Real-time evaluation of an optimized real-time PCR assay versus Brilliance chromogenic MRSA agar for the detection of meticillin-resistant Staphylococcus aureus from clinical specimens.

A total of 1204 meticillin-resistant Staphylococcus aureus (MRSA) screens (3340 individual swabs) were tested to evaluate a staphylococcal cassette chromosome mec (SCCmec) real-time PCR. In total, 148 (12.3 %) of the screens were MRSA-positive, where 146 (12.1 %) were MRSA-positive by the SCCmec real-time PCR assay. In contrast, 128 (10.6 %) screens were MRSA-positive by culture. One hundred and twenty-six (10.5 %) of the screens were positive by both culture and PCR. Twenty of the 1204 screens (1.66 %) were negative by culture but positive by PCR; these samples were sequenced. In 14 of the cases, a homology search confirmed the sequence as SCCmec, indicating that these samples could be considered true positives. Two of the 1204 (0.2 %) screens were positive by culture and negative by PCR. The mean turnaround time (TAT) for PCR-negative swabs was 6 h 12 min and for PCR-positive swabs was 6 h 48 min. In comparison, for culture-negative swabs the mean TAT was 29 h 30 min and for culture-positive swabs was 69 h. The cost per swab for routine culture was £0.41 (€0.48) and that of the real-time PCR assay was £2.35 (€2.75). This optimized, in-house, inexpensive, real-time PCR test maintained a very high sensitivity and specificity when evaluated under real-time laboratory conditions. The TAT of this real-time PCR assay was substantially lower than that of chromogenic culture. It was also maintained throughout the entire process, which can be taken as an indirect measure of test performance. This study showed that implementation of a molecular test can be achieved with limited resources in a standard microbiology laboratory.

The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study.

PURPOSE: Atrial fibrillation is a common arrhythmia associated with increased cardiovascular morbidity and mortality. This study was undertaken to identify the natural history of this condition, including risk factors for its development, and outcome. PATIENTS AND METHODS: The incidence of atrial fibrillation among 3,983 male air crew recruits observed continuously for 44 years was calculated based on person-years of observation. Age and 23 variables were examined to identify risk factors for atrial fibrillation. Controlling for age and 9 prognostic variables, the effect of atrial fibrillation on 8 outcomes was examined. Analysis of risk factors for atrial fibrillation and outcome after atrial fibrillation was based on a Cox proportional hazard model using time-dependent covariates. RESULTS: Of the 3,983 study members, 299 (7.5%) developed atrial fibrillation during 154,131 person-years of observation. The incidence rose with age from less than 0.5 per 1,000 person-years before age 50 to 9.7 per 1,000 person-years after age 70. Risk for atrial fibrillation was increased with myocardial infarction (relative risk [RR] 3.62), angina (RR 2.84), and ST-T wave abnormalities in the absence of ischemic heart disease (RR 2.21). The RR for atrial fibrillation was strongest at the onset of ischemic heart disease and diminished over time. The rate of atrial fibrillation was 1.42 times increased in men with a history of hypertension. Congestive heart failure, valvular heart disease, and cardiomyopathy were important but uncommon risk factors. Atrial fibrillation independently increased the risk for stroke (RR 2.07) and congestive heart failure (RR 2.98). Total mortality rate was increased 1.31 times; cardiovascular mortality including and excluding fatal stroke were also increased (RR 1.41 and 1.37, respectively). CONCLUSIONS: The incidence of atrial fibrillation in men increases with advancing age. Clinical cardiac abnormalities, particularly recent ischemic heart disease and hypertension, are strongly associated with increased risk for atrial fibrillation. Atrial fibrillation increases morbidity and mortality, but the magnitude of the increase may be less than previously reported.

The natural history of asymptomatic complete heart block. A case series from the Manitoba Follow-up Study.

Long-standing asymptomatic complete heart block is unusual in adults. The natural history of this condition with advancing age is unknown. Four cases of complete heart block documented in patients for 23 to 48 years are reported. These men had no evidence of structural heart disease and functioned normally without symptoms for many years. Three of the four subsequently developed symptoms and required permanent pacemaker insertion. These cases illustrate the good prognosis of asymptomatic complete heart block, but raise the concern that with advancing age, intervention with pacing frequently is necessary.

Regular narrow QRS complex tachycardias in the Manitoba Follow-up Study (1948-88).

OBJECTIVE: To determine the incidence, risk factors and prognosis of regular narrow QRS complex tachycardia (NQT), which develops in the absence of pre-excitation in subjects free from ischemic heart disease in the Manitoba Follow-up Study. DESIGN AND SETTING: The Manitoba Follow-up Study is a longitudinal cardiovascular study of 3983 initially healthy men (primarily living in Canada) followed prospectively for 40 years. Risk factors and prognosis were assessed in a nested case-control study. MAIN RESULTS: Twenty-two individuals were diagnosed with NQT before clinical and/or electrocardiographic manifestation of ischemic heart disease (145,408 person-years of observation). Between the ages of 30 and 80, the incidence of NQT was one per 6000 person-years and increased with age. History of childhood diseases, valvular disease, smoking, elevated blood pressure and body mass index did not increase the likelihood for NQT development. NQT was diagnosed concurrently with a serious noncardiac condition in seven cases; excess mortality resulted as six of these subjects died within one year of NQT diagnosis while only two subjects without concurrent disease at NQT diagnosis died during follow-up. In comparison with 2% of control subjects, 27% of subjects with NQT subsequently developed electrocardiographical evidence of atrial fibrillation (relative risk was 12 with lower 95% confidence limit of 1.8). CONCLUSIONS: NQT in an otherwise healthy individual is a benign condition and increases the likelihood of atrial fibrillation development.

The natural history of electrocardiographic preexcitation in men. The Manitoba Follow-up Study.

OBJECTIVE: To examine the natural history of preexcitation occurring on the routine electrocardiogram (ECG). DESIGN: A longitudinal cohort study of 3983 originally healthy men followed prospectively for 40 years. SETTING: Free-living (community-dwelling) study members residing predominantly in Canada. PARTICIPANTS: Nineteen male study members with preexcitation occurring during routine examination in the 40-year follow-up of the Manitoba Follow-up Study. MEASUREMENTS: Routinely requested clinical examinations and ECGs, supplemented by information supplied by the study member or his physician. MAIN RESULTS: Ten study members were found to have preexcitation at enrollment, for a prevalence of 2.5 per 1000 (95% CI, 1.2 to 4.6). A delta wave was first detected during follow-up in an additional nine study members. Seventeen of 19 study members did not have the delta wave at some later time, and preexcitation was intermittently present in most of these members. Over time there was a loss of preexcitation, with 15 of 19 study members no longer exhibiting a delta wave by the end of follow-up. Five of 11 study members with symptoms had physician confirmation of an arrhythmia. Fourteen study members remain alive, and none of the five deaths was attributed to preexcitation. CONCLUSIONS: Preexcitation found on routine ECG in our originally healthy male study group did not confer excess morbidity or mortality, even in those study members who developed symptomatic arrhythmias. Most preexcitation was intermittent and disappeared over time.

The natural history of primary first-degree atrioventricular heart block.

The long-term prognosis of first-degree heart block in the absence of organic heart disease has not been clearly defined. We addressed this question in a 30-year longitudinal study of 3983 healthy men. We identified 52 cases that were present on entry into the study and 124 incident cases during follow-up. The incidence rose steadily after age 40 and was 1.13 per 1000 person-years over the entire period. Two thirds of the cases had only moderate prolongation of the PR interval (0.22 to 0.23 second). We compared four age-matched controls with each case for histories of scarlet fever, rheumatic fever, diphtheria, smoking, blood pressure, and body-mass index. No significant differences (P greater than 0.05) were found. Likewise, mortality from all causes did not differ between cases and controls. Although somewhat higher rates of morbidity and mortality from ischemic heart disease were observed in the cases than in the controls, the differences were not significant. Progression to higher grades of heart block occurred in only two cases. In view of the prognostic findings and the rare occurrence of advanced degrees of heart block, we conclude that primary first-degree heart block with moderate PR prolongation is a benign condition. This conclusion may not apply, however, to persons with more marked prolongation of the PR interval, a very rare condition.

The electrocardiogram in apparently healthy men and the risk of sudden death.

The purpose of this study was to determine whether electrocardiographic abnormalities detected on a routine examination in men without clinical evidence of heart disease predicted sudden death in the absence of pre-existing clinical manifestations of heart disease. The Manitoba study consists of a cohort of 3983 men with a mean age at entry of 30.8 years who have been followed with regular examinations including electrocardiograms since 1948. During the 30 year observation period, 70 cases of sudden death have occurred in men without previous clinical manifestations of heart disease. The prevalence of electrocardiographic abnormalities before sudden death was 71.4% (50/70). The frequency of abnormalities was 31.4% (22) major ST segment and T wave abnormalities, 15.7/ (11) ventricular extrasystoles, 12.9% (nine) left ventricular hypertrophy (voltage criteria), 7.1% (five) complete left bundle-branch block, and 5.7% (four) pronounced left axis deviation. When these electrocardiographic findings in men without clinical manifestations of heart disease were related prospectively to incidence of sudden death each one except pronounced left axis deviation was a significant predictor of sudden death. Two of the variables were examined in more detail. Increased severity of primary T wave abnormalities and the association of ST segment and T wave abnormalities with increased QRS voltage further increased sudden death risk. The combination of ventricular extrasystoles with either ST-T abnormalities or left ventricular hypertrophy much increased the risk of sudden death. Thus these data indicate that electrocardiographic abnormalities detected on routine examination in men without clinical evidence of heart disease are significantly related to the occurrence of sudden death.

Relationship of blood pressure in 20-39-year-old men to subsequent blood pressure and incidence of hypertension over a 30-year observation period.

The objective of this investigation was to determine the relationship of blood pressure (BP) in young men, ages 20-39 years, to their subsequent BP from the perspective of BP tracking, position in BP distribution and later evidence of hypertensive BP values. Since 1948, the Manitoba Study group has followed 3983 men, 90% of whom were 20-39 years old at entry. BP in persons not prescribed antihypertensive medications was examined at 5-year intervals during the 30-year observation period to 1978. To adjust for age, BP was examined within 5-year age groups at entry. The correlations between entry and subsequent BP at the same length of follow-up were greater for systolic than diastolic BP and increased with older ages. The correlation decreased wtih every 5-year examination after entry for all ages. Men whose BP was below the mean at entry were less likely to have a BP greater than 1 standard deviation (SD) above the mean at any of the examinations. Men with an entry BP greater than 1 SD above the mean were more likely to have BP greater than 1 SD above the mean later, but the relationship decreased considerably after 20 years, especially in 20-24-year age group. The results were similar for the probability of hypertension values (systolic BP greater than or equal to 140 or 150 mm Hg, diastolic BP greater than or equal to 90 or 95 mm Hg) at later examinations. Thus, BP in later life can be predicted from BP at ages 20-39 years and can identify groups at high or low risk for hypertension.

The natural history of right bundle branch block and frontal plane QRS axis in apparently healthy men.

We examined the characteristics, long-term follow-up, and prognosis of right bundle branch block (RBBB) detected on a routine ECG in men with no apparent heart disease. During the 29-year period, 59 cases of RBBB were observed in men with a mean age of 44.4 +/- 1.9 years. Because marked right or left axis deviation may identify cases with concomitant involvement of the left bundle branch system, subsets of frontal plane QRS (A QRS) were examined. Comparisons were made with groups of similar ages who were free of RBBB. Cases with RBBB were observed for 936 person-years (mean 15.9 +/- 1.6 years per case), showing no excess ischemic heart disease incidence, no cases of progression to advanced AV block (second- or third-degree), or sudden death. Right bundle branch block was associated with a greater proportion of both right axis (greater than or equal to +90 degrees) and marked left axis (-45 degrees to -90 degrees) deviation compared with those of the same age without this conduction disturbance. In apparently healthy men, RBBB had no adverse long-term prognosis regardless of frontal plane QRS axis.

Relationship of ventricular ectopy in men without apparent heart disease to occurrence of ischemic heart disease and sudden death.

The purpose of this investigation was to determine whether ventricular ectopic beats, or ventricular premature beats (VPBs), on routine electrocardiograms in men without apparent heart disease predict the later occurrence of clinical manifestations of ischemic heart disease (IHD). The Manitoba Study cohort consisted of 3983 men predominantly between 25 and 34 years of age and free of IHD at entry. During the 29-year observation period, 401 persons without clinical evidence of heart disease had VPBs on an electrocardiogram at a routine examination. They were followed 10.8 +/- 0.5 (SEM) years and 13.5% (54 men) later manifested IHD. Age-specific total IHD incidence was significantly (p less than 0.05) greater for men 40 to 59 years of age at VPB occurrence compared to men of the same age without VPBs. The clinical manifestation with the strongest association with VPBs was sudden death. VPB characteristics of frequency, configuration, coupling interval, and postextrasystolic T-wave change did not distinguish those who developed IHD. Prematurity index (R-R'/QT) showed a trend toward an association of late coupled ectopic beats (R-R'/QT greater than 1.6) and IHD risk. However, faster basic ventricular rate plus VPBs significantly correlated with greater IHD probability. Thus ventricular ectopic beats on a routine electrocardiogram in men over 40 years of age without apparent heart disease identify those at high risk for a clinical IHD event, especially sudden death.

The relationship of marked left axis deviation to the risk of ischemic heart disease.

The purpose of this study was to examine the value of marked left axis deviation in men without apparent heart disease in the assessment of ischemic heart disease risk. In the Manitoba Study, a cohort of 3983 men who were predominantly between 25 to 34 yr of age at entry in 1948, 247 cases of marked left axis deviation (mean frontal plane QRS vector of -45 degrees to -90 degrees) were identified at a mean age of 46.1 +/- 0.7 (+/- 1 SEM) yr with a mean follow-up of 12.1 +/- 0.6 yr. The results were that the development of left axis deviation in men 40 to 59 yr of age, independent of blood pressure is a significant predictor of ischemic heart disease events that are usually manifest 5 to 10 yr after the onset of this electrocardiographic abnormality. Subsets of QRS variables examined to identify cases with different degrees of ischemic heart disease risk revealed that neither Q waves in leads I or aVL, or QRS duration or actual frontal plane QRS vector identified groups with different ischemic heart disease risk. However, subsets of age (less than 40 and 60 yr or greater) perhaps reflecting different etiologies of marked left axis deviation and previous electrocardiographic findings (S1S2S3 pattern) identify a low risk group.

Chronobiology of cardiac sudden death in men.

Daily variation in occurrence of sudden cardiac death was examined in 3,983 men observed since 1948. For men without previous clinical evidence of ischemic heart disease, an excess proportion of sudden cardiac deaths occurred on Mondays. For men with previous clinical evidence of ischemic heart disease, sudden cardiac death occurred more uniformly throughout the week. By comparison there was no significant daily variation in cancer mortality or in day of occurrence of myocardial infarction. Thus, for men without clinically manifest heart disease, the warning "beware on Monday" should stimulate further investigation.

Natural history of left bundle-branch block.

The purpose of this study was to examine factors associated with the development of complete left bundle-branch block and the prognosis in a group of people not in hospital, who had no clinical evidence of ischaemic or valvular heart disease. Twenty-nine cases of left bundle-branch block without clinical evidence of ischaemic heart disease were noted in the Manitoba cohort of 3983 men under observation since 1948. The most frequent electrocardiographic finding before development of left bundle-branch block was a normal electrocardiogram; left ventricular hypertrophy though infrequent, was the only abnormality significantly more common than in the rest of the group. The development of left bundle-branch block was associated with distinct leftward shift of the frontal plane mean QRS axis. The most frequent clinical cardiovascular event observed after development of the block was sudden death without previous clinical evidence of ischaemic heart disease. The five-year incidence of sudden death as the first manifestation of heart disease was 10 times greater in men with left bundle-branch block than in those without it.

The relation of blood pressure to stroke prognosis.

The relation between blood pressure before stroke and survival after the event, was examined in the Manitoba study cohort of 3983 men. The last recorded blood pressure before the first stroke and the change in blood pressure from a measurement 5 years earlier were used. Increasing magnitude of systolic blood pressure and its 5-year changes were associated with worsening prognosis. The same association was less apparent for diastolic blood pressure and was not found for 5-year change in diastolic pressure. After adjusting for the effect of age at stroke and previous evidence of ischemic heart disease in multivariate analysis, systolic blood pressure and its 5-year change were each significant predictors of short-term (30 days) mortality. Considering all these factors as well as diastolic blood pressure, systolic blood pressure was the best predictor of short-term mortality. Thus, high blood pressure and large positive 5-year change in systolic blood pressure before stroke occurrence are significant predictors of a poor prognosis.