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Biomedical subjects

Peter H Stone

Publications and source records attributed to Peter H Stone.

At least 19 recordsLinked to original sources
PubMed2007

Focused exposures to airborne traffic particles and heart rate variability in the elderly.

BACKGROUND: : Exposure to airborne particles may increase cardiac risk by altering autonomic balance. Because these risks may be particularly great for traffic-related particles, we examined associations between particles and heart rate variability as 44 subjects participated in 4 repeated trips aboard a diesel bus. METHODS: : Twenty-four hour electrocardiograms were correlated with continuous particle concentrations using generalized additive models controlling for subject, weekday, time, apparent temperature, trip type, activity, medications, and autoregressive terms. Associations were assessed for short- and medium-term moving averages of measured concentrations. RESULTS: : Heart rate variability was negatively associated with fine particulate matter. Positive associations were demonstrated with heart rate and the low-to-high frequency power ratio. Associations were strongest with 24-hour mean concentrations, although strong short-term associations also were found during bus periods, independent of daily exposures. Overall, associations were greatest for high-frequency power with the following effects per interquartile change in the 24-hour mean concentrations: -15% (95% confidence interval = -17% to -14%) for PM2.5 (4.6 mug/m); -19% (-21% to -17%) for black carbon (459 ng/m); and -14% (-15% to -12%) for fine particle counts (39 pt/cm). For each interquartile change in the 5-minute PM2.5 concentration (10 mug/m) aboard the bus, an 11% (95% confidence interval = -14% to -8%) decrease in high-frequency power was observed. CONCLUSIONS: : This investigation indicates that fine particles are negatively associated with heart rate variability, with an overall trend towards reduced parasympathetic tone. Although daily associations were evident for all particles, short-term associations were predominantly limited to traffic-related particles.

Age Factors↗
PubMed2006

A randomized trial to evaluate the relative protection against post-percutaneous coronary intervention microvascular dysfunction, ischemia, and inflammation among antiplatelet and antithrombotic agents: the PROTECT-TIMI-30 trial.

OBJECTIVES: The goal of this study was to evaluate glycoprotein IIb/IIIa inhibition with eptifibatide when administered with indirect thrombin inhibition as compared with monotherapy with direct thrombin inhibition with bivalirudin among patients with non-ST-segment elevation acute coronary syndromes (ACS). BACKGROUND: The optimal combination of antiplatelet and antithrombin regimens that maximizes efficacy and minimizes bleeding among patients with non-ST-segment elevation ACS undergoing percutaneous coronary intervention (PCI) is unclear. METHODS: A total of 857 patients with non-ST-segment elevation ACS were assigned randomly to eptifibatide + reduced dose unfractionated heparin (n = 298), eptifibatide + reduced-dose enoxaparin (n = 275), or bivalirudin monotherapy (n = 284). RESULTS: Among angiographically evaluable patients (n = 754), the primary end point of post-PCI coronary flow reserve was significantly greater with bivalirudin (1.43 vs. 1.33 for pooled eptifibatide arms, p = 0.036). Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade more often was normal with eptifibatide treatment compared with bivalirudin (57.9% vs. 50.9%, p = 0.048). The duration of ischemia on continuous Holter monitoring after PCI was significantly longer among patients treated with bivalirudin (169 vs. 36 min, p = 0.013). There was no excess of TIMI major bleeding among patients treated with eptifibatide compared with bivalirudin (0.7%, n = 4 vs. 0%, p = NS), but TIMI minor bleeding was increased (2.5% vs. 0.4%, p = 0.027) as was transfusion (4.4% to 0.4%, p < 0.001). CONCLUSIONS: Among moderate- to high-risk patients with ACS undergoing PCI, coronary flow reserve was greater with bivalirudin than eptifibatide. Eptifibatide improved myocardial perfusion and reduced the duration of post-PCI ischemia but was associated with higher minor bleeding and transfusion rates. Ischemic events and biomarkers for myonecrosis, inflammation, and thrombin generation did not differ between agents.

Acute Disease↗
PubMed2006

Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial.

OBJECTIVES: The purpose of this study was to determine if ranolazine improves angina in stable coronary patients with persisting symptoms despite maximum recommended dose of amlodipine. BACKGROUND: Ranolazine is a unique antianginal agent that has been effective in stable angina, but it has not been studied in the setting of maximum recommended doses of conventional antianginal agents. METHODS: Stable patients with coronary disease and > or =3 anginal attacks per week despite maximum recommended dosage of amlodipine (10 mg/day) were randomized to 1,000 mg ranolazine or placebo twice a day for 6 weeks. Primary end point was the frequency of angina episodes per week during the double-blind treatment phase. Efficacy was also assessed by nitroglycerin consumption per week and the Seattle Angina Questionnaire (SAQ). Adjustment for multiple testing of secondary end points used a hierarchic closed testing procedure. Efficacy was assessed in subgroups based on baseline angina frequency, concomitant long-acting nitrate use, gender, and age. Safety was assessed by adverse events and electrocardiogram evaluations. RESULTS: A total of 565 patients were randomized: 281 patients to ranolazine and 284 patients to placebo. Baseline characteristics were similar between treatment groups. At baseline, angina frequency averaged 5.63 +/- 0.18 episodes/week, and nitroglycerin consumption averaged 4.72 +/- 0.21 tablets/week. Compared with placebo, ranolazine significantly reduced frequency of angina episodes (2.88 +/- 0.19 on ranolazine vs. 3.31 +/- 0.22 on placebo; p = 0.028) and nitroglycerin consumption (2.03 +/- 0.20 on ranolazine vs. 2.68 +/- 0.22; p = 0.014), with treatment effect that appeared consistent across subgroups. The median angina weekly episode rate at baseline was 4.5 per week. Subgroup analysis showed statistically significant reductions of angina frequency, nitroglycerin use, and SAQ angina frequency for patients with a baseline frequency >4.5 per week but only of angina frequency for those with baseline frequency < or =4.5 per week. Patients with more frequent angina appeared to have a more pronounced treatment effect. No hemodynamic changes were observed. Ranolazine was well tolerated. CONCLUSIONS: Ranolazine significantly reduced frequency of angina and nitroglycerin consumption compared with placebo and was well tolerated. (The ERICA [Efficacy of Ranolazine In Chronic Angina] Trial; http://clinicaltrials.gov; NCT00091429).

Acetanilides↗
PubMed2006

Association between thrombolysis in myocardial infarction myocardial perfusion grade, biomarkers, and clinical outcomes among patients with moderate- to high-risk acute coronary syndromes: observations from the randomized trial to evaluate the relative PROTECTion against post-PCI microvascular dysfunction and post-PCI ischemia among antiplatelet and antithrombotic agents-Thrombolysis In Myocardial Infarction 30 (PROTECT-TIMI 30).

BACKGROUND: A variety of imaging modalities have implicated impaired myocardial perfusion in the pathogenesis of acute coronary syndromes (ACSs). METHODS: We hypothesized that an abnormal TIMI myocardial perfusion grade (TMPG 0/1/2) and an impaired coronary flow reserve (CFR) as assessed angiographically using the TIMI frame count would be associated with biomarker release, ischemia on Holter monitoring, and adverse clinical outcomes in the PROTECT-TIMI 30 trial of patients with non-ST-elevation ACS undergoing percutaneous coronary intervention (PCI). RESULTS: The pre-PCI TMPG was correlated with the baseline as well as peak levels of troponin I (P < .001) and creatine kinase-MB (P < .001) and the post-PCI rise in troponin I (P = .03). The incidence of an ischemic event on Holter by 48 hours was more common among patients with an abnormal post-PCI TMPG (12.5% vs 7.0%, P = .013), and the mean normalized duration of ischemia by 24 hours after PCI on Holter monitoring trended longer among patients with an abnormal post-PCI TMPG (8.9 vs 3.2 minutes, P = .068). In multivariable analyses, an abnormal post-PCI TMPG was the strongest correlate of death, myocardial infarction, or an ischemic event by 48 hours after randomization. In contrast, the post-PCI CFR as assessed angiographically using the TIMI frame count was not associated with the baseline, peak, or absolute rise of any biomarker, Holter findings, or clinical events. CONCLUSIONS: An abnormal TMPG, but not an angiographic CFR, is associated with biomarker status, the occurrence and duration of Holter ischemia, and adverse clinical outcomes among patients with moderate- to high-risk non-ST-elevation ACS undergoing PCI.

Acute Disease↗
PubMed2006

Current strategies for the prevention of angina in patients with stable coronary artery disease.

PURPOSE OF REVIEW: Angina pectoris affects at least 6.6 million people in the US and approximately 400,000 new cases of stable angina occur each year. Angina may be one of the first signs of ischemic heart disease, although it is likely not causally related to the likelihood of plaque rupture leading to an acute coronary syndrome. Modalities for treatment of angina should be used maximally to improve quality of life and decrease cardiovascular morbidity and mortality. The current recommended pharmacologic and invasive approaches, as well as novel therapies, are reviewed. RECENT FINDINGS: Antiischemic agents, including beta-blockers, nitrates and calcium channel blockers, remain the mainstay in the prevention of angina. Revascularization via percutaneous interventions or coronary bypass surgery are appropriate in specific cases or when medical treatment fails. Noninvasive treatment options for refractory angina, metabolic agents, and vasodilator therapies are adding to the armamentarium to prevent and treat angina. SUMMARY: A multifaceted approach is optimal to address the prevention of angina. Once angina is recognized, there are many modalities that lessen the incidence of daily life-induced and exercise-induced angina and ischemia. Angina management is best addressed by pharmacologic and lifestyle interventions.

Adrenergic beta-Antagonists↗
PubMed2006

Short-term effects of air pollution on heart rate variability in senior adults in Steubenville, Ohio.

OBJECTIVE: We examined the association between ambient air pollution levels and heart rate variability (HRV) in a panel study of 32 subjects. METHODS: We used linear mixed models to analyze the effects of fine particles (PM2.5), sulfate (SO4), elemental carbon (EC), and gases on log-transformed standard deviation of normal RR intervals (SDNN), mean square of differences between adjacent RR intervals (r-MSSD), and high- and low-frequency power (HF, LF). RESULTS: An interquartile range (IQR) increase of 5.1 mug/m in SO4 on the previous day was associated with a decrease of -3.3% SDNN (95% confidence = -6.0% to -0.5%), -5.6% r-MSSD (-10.7% to -0.2%), and -10.3% HF (-19.5% to -0.1%). Associations with total PM2.5 were similar. HRV was not associated with EC, NO2, SO2, or O3. CONCLUSION: In addition to traffic-related particles, elevated levels of sulfate particles may also adversely affect autonomic function.

Aged↗
PubMed2006

Personal coronary risk profiles modify autonomic nervous system responses to air pollution.

OBJECTIVE: We investigated whether PM2.5-mediated autonomic modulation depends on individual coronary risk profiles. METHODS: Five-minute average heart rate (HR) and heart rate variability (HRV, including standard deviation of normal-to-normal intervals [SDNN], square root of the mean squared differences of successive NN intervals [rMSSD], high frequency [HF]) were measured from 24-hour ambulatory electrocardiograms, and personal PM(2.5) exposures were monitored in a prospective study of 10 male boilermakers (aged 34.3 +/- 8.1 years). We used the Framingham score to classify individuals into low (score = 1-3) and high (score = 5-6) risk categories. Mixed-effect models were used for statistical analyses. RESULTS: Each 1-mg/m(3) increase in the preceding 4-hour moving average PM(2.5) was associated with HR increase (5.3 beats/min) and HRV reduction (11.7%, confidence interval [CI] = 6.2-17.1% for SDNN; 11.1%, CI = 3.1-19.1% for rMSSD; 16.6%, CI = 1.5-31.7% for HF). Greater responses (2- to 4-fold differences) were observed in high-risk subjects than in low-risk subjects. CONCLUSIONS: Our study suggests that adverse autonomic responses to metal particulate are aggravated in workers with higher coronary risk profiles.

Adult↗
PubMed2005

Remodeling characteristics of minimally diseased coronary arteries are consistent along the length of the artery.

Using a method that creates anatomically correct, 3-dimensional arterial reconstructions, 55 minimally diseased coronary arteries from 40 patients were studied. Homogenous remodeling characteristics along the entire length of the artery were observed in 48 arteries (87%). In the aggregate, arteries exhibited compensatory expansive remodeling. Individually, the full spectrum of compensatory expansive remodeling (60%), excessive expansive remodeling (21%), and constrictive remodeling (19%) was observed across arteries. Each artery was consistent in its remodeling characteristics from proximal to distal portions of the artery, and the remodeling pattern of each artery was independent within the same patient.

Adult↗
PubMed2005

Effect of intensive lipid lowering, with or without antioxidant vitamins, compared with moderate lipid lowering on myocardial ischemia in patients with stable coronary artery disease: the Vascular Basis for the Treatment of Myocardial Ischemia Study.

BACKGROUND: Lipid lowering with statins prevents adverse cardiac events. Both lipid-lowering and antioxidant therapies may favorably affect vasomotor function and thereby improve ischemia. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, 300 patients with stable coronary disease, a positive exercise treadmill test, 48-hour ambulatory ECG with > or =1 episode of ischemia, and fasting total cholesterol of 180 to 250 mg/dL were assigned to 1-year treatment with intensive atorvastatin to reduce LDL to <80 mg/dL (n=96), intensive atorvastatin to reduce LDL to <80 mg/dL plus antioxidant vitamins C (1000 mg/d) and E (800 mg/d) (n=101), or diet and low-dose lovastatin, if needed, to reduce LDL to <130 mg/dL (n=103; control group). Ischemia end points, including ambulatory ECG monitoring and exercise treadmill testing, and endothelial assessment using brachial artery flow-mediated dilation were obtained at baseline and at 6 and 12 months. Baseline characteristics were similar in all groups. LDL decreased from approximately 153 mg/dL at baseline in the 2 atorvastatin groups to approximately 83 mg/dL at 12 months (each P<0.0001) and from 147 to 120 mg/dL in the control group (P<0.0001). During ambulatory ECG monitoring, mean number of ischemic episodes per 48 hours decreased 31% to 61% in each group (each P<0.001; P=0.15 across groups), without a change in daily heart rate activity. Mean duration of ischemia for 48 hours decreased 26% to 62% in each group (each P<0.001; P=0.06 across groups). Mean exercise duration to 1-mm ST-segment depression significantly increased in each group, but total exercise duration and mean sum of maximum ST depression were unchanged. Angina frequency decreased in each group. There was no incremental effect of supplemental vitamins C and E on any ischemia outcome. Flow-mediated dilation studies indicated no meaningful changes. CONCLUSIONS: Intensive lipid lowering with atorvastatin to an LDL level of 80 mg/dL, with or without antioxidant vitamins, does not provide any further benefits in ambulatory ischemia, exercise time to onset of ischemia, and angina frequency than moderate lipid lowering with diet and low-dose lovastatin to an LDL level of <120 mg/dL.

Angina Pectoris↗
PubMed2005

The Critical Care Safety Study: The incidence and nature of adverse events and serious medical errors in intensive care.

OBJECTIVE: Critically ill patients require high-intensity care and may be at especially high risk of iatrogenic injury because they are severely ill. We sought to study the incidence and nature of adverse events and serious errors in the critical care setting. DESIGN: We conducted a prospective 1-year observational study. Incidents were collected with use of a multifaceted approach including direct continuous observation. Two physicians independently assessed incident type, severity, and preventability as well as systems-related and individual performance failures. SETTING: Academic, tertiary-care urban hospital. PATIENTS: Medical intensive care unit and coronary care unit patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcomes of interest were the incidence and rates of adverse events and serious errors per 1000 patient-days. A total of 391 patients with 420 unit admissions were studied during 1490 patient-days. We found 120 adverse events in 79 patients (20.2%), including 66 (55%) nonpreventable and 54 (45%) preventable adverse events as well as 223 serious errors. The rates per 1000 patient-days for all adverse events, preventable adverse events, and serious errors were 80.5, 36.2, and 149.7, respectively. Among adverse events, 13% (16/120) were life-threatening or fatal; and among serious errors, 11% (24/223) were potentially life-threatening. Most serious medical errors occurred during the ordering or execution of treatments, especially medications (61%; 170/277). Performance level failures were most commonly slips and lapses (53%; 148/277), rather than rule-based or knowledge-based mistakes. CONCLUSIONS: Adverse events and serious errors involving critically ill patients were common and often potentially life-threatening. Although many types of errors were identified, failure to carry out intended treatment correctly was the leading category.

Aged↗
PubMed2005

Evaluating cardiovascular pathophysiology and anatomy in atherosclerosis.

The process of atherosclerosis begins with endothelial dysfunction from impaired bioavailability of NO and progresses through multiple stages of plaque development. Impaired endothelial function decreases NO and increases oxidized macromolecules such as low-density lipoprotein cholesterol. Oxidized low-density lipoprotein cholesterol accumulates in subendothelial space, forming plaques that may eventually compromise the lumen. Acute coronary events result from plaque rupture and consequent thrombus formation and abrupt occlusion of the vessel lumen. New diagnostic methods such as flow-mediated dilation of the brachial artery can detect endothelial dysfunction, and intravascular ultrasound can detect early plaque formation in the arterial wall. These techniques may provide a means to identify patients at risk for adverse cardiovascular outcomes, thereby enabling physicians to potentially prevent adverse events by early initiation of lipid-lowering therapy.

Cholesterol, LDL↗
PubMed2005

Air pollution and ST-segment depression in elderly subjects.

Increased levels of daily ambient particle pollution have been associated with increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the traffic-related component of particles. We investigated associations between ambient pollution and ST-segment levels in a repeated-measures study including 269 observations on 24 active Boston residents 61-88 years of age, each observed up to 12 times from June through September 1999. The protocol involved continuous Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5 min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing. Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile change in BC. We calculated the average ST-segment level, referenced to the P-R isoelectric values, for each portion of the protocol. The mean BC level in the previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment depression in most portions of the protocol, but the effect was strongest in the postexercise periods. During postexercise rest, an elevated BC level was associated with -0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p = 0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased risk of ST-segment depression > or = 0.5 mm among those with at least one episode of that level of ST-segment depression. Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inflammation, is associated with increased exposure to particles whose predominant source is traffic.

Aged↗
PubMed2004

Effect of reducing interns' weekly work hours on sleep and attentional failures.

BACKGROUND: Knowledge of the physiological effects of extended (24 hours or more) work shifts in postgraduate medical training is limited. We aimed to quantify work hours, sleep, and attentional failures among first-year residents (postgraduate year 1) during a traditional rotation schedule that included extended work shifts and during an intervention schedule that limited scheduled work hours to 16 or fewer consecutive hours. METHODS: Twenty interns were studied during two three-week rotations in intensive care units, each during both the traditional and the intervention schedule. Subjects completed daily sleep logs that were validated with regular weekly episodes (72 to 96 hours) of continuous polysomnography (r=0.94) and work logs that were validated by means of direct observation by study staff (r=0.98). RESULTS: Seventeen of 20 interns worked more than 80 hours per week during the traditional schedule (mean, 84.9; range, 74.2 to 92.1). All interns worked less than 80 hours per week during the intervention schedule (mean, 65.4; range, 57.6 to 76.3). On average, interns worked 19.5 hours per week less (P<0.001), slept 5.8 hours per week more (P<0.001), slept more in the 24 hours preceding each working hour (P<0.001), and had less than half the rate of attentional failures while working during on-call nights (P=0.02) on the intervention schedule as compared with the traditional schedule. CONCLUSIONS: Eliminating interns' extended work shifts in an intensive care unit significantly increased sleep and decreased attentional failures during night work hours.

Adult↗
PubMed2004

Effect of reducing interns' work hours on serious medical errors in intensive care units.

BACKGROUND: Although sleep deprivation has been shown to impair neurobehavioral performance, few studies have measured its effects on medical errors. METHODS: We conducted a prospective, randomized study comparing the rates of serious medical errors made by interns while they were working according to a traditional schedule with extended (24 hours or more) work shifts every other shift (an "every third night" call schedule) and while they were working according to an intervention schedule that eliminated extended work shifts and reduced the number of hours worked per week. Incidents were identified by means of a multidisciplinary, four-pronged approach that included direct, continuous observation. Two physicians who were unaware of the interns' schedule assignments independently rated each incident. RESULTS: During a total of 2203 patient-days involving 634 admissions, interns made 35.9 percent more serious medical errors during the traditional schedule than during the intervention schedule (136.0 vs. 100.1 per 1000 patient-days, P<0.001), including 56.6 percent more nonintercepted serious errors (P<0.001). The total rate of serious errors on the critical care units was 22.0 percent higher during the traditional schedule than during the intervention schedule (193.2 vs. 158.4 per 1000 patient-days, P<0.001). Interns made 20.8 percent more serious medication errors during the traditional schedule than during the intervention schedule (99.7 vs. 82.5 per 1000 patient-days, P=0.03). Interns also made 5.6 times as many serious diagnostic errors during the traditional schedule as during the intervention schedule (18.6 vs. 3.3 per 1000 patient-days, P<0.001). CONCLUSIONS: Interns made substantially more serious medical errors when they worked frequent shifts of 24 hours or more than when they worked shorter shifts. Eliminating extended work shifts and reducing the number of hours interns work per week can reduce serious medical errors in the intensive care unit.

Humans↗
PubMed2004

Ambient pollution and blood pressure in cardiac rehabilitation patients.

BACKGROUND: Multiple studies have demonstrated a consistent association between ambient particulate air pollution and increased risk of hospital admissions and deaths for cardiovascular causes. We investigated the associations between fine particulate pollution (PM2.5) and blood pressure during 631 repeated visits for cardiac rehabilitation in 62 Boston residents with cardiovascular disease. METHODS AND RESULTS: Blood pressure, cardiac risk factor, and exercise data were abstracted from records of rehabilitation visits between 1999 and 2001. We applied mixed-effect models, controlling for body mass index, age, gender, number of visits, hour of day, and weather variables. For an increase from the 10th to the 90th percentile in mean PM2.5 level during the 5 days before the visit (10.5 microg/m3), there was a 2.8-mm Hg (95% CI, 0.1 to 5.5) increase in resting systolic, a 2.7-mm Hg (95% CI, 1.2 to 4.3) increase in resting diastolic, and a 2.7-mm Hg (95% CI, 1.0 to 4.5) increase in resting mean arterial blood pressure. The mean PM2.5 level during the 2 preceding days (13.9 microg/m3) was associated with a 7.0-mm Hg (95% CI, 2.3 to 12.1) increase in diastolic and a 4.7-mm Hg (95% CI, 0.5 to 9.1) increase in mean arterial blood pressure during exercise in persons with resting heart rate > or =70 bpm, but it was not associated with an increase in blood pressure during exercise in persons with heart rate <70 bpm. CONCLUSIONS: In patients with preexisting cardiac disease, particle pollution may contribute to increased risk of cardiac morbidity and mortality through short-term increases in systemic arterial vascular narrowing, as manifested by increased peripheral blood pressure.

Adult↗