May 072013
 
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Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type.

CMAJ. 2013 Mar 19;185(5):E229-37

Authors: Sode BF, Allin KH, Dahl M, Gyntelberg F, Nordestgaard BG

Abstract
BACKGROUND: ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated with the risk of venous thromboembolism and myocardial infarction in the general population.
METHODS: We used data from 2 Danish studies that followed members of the general public from 1977 through 2010. We obtained the genotype of 66 001 white participants for ABO blood type, factor V Leiden R506Q and prothrombin G20210A. We calculated hazard ratios (HRs) and population attributable risk. Our main outcome measures were venous thromboembolism and myocardial infarction.
RESULTS: The multivariable adjusted HR for venous thromboembolism was 1.4 (95% confidence interval [CI] 1.3-1.5) for non-O blood type (v. O blood type). For the factor V Leiden R506Q mutation, the adjusted HR was 2.2 (95% CI 2.0-2.5) for heterozygous participants and 7.0 (95%CI 4.8-10) for homozygous participants (v. participants without the mutation). For prothrombin G20210A, the adjusted HR was 1.5 (95%CI 1.2-1.9) for heterozygous participants and 11 (95% CI 2.8-44) for homozygous participants (v. participants without the mutation). When we combined ABO blood type and factor V Leiden R506Q or prothrombin G20210A genotype, there was a stepwise increase in the risk of venous thromboembolism (trend, p<0.001). The population attributable risk of venous thromboembolism was 20% for ABO blood type, 10% for factor V Leiden R506Q and 1% for prothrombin G20210A. Multivariable adjusted HRs for myocardial infarction by genotypes did not differ from 1.0.
INTERPRETATION: ABO blood type had an additive effect on the risk of venous thromboembolism when combined with factor V Leiden R506Q and prothrombin G20210A mutations; blood type was the most important risk factor for venous thromboembolism in the general population.

PMID: 23382263 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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Apr 112013
 
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Rates of hemorrhage during warfarin therapy for atrial fibrillation.

CMAJ. 2013 Feb 5;185(2):E121-7

Authors: Gomes T, Mamdani MM, Holbrook AM, Paterson JM, Hellings C, Juurlink DN

Abstract
BACKGROUND: Although warfarin has been extensively studied in clinical trials, little is known about rates of hemorrhage attributable to its use in routine clinical practice. Our objective was to examine incident hemorrhagic events in a large population-based cohort of patients with atrial fibrillation who were starting treatment with warfarin.
METHODS: We conducted a population-based cohort study involving residents of Ontario (age ≥ 66 yr) with atrial fibrillation who started taking warfarin between Apr. 1, 1997, and Mar. 31, 2008. We defined a major hemorrhage as any visit to hospital for hemorrage. We determined crude rates of hemorrhage during warfarin treatment, overall and stratified by CHADS(2) score (congestive heart failure, hypertension, age ≥ 75 yr, diabetes mellitus and prior stroke, transient ischemic attack or thromboembolism).
RESULTS: We included 125 195 patients with atrial fibrillation who started treatment with warfarin during the study period. Overall, the rate of hemorrhage was 3.8% (95% confidence interval [CI] 3.8%-3.9%) per person-year. The risk of major hemorrhage was highest during the first 30 days of treatment. During this period, rates of hemorrhage were 11.8% (95% CI 11.1%-12.5%) per person-year in all patients and 16.7% (95% CI 14.3%-19.4%) per person-year among patients with a CHADS(2) scores of 4 or greater. Over the 5-year follow-up, 10 840 patients (8.7%) visited the hospital for hemorrhage; of these patients, 1963 (18.1%) died in hospital or within 7 days of being discharged.
INTERPRETATION: In this large cohort of older patients with atrial fibrillation, we found that rates of hemorrhage are highest within the first 30 days of warfarin therapy. These rates are considerably higher than the rates of 1%-3% reported in randomized controlled trials of warfarin therapy. Our study provides timely estimates of warfarin-related adverse events that may be useful to clinicians, patients and policy-makers as new options for treatment become available.

PMID: 23184840 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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Jan 172013
 
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Alcohol consumption and the risk of incident atrial fibrillation among people with cardiovascular disease.

CMAJ. 2012 Nov 6;184(16):E857-66

Authors: Liang Y, Mente A, Yusuf S, Gao P, Sleight P, Zhu J, Fagard R, Lonn E, Teo KK, ONTARGET and TRANSCEND Investigators

Abstract
BACKGROUND: Moderate alcohol consumption may reduce cardiovascular events, but little is known about its effect on atrial fibrillation in people at high risk of such events. We examined the association between moderate alcohol consumption and the risk of incident atrial fibrillation among older adults with existing cardiovascular disease or diabetes.
METHODS: We analyzed data for 30 433 adults who participated in 2 large antihypertensive drug treatment trials and who had no atrial fibrillation at baseline. The patients were 55 years or older and had a history of cardiovascular disease or diabetes with end-organ damage. We classified levels of alcohol consumption according to median cut-off values for low, moderate and high intake based on guidelines used in various countries, and we defined binge drinking as more than 5 drinks a day. The primary outcome measure was incident atrial fibrillation.
RESULTS: A total of 2093 patients had incident atrial fibrillation. The age- and sex-standardized incidence rate per 1000 person-years was 14.5 among those with a low level of alcohol consumption, 17.3 among those with a moderate level and 20.8 among those with a high level. Compared with participants who had a low level of consumption, those with higher levels had an increased risk of incident atrial fibrillation (adjusted hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.04-1.26, for moderate consumption; 1.32, 95% CI 0.97-1.80, for high consumption). Results were similar after we excluded binge drinkers. Among those with moderate alcohol consumption, binge drinkers had an increased risk of atrial fibrillation compared with non-binge drinkers (adjusted HR 1.29, 95% CI 1.02-1.62).
INTERPRETATION: Moderate to high alcohol intake was associated with an increased incidence of atrial fibrillation among people aged 55 or older with cardiovascular disease or diabetes. Among moderate drinkers, the effect of binge drinking on the risk of atrial fibrillation was similar to that of habitual heavy drinking.

PMID: 23027910 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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Jan 112013
 
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Comparing methods to calculate hospital-specific rates of early death or urgent readmission.

CMAJ. 2012 Oct 16;184(15):E810-7

Authors: van Walraven C, Wong J, Hawken S, Forster AJ

Abstract

BACKGROUND: Hospital readmissions are important patient outcomes that can be accurately captured with routinely collected administrative data. Hospital-specific readmission rates have been reported as a quality-of-care indicator. However, the extent to which these measures vary with different calculation methods is uncertain.

METHODS: We identified all discharges from Ontario hospitals from 2005 to 2010 and determined whether patients died or were urgently readmitted within 30 days. For each hospital, we calculated 4 distinct observed-to-expected ratios, estimating the expected number of events using different adjustments for confounders (age and sex v. complete) and different units of analysis (all admissions v. single admission per patient).

RESULTS: We included 3 148 648 admissions to hospital for 1 802 704 patients in 162 hospitals. Ratios adjusted for age and sex alone had the greatest variation. Within hospitals, ranges of the 4 ratios averaged 31% of the overall estimate. Readmission ratios adjusted for age and sex showed the lowest correlation (Spearman correlation coefficient 0.48-0.68). Hospital rankings based on the different measures had an average range of 47.4 (standard deviation 32.2) out of 162.

INTERPRETATION: We found notable variation in rates of death or urgent readmission within 30 days based on the extent of adjustment for confounders and the unit of analysis. Slight changes in the methods used to calculate hospital-specific readmission rates influence their values and the consequent rankings of hospitals. Our results highlight the caution required when comparing hospital performance using rates of death or urgent readmission within 30 days.

PMID: 23048081 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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Dec 122012
 
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Effects of assessing the productivity of faculty in academic medical centres: a systematic review.

CMAJ. 2012 Aug 7;184(11):E602-12

Authors: Akl EA, Meerpohl JJ, Raad D, Piaggio G, Mattioni M, Paggi MG, Gurtner A, Mattarocci S, Tahir R, Muti P, Schünemann HJ

Abstract

BACKGROUND: Many academic medical centres have introduced strategies to assess the productivity of faculty as part of compensation schemes. We conducted a systematic review of the effects of such strategies on faculty productivity.

METHODS: We searched the MEDLINE, Healthstar, Embase and PsycInfo databases from their date of inception up to October 2011. We included studies that assessed academic productivity in clinical, research, teaching and administrative activities, as well as compensation, promotion processes and satisfaction.

RESULTS: Of 531 full-text articles assessed for eligibility, we included 9 articles reporting on eight studies. The introduction of strategies for assessing academic productivity as part of compensation schemes resulted in increases in clinical productivity (in six of six studies) in terms of clinical revenue, the work component of relative-value units (these units are nonmonetary standard units of measure used to indicate the value of services provided), patient satisfaction and other departmentally used standards. Increases in research productivity were noted (in five of six studies) in terms of funding and publications. There was no change in teaching productivity (in two of five studies) in terms of educational output. Such strategies also resulted in increases in compensation at both individual and group levels (in three studies), with two studies reporting a change in distribution of compensation in favour of junior faculty. None of the studies assessed effects on administrative productivity or promotion processes. The overall quality of evidence was low.

INTERPRETATION: Strategies introduced to assess productivity as part of a compensation scheme appeared to improve productivity in research activities and possibly improved clinical productivity, but they had no effect in the area of teaching. Compensation increased at both group and individual levels, particularly among junior faculty. Higher quality evidence about the benefits and harms of such assessment strategies is needed.

PMID: 22641686 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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Sep 202012
 
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Baseline Q waves as a prognostic modulator in patients with ST-segment elevation: insights from the PLATO trial.

CMAJ. 2012 Jul 10;184(10):1135-42

Authors: Siha H, Das D, Fu Y, Zheng Y, Westerhout CM, Storey RF, James S, Wallentin L, Armstrong PW

Abstract

BACKGROUND: Baseline Q waves may provide additional value compared with time from the onset of symptoms in predicting outcomes for patients with ST-segment elevation. We evaluated whether baseline Q waves superseded time from symptom onset as a prognostic marker of one-year mortality in patients with ST-segment elevation acute coronary syndrome. Our study was derived from data from patients undergoing primary percutaneous coronary intervention within 24 hours in the PLATelet inhibition and patient Outcomes trial

METHODS: Q waves on the baseline electrocardiogram were evaluated by a blinded core laboratory. We assessed the associations between baseline Q waves and time from symptom onset to percutaneous coronary intervention with peak biomarkers, ST-segment resolution on the discharge electrocardiogram, and one-year all-cause and vascular mortality.

RESULTS: Of 4341 patients with ST-segment elevation, 46% had baseline Q waves. Compared to those without Q waves, those with baseline Q waves were older, more frequently male, had higher heart rates, more advanced Killip class and had a longer time between the onset of symptoms and percutaneous coronary intervention. They also had higher one-year all-cause mortality than patients without baseline Q waves (baseline Q waves: 4.9%; no baseline Q waves: 2.8%; hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.29-2.45, p < 0.001). Complete ST-segment resolution was greatest and all-cause mortality lowest among those with symptom onset three hours or less before percutaneous coronary intervention and no baseline Q waves. After multivariable adjustment, baseline Q waves, but not time from symptom onset, were associated with a significant increase in all-cause mortality (adjusted HR 1.42, 95% CI 1.10-2.01, p = 0.046) and vascular mortality (adjusted HR 1.58, 95% CI 1.09-2.28, p = 0.02).

INTERPRETATION: The presence of baseline Q waves provides useful additional prognostic insight into the clinical outcome of patients with ST-segment elevation. Clinical Trials.gov registration no. NCT00391872.

PMID: 22546885 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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