Utilizing centralized biorepository samples for biomarkers of cystic fibrosis lung disease severity.

BACKGROUND: Circulating biomarkers reflective of lung disease activity and severity have the potential to improve patient care and accelerate drug development in CF. The objective of this study was to leverage banked specimens to test the hypothesis that blood-based biomarkers discriminate CF children segregated by lung disease severity. METHODS: Banked serum samples were selected from children who were categorized into two extremes of phenotype associated with lung function ('mild' or 'severe') based on CF-specific data and were matched on age, gender, CFTR genotype, and P. aeruginosa infection status. Targeted inflammatory proteins, lipids, and discovery metabolite profiles were measured in these serum samples. RESULTS: The severe cohort, characterized by a lower CF-specific FEV1 percentile, had significantly higher circulating concentrations of high sensitivity C-reactive protein, serum amyloid A, granulocyte colony stimulating factor, and calprotectin compared to the mild cohort. The mild cohort tended to have higher serum linoleic acid concentrations. The metabolite arabitol was lower in the severe cohort while other CF relevant metabolic pathways showed non-significant differences after adjusting for multiple comparisons. A sensitivity analysis to correct for biased estimates that may result from selecting subjects using an extremes of phenotype approach confirmed the protein biomarker findings. CONCLUSIONS: Circulating inflammatory proteins differ in CF children segregated by lung function. These findings serve to demonstrate the value of maintaining centralized, high quality patient derived samples for future research, with linkage to clinical information to answer testable hypotheses in biomarker development.

Physical Therapy-Based Exercise Protocol for Cancer Patients: Evaluating Outcomes for Cardiopulmonary Performance and Cancer-Related Fatigue.

BACKGROUND: Studies have shown that rehabilitation and fitness throughout cancer treatment interventions have been linked to improved outcomes for morbidity and mortality of cancer patients. This study serves to detail the efficacy of the Cancer Rehabilitation Physical Therapy Fitness and Debility (Ca PT) Program in cancer patients. OBJECTIVE: To describe the clinical population of cancer patients referred to the Ca PT Program and evaluate the efficacy of the program's therapy protocol in improving cardiopulmonary performance and cancer-related fatigue and pain. DESIGN: Retrospective study. SETTING: Outpatient clinics. PATIENTS: One hundred two adults who had been referred from a variety of referral sources and supervised individualized exercise programs. METHODS: Participation in the Ca PT Program. MAIN OUTCOME MEASUREMENTS: The primary outcome measure was a change in baseline-to-discharge scores in the 6-Minute Walk Test (6MWT), a cardiopulmonary performance measure. The secondary measures were changes in baseline-to-discharge scores of cancer-related fatigue and general pain, measured by patient self-report using a visual analogue scale. RESULTS: 6MWT values were significantly higher at discharge (mean 523 yards) than at baseline (mean 436), (P < .001, r = 0.57). Ninety-two percent of cases showed improvement and 58% of cases had a change on the 6MWT that met threshold for minimal important difference. Quality of life factors, fatigue (P < .001) and pain (P < .001) also significantly improved. CONCLUSIONS: The results indicate the Ca PT Program yields significant improvement in cardiovascular fitness, fatigue, and pain in people with cancer history. Personalized physical therapy fitness programs for individuals recovering from cancer treatment should be a standard component of cancer intervention. LEVEL OF EVIDENCE: III.

Biomarkers for cystic fibrosis drug development.

PURPOSE: To provide a review of the status of biomarkers in cystic fibrosis drug development, including regulatory definitions and considerations, a summary of biomarkers in current use with supportive data, current gaps, and future needs. METHODS: Biomarkers are considered across several areas of CF drug development, including cystic fibrosis transmembrane conductance regulator modulation, infection, and inflammation. RESULTS: Sweat chloride, nasal potential difference, and intestinal current measurements have been standardized and examined in the context of multicenter trials to quantify CFTR function. Detection and quantification of pathogenic bacteria in CF respiratory cultures (e.g.: Pseudomonas aeruginosa) are commonly used in early phase antimicrobial clinical trials, and to monitor safety of therapeutic interventions. Sputum (e.g.: neutrophil elastase, myeloperoxidase, calprotectin) and blood biomarkers (e.g.: C reactive protein, calprotectin, serum amyloid A) have had variable success in detecting response to inflammatory treatments. CONCLUSIONS: Biomarkers are used throughout the drug development process in CF, and many have been used in early phase clinical trials to provide proof of concept, detect drug bioactivity, and inform dosing for later-phase studies. Advances in the precision of current biomarkers, and the identification of new biomarkers with 'omics-based technologies, are needed to accelerate CF drug development.

Reclaim your creative confidence.

Most people are born creative. But over time, a lot of us learn to stifle those impulses. We become warier of judgment, more cautious more analytical. The world seems to divide into "creatives" and "noncreatives," and too many people resign themselves to the latter category. And yet we know that creativity is essential to success in any discipline or industry. The good news, according to authors Tom Kelley and David Kelley of IDEO, is that we all can rediscover our creative confidence. The trick is to overcome the four big fears that hold most of us back: fear of the messy unknown, fear of judgment, fear of the first step, and fear of losing control. The authors use an approach based on the work of psychologist Albert Bandura in helping patients get over their snake phobias: You break challenges down into small steps and then build confidence by succeeding on one after another. Creativity is something you practice, say the authors, not just a talent you are born with.