Stephen M. Downs

Technical Report: Urinary Tract Infections in Febrile Infants and Young Children

Overview.  The Urinary Tract Subcommittee of the American Academy of Pediatrics Committee on Quality Improvement has analyzed alternative strategies for the diagnosis and management of urinary tract infection (UTI) in children. The target population is limited to children between 2 months and 2 years of age who are examined because of fever without an obvious cause. Diagnosis and management of UTI in this group are especially challenging for these three reasons: 1) the manifestation of UTI tends to be nonspecific, and cases may be missed easily; 2) clean voided midstream urine specimens rarely can be obtained, leaving only urine collection methods that are invasive (transurethral catheterization or bladder tap) or result in nonspecific test results (bag urine); and 3) a substantial number of infants with UTI also may have structural or functional abnormalities of the urinary tract that put them at risk for ongoing renal damage, hypertension, and end-stage renal disease (ESRD). Methods.  To examine alternative management strategies for UTI in infants, a conceptual model of the steps in diagnosis and management of UTI was developed. The model was expanded into a decision tree. Probabilities for branch points in the decision tree were obtained by review of the literature on childhood UTI. Data were extracted on standardized forms. Cost data were obtained by literature review and from hospital billing data. The data were collated into evidence tables. Analysis of the decision tree was used to produce risk tables and incremental cost-effectiveness ratios for alternative strategies. Results.  Based on the results of this analysis and, when necessary, consensus opinion, the Committee developed recommendations for the management of UTI in this population. This document provides the evidence the Subcommittee used in the development of its recommendations. Conclusions.  The Subcommittee agreed that the objective of the practice parameter would be to minimize the risk of chronic renal damage within reasonable economic constraints. Steps involved in achieving these objectives are: 1) identifying UTI; 2) short-term treatment of UTI; and 3) evaluation for urinary tract abnormalities.

Cost-effectiveness of transesophageal echocardiography to determine the duration of therapy for intravascular catheter-associated Staphylococcus aureus bacteremia

Staphylococcus aureus bacteremia is an increasingly common and potentially catastrophic complication of intravascular catheters (1-3). After S. aureus bacteremia develops, it can be difficult to distinguish uncomplicated bacteremia from occult endocarditis (4-7). For this reason, controversy exists about the appropriate duration of therapy. Prolonged courses (4 to 6 weeks) of parenteral antibiotics have traditionally been recommended because of the high rates of endocarditis found in early studies (8). However, this approach is expensive and may result in complications of therapy. Noting the decreased rates of endocarditis in patients with infection secondary to intravascular devices (2, 5, 9-16), some investigators recommend treating patients with catheter removal and abbreviated ( 14 days) courses of therapy (2, 13, 14, 17, 18). Although 4 to 6 weeks of therapy may be unnecessary for most patients with catheter-associated S. aureus bacteremia, short-course therapy will fail in a subset of patients because of inadequately treated occult endocarditis (19). Transesophageal echocardiography (TEE) has been suggested as a technique with which to prospectively identify patients with endocarditis; this technique would allow more appropriate assignment to short or long courses of therapy (20). Because of its high sensitivity (21-31) and specificity (21, 25, 27, 28) for endocarditis on native cardiac valves, TEE allows improved diagnosis and therapeutic regimens that target specific patients. However, TEE is an invasive and expensive procedure, and it is unclear whether its benefits justify its costs. The purpose of our investigation was to determine the cost-effectiveness of TEE for stratifying patients with catheter-associated S. aureus bacteremia to a specific duration of therapy. Methods Decision Model Following standard cost-effectiveness methods (32), we used decision analysis (33) to model the clinical and cost consequences of alternate management strategies in patients with catheter-associated S. aureus bacteremia. The model (Figure 1)compared three approaches to management of catheter-related S. aureus bacteremia in patients with no indwelling prosthetic devices who appeared to have a clinically uncomplicated disease course (that is, prompt defervescence, no clinical evidence of metastatic sites of infection, and rapid resolution of bacteremia); the catheter had been removed from all patients (15, 18, 34). The first approach (the TEE strategy) used TEE at the time of initial diagnosis to stratify patients to short-course or long-course intravenous antibiotic therapy. Patients who showed evidence of endocarditis on TEE were treated with intravenous antibiotics for 4 weeks. If there was no evidence of endocarditis, patients were treated with intravenous antibiotics for 2 weeks. The second approach (the long-course strategy) called for all patients to receive a 4-week course of parenteral antibiotics. With the third approach (the short-course strategy), all patients were treated with a 2-week course of intravenous antibiotics. This model is not applicable to patients at increased risk for complications (that is, immunosuppressed patients, patients who have used intravenous drugs, or patients with indwelling prosthetic devices). Figure 1. Figure 1. Decision model for the treatment of catheter-associated Staphylococcus aureus bacteremia. Assumptions of the Model We modeled the most serious complications of infective endocarditis: stroke, valvular insufficiency necessitating surgical replacement, and death. We assumed that valve replacement, if required, would be done during the initial hospitalization. Furthermore, we assumed that patients who experienced a relapse had the same probability of adverse events as they did during their initial disease episode. This assumption biased the model in favor of short-course therapy because patients who have relapse are likely to have more serious infections. In accordance with previous studies (14, 19), we assumed that relapses of S. aureus bacteremia were caused by inadequately treated occult endocarditis. For the base-case analysis, we assumed that cases of occult endocarditis treated with short-course therapy would not be cured. This assumption biased the model in favor of long-course therapy and was tested extensively in sensitivity analyses. We assumed that patients could have relapse only once. Patients who had relapse were hospitalized again with presumed endocarditis and were re-treated with long-course therapy. On the basis of evidence from previous work (35-37), we assumed that endocarditis could be adequately treated on an outpatient basis. Therefore, parenteral antibiotic treatment was initiated in the hospital and completed on an outpatient basis. Likelihood of Events The natural history of catheter-associated S. aureus bacteremia was estimated from our institutional data and data from the literature. The clinical data involved 60 consecutive patients with S. aureus endocarditis and 196 consecutive patients with uncomplicated catheter-associated S. aureus bacteremia who were included in an institutional registry maintained since September 1994. Using MEDLINE (1966 to February 1998) and bibliographical review of relevant articles, we searched the literature for studies on the natural history of catheter-associated S. aureus bacteremia and S. aureus endocarditis. We reviewed endocarditis case series for data specifically pertaining to S. aureus regardless of catheter involvement. We also reviewed reports on endocarditis from any causal microorganism for mortality rates associated with strokes and valve replacement operations. Studies that dealt primarily with pediatric patients, immunocompromised patients, patients who used intravenous drugs, patients with prosthetic valve endocarditis, or patients with methicillin-resistant S. aureus were excluded. When studies reported data for patients with native and prosthetic valves, we excluded data for patients with prosthetic valves if the data were reported separately. When outcomes could not be separated, we excluded studies in which more than 20% of the reported data were from patients with prosthetic valves and studies in which more than 40% of the reported data were from patients who used intravenous drugs. The probabilities used in the decision model are presented in Table 1. We derived the natural history of endocarditis and the mortality rate in uncomplicated bacteremia by pooling data from the literature and clinical data. Event probabilities for patients with bacteremia uncomplicated by endocarditis were derived by using data specific to patients with catheter-associated S. aureus bacteremia. Because of the paucity of data on catheter-related endocarditis, we derived event probabilities for patients who developed endocarditis from studies of patients with S. aureus endocarditis from any cause. When the pooled sample size was fewer than 100 S. aureus-infected patients, literature sources were expanded to include studies reporting event rates for endocarditis caused by any infectious microorganism. Derivation of these estimates is available from the authors in a technical report (www.dcri.duke.edu). Table 1. Probabilities for Decision Model The reported prevalence of endocarditis in patients with catheter-associated S. aureus bacteremia ranged from 0% to 38% (2, 5, 9-16) across heterogeneous patient groups. Because of this wide range among different patient populations, we did not use a pooled estimate for endocarditis prevalence. Rather, we worked backward from an accepted short-course relapse rate to derive an estimate of prevalence. The short-course relapse rate was adopted from a meta-analysis by Jernigan and Farr (19), which found a late complication rate of 6.1% in patients receiving short-course therapy for catheter-associated S. aureus bacteremia. Using this rate of relapse (cases attributed to occult endocarditis) and our assumption that short-course therapy would not cure any cases of endocarditis, we assigned an endocarditis prevalence rate of 6.1%. These estimates were tested extensively in sensitivity analyses. For patients with endocarditis, the relapse rate after long-course therapy was set at 2.6% (19). Published estimates of the sensitivity of TEE for vegetations or other intracardiac complications of endocarditis on native valves (including valve dehiscence and intracardiac abscess) range from 87% to 100% (21-31). Reported specificities range from 89% to 100% (21, 25, 27, 28). For the base-case analysis, we used a sensitivity of 96% from a study by Mugge and colleagues (22) in which surgical and autopsy findings were the gold standard for comparison. A value of 95% was used for the specificity because it falls in the mid-range of reported values. The morbidity (0.18%) and mortality (0.01%) rates associated with TEE were obtained from an analysis of more than 10 200 patients (80). One complication of intravenous antimicrobial therapy, phlebitis necessitating line removal with subsequent reinsertion for therapy completion, was also considered in this analysis. Catheter-survival rates were obtained from the literature (81). Because this complication is expressed as a per catheter-day rate, it was applied to all patients according to the number of days of antibiotic therapy received at home. The inclusion of only one complication of antimicrobial therapy biased the model in favor of long-course therapy. Costs The model took the societal perspective and included direct medical costs, direct nonmedical costs, and productivity costs (costs associated with lost ability to work because of illness or death) but excluded the intangible costs of pain and suffering. All medical costs were standardized to 1997 U.S. dollars by using the medical care component of the Consumer Price Index (87). All other costs were standardized by using the Consumer Price Index for All Urban Consumers (87). All costs are summari

Technical Report—Diagnosis and Management of an Initial UTI in Febrile Infants and Young Children

OBJECTIVES: The diagnosis and management of urinary tract infections (UTIs) in young children are clinically challenging. This report was developed to inform the revised, evidence-based, clinical guideline regarding the diagnosis and management of initial UTIs in febrile infants and young children, 2 to 24 months of age, from the American Academy of Pediatrics Subcommittee on Urinary Tract Infection. METHODS: The conceptual model presented in the 1999 technical report was updated after a comprehensive review of published literature. Studies with potentially new information or with evidence that reinforced the 1999 technical report were retained. Meta-analyses on the effectiveness of antimicrobial prophylaxis to prevent recurrent UTI were performed. RESULTS: Review of recent literature revealed new evidence in the following areas. Certain clinical findings and new urinalysis methods can help clinicians identify febrile children at very low risk of UTI. Oral antimicrobial therapy is as effective as parenteral therapy in treating UTI. Data from published, randomized controlled trials do not support antimicrobial prophylaxis to prevent febrile UTI when vesicoureteral reflux is found through voiding cystourethrography. Ultrasonography of the urinary tract after the first UTI has poor sensitivity. Early antimicrobial treatment may decrease the risk of renal damage from UTI. CONCLUSIONS: Recent literature agrees with most of the evidence presented in the 1999 technical report, but meta-analyses of data from recent, randomized controlled trials do not support antimicrobial prophylaxis to prevent febrile UTI. This finding argues against voiding cystourethrography after the first UTI.

Comprehensive cost-utility analysis of newborn screening strategies

BACKGROUND. Inborn errors of metabolism are a significant cause of morbidity and death among children. Inconsistencies in how individual states arrive at screening strategies, however, lead to marked variations in testing between states. OBJECTIVE. To determine the cost-effectiveness of each component test of a multitest newborn screening program, including screening for phenylketonuria, congenital adrenal hyperplasia, congenital hypothyroidism, biotinidase deficiency, maple syrup urine disease, galactosemia, homocystinuria, and medium-chain acyl-CoA dehydrogenase deficiency. METHODS. A decision model was used, with cohort studies, government reports, secondary analyses, and other sources. Discounted costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were measured. RESULTS. All except 2 screening tests dominated the “no-test” strategy. The 2 exceptions were screening for congenital adrenal hyperplasia, which cost slightly more than

Variations in risk attitude across race, gender, and education

20000 per QALY gained, and screening for galactosemia, which cost

Improving Decision Analyses: Parent Preferences (Utility Values) for Pediatric Health Outcomes

94000 per QALY gained. The screening test with the lowest expected cost was tandem mass spectrometry. The results found in our base-case analysis were stable across variations in nearly all variables. In instances in which changes in risks, sequelae, costs, or utilities did affect our results, the variation from base-case estimates was quite large. CONCLUSIONS. Newborn screening seems to be one of the rare health care interventions that is beneficial to patients and, in many cases, cost saving. Over the long term, funding comprehensive newborn screening programs is likely to save money for society.

Screening for Celiac Disease in Asymptomatic Children With Down Syndrome: Cost-effectiveness of Preventing Lymphoma

Background. Significant disparities in health care utilization exist across gender and race. Little is known about the patient-specific factors that may contribute to this variation. This study examined variations in risk attitude across major sociodemographic groups.Methods. A survey elicited utility measures for health states under risk-insensitive and risksensitive conditions (time tradeoff and standard gamble methods, respectively). Risk attitude was modeled assuming constant proportional risk posture, thus the utility function used was a power function. A multivariable linear regression model was used to examine the relationship between risk attitude and sociodemographic factors.Results.Of the 62 study subjects, the mean age was 47.6 years, 47% were female, and 33% were African American. Overall, 37% of respondents-were decidedly risk averse, 37% moderately risk averse, 15% moderately risk seeking, and 11% decidedly risk seeking. Significant predictors of increasing risk aversion in multivariate modeling were white race (P < 0.01) and lower education (P < 0.05). Women also tended to be more risk averse (P = 0.07).Conclusions.This study found significant differences in risk attitude across race and educational status, with a smaller difference across gender. Further research is needed to validate these findings and clarify their contribution to racial and gender variations in health care utilization and their future role in decision and cost-effectiveness analyses.

Hospital-acquired urinary tract infections in the pediatric patient: A prospective study

OBJECTIVE To gather and calculate utilities for a wide range of health states in the pediatric population. STUDY DESIGN The study subjects, parents or guardians at least 18 years of age with at least 1 child under age 18 years, were recruited through our Pediatric Research Network (PResNet). Recruitment locations included pediatric clinics, the Indiana State Fair, and public and private conventions. Each subjects utilities were assessed on 3 random health states out of 29 chosen for the study. Both the time trade-off and standard gamble methods were used to measure utilities. RESULTS Utilities were assessed in a total of 4016 participants (a recruitment rate of 88%). Utility values ranged from a high for acute otitis media (0.96 by standard gamble; 0.97 by time trade-off) to a low for severe mental retardation (0.59 by standard gamble; 0.51 by time trade-off). CONCLUSIONS Our extensive data set of utility assessments for a wide range of disease states can aid future economic evaluations of pediatric health care.

The Role of Herd Immunity in Parents’ Decision to Vaccinate Children: A Systematic Review

BACKGROUND. Studies demonstrate an increased prevalence of celiac disease in persons with Down syndrome, leading some organizations and authors to recommend universal screening of children with Down syndrome. However, many children with Down syndrome are asymptomatic, and the long-term implications of screening are unknown. The complication of celiac disease that leads to mortality in the general population is non-Hodgkins lymphomas. OBJECTIVES. The purpose of this research in asymptomatic children with Down syndrome was to (1) calculate the number needed to screen to prevent a single case of lymphoma and (2) present a cost-effectiveness study of screening. METHODS. We constructed a decision tree using probabilities derived from the published literature for Down syndrome or from the general population where Down syndrome-specific data were not available. Celiac disease was determined by serologic screening and confirmation with intestinal biopsy. Sensitivity analysis was used to alter probability estimates affecting the cost of preventing lymphoma. RESULTS. Using our baseline values, the no-screen strategy is dominant; that is, screening not only costs more but also results in fewer quality-adjusted life-years. A screening strategy costs more than

Automated Primary Care Screening in Pediatric Waiting Rooms

500000 per life-year gained. Screening all asymptomatic children with Down syndrome for celiac disease costs almost