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Biomedical subjects

Brahm Goldstein

Publications and source records attributed to Brahm Goldstein.

At least 19 recordsLinked to original sources

Complex analysis of intracranial hypertension using approximate entropy.

OBJECTIVE: To determine whether decomplexification of intracranial pressure dynamics occurs during periods of severe intracranial hypertension (intracranial pressure >25 mm Hg for >5 mins in the absence of external noxious stimuli) in pediatric patients with intracranial hypertension. DESIGN: Retrospective analysis of clinical case series over a 30-month period from April 2000 through January 2003. SETTING: Multidisciplinary 16-bed pediatric intensive care unit. PATIENTS: Eleven episodes of intracranial hypertension from seven patients requiring ventriculostomy catheter for intracranial pressure monitoring and/or cerebral spinal fluid drainage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured changes in the intracranial pressure complexity, estimated by the approximate entropy (ApEn), as patients progressed from a state of normal intracranial pressure (<25 mm Hg) to intracranial hypertension. We found the ApEn mean to be lower during the intracranial hypertension period than during the stable and recovering periods in all the 11 episodes (0.5158 +/- 0.0089, 0.3887 +/- 0.077, and 0.5096 +/- 0.0158, respectively, p < .01). Both the mean reduction in ApEn from the state of normal intracranial pressure (stable region) to intracranial hypertension (-0.1271) and the increase in ApEn from the ICH region to the recovering region (0.1209) were determined to be statistically significant (p < .01). CONCLUSIONS: Our results indicate that decreased complexity of intracranial pressure coincides with periods of intracranial hypertension in brain injury. This suggests that the complex regulatory mechanisms that govern intracranial pressure may be disrupted during acute periods of intracranial hypertension. This phenomenon of decomplexification of physiologic dynamics may have important clinical implications for intracranial pressure management.

Acute Disease↗

ENHANCE: results of a global open-label trial of drotrecogin alfa (activated) in children with severe sepsis.

OBJECTIVE: To gather additional 28-day all-cause mortality data and safety information for pediatric patients with severe sepsis who received drotrecogin alfa (activated) (DrotAA). DESIGN AND SETTING: Single-arm, open-label, multicentered study conducted in 59 study sites in 15 countries. PATIENTS: One-hundred eighty-eight children (term newborn to <18 yrs old) with severe sepsis were consecutively enrolled in the study. INTERVENTION: Administration of DrotAA, 24 microg/kg/hr for 96 hrs. MAIN OUTCOME MEASURES: Four-day and 28-day all-cause mortality, safety information, and protein C levels. RESULTS: : One-hundred eighty-seven patients completed the study. The 4-day mortality rate was 7.0%, and the 28-day mortality rate was 13.4%. At baseline, 57.6% of patients were severely deficient in protein C (a level < or = 40% of normal). There was a statistically significant association between increased 28-day mortality and decreased end-of-infusion protein C levels (p < .001), greater number of baseline organ dysfunctions (p < .001), and greater baseline ventilator use (p = .03). Bleeding was the most significant complication observed. Serious bleeding events (including anemia without a bleeding source) were experienced by 27.7% of patients (n = 52). Six of the serious bleeding events (3.2%) were considered related to administration of DrotAA. During infusion, serious bleeding events with an identified source of bleeding were experienced by 5.9% of patients (n = 11). Central nervous system bleeding was experienced by 2.7% (n = 5). Two of the intracranial hemorrhages were fatal and occurred postinfusion. CONCLUSIONS: Without a placebo control, no efficacy conclusions are possible. Subgroups at higher risk of death were identified, and the change in protein C level from baseline was predictive of survival. The most significant complication observed was bleeding. Risk factors for serious bleeding appear to be multiple organ failure, thrombocytopenia, and coagulopathy.

Adolescent↗

International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.

OBJECTIVE: Although general definitions of the sepsis continuum have been published for adults, no such work has been done for the pediatric population. Physiologic and laboratory variables used to define the systemic inflammatory response syndrome (SIRS) and organ dysfunction require modification for the developmental stages of children. An international panel of 20 experts in sepsis and clinical research from five countries (Canada, France, Netherlands, United Kingdom, and United States) was convened to modify the published adult consensus definitions of infection, sepsis, severe sepsis, septic shock, and organ dysfunction for children. DESIGN: Consensus conference. METHODS: This document describes the issues surrounding consensus on four major questions addressed at the meeting: a) How should the pediatric age groups affected by sepsis be delineated? b) What are the specific definitions of pediatric SIRS, infection, sepsis, severe sepsis, and septic shock? c) What are the specific definitions of pediatric organ failure and the validity of pediatric organ failure scores? d) What are the appropriate study populations and study end points required to successfully conduct clinical trials in pediatric sepsis? Five subgroups first met separately and then together to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiological data, and coagulation variables. All conference participants approved the final draft of the proceedings of the meeting. RESULTS: Conference attendees modified the current criteria used to define SIRS and sepsis in adults to incorporate pediatric physiologic variables appropriate for the following subcategories of children: newborn, neonate, infant, child, and adolescent. In addition, the SIRS definition was modified so that either criteria for fever or white blood count had to be met. We also defined various organ dysfunction categories, severe sepsis, and septic shock specifically for children. Although no firm conclusion was made regarding a single appropriate study end point, a novel nonmortality end point, organ failure-free days, was considered optimal for pediatric clinical trials given the relatively low incidence of mortality in pediatric sepsis compared with adult populations. CONCLUSION: We modified the adult SIRS criteria for children. In addition, we revised definitions of severe sepsis and septic shock for the pediatric population. Our goal is for these first-generation pediatric definitions and criteria to facilitate the performance of successful clinical studies in children with sepsis.

Adolescent↗

Pilot study of preoperative heart rate variability and adverse events in children emerging from anesthesia.

OBJECTIVE: To assess correlations between preoperative heart rate variability (a noninvasive measure of autonomic cardiac activity) and adverse respiratory events during anesthesia emergence in children. DESIGN: Case control study. SETTING: Tertiary care pediatric operating room. PATIENTS: Sixty-one children, aged 8 months to 13 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Heart rate power spectra were obtained from two 5-min immediate-preoperative electrocardiographs with an orthostatic posture change interposed and (n = 32) from a 24-hr preoperative Holter monitor. Observers recorded emergence from standardized anesthesia for coughing, laryngospasm, and desaturation. Low-frequency/high-frequency ratios (LF/HF) were derived from power spectra of heart rate variability. The orthostatic change in heart rate variability derived from brief preoperative recordings was significantly different if adverse events occurred during emergence from anesthesia (LF/HF standing/LF/HF supine = 1.3 vs. 2.8, p = .019). Holter-derived heart rate variability had no correlation with adverse events. Receiver operating characteristic analysis showed a sensitivity of 85% and specificity of 52% for predicting adverse events with preoperative recordings. CONCLUSIONS: This study provides new information regarding pathophysiology in children with upper respiratory infection. The magnitude of difference demonstrated is insufficient to propose this method as a preoperative screening test.

Adolescent↗

Pediatric sepsis definitions: past, present, and future.

OBJECTIVE: To review the past, present, and future definitions of sepsis and the systemic inflammatory response syndrome in children. METHODS: Review of the literature. RESULTS: The history and development of the adult-derived sepsis syndrome and its application to pediatric-specific sepsis definitions is provided. Initially, only adult definitions were applied to pediatric studies. Recently, pediatric-specific definitions have been published. The pediatric consensus conference-derived definitions for systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock are summarized, and their limitations are discussed. CONCLUSIONS: The potential value and inconsistencies of the current pediatric-specific sepsis definitions are discussed. Future direction of the definitions and their applications are presented.

Child↗

Adaptive modeling and spectral estimation of nonstationary biomedical signals based on Kalman filtering.

We describe an algorithm to estimate the instantaneous power spectral density (PSD) of nonstationary signals. The algorithm is based on a dual Kalman filter that adaptively generates an estimate of the autoregressive model parameters at each time instant. The algorithm exhibits superior PSD tracking performance in nonstationary signals than classical nonparametric methodologies, and does not assume local stationarity of the data. Furthermore, it provides better time-frequency resolution, and is robust to model mismatches. We demonstrate its usefulness by a sample application involving PSD estimation of intracranial pressure signals (ICP) from patients with traumatic brain injury (TBI).

Computer Simulation↗

Interpretation of approximate entropy: analysis of intracranial pressure approximate entropy during acute intracranial hypertension.

We studied changes in intracranial pressure (ICP) complexity, estimated by the approximate entropy (ApEn) of the ICP signal, as subjects progressed from a state of normal ICP (< 20-25 mmHg) to acutely elevated ICP (an ICP "spike" defined as ICP > 25 mmHg for < or = 5 min). We hypothesized that the measures of intracranial pressure (ICP) complexity and irregularity would decrease during acute elevations in ICP. To test this hypothesis we studied ICP spikes in pediatric subjects with severe traumatic brain injury (TBI). We conclude that decreased complexity of ICP coincides with episodes of intracranial hypertension (ICH) in TBI. This suggests that the complex regulatory mechanisms that govern intracranial pressure are disrupted during acute rises in ICP. Furthermore, we carried out a series of experiments where ApEn was used to analyze synthetic signals of different characteristics with the objective of gaining a better understanding of ApEn itself, especially its interpretation in biomedical signal analysis.

Adolescent↗

An automatic beat detection algorithm for pressure signals.

Beat detection algorithms have many clinical applications including pulse oximetry, cardiac arrhythmia detection, and cardiac output monitoring. Most of these algorithms have been developed by medical device companies and are proprietary. Thus, researchers who wish to investigate pulse contour analysis must rely on manual annotations or develop their own algorithms. We designed an automatic detection algorithm for pressure signals that locates the first peak following each heart beat. This is called the percussion peak in intracranial pressure (ICP) signals and the systolic peak in arterial blood pressure (ABP) and pulse oximetry (SpO2) signals. The algorithm incorporates a filter bank with variable cutoff frequencies, spectral estimates of the heart rate, rank-order nonlinear filters, and decision logic. We prospectively measured the performance of the algorithm compared to expert annotations of ICP, ABP, and SpO2 signals acquired from pediatric intensive care unit patients. The algorithm achieved a sensitivity of 99.36% and positive predictivity of 98.43% on a dataset consisting of 42,539 beats.

Algorithms↗

Interactive Web sites for families and physicians of pediatric intensive care unit patients: a preliminary report.

OBJECTIVE: To describe our experience with a Web-based communications program for the patients, families, and referring physicians of patients admitted to our pediatric intensive care unit. DESIGN: Prospective descriptive case series for a 32-month period from April 2000 through January 2003. SETTING: Sixteen-bed multidisciplinary medical-surgical pediatric intensive care unit (PICU). SUBJECTS: Seventy-three of 78 patients admitted to the PICU for > or =3 days and their families participated in the study, along with 26 referring physicians. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We found that 77% (474/619) of surveyed family members and friends thought that the Web page helped them share information, 13% (82/619) were unsure, and only <1% (4/619) thought it did not help them share information. When comparing respondents who thought the Web page helped them share information with those who did not or those who did not know, internet use was significantly associated with thinking that the Web page helped them share information (p =.0007). Seventy-three percent (19/26) of physicians thought that Web page-based communication was easier than present methods to convey patient information, and 62% (16/26) replied that the Web-based communication met their expectation. Fifty-four percent (14/26) of physicians thought they were more likely to refer patients to our PICU because of the Web-based communication; this was significantly associated with physician assessment that the Web-based communication was easier than the present methods of communicating with referring physicians (p =.003). CONCLUSIONS: We conclude that both families and referring physicians find Web-based communications during a child's PICU hospitalization to be very helpful. We suggest that the Web-based PICU communications be developed and studied for both medical and economic impact.

Child↗

Prediction of paroxysmal atrial fibrillation by analysis of atrial premature complexes.

Currently, no reliable method exists to predict the onset of paroxysmal atrial fibrillation (PAF). We propose a predictor that includes an analysis of the R-R time series. The predictor uses three criteria: the number of premature atrial complexes (PAC) not followed by a regular R-R interval, runs of atrial bigeminy and trigeminy, and the length of any short run of paroxysmal atrial tachycardia. An increase in activity detected by any of these three criteria is an indication of an imminent episode of PAF. Using the Physionet database of the Computers in Cardiology 2001 Challenge, the predictor achieved a sensitivity of 89% and a specificity of 91%.

Algorithms↗