Outcomes attributable to neonatal candidiasis.

BACKGROUND: The incidence of candidiasis has increased in neonatal intensive care units, and invasive candidiasis is associated with significant morbidity and mortality. However, few data exist on outcomes directly attributable to neonatal candidiasis. METHODS: We estimated the incidence of systemic candidiasis in hospitalized neonates within the United States and determined the attributable mortality, length of hospital stay, and associated costs. We used the 2003 Kid's Inpatient Database from the Healthcare Cost and Utilization Project. Systemic candidiasis and comorbidities were defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Neonates with uncomplicated births and neonates who died within the first 3 days of life were excluded. We used propensity score methods to balance covariates between the neonates with and neonates without candidiasis. Attributable outcomes were calculated between propensity score-matched neonates with and neonates without candidiasis. Because of the known confounding effect of birth weight, we performed separate propensity score analyses for extremely low birth weight (ELBW) neonates (i.e., neonates weighing < 1000 g). RESULTS: The overall incidence of invasive candidiasis in neonates is 15 cases per 10,000 neonatal admissions (95% confidence interval [CI], 13-16 cases per 10,000 neonatal admissions). ELBW neonates with invasive candidiasis were 2 times more likely to die (odds ratio, 2.2; 95% CI, 1.4-3.5) than propensity-matched ELBW neonates without candidiasis. The propensity score-adjusted mortality rate attributable to candidiasis among ELBW neonates was 11.9%. Candidiasis in ELBW infants was not associated with an increase in length of hospital stay but was associated with a mean increase in total charges of $39,045 (95% CI, $1374-$76,715). Among infants with a birth weight > or = 1000 g, those who had candidiasis did not experience a significant increase in mortality, compared with infants without candidiasis. However, the propensity score-adjusted length of stay and charges attributable to candidiasis among neonates with a birth weight > or = 1000 g were 16 days (95% CI, 8-24 days) and $122,302 (95% CI, $80,457-$164,148), respectively. CONCLUSIONS: Invasive candidiasis is associated with a significantly increased risk of death and excess hospital charges in ELBW neonates and with excess hospital stay and excess hospital charges in neonates with a birth weight > or = 1000 g.

Neurologic complications in children hospitalized with influenza: characteristics, incidence, and risk factors.

OBJECTIVE: To determine the characteristics, incidence, and risk factors for influenza-related neurologic complications (INC). STUDY DESIGN: A retrospective cohort study of INC in children hospitalized with laboratory-confirmed influenza infection (LCI) from June 2000 to May 2004 was conducted. Systematic chart review was performed to identify clinical characteristics and outcomes. A neighborhood cohort was constructed to estimate the incidence of INC. Logistic regression was used to identify independent risk factors for INC. RESULTS: Of 842 patients with LCI, 72 patients had an INC: influenza-related encephalopathy (8), post-infectious influenza encephalopathy (2), seizures (56), and other (6). Febrile seizures were the most common type of seizures (27). No patient died from an INC. In our neighborhood cohort, the incidence of INC was 4 cases per 100,000 person-years. An age of 6 to 23 months (odds ratio [OR], 4.2; 95% CI, 1.4-12.5) or 2 to 4 years (OR, 6.3; 95% CI, 2.1-19.1) and an underlying neurologic or neuromuscular disease (OR, 5.6; 95% CI, 3.2-9.6) were independent risk factors for the development of INC. CONCLUSION: Seizures are the most common neurologic complication experienced by children hospitalized with influenza. In the United States, encephalopathy is uncommon. Young children and patients with neurologic or neuromuscular disease are at increased risk for INC.

Observational trial of antibiotic-coated central venous catheters in critically ill pediatric patients.

BACKGROUND: Catheter-associated bloodstream infections (CABSI) are among the most common and serious adverse events experienced by critically ill children. Randomized trials have demonstrated that the use of central venous catheters (CVC) coated with antiseptic solutions reduces rates of CABSI in adult patients; however, their efficacy in children has not been evaluated. OBJECTIVE: To compare the incidence of CABSI, rate of complications, and microbiology of infection in critically ill children treated with antibiotic-coated or noncoated CVC (NC-CVC). METHODS: A prospective observational trial was conducted in the pediatric intensive care unit (PICU) during a 13-month period. A minocycline-rifampin-coated CVC (MR-CVC) or NC-CVC was placed by PICU physicians who nonpreferentially selected CVC type. RESULTS: We studied the outcomes associated with the first CVC placed in 225 patients, including 69 MR-CVC and 156 NC-CVC. Patients who received MR-CVC, as compared with NC-CVC, were similar in gender, age, and severity of illness at time of PICU admission. The incidence density of CABSI did not vary by catheter type [MR-CVC: 7.53 per 1000 catheter-days (95% confidence interval 2.05-19.17); NC-CVC: 8.64 CABSI per 1000 catheter-days (95% confidence interval 3.74-16.96)]. However, the median time to infection in children with MR-CVC was 3-fold longer than in children with NC-CVC [18 versus 5 days (P = 0.053)]. No difference was seen in the incidence of complications, including thrombosis and catheter site reaction, between MR- and NC-CVC. No significant difference was observed in the types of organisms recovered from patients with MR- and NC-CVC. CONCLUSIONS: The use of MR-CVC significantly delayed the onset of CABSI in PICU patients. Larger, randomized trials are needed to better define potential differences in the incidence of CABSI, rate of complications, and microbiology of infection among pediatric patients treated with antiseptic-coated CVC and NC-CVC.

Hospitalizations for endemic mycoses: a population-based national study.

We performed a retrospective cohort study, using the 2002 Nationwide Inpatient Sample, a national database of hospital inpatient stays, to describe the incidence and epidemiology of endemic mycoses requiring hospitalization. An estimated 332 pediatric and 6003 adult patients with endemic mycoses required hospitalization (4.6 and 28.7 cases per 1 million children and adults, respectively). Crude mortality rates were 5% and 7% among children and adults, respectively.

Administrative data fail to accurately identify cases of healthcare-associated infection.

OBJECTIVE: Some policy makers have embraced public reporting of healthcare-associated infections (HAIs) as a strategy for improving patient safety and reducing healthcare costs. We compared the accuracy of 2 methods of identifying cases of HAI: review of administrative data and targeted active surveillance. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional prospective study was performed during a 9-month period in 2004 at the Children's Hospital of Philadelphia, a 418-bed academic pediatric hospital. "True HAI" cases were defined as those that met the definitions of the National Nosocomial Infections Surveillance System and that were detected by a trained infection control professional on review of the medical record. We examined the sensitivity and the positive and negative predictive values of identifying HAI cases by review of administrative data and by targeted active surveillance. RESULTS: We found similar sensitivities for identification of HAI cases by review of administrative data (61%) and by targeted active surveillance (76%). However, the positive predictive value of identifying HAI cases by review of administrative data was poor (20%), whereas that of targeted active surveillance was 100%. CONCLUSIONS: The positive predictive value of identifying HAI cases by targeted active surveillance is very high. Additional investigation is needed to define the optimal detection method for institutions that provide HAI data for comparative analysis.

Risk factors for mortality in children with candidemia.

We performed a retrospective cohort study of hospitalized children with positive blood cultures for Candida species. Independent risk factors for mortality by multivariable analysis were location in the pediatric intensive care unit at the time of infection (hazard ratio, 6.3; 95% confidence interval, 1.6-24.3) and the presence of an arterial catheter (hazard ratio, 2.4; 95% confidence interval, 1.1-5.8). Our findings help identify a group of pediatric patients that should be targeted for future interventions to prevent and treat candidemia.

Ki-67 staining index predicts distant metastasis and survival in locally advanced prostate cancer treated with radiotherapy: an analysis of patients in radiation therapy oncology group protocol 86-10.

PURPOSE: Proliferative activity defined by Ki-67 staining index (SI) has been correlated with progression and prognosis in a number of malignant tumors including prostate cancer. However, few studies have examined Ki-67 SI in pretreatment diagnostic material from patients treated with definitive radiotherapy. In a prior study, we found that a Ki-67 SI of >3.5% was associated with poorer patient outcome. The goals of this analysis were to validate the prognostic value of Ki-67 SI and this cut point. EXPERIMENTAL DESIGN: Of 456 assessable patients in Radiation Therapy Oncology Group Protocol 86-10, diagnostic material from 108 patients was available for Ki-67 analysis using MIB-1 antibody. Sixty patients were treated with external beam radiotherapy (EBRT) alone, and 48 patients were treated with short-term androgen deprivation + EBRT. Median follow-up was 9 years for those living. The relationship of Ki-67 with distant metastasis (DM), disease-specific survival (DSS), and overall survival (OS) was examined. RESULTS: The median Ki-67 SI was 7.1% (range, 0.2-45.5%). The 7.1% cut point was associated with DM and DSS; however, the 3.5% cut point was as strong a determinant and was the focus of this analysis. In Cox proportional hazards regression, Ki-67 SI was independently associated with DM and DSS. When the Ki-67 SI was 3.5%, the 5-year risk of DM was 13.5% and 50.8% (P = 0.0005), respectively, and the 5-year risk of DSS was 97.3% and 67.7% (P = 0.0039), respectively. No association of Ki-67 SI with OS was observed. CONCLUSIONS: Higher Ki-67 SI was significantly associated with a greater risk of DM and DSS in locally advanced prostate cancer after definitive EBRT or AD + EBRT.

Effect of a short course of neoadjuvant hormonal therapy on the response to subsequent androgen suppression in prostate cancer patients with relapse after radiotherapy: a secondary analysis of the randomized protocol RTOG 86-10.

PURPOSE: To compare, by a secondary analysis, the therapeutic benefits of androgen suppression in protocol prostate cancer patients with relapse after radiotherapy (RT) for locally advanced disease who, in the Phase III trial beginning in 1987, were assigned to receive or not receive a short course of neoadjuvant maximal androgen suppression before definitive RT. METHODS AND MATERIALS: Between 1987 and 1991, 456 patients were entered in the Radiation Therapy Oncology Group trail 86-10 and randomized to receive (Arm I) or not to receive (Arm II) neoadjuvant hormonal therapy (HT), which was 4 months of goserelin (3.6 mg every 4 weeks) and flutamide (250 mg t.i.d.) before and during RT for bulky T2-T4 tumors. The overall and disease-specific survival after both randomization and salvage HT for patients with relapse was evaluated, as well as the duration of response in those patients undergoing salvage HT. The outcomes in patients who had received neoadjuvant HT vs. those who had not were compared. The median follow-up after randomization for all alive patients was 9.0 years and was 5.5 years for alive patients after beginning salvage HT. RESULTS: Fewer patients received salvage HT on Arm I than on Arm II (45% vs. 63%, p <0.001). The outcomes by randomized treatment arm (I vs. II) from the time of beginning salvage HT were similar. At 5 years after salvage HT, the overall survival rates were 41% and 41% and the disease-specific survival rates were 50% and 50%. At 8 years after randomization, the overall survival rates were 47% and 44% and the disease-specific survival rates were 55% and 56%. CONCLUSION: Although a 4-month course of neoadjuvant and concurrent maximum androgen suppression and RT (compared with RT alone) significantly increases the freedom from relapse rate and freedom from receiving salvage HT, it does not compromise the long-term beneficial effect of subsequent salvage HT, if needed for relapse. These findings with long follow-up in patients treated for locally advanced disease diagnosed 9-14 years previously should help allay concerns of the possible development of "resistance" to androgen suppression when 4-month courses of neoadjuvant HT are used before primary treatment.

Incidence, complications, and risk factors for prolonged stay in children hospitalized with community-acquired influenza.

OBJECTIVES: Few studies have examined the characteristics and clinical course of children hospitalized with laboratory-confirmed influenza. We sought to (1) estimate the age-specific incidence of influenza-related hospitalizations, (2) describe the characteristics and clinical course of children hospitalized with influenza, and (3) identify risk factors for prolonged hospitalization. PATIENTS AND METHODS: Children < or = 21 years of age hospitalized with community-acquired laboratory-confirmed influenza at a large urban children's hospital were identified through review of laboratory records and administrative data sources. A neighborhood cohort embedded within our study population was used to estimate the incidence of community-acquired laboratory-confirmed influenza hospitalizations among children < 18 years old. Risk factors for prolonged hospitalization (> 6 days) were determined by using logistic regression. RESULTS: We identified 745 children hospitalized with community-acquired laboratory-confirmed influenza during the 4-year study period. In this urban cohort, the incidence of community-acquired laboratory-confirmed influenza hospitalization was 7 per 10,000 child-years of observation. The median age was 1.8 years; 25% were infants < 6 months old, and 77% were children < 5 years old. Many children (49%) had a medical condition associated with an increased risk of influenza-related complications. The incidence of influenza-related complications was higher among children with a preexisting high-risk condition than for previously healthy children (29% vs 21%). However, only cardiac and neurologic/neuromuscular diseases were found to be independent risk factors for prolonged hospitalization. CONCLUSIONS: Influenza is a common cause of hospitalization among both healthy and chronically ill children. Children with cardiac or neurologic/neuromuscular disease are at increased risk of prolonged hospitalization; therefore, children with these conditions and their contacts should be a high priority to receive vaccine. The impact on pediatric hospitalization of the new recommendation to vaccinate all children 6 months to < 5 years old should be assessed.

Epidemiology, outcomes, and costs of invasive aspergillosis in immunocompromised children in the United States, 2000.

OBJECTIVE: Invasive aspergillosis (IA) is the most common filamentous fungal infection observed in immunocompromised patients. The incidence of invasive aspergillosis has increased significantly in recent decades in parallel with the increasing number and improved survival of immunocompromised patients. IA in adults has been well characterized; however, only a few small studies of IA in children have been reported. Therefore, the objective of this study was to describe the incidence and outcomes of children with IA. METHODS: We performed a retrospective cohort study using the 2000 Kids Inpatient Database, a national database of hospital inpatient stays during 2000. IA was defined as aspergillosis that occurred in a child with malignancy (solid tumor, leukemia, or lymphoma), hematologic/immunologic deficiency, or transplant (bone marrow or solid organ). Discharge weighting was applied to the data to obtain nationally representative estimates of disease. RESULTS: During 2000, there were an estimated 666 pediatric cases of IA among 152,231 immunocompromised children, yielding an annual incidence of 437/100,000 (0.4%) among hospitalized immunocompromised children. Children with malignancy accounted for the majority (74%) of cases of IA. The highest incidence of IA was seen in children who had undergone allogeneic bone marrow transplantation (4.5%) and those with acute myelogenous leukemia (4%). The overall in-hospital mortality of immunocompromised children with IA was 18%. Children with malignancy and IA were at higher risk for death than children with malignancy and without IA. Pediatric patients with IA had a significantly longer median length of hospital stay (16 days) than immunocompromised children without IA (3 days). The median total hospital charges for patients with IA were $49309 compared with immunocompromised children without IA ($9035). CONCLUSIONS: The impact of IA on increases in mortality, length of hospital stay, and the burden of cost in the hospital setting underscores the need for improved means of diagnosis, prevention, and treatment of IA in immunocompromised children.