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Abstract Introduction Candida lusitaniae was originally described as a human pathogen in 1979 and typically affects immunocompromised patients. Case presentation We describe a case of prosthetic valve endocarditis with Candida lusitaniae in an immunocompetent 62-year-old woman following aortic valve replacement. In vitro testing demonstrated that our isolate was sensitive to amphotericin B, caspofungin and fluconazole. Conclusion The infection was lethal despite aggressive medical and surgical management and sterilization of blood cultures. The outcome of our case illustrates the need to recognize Candida lusitaniae fungemia as a life-threatening infection in a patient with a prosthetic aortic valve.

Purpose: Cement usage in total hip arthroplasty (THA) is increasingly common. However, osteoporosis-related fracture risk in cemented vs uncemented THA patients is poorly characterized. We aim to analyze the usage of metabolic bone care and osteoporosis fracture risk in cemented vs uncemented THA patients using FRAX and radiographic bone measurements., Methods: Chart review on 250 THA patients was performed retrospectively. Demographics, FRAX scores, hip radiograph measurements, osteoporosis diagnosis, treatment and screening were compared between cemented and uncemented THA patients. Logistic regression model was used to analyze factors influencing cement usage., Results: Cemented THA patients have significantly higher osteoporosis-related fracture risk as measured by FRAX major (20% vs 13%) and FRAX hip (8% vs 5%). There is no significant difference in osteoporosis treatment, vitamin D / calcium supplementation, or metabolic bone disease screening based on patients' cement status. Female sex and rheumatoid arthritis status significantly predict cement usage, but FRAX scores do not predict cement usage. Additionally, 50% (10/20) of patients with Dorr C classification were uncemented., Conclusion: Although some patients undergoing THA with high osteoporosis-related fracture risk were identified and cemented, some risk factors including poor proximal femur shape (by Dorr classification) and poor bone quality (as measured by FRAX score) were potentially overlooked. Cemented patients had an increased risk for fractures but did not receive appropriately increased osteoporosis screening or treatment., Level of Evidence: III., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

A retrospective study of 121 patients who stopped denosumab (Dmab) then received no treatment (NT), risedronate (RIS), alendronate (ALN), or zoledronic acid (ZOL). Bone density (spine and hip) during and after Dmab discontinuation was measured. Treatment with ALN or ZOL, not NT and RIS, mitigated BMD loss after Dmab discontinuation., Introduction: Denosumab (Dmab) discontinuation is associated with bone loss and multiple vertebral fractures. The purpose was to compare bone mineral density (BMD) change in patients following Dmab discontinuation with no subsequent treatment (NT) and three bisphosphonate (BP) treatments: risedronate (RIS), alendronate (ALN), and zoledronic acid (ZOL)., Methods: In a review of 121 patients aged 71.2 ± 8.1 years, discontinuing Dmab (mean 5.4 doses), 33 received NT and 88 received BP (22 RIS; 34 ALN; 32 ZOL). BMD change after 1 year was compared between groups at the lumbar spine (LS), femoral neck (FN), and total hip (TH). Risk factors for bone loss after Dmab discontinuation were compared between groups and incidence of vertebral fractures was determined., Results: Following Dmab discontinuation, LS mean change (g/cm 2 ; 95% CI) was for NT: - 0.041 (- 0.062 to - 0.021); RIS: - 0.035 (- 0.052 to - 0.017); ALN: - 0.005 (- 0.020 to 0.009); and ZOL: - 0.009 (- 0.025 to 0.008). Differences in LS were found between NT and ALN (p =  0.015), and NT and ZOL (p=0.037), but not between NT and RIS. The only significant difference in TH was found between NT and ZOL (p 0.034) with no group differences in FN. BMD gains during Dmab treatment were associated with BMD loss after Dmab discontinuation. In a subset, discontinuation after Dmab treatment (> 5 doses) followed by ALN (n = 22) and ZOL (n = 11) showed no difference in BMD. Five of 7 vertebral fractures occurred after Dmab discontinuation in NT., Conclusion: Subsequent treatment with ALN or ZOL but not NT and RIS mitigates BMD loss after Dmab discontinuation., (© 2023. The Author(s).)

Background: Osteoporosis is a major risk factor for periprosthetic fractures (PPFx) in total hip arthroplasty (THA) patients but is not routinely screened for in this population. Given the availability of hip x-rays and preoperative screenings, Fracture Risk Assessment Tool (FRAX) scores and radiographic bone measurements are potentially promising, novel risk stratification tools. This study aims to characterize FRAX scores and radiographic bone measurements in THA and PPFx patients., Methods: A retrospective chart review for demographic variables and FRAX scores was performed on 250 THA and 40 PPFx patients. Radiographic bone measurements including cortical thicknesses (both antero-posterior [AP] and lateral), canal to calcar ratio, canal flare index, and Dorr classifications were obtained from preoperative x-rays. Correlation between FRAX scores and radiographic bone measurements was investigated with linear regressions. FRAX scores and radiographic bone measurements were compared between the THA and PPFx patients. Multivariate logistic regressions were used to identify factors predicting PPFx., Results: FRAX scores were significantly correlated with both AP (P < .001) and lateral (P = .007) cortical thicknesses. Compared to THA patients, those with PPFx had significantly higher FRAX scores (P = .003) and lower AP cortical thickness (P = .005). Multivariate logistic regressions demonstrated that FRAX major osteoporotic fracture risk score and AP cortical thickness were independent predictors of PPFx (P = .001 and .024, respectively)., Conclusion: Cortical thicknesses are good proxy measurements of osteoporosis-related fracture risk in THA patients. In addition, both major and AP cortical thickness indices are promising tools for identifying patients who are at a high risk of PPFx in the THA population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Metabolic bone diseases in the total joint arthroplasty (TJA) population are undertested and undertreated, leading to increased risk of adverse outcomes such as periprosthetic fractures. This study aims to better characterize the current state of bone care in TJA patients using Fracture Risk Assessment Tool (FRAX) score risk stratifications., Methods: In total, 505 consecutive TJA patients who meet the Endocrine Society guidelines for osteoporosis screening were included for review. They were divided into a high risk or low risk group depending on FRAX scores and were compared based on screening, diagnosis, and treatment of metabolic bone disease. Logistic regression models were used to analyze factors influencing screening and treatment. A population analysis involving 2,000 TJA patients, and a complication analysis involving 40 periprosthetic fracture patients were conducted., Results: Among high risk patients undergoing TJA, 90% did not receive any pharmacological treatment for osteoporosis, 45% were not treated with vitamin D or calcium, and 88% did not receive bone density testing in the routine care period. Among patients with pre-existing osteoporosis undergoing TJA, 80% were not treated with any osteoporosis medications and 33% of these patients were not taking vitamin D or calcium. Female gender and past fracture history contributed to whether patients received screening and treatment. Patients with periprosthetic hip fractures have significantly higher FRAX scores compared to control THA patients., Conclusion: There are significant gaps in metabolic bone care of the geriatric TJA population regarding both screening and treatment. Metabolic bone care and risk identification with FRAX should be highly considered for TJA patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 by the American Academy of Pediatrics.)

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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.

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.

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.

Order sets as part of the Computerized Provider Order Entry (CPOE) system can improve care delivery through allowing faster and easier physician order entry guided by known best practices. This study examines current utilization patterns of order sets and "a la carte" orders in a pediatric environment with a preliminary investigation of methods to automate the creation and modification of order sets using historical ordering data. We examine the current usage of order sets associated with Asthma Minor and Appendectomy Minor patients to understand how physicians are utilizing order sets, and how order set usage is associated with the time of ordering and characteristics of order sets. K-means clustering was applied to orders to generate evidence-based order sets that are learned from historical hospital data. We demonstrate that coverage rate of order sets and ordering efficiency can be increased through modifications of existing sets and creation of new sets.

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.

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., (Copyright © 2011 Society of Hospital Medicine.)

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.

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., (© 2011 by the Society for Academic Emergency Medicine.)

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.

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.

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.

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.

Objectives: To describe the magnitude of off-label drug use, to identify drugs most commonly used off-label, and to identify factors associated with off-label drug use in children hospitalized in the United States., Design: Retrospective cohort study., Setting: Administrative database containing inpatient resource utilization data from January 1 to December 31, 2004, from 31 tertiary care pediatric hospitals in the United States., Participants: Hospitalized patients 18 years or younger., Main Exposures: Institution and patient characteristics., Main Outcome Measures: Off-label drug use was defined as use of a specific drug in a patient younger than the Food and Drug Administration-approved age range for any indication of that drug., Results: At least 1 drug was used off-label in 297 592 (78.7%) of 355 409 patients discharged during the study. Off-label use accounted for $270 275 849 (40.5%) of the total dollars spent on these medications. Medications classified as central or autonomic nervous system agents or as fluids or nutrients, or gastrointestinal tract agents were most commonly used off-label, whereas antineoplastic agents were rarely used off-label. Factors associated with off-label use in multivariate analysis were as follows: undergoing a surgical procedure, age older than 28 days, greater severity of illness, and all-cause in-hospital mortality., Conclusions: Most patients hospitalized at tertiary care pediatric institutions receive at least 1 medication outside the terms of the Food and Drug Administration product license. Substantial variation in the frequency of off-label use was observed across diagnostic categories and drug classes. Despite the frequent off-label use of drugs, using an administrative database, we cannot determine which of these treatments are unsafe or ineffective and which treatments result in substantial benefit to the patient.

Using data from over 450,000 pediatric encounters three data sources were evaluated for their ability to support early detection of a yearly outbreak of rotavirus disease: 1) Laboratory studies ordered, 2) Diagnosis codes, and 3) Free text "reason for visit" strings categorized as Gastrointestinal syndrome by a support vector machine software classifier. We found that in this setting the categorized free text analyzed through simple control charts detected each outbreak within 10 days of their beginning as determined by laboratory detection of rotavirus antigen (the gold standard). Outbreak detection by laboratory studies was delayed an average of 14 days and by diagnosis codes by an average of 20 days. We conclude that categorized text may provide a valuable basis for real-time detection of disease outbreaks.

Sensory systems are often required to detect a small amplitude signal embedded in broadband background noise. Traditionally, ambient noise is regarded as detrimental to encoding accuracy. Recently, however, a phenomenon known as stochastic resonance has been described in which, for systems with a nonlinear threshold, increasing the input noise level can actually improve the output signal-to-noise ratio over a limited range of signal and noise strengths. Previous theoretical and experimental studies of stochastic resonance in physical and biological systems have dealt exclusively with single-frequency sine stimuli embedded in a broadband noise background. In the past year it has been shown in a theoretical and modelling study that stochastic resonance can be observed with broadband signals. Here we demonstrate that broadband stochastic resonance is manifest in the peripheral layers of neural processing in a simple sensory system, and that it plays a role over a wide range of biologically relevant stimulus parameters. Further, we quantify the functional significance of the phenomenon within the context of signal processing, using information theory.

We describe the development and analysis of a quantitative database representing the global structural and functional organization of an entire sensory map. The database was derived from measurements of anatomical characteristics of a statistical sample of typical mechanosensory afferents in the cricket cercal sensory system. Anatomical characteristics of the neurons were measured quantitatively in three dimensions using a computer reconstruction system. The reconstructions of all neurons were aligned and scaled to a common standard set of dimensions, according to a highly reproducible set of intrinsic fiducial marks. The database therefore preserves accurate information about spatial relationships between the neurons within the ensemble. Algorithms were implemented to allow the integration of electrophysiological data about the stimulus/response characteristics of the reconstructed neurons into the database. The algorithms essentially map a physiological function onto a "field" representing the continuous distribution of synaptic terminals throughout the neural structure. Subsequent analysis allowed quantitative predictions of several important functional characteristics of the sensory map that emerge from its global organization. First, quantitative and testable predictions were made about ensemble response patterns within the map. The predicted patterns are presented as graphical images, similar to images that might be observed with activity-dependent dyes in the real neural system. Second, the synaptic innervation patterns from the sensory afferent map onto the dendrites of a postsynaptic target interneuron were predicted by calculating the overlap between the interneuron's dendrites with the afferent map. By doing so, several aspects of the stimulus/response properties of the interneuron were accurately predicted.

Managed care has inherent limitations that, perhaps out of desperation for some degree of control of health care costs, we tend to disregard. A better understanding of the "crisis" and a host of new strategies become apparent when we separately consider the health care elements and cost elements of the crisis. Managed care is essentially palliative in that it eases symptoms without curing conditions. While this is not a call for the abandonment of managed care, it is a warning that our efforts will prove futile if we do not also address other fundamental elements of impaired health.

A human myosin heavy-chain gene, cloned in gamma Charon 4A phage (and as a clone designated lambda gMHC-1), was shown to code for a cardiac myosin heavy chain of the beta-type. The 5' end of the 14,200-base-pair genomic DNA clone is located in the head region of the myosin chain. The 3' end was shown to extent to the COOH terminus and includes the 3'-nontranslated sequence of the corresponding mRNA. The identification of lambda gMHC-1 as coding for a cardiac beta-myosin heavy chain was achieved by heteroduplex mapping using genomic cardiac myosin heavy-chain DNA of rabbit as a probe and, furthermore, by DNA sequence analysis of three selected subregions of the clones DNA including the 3'-nontranslated sequence. It was demonstrated by the S1 nuclease protection technique that the beta-myosin heavy-chain gene is transcribed in human heart muscle. In addition, we have found by the same technique that it is also expressed in human skeletal muscle.

The quality of life of 23 adults with growth hormone deficiency (GHD) who had received growth hormone (GH) therapy was compared with that of 47 normal individuals in a control group. The GHD group had a poorer quality of life than the control group. Statistically significant differences were found between the groups for social isolation, physical mobility, sleep, and emotional status. More individuals in the control group had a driving licence and were married than in the GHD group.

An innovative health education curriculum, "Health Careers", intended for adolescents leaving school, was evaluated using a quasi-experimental pre-/post control group design. The objective of the project was the modification of knowledge, attitudes and behaviour in relation to health. Attempts were made to counteract factors restricting the effect of traditional health education at school. Changes were estimated using questionnaires. Two types of schools were studied, schools A and B, student age averaged 17.3 years and 15.5 years, respectively. The number of students in the experimental groups was 220 and 112, respectively. At school B, in addition, 35 parents participated voluntarily in evening courses arranged by the project staff. Significant improvement was shown in two variables of a possible 60 at school A and in four variables at school B. Analysis by subgroups, however, demonstrated improvements in merely one variable at school B. It is evident that the innovative curriculum did not induce significant behavioural improvement in relation to health. Frame factors of the school--obligatory student participation and teacher role perception--may explain this outcome.

We have examined the transcriptional regulation of the rabbit myosin heavy chain (HC) beta gene by using DNA-mediated transfection experiments. To analyze the activity of the myosin HC beta promoter in a myogenic background, cultured myoblasts from 12-day-old chick embryonic breast muscle were transfected with a chimeric gene containing 781 base pairs of the promoter region fused to the gene for chloramphenicol acetyltransferase (CAT). As indicated by the transient expression of chloramphenicol acetyltransferase, the activity of the promoter in myoblast cultures increased at least 32-fold following differentiation and was selectively inhibited when myogenesis was blocked with 5-bromodeoxyuridine. Furthermore, RNase protection experiments showed that the in vivo myosin HC beta transcriptional initiation (or cap) site was utilized in the transfected skeletal muscle cells and also that the regulation of the exogenous promoter was similar to the induction of the endogenous skeletal alpha-actin gene. The results indicated that the exogenous promoter is regulated in a tissue- and stage-specific manner. By creating progressive 5' deletions of the promoter, we showed that only the region extending -294 base pairs upstream from the cap site is necessary for the muscle-specific expression. Linker-scanner mutagenesis of this region indicated that the positive regulation in differentiated skeletal muscle is mediated by at least two distinct elements within the 5'-flanking region of the myosin HC beta gene.

Two cardiac myosin heavy chain cDNA clones, pMHC alpha 252 and pMHC beta 174, were constructed using rabbit ventricular mRNA isolated from adult thyrotoxic and normal hearts, respectively. The complete DNA sequences of the 2.2- and 1.4-kilobase inserts of pMHC beta 174 and pMHC alpha 252, respectively, were obtained. The 736 amino acids specified by pMHC beta 174 begin 439 (1.3 kilobases) residues from the heavy chain NH2 terminus and include a 400-amino acid segment of subfragment 1 and the entire subfragment 2 region. Clone pMHC alpha 252 encodes 465 amino acids encompassing all of subfragment 2 and a portion of light meromyosin. Comparison of these two clones revealed extensive sequence overlap which included 1107 nucleotides specifying a 369-amino acid segment corresponding to subfragment 2. Within this region 78 (7%) base and 32 (8.7%) amino acid mismatches were noted. These differences were clustered within discrete regions, with the subfragment 1/subfragment 2 junctional region being particularly divergent. Structural differences between pMHC alpha 252 and pMHC beta 174 indicate that these two clones represent two similar but distinct myosin heavy chain genes whose expression is responsible for ventricular myosin heavy chain isoforms alpha and beta, respectively. The derived amino acid sequences of both clones exhibit extensive homology (greater than 81%) with sequences obtained by direct analysis of adult rabbit skeletal muscle myosin heavy chain protein. The sequences corresponding to the subfragment 2 region are consistent with an alpha-helical conformation with a characteristic 7-residue periodicity in the linear distribution of nonpolar amino acids. Conversely, subfragment 1 sequences specified by pMHC beta 174 suggest a folded highly irregular structure.