Identification of inflammatory markers suitable for non-invasive, repeated measurement studies in biobehavioral research: A feasibility study.

INTRODUCTION: Studying the role of the immune system in the interaction between mental and physical health is challenging. To study individuals with an intensive, longitudinal study design that requires repetitive sampling in their daily life, non-invasive sampling techniques are a necessity. Urine can be collected in a non-invasive way, but this may be demanding for participants and little is known about fluctuation of inflammatory markers in urine over time. The aim of this study was to investigate the feasibility of non-invasive sampling, and to explore intra-individual differences in inflammatory markers in urine. MATERIALS & METHODS: Ten healthy individuals collected 24-hour urine for 63 consecutive days. In a pilot analysis, 39 inflammatory markers were examined for detectability in urine, stability over time and under storage conditions, and daily fluctuations. Multiplex analyses were used to quantify levels of eight selected markers: C-reactive protein (CRP), Fractalkine, Interleukin-1 receptor-antagonist (IL-1RA), interferon-α (IFNα), interferon-γ (IFNγ), Interferon gamma-induced protein 10 (IP10), Macrophage inflammatory protein-1ß (MIP-1ß), and Vascular Endothelial Growth Factor (VEGF). Cross-correlations were calculated between the overnight and 24-hour samples were calculated, to examine whether 24-hour urine could be replaced by the overnight portion for better feasibility. We examined intra- and interindividual differences in the levels of inflammatory markers in urine and the fluctuations thereof. RESULTS: This study showed that levels of selected inflammatory markers can be detected in urine. Cross-correlation analyses showed that correlations between levels of inflammatory markers in the night portion and the 24-hour urine sample varied widely between individuals. In addition, analyses of time series revealed striking inter- and intra-individual variation in levels of inflammatory markers and their fluctuations. CONCLUSION: We show that the assessment of urinary inflammatory markers is feasible in an intensive day-to-day study in healthy individuals. However, 24-hour urine cannot be replaced by an overnight portion to alleviate the protocol burden. Levels of inflammatory markers show substantial variation between and within persons.

Change Theory Contributes to Choosing Wisely for Immune Thrombocytopenia.

OBJECTIVES: Despite 2011 guidelines in which it is suggested that treatment of acute immune thrombocytopenia purpura (aITP) is not needed for patients without significant bleeding, only 14% of children treated for aITP have bleeding symptoms. Our aim was to decrease the percentage of children with first-episode aITP who were unnecessarily treated by 50% within 12 months of guideline implementation. METHODS: An intervention was designed by using the precaution-adoption-process model. A standard-of-practice meeting was organized and focused on clinician readiness for change. After education on current evidence and common cognitive errors, consensus clinical guidelines were created. After implementation, an article in a statewide professional newsletter was published to educate community providers. Unnecessary treatment (UT) was defined as treatment of any patient who only had bruising and/or self-resolving nose bleeds. Statistical process control charts were used to track progress, midline shifts were determined by Nelson's rules, and hospital costs were derived from administrative billing data. RESULTS: One hundred children with aITP were seen from January 2013 to September 2018. UT decreased from 70% to a sustained rate of <30% (P = .008), including a mean of 7% over the past 12 months. The admission rate decreased from 100% to 52% (P = .013), and the total percentage of patients treated decreased from 100% to 48% (P = .016), with both numbers continuing to decline. No adverse bleeding events occurred. An estimated 12 admissions, 4 readmissions, and 5 adverse events were avoided annually. CONCLUSIONS: We demonstrated successful improvement in UT of aITP through an educational intervention informed by the precaution-adoption-process model change theory.

Conducting Biobehavioral Research in Patients With Advanced Cancer: Recruitment Challenges and Solutions.

Despite significant advances in cancer treatment and symptom management interventions over the last decade, patients continue to struggle with cancer-related symptoms. Adequate baseline and longitudinal data are crucial for designing interventions to improve patient quality of life and reduce symptom burden; however, recruitment of patients with advanced cancer in longitudinal research is difficult. Our purpose is to describe challenges and solutions to recruitment of patients with advanced cancer in two biobehavioral research studies examining cancer-related symptoms. Study 1: Symptom data and peripheral blood for markers of inflammation were collected from newly diagnosed patients receiving chemotherapy on the first day of therapy and every 3-4 weeks for up to 6 months. Study 2: Symptom data, blood, and skin biopsies were collected from cancer patients taking epidermal growth factor receptor inhibitors at specific time points over 4 months. Screening and recruitment results for both studies are summarized. Timing informed consent with baseline data collection prior to treatment initiation was a significant recruitment challenge for both the studies. Possible solutions include tailoring recruitment to fit clinic needs, increasing research staff availability during clinic hours, and adding recruitment sites. Identifying solutions to these challenges will permit the conduct of studies that may lead to identification of factors contributing to variability in symptoms and development of tailored patient interventions for patients with advanced cancer.

Test-Retest Reliability of Traumatic Brain Injury Outcome Measures: A Traumatic Brain Injury Model Systems Study.

OBJECTIVE: Evaluate the test-retest reliability of measures that comprise the Traumatic Brain Injury Model Systems follow-up data set. PARTICIPANTS: A total of 224 persons with a moderate-severe traumatic brain injury (TBI) enrolled in the Traumatic Brain Injury Model Systems National Database. DESIGN: Following standard administration of the follow-up interview, a second interview was administered 14 to 28 days later using the same interviewer and the same mode of administration. MAIN MEASURES: Traumatic Brain Injury Model Systems follow-up interview that includes 66 variables comprised (a) single item measures of demographics; employment; general health as well as specific health conditions; rehospitalization; tobacco, alcohol, and other drug use; transportation; and mental health and (b) multi-item instruments: FIM; Participation Assessment With Recombined Tools-Objective; Disability Rating Scale; Glasgow Outcome Scale-Extended; Supervision Rating Scale; Satisfaction With Life Scale; TBI Quality of Life Anxiety and Depression items; and The Ohio State University TBI Identification Method. RESULTS: Intraclass correlation coefficient values ranged from 0.65 to 0.99, weighted kappa values ranged from 0.54 to 0.99, and kappa values ranged from 0.43 to 1.00. Four kappa/weighted kappa estimates fell below 0.60: arrested, psychiatric hospitalization, number of days not in good physical health, and rating of general emotional health. CONCLUSIONS: With few exceptions, good to excellent test-retest reliability estimates were obtained. The findings support the use of these measures in prior and future studies and indicate that persons with moderate-severe TBI can provide reliable self-report.

Design and development of a modified runway model of mouse drug self-administration.

The present study established a novel mouse model of a runway drug self-administration in our laboratory. The operant runway apparatus consisted of three long runways arranged in a zig-zag manner. The methodology consisted of six distinct phases: habituation, preconditioning, conditioning, post-conditioning, extinction and reinstatement. The effects of saline were compared with escalating doses of either ethanol (0.5-4.0 g/kg, i.p), heroin (5-40 mg/kg, i.p), or nicotine (0.1-0.5mg/kg, i.p) administered in the goal box during the conditioning phase (day 1 to day 5). A significant decrease in the time of trained (conditioned) mice to reach the goal box confirmed the subjects' motivation to seek those drugs on day 6 (expression). The mice were then subjected to non-rewarded extinction trials for 5 days over which run times were significantly increased. After 5 days of abstinence, a priming dose of ethanol or heroin (1/5th of maximum dose used in conditioning) significantly reinstated the drug-seeking behavior. These results suggest that the modified runway model can serve as a powerful behavioral tool for the study of the behavioral and neurobiological bases of drug self-administration and, as such, is appropriate simple but powerful tool for investigating the drug-seeking behavior of laboratory mice.