Long-term follow-up of clinical trial patients treated for chronic HCV infection with daclatasvir-based regimens.

BACKGROUND & AIMS: Daclatasvir has achieved high sustained virologic response (SVR) rates in diverse hepatitis C virus (HCV) populations. This study evaluated the long-term efficacy and safety of daclatasvir-based regimens administered during clinical studies. METHODS: Patients enrolled within 6 months of parent study completion or protocol availability at the study sites. The primary objective was durability of SVR at follow-up Week 12 (SVR12). Secondary objectives included analysing HCV sequences in non-responders or responders who relapsed, and characterization of liver disease progression. RESULTS: Between 24 February 2012 and 17 July 2015, this study enrolled and began following 1503 recipients of daclatasvir-based regimens (follow-up cut-off, 13 October 2015); 60% were male, 18% aged ≥65 years, 87% had genotype-1a (42%) or -1b (45%) infection, and 18% had cirrhosis. Median follow-up from parent study follow-up Week 12 was 111 (range, 11-246) weeks. 1329/1489 evaluable patients were SVR12 responders; 1316/1329 maintained SVR until their latest visit. Twelve responders relapsed by (n = 9) or after (n = 3) parent study follow-up Week 24; one was reinfected. Relapse occurred in 3/842 (0.4%) and 9/487 (2%) responders treated with interferon-free or interferon-containing regimens, respectively. Hepatic disease progression and new hepatocellular carcinoma were diagnosed in 15 and 23 patients, respectively. Among non-responders, emergent non-structural protein-5A (NS5A) and -3 (NS3) substitutions were replaced by wild-type sequences in 27/157 (17%) and 35/47 (74%) patients, respectively. CONCLUSIONS: SVR12 was durable in 99% of recipients of daclatasvir-based regimens. Hepatic disease progression and new hepatocellular carcinoma were infrequent. Emergent NS5A substitutions persisted longer than NS3 substitutions among non-responders.

New Diagnosis of AIDS Based on Salmonella enterica subsp. I (enterica) Enteritidis (A) Meningitis in a Previously Immunocompetent Adult in the United States.

Salmonella meningitis is a rare manifestation of meningitis typically presenting in neonates and the elderly. This infection typically associates with foodborne outbreaks in developing nations and AIDS-endemic regions. We report a case of a 19-year-old male presenting with altered mental status after 3-day absence from work at a Wisconsin tourist area. He was febrile, tachycardic, and tachypneic with a GCS of 8. The patient was intubated and a presumptive diagnosis of meningitis was made. Treatment was initiated with ceftriaxone, vancomycin, acyclovir, dexamethasone, and fluid resuscitation. A lumbar puncture showed cloudy CSF with Gram negative rods. He was admitted to the ICU. CSF culture confirmed Salmonella enterica subsp. I (enterica) Enteritidis (A). Based on this finding, a 4th-generation HIV antibody/p24 antigen test was sent. When this returned positive, a CD4 count was obtained and showed 3 cells/mm3, confirming AIDS. The patient ultimately received 38 days of ceftriaxone, was placed on elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (Genvoya) for HIV/AIDS, and was discharged neurologically intact after a 44-day admission.

Development and validation of a continuously age-adjusted measure of patient condition for hospitalized children using the electronic medical record.

Awareness of a patient's clinical status during hospitalization is a primary responsibility for hospital providers. One tool to assess status is the Rothman Index (RI), a validated measure of patient condition for adults, based on empirically derived relationships between 1-year post-discharge mortality and each of 26 clinical measurements available in the electronic medical record. However, such an approach cannot be used for pediatrics, where the relationships between risk and clinical variables are distinct functions of patient age, and sufficient 1-year mortality data for each age group simply do not exist. We report the development and validation of a new methodology to use adult mortality data to generate continuously age-adjusted acuity scores for pediatrics. Clinical data were extracted from EMRs at three pediatric hospitals covering 105,470 inpatient visits over a 3-year period. The RI input variable set was used as a starting point for the development of the pediatric Rothman Index (pRI). Age-dependence of continuous variables was determined by plotting mean values versus age. For variables determined to be age-dependent, polynomial functions of mean value and mean standard deviation versus age were constructed. Mean values and standard deviations for adult RI excess risk curves were separately estimated. Based on the "find the center of the channel" hypothesis, univariate pediatric risk was then computed by applying a z-score transform to adult mean and standard deviation values based on polynomial pediatric mean and standard deviation functions. Multivariate pediatric risk is estimated as the sum of univariate risk. Other age adjustments for categorical variables were also employed. Age-specific pediatric excess risk functions were compared to age-specific expert-derived functions and to in-hospital mortality. AUC for 24-h mortality and pRI scores prior to unplanned ICU transfers were computed. Age-adjusted risk functions correlated well with similar functions in Bedside PEWS and PAWS. Pediatric nursing data correlated well with risk as measured by mortality odds ratios. AUC for pRI for 24-h mortality was 0.93 (0.92, 0.94), 0.93 (0.93, 0.93) and 0.95 (0.95, 0.95) at the three pediatric hospitals. Unplanned ICU transfers correlated with lower pRI scores. Moreover, pRI scores declined prior to such events. A new methodology to continuously age-adjust patient acuity provides a tool to facilitate timely identification of physiologic deterioration in hospitalized children.

Retrospective analysis of hepatitis C infected patients treated through an integrated care model.

AIM: To determine if our health system's integrated model reflects sustained virologic response (SVR) outcomes similar to those in clinical trial data, maximizes adherence, and averts drug interactions. METHODS: Subjects with chronic hepatitis C had their medical records reviewed from November 1st, 2014 through March 1st, 2016. Patients eligible for treatment were entered into an integrated care model therapy algorithm. The primary outcome was SVR12 based on intention to treat (ITT) analysis. Inclusion criteria consisted of both treatment naïve and experienced patients over the age of 18 who were at least twelve weeks post-therapy completion with any genotype (GT) or METAVIR score. Secondary outcomes included adherence, adverse events, and number of drug interaction interventions. RESULTS: At the time of analysis, 133 patients had reached twelve weeks post therapy with ITT. In the ITT analysis 70 patients were GT 1a, 26 GT 1b, 23 could not be differentiated between GT 1a or 1b, 8 GT 2, 4 GT 3, and 2 patients with multiple genotypes. The ITT treatment regimens consisted of 97 sofosbuvir (SOF)/ledipasvir (LDV), 8 SOF/LDV and ribavirin (RBV), 7 SOF and Simeprevir (SMV), 6 3D and RBV, 1 3D, 11 SOF and RBV, and 1 SOF, peg interferon alpha, and RBV. The overall SVR12 rate was 93% in the ITT analysis with a total of 6 patients relapsing. In patients with cirrhosis, 89% obtained SVR12. All 33 patients who were previous treatment failures achieved SVR12. Drug-drug interactions were identified in 56.4% of our patient population, 69 of which required interventions made by the pharmacist. The most common side effects were fatigue (41.4%), headache (28.6%), nausea (18.1%), and diarrhea (8.3%). No serious adverse effects were reported. CONCLUSION: Dean Health System's integrated care model successfully managed patients being treated for hepatitis C virus (HCV). The integrated care model demonstrates high SVR rates amongst patients with different levels of fibrosis, genotypes, and HCV treatment history.

A Quality Assessment of a Collaborative Model of a Pediatric Antimicrobial Stewardship Program.

BACKGROUND: Infectious Diseases Society of America guidelines recommend that key antimicrobial stewardship program (ASP) personnel include an infectious disease (ID) physician leader and dedicated ID-trained clinical pharmacist. Limited resources prompted development of an alternative model by using ID physicians and service-based clinical pharmacists at a pediatric hospital. The aim of this study was to analyze the effectiveness and impact of this alternative ASP model. METHODS: The collaborative ASP model incorporated key strategies of education, antimicrobial restriction, day 3 audits, and practice guidelines. High-use and/or high-cost antimicrobial agents were chosen with audits targeting vancomycin, caspofungin, and meropenem. The electronic medical record was used to identify patients requiring day 3 audits and to communicate ASP recommendations. Segmented regression analyses were used to analyze quarterly antimicrobial agent prescription data for the institution and selected services over time. RESULTS: Initiation of ASP and day 3 auditing was associated with blunting of a preexisting increasing trend for caspofungin drug starts and use and a significant downward trend for vancomycin drug starts (relative change -12%) and use (-25%), with the largest reduction in critical care areas. Although meropenem use was already low due to preexisting requirements for preauthorization, a decline in drug use (-31%, P = .021) and a nonsignificant decline in drug starts (-21%, P = .067) were noted. A 3-month review of acceptance of ASP recommendations found rates of 90%, 93%, and 100% for vancomycin, caspofungin, and meropenem, respectively. CONCLUSIONS: This nontraditional ASP model significantly reduced targeted drug usage demonstrating acceptance of integration of service-based clinical pharmacists and ID consultants.

Daclatasvir + asunaprevir + beclabuvir ± ribavirin for chronic HCV genotype 1-infected treatment-naive patients.

BACKGROUND AND AIMS: This phase-2b study examined the safety and efficacy of an all-oral, interferon-free combination of the NS5A replication complex inhibitor daclatasvir (DCV), the NS3 protease inhibitor asunaprevir (ASV), and the nonnucleoside NS5B polymerase inhibitor beclabuvir (BCV) with or without ribavirin in patients with HCV genotype (GT) 1 infection. METHODS: A total of 187 patients received 12 weeks of DCV 30 mg BID plus ASV 200 mg BID and BCV 150 mg BID (n = 86) or 75 mg BID with (n = 21) or without (n = 80) weight-based ribavirin BID. The primary endpoint was HCV RNA <25 IU/ml at post-treatment week 12 (SVR12). RESULTS: Overall, 90% of patients (169/187) in the combined treatment groups achieved SVR on or after post-treatment week 12. SVR rates were similar across subgroups (by mITT analysis), i.e. patients with cirrhosis (88%, 14/16), HCV GT-1a (90%, 137/155), and IL28B non-CC genotype (90%, 115/128). There were no drug-related serious AEs or grade 4 AEs. The most frequently reported AEs were headache, diarrhoea, fatigue and nausea. Addition of ribavirin to DCV+ASV+BCV was associated with decreased haemoglobin, compared with DCV+ASV+BCV alone. There were six grade 3/4 laboratory abnormalities noted, all unrelated to the study drugs. Viral breakthrough occurred in 2.5-4.8% of patients across groups and appeared unrelated to BCV dose or ribavirin inclusion. CONCLUSIONS: Results support phase 3 evaluation of a twice-daily, fixed-dose formulation of this DCV+ASV+BCV regimen with or without ribavirin in HCV GT-1-infected patients.

Fixed-dose combination therapy with daclatasvir, asunaprevir, and beclabuvir for noncirrhotic patients with HCV genotype 1 infection.

IMPORTANCE: The antiviral activity of all-oral, ribavirin-free, direct-acting antiviral regimens requires evaluation in patients with chronic hepatitis C virus (HCV) infection. OBJECTIVE: To determine the rates of sustained virologic response (SVR) in patients receiving the 3-drug combination of daclatasvir (a pan-genotypic NS5A inhibitor), asunaprevir (an NS3 protease inhibitor), and beclabuvir (a nonnucleoside NS5B inhibitor). DESIGN, SETTING, AND PARTICIPANTS: This was an open-label, single-group, uncontrolled international study (UNITY-1) conducted at 66 sites in the United States, Canada, France, and Australia between December 2013 and August 2014. Patients without cirrhosis who were either treatment-naive (n = 312) or treatment-experienced (n = 103) and had chronic HCV genotype 1 infection were included. INTERVENTIONS: Patients received a twice-daily fixed-dose combination of daclatasvir, 30 mg; asunaprevir, 200 mg; and beclabuvir, 75 mg. MAIN OUTCOMES AND MEASURES: The primary study outcome was SVR12 (HCV-RNA <25 IU/mL at posttreatment week 12) in patients naive to treatment. A key secondary outcome was SVR12 in the treatment-experienced cohort. RESULTS: Baseline characteristics were comparable between the treatment-naive and treatment-experienced cohorts. Patients were 58% male, 26% had IL28B (rs12979860) CC genotype, 73% were infected with genotype 1a, and 27% were infected with genotype 1b. Overall, SVR12 was observed in 379 of 415 patients (91.3%; 95% CI, 88.6%-94.0%): 287 of 312 treatment-naive patients (92.0%; 95% CI, 89.0%-95.0%) and 92 of 103 treatment-experienced patients (89.3%; 95% CI, 83.4%-95.3%). Virologic failure occurred in 34 patients (8%) overall. One patient died at posttreatment week 3; this was not considered related to study medication. There were 7 serious adverse events, all considered unrelated to study treatment, and 3 adverse events (<1%) leading to treatment discontinuation, including 2 grade 4 alanine aminotransferase elevations. The most common adverse events (in ≥10% of patients) were headache, fatigue, diarrhea, and nausea. CONCLUSIONS AND RELEVANCE: In this open-label, nonrandomized, uncontrolled study, a high rate of SVR12 was achieved in treatment-naive and treatment-experienced noncirrhotic patients with chronic HCV genotype 1 infection who received 12 weeks of treatment with the oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01979939.

Paving the COWpath: data-driven design of pediatric order sets.

OBJECTIVE: Evidence indicates that users incur significant physical and cognitive costs in the use of order sets, a core feature of computerized provider order entry systems. This paper develops data-driven approaches for automating the construction of order sets that match closely with user preferences and workflow while minimizing physical and cognitive workload. MATERIALS AND METHODS: We developed and tested optimization-based models embedded with clustering techniques using physical and cognitive click cost criteria. By judiciously learning from users' actual actions, our methods identify items for constituting order sets that are relevant according to historical ordering data and grouped on the basis of order similarity and ordering time. We evaluated performance of the methods using 47,099 orders from the year 2011 for asthma, appendectomy and pneumonia management in a pediatric inpatient setting. RESULTS: In comparison with existing order sets, those developed using the new approach significantly reduce the physical and cognitive workload associated with usage by 14-52%. This approach is also capable of accommodating variations in clinical conditions that affect order set usage and development. DISCUSSION: There is a critical need to investigate the cognitive complexity imposed on users by complex clinical information systems, and to design their features according to 'human factors' best practices. Optimizing order set generation using cognitive cost criteria introduces a new approach that can potentially improve ordering efficiency, reduce unintended variations in order placement, and enhance patient safety. CONCLUSIONS: We demonstrate that data-driven methods offer a promising approach for designing order sets that are generalizable, data-driven, condition-based, and up to date with current best practices.

Design of electronic medical record user interfaces: a matrix-based method for improving usability.

This study examines a new approach of using the Design Structure Matrix (DSM) modeling technique to improve the design of Electronic Medical Record (EMR) user interfaces. The usability of an EMR medication dosage calculator used for placing orders in an academic hospital setting was investigated. The proposed method captures and analyzes the interactions between user interface elements of the EMR system and groups elements based on information exchange, spatial adjacency, and similarity to improve screen density and time-on-task. Medication dose adjustment task time was recorded for the existing and new designs using a cognitive simulation model that predicts user performance. We estimate that the design improvement could reduce time-on-task by saving an average of 21 hours of hospital physicians' time over the course of a month. The study suggests that the application of DSM can improve the usability of an EMR user interface.

Reducing provider cognitive workload in CPOE use: optimizing order sets.

Higher cognitive workload due to poor usability is a significant, unanticipated consequence of healthcare information technology (IT), resulting in new types of medical errors. An important example of this can be observed in the use of order sets, which allow safe and efficient provider order entry guided by known best practices. This paper aims to improve IT-enabled order entry by re-designing order sets using data-driven approaches to develop new order sets that match current usage and workflow, while incurring minimum cognitive workload. Applying optimization models embedded with clustering techniques, our methods identify items for constituting order sets that are relevant based on historical ordering data wherein items for a single patient are often placed together or in close temporal proximity during hospital stay. Results indicate that the new approaches dominate current solutions, significantly reducing cognitive workload, and improving order set content. Data driven methods thus offer a promising approach for designing order sets that are generalizable, evidence-based and up-to-date with current best practices.

Federating clinical data from six pediatric hospitals: process and initial results for microbiology from the PHIS+ consortium.

Microbiology study results are necessary for conducting many comparative effectiveness research studies. Unlike core laboratory test results, microbiology results have a complex structure. Federating and integrating microbiology data from six disparate electronic medical record systems is challenging and requires a team of varied skills. The PHIS+ consortium which is partnership between members of the Pediatric Research in Inpatient Settings (PRIS) network, the Children's Hospital Association and the University of Utah, have used "FURTHeR' for federating laboratory data. We present our process and initial results for federating microbiology data from six pediatric hospitals.

"I meant that med for Baylee not Bailey!": a mixed method study to identify incidence and risk factors for CPOE patient misidentification.

Computerized physician order entry (CPOE) systems can create unintended consequences. These include medication errors and adverse drug events. We look at a less understood error; patient misidentification. First, two email surveys were used to establish potential risk factors for this error. Next, an automated detection trigger was designed and validated with inpatient medication orders at a large pediatric hospital. The incidence was 0.064% per medication ordered. Finally, a case-control study identified the following as significant risk factors on multivariate analysis: patient age, last name spelling, bed proximity, medical service, time/date of order, and ordering intensity. These results can be used to improve patient safety by increasing awareness of high risk situations and guiding future research.

Comparative effectiveness of pleural drainage procedures for the treatment of complicated pneumonia in childhood.

OBJECTIVE: To determine the comparative effectiveness of common pleural drainage procedures for treatment of pneumonia complicated by parapneumonic effusion (ie, complicated pneumonia). DESIGN: Multicenter retrospective cohort study. SETTING: Forty children's hospitals contributing data to the Pediatric Health Information System. PARTICIPANTS: Children with complicated pneumonia requiring pleural drainage. MAIN EXPOSURES: Initial drainage procedures were categorized as chest tube without fibrinolysis, chest tube with fibrinolysis, video-assisted thoracoscopic surgery (VATS), and thoracotomy. MAIN OUTCOME MEASURES: Length of stay (LOS), additional drainage procedures, readmission within 14 days of discharge, and hospital costs. RESULTS: Initial procedures among 3500 patients included chest tube without fibrinolysis (n = 1762), chest tube with fibrinolysis (n = 623), VATS (n = 408), and thoracotomy (n = 797). Median age was 4.1 years. Overall, 716 (20.5%) patients received an additional drainage procedure (range, 6.8-44.8% across individual hospitals). The median LOS was 10 days (range, 7-14 days across individual hospitals). The median readmission rate was 3.8% (range, 0.8%-33.3%). In multivariable analysis, differences in LOS by initial procedure type were not significant. Patients undergoing initial chest tube placement with or without fibrinolysis were more likely to require additional drainage procedures. However, initial chest tube without fibrinolysis was the least costly strategy. CONCLUSION: There is variability in the treatment and outcomes of children with complicated pneumonia. Outcomes were similar in patients undergoing initial chest tube placement with or without fibrinolysis. Those undergoing VATS received fewer additional drainage procedures but had no differences in LOS compared with other strategies.

Cerebrospinal fluid characteristics of infants who present to the emergency department with fever: establishing normal values by week of age.

UNLABELLED: BACKGROUND This study describes differences in the values of cerebrospinal fluid (CSF) white blood cell (WBC), glucose, and protein counts in infants less than 60 days of age with fever who were not proven to have viral or bacterial meningitis. METHODS: Three independent retrospective medical record reviews were conducted using a population of infants less than 60 days of age who presented to the Emergency Department with fever. Full-term infants were included if a lumbar puncture was performed within 24 hours of admittance and bacterial or viral meningitis was not identified as the cause of fever. RESULTS: A total of 1091 infants were included and grouped by week of age. Significant trends were found for CSF WBC and CSF protein with the highest values observed during the first week of life. Mean for CSF WBC was 8.63 cells/mm for infants aged 0 to 1 week and decreased for each age group ending with infants 8 weeks of age having a mean of 2.22 cell/mm. For CSF protein, a similar trend was observed. No significant differences were found for CSF glucose. CONCLUSIONS: Significant differences exist for infants by week of age for CSF WBC and CSF protein. These values can be used to assist in interpreting laboratory findings and making management decisions for infants less than 60 days of age.

Resource burden at children's hospitals experiencing surge volumes during the spring 2009 H1N1 influenza pandemic.

OBJECTIVES: The objective was to describe the emergency department (ED) resource burden of the spring 2009 H1N1 influenza pandemic at U.S. children's hospitals by quantifying observed-to-expected utilization. METHODS: The authors performed an ecologic analysis for April through July 2009 using data from 23 EDs in the Pediatric Health Information System (PHIS), an administrative database of widely distributed U.S. children's hospitals. All ED visits during the study period were included, and data from the 5 prior years were used for establishing expected values. Primary outcome measures included observed-to-expected ratios for ED visits for all reasons and for influenza-related illness (IRI). RESULTS: Overall, 390,983 visits, and 88,885 visits for IRI, were included for Calendar Weeks 16 through 29, when 2009 H1N1 influenza was circulating. The subset of 106,330 visits and 31,703 IRI visits made to the 14 hospitals experiencing the authors' definition of ED surge during Weeks 16 to 29 was also studied. During surge weeks, the 14 EDs experienced 29% more total visits and 51% more IRI visits than expected (p < 0.01 for both comparisons). Of ED IRI visits during surge weeks, only 4.8% were admitted to non-intensive care beds (70% of expected, p < 0.01), 0.19% were admitted to intensive care units (44% of expected, p < 0.01), and 0.01% received mechanical ventilation (5.0% of expected, p < 0.01). Factors associated with more-than-expected visits included ages 2-17 years, payer type, and asthma. No factors were associated with more-than-expected hospitalizations from the ED. CONCLUSIONS: During the spring 2009 H1N1 influenza pandemic, pediatric EDs nationwide experienced a marked increase in visits, with far fewer than expected requiring nonintensive or intensive care hospitalization. The data in this study can be used for future pandemic planning.

State-level child health system performance and the likelihood of readmission to children's hospitals.

OBJECTIVES: To assess the relationship between children's hospital readmission and the performance of child health systems in the states in which hospitals are located. STUDY DESIGN: We conducted a retrospective cohort study of 197,744 patients 2 to 18 years old from 39 children's hospitals located in 24 states in the United States in 2005. Subjects were observed for a year after discharge for readmission to the same hospital. The odds of readmission were modeled on the basis of patient-level characteristics and state child health system performance as ranked by the Commonwealth Fund. RESULTS: A total of 1.8% of patients were readmitted within a week, 4.8% within a month, and 16.3% within 365 days. After adjustment for patient-level characteristics, the probability of readmission varied significantly between states (P=.001), and the likelihood of readmission during the ensuing year increased as the states' health system performance ranking improved. States in the best ranking quartile had a 2.03% higher readmission rate than states in the lowest quartile (P=.02); the same directional relationship was observed for readmission intervals from 1 to 365 days after discharge. CONCLUSIONS: Hospital readmission rates are significantly related to the performance of the surrounding health care system.

Discovering knowledge on pediatric fluid therapy and dysnatremias from quantitative data found in electronic medical records.

It is accepted that intravenous fluid (IVF) therapy can result in hospital-acquired dysnatremias in pediatric patients, with associated morbidity and mortality. There is interest in improving IVF therapy to prevent dysnatremias, but the optimal approach is controversial. In this study, we develop Natremia Deviation and Intravenous Renderer (NaDIR), a tool that preprocesses large volumes of electronic medical record data obtained from an academic pediatric hospital in order to analyze (1) IVF therapy, (2) the epidemiology of dysnatremias, and (3) the impact of IVFs on changes in serum sodium (ΔS(Na)). We then applied NaDIR to 3,256 inpatient records over a 3 month period, which revealed (1) a 19.9% incidence of dysnatremias, (2) a significant increase in lengths of stay associated with dysnatremias, and (3) a novel linear relationship between ΔS(Na) and IVF tonicity. This demonstrates that EMR data that can be readily analyzed to discover epidemiologic and predictive knowledge.

Intravenous immunoglobulin in children with streptococcal toxic shock syndrome.

BACKGROUND: Streptococcal toxic shock syndrome (TSS) is a rare and severe manifestation of group A streptococcal infection. The role of intravenous immunoglobulin (IVIG) for streptococcal TSS in children is controversial. This study aims to describe the epidemiology of streptococcal TSS in children and to determine whether adjunctive therapy with IVIG is associated with improved outcomes. METHODS: A multicenter, retrospective cohort study of children with streptococcal TSS from 1 January 2003 through 31 December 2007 was conducted. Propensity scores were used to determine each child's likelihood of receiving IVIG. Differences in the primary outcomes of death, hospital length of stay, and total hospital costs were compared after matching IVIG recipients and nonrecipients on propensity score. RESULTS: The median patient age was 8.2 years. IVIG was administered to 84 (44%) of 192 patients. The overall mortality rate was 4.2% (95% confidence interval, 1.8%-8.0%). Differences in mortality between IVIG recipients (n = 3; 4.5%) and nonrecipients (n = 3; 4.5%) were not statistically significant (p > .99). Although patients receiving IVIG had higher total hospital and drug costs than nonrecipients, differences in hospital costs were not significant once drug costs were removed (median difference between matched patients, $6139; interquartile range, -$8316 to $25,993; P = .06). No differences were found in length of hospital stay between matched IVIG recipients and nonrecipients. CONCLUSION: This multicenter study is, to our knowledge, the largest to describe the epidemiology and outcomes of children with streptococcal TSS and the first to explore the association between IVIG use and clinical outcomes. IVIG use was associated with increased costs of caring for children with streptococcal TSS but was not associated with improved outcomes.

How well can hospital readmission be predicted in a cohort of hospitalized children? A retrospective, multicenter study.

BACKGROUND: Children with complex chronic conditions depend on both their families and systems of pediatric health care, social services, and financing. Investigations into the workings of this ecology of care would be advanced by more accurate methods of population-level predictions of the likelihood for future hospitalization. METHODS: This was a retrospective cohort study. Hospital administrative data were collected from 38 children's hospitals in the United States for the years 2003-2005. Participants included patients between 2 and 18 years of age discharged from an index hospitalization during 2004. Patient characteristics documented during the index hospitalization or any previous hospitalization during the preceding 365 days were included. The main outcome measure was readmission to the hospital during the 365 days after discharge from the index admission. RESULTS: Among the cohort composed of 186856 patients discharged from the participating hospitals during 2004, the mean age was 9.2 years, with 54.4% male and 52.9% identified as non-Hispanic white. A total of 17.4% were admitted during the previous 365 days, and among those discharged alive (0.6% died during the admission), 16.7% were readmitted during the ensuing 365 days. The final readmission model exhibited a c statistic of 0.81 across all hospitals, with a range from 0.76 to 0.84 for each hospital. Bootstrap-based assessments demonstrated the stability of the final model. CONCLUSIONS: Accurate population-level prediction of hospital readmissions is possible, and the resulting predicted probability of hospital readmission may prove useful for health services research and planning.

Therapeutic potential of a fully human monoclonal antibody against influenza A virus M2 protein.

Influenza is one of the most prevalent viral diseases in humans. For some high-risk human populations, including the infant, the elderly, and the immunocompromised, who may not benefit from active immunization, passive immunotherapy with antibodies reactive with all influenza A strains may be an alternative. In this study, we characterized several fully human monoclonal antibodies (MAb) reactive with M2e, which were generated from transchromosomic mice engineered to produce fully human antibodies following immunization with a consensus-sequence M2e peptide. The MAbs showed strong binding to M2e peptide and to virus infected MDCK cells. One MAb recognizing the highly conserved N-terminal portion of consensus M2e displayed high binding to the majority of M2e variants from natural viral isolates, including highly pathogenic avian strains, which were recently reported to infect humans. Passive immunotherapy with this MAb in mice resulted in significant reduction in virus replication in the lung and protection from lethal infection when administered either prophylactically or therapeutically. These results suggest the potential of the anti-M2e human MAb with broad binding spectrum as a universal passive immunotherapeutic agent to infection by influenza A virus.