Investigation of the Optimal Timing of Treatment Change to Maximize the Delay of Onset Mucoid Pseudomonas Aeruginosa Pulmonary Infection in Pediatric Cystic Fibrosis Patients
Creators: name: Jiao, Tianze
Publisher: name: University of Utah
Year: 2019
Subjects: Pharmaceutical sciences
Epidemiology
Biostatistics

description: Cystic Fibrosis (CF) is the most common life-shortening autosomal recessive disorder. Those patients who have CF suffer from multiple comorbidities. Nearly 85% of the deaths related to CF are caused by lung disease. CF lung disease begins early in life with inflammation, impaired mucociliary clearance, and initial airway colonization by pathogens; it then progresses to chronic infection of the airways. To treat the continuous deterioration of lung function, CF patients need to use lung maintenance therapies continuously. These treatments are applied to patients for more than 30 years on average. However, the majority of evidence was identified using short-term follow-ups (less than 1 year). Moreover, no guidelines suggest when a treatment change is needed, nor do they suggest the order of prescribing those treatments. Therefore, a retrospective observational study was conducted using a national patient registry, the Cystic Fibrosis Foundation Patient Registry (CFFPR). By emulating randomized clinical trials (RCTs), this study investigated the treatment change pattern and the causality between suboptimal treatment status and the time to delay in acquisition of mucoid Pseudomonas aeruginosa pulmonary infection (mucoid PaPI). A cohort of pediatric CF patients (n=4,970) who were diagnosed with nonmucoid PaPI before mucoid PaPI during 2006-2011 was identified. Those patients were young, healthy, and received multiple chronic treatments only at the baseline. An instrument that indicated when the suboptimal treatment status has been achieved and a rational treatment change is needed was successfully generated by including demographic characteristics, comorbidities, clinical signals, and treatment histories. According to various thresholds of the instrument, which steered the decision of treatment change, 25 regimes were built. Each patient was hypothetically randomized to follow each one of 25 regimes independently. A fixed parameterization of the dynamic logistic marginal structural model with the constant-time hazard was applied to investigate the effectiveness of following each one of the 25 regimes. Using the effect of following one regime as the reference, if a physician changed treatment and was not following any regime, it would cause 17% more hazard of developing mucoid PaPI in his/her patient, during the 6-year follow-up. The hazard ratio ranged from 0.98 to 1.07 for other regimes. To summarize, for a physician, changing treatment without following any regime caused the worst outcome. The differences of treatment effect were trivial for the same patient who followed varied regimes to receive treatment. To achieve a better outcome, a physician should follow a regime, which is, perhaps, the optimal one, to change lung maintenance therapies, prudently prescribing an additional treatment from one of the three treatment classes: inhaled antibiotic, mucolytic, or anti-inflammatory.