Lyme disease overdiagnosis in a large healthcare system: a population-based, retrospective study.

OBJECTIVES: To evaluate the impact of false-positive IgM immunoblots on Lyme disease treatment and case reporting in a large healthcare system. METHODS: We obtained the results of all Lyme disease serological tests ordered at U.S. Air Force healthcare facilities in the USA between January 2013 and December 2017. We conducted chart reviews to adjudicate positive IgM immunoblots (from two-tier and independent testing) as true positives or false positives using established criteria, and we assessed whether these cases were reported to the U.S. Department of Defense surveillance system. RESULTS: Of the 18 410 serum tests (17 058 immunoassays and 1352 immunoblots) performed on 15 928 unique individuals, 249/1352 (18.4%) IgM immunoblots were positive. After excluding repeat tests, insufficiently documented cases, and participants with a history of Lyme disease, 212 positive IgM immunoblot cases were assessed. A total of 113/212 (53.3%) were determined to be false positives. Antibiotics were prescribed for Lyme disease for 97/99 (98.0%) participants with a true-positive test and 91/113 (80.5%) participants with a false-positive test. The number of false-positive cases reported to the surveillance system was identical to the number of unreported true-positive cases (n = 44). CONCLUSIONS: Lyme disease serological tests were overused in a large healthcare system, and positive results were frequently misinterpreted, leading to misdiagnosis and widespread antibiotic misuse. Underreporting of true-positive cases was offset by overreporting of false-positive cases, suggesting that the discrepancy between the reported incidence and true incidence of Lyme disease may not be as significant as previously assumed.

Association of elevation, urbanization and ambient temperature with obesity prevalence in the United States.

BACKGROUND: The macrogeographic distribution of obesity in the United States, including the association between elevation and body mass index (BMI), is largely unexplained. This study examines the relationship between obesity and elevation, ambient temperature and urbanization. METHODS AND FINDINGS: Data from a cross-sectional, nationally representative sample of 422603 US adults containing BMI, behavioral (diet, physical activity, smoking) and demographic (age, sex, race/ethnicity, education, employment, income) variables from the 2011 Behavioral Risk Factor Surveillance System were merged with elevation and temperature data from WorldClim and with urbanization data from the US Department of Agriculture. There was an approximately parabolic relationship between mean annual temperature and obesity, with maximum prevalence in counties with average temperatures near 18 °C. Urbanization and obesity prevalence exhibited an inverse relationship (30.9% in rural or nonmetro counties, 29.2% in metro counties with <250000 people, 28.1% in counties with population from 250000 to 1 million and 26.2% in counties with >1 million). After controlling for urbanization, temperature category and behavioral and demographic factors, male and female Americans living <500 m above sea level had 5.1 (95% confidence interval (CI) 2.7-9.5) and 3.9 (95% CI 1.6-9.3) times the odds of obesity, respectively, as compared with counterparts living ≥ 3000 m above sea level. CONCLUSIONS: Obesity prevalence in the United States is inversely associated with elevation and urbanization, after adjusting for temperature, diet, physical activity, smoking and demographic factors.

Lack of association between baseline plasma homocysteine concentrations and restenosis rates after a first elective percutaneous coronary intervention without stenting.

OBJECTIVE: To evaluate the association between baseline homocysteine concentrations and restenosis rates in patients electively undergoing their first percutaneous coronary intervention (PCI) without stenting. DESIGN: Prospective, single centre, observational study. SETTING AND PATIENTS: Patients electively undergoing their first PCI without stenting at a tertiary referral centre between 1990 and 1998. METHODS: Blood samples were collected from all patients at baseline and assayed to determine the patients' homocysteine concentrations. Patients whose PCI was successful underwent repeat angiography at a median of 6.4 (interquartile range 6-6.8) months. Their baseline and follow up angiograms were compared by quantitative coronary angiography to assess the incidence of restenosis. For the analysis, the patients were divided into two groups based on whether their baseline homocysteine concentrations were above or below the median value. These two groups were compared to determine whether there was any association between their baseline homocysteine concentrations and the incidence of restenosis at six months. RESULTS: 134 patients had a successful first PCI without stenting (involving 200 lesions). At six month angiography, restenosis was observed in 33 patients (49.3%) with baseline homocysteine concentrations above the median value and in 31 patients (46.3%) with concentrations below the median value (p = 0.74). There was no difference in the percentage of lesions developing restenosis (38 (39.6%) v 40 (38.5%), respectively, p = 0.87) or late lumen loss (0.40 mm v 0.31 mm, respectively, p = 0.24). On multivariable analysis, there was no association between homocysteine concentrations and late lumen loss (r = -0.11, p = 0.11) or the percentage diameter stenosis at follow up (r = -0.07, p = 0.32). CONCLUSION: Baseline homocysteine concentrations were not associated with six month restenosis rates in patients electively undergoing their first PCI without stenting.

Relationship between corrected TIMI frame counts at three weeks and late survival after myocardial infarction.

OBJECTIVES: To evaluate the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC) as a predictor of late survival after myocardial infarction. BACKGROUND: Thrombolysis in Myocardial Infarction flow grades predict late survival after myocardial infarction. The CTFC provides a more reproducible measurement of infarct-related artery blood flow than the TIMI flow grade, and has been linked to 30-day outcomes, but it has not yet been established how the CTFC correlates with late survival. METHODS: Of 1,001 patients with acute myocardial infarction presenting within 4 h of symptom onset, 882 underwent angiography at approximately three weeks. Infarct artery flow was assessed, blinded to clinical outcomes, according to the CTFC and TIMI flow grade. Late cardiac mortality and survival were determined in 97.5% of patients. RESULTS: The mean CTFC was 40 +/- 29 in 644 patent infarct arteries (median, 34 [interquartile range, 24 to 47]). The CTFC, assessed as a continuous univariate variable, was found to be a predictor of five-year survival, as was the TIMI flow grade (both p < 0.001). On multivariate analysis, factors associated with five-year survival included the ejection fraction or end-systolic volume index (both p < 0.001); exercise duration (p = 0.005), age (p = 0.008), diabetes (p = 0.02) and CTFC (p = 0.02) or TIMI flow (p = 0.02). The same factors, except for the CTFC and TIMI flow grade, were predictors of 10-year survival. CONCLUSIONS: The CTFC three weeks after myocardial infarction was an independent predictor of five-year survival, but not 10-year survival. Although the CTFC provided additional prognostic information within TIMI flow grades, its superiority was not demonstrated.

Survival 12 years after randomization to streptokinase: the influence of thrombolysis in myocardial infarction flow at three to four weeks.

OBJECTIVES: The purpose of this study was to determine whether the mortality benefit of intravenous streptokinase administered within 4 h of the onset of acute myocardial infarction is maintained at 12 years, and whether Thrombolysis in Myocardial Infarction (TIMI) flow grades independently influence late survival. BACKGROUND: Treatment with reperfusion therapies and achievement of TIMI 3 flow are associated with increased short- and medium-term survival after infarction. Whether infarct artery flow independently influences survival more than five years after infarction is unknown. METHODS: The late survival of patients randomized to receive either streptokinase (1,500,000 IU over 30 to 60 min) or a matching placebo within 4 h of symptom onset in 1984-1986 was determined. Angiography was performed in surviving patients at three to four weeks, and TIMI flow grades were assessed blind to randomization and outcomes. The late vital status was determined in 99% of patients. RESULTS: Patients randomized to receive streptokinase (n = 107) had improved survival compared with those randomized to placebo (n = 112) at five years (84% vs. 70%; p = 0.023) and 12 years (66% vs. 51%; p = 0.022). At five years 94% of patients with TIMI grade 3 flow, 81% of those with TIMI grade 2 flow and 72% of those with TIMI grade 0-1 flow survived (p = 0.005). At 12 years 72% of patients with TIMI 3, 67% of those with TIMI 2 and 54% of those with TIMI 0-1 flow survived (p = 0.023). Multivariate analysis identified the ejection fraction (p = 0.014), exercise duration (p = 0.013) and TIMI 3 flow (p = 0.04 compared with TIMI 0-2 flow) as important factors for five-year survival. At 12 years multivariate predictors of late survival were the ejection fraction (p = 0.006), exercise duration (p = 0.003) and myocardial score (p = 0.013). The end-systolic volume index was similar to the ejection fraction as a predictor of survival at five and 12 years. CONCLUSIONS: The survival benefits of streptokinase persist for 12 years after infarction. TIMI flow at three to four weeks is an independent predictor of five-year survival.

Angiographic frame counts 90 minutes after streptokinase predict left ventricular function at 48 hours following myocardial infarction.

OBJECTIVE: To assess whether the 90 minute corrected thrombolysis in myocardial infarction frame count (CTFC) in the infarct related artery predicts left ventricular function at 48 hours in patients with myocardial infarction treated with aspirin, streptokinase, and either heparin or Hirulog. DESIGN AND SETTING: Analysis of 251 patients with acute myocardial infarction enrolled in the international, multicentre Hirulog early reperfusion/occlusion (HERO-1) trial, who underwent both 90 minute coronary angiography and 48 hour left ventriculography. MAIN OUTCOME VARIABLES: The CTFC was determined in the infarct related artery 90 minutes after starting intravenous streptokinase (1.5 x 106 U over 30 to 60 minutes), and compared with indices of left ventricular function assessed by contrast ventriculography at 48 hours. RESULTS: A CTFC of 2 SD below normal (37% v 51%, p = 0.005), and trends towards higher left ventricular ejection fractions (60.9% v 58.2%, p = 0.11) and lower end systolic volumes (50.1 ml v 55.9 ml, p = 0.23). A CTFC of 2 SD below normal (41% v 52%, p = 0.025), a smaller end systolic volume (49.1 ml v 59.3 ml, p = 0.02), and a higher left ventricular ejection fraction (60.4% v 56.5%, p = 0.03). CONCLUSIONS: The 90 minute CTFC predicts left ventricular function at 48 hours following streptokinase. The CTFC associated with better ventricular function may be higher than values determined from a non-infarct population.

Abnormal coronary flow in infarct arteries 1 year after myocardial infarction is predicted at 4 weeks by corrected Thrombolysis in Myocardial Infarction (TIMI) frame count and stenosis severity.

Because 24% to 30% of patent infarct-related arteries occlude in the year following thrombolytic therapy for acute myocardial infarction, angiographic factors including corrected Thrombolysis in Myocardial Infarction (TIMI) frame count which may predict abnormal infarct-artery flow, require definition. We examined changes in coronary flow and infarct-artery lesion severity by computerized quantitative angiography over 1 year in 154 patients with a patent infarct-related artery 4 weeks after myocardial infarction. These patients were randomized to receive either ongoing daily therapy of 50 mg aspirin and 400 mg dipyridamole, or placebo. All angiograms were interpreted blind in our core angiographic laboratory. Infarct-artery flow, assessed by corrected TIMI frame counts, was normal (< or = 27) in 46% and 45% of patients at 4 weeks and 1 year, respectively. At 4 weeks, patients with corrected TIMI frame counts < or = 27 had higher ejection fractions (60+/-11% vs 56+/-12%; p = 0.04) than those with corrected TIMI frame counts >27. On multivariate analysis, corrected TIMI frame count and stenosis severity were predictive of late abnormal infarct-artery flow (TIMI 0 to 2 flow, both p <0.01). Only stenosis severity at 4 weeks predicted reocclusion at 1 year (p <0.0001). Aspirin and dipyridamole had no effect on flow or reocclusion. Thus, corrected TIMI frame count and stenosis severity at 4 weeks was highly correlated with infarct-artery flow at 1 year.

Late regression of the dilated site after coronary angioplasty: a 5-year quantitative angiographic study.

BACKGROUND: Limited data are available on the changes that occur at the dilated site late after coronary angioplasty. The aim of this study was to evaluate with quantitative angiography the natural history of changes that occur in the dilated segment between "early" (approximately 6 months) and "late" (approximately 5 years) follow-up after angioplasty. METHODS AND RESULTS: Of 127 consecutive patients (174 lesions) with successful angioplasty, 125 underwent early angiography. Three patients subsequently died, and 24 underwent revascularization surgery or repeated angioplasty, giving a study-eligible population of 98 patients. Quantitative angiographic analysis was performed before and immediately after angioplasty and at early and late follow-up in the study population of 84 patients (115 lesions), which was 86% of study-eligible patients. Mean lesion diameter stenosis decreased from 36.3+/-14.2% at early to 29.6+/-13.5% at late follow-up (P<.0001). No lesion developed late restenosis by the 50% diameter loss criterion. Late regression was related to stenosis severity at early angiography (r=-.58, P<.001). Subgroups at early angiography of 40% to 49% stenosis and > or = 50% stenosis showed significant regression at late angiography. CONCLUSIONS: Lesion regression at the dilated site is common late after angioplasty. The more severe a stenosis is at early angiography, the more likely the chance that there will be late regression. A strategy of watchful waiting may be appropriate for patients with restenotic lesions of borderline severity.

The role of dipyridamole in addition to low dose aspirin in the prevention of occlusion of coronary artery bypass grafts.

One hundred and one subjects were randomised to receive either aspirin 100 mg or aspirin 100 mg + dipyridamole 300 mg daily before undergoing coronary bypass surgery. The drugs were commenced at least 36 hours before operation and patients were followed for one year. There were three perioperative deaths and 37 withdrawals, of which 14 were drug related (aspirin four, aspirin + dipyridamole ten). Cineangiocardiograms at nine weeks and one year showed vein graft patency rates of 93% and 87% for subjects treated with aspirin alone; and 90% and 89% in those who received aspirin+dipyridamole. During the follow-up period 14% of 232 coronary lesions in the aspirin treated group advanced by more than two grades compared with 15% of 315 lesions in the aspirin+dipyridamole group. The study did not establish superiority of one regimen over another in terms of graft patency or progress of lesions in native vessels. However, low dose aspirin was better tolerated than combination therapy.