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Douglas E Lake

Publications and source records attributed to Douglas E Lake.

14 recordsLinked to original sources
PubMed2006

Renyi entropy measures of heart rate Gaussianity.

Sample entropy and approximate entropy are measures that have been successfully utilized to study the deterministic dynamics of heart rate (HR). A complementary stochastic point of view and a heuristic argument using the Central Limit Theorem suggests that the Gaussianity of HR is a complementary measure of the physiological complexity of the underlying signal transduction processes. Renyi entropy (or q-entropy) is a widely used measure of Gaussianity in many applications. Particularly important members of this family are differential (or Shannon) entropy (q = 1) and quadratic entropy (q = 2). We introduce the concepts of differential and conditional Renyi entropy rate and, in conjunction with Burg's theorem, develop a measure of the Gaussianity of a linear random process. Robust algorithms for estimating these quantities are presented along with estimates of their standard errors.

Algorithms↗
PubMed2006

Toward quantitative fetal heart rate monitoring.

Continuous electronic fetal heart rate (FHR) monitoring during labor is motivated by the clinical experience that fetal distress causes loss of FHR variation and the occurrence of decelerations late during uterine contraction. This practice is of uncertain clinical benefit, perhaps because the interpretation is qualitative. We have developed new quantitative measures and analyzed cardiotocograph records from 148 consecutive patients, 44 of whom had at least one "nonreassuring" epoch. In multivariate regression models, measures of deceleration and variability were significantly associated with the obstetrician's diagnosis (receiver operating characteristic area 0.84, p < 0.05). This approach may be useful clinically.

Algorithms↗
PubMed2006

Heart rate characteristics monitoring for neonatal sepsis.

While heart rate variability has been measured in many clinical settings and has offered insights into how HR is controlled, rarely has it offered unique information that has led to changes in patient management. We review our experience in developing continuous HR characteristics monitoring to aid in the early diagnosis of sepsis in premature infants in the neonatal intensive care unit. A predictive algorithm, developed at one center and validated at another, has led to diagnosis and treatment of this subacute and potentially catastrophic illness prior to appearance of symptoms of severe illness.

Algorithms↗
PubMed2005

Phospholemman overexpression inhibits Na+-K+-ATPase in adult rat cardiac myocytes: relevance to decreased Na+ pump activity in postinfarction myocytes.

Messenger RNA levels of phospholemman (PLM), a member of the FXYD family of small single-span membrane proteins with putative ion-transport regulatory properties, were increased in postmyocardial infarction (MI) rat myocytes. We tested the hypothesis that the previously observed reduction in Na+-K+-ATPase activity in MI rat myocytes was due to PLM overexpression. In rat hearts harvested 3 and 7 days post-MI, PLM protein expression was increased by two- and fourfold, respectively. To simulate increased PLM expression post-MI, PLM was overexpressed in normal adult rat myocytes by adenovirus-mediated gene transfer. PLM overexpression did not affect the relative level of phosphorylation on serine68 of PLM. Na+-K+-ATPase activity was measured as ouabain-sensitive Na+-K+ pump current (Ip). Compared with control myocytes overexpressing green fluorescent protein alone, Ip measured in myocytes overexpressing PLM was significantly (P < 0.0001) lower at similar membrane voltages, pipette Na+ ([Na+]pip) and extracellular K+ ([K+]o) concentrations. From -70 to +60 mV, neither [Na+]pip nor [K+]o required to attain half-maximal Ip was significantly different between control and PLM myocytes. This phenotype of decreased V(max) without appreciable changes in K(m) for Na+ and K+ in PLM-overexpressed myocytes was similar to that observed in MI rat myocytes. Inhibition of Ip by PLM overexpression was not due to decreased Na+-K+-ATPase expression because there were no changes in either protein or messenger RNA levels of either alpha1- or alpha2-isoforms of Na+-K+-ATPase. In native rat cardiac myocytes, PLM coimmunoprecipitated with alpha-subunits of Na+-K+-ATPase. Inhibition of Na+-K+-ATPase by PLM overexpression, in addition to previously reported decrease in Na+-K+-ATPase expression, may explain altered V(max) but not K(m) of Na+-K+-ATPase in postinfarction rat myocytes.

Animals↗
PubMed2005

Extent of myocardial viability predicts response to biventricular pacing in ischemic cardiomyopathy.

BACKGROUND: The clinical response to biventricular pacing is unpredictable, especially in patients with ischemic cardiomyopathy. OBJECTIVES: The purpose of this study was to prospectively examine the relationship between the extent of myocardial viability and the response to cardiac resynchronization therapy. METHODS: Twenty-one patients with ischemic left ventricular (LV) dysfunction (left ventricular ejection fraction [LVEF] 21 +/- 5%), New York Heart Association (NYHA) functional class III-IV, and QRS >120 ms received biventricular devices. Myocardial viability was assessed by myocardial contrast echocardiography, and a perfusion score index (PSI) was calculated from summed segmental perfusion scores. LV performance was assessed by echocardiography on the day after implantation and at 6 months. RESULTS: PSI was closely correlated with acute improvement in LVEF (P = .003, r = 0.65), stroke volume (P = .02, r = 0.54), and end-systolic volume (P = .05, r = -0.49). PSI also correlated with early diastolic LV relaxation (E', P < .05, r = 0.50) and global myocardial performance or Tei index (P = .003, r = 0.63). By multiple linear regression analysis, PSI provided incremental predictive value to the degree of dyssynchrony, measured by tissue Doppler imaging, for predicting improvement in LVEF. At 6 months, PSI remained positively correlated with improvement in ventricular performance and with reduction in LV end-diastolic dimension (P = .003, r = -0.68). PSI also influenced the clinical variables of NYHA class, 6-minute walk distance, quality-of-life score, and number of hospitalizations for heart failure. CONCLUSION: In patients with ischemic cardiomyopathy, the extent of myocardial viability predicts acute and long-term improvement in LV performance, exercise tolerance, and reduction in LV end-diastolic dimension with biventricular pacing.

Aged↗
PubMed2005

Heart rate characteristics and laboratory tests in neonatal sepsis.

OBJECTIVE: The evaluation of an infant for suspected sepsis often includes obtaining blood for laboratory tests. The shortcomings of the current practice are that the infant has to appear clinically ill for the diagnosis to be entertained, and the conventional laboratory tests are invasive. We have found that the clinical diagnosis of neonatal sepsis is preceded by abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations, and we have devised a predictive HRC monitoring strategy based on multivariable logistic regression analysis that was developed at one tertiary care NICU and validated at another. We hypothesized that HRC monitoring, which is continuous and noninvasive, might be an adjunct to conventional laboratory tests in the diagnosis of neonatal sepsis. The objective of this study was to test the hypothesis that HRC monitoring adds information to conventional laboratory tests in diagnosing neonatal sepsis. METHODS: We prospectively collected heart rate data in 678 consecutive infants who stayed >7 days in the University of Virginia NICU from July 1999 to July 2003. We prospectively measured HRC and noted 149 episodes of sepsis with positive blood cultures for which data were available in 137. We obtained all laboratory test results for ratio of immature to total neutrophil count, white blood cell count, glucose, platelet count, HCO3, arterial partial pressure of carbon dioxide, and pH. We tested hypotheses using multivariable logistic regression modeling adjusted for repeated measures. RESULTS: We found that the HRC index, which was available 92% of the time, was highly significantly associated with sepsis (receiver-operating characteristic [ROC] area: 0.73). The ratio of immature to total neutrophil count, white blood cell count (available 4%-8% of the time, usually around the time of suspected sepsis), and blood glucose and pH (available 28% and 38% of the time) were also significantly associated with sepsis (ROC area: 0.75). HRC and laboratory values added independent information to each other, and a predictive model using all significant variables had ROC area of 0.82. CONCLUSIONS: HRC monitoring adds independent information to laboratory tests in the diagnosis of culture-positive neonatal sepsis.

Blood Chemical Analysis↗
PubMed2005

Heart rate characteristics: novel physiomarkers to predict neonatal infection and death.

OBJECTIVE: Monitoring of regulated physiologic processes using physiomarkers such as heart rate variability may be important in the early diagnosis of subacute, potentially catastrophic illness. Early in the course of neonatal sepsis, there are physiomarkers of reduced heart rate variability and transient decelerations similar to fetal distress. The goal of this study was to determine the degree of increased risk for sepsis, urinary tract infection (UTI), and death when these abnormal heart rate characteristics (HRC) were observed. METHODS: We monitored 1022 infants at 2 tertiary care NICUs, 458 of whom were very low birth weight. We calculated an HRC index from validated regression models relating mathematical features of heart rate time series and histograms to episodes of illness. We calculated the risks for adverse events of sepsis, UTI, and death for infants stratified by HRC measurements. RESULTS: Compared with infants with low-risk HRC measurements, infants with high-risk HRC measurements had 5- to 6-fold increased risk for an adverse event in the next day and 3-fold increased risk in the next week. Laboratory tests that were relevant to infection added information to HRC measurements. Infants with both high-risk HRC and abnormal laboratory tests had 6- to 7-fold increased risk for an adverse event in the next day compared with infants who had neither. CONCLUSION: HRC are noninvasively monitored physiomarkers that identify infants in the NICU who are at high risk for sepsis, UTI, and death.

Gestational Age↗
PubMed2004

Abnormal heart rate characteristics are associated with neonatal mortality.

Estimating the risk of in-hospital mortality in the newborn intensive care unit can provide important information for health-care providers, and illness severity scores have been devised to provide mortality risk estimates. Calculation of illness severity scores is time-consuming, and the information used to predict mortality is collected only for the first 12 to 24 h of life. A noninvasive continuous measure that uses information collected throughout the hospitalization and that requires no data entry could be less costly and more informative. We have previously shown that the abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations accompany neonatal illness such as late-onset sepsis. We hypothesized that more frequent and severe abnormal HRC are associated with an increased risk of death. We tested this hypothesis in two ways. Using data on infants older than 7 d of age, we first determined the association of the HRC index with death in the next week. Second, we devised a cumulative HRC score and determined its association with in-hospital death. There were 37 deaths in the 685 patients. The major findings were 1) the HRC index showed highly significant association with death in the succeeding 7 d (receiver-operating characteristic area > 0.7, p < 0.001), and 2) the cumulative HRC was highly significantly associated with neonatal in-hospital mortality (receiver-operating characteristic area > 0.80, p < 0.001). In both analyses, HRC added information to birth weight, gestational age, and postnatal age (p < 0.01). The HRC index provides independent information about the risk of neonatal death in the upcoming 7 d, and the cumulative HRC is an estimate of the risk of in-hospital neonatal mortality.

Birth Weight↗
PubMed2004

Sample entropy.

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Journal Article↗
PubMed2004

Increased nonstationarity of neonatal heart rate before the clinical diagnosis of sepsis.

The clinical diagnosis of neonatal sepsis is preceded by abnormal heart rate (HR) characteristics of transient decelerations and reduced variability, which intuitively appear to be more nonstationary than normal HR variability. Our goals were to investigate stationarity of HR, and to devise measures useful for early diagnosis of neonatal sepsis. In this context, we define non-stationarity to be present when the observed data differ from surrogate data generated by stationary Gaussian noise with arbitrary linear correlations. We devised statistical methods for determining stationarity of HR data based on the two-sample Kolmogorov-Smirnov (KS) test. We compared distributions of KS distances between small sample epochs from clinical data with those of isospectral surrogates and of surrogates generated using the amplitude-adjusted Fourier transform technique, reasoning that they should differ significantly for nonstationary data. We found significant evidence of non-stationarity for records longer than 1 min. We developed new HR measures based on the empirical cumulative distribution function (ECDF) that are highly significantly associated with sepsis, but are not correlated with HR measures such as moments or sample entropy. We conclude that neonatal HR data cannot be assumed to be stationary, and become even less stationary prior to sepsis.

Algorithms↗
PubMed2003

Sample asymmetry analysis of heart rate characteristics with application to neonatal sepsis and systemic inflammatory response syndrome.

We introduce the sample asymmetry analysis (SAA) and illustrate its utility for assessment of heart rate characteristics occurring early in the course of neonatal sepsis and systemic inflammatory response syndrome (SIRS). Conceptually, SAA describes changes in the shape of the histogram of RR intervals that are caused by reduced accelerations and/or transient decelerations of heart rate. Unlike other measures of heart rate variability, SAA allows separate quantification of the contribution of accelerations and decelerations. The application of SAA is exemplified by a study comparing 50 infants, who experienced a total of 75 episodes of sepsis and SIRS, with 50 control infants. The two groups were matched by birth weight and gestational age. RR intervals were recorded for all infants throughout their course in the Neonatal Intensive Care Unit. The sample asymmetry of the RR intervals increased in the 3-4 d preceding sepsis and SIRS, with the steepest increase in the last 24 h, from a baseline value of 3.3 (SD = 1.6) to 4.2 (SD = 2.3), p = 0.02. After treatment and recovery, sample asymmetry returned to its baseline value of 3.3 (SD = 1.3). The difference between sample asymmetry in health and before sepsis and SIRS was mainly due to fewer accelerations than to decelerations. Compared with healthy infants, infants who experienced sepsis had similar sample asymmetry in health, and elevated values before sepsis and SIRS (p = 0.002). We conclude that SAA is a useful new mathematical technique for detecting the abnormal heart rate characteristics that precede neonatal sepsis and SIRS.

Birth Weight↗
PubMed2003

Abnormal heart rate characteristics preceding neonatal sepsis and sepsis-like illness.

Late-onset neonatal sepsis is a significant cause of morbidity and mortality, and early detection could prove beneficial. Previously, we found that abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations occurred early in the course of neonatal sepsis and sepsis-like illness in infants in a single neonatal intensive care unit (NICU). We hypothesized that this finding can be generalized to other NICUs. We prospectively collected clinical data and continuously measured RR intervals in all infants in two NICUs who stayed for >7 d. We defined episodes of sepsis and sepsis-like illness as acute clinical deteriorations that prompted physicians to obtain blood cultures and start antibiotics. A predictive statistical model yielding an HRC index was developed on a derivation cohort of 316 neonates in the University of Virginia NICU and then applied to the validation cohort of 317 neonates in the Wake Forest University NICU. In the derivation cohort, there were 155 episodes of sepsis and sepsis-like illness in 101 infants, and in the validation cohort, there were 118 episodes in 93 infants. In the validation cohort, the HRC index 1) showed highly significant association with impending sepsis and sepsis-like illness (receiver operator characteristic area 0.75, p < 0.001) and 2) added significantly to the demographic information of birth weight, gestational age, and days of postnatal age in predicting sepsis and sepsis-like illness (p < 0.001). Continuous HRC monitoring is a generally valid and potentially useful noninvasive tool in the early diagnosis of neonatal sepsis and sepsis-like illness.

Heart Rate↗
PubMed2002

Sample entropy analysis of neonatal heart rate variability.

Abnormal heart rate characteristics of reduced variability and transient decelerations are present early in the course of neonatal sepsis. To investigate the dynamics, we calculated sample entropy, a similar but less biased measure than the popular approximate entropy. Both calculate the probability that epochs of window length m that are similar within a tolerance r remain similar at the next point. We studied 89 consecutive admissions to a tertiary care neonatal intensive care unit, among whom there were 21 episodes of sepsis, and we performed numerical simulations. We addressed the fundamental issues of optimal selection of m and r and the impact of missing data. The major findings are that entropy falls before clinical signs of neonatal sepsis and that missing points are well tolerated. The major mechanism, surprisingly, is unrelated to the regularity of the data: entropy estimates inevitably fall in any record with spikes. We propose more informed selection of parameters and reexamination of studies where approximate entropy was interpreted solely as a regularity measure.

Entropy↗