Comparative Effects of CT Imaging Measurement on RECIST End Points and Tumor Growth Kinetics Modeling.

Quantitative assessments of tumor burden and modeling of longitudinal growth could improve phase II oncology trials. To identify obstacles to wider use of quantitative measures we obtained recorded linear tumor measurements from three published lung cancer trials. Model-based parameters of tumor burden change were estimated and compared with similarly sized samples from separate trials. Time-to-tumor growth (TTG) was computed from measurements recorded on case report forms and a second radiologist blinded to the form data. Response Evaluation Criteria in Solid Tumors (RECIST)-based progression-free survival (PFS) measures were perfectly concordant between the original forms data and the blinded radiologist re-evaluation (intraclass correlation coefficient = 1), but these routine interrater differences in the identification and measurement of target lesions were associated with an average 18-week delay (range, -20 to 55 weeks) in TTG (intraclass correlation coefficient = 0.32). To exploit computational metrics for improving statistical power in small clinical trials will require increased precision of tumor burden assessments.

Evaluation of blood lead proficiency testing: comparison of open and blind paradigms.

BACKGROUND: Most proficiency testing (PT) programs operate with an open design in which clearly identified performance samples are distributed directly to participating laboratories on a shipping schedule announced in advance. In this study, we examine the effectiveness of assessing clinical laboratory performance for blood lead with an open PT by comparing its results with a double-blinded testing protocol. METHODS: Aliquots from up to 72 blood lead performance pools from the New York State Department of Health and the Wisconsin State Laboratory of Hygiene were disguised as routine patient specimens and submitted in two phases to up to 42 certified clinical laboratories for blood lead analysis. These 42 laboratories also received aliquots of the same performance samples for blood lead analysis directly from the "open" PT program provider. RESULTS: Data reported under blind and open strategies were scored against acceptable target ranges using the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) criteria established for blood lead, i.e., +/- 0.19 micromol/L (+/- 4 microg/dL) or +/- 10%, whichever is greater. Performance differences between the strategies were also assessed. We found that 17.7% of all blind PT results were classified as unacceptable compared with only 4.5% of open PT results (P <0.001). In phase 1, 13 of 22 laboratories (60%) exhibited a statistically significant difference (P <0.05) between their blind and open PT performances, although for 6 laboratories the poorer blind performance may not necessarily have led to unsuccessful PT participation under CLIA '88 criteria. Seven (32%) laboratories had unsuccessful aggregate performance (<80%) under blind testing while maintaining successful performance in open testing. Of these seven, two had gross discrepancies motivating further investigation. CONCLUSIONS: The data suggest that although approximately 60% of clinical laboratories make special efforts to improve analytical performance on open PT samples relative to performance achieved for routine patient specimens, in most cases the differences are clinically insignificant and would not likely affect cumulative PT performance. Occasional use of blind PT may deter the inclination to treat performance samples more carefully.

Beliefs about diagnosing asthma in young children.

OBJECTIVES: To determine what factors primary care pediatricians believe are important in establishing the initial diagnosis of childhood asthma and to identify variations in physicians' beliefs concerning this clinical decision. STUDY DESIGN: Massachusetts American Academy of Pediatrics Fellows were surveyed about their beliefs concerning the importance of 20 clinical factors associated with establishing the initial diagnosis of asthma. RESULTS: Most clinicians considered recurrent wheeze (96%), symptomatic improvement with a bronchodilator (90%), recurrent cough (89%), exclusion of alternative diagnoses (87%), and suggestive peak flow findings (82%) as important in diagnosing asthma. However, there was substantial heterogeneity among clinicians as to which combinations of factors they each considered relevant; for example, only 60% identified all 5 of the above factors to be necessary or important. Further, <50% identified presence of any of the 20 factors as necessary. Although national guidelines cite objective assessment of pulmonary function as essential, spirometry and peak expiratory flow testing were identified as necessary by only 8% and 10%, respectively. Two factors believed to contribute to establishing the asthma diagnosis contradicted the National Asthma Education and Prevention Program guidelines and expert opinion (age >2 years and absence of fever during episodes) and these beliefs were more likely held by those clinicians in practice for >5 years. CONCLUSIONS: The majority of pediatricians believe several common clinical factors establish a diagnosis of childhood asthma, but disagree over what combinations of these factors are important. Some misconceptions persist despite wide dissemination of clinical practice guidelines. We believe that future asthma guidelines will need to organize diagnostic criteria in an easily understood format, like a decision tree, to facilitate early recognition of asthma in young children.

Practical considerations when treating children with antimicrobials in the outpatient setting.

Over the past decade new antimicrobial agents have been introduced used to treat common paediatric infectious diseases such as acute otitis media and sinusitis. These agents vary with respect to their mechanism of action, dosage and duration of therapy, cost, taste and type of adverse effects. More recently, there has been concern about the overuse of antibiotics and increasing bacterial resistance, particularly Streptococcus pneumoniae, to these agents. Dosage and duration of therapy, cost, taste, and adverse effects play important roles in determining success or failure of antimicrobial medications in paediatric patients. Use of potential alternatives and adjuncts to antimicrobial treatment, such as vaccination, control of environmental risk factors, surgical techniques and alternative medical therapies may also be employed, and the practitioner must ascertain if their paediatric patients are being treated by any of these methods. Rather than listing the therapeutic challenges for all common outpatient paediatric infectious diseases, acute otitis media (accounting for over 50% of the antimicrobial prescriptions dispensed in childhood) is used to illustrate each issue. Clinicians are faced with a growing number of possible antimicrobial choices; concomitantly, there is increasing concern that these agents are overused. When prescribing antimicrobial agents, we need to be familiar with what we can do to optimise the care we provide. By avoiding inappropriate or trivial use of antimicrobials, we can preserve and even strengthen our armamentarium against disease. Simple strategies can improve compliance with therapeutic regimens and improve parental satisfaction.