When clinical guidelines affect large numbers of individuals or substantial resources, it is important to understand their benefits, harms and costs from a population perspective. Many countries' dyslipidemia guidelines include these perspectives.
To compare the effectiveness and efficiency of the 2003 and 2006 Canadian dyslipidemia guidelines for statin treatment in reducing deaths from coronary artery disease (CAD) in the Canadian population.
The 2003 and 2006 Canadian dyslipidemia guidelines were applied to data from the Canadian Heart Health Survey (weighted sample of 12,300,000 people), which includes information on family history and physical measurements, including fasting lipid profiles. The number of people recommended for statin treatment, the potential number of CAD deaths avoided and the number needed to treat to avoid one CAD death with five years of statin therapy were determined for each guideline.
Compared with the 2003 guidelines, 1.4% fewer people (20 to 74 years of age) are recommended statin treatment, potentially preventing 7% more CAD deaths. The number needed to treat to prevent one CAD death over five years decreased from 172 (2003 guideline) to 147 (2006 guideline).
From a population perspective, the 2006 Canadian dyslipidemia recommendations are an improvement of earlier versions, preventing more CAD events and deaths with fewer statin prescriptions. Despite these improvements, the Canadian dyslipidemia recommendations should explicitly address issues of absolute benefit and cost-effectiveness in future revisions.
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Comment In: Can J Cardiol. 2008 Aug;24(8):62118697284
The 2011 Canadian Cardiovascular Society Heart Failure (HF) Guidelines Focused Update reviews the recently published clinical trials that will potentially impact on management. Also reviewed is the less studied but clinically important area of sleep apnea. Finally, patients with advanced HF represent a group of patients who pose major difficulties to clinicians. Advanced HF therefore is examined from the perspectives of HF complicated by renal failure, the role of palliative care, and the role of mechanical circulatory support (MCS). All of these topics are reviewed from a perspective of practical applications. Important new studies have demonstrated in less symptomatic HF patients that cardiac resynchronization therapy will be of benefit. As well, aldosterone receptor antagonists can be used with benefit in less symptomatic HF patients. The important role of palliative care and the need to address end-of-life issues in advanced HF are emphasized. Physicians need to be aware of the possibility of sleep apnea complicating the course of HF and the role of a sleep study for the proper assessment and management of the conditon. Patients with either acute severe or chronic advanced HF with otherwise good life expectancy should be referred to a cardiac centre capable of providing MCS. Furthermore, patients awaiting heart transplantation who deteriorate or are otherwise not likely to survive until a donor organ is found should be referred for MCS.
Comment In: Can J Cardiol. 2011 Nov-Dec;27(6):871.e721885242
To identify predictors of survival in a retrospective multicentre cohort of patients with cardiogenic shock undergoing coronary angiography and to address whether complete revascularization is associated with improved survival in this cohort.
Early revascularization is the standard of care for cardiogenic shock. Coronary bypass grafting and percutaneous intervention have complimentary roles in achieving this revascularization.
A total of 210 consecutive patients (mean age 66 ± 12 years) at two tertiary centres from 2002 to 2006 inclusive with a diagnosis of cardiogenic shock were evaluated. Univariate and multivariate predictors of in-hospital survival were identified utilizing logistic regression.
ST elevation infarction occurred in 67% of patients. Thrombolysis was administered in 34%, PCI was attempted in 62% (88% stented, 76% TIMI 3 flow), CABG was performed in 22% (2.7 grafts, 14 valve procedures), and medical therapy alone was administered to the remainder. The overall survival to discharge was 59% (CABG 68%, PCI 57%, medical 48%). Independent predictors of mortality included complete revascularization (P = 0.013, OR = 0.26 (95% CI: 0.09-0.76), hyperlactatemia (P = 0.046, OR = 1.14 (95% CI: 1.002-1.3) per mmol increase), baseline renal insufficiency (P = 0.043, OR = 3.45, (95% CI: 1.04-11.4), and the presence of anoxic brain injury (P = 0.008, OR = 8.22 (95% CI: 1.73-39.1). Within the STEMI with concomitant multivessel coronary disease subgroup of this population (N = 101), independent predictors of survival to discharge included complete revascularization (P = 0.03, OR = 2.5 (95% CI: 1.1-6.2)) and peak lactate (P = 0.02).
The ability to achieve complete revascularization may be strongly associated with improved in-hospital survival in patients with cardiogenic shock.
Comment In: Catheter Cardiovasc Interv. 2011 Oct 1;78(4):549-5021953751
Type XIII collagen is a type II transmembrane protein found at sites of cell adhesion. Transgenic mouse lines were generated by microinjection of a DNA construct directing the synthesis of truncated alpha1(XIII) chains. Shortened alpha 1(XIII) chains were synthesized by fibroblasts from mutant mice, and the lack of intracellular accumulation in immunofluorescent staining of tissues suggested that the mutant molecules were expressed on the cell surface. Transgene expression led to fetal lethality in offspring from heterozygous mating with two distinct phenotypes. The early phenotype fetuses were aborted by day 10.5 of development due to a lack of fusion of the chorionic and allantoic membranes. The late phenotype fetuses were aborted by day 13.5 of development and displayed a weak heartbeat, defects of the adherence junctions in the heart with detachment of myofilaments and abnormal staining for the adherence junction component cadherin. Decreased microvessel formation was observed in certain regions of the fetus and the placenta. These results indicate that type XIII collagen has an important role in certain adhesive interactions that are necessary for normal development.
OBJECTIVES: High tumor grade and lymph node positivity are associated with poor prognosis in breast carcinoma. Prognostic markers are used to define which patient groups benefit from different treatment modalities, some of which are potentially very toxic. Matrix metalloproteinases (MMPs) degrade the extracellular matrix, and type IV collagenases MMP-2 and -9 have been linked to invasive behavior of several malignancies. Tissue inhibitors of metalloproteinases (TIMPs) -1 and -2 inhibit their activity and are therefore considered to have an inhibitory effect on tumor progression. The role of TIMPs in progression of breast carcinoma is, however, still poorly known. Here the effect of TIMP-1 and -2 on survival was examined in lymph node-positive breast carcinoma patients. METHODS: TIMP-1 or -2 was evaluated with avidin-biotin immunohistochemical staining from paraffin-embedded sections of primary breast carcinoma of 132 cases. RESULTS: Positive staining for TIMP-1 and -2 was observed in 81 and 84% of the tumors respectively. TIMP-1 correlated to the grade of the tumor (p = 0.047). Absence of TIMP-1 protein correlated with favorable disease-specific survival of the patients with high-grade tumors. After 10 years of follow-up as high as 88% of patients with a grade 2-3, but TIMP-1-negative tumor were alive, when only 61% of the TIMP-1-positive cases in this group survived by that time (p = 0.03). CONCLUSION: Our results suggest that lack of TIMP-1 protein expression is associated with a favorable prognosis in patients with node-positive high-grade breast carcinoma.
Cox proportional hazards regression models are frequently used to determine the association between exposure and time-to-event outcomes in both randomized controlled trials and in observational cohort studies. The resultant hazard ratio is a relative measure of effect that provides limited clinical information.
A method is described for deriving absolute reductions in the risk of an event occurring within a given duration of follow-up time from a Cox regression model. The associated number needed to treat can be derived from this quantity. The method involves determining the probability of the outcome occurring within the specified duration of follow-up if each subject in the cohort was treated and if each subject was untreated, based on the covariates in the regression model. These probabilities are then averaged across the study population to determine the average probability of the occurrence of an event within a specific duration of follow-up in the population if all subjects were treated and if all subjects were untreated.
Risk differences and numbers needed to treat.
Absolute measures of treatment effect can be derived in prospective studies when Cox regression is used to adjust for possible imbalance in prognostically important baseline covariates.
The aim of this study is to determine if there has been a true, absolute, or apparent relative increase in congenital diaphragmatic hernia (CDH) survival for the last 2 decades.
All neonatal Bochdalek CDH patients admitted to an Ontario pediatric surgical hospital during the period when significant improvements in CDH survival was reported (from January 1, 1992, to December 31, 1999) were analyzed. Patient characteristics were assessed for CDH population homogeneity and differences between institutional and vital statistics-based population survival outcomes. SAS 9.1 (SAS Institute, Cary, NC) was used for analysis.
Of 198 cohorts, demographic parameters including birth weight, gestational age, Apgar scores, sex, and associated congenital anomalies did not change significantly. Preoperative survival was 149 (75.2%) of 198, whereas postoperative survival was 133 (89.3%) of 149, and overall institutional survival was 133 (67.2%) of 198. Comparison of institution and population-based mortality (n = 65 vs 96) during the period yielded 32% of CDH deaths unaccounted for by institutions. Yearly analysis of hidden mortality consistently showed a significantly lower mortality in institution-based reporting than population.
A hidden mortality exists for institutionally reported CDH survival rates. Careful interpretation of research findings and more comprehensive population-based tools are needed for reliable counseling and evaluation of current and future treatments.
It has been well known that ignoring measurement error may result in substantially biased estimates in many contexts including linear and nonlinear regressions. For survival data with measurement error in covariates there has been extensive discussion in the literature with the focus being on the Cox proportional hazards models. However, the impact of measurement error on accelerated failure time (AFT) models has received little attention, though AFT models are very useful in survival data analysis. In this paper, we discuss AFT models with error-prone covariates and study the bias induced by the naive approach of ignoring measurement error in covariates. To adjust for such a bias, we describe a simulation and extrapolation method. This method is appealing because it is simple to implement and it does not require modelling the true but error-prone covariate process that is often not observable. Asymptotic normality for the resulting estimators is established. Simulation studies are carried out to evaluate the performance of the proposed method as well as the impact of ignoring measurement error in covariates. The proposed method is applied to analyse a data set arising from the Busselton Health study (Australian J. Public Health 1994; 18:129-135).