Bruce C Marshall

University of Chicago, Chicago, Illinois, United States

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Publications (50)460.37 Total impact

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    ABSTRACT: People with cystic fibrosis (CF) are managed differently in the USA and UK providing an opportunity to learn from differences in practice patterns.
    Thorax 09/2014; · 8.38 Impact Factor
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    ABSTRACT: Advances in treatments for cystic fibrosis (CF) continue to extend survival. An updated estimate of survival is needed for better prognostication and to anticipate evolving adult care needs.
    Annals of internal medicine 08/2014; 161(4):233-241. · 13.98 Impact Factor
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    08/2014; 35(S1):S1-S67.
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    ABSTRACT: Bringing new therapies to patients with rare diseases depends in part on optimizing clinical trial conduct through efficient study start-up processes and rapid enrollment. Suboptimal execution of clinical trials in academic medical centers not only results in high cost to institutions and sponsors, but also delays the availability of new therapies. Addressing the factors that contribute to poor outcomes requires novel, systematic approaches tailored to the institution and disease under study.
    Journal of general internal medicine. 07/2014;
  • Bruce C Marshall, Eugene C Nelson
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    ABSTRACT: Remarkable biomedical research advances have led to innovative and increasingly effective therapies. We highlight several scientific milestones in elucidating the pathophysiology of cystic fibrosis (CF) and review the therapies that have become available over the past 20 years. In 2002, the CF Foundation launched a multifaceted quality improvement initiative to accelerate improvement in CF care. We present evidence of substantial improvement in process measures, such as more consistent outpatient follow-up, and key medical outcomes, including survival, pulmonary function and nutritional status. We offer our perspective on factors critical to the success of the quality improvement initiative, including a compelling strategic plan and the commitment of the CF Foundation to its implementation; the investment in building improvement capacity at CF care centres; the engagement of people with CF and their families as partners; and the integration of quality improvement into the existing CF care framework. In addition to a continued investment in building and sustaining improvement capacity at CF care centres, and deeper patient engagement, we will address the oppressive treatment burden. We will also complement the measurement of clinical outcomes with patient reported outcomes and healthcare costs for a balanced assessment of the quality and value of care. Major advances in basic science and therapeutic development coupled with improvements in healthcare delivery have resulted in striking gains in medical outcomes for people with CF.
    BMJ quality & safety 04/2014; 23(Suppl_1):i95-i103. · 2.39 Impact Factor
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    ABSTRACT: Benchmarking is the process of using outcome data to identify high-performing centres and determine practices associated with their outstanding performance. The US Cystic Fibrosis Foundation (CFF) Patient Registry contains centre-specific outcomes data for all CFF-certified paediatric and adult cystic fibrosis (CF) care programmes in the USA. The CFF benchmarking project analysed these registry data, adjusting for differences in patient case mix known to influence outcomes, and identified the top-performing US paediatric and adult CF care programmes for pulmonary and nutritional outcomes. Separate multidisciplinary paediatric and adult benchmarking teams each visited 10 CF care programmes, five in the top quintile for pulmonary outcomes and five in the top quintile for nutritional outcomes. Key practice patterns and approaches present in both paediatric and adult programmes with outstanding clinical outcomes were identified and could be summarised as systems, attitudes, practices, patient/family empowerment and projects. These included: (1) the presence of strong leadership and a well-functioning care team working with a systematic approach to providing consistent care; (2) high expectations for outcomes among providers and families; (3) early and aggressive management of clinical declines, avoiding reliance on 'rescues'; and (4) patients/families that were engaged, empowered and well informed on disease management and its rationale. In summary, assessment of practice patterns at CF care centres with top-quintile pulmonary and nutritional outcomes provides insight into characteristic practices that may aid in optimising patient outcomes.
    BMJ quality & safety 04/2014; 23(Suppl_1):i15-i22. · 2.39 Impact Factor
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    ABSTRACT: Current definitions of pulmonary exacerbation (PE) in cystic fibrosis are based on studies in participants with significant lung disease and may not reflect the spectrum of findings observed in younger patients with early lung disease. We used data from a recent trial assessing the efficacy of azithromycin in children to study signs and symptoms associated with PEs and related changes in lung function and weight. While increased cough was present in all PEs, acute weight loss and reduction in oxygen saturation were not observed. Changes in lung function did not differ between subjects who did experience a PE and those who were exacerbation-free. Cough was the predominant symptom in CF patients with early lung disease experiencing a PE. There was no significant difference in mean 6-month change in lung function or weight among subjects with one or more exacerbations and those without an exacerbation.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 09/2013; · 3.19 Impact Factor
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    ABSTRACT: Rationale: Cystic fibrosis (CF) is an autosomal recessive disease characterized by abnormal airways secretions, chronic endobronchial infection, and progressive airway obstruction. The use of medications to slow the progression of lung disease has led to significant improvement in survival. An evidence review of chronic medications for CF lung disease was performed in 2007 to provide guidance to clinicians in evaluating and selecting appropriate treatment for individuals with this disease. We have undertaken a new review of the literature to update the recommendations, including consideration of new medications and additional evidence on previously reviewed therapies. A multidisciplinary committee of experts in CF pulmonary care was established to review the evidence for use of chronic medications for CF lung disease and make treatment recommendations. Published evidence for chronic lung therapies was systematically reviewed and resulting treatment recommendations were graded based on the United States Preventive Services Task Force scheme. These guidelines provide up-to-date evidence of safety and efficacy of chronic treatments of CF lung disease, including the use of novel therapies that have not previously been included in CF pulmonary guidelines.
    American Journal of Respiratory and Critical Care Medicine 04/2013; 187(7):680-9. · 11.04 Impact Factor
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    ABSTRACT: Background Many patients with cystic fibrosis (CF) now reach adulthood, at which time the risk of cancer is increased. The aim of this study was to determine cancer risks in nontransplanted and transplanted CF patients.Methods From 1990 to 2009, we followed 41,188 patients who received care at one of the 250 CF care center programs in the United States and compared the observed number of cancers in nontransplanted and transplanted patients with that expected in the general US population.ResultsIn 344,114 patient-years of observation of nontransplanted patients, the overall cancer risk was similar to the background risk (standardized incidence ratio [SIR] = 1.1, 95% confidence interval [CI] = 1.0 to 1.3). However, we observed an elevated risk of digestive tract cancer (SIR = 3.5, 95% CI = 2.6 to 4.7) involving the esophago-gastric junction, biliary tract, small bowel, and colon. There was also an increased risk of testicular cancer (SIR = 1.7, 95% CI = 1.02 to 2.7) and lymphoid leukemia (SIR = 2.0, 95% CI = 1.2 to 3.1) and a decreased risk of malignant melanoma (SIR = 0.4, 95% CI = 0.2 to 0.9). In 8235 patient-years of observation of transplanted patients, 26 tumors were observed compared with 9.6 expected (SIR = 2.7, 95% CI = 1.8 to 3.9). The increased risk was particularly high for digestive tract cancers (SIR = 17.3, 95% CI = 10.7 to 26.5), with most cases arising in the bowel.Conclusions The overall burden of cancer in CF patients remains low; however they have an increased risk of digestive tract cancer, particularly following transplantation. They also have increased risk of lymphoid leukemia and testicular cancer, and decreased risk of melanoma.
    CancerSpectrum Knowledge Environment 11/2012; · 14.07 Impact Factor
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    ABSTRACT: We previously performed a randomized placebo-controlled trial to examine the effects of azithromycin in children and adolescents 6-18 years of age with cystic fibrosis uninfected with Pseudomononas aeruginosa and demonstrated that while azithromycin did not acutely improve pulmonary function, azithromycin-reduced pulmonary exacerbations, decreased the initiation of new oral antibiotics, and improved weight gain. We now report the results of the open-label, follow-on study to assess durability of response to azithromycin and continued safety and tolerability. Eligible participants were enrolled in a 24-week open-label study of azithromycin to compare efficacy and safety endpoints during the placebo-controlled trial versus open-label study in two groups: participants initially on azithromycin continued azithromycin (azithromycin-azithromycin) and participants initially on placebo who then received azithromycin (placebo-azithromycin). As in the placebo-controlled trial, the azithromycin dose in the open-label study was 250 mg Monday-Wednesday-Friday for participants weighing 18-35.9 kg and 500 mg Monday-Wednesday-Friday for participants weighing 36 kg or greater. Of 174 eligible participants, 146 (83.9%) enrolled in the open-label study. No significant improvements in lung function were observed within either group. There were no differences in outcomes in the placebo-azithromycin group during the placebo-controlled versus open-label phase. The azithromycin-azithromycin group had comparable odds of experiencing an exacerbation during the two phases (OR 1.6, CI(95) 0.8, 3.0) and stable weight gain, but new oral antibiotics were initiated more frequently during the open-label study (OR 1.9, CI(95) 1.0, 3.5). In both groups, adverse event rates were comparable during the placebo-controlled and open-label study and treatment-emergent pathogens were rare. During the open-label study, we observed continued durability of treatment response to azithromycin, as measured by pulmonary exacerbations and continued weight gain, although use of oral antibiotics increased. There were no new safety concerns. Currently available data suggest that azithromycin reduces exacerbations and improves weight gain for 6-12 months among children and adolescents with CF uninfected with P. aeruginosa.
    Pediatric Pulmonology 07/2012; 47(7):641-8. · 2.38 Impact Factor
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    ABSTRACT: Abstract BACKGROUND:While the mechanism of action by which azithromycin exerts positive effects in cystic fibrosis (CF) patients remains unclear, evidence suggest that azithromycin may act as an immunomodulatory agent. We examined changes in systemic inflammatory markers in a recent double blind randomized controlled trial of oral azithromycin in CF patients 6-18 years of age uninfected with Pseudomonas aeruginosa (NCT00431964). METHODS:White cell counts and differential, serum myeloperoxidase (MPO), high sensitivity C reactive protein (hsCRP), intracellular adhesion molecule 1 (ICAM 1), interleukin 6 (IL-6), calprotectin, serum amyloid A (SAA), and granulocyte colony stimulating factor (G-CSF) were measured at baseline, after 28 and 168 days of treatment in patients receiving either oral azithromycin or placebo. RESULTS:Inflammatory markers were similar in both groups at baseline. HsCRP, MPO, SAA, and calprotectin, as well as the absolute neutrophil count (ANC), significantly decreased from baseline to Day 28 in the azithromycin group as compared to the placebo group (p < 0.05). This treatment effect was sustained at Day 168 for ANC, calprotectin and SAA (p < 0.05). Changes in hsCRP, calprotectin and SAA at day 28 were negatively correlated with changes in FEV(1) (L) and FEV(1) (% predicted) as well as both absolute and relative changes in weight (p < 0.05). Except for weight (%), the associations remained significant for calprotectin; FEV(1)(L) and weight (%) remained significantly correlated with 168-day change in hsCRP. The 168-day change in ANC was significantly correlated with changes in lung function, but not in weight; the change in G-CSF was significantly correlated with the change in weight (%) only. CONCLUSIONS:In patients not infected with P. aeruginosa, oral azithromycin significantly reduced neutrophil counts and serum inflammatory markers within 28 days of initiating treatment.
    Chest 05/2012; · 7.13 Impact Factor
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    ABSTRACT: The current lifetable approach to survival estimation is favoured by CF registries. Recognising the limitation of this approach, we examined the utility of a parametric survival model to project birth cohort survival estimates beyond the follow-up period, where short duration of follow-up meant median survival estimates were indeterminable. Parametric models were fitted to observed survivorship data from the US CF Foundation (CFF) Patient Registry 1980-1994 birth cohort. Model-predicted median survival was estimated. The best fitting model was applied to a Cystic Fibrosis Registry of Ireland dataset to allow an evaluation of the model's ability to estimate predicted median survival. This involved a comparison of birth cohort lifetable predicted and observed (Kaplan-Meier) median survival estimates. A Weibull model with main effects of gender and birth cohort was developed using a US CFF dataset (n=13,115) for which median survival was not directly estimable. Birth cohort lifetable predicted median survival for male and female patients born between 1985 and 1994 and surviving their first birthday was 50.9 and 42.4 years respectively. To evaluate the accuracy of a Weibull model in predicting median survival, a model was developed for the 1980-1984 Cystic Fibrosis Registry of Ireland birth cohort (n=243), which had an observed (Kaplan-Meier) median survival of 27.7 years. Model-predicted median survival estimates were calculated using data censored at different follow-up periods. The estimates converged to the true value as length of follow-up increased. Accurate prognostic information that is clinically critical for care of patients affected by rare, life-limiting disorders can be provided by parametric survival models. Problems associated with short duration of follow-up for recent birth cohorts can be overcome using this approach, providing better opportunities to monitor survival and plan services locally.
    Thorax 06/2011; 66(8):674-9. · 8.38 Impact Factor
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    Diabetes care 12/2010; 33(12):2677-83. · 7.74 Impact Factor
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    Diabetes care 12/2010; 33(12):2697-708. · 7.74 Impact Factor
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    ABSTRACT: Comparing international estimates of survival can be a useful way of highlighting differences in life expectancy between cystic fibrosis (CF) populations. In this study, we compared survival in two CF populations. The current lifetable method takes age-specific mortality rates observed in a given year and applies them to a hypothetical population assuming those rates will remain the same in the future. This was used to compare median predicted survival in the United States (US) and the Republic of Ireland (RoI) (1986-2008). Median age at death among decedents was also examined. In both countries, median age at death was lower than median predicted survival. Successive increases in annual median predicted survival were not observed; rather an overall improvement was discerned over time. In the RoI, where absolute numbers of deaths were small, year-on-year fluctuations in age-specific mortality rates resulted in wide-ranging annual median predicted survival estimates. Median age at death is not a good measure of CF survival. Though median predicted survival improved in each country over the study period, between-country comparison at a given time point may be misleading for rare disorders like CF. Longitudinal outcomes must be examined.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 09/2010; 10(1):62-5. · 3.19 Impact Factor
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    ABSTRACT: Cystic fibrosis (CF) is a recessive genetic disease characterized by dehydration of the airway surface liquid and impaired mucociliary clearance. As a result, individuals with the disease have difficulty clearing pathogens from the lung and experience chronic pulmonary infections and inflammation. There may be intermittent pulmonary exacerbations or acute worsening of infection and obstruction, which require more intensive therapies. Hemoptysis and pneumothorax are complications commonly reported in patients with cystic fibrosis. This document presents the CF Foundation's Pulmonary Therapies Committee recommendations for the treatment of hemoptysis and pneumothorax. The committee recognized that insufficient data exist to develop evidence-based recommendations and so used the Delphi technique to formalize an expert panel's consensus process and develop explicit care recommendations. The expert panel completed the survey twice, allowing refinement of recommendations. Numeric responses to the questions were summarized and applied to a priori definitions to determine levels of consensus. Recommendations were then developed to practical treatment questions based upon the median scores and the degree of consensus. These recommendations for the management of the patient with CF with hemoptysis and pneumothorax are designed for general use in most individuals but should be adapted to meet specific needs as determined by the individuals, their families, and their health care providers. It is hoped that the guidelines provided in this manuscript will facilitate the appropriate application of these treatments to improve and extend the lives of all individuals with cystic fibrosis.
    American Journal of Respiratory and Critical Care Medicine 08/2010; 182(3):298-306. · 11.04 Impact Factor
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    ABSTRACT: The authors were given the charge of providing a vision of the future in paediatric respirology. Themes selected for being ripe for this visionary analysis include bronchopulmonary dysplasia (BPD), asthma, cystic fibrosis (CF), lung infections, obstructive sleep disordered breathing (OSDB) and pulmonary diagnostics and monitoring. A profound reduction or elimination of BPD is seen. Given the strong genetic component of this disease, genetic biomarkers will likely be identified that will permit much earlier recognition of BPD susceptibility and potentially the ability to modify disease course by altering gene expression. The ultimate prevention of BPD will be to prevent prematurity, but recognition of both the genetic basis of BPD and the inflammatory background should lead to improved prevention and therapy. A clear understanding and definition of asthma phenotypes will lead to more specific and targeted therapy, earlier detection and prevention, better monitoring of severity and adherence to therapy, lower mortality and decreased inappropriate diagnosis of asthma. The greatest opportunities in asthma care will likely come through tools to improve adherence to effective therapy. Also, areas are identified where better therapies are needed such as in patients with severe mucus hypersecretion (secretory hyperresponsiveness) especially in those with life-threatening asthma. The future of CF is easier to foresee with early successes seen in clinical trials. After the expected ability to correct the CF transmembrane regulator, care will need to change and additional research will be needed. Additionally, the face of CF is changing with more adults than children presently having the disease. This will necessitate changes to our approach to treating this disease in a fortunately aging population. If we are going to affect the worldwide lung health of children, we will need to address respiratory infections particularly pneumonia, tuberculosis and HIV-associated infections. Preventive, diagnostic and treatment strategies will shape the future face of these problems. The availability of inexpensive, readily available, and rapid molecular techniques to identify true infection (including HIV and tuberculosis) may permit earlier use of effective therapy while preventing the inappropriate use of antibiotics for common viral diseases. Sleep medicine will continue to be an important aspect of paediatric pulmonology. The evaluation of OSDB cannot rely on full-night attended polysomnography due to limited access. Identifying reliable markers of end organ dysfunction in children with OSDB may permit more rapid identification of patients in need of intervention like CPAP and assisted breathing. In addition, management options, as an alternative to adenotonsilectomy, are listed with a call for further research. Pulmonary diagnostics and monitoring will see the development and refinement of tools like the lung clearance index and the analysis of exhaled gases, volatiles and dissolved biomarkers of inflammation as techniques that might help clinicians identify both the initiation of inflammation while it is more amenable to therapy, and to identify more readily the early changes associated with chronic lung diseases in children. The authors hope that these visionary articles will generate comments, arguments, inspiration, and perhaps even motivate funding agencies.
    Respirology 07/2010; 15(5):733-41. · 2.78 Impact Factor
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    ABSTRACT: Azithromycin is recommended as therapy for cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa infection, but there has not been sufficient evidence to support the benefit of azithromycin in other patients with CF. To determine if azithromycin treatment improves lung function and reduces pulmonary exacerbations in pediatric CF patients uninfected with P. aeruginosa. A multicenter, randomized, double-blind placebo-controlled trial was conducted from February 2007 to July 2009 at 40 CF care centers in the United States and Canada. Of the 324 participants screened, 260 were randomized and received study drug. Eligibility criteria included age of 6 to 18 years, a forced expiratory volume in the first second of expiration (FEV(1)) of at least 50% predicted, and negative respiratory tract cultures for P. aeruginosa for at least 1 year. Randomization was stratified by age of 6 to 12 years vs 13 to 18 years and by CF center. The active group (n = 131) received 250 mg (weight 18-35.9 kg) or 500 mg (weight > or = 36 kg) of azithromycin 3 days per week (Monday, Wednesday, and Friday) for 168 days. The placebo group (n = 129) received identically packaged placebo tablets on the same schedule. The primary outcome was change in FEV(1). Exploratory outcomes included additional pulmonary function end points, pulmonary exacerbations, changes in weight and height, new use of antibiotics, and hospitalizations. Changes in microbiology and adverse events were monitored. The mean (SD) age of participants was 10.7 (3.17) years. The mean (SD) FEV(1) at baseline and 168 days were 2.13 (0.85) L and 2.22 (0.86) L for the azithromycin group and 2.12 (0.85) L and 2.20 (0.88) L for the placebo group. The difference in the change in FEV(1) between the azithromycin and placebo groups was 0.02 L (95% confidence interval [CI], -0.05 to 0.08; P = .61). None of the exploratory pulmonary function end points were statistically significant. Pulmonary exacerbations occurred in 21% of the azithromycin group and 39% of the placebo group. Participants in the azithromycin group had a 50% reduction in exacerbations (95% CI, 31%-79%) and an increase in body weight of 0.58 kg (95% CI, 0.14-1.02) compared with placebo participants. There were no significant differences between groups in height, use of intravenous or inhaled antibiotics, or hospitalizations. Participants in the azithromycin group had no increased risk of adverse events, but had less cough (-23% treatment difference; 95% CI, -33% to -11%) and less productive cough (-11% treatment difference; 95% CI, -19% to -3%) compared with placebo participants. In children and adolescents with CF uninfected with P. aeruginosa, treatment with azithromycin for 24 weeks did not result in improved pulmonary function. clinicaltrials.gov Identifier: NCT00431964.
    JAMA The Journal of the American Medical Association 05/2010; 303(17):1707-15. · 29.98 Impact Factor
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    ABSTRACT: RATIONALE: Cystic fibrosis is a recessive genetic disease characterized by dehydration of the airway surface liquid and impaired mucociliary clearance. As a result, individuals with the disease have difficulty clearing pathogens from the lung and experience chronic pulmonary infections and inflammation. There may be intermittent pulmonary exacerbations, or acute worsening of infection and obstruction, which require more intensive therapies. Hemoptysis and pneumothorax are complications commonly reported in patients with cystic fibrosis. OBJECTIVES: This document presents the CF Foundation√Ęs Pulmonary Therapies Committee recommendations for the treatment of hemoptysis and pneumothorax. METHODS: The committee recognized that insufficient data exist to develop evidence-based recommendations and so used the Delphi technique to formalize an expert panel√Ęs consensus process and develop explicitly care recommendations. CONCLUSIONS: These recommendations for the management of the CF patient with hemoptysis and pneumothorax are designed for general use in most individuals but should be adapted to meet specific needs as determined by the individuals, their families, and their health care providers. It is hoped that the guidelines provided in this manuscript will facilitate the appropriate application of these treatments to improve and extend the lives of all individuals with cystic fibrosis.
    American Journal of Respiratory and Critical Care Medicine 03/2010; · 11.04 Impact Factor

Publication Stats

2k Citations
460.37 Total Impact Points

Institutions

  • 2014
    • University of Chicago
      Chicago, Illinois, United States
  • 2013
    • University of Kentucky
      • Department of Pediatrics
      Lexington, Kentucky, United States
    • Johns Hopkins Medicine
      • Department of Pediatrics
      Baltimore, MD, United States
  • 2005–2012
    • Columbia University
      • Department of Pediatrics
      New York City, NY, United States
  • 2009
    • University of Colorado
      • Department of Pediatrics
      Denver, CO, United States
    • University at Buffalo, The State University of New York
      Buffalo, New York, United States
  • 2007–2009
    • Medical University of South Carolina
      • Department of Medicine
      Charleston, SC, United States
  • 2001–2005
    • University of Utah
      • Department of Internal Medicine
      Salt Lake City, Utah, United States
    • The University of Tokyo
      • Faculty & Graduate School of Medicine
      Tokyo, Tokyo-to, Japan
  • 1998–2002
    • Intermountain Medical Center
      Salt Lake City, Utah, United States