Browsing by Author "Marshall, Bruce C."

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    A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment
    (American Thoracic Society, 2021) Goss, Christopher H.; Heltshe, Sonya L.; West, Natalie E.; Skalland, Michelle; Sanders, Don B.; Jain, Raksha; Barto, Tara L.; Fogarty, Barbra; Marshall, Bruce C.; VanDevanter, Donald R.; Flume, Patrick A.; STOP2 Investigators; Pediatrics, School of Medicine
    Rationale: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. Objectives: To test differing durations of intravenous antimicrobials for CF exacerbations. Methods: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7–10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days’ total antimicrobial duration; all others were randomized to 14 or 21 days’ duration. Measurements and Main Results: The primary outcome was percent predicted FEV1 (ppFEV1) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV1 change was 12.8 and 13.4 for 10 and 14 days, respectively, a ‒0.65 difference (95% CI [‒3.3 to 2.0]), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV1 changes, a difference of ‒0.10 (‒1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive. Conclusions: Among adults with CF with early treatment improvement during exacerbation, ppFEV1 after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days.
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    Baseline ultrasound and clinical correlates in children with cystic fibrosis.
    (Elsevier, 2015-10) Leung, Daniel H.; Ye, Wen; Molleston, Jean P.; Weymann, Alexander; Ling, Simon; Paranjape, Shruti M.; Romero, Rene; Schwarzenberg, Sara Jane; Palermo, Joseph; Alonso, Estella M.; Murray, Karen F.; Marshall, Bruce C.; Sherker, Averell H.; Siegel, Marilyn J.; Krishnamurthy, Rajesh; Harned, Roger; Karmazyn, Boaz; Magee, John C.; Narkewicz, Michael R.; Department of Pediatrics, IU School of Medicine
    Objective: To investigate the relationship between abdominal ultrasound (US) findings and demographic, historical and clinical features in children with CF. Study design: Children age 3-12 years with CF without known cirrhosis, were enrolled in a prospective, multi-center study of US to predict hepatic fibrosis. Consensus US patterns were assigned by 3 radiologists as normal, heterogeneous, homogeneous, or cirrhosis. Data were derived from direct collection and U.S. or Toronto CF registries. Chi-square or ANOVA were used to compare variables among US groups and between normal and abnormal. Logistic regression was used to study risk factors for having abnormal US. Results: Findings in 719 subjects were normal (n=590, 82.1%), heterogeneous (64, 8.9%), homogeneous (41, 5.7%), and cirrhosis (24, 3.3%). Cirrhosis (p=0.0004), homogeneous (p<0.0001) and heterogeneous (p=0.03) were older than normal. More males were heterogeneous (p=0.001). More heterogeneous (15.0%, p=0.009) and cirrhosis (25.0%, p=0.005) had
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    Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation
    (Elsevier, 2017-02) Farrell, Philip M.; White, Terry B.; Ren, Clement L.; Hempstead, Sarah E.; Accurso, Frank; Derichs, Nico; Howenstine, Michelle; McColley, Susanna A.; Rock, Michael; Rosenfeld, Margaret; Sermet-Gaudelus, Isabelle; Southern, Kevin W.; Marshall, Bruce C.; Sosnay, Patrick R.; Department of Pediatrics, School of Medicine
    Objective Cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, continues to present diagnostic challenges. Newborn screening and an evolving understanding of CF genetics have prompted a reconsideration of the diagnosis criteria. Study design To improve diagnosis and achieve standardized definitions worldwide, the CF Foundation convened a committee of 32 experts in CF diagnosis from 9 countries to develop clear and actionable consensus guidelines on the diagnosis of CF and to clarify diagnostic criteria and terminology for other disorders associated with CFTR mutations. An a priori threshold of ≥80% affirmative votes was required for acceptance of each recommendation statement. Results After reviewing relevant literature, the committee convened to review evidence and cases. Following the conference, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 27 of 28 statements, 7 of which needed revisions and a second round of voting. Conclusions It is recommended that diagnoses associated with CFTR mutations in all individuals, from newborn to adult, be established by evaluation of CFTR function with a sweat chloride test. The latest mutation classifications annotated in the Clinical and Functional Translation of CFTR project (http://www.cftr2.org/index.php) should be used to aid in diagnosis. Newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may be designated CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis; these terms are now merged and equivalent, and CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis may be used. International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for use in diagnoses associated with CFTR mutations are included.