Judy Williams

Seattle Children's Hospital, Seattle, Washington, United States

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Publications (5)11.98 Total impact

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    ABSTRACT: To investigate the efficacy and safety of 4 antipseudomonal treatments in children with cystic fibrosis with recently acquired Pseudomonas aeruginosa infection. Randomized controlled trial. Multicenter trial in the United States. Three hundred four children with cystic fibrosis aged 1 to 12 years within 6 months of P aeruginosa detection. Participants were randomized to 1 of 4 antibiotic regimens for 18 months (six 12-week quarters) between December 2004 and June 2009. Participants randomized to cycled therapy received tobramycin inhalation solution (300 mg twice a day) for 28 days, with oral ciprofloxacin (15-20 mg/kg twice a day) or oral placebo for 14 days every quarter, while participants randomized to culture-based therapy received the same treatments only during quarters with positive P aeruginosa cultures. The primary end points were time to pulmonary exacerbation requiring intravenous antibiotics and proportion of P aeruginosa -positive cultures. The intention-to-treat analysis included 304 participants. There was no interaction between treatments. There were no statistically significant differences in exacerbation rates between cycled and culture-based groups (hazard ratio, 0.95; 95% confidence interval [CI], 0.54-1.66) or ciprofloxacin and placebo (hazard ratio, 1.45; 95% CI, 0.82-2.54). The odds ratios of P aeruginosa- positive culture comparing the cycled vs culture-based group were 0.78 (95% CI, 0.49-1.23) and 1.10 (95% CI, 0.71-1.71) comparing ciprofloxacin vs placebo. Adverse events were similar across groups. No difference in the rate of exacerbation or prevalence of P aeruginosa positivity was detected between cycled and culture-based therapies. Adding ciprofloxacin produced no benefits. ClinicalTrials.gov Identifier: NCT00097773.
    JAMA Pediatrics 09/2011; 165(9):847-56. · 4.28 Impact Factor
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    ABSTRACT: The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive pulmonary disease due to chronic endobronchial infection, particularly with Pseudomonas aeruginosa (Pa). Risk factors for and clinical impact of early Pa infection in young CF patients are less well understood. The present studies are designed to evaluate risk factors and outcomes associated with early Pa acquisition, and the benefits and harms of four anti-pseudomonal treatment regimens in young CF patients initiated after the first Pa positive respiratory culture. The Early Pseudomonas Infection Control (EPIC) program consists of two studies, a randomized multicenter trial in CF patients ages 1-12 years at first isolation of Pa from a respiratory culture, and a longitudinal cohort study enrolling Pa-negative patients. Using a factorial design, trial participants are assigned for 18 months to either anti-pseudomonal treatment on a scheduled quarterly basis (cycled therapy) or based on recovery of Pa from quarterly respiratory cultures (culture-based therapy). The study drugs include inhaled tobramycin (300 mg BID) for 28 days, combined with either oral ciprofloxacin (15-20 mg/kg BID) or oral placebo for 14 days. The primary endpoints of the trial are the time to pulmonary exacerbation requiring IV antibiotics or hospitalization for respiratory symptoms, and the proportion of patients with new Pa-positive respiratory cultures during the study. The broad goals of the observational study are to describe the risk factors and outcomes associated with early acquisition of Pa. 306 patients were randomized in the clinical trial and 1787 were enrolled in the cohort study. These companion studies will provide valuable epidemiological and microbiological information on early CF lung disease and Pa acquisition, and safety and clinical efficacy data on anti-pseudomonal treatment strategies for early Pa infections in the airways of young children with CF.
    Contemporary clinical trials 02/2009; 30(3):256-68. · 1.51 Impact Factor
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    ABSTRACT: Clinical trial networks that provide centralized coordination of multicenter studies have become critical to the advancement of clinical research. We describe a national effort by the U.S. Cystic Fibrosis Foundation (CFF) to build a network to evaluate therapeutic interventions in cystic fibrosis (CF). The CFF Therapeutics Development Network (CFF TDN) was established in 1998 and has since promoted the safe and efficient conduct of multiple clinical trials. The orphan disease setting presents many challenges for clinical research, and the CFF TDN has met these challenges by advancing CF outcome measures development and fostering innovative approaches toward the design and analysis of clinical trials.
    Children s Health Care 01/2008; 37(1):5-20. · 0.95 Impact Factor
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    ABSTRACT: Among young children with cystic fibrosis (CF), Pseudomonas aeruginosa (Pa) airway infection is associated with increased morbidity and mortality. Early intervention strategies include tobramycin solution for inhalation (TSI), which can eradicate lower airway Pa from cultures obtained at the end of 28 days of treatment in young children. We conducted an open label, sequential cohort study of TSI in young children with CF to investigate duration of antimicrobial treatment effect. The primary outcome was lower airway Pa eradication per bronchoalveolar lavage (BAL) fluid culture. Sequential treatment cohorts varied by duration of treatment (28 or 56 days) and timing of follow-up BAL (at Days 56, 84, or 112). Subjects (N = 36) were treated with TSI, 300 mg twice daily, for 28 days or 56 days per cohort assignment. Among 31 evaluable subjects, culture based, lower airway Pa eradication was observed in the majority of subjects for up to 1-3 months following TSI treatment: 75% in Cohort 28/56 (days of treatment/day of follow-up BAL), 63% in Cohort 28/84, 82% in Cohort 56/112, and 75% in Cohort 28/112. Non-mucoid Pa at baseline and/or exotoxin A seronegativity were associated with higher rates of eradication. There was a less pronounced effect of TSI treatment on Pa eradication from oropharyngeal cultures in all cohorts. TSI treatment was associated with reduced neutrophilic airway inflammation and was not related to any serious adverse events. TSI monotherapy is safe and can eradicate lower airway Pa for up to 3 months after treatment in young children with CF.
    Pediatric Pulmonology 08/2007; 42(7):610-23. · 2.38 Impact Factor
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    ABSTRACT: Clinical trials in cystic fibrosis (CF) currently use laboratory-specific reference ranges to evaluate chemistry and hematology measurements. Laboratory-specific normal reference ranges may not accurately reflect what is abnormal but clinically insignificant among CF patients. To address this concern, data from the Phase III trial of inhaled tobramycin in CF patients was used to describe the distribution and variability of laboratory parameters. The laboratory specimens were analyzed at a central laboratory after being obtained at baseline and throughout the 24-week trial. At the time of entry into the clinical trial, 91% (463 of 508) of patients had at least a single value outside the normal range. Liver function tests (AST, ALT) were above the normal range in 16% and 12% of the patients respectively, with 2.4% of patients having an AST>2.0 times the upper limit of normal. Of the 243 patients on placebo, 242 (99.6%) had at least one laboratory parameter that changed from normal to abnormal during the 24-week follow-up period. Of those same placebo patients, 11.5% (N=28) had a laboratory parameter change from a Common Toxicity Criteria (CTC) grade 0 to grade 2 or higher during follow-up. Patients with CF frequently have laboratory values outside the normal range and have significant longitudinal variability of laboratory values. Interpretation of adverse events in the clinical trial setting may be complicated by the underlying high rates of some laboratory abnormalities in the CF population. This data was presented in poster format at the American Thoracic Society International Conference, Atlanta, USA, 2002, appearing subsequently in the Conference proceedings [Goss CH, Mayer-Hamblett N, Yunker A, Waltz DA, Kronmal RA, Ramsey BW. Laboratory parameter profiles among patients with cystic fibrosis. Am J Rep Crit Care Med 2002;165(8):A283].
    Journal of Cystic Fibrosis 04/2007; 6(2):117-23. · 2.87 Impact Factor

Publication Stats

103 Citations
11.98 Total Impact Points

Institutions

  • 2011
    • Seattle Children's Hospital
      Seattle, Washington, United States
  • 2009
    • Trinity Washington University
      Washington, Washington, D.C., United States
  • 2007–2009
    • University of Washington Seattle
      • • Department of Anesthesiology and Pain Medicine
      • • Department of Medicine
      Seattle, WA, United States
    • Washington Regional Medical Center
      Fayetteville, Arkansas, United States