compared to placebo). APOE4 heterozygotes showed intermediate efficacy, and non-carriers showed no benefit. In 426 patients with MRI scans, no cases of treatment-emergent vasogenic edema were observed. In the three subgroups, the most common adverse events were nausea, vomiting, and decreased weight. CONCLUSIONS: The "APOE4 Gene-Dose effect" is likely explained by the high prevalence of amyloid pathology in symptomatic APOE4 carriers. In APOE4/4 Alzheimer's disease patients, the high dose of tramiprosate showed favorable safety and clinically meaningful efficacy in addition to standard of care.

Osteocutaneous free flaps for mandibular reconstruction: systematic review of their frequency of use and a preliminary quality of life comparison.

OBJECTIVES: To determine whether the fibula free flap is the most frequently used osteocutaneous flap for mandible reconstruction, and whether it provides quality of life, depression and anxiety advantages. METHODS: A systematic review of the public Medline database was conducted. Thirteen patients who underwent mandibular reconstruction at our hospital centre completed questionnaires to evaluate quality of life, depression and anxiety outcomes. RESULTS: The most frequently used free flaps are those of the fibula (n = 982), radial forearm (n = 201), iliac crest (n = 113), subscapular system (n = 50) and rib-serratus (n = 7). In our patient population, there was a trend towards a better quality of life in those with a fibula free flap. However, patients in this group were significantly younger than patients with other flap types (p = 0.025). Patients with a subscapular system free flap were more depressed (p = 0.031); however, they had large through-and-through defects. CONCLUSION: The flap used most frequently in the literature is the fibula free flap. Comparative quality of life data are lacking, and homogeneous populations should be used to reach significant conclusions.

Impact of adherence to treatment with fluticasone propionate/salmeterol in asthma patients.

OBJECTIVE: Low adherence with asthma treatment may be associated with suboptimal outcomes and hence create a treatment gap in the real-life setting. The objective of this study was to assess the long-term association between adherence to treatment with fixed-dose fluticasone propionate/salmeterol (FSC) and the risk of exacerbations and health care utilization in patients with asthma. RESEARCH DESIGN AND METHODS: Observational single cohort study utilizing the Quebec Health Insurance databases. All patients (age >12 years) with a diagnosis of asthma (ICD9-CM 493.xx) between 2001 and 2010 were entered into the study cohort at the time of their first prescription for FSC at any dose. Follow-up continued to the last known claim or death. Adherence to treatment was ascertained as compliance (medication possession ratio ≥80%) and persistence (absence of treatment gap ≥30 days). MAIN OUTCOME MEASURES: Outcomes assessed were exacerbations defined as one of the following: use of oral corticosteroid (OCS), emergency room (ER) visit for asthma or hospitalization for asthma. Asthma related health care resource utilizations ascertained were number of prescription claims for rescue medications, ER visits, hospitalizations, intensive care unit (ICU) stay, intubations, and general practitioner (GP) and respirologist visits. RESULTS: A total of 19,126 patients were included in the study. The proportion of compliant and persistent patients were 42.7% and 29.3% respectively. Multivariate logistic regression analyses showed a significantly reduced adjusted odds of exacerbations for compliant (OR = 0.48; 95% CI: 0.44-0.54) and persistent patients (OR = 0.42; 95% CI: 0.38-0.48). Similarly, significantly lower rates of health care utilization were observed for compliant and persistent patients. CONCLUSIONS: The results of this large population-based study have shown that increased adherence to treatment with FSC is associated with lower risk for exacerbations, lower rescue medication use and lower health care utilization in asthma patients. Despite the typical limitations of an administrative database study including validity of the diagnosis, the fact that compliance and persistence are calculated based on filled claims which does not guarantee that the patients actually took their medications, and the absence of clinical and laboratory data, the findings have implications for physician and patient awareness of the importance of adherence in the management of asthma.

Impact of adherence to treatment with tiotropium and fluticasone propionate/salmeterol in chronic obstructive pulmonary diseases patients.

OBJECTIVE: Poor adherence to treatment may contribute to the treatment gap in chronic obstructive pulmonary diseases (COPD). The aim of the current study was to describe the association between adherence to treatment and the risk of COPD moderate (ME) and severe (SE) exacerbations, and health care utilization. RESEARCH DESIGN AND METHODS: Observational single cohort study utilizing the Quebec Provincial Health Insurance databases. All patients older than 40 years with a diagnosis of COPD between 2001 and 2010 were entered in the study cohort at the time of their first prescription for tiotropium (TIO) alone or co-administered with fluticasone propionate/salmeterol (TIO + FSC). Follow-up continued to the last known claim or death. Adherence was measured by the medication possession ratio (MPR) ≥80% and persistence defined as no treatment gap ≥30 days. MAIN OUTCOME MEASURES: ME was defined as use of an oral corticosteroid or antibiotic, SE as COPD related hospitalization or an emergency room (ER) visit. COPD related health care resource utilization ascertained was prescription of rescue medications, ER visits, hospitalizations, intensive care unit (ICU) admissions, intubations, and general practitioner (GP) and respirologist visits. RESULTS: There were 23,707 patients included in this study. Compliance and persistence with TIO for monotherapy patients were 61.1% and 47.6% respectively. For patients treated with TIO + FSC, compliance and persistence for TIO were 62.9% and 45.3% respectively, and for FSC they were 35.4% and 33.0%. Multivariate analyses showed a significant (P < 0.001) adjusted odds ratios for ME (OR(ME)) and SE (OR(SE)) for TIO compliant vs. non-compliant patients (TIO: OR(ME) = 0.543, OR(SE) = 0.712; TIO + FSC: OR(ME) = 0.436, OR(SE) = 0.570). Similarly for FSC compliance: OR(ME) = 0.546; OR(SE) = 0.749. Similar results were observed for persistence. Compliance and persistence with TIO and FSC were associated with significantly reduced rates of health care utilization. CONCLUSIONS: Despite the typical limitations of an administrative database study, the results of this large population-based study have shown that reduced adherence to treatment with TIO and FSC is associated with increased risk for exacerbations and higher health care utilization in COPD patients.

Treatment durability, effectiveness, and safety with atazanavir/ritonavir-based HAART regimen in treatment-naïve HIV-infected patients.

PURPOSE: To describe the durability of treatment, virological and immunological response, and safety of an atazanavir/ritonavir (ATV/RTV)-based highly active antiretroviral therapy (HAART) regimen in treatment-naïve HIV-infected patients. METHODS: This was a multicentre retrospective study. Medical charts of antiretroviral-na'i've HIV-infected adults who initiated ATV/RTV (300/100 mg) from January 2004 to December 2007 in 10 Canadian clinics were reviewed. Data were collected from time of ATV/RTV treatment initiation until discontinuation of ATV. Durability of treatment and time to virological response were estimated with Kaplan-Meier functions. Change in viral load, CD4 cell counts, and lipid parameters were assessed with linear regression analyses. RESULTS: 176 patients were enrolled, 153 (86.9%) were male, and the majority (52.3%) were 40 to 54 years old. Duration of observation ranged from 1.6 to 56 months. The mean (SE) durability of treatment was 33.5 (0.7) months. There were 37 (21.0%) patients who discontinued ATV/ RTV, among whom 18 (10.2%) discontinued due to toxicity, suboptimal virological response, loss to follow-up, or death. The mean (SE) time to HIV viral load of <50 and <400 copies/mL was 6.6 (0.4) and 4.3 (0.3) months, respectively. At 96 weeks of treatment, least squares mean (LSM) estimated change in log10(HIV copies/mL) was -2.94 (P < .001) and +245 cells/mL (P < .001) for CD4 cell count. A significant LSM increase in HDL-C of 0.24 mmol/L (P = .007 for trend over time) was also observed; total cholesterol, triglycerides, and LDL-C increased over time but their change did not reach statistical significance. The most frequently reported adverse event was increased bilirubin (16.5%). CONCLUSIONS: ATV/RTV-based first-line HAART regimen demonstrated durability and effectiveness and was well tolerated in treatment-naïve HIV-infected patients.

A 52-week prospective, cohort study of the effects of losartan with or without hydrochlorothiazide (HCTZ) in hypertensive patients with metabolic syndrome.

The impact of an ARB, with or without hydrochlorothiazide (HCTZ), on glycaemic factors and the risk for developing diabetes in hypertensive patients with the metabolic syndrome have not been fully assessed. This was a 52-week multicentre, prospective, phase-IV, open-label, cohort study of losartan or losartan/HCTZ in hypertensive patients with metabolic syndrome. All subjects were treated initially with losartan 50 mg day(-1). Those not achieving target blood pressure (BP <140/90 mm Hg) were titrated sequentially to losartan 100 mg, losartan 100 mg/HCTZ 12.5 mg, losartan 100 mg/HCTZ 25 mg and finally to losartan 100 mg/HCTZ 25 mg and calcium-channel blocker (CCB), as required. The primary glycaemic outcome measure was change in fasting blood glucose (FBG) and glycosylated haemoglobin A1c (HbA1c) at 52 weeks of treatment. Among the 1897 potentially eligible patients enrolled in the study, 1714 fulfilled the screening criteria. During the 52-week treatment period of the study, FBG and HbA1c did not change significantly. Clinically important and statistically significant changes were observed for both the systolic (SBP) and diastolic BP (DBP) during the study treatment period, with an overall mean decrease of 16.95 mm Hg in SBP (P=0.001) and 9.84 mm Hg in DBP (P=0.001). The majority of the patients (77.3%) achieved a target BP of <140/90 mm Hg. In conclusion, losartan, either alone or in combination with HCTZ, is effective in managing hypertension without inducing any change in glycaemic parameters or increasing the risk for developing diabetes in hypertensive patients with the metabolic syndrome.

Domain-specific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer's disease: ADAS-cog subscale results from the Alphase Study.

OBJECTIVES: Tramiprosate (homotaurine, ALZHEMEDTM) was recently investigated for its efficacy, safety and disease-modification effects in a Phase III clinical study in mild to moderate Alzheimer's disease (AD) patients (the Alphase study). The primary cognitive endpoint measure of that study was the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). To characterize potential cognitive benefits of tramiprosate, the present study describes exploratory analyses performed on scores obtained from the specific ADAS-cog subscales in order to determine whether specific domains of cognition may be differentially affected by tramiprosate, which would not have been evident from the measure's total score. DESIGN: Multi-center, double-blind, randomized, placebo-controlled study. SETTING: 67 investigative sites in the United States and Canada. PARTICIPANTS: A total of 1,052 patients were randomized. INTERVENTIONS: Patients were randomized to receive twice a day Placebo (n=353), tramiprosate 100 mg (n=352) and tramiprosate 150 mg (n=347). MEASUREMENTS: ADAS-cog assessments were conducted every three months over the 78-week study period. Exploratory analyses were performed by comparing ADAS-cog subscale scores between Placebo and each active treatment arm at each visit. RESULTS: The findings of this analysis revealed statistically significant differences or statistical trends in favour of tramiprosate on six ADAS-cog subscales, namely Following Commands, Language Comprehension, Ideational Praxis, Object Naming, Remembering Test Instructions, and Spoken Language Ability. Differences in favor of Placebo were only observed on the Constructional Praxis subscale. CONCLUSION: This exploratory analysis suggests that tramiprosate may have some benefit on memory, language and praxis skills in mild to moderate AD individuals. Future clinical studies of tramiprosate should include specialized neuropsychological tests to validate its effects within these cognitive domains.

Effect of tramiprosate in patients with mild-to-moderate Alzheimer's disease: exploratory analyses of the MRI sub-group of the Alphase study.

OBJECTIVES: The efficacy, safety and disease-modification of tramiprosate (homotaurine)were investigated in a recently completed large-scale Phase III clinical study in patients with mild to moderate Alzheimer's disease (AD), the Alphase study. Disease-modification was assessed using longitudinal volumetric MRI (vMRI) measurements of the hippocampus in a subgroup of patients. The present study describes the vMRI, cognitive and clinical results obtained in this subgroup. DESIGN: Multi-center, double-blind, randomized, placebo-controlled study in a subset of the 1052 patients of the Alphase study. SETTING: 51 vMRI investigative sites in the United States and Canada. PARTICIPANTS: A total of 508 patients underwent vMRI scanning. Of these, 312 provided scan pairs for assessing hippocampus volume changes and were included in the analyses. INTERVENTIONS: Patients were randomized to receive Placebo BID (n = 109), tramiprosate 100 mg BID (n = 103), or tramiprosate 150 mg BID (n = 100) for 78 weeks. MEASUREMENTS: Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinical Dementia Rating-Sum-of-boxes CDR-SB assessments were conducted at Baseline and at Weeks 13, 26, 39, 52, 65 and 78. Exploratory analyses were performed using similar First and Final mixed-effects repeated-measures models that were used for the analysis of the entire patient dataset. RESULTS: Psychometric score results showed numerical trends in favour of tramiprosate that did not reach statistical significance. While there were no statistically significant group differences in hippocampus volume using the First modeling approach, a significant dose-response reduction in hippocampus volume change was found in the Final models. Moreover, there was a marginally significant overall treatment main effect and a significant slope difference in favour of tramiprosate according to the Final model analysis of the ADAS-cog scores. ADAS-cog scores analyzed according to this model also revealed differences in favor of the tramiprosate 150 mg group at weeks 26 and 52, with marginally significant differences at Weeks 13 and 39. Slope analyses of ADAS-cog score changes showed significant differences in favor of the 150 mg BID group, and when both active groups were combined, in comparison to the placebo group. No between-group differences with respect to changes to each visit in the CDR-SB were observed with either modeling approach. Although there was a similar dose-response relationship observed in the hippocampus volume and ADAS-cog Final model analyses, the overall changes in psychometric scores and hippocampus volume were not significantly correlated. CONCLUSION: Exploratory analysis of the vMRI subgroup suggests that tramiprosate slows hippocampal atrophy, and reveals some evidence of a beneficial effect on cognition. The clinical validity of the vMRI biomarker is discussed.

Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index.

BACKGROUND: Enthesitis is a recommended core domain for assessment of ankylosing spondylitis (AS), but no measurement has yet been validated according to Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) criteria. OBJECTIVE: The purpose of this study was to seek to validate an enthesitis index for patients with AS according to OMERACT criteria. METHODS: An enthesitis index was validated in two AS patient cohorts: (1) a longitudinal cohort (n = 223) and (2) 22 patients from three Canadian sites participating in a 24-week randomised placebo-controlled trial of adalimumab in AS. Construct validity was evaluated by correlation analysis with the Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI) and quality of life instruments. Reproducibility was assessed by intraclass correlation coefficient (ICC), and responsiveness was assessed by Guyatt's effect size and standardised response mean. RESULTS: The most frequently affected sites were the greater trochanter and supraspinatus insertion ( approximately 20%). Patients with enthesitis had significantly greater scores for the BASDAI, BASFI, patient global, AS-specific quality of life index (ASQOL) and the Short Form 36 (SF-36) General Health Survey (p<0.001). The enthesitis score contributed significantly to variance in the BASDAI and BASFI. Interobserver ICCs were 0.96 in the longitudinal cohort and 0.89 and 0.77 in the adalimumab clinical trial cohort (for status and change score, respectively). Significant differences in change scores were evident for all patients after 24 weeks of adalimumab treatment, (p = 0.04), this being more significant when a subset of the most commonly affected entheses were analysed (p = 0.01). CONCLUSION: AS patients with enthesitis constitute a more severe subset of disease, and the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index is feasible and reliable for measurement of this condition. Discrimination requires further study in larger trials.

International prospective evaluation of scintimammography with technetium-99m sestamibi: interim results.

OBJECTIVE: The purpose of this study is to evaluate the validity and reliability of scintimammography with technetium-99m (99mTc)-labeled sestamibi as an adjunct radiodiagnostic agent in the diagnosis of breast cancer. METHODS: This is a multicenter prospective cohort clinical trial that was initiated in June 1999 and will terminate May 2001. All patients with a physical or mammographic finding visiting any of the participating clinics are enrolled in the study. Patients who are younger than 18 years, pregnant, not willing to sign the consent form, or who have undergone an invasive procedure on the breast 30 days or less before scintimammography are excluded. At the time of the first interim report, 633 patients had been recruited from six Canadian centers. To date complete data have been collected for 530 patients. RESULTS: The mean (SD) age of the patients is 56 (12) years with a range between 24 and 85. There were 122 (23%) of the women in the sample who were postmenopausal and 36 (7%) who were perimenopausal. Breast density was graded as dense for 127 (24%), normal for 260 (50%), and fatty for 138 (26%). Of the 530 women in the study 156 (29%) had a palpable mass at physical examination. The mammographic results were classified as 76 (14%) breast imaging reporting and data system (BIRADS) 5, 60 (11%) BIRADS 4, 70 (13%) BIRADS 3 and the remaining BIRADS 2 or 1. The scintimammography results were positive for 118 (23%) of the patients and negative for 412 (78%). The histopathology showed malignant breast disease for 66 (12.5%) of the patients in the sample. Sensitivity and specificity of scintimammography for the detection of breast cancer was estimated 90.9% and 87.5%, respectively. A positive predictive value (PPV) of 50.8% with a negative predictive value of 98.5% and an accuracy of 87.5% were calculated. The PPV is interpreted as the posttest probability of disease given a positive test result. In this sample the pretest probability of disease would be best estimated by the prevalence of disease, which is equal to 12.5%. A positive scintimammography result would change the estimated probability to 51%, which is equivalent to a 400% change from the pretest value. Therefore a positive scintimammography result significantly increases our ability to predict the presence of malignant disease in this population. CONCLUSION: The interim results of the present study suggest that scintimammography with 99mTc-sestamibi is accurate and potentially useful as an adjunct to mammography for the detection of breast cancer.

Impact of waiting time on the quality of life of patients awaiting coronary artery bypass grafting.

BACKGROUND: A lack of resources has created waiting lists for many elective surgical procedures within Canada's universal health care system. Coronary artery bypass grafting (CABG) for the treatment of atherosclerotic ischemic heart disease is one of these affected surgical procedures. We studied the impact of waiting times on the quality of life of patients awaiting CABG. METHODS: A prospective cohort of 266 patients from 3 hospitals in Montreal was used. Patients who gave informed consent were followed from the time they were registered for CABG until 6 months after surgery; recruitment began in November 1993, and the last follow-up was completed in July 1995. Patient groups were classified according to the duration of the wait for CABG (< or = 97 days or > 97 days). We measured the following outcomes: quality of life (using the Medical Outcomes Study 36-item Short Form [SF-36]), incidence of chest pain (using the New York Heart Association angina classification), frequency of symptoms (using the Cardiac Symptom Inventory) and rates of complications and death before and after surgery. RESULTS: There were no differences in quality of life at baseline between the 2 groups. Immediately before surgery, compared with patients who waited 97 days or less, those who waited longer had significantly reduced physical functioning (change from baseline SF-36 score 0 v. -4 respectively, p = 0.001), vitality (change from baseline score -0.1 v. -1.3, p = 0.01), social functioning (change from baseline score 0.4 v. -0.4, p = 0.03) and general health (change from baseline score 1.1 v. -1.7, p = 0.001). At 6 months after surgery, compared with patients who waited 97 days or less for CABG, those who waited longer had reduced physical functioning (change from baseline SF-36 score 4.0 v. -0.1 respectively, p = 0.001), physical role (change from baseline score 0.8 v. 0.0, p = 0.001), vitality (change from baseline score 2.2 v. 0.9, p = 0.001), mental health (change from baseline score 1.2 v. 0.0, p = 0.001) and general health (change from baseline score 1.8 v. -0.3, p = 0.001). The incidence of postoperative adverse events was significantly greater among the patients with longer waits for CABG than among those with shorter waits (32 v. 14 events respectively, p = 0.005). Longer waits before CABG were associated with an increased likelihood of not returning to work after surgery (p = 0.08): 10 (53%) of the 19 patients with longer waiting times remained employed after CABG, as compared with 17 (85%) of the 20 with shorter waiting times. INTERPRETATION: The significant decrease in physical and social functioning, both before and after surgery, for patients waiting more than 3 months for CABG is an important observation. Longer waiting times were also associated with increased postoperative adverse events. By decreasing waiting times for CABG, we may improve patients' quality of life and decrease the psychological morbidity associated with CABG.

Teaching cardiopulmonary resuscitation to CEGEP students in Quebec--a pilot project.

In order to increase CPR training in Quebec, we designed a pilot study to test out the efficacy of training CEGEP (junior college) students in CPR. We tried out four different methods of teaching CPR on students (Group A 'control', 4 h course, manikin to student ratio 1:4; Group B, 4 h course, manikin to student ratio 1:1; Group C, 2 h course, manikin to student ratio 1:1; Group D, video-assisted CPR instruction, manikin to student ratio 1:1). CPR skills were tested on a computerized manikin at the end of the initial course and again at the end of the semester in order to evaluate short and long-term retention of skills. There were no significant differences between the test groups and the control group in terms of compressions or ventilations at the beginning and end of the semester, however groups C and D performed significantly better primary surveys (Airway, Breathing, Circulation - ABC sequences) during the initial testing. The most common reasons reported by students for not taking CPR courses were the cost of courses (49.2%) and the inconvenience of courses (26.2%), similarly the two most common incentives which could get students to take CPR courses were; free courses (65.6%) and greater accessibility of courses (54.1%). Video-assisted CPR training appears to be feasible, enjoyable and as, if not more effective than traditional CPR courses. Instituting a mandatory video-assisted CPR program in the CEGEP system in Quebec and in high schools and colleges throughout the world, would be a cost-effective way to train massive amounts of young people in CPR.

Advanced or basic life support for trauma: meta-analysis and critical review of the literature.

BACKGROUND: The question of whether to use advanced life support (ALS) or basic life support (BLS) for trauma patients in the prehospital setting has been much debated and still lacks a clear answer. The purpose of this study was to conduct a comprehensive critical review of the literature regarding this controversy METHODS: A total of 174 articles on prehospital ALS or BLS for trauma were reviewed. Fifteen of these studies were found to involve mortality statistics for both ALS- and BLS-treated patients. Odds ratios were calculated for survival in ALS versus BLS and summarized across studies on the basis of multivariate scoring systems that incorporated both design and methodological assessment. Overall odds ratios for all studies were calculated on the basis of both raw data from the papers, and weighted odds ratios were calculated from the scoring systems. RESULTS: Six studies were scored as being methodologically average (5 favoring BLS and 1 favoring ALS), two were scored as good (1 favoring BLS and 1 favoring ALS), seven as excellent (6 favoring BLS and 1 favoring ALS). Ten studies had an average study design score (6 favoring BLS and 4 favoring ALS) and seven had a good study design score (6 favoring BLS and 1 favoring ALS). Weighted odds ratio for dying was 2.59 for patients receiving ALS compared with those receiving BLS. The crude odds ratio was 2.92. CONCLUSION: The aggregated data in the literature have failed to demonstrate a benefit for on-site ALS provided to trauma patients and support the scoop and run approach.

Cardiopulmonary resuscitation: errors made by pre-hospital emergency medical personnel.

The purpose of the current study was to evaluate the CPR techniques of emergency healthcare professionals (emergency medical technicians, firemen, emergency first responders, CPR instructors). Skills were evaluated using a Laerdal Skillmeter Manikin, which provided a computerized printout of the quantifiable data during the CPR sequence. All of the 66 subjects in the study had completed a recertification course within the last 2 years (mean = 0.86 +/- 0.18, 95% CI). The sequence was videotaped for later viewing and for correlating the errors with the data. In addition, the participants were required to fill in a questionnaire. The most frequently occurring errors were observed in landmarking, overcompression, palpating a carotid pulse and insufficient ventilation. Although 98.5% of participants made an attempt to landmark their position for compression on the sternum, 35.9% of the total compressions performed by all subjects were incorrectly positioned on the patient's chest. Overcompression of the patient's chest accounted for 55.3% of incorrect compressions. Although 94% of participants attempted to verify a carotid pulse, only 45% were able to feel it and therefore stop performing cardiac massage. Of the total ventilations, 49% were below the American Heart Association (AHA) recommended minimum (800 ml). The results of this study showed a high rate of errors occurring in the CPR provided by emergency healthcare professionals.

Trauma care regionalization: a process-outcome evaluation.

BACKGROUND: Regionalization of trauma care services in our region was initiated in 1993 with the designation of four tertiary trauma centers. The process continued in 1995 with the implementation of patient triage and transfer protocols. Since 1995, the network of trauma care has been expanded with the designation of 33 secondary, 30 primary, and 32 stabilization trauma centers. In addition, during this period emergency medical personnel have been trained to assess and triage trauma victims within minimal prehospital time. The objective of the present study was to evaluate the impact of trauma care regionalization on the mortality of major trauma patients. METHODS: This was a prospective study in which patients were entered at the time of injury and were followed to discharge from the acute-care hospital. The patients were identified from the Quebec Trauma Registry, a review of the records of acute-care hospitals that treat trauma, and records of the emergency medical services in the region. The study sample consisted of all patients fulfilling the criteria of a major trauma, defined as death, or Injury Severity Score (ISS) > 12, or Pre-Hospital Index > 3, or two or more injuries with Abbreviated Injury Scale scores > 2, or hospital stay of more than 3 days. Data collection took place between April 1, 1993, and March 31, 1998. During this period, four distinct phases of trauma care regionalization were defined: pre-regionalization (phase 0), initiation (phase I), intermediate (phase II), and advanced (phase III). RESULTS: A total of 12,208 patients were entered into the study cohort, and they were approximately evenly distributed over the 6 years of the study. During the study period, there was a decline in the mean age of patients from 54 to 46 years, whereas the male/female ratio remained constant at 2:1. There was also an increase in the mean ISS, from 25.5 to 27.5. The proportion of patients injured in motor vehicle collisions increased from less than 45% to more than 50% (p < 0.001). The mortality rate during the phases of regionalization were: phase 0, 52%; phase I, 32%; phase II, 19%; and phase III, 18%. These differences were clinically important and statistically significant (p < 0.0001). Stratified analysis showed a significant decline in mortality among patients with ISS between 12 and 49. The change in mortality for patients with fatal injuries (ISS > or = 50) was not significant. During the study period, the mean prehospital time decreased significantly, from 62 to 44 minutes. The mean time to admission after arrival at the hospital decreased from 151 to 128 minutes (p < 0.001). The latter decrease was primarily attributable to changes at the tertiary centers. The proportion of patients with ISS between 12 and 24 and between 25 and 49 who were treated at tertiary centers increased from 56 to 82% and from 36 to 84%, respectively (p < 0.001). Compared with the secondary and primary centers, throughout the course of the study the mortality rate in the secondary and tertiary centers showed a consistent decline (p < 0.001). In addition, the mortality rate in the tertiary centers remained consistently lower (p < 0.001). The results of multivariate analyses showed that after adjusting for injury severity and patient age, the primary factors contributing to the reduced mortality were treatment at a tertiary center, reduced prehospital time, and direct transport from the scene to tertiary centers. CONCLUSION: This study produced empirical evidence that the integration of trauma care services into a regionalized system reduces mortality. The results showed that tertiary trauma centers and reduced prehospital times are the essential components of an efficient trauma care system.