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Background: Previous single-center studies have shown that telemedicine improves care in newborns with suspected heart disease. The aim of this study was to test the hypothesis that telemedicine would shorten time to diagnosis, prevent unnecessary transports, reduce length of stay, and decrease exposure to invasive treatments., Methods: Nine pediatric cardiology centers entered data prospectively on patients aged <6 weeks, matched by gestational age, weight, and diagnosis. Subjects born at hospitals with and without access to telemedicine constituted the study group and control groups, respectively. Data from patients with mild or no heart disease were analyzed., Results: Data were obtained for 337 matched pairs with mild or no heart disease. Transport to a tertiary care center (4% [n = 15] vs 10% [n = 32], P = .01), mean time to diagnosis (100 vs 147 min, P < .001), mean length of stay (1.0 vs 26 days, P = .005) and length of intensive care unit stay (0.96 vs 2.5 days, P = .024) were significantly less in the telemedicine group. Telemedicine patients were significantly farther from tertiary care hospitals than control subjects. The use of inotropic support and indomethacin was significantly less in the telemedicine group. By multivariate analysis, telemedicine patients were less likely to be transported (odds ratio, 0.44; 95% confidence interval, 0.23-0.83) and less likely to be placed on inotropic support (odds ratio, 0.16; 95% confidence interval, 0.10-0.28)., Conclusions: Telemedicine shortened the time to diagnosis and significantly decreased the need for transport of infants with mild or no heart disease. The length of hospitalization and intensive care stay and use of indomethacin and inotropic support were less in telemedicine patients., (Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Objective: Sepsis is common in children and often results in cardiac dysfunction. Assessment of patients with sepsis-associated myocardial depression using ejection fraction and fractional shortening with conventional echocardiography is load dependent and often reveals cardiac dysfunction only after clinical deterioration has occurred. Speckle tracking imaging is a novel technology that can assess deformation and strain by tracking displacement of acoustic markers in the myocardium. We hypothesize that speckle tracking imaging will detect cardiac impairments during sepsis that are not appreciated by conventional echocardiography., Design: Retrospective, observational study., Setting: A large, tertiary-care pediatric intensive care unit., Patients: Fifteen pediatric patients with septic shock, and 30 age- and gender-matched healthy controls., Interventions: Transthoracic echocardiograms from subjects with septic shock (by American College of Chest Physicians/Society of Critical Care Medicine consensus criteria) and controls were evaluated. Speckle tracking imaging was used to obtain tissue displacement, velocity, strain, and strain rate in radial, longitudinal, and circumferential planes. Ejection fraction and fractional shortening were determined by conventional methods. Comparisons between groups were made using a paired t test., Measurements and Main Results: Compared to control subjects, children with septic shock demonstrated impaired myocardial performance as quantified by speckle tracking imaging. Significant differences were seen in circumferential and longitudinal strain (p < .001), strain rate (p < .05), radial displacement (p < .001), and rotational velocity and displacement (p < .01). There was no significant difference in ejection fraction and fractional shortening between septic patients and controls., Conclusions: Speckle tracking imaging detected a number of significantly impaired measures of ventricular performance in children with sepsis, not appreciated by conventional echocardiography. This technology may improve our understanding and identification of myocardial depression in the critically ill septic child.

Background: Patients with Chuvash polycythemia, (homozygosity for the R200W mutation in the von Hippel Lindau gene (VHL)), have elevated levels of hypoxia inducible factors HIF-1 and HIF-2, often become iron-deficient secondary to phlebotomy, and have elevated estimated pulmonary artery pressure by echocardiography. The objectives of this study were to provide a comprehensive echocardiographic assessment of cardiovascular physiology and to identify clinical, hematologic and cardiovascular risk factors for elevation of tricuspid regurgitation velocity in children and adults with Chuvash polycythemia., Design and Methods: This cross-sectional observational study of 120 adult and pediatric VHL(R200W) homozygotes and 31 controls at outpatient facilities in Chuvashia, Russian Federation included echocardiography assessment of pulmonary artery pressure (tricuspid regurgitation velocity), cardiac volume, and systolic and diastolic function, as well as hematologic and clinical parameters. We determined the prevalence and risk factors for elevation of tricuspid regurgitation velocity in this population and its relationship to phlebotomy., Results: The age-adjusted mean ± SE tricuspid regurgitation velocity was higher in VHL(R200W) homozygotes than controls with normal VHL alleles (2.5±0.03 vs. 2.3±0.05 m/sec, P=0.005). The age-adjusted left ventricular diastolic diameter (4.8±0.05 vs. 4.5±0.09 cm, P=0.005) and left atrial diameter (3.4±0.04 vs. 3.2±0.08 cm, P=0.011) were also greater in the VHL(R200W) homozygotes, consistent with increased blood volume, but the elevation in tricuspid regurgitation velocity persisted after adjustment for these variables. Among VHL(R200W) homozygotes, phlebotomy therapy was associated with lower serum ferritin concentration, and low ferritin independently predicted higher tricuspid regurgitation velocity (standardized beta=0.29; P=0.009)., Conclusions: Children and adults with Chuvash polycythemia have higher estimated right ventricular systolic pressure, even after adjustment for echocardiography estimates of blood volume. Lower ferritin concentration, which is associated with phlebotomy, independently predicts higher tricuspid regurgitation velocity (www.clinicaltrials.gov identifier NCT00495638).

In a non-comparative study, caspofungin was effective salvage therapy for approximately half of the patients refractory to or intolerant of standard antifungal agents for invasive aspergillosis. To establish a frame of reference for these results, we compared the response to caspofungin with responses to other antifungal agents in a historical cohort of similar patients. The efficacy could be evaluated in 83 patients who received caspofungin 50 mg daily after a 70-mg loading dose. The historical control group, identified through a retrospective review of medical records, included 214 evaluable patients possibly refractory to or intolerant of ≥1 week of standard antifungal therapy. All patients had documented invasive aspergillosis. Favorable response was defined as a complete or partial response to therapy. Underlying diseases, baseline neutropenia, corticosteroid use, and sites of infection were similar in both studies. Most patients had received amphotericin B formulations and/or itraconazole, and were refractory to standard therapy. Favorable response rates were 45% with caspofungin and 16% with standard therapy. The unadjusted odds ratio for a favorable response (caspofungin/standard therapy) was 4.1 (95% confidence interval: 2.2, 7.5). After adjusting for potential imbalances in the frequency of disseminated infection, neutropenia, steroid use, and bone marrow transplantation between groups, the odds ratio remained at 4.1 (2.1, 7.9). Although only tentative conclusions about relative efficacy can be drawn from retrospective comparisons, caspofungin appeared to be at least as efficacious as an amphotericin B formulation and/or itraconazole for the treatment of invasive aspergillosis in patients refractory to or intolerant of their initial antifungal therapy.

Preliminary speckle-tracking echocardiographic studies show that patients with single ventricles (SVs) have significantly decreased twisting and dyssynchrony of twisting. This could be related to abnormal cardiac looping, which leads to hearts that lack helical fiber patterns. The aim of this study was to analyze gradient cine magnetic resonance imaging (MRI) using Velocity Vector Imaging to assess cardiac mechanics. Subjects were 38 patients (aged 8 to 37 years) with SVs of left ventricular (n = 30) and indeterminate (n = 8) type who underwent cardiac MRI. Controls were 14 normal children and adults. Gradient cine MRI sequences close to the apex were subjected to a Velocity Vector Imaging analysis program adapted for MRI. In the control group, mean circumferential strain was -18.02 +/- 7.31%, mean dispersion of peak circumferential strain was 44.23 +/- 37.14 ms, and average rotation was -7.7 +/- 1.38 degrees . The rotation values were negative, or counterclockwise. In patients with SVs, mean circumferential strain was -8.87 +/- 7.30%, mean dispersion of peak circumferential strain was 181.55 +/- 76.07 ms, and average rotation was -2.6 +/- 1.24 degrees (p <0.001). Mean dispersion of the peak of rotation in the control group was 39.6 +/- 22.8 ms, compared to 166.5 +/- 72.4 ms in patients with SVs. In conclusion, this study showed a dramatic decrease in apical rotation and circumferential strain in the SV group compared to the control group. Strain and rotation mechanics at the apex in patients with SVs showed marked dyssynchrony., (Copyright 2010 Elsevier Inc. All rights reserved.)

The objective of this study was to identify the patient, institutional, and utilization characteristics associated with outcome in hospitalized pediatric patients with myocarditis. This was a nonconcurrent cohort study of all consecutive pediatric discharges from the 35 academic children's hospitals that are members of the Pediatric Health Information System (PHIS): patients from birth through age 21 years discharged from participating hospitals between January 1, 2005, and December 31, 2005. Patient-level, institution-level, and utilization variables were examined. A total of 427,615 patients were discharged, and 216 (0.05%) were diagnosed with myocarditis. Common etiologies were idiopathic (82%), related to other diseases (6%), and bacterial or viral (3%). Myocarditis patients required considerable support including intravenous immunoglobulin (IVIG; 49.1%), milrinone (45%), epinephrine (35%), mechanical ventilation (25%), extracorporeal membrane oxygenation (7%), and cardiac transplantation (5%). Even in patients with extreme illness scores, IVIG use did not impact survival (P = 0.67). Overall survival of myocarditis patients was 92%. Myocarditis patients who died presented with a higher severity of illness and required frequent use of extracorporeal membrane oxygenation and other ICU therapies. In conclusion, pediatric patients with myocarditis have considerable variability in their presentations and outcomes, use more resources, and die more often than children with other diagnoses. Attempts at using characteristics that uniformly predict illness severity or survival were not successful. Despite increased use in the sickest patients, IVIG conferred no survival advantage.

Objective: To assess the prevalence of cardiac abnormalities in fetuses of women with clinical or serologic evidence of systemic lupus erythematosus (SLE)., Methods: A retrospective review of fetal echocardiograms performed secondary to maternal SLE or connective tissue antibodies with or without fetal complete heart block (CHB) was performed to evaluate the prevalence of fetal structural heart disease, valve regurgitation, abnormal ventricular function, pericardial effusion, endocardial fibroelastosis and rhythm abnormalities., Results: Forty-one fetuses were studied. One fetal demise occurred. Three fetuses had structural abnormalities, including d-transposition of the great arteries (n = 1) and pulmonic stenosis (n = 2). Seventeen fetuses had valve regurgitation. The prevalence of valve regurgitation was: tricuspid (n = 15), mitral (n = 6), pulmonic (n = 4) and aortic (n = 2). Two fetuses with pulmonic insufficiency had pulmonic stenosis. Four fetuses had CHB, one of which developed atrial flutter. Prolongation of the mechanical AV interval occurred in five fetuses; none developed CHB., Conclusions: In addition to CHB and myocardial dysfunction, structural heart defects occur in fetuses of women with serologic or clinical evidence of SLE. In our series, this occurred more frequently than reported for the general population. Valve regurgitation was present in all fetuses with CHB and many in sinus rhythm and may represent cardiac inflammation. Pulmonic insufficiency in utero may be a marker for a structural valve abnormality.

Invasive fungal infections (IFIs) are serious complications in elderly adults. Caspofungin may provide a useful therapeutic option for elderly patients with or at high risk for IFIs. We retrospectively compared efficacy and safety outcomes in elderly (> or = 65 years of age) and non-elderly patients in three clinical trials of caspofungin: a double-blind, randomized trial versus amphotericin B for documented invasive candidiasis (IC); an open-label, non-comparative study of definite or probable invasive aspergillosis (IA); and a double-blind, randomized trial versus liposomal amphotericin B as empirical therapy (ET) in febrile neutropenic patients. A total of 159 elderly patients with a median age of 71 years (range, 65-84) received caspofungin in these studies. The median duration of caspofungin therapy was 12 days for IC and ET, and 28 days for IA. Point estimates for the favorable response rates to caspofungin were numerically higher in elderly versus non-elderly patients with IC (83% vs. 68%) or IA (64% vs. 44%) and were similar in patients receiving ET (36% vs. 34%). Adverse events related to caspofungin occurred in generally similar proportions of elderly versus non-elderly patients with IC (clinical, 33% vs. 27%; laboratory, 17% vs. 29%), with IA (clinical, 7% vs. 13%; laboratory, 13% vs. 14%), or receiving ET (clinical, 47% vs. 47%; laboratory, 24% vs. 22%). Nephrotoxicity and infusion-related toxicity developed in comparable proportions of elderly and non-elderly caspofungin recipients in all three studies. In this post-hoc analysis, caspofungin appeared to be as efficacious and well tolerated in elderly patients as in non-elderly patients.

The prevalence of invasive fungal infections (IFIs) has increased over the past three decades owing to the increasing numbers of immunocompromised hosts. These infections are associated with significant morbidity and mortality. Recent significant advances in antifungal therapy include the broad-spectrum triazoles (voriconazole and posaconazole) and a new class of antifungals, the echinocandins (caspofungin, micafungin, and anidulafungin). New treatment strategies, such as combination therapy and pre-emptive therapy, are being investigated. There have also been significant improvements in diagnostics; the galactomannan enzyme immunoassay and the beta-glucan test are now part of the EORTC/MSG criteria for diagnosis of IFI. Despite these advances, there remain a number of unanswered questions regarding optimal management of serious fungal infections, and research continues to discover and develop new therapies and evaluate new management strategies.

Objectives: The objectives of this study were to contrast risk factors, microbiology, and outcomes in patients with invasive candidiasis treated in an intensive care unit (ICU) with those in patients with invasive candidiasis treated outside an ICU and to describe therapeutic results with caspofungin in ICU patients., Materials and Methods: We retrospectively identified patients with documented invasive candidiasis who received their first dose of the study drug in the ICU as part of a double-blind randomized trial. Participants were not stratified at entry by their ICU status. Patients received caspofungin (50 mg/d after a 70-mg loading dose) or conventional amphotericin B (0.6-1.0 mg/kg per day) for 10 to 14 days. A favorable response required resolution of signs and symptoms as well as eradication of Candida pathogens., Results: Of the 224 patients, 97 (43%) received their first dose of the study drug in the ICU. Most patients had well-recognized risk factors for invasive candidiasis, including broad-spectrum antibiotics, central venous catheters, and hyperalimentation. Recent surgery was more common whereas malignancy, neutropenia, and immunosuppression were less common among ICU patients than among non-ICU patients. Candidemia was demonstrated in 81% of ICU patients and in 84% of non-ICU patients. Favorable response rates in the ICU patients vs the non-ICU patients were 68% (95% confidence interval [CI] = 53%, 82%) vs 77% (95% CI = 67%, 87%) for caspofungin and 56% (95% CI = 43%, 69%) vs 67% (95% CI = 55%, 79%) for amphotericin B. After accounting for differences in APACHE (Acute Physiology and Chronic Health Evaluation) II score, neutropenia status, and geographic region, we found that patients initiating the study therapy in an ICU were still more likely to die than patients initiating study therapy outside an ICU. For ICU patients, all-cause mortality rates were 45% (95% CI = 30%, 60%) for caspofungin recipients and 40% (95% CI = 28%, 53%) for amphotericin B recipients, whereas candidiasis-attributable mortality rates were 5% (95% CI = 0%, 12%) for caspofungin recipients and 11% (95% CI = 3%, 19%) for amphotericin B recipients. Overall, drug-related adverse events were reported less often among the ICU patients than among the non-ICU patients., Conclusions: In ICU patients treated with antifungal therapy, invasive candidiasis is associated with substantial mortality, but most deaths cannot be directly attributed to this infection.

The intent of this review is to provide the clinician with a summary of what is currently known about the contribution of genetics to the origin of congenital heart disease. Techniques are discussed to evaluate children with heart disease for genetic alterations. Many of these techniques are now available on a clinical basis. Information on the genetic and clinical evaluation of children with cardiac disease is presented, and several tables have been constructed to aid the clinician in the assessment of children with different types of heart disease. Genetic algorithms for cardiac defects have been constructed and are available in an appendix. It is anticipated that this summary will update a wide range of medical personnel, including pediatric cardiologists and pediatricians, adult cardiologists, internists, obstetricians, nurses, and thoracic surgeons, about the genetic aspects of congenital heart disease and will encourage an interdisciplinary approach to the child and adult with congenital heart disease.

Background: Sensitivity analyses were incorporated in a Phase III study of caspofungin vs. liposomal amphotericin B as empirical antifungal therapy for febrile neutropenic patients to determine the impact of varying definitions of fever resolution on response rates., Methods: The primary analysis used a 5-part composite endpoint: resolution of any baseline invasive fungal infection, no breakthrough invasive fungal infection, survival, no premature discontinuation of study drug, and fever resolution for 48 h during the period of neutropenia. Pre-specified analyses used 3 other definitions for fever resolution: afebrile for 24 h during the period of neutropenia, afebrile at 7 days post therapy, and eliminating fever resolution altogether from the composite endpoint. Patients were stratified on entry by use of antifungal prophylaxis and risk of infection. Allogeneic hematopoietic stem cell transplants or relapsed acute leukemia defined high-risk patients., Results: In the primary analysis, 41% of patients in each treatment group met the fever-resolution criteria. Low-risk patients had shorter durations of neutropenia but failed fever-resolution criteria more often than high-risk patients. In each exploratory analysis, response rates increased in both treatment groups compared to the primary analysis, particularly in low-risk patients., Conclusions: Response rates for the primary composite endpoint for both treatment groups in this study were driven by low rates of fever resolution. Requiring fever resolution during neutropenia in a composite endpoint can mask more clinically relevant outcomes.

A 12-year-old male presented with a 6-week history of apparent digital vasculitis with color changes of the distal fingers and erythematous macules of the palms and soles. Physical examination revealed skin findings of Carney complex and an abnormal cardiac examination. Echocardiography demonstrated a large left atrial mass, which caused partial obstruction during diastole and moderate mitral valve insufficiency. Surgical excision and pathological examination of the mass confirmed the presence of a large, peduculated myxoma. This case illustrates the presentation of Carney complex with left atrial myxoma as apparent vasculitis and Raynaud's phenomenon.

The etiology and pathogenesis of Kawasaki disease (KD) is largely unknown. Certain demographic factors and laboratory findings are predictive of the development of coronary artery (CA) aneurysms. The objectives of this study were to determine the epidemiology of KD patients in an urban hospital and determine risk factors associated with their development of CA abnormalities. A longitudinal case series of KD patients admitted to Children's National Medical Center from 1990 to 2002 was examined. Age, sex, ethnic background, duration of fever prior to diagnosis, address, month diagnosed, and CA abnormalities (ectasia or aneurysms) on echocardiography were recorded. Median household income was obtained from the U.S. Census Bureau Web site. The Student t-test, logistic regression analyses, and the Kruskal-Wallis test were used, with significance assumed at p < 0.05. A total of 302 patients were evaluated. CA abnormalties were found in 27 patients (9%), with aneurysms identified in 13 patients (4%). Age was 2.9 +/- 2.4 years (range, 2 months to 14 years). A total of 51 patients (16%) were < or =1 year and 35 patients (12%) were > or =5 years. Ethnic distribution was 54% (164) African American, 24% (72) Caucasian, 9% (29) Asian/Pacific Islander, 8% (23) Hispanic, and 5% (14) Middle Eastern. Only 2/164 (1.2%) African Americans developed CA aneurysms. Neighborhood median income of the cohort was $45,400 +/- $21,200 ($52,200 +/-$25,800 for patients with aneurysms). A total of 28% of cases clustered between December and January. Cases doubled annually in 1999-2001 compared to 1990-1998 (39 vs 19). Multivariate logistic regression found age between 1 and 5 years [p = 0.045; odds ratio, 0.31; 95% confidence interval (CI), 0.10-0.97] and African American race (p = 0.014; odds ratio, 0.15; 95% CI, 0.03-0.68) to be independently protective against CA aneurysms. Duration of fever prior to diagnosis, considered in 210 patients, was different between patients with and without aneurysms (11 +/- 5.3 vs 6.5 +/- 3.8 days, respectively, p = 0.0007). Multivariate logistic regression found fever longer than 5 days to be the only predictive factor associated with the development of aneurysms and any abnormality. African Americans had a shorter duration of fever than the rest of the cohort (6.03 vs 7.31 days), (p = 0.0087). The epidemiology of KD at our hospital is similar to that at other centers except for the predominance of African Americans with a shorter duration of fever prior to diagnosis and a decreased incidence of CA aneurysms compared to other ethnicities. The protective nature of African American ethnicity against the development of CA aneurysms raises speculation about the role of genetics and its interaction with immunity in the pathogenesis of KD.

Caspofungin is a parenteral antifungal that inhibits beta-1,3-D-glucan synthesis. Although licensed for adult use, the appropriate caspofungin dosing regimen in pediatric patients is not yet known. We therefore investigated the pharmacokinetics and safety of caspofungin in pediatric patients. Thirty-nine children (ages 2 to 11 years) and adolescents (ages 12 to 17 years) with neutropenia were administered caspofungin using either a weight-based regimen (1 mg/kg of body weight/day) or a body surface area regimen (50 mg/m2/day or 70 mg/m2/day). Plasma samples for caspofungin profiles were collected on days 1 and 4. These results were compared to those from adults treated with either 50 or 70 mg/day for mucosal candidiasis. In children receiving 1 mg/kg/day (maximum, 50 mg/day), the area under the concentration-time curve over 24 h (AUC(0-24)) was significantly smaller (46% after multiple doses) than that observed in adults receiving 50 mg/day (P < 0.001). In children and adolescents receiving 50 mg/m2/day (maximum, 70 mg/day), the AUC(0-24) following multiple doses was similar to that for the exposure in adults receiving 50 mg/day. The AUC(0-24) and concentration trough (at 24 h) in pediatric patients receiving the 50-mg/m2 daily regimen were consistent across the range of ages. Caspofungin was generally well tolerated in this study. None of the patients developed a serious drug-related adverse event or were discontinued for toxicity. These results demonstrate that caspofungin at 1 mg/kg/day in pediatric patients is suboptimal. Caspofungin administration at 50 mg/m2/day provides a comparable exposure to that of adult patients treated with 50 mg/day.

Background: Invasive candidiasis is a common and serious complication of cancer and its therapy., Methods: We retrospectively identified patients with malignancies enrolled in a double-blind randomized trial of caspofungin (50 mg/day after a 70 mg loading dose) vs. conventional amphotericin B (0.6-1.0 mg/kg/day) as treatment of documented invasive candidiasis. A favorable response required complete resolution of signs and symptoms plus eradication of the Candida pathogen(s). The primary efficacy analysis used a modified intention-to-treat (MITT) approach that included all patients with a confirmed diagnosis of invasive candidiasis who received > or =1 dose of study medication., Results: 74/224 (33%) patients in the MITT population had active malignancies. 25/30 (83%) hematological malignancies were acute or chronic leukaemias. 22/44 (50%) solid tumors were related to the gastrointestinal tract. Patients with hematological malignancies tended to be younger (median [range] age: 49 [19-74] vs. 59 [19-81] years) and have higher baseline acute physiology and chronic health evaluation (APACHE) II scores (mean [range]: 17 [0-28] vs. 15 [5-35]) than patients with solid tumors. Neutropenia [< or =500/microl] was present on entry in 23 (77%) patients with hematological malignancies and in one (3%) patient with a solid tumor. Candidemia was demonstrated in 56 (88%) cancer patients. C. albicans was the single most frequent isolate in cancer patients, although the majority of cases were caused by non-albicans species. Cancer patients in the caspofungin arm had more hematological malignancies (55 vs. 29%), higher baseline APACHE II scores (>20 in 36 vs. 15%), more frequent neutropenia (42 vs. 24%), and less C. albicans infections (27 vs. 49%) than the amphotericin B-treated cancer patients. Favorable response rates were 11/18 (61%) and 6/12 (50%) for patients with hematological malignancies treated with caspofungin or amphotericin B, respectively; the corresponding outcomes in patients with solid tumors were 12/15 (80%) and 17/29 (59%) for the 2 treatment arms. 7/14 (50%) caspofungin- and 4/10 (40%) amphotericin B-treated patients who were neutropenic on entry responded favorably. All-cause mortality rates during the study for caspofungin recipients were 11/18 (61%) with hematological malignancies and 6/15 (40%) with solid tumors, and for amphotericin recipients were 4/12 (33%) with hematological malignancies and 6/29 (21%) with solid tumors., Conclusions: Underlying cancers, most commonly leukaemias and gastrointestinal tumors, were present in one-third of patients enrolled in this study of invasive candidiasis. Overall, 70% of caspofungin-treated and 56% of amphotericin B-treated cancer patients responded favorably. Response rates were lower for neutropenic leukaemic patients than for non-neutropenic patients with solid tumors in both treatment groups.

Objectives: The objective was to prospectively assess the efficacy and safety of caspofungin as salvage therapy for invasive aspergillosis in patients enrolled in the caspofungin compassionate-use study., Methods: Forty-eight patients with invasive Aspergillus infections (36 with pulmonary infection, 12 with extrapulmonary or disseminated infection) were enrolled in this study. All patients were refractory to or intolerant of intravenous amphotericin B or a lipid amphotericin formulation(s). Efficacy was assessed at end of intravenous caspofungin therapy based on the clinical (symptom/sign and radiographic) response., Results: Underlying diseases included hematological malignancy (69%), organ transplant (8%), and AIDS (6%). Forty-three (90%) patients were refractory to prior antifungal treatment, including 25 patients refractory to multiple agents. Sixteen (33%) were neutropenic at study entry. Following caspofungin therapy, a favorable response was noted in 44% (20/45) of the patients, including nine (20%) and 11 (24%) patients with complete and partial responses, respectively. Caspofungin was generally well tolerated one serious drug-related adverse event was reported., Conclusions: In this study, caspofungin was an effective alternative for patients with refractory Aspergillus infections.

Prompt diagnosis of children with suggested cardiac disease in the acute care setting is critical for initiation of life-saving therapy. We hypothesized that pediatric critical care physicians could perform limited portable echocardiography in children. Portable hand-carried cardiac ultrasound units with 2.5-MHz phased-array transducers were used (Optigo, Philips Medical Systems, Andover, Mass). Noncardiologists were trained through a 1-hour introductory course and 2 hours of practical training. Portable echocardiography performed by noncardiologists was compared with a standard echocardiogram for diagnostic accuracy. In all, 23 patients (age 3 months-20 years) were screened during 18 months. The presence or absence of a pericardial effusion was correctly diagnosed in 21 of 23 patients (91%). Left ventricular size was correctly determined in 22 of 23 patients (96%). Left ventricular systolic function was correctly diagnosed in 22 of 23 patients (96%). These results show that, with appropriate instruction, pediatric critical care physicians are effective using limited portable echocardiography.

Hearts from 1-yr-old Erythrocebus patas monkeys were examined after in utero and 6-wk-postbirth exposure to antiretroviral nucleoside reverse transcriptase inhibitors (NRTIs). Protocols were modeled on those given to human immunodeficiency virus (HIV)-1-infected pregnant women. NRTIs were administered daily to the dams for the last 20% or 50% of gestation, and to the infants for 6 wk after birth. Exposures included: no drug (n = 4); Zidovudine, 3'-azido-3'-deoxythymidine (AZT; n = 4); AZT/Lamivudine, (-)-beta-L-2', 3'-Dideoxy-3'-thiacytidine (Epivir, 3TC) (n = 4); AZT/Didanosine (Videx, ddI) (n = 4); and Stavudine (Zerit, d4T)/3TC (n = 4). Echocardiograms and clinical chemistry showed no drug-related changes, but the d4T/3TC-exposed fetuses at 6 and 12 mo had increased white cell counts (p < 0.05). At 1 yr of age, oxidative phosphorylation (OXPHOS) enzyme activities were similar in heart mitochondria from all groups. Mitochondrial pathology, that included clones of damaged mitochondria (p < 0.05), was found in hearts of all 1-yr drug-exposed infants. Levels of mtDNA were elevated (p < 0.05) in hearts of all NRTI-exposed monkeys in the following order: control < d4T/3TC < AZT < AZT/3TC < AZT/ddI. The clinical status of NRTI-exposed infants, as evidenced by behavior, clinical chemistry, OXPHOS activity and echocardiogram, was normal. However, extensive mitochondrial damage with clusters of similar-appearing damaged heart mitochondria observed by electron microscopy, and an increase in mtDNA quantity, that persisted at 1 yr of age, suggest the potential for cardiotoxicity later in life.

Background: Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised patients. Echinocandins are novel antifungal molecules with in vitro and in vivo activity against Aspergillus species., Methods: We investigated the efficacy and safety of caspofungin in the treatment of IA. Ninety patients with IA who were refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B, or triazoles were enrolled to receive caspofungin., Results: Efficacy was assessed for 83 patients who had infection consistent with definitions of IA and who received >or=1 dose of study drug. Common underlying conditions included hematologic malignancy (48% of patients), allogeneic blood and marrow transplantation (25% of patients), and solid-organ transplantation (11% of patients). Seventy-one patients (86%) were refractory to and 12 patients (14%) were intolerant of previous therapy. A favorable response to caspofungin therapy was observed in 37 (45%) of 83 patients, including 32 (50%) of 64 with pulmonary aspergillosis and 3 (23%) of 13 with disseminated aspergillosis. Two patients discontinued caspofungin therapy because of drug-related adverse events. Drug-related nephrotoxicity and hepatotoxicity occurred infrequently., Conclusion: Caspofungin demonstrated usefulness in the salvage treatment of IA.

Background: Live transmission of echocardiograms over integrated services digital network lines is accurate and has led to improvements in the delivery of pediatric cardiology care. Permanent archiving of the live studies has not previously been reported. Specific obstacles to permanent storage of telemedicine files have included the ability to produce accurate images without a significant increase in storage requirements., Objective: We evaluated the accuracy of Motion Pictures Expert Group (MPEG) digitization of incoming video streams and assessed the storage requirements of these files for infants in a real-time pediatric tele-echocardiography program., Results: All major cardiac diagnoses were correctly diagnosed by review of MPEG images. MPEG file size ranged from 11.1 to 182 MB (56.5 +/- 29.9 MB)., Conclusions: MPEG digitization during live neonatal telemedicine is accurate and provides an efficient method for storage. This modality has acceptable storage requirements; file sizes are comparable to other digital modalities.

Objectives: To prospectively assess the efficacy and safety of caspofungin as second-line therapy for mucosal or invasive candidiasis in patients enrolled in the caspofungin compassionate-use study., Materials and Methods: Thirty-seven patients with mucosal or invasive candida infections (17 oesophageal, four oropharyngeal and 16 invasive candidiasis) were enrolled in the caspofungin compassionate-use study. All patients were refractory to or intolerant of intravenous amphotericin B or lipid amphotericin formulation(s). Efficacy was assessed at the end of intravenous caspofungin therapy based on clinical (and, where appropriate, microbiological) response., Results: HIV was the most common (91%) risk factor in patients with mucosal candidiasis; patients with invasive candidiasis commonly had acute leukaemia/lymphoma (50%) or diabetes mellitus (31%). Most patients with mucosal candidiasis (91%) and invasive candidiasis (94%) were refractory to >/=1 antifungal agent(s). A favourable response was noted in 82% (14/17) with oesophageal candidiasis, 100% (4/4) with oropharyngeal candidiasis and 87% (13/15) with invasive candidiasis. Caspofungin was generally well tolerated; one serious drug-related adverse event was reported., Conclusion: In this study, caspofungin was an effective alternative for patients with refractory candida infections.

An arterial switch is the corrective procedure of choice for d-transposition of the great arteries but may be associated with increased morbidity and mortality when performed in low-birth-weight infants. Conversely, delaying surgery often leads to left ventricular "deconditioning" as pulmonary arteriolar resistance decreases. We present an infant with a birth weight of 940 g with d-transposition of the great arteries with an intact ventricular septum whose bilateral pulmonary artery branch stenosis allowed for maintenance of near systemic left ventricular pressure, thereby protecting against deconditioning. This case also represents the smallest reported patient to undergo a successful balloon atrial septostomy.

Caspofungin is a new echinocandin drug with comparable in vitro activity against azole-susceptible and -resistant isolates of that could provide a less toxic alternative to amphotericin B for the management of esophageal candidiasis with clinical or laboratory evidence of decreased susceptibility to fluconazole. The authors retrospectively analyzed its efficacy in adults with endoscopically documented esophagitis from four Phase II and III studies using two definitions of resistance to fluconazole: 1) clinically refractory infection based on failure of esophageal symptoms to improve despite at least 1 week of >or=200 mg/d of fluconazole; or 2) microbiologically resistant infection with either "susceptible dose-dependent" or "resistant" isolates based on MICs of 16 to 32 and >or=64 microg fluconazole/mL, respectively. A favorable response required resolution of all symptoms and substantial improvement in endoscopic findings. Seven of 11 patients (64%) who had been clinically refractory to fluconazole had favorable responses to caspofungin. Eleven of 14 patients (79%) whose isolates had decreased susceptibility to fluconazole had favorable responses to caspofungin, including 5 (83%) of 6 patients infected by isolates with MICs of >or=64 microg fluconazole/mL. Caspofungin appeared to be efficacious therapy for some patients with esophageal candidiasis who were clinically refractory to fluconazole or infected by with reduced susceptibility to fluconazole in vitro.

Caspofungin is a new antifungal drug of the echinocandin class. We analyzed the clinical efficacy of caspofungin (50 mg/day) in the treatment of HIV-infected adults with endoscopically documented Candida esophagitis and enrolled in four clinical trials of caspofungin. Symptoms were evaluated daily; a favorable outcome required complete resolution of all esophageal symptoms assessed at the time of discontinuation of therapy. Relapse was defined as recurrent symptoms during the subsequent 2 weeks. A multivariate logistic regression model was developed to identify potential factors (including severity of symptoms at presentation, CD4(+) cell count on entry, extent of disease [assessed endoscopically at baseline], causative Candida species, duration of therapy [overall and after resolution of symptoms], time on treatment before symptom resolution, and antifungal prophylaxis) that might predict symptomatic relapse in the 2 weeks following completion of therapy. The median CD4(+) lymphocyte count for the entire population was 31/mm(3). Candida albicans was isolated from 109 of 110 patient samples cultured for the pathogen and constituted the sole isolate in 77%. Extensive esophageal involvement was present in 55% of patients at the time of pretreatment endoscopy. The duration of therapy ranged from 7 to 20 days (median, 12 days). Symptoms resolved in 117 of 123 patients (95%; 95% confidence interval, 90-98%) with a median time of ~4 days. Response rates were 43 of 46 (93%) and 70 of 73 (96%) for patients with greater or fewer than 50 CD4(+) cells/mm(3), and 80 of 85 (94%) and 23 of 24 (96%) in infections caused by C. albicans alone or in association with non-albicans isolates, respectively. Symptoms recurred within 2 weeks of stopping caspofungin in 19 of 115 evaluable patients (17%), including 3 of 16 (19%) receiving antifungal prophylaxis. Relapse rates were similar for patients with greater or fewer than 50 CD4(+) cells/mm(3). In this relatively small number of patients, only symptom severity and extent of disease judged endoscopically at baseline were significantly (p < 0.10) associated with early relapse in the multivariate model.

Background: Candida esophagitis remains an important cause of morbidity in patients with advanced human immunodeficiency virus (HIV) infection. Fluconazole is widely regarded as the treatment of choice for this condition., Methods: The efficacy and safety of caspofungin were compared with fluconazole in adult patients with Candida esophagitis in a double-blind randomized trial. Eligible patients had symptoms compatible with esophagitis, endoscopic demonstration of mucosal plaques, and microscopic demonstration of Candida from the esophageal lesions. Patients were randomly assigned to receive caspofungin (50 mg) or fluconazole (200 mg) intravenously once daily for 7 to 21 days. The primary endpoint was the combined response of symptom resolution and significant endoscopic improvement 5 to 7 days after discontinuation of treatment. Data were analyzed with a modified intention-to-treat analysis, which excluded 2 ineligible patients., Results: Most patients (154/177; 87%) had HIV infection, with a median CD4 count of 30 cells/mm(3). Candida albicans was the predominant isolate. Favorable response rates were achieved in 66 (81%) of the 81 patients in the caspofungin arm and in 80 (85%) of the 94 patients in the fluconazole arm (difference = -4%; 95% confidence interval: -15% to +8%). Symptoms had resolved in >50% of patients in both groups by the fifth day of treatment. No patient in the caspofungin group developed a serious drug-related adverse event; therapy was only discontinued in 1 patient (receiving fluconazole) due to a drug-related adverse experience. Four weeks after stopping study drug, symptoms had recurred in 18 (28%) of 64 patients given caspofungin and in 12 (17%) of 72 patients given fluconazole (P = 0.19)., Conclusions: In this study, caspofungin appeared to be as efficacious and generally as well tolerated as fluconazole in patients with advanced HIV infection and documented Candida esophagitis.

Caspofungin acetate is the first member of the novel echinocandin class of antifungal drugs to be marketed in the United States. It has recently been approved for use in patients with invasive aspergillosis who are refractory to or intolerant of conventional therapy. Accordingly, its safety profile is particularly important to review. The safety and tolerability of caspofungin have been examined in 623 persons, including 295 patients who received >/= 50 mg/day for at least one week in clinical studies. In the 263 patients, given caspofungin in randomized double-blind active-control trials to date, there have been no serious clinical or laboratory drug-related adverse events; caspofungin was discontinued in only 2% of these patients because of drug-related adverse experiences. Caspofungin may have potentially important drug interactions with cyclosporine and tacrolimus.

Caspofungin is an antifungal agent of the novel echinocandin class. We investigated its efficacy, safety, and tolerability as therapy for oropharyngeal and/or esophageal candidiasis in a phase II dose-ranging study. Patients were randomized in a double-blind manner to receive either caspofungin acetate (35, 50, or 70 mg) or amphotericin B (0.5 mg/kg of body weight) intravenously once daily for 7 to 14 days. A favorable response required both complete resolution of symptoms and quantifiable improvement of mucosal lesions 3 to 4 days after discontinuation of study drug. Efficacy was assessed using a modified intent-to-treat analysis. No hypothesis testing of efficacy was planned or performed. Of 140 enrolled patients, 63% had esophageal involvement and 98% were infected with the human immunodeficiency virus (HIV) (median CD4 count, 30/mm(3)). A modestly higher proportion of patients in each of the caspofungin groups (74 to 91%) achieved favorable responses compared to amphotericin B recipients (63%), but there was considerable overlap in the 95% confidence intervals surrounding these point estimates. Similar trends were found in the subgroups with esophageal involvement, a history of fluconazole failure, and CD4 counts of < or =50/mm(3). A smaller proportion of patients receiving any dose of caspofungin experienced drug-related adverse events compared to patients given standard doses of conventional amphotericin B (P < 0.01). Caspofungin provided a generally well-tolerated parenteral therapeutic option for HIV-infected patients with oropharyngeal and/or esophageal candidiasis in this study.

Background: Tele-echocardiography has the potential to bring real-time diagnoses to neonatal facilities without in-house pediatric cardiologists. Many neonates in rural areas, smaller cities, and community hospitals do not have immediate access to pediatric sonographers or echocardiogram interpretation by pediatric cardiologists. This can result in suboptimal echocardiogram quality, delay in initiation of medical intervention, unnecessary patient transport, and increased medical expenditures. Telemedicine has been used with increased frequency to improve efficiency of pediatric cardiology care in hospitals that are not served by pediatric cardiologists. Initial reports suggest that telecardiology is accurate, improves patient care, is cost-effective, enhances echocardiogram quality, and prevents unnecessary transports of neonates in locations that are not served by pediatric cardiologists., Objective: We report the largest series to evaluate the impact of telemedicine on delivery of pediatric cardiac care in community hospitals. We hypothesized that live telemedicine guidance and interpretation of neonatal echocardiograms from community hospitals is accurate, improves patient care, enhances sonographer proficiency, allows for more efficient physician time management, increases patient referrals, and does not result in increased utilization of echocardiography., Methods: Using desktop videoconferencing computers, pediatric cardiologists guided and interpreted pediatric echocardiograms from 2 community hospital nurseries 15 miles from a tertiary care center. Studies were transmitted in real-time using the H.320 videoconferencing protocol over 3 integrated services digital network lines (384 kilobits per second). This resulted in a frame rate of 23 to 30 frames per second. Sonographers who primarily scanned adult patients but had received additional training in echocardiography of infants performed the echocardiograms. Additional views were suggested as deemed necessary by the interpreting physician, and interpretations were made during the videoconference. The results of the echocardiogram and recommendations for patient care were communicated to the referring physician over the telemedicine system. Analyses of accuracy, patient treatment, echocardiogram quality, time to diagnosis, pediatric cardiologist practice time management, patient referral patterns, and echocardiography utilization were conducted prospectively., Results: A total of 500 studies in 364 patients were transmitted during a 30-month period. The most common indication for echocardiography was to rule out congenital heart disease (208 of 500 studies). Signs and symptoms that prompted this concern included cyanosis, murmur, tachypnea, genetic syndrome, arrhythmia, abnormal fetal echocardiogram, and maternal diabetes. Other indications included suspected patent ductus arteriosus (PDA; 182 of 500 studies), intracardiac clot or catheter position, persistent pulmonary hypertension, and hemodynamic instability. Cardiac diagnoses included complex congenital heart disease (n = 16), noncritical heart disease (n = 107), and PDA (n = 86). Additional diagnoses included persistent pulmonary hypertension (n = 12), septal hypertrophy (n = 18), right atrial mass/clot/vegetation (n = 11), and decreased cardiac function (n = 6). An umbilical venous catheter was visualized in the left atrium in 9% (45 of 500) of all studies. No significant abnormalities were found in 244 studies. Major diagnoses were confirmed by subsequent review of videotape in all studies. Comparison of final videotape interpretation to initial telemedicine diagnosis resulted in 1 minor diagnostic change (membranous versus inlet ventricular septal defect). Echocardiograms were performed in subsequent visits in 264 patients. The diagnosis was altered in 3 patients. Telemedicine had an immediate impact on patient care in 151 transmissions. The most common interventions were indomethacin treatment for PDA (n = 76), retraction of umbilical venous catheters from the left atrium (n = 45), inotropic or anticongestive therapy (n = 19), anticoagulation (n = 8), and prostaglandin infusion (n = 8). Nineteen patients were transported to our hospital because of the telemedicine diagnosis. Inpatient or outpatient cardiology follow-up was recommended in an additional 131 studies and did not result in any change in the initial management. The most common diagnoses in these patients were ventricular septal defect (n = 56), atrial septal defect (n = 21), septal hypertrophy (n = 9), intracardiac thrombosis (n = 8), and pulmonary valve stenosis (n = 4). We speculate that the immediate availability of an echocardiographic diagnosis likely prevented unnecessary transport in 14 cases. Recommendations for additional views or adjustment of echocardiography machine settings were made in 95% of transmissions. Real-time guidance was especially helpful in suprasternal notch and subcostal sagittal imaging. Depth, color Doppler sector size, and color Doppler scale were frequently adjusted from routine adult settings during the teleconference. The average time from request for echocardiogram to completion of the videoconference was 28 +/- 14 minutes. This was significantly shorter than the waiting time (12 +/- 16 hours) for the videotape to be delivered by courier. Telemedicine eliminated the need for consultation in 194 cases and allowed the cardiologist to delay the visit until the end of the day in an additional 26 cases. This resulted in average time savings of 4.2 person-hours/wk based on travel and consultation time. Utilization of echocardiography was similar before (35 of 1000 births) and after (33 of 1000 to 43 of 1000) telemedicine installation. The percentage of neonatal echocardiograms that were interpreted by our practice increased from 63% to 81% at 1 hospital and from 0% to 100% at the other hospital., Conclusion: Real-time transmission of neonatal echocardiograms from community hospitals over 3 integrated services digital network lines is accurate and has the potential to improve patient care, enhance echocardiogram quality, aid sonographer education, and have a positive impact on referral patterns and time management without increasing the utilization of echocardiography.

Caspofungin is a new broad-spectrum antifungal drug. A multicenter, double-blind, randomized trial was conducted to assess the efficacy, safety, and tolerability of caspofungin relative to amphotericin B in adults with endoscopically documented symptomatic Candida esophagitis. By use of a modified intent-to-treat analysis, endoscopically verified clinical success was achieved in 74% (95% confidence interval [CI], 59%-86%) and 89% (95% CI, 72%-98%) of patients receiving caspofungin at 50 and 70 mg/day, respectively, and in 63% (95% CI, 49%-76%) of patients given amphotericin B at 0.5 mg/kg/day. Therapy was stopped because of drug-related adverse events in 24% of patients in the amphotericin B group and 4% and 7%, respectively, for the caspofungin groups. This report provides the first demonstration of clinical utility for an echinocandin compound. Caspofungin appeared in this study to be as effective as and better tolerated than amphotericin B for the treatment of esophageal candidiasis.

Paroxysmal atrial fibrillation and atrial tachycardia may originate from a focal source in one or multiple pulmonary veins. A focal origin facilitates a potential cure amendable to radiofrequency ablation. Herein we report the case of a 16 year old adolescent male with a tachycardia induced cardiomyopathy who presented with very frequent paroxysmal episodes of atrial fibrillation, atrial flutter and atrial tachycardia. The origin of the arrhythmia was mapped to the secondary branches of the left lower pulmonary vein using an octapolar micro-mapping catheter. Immediately following application of three radiofrequency lesions, angiography of the left lower pulmonary vein revealed a region of focal stenosis at the site of energy application, with delayed pulmonary venous emptying. Attempts to relieve any element of spasm using direct administration of nitroglycerin were unsuccessful. Three months later repeat catheterization revealed an unchanged region of tight anatomical stenosis. Balloon dilation of two stenotic areas resulted in dramatic relief of the obstruction and improved venous drainage. Recatheterization 6 months later revealed mild restenosis that was successfully redilated. Intracardiac ultrasound demonstrated focal constriction. Care should be exercised in attempting RF ablation in distal arborization sites of the pulmonary veins in children, because of the small caliber compared to adult subjects. Radiofrequency induced focal areas of stenosis may be amenable to balloon catheter dilation.

Objectives: This study analyzed waiting times and outcomes of neonates listed for heart transplantation at two medical centers from 1991 through 1994., Study Design: Retrospective analysis was performed to examine waiting times, charges, morbidity, and outcomes., Results: Of the 30 neonates listed for transplantation, 15 received hearts, with 10 late survivors. Waiting time increased from 25 +/- 8 days in 1991 and 1992 to 58 +/- 7 days in 1993 and 1994 (p < 0.01), and the hospital charge per patient increased from $118,300 +/- $31,500 to $198,700 +/- $25,400 (p < 0.05). Freedom from sepsis predicted receiving heart transplantation (p < 0.01). Lack of a preoperative central intravenous catheter, no preoperative mechanical ventilation, and A-negative blood type predicted heart transplantation survival (p < 0.05). The chances of receiving and surviving transplantation were the same in the two periods. There was a trend toward greater morbidity among neonates waiting more than 35 days., Conclusions: Waiting times and charges have increased significantly over the last 4 years. Patients who are free of sepsis, lack a preoperative central intravenous catheter, are not mechanically ventilated preoperatively, and have A-negative blood type have better outcomes.

Emerging infections are defined as infections that are newly identified or recognized, or those whose incidence in humans has significantly increased over the past 20 years. The interaction of several factors contributes to the emergence of infectious disease, including changes in human behavior, technological advances, economic development, increased international travel, microbial adaptation and lapses in public health measures. Biomedical research has allowed us to identify and classify previously uncultured pathogens, characterize microbial virulence factors, create new diagnostic tests and develop vaccines. Here, we highlight a few emerging infections and illustrate the role that molecular medicine has played in furthering our understanding of these diseases.

Three patients with severe lower respiratory tract influenza or parainfluenzavirus infections were treated with continuous ribavirin infusion, given as a 5 mg/kg/hour (h) loading infusion for 8 h followed by 1.5 mg/kg/h for 2 to 6 days. This regimen was generally well tolerated. Plasma ribavirin concentrations were 40 to 60 microM in two patients during the continuous infusion phase and lower concentrations were detectable in tracheobronchial secretions. In temporal association with ribavirin administration, viral shedding diminished in one patient and ceased in two patients, one of whom had developed virus resistant to amantadine. The strategy of continuous ribavirin infusion warrants controlled testing for its antiviral and possible clinical effectiveness.

In summary, orthomyxo- and paramyxoviruses cause clinically important infections in transplant patients. Patients often develop lower respiratory tract involvement and sometimes respiratory failure, which almost is uniformly fatal. Bone marrow transplant recipients appear to be at higher risk of severe disease than are solid-organ recipients, but well defined criteria to predict those patients who will be severely affected are not available. Factors associated with more severe disease include the type of viral pathogen, with pneumonia occurring more commonly with RSV and PIV infection, and the degree of immunosuppression of the patient, particularly the pre-engraftment phase in bone marrow transplant recipients. Because mortality is associated with development of pneumonia, prompt diagnosis and studies for concurrent infections are essential. Evaluation of fever and upper respiratory tract symptoms in patients in the peritransplant period should include sampling of nasopharyngeal and throat for virus isolation and antigen detection for respiratory viruses. If patients develop lower respiratory tract symptoms, early bronchoscopy with BAL is indicated. No specific antiviral therapy has proved effective in the treatment of established respiratory viral infections of transplant patients. Aerosolized ribavirin or, in the instance of influenza A virus infection, oral rimantadine might be considered as early therapy to prevent severe lower respiratory disease. Intravenous ribavirin, currently available on a compassionate use basis, might be considered for treating measles virus infection. In patients with lower tract disease due to RSV, the addition of immunoglobulin with high neutralizing antibody titers to RSV or intravenous ribavirin are additional considerations to forestall respiratory failure. Controlled studies of these interventions are needed in transplant patients before their use can be recommended routinely.

The role of transthoracic echocardiography as a diagnostic tool in children suspected of having infective endocarditis (IE) has not been defined. We hypothesized that echocardiography is only useful in children in whom there is high clinical suspicion of IE based on physical examination findings or persistently positive blood cultures. Echocardiographic reports and medical records of all inpatients (n = 133) from 1990 to 1992 who underwent echocardiography for suspected IE were reviewed. Fifty-nine of the 133 patients (44%) identified had either persistently positive blood cultures (n = 48), physical examination findings of IE (n = 20), or both (n = 9). The echocardiogram was positive in 7 of these patients (12%) and negative in all 74 patients without positive physical findings or positive blood cultures (p = 0.003). A new or changing precordial murmur, embolic phenomena, congestive heart failure, mechanical ventilation, and positive blood cultures were predictive of positive echocardiograms for IE by univariate analysis. The presence of fever, immune deficiency, and central lines, alone or in combination, was not predictive of a positive echocardiogram. In the absence of physical findings or persistently positive blood cultures, echocardiography is a low-yield study and is unlikely to aid in the diagnosis of IE in children.

Background: The incidence of infection increases with the prolonged use of central vascular catheters, but it is unclear whether changing catheters every three days, as some recommend, will reduce the rate of infection, It is also unclear whether it is safer to change a catheter over a guide wire or insert it at a new site., Methods: We conducted a controlled trial in adult patients in intensive care units who required central venous or pulmonary-artery catheters for more than three days. Patients were assigned randomly to undergo one of four methods of catheter exchange: replacement every three days either by insertion at a new site (group 1) or by exchange over a guide wire (group 2), or replacement when clinically indicated either by insertion at a new site (group 3) or by exchange over a guide wire (group 4)., Results: Of the 160 patients, 5 percent had catheter-related bloodstream infections, 16 percent had catheters that became colonized, and 9 percent had major mechanical complications. The incidence rates (per 1000 days of catheter use) of bloodstream infection were 3 in group 1, 6 in group 2, 2 in group 3, and 3 in group 4; the incidence rates of mechanical complications were 14, 4, 8, and 3, respectively. Patients randomly assigned to guide-wire-assisted exchange were more likely to have bloodstream infection after the first three days of catheterization (6 percent vs. 0, P = 0.06). Insertions at new sites were associated with more mechanical complications (5 percent vs. 1 percent, P = 0.005)., Conclusions: Routine replacement of central vascular catheters every three days does not prevent infection. Exchanging catheters with the use of a guide wire increases the risk of bloodstream infection, but replacement involving insertion of catheters at new sites increases the risk of mechanical complications.

In summary, an increased understanding of the pathogenesis and pathophysiology of septic shock has led to the development and evaluation of potential adjunctive therapies. Although several agents show promise in certain experimental settings, definitive recommendations regarding the use of these agents are not yet possible. Although several therapies have shown benefit when the subject receives treatment prior to the onset of sepsis, most have had varying degrees of success following the development of septicemia.