Interaction Between 2 Nutraceutical Treatments and Host Immune Status in the Pediatric Critical Illness Stress-Induced Immune Suppression Comparative Effectiveness Trial.

BACKGROUND AND AIMS: The pediatric Critical Illness Stress-induced Immune Suppression (CRISIS) trial compared the effectiveness of 2 nutraceutical supplementation strategies and found no difference in the development of nosocomial infection and sepsis in the overall population. We performed an exploratory post hoc analysis of interaction between nutraceutical treatments and host immune status related to the development of nosocomial infection/sepsis. METHODS: Children from the CRISIS trial were analyzed according to 3 admission immune status categories marked by decreasing immune competence: immune competent without lymphopenia, immune competent with lymphopenia, and previously immunocompromised. The comparative effectiveness of the 2 treatments was analyzed for interaction with immune status category. RESULTS: There were 134 immune-competent children without lymphopenia, 79 previously immune-competent children with lymphopenia, and 27 immunocompromised children who received 1 of the 2 treatments. A significant interaction was found between treatment arms and immune status on the time to development of nosocomial infection and sepsis ( P < .05) and on the rate of nosocomial infection and sepsis per 100 patient days ( P < .05). Whey protein treatment protected immune-competent patients without lymphopenia from infection and sepsis, both nutraceutical strategies were equivalent in immune-competent patients with lymphopenia, and zinc, selenium, glutamine, and metoclopramide treatment protected immunocompromised patients from infection and sepsis. CONCLUSIONS: The science of immune nutrition is more complex than previously thought. Future trial design should consider immune status at the time of trial entry because differential effects of nutraceuticals may be related to this patient characteristic.

Inherent Risk Factors for Nosocomial Infection in the Long Stay Critically Ill Child Without Known Baseline Immunocompromise: A Post Hoc Analysis of the CRISIS Trial.

BACKGROUND: Nosocomial infection remains an important health problem in long stay (>3 days) pediatric intensive care unit (PICU) patients. Admission risk factors related to the development of nosocomial infection in long stay immune competent patients in particular are not known. METHODS: Post-hoc analysis of the previously published Critical Illness Stress induced Immune Suppression (CRISIS) prevention trial database, to identify baseline risk factors for nosocomial infection. Because there was no difference between treatment arms of that study in nosocomial infection in the population without known baseline immunocompromise, both arms were combined and the cohort that developed nosocomial infection was compared with the cohort that did not. RESULTS: There were 254 long stay PICU patients without known baseline immunocompromise. Ninety (35%) developed nosocomial infection, and 164 (65%) did not. Admission characteristics associated with increased nosocomial infection risk were increased age, higher Pediatric Risk of Mortality version III score, the diagnoses of trauma or cardiac arrest and lymphopenia (P < 0.05). The presence of sepsis or infection at admission was associated with reduced risk of developing nosocomial infection (P < 0.05). In multivariable analysis, only increasing age, cardiac arrest and existing lymphopenia remained significant admission risk factors (P < 0.05); whereas trauma tended to be related to nosocomial infection development (P = 0.07). CONCLUSIONS: These data suggest that increasing age, cardiac arrest and lymphopenia predispose long stay PICU patients without known baseline immunocompromise to nosocomial infection. These findings may inform pre-hoc stratification randomization strategies for prospective studies designed to prevent nosocomial infection in this population.

Therapeutic hypothermia after pediatric cardiac arrest trials: the vanguard phase experience and implications for other trials.

OBJECTIVE: To determine whether an 18-month vanguard phase, in the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials, confirmed study feasibility and patient safety, a prerequisite to continued funding by the sponsor. DESIGN: Randomized controlled trial. SETTING: Pediatric intensive care and pediatric cardiac care units in 15 clinical sites in the United States and Canada. PATIENTS: Children aged 48 hrs to 18 yrs of age, with return of circulation after cardiac arrest. INTERVENTIONS: Therapeutic hypothermia vs. therapeutic normothermia. MEASUREMENTS AND MAIN RESULTS: The first 15 of 20 potential sites to obtain Institutional Review Board and subcontract approvals were selected as vanguard sites. Institutional Review Board approvals were obtained 92 days (median, interquartile range 65-114) and subcontracts signed 34 days (interquartile range 20-48) after distribution. Sites screened subjects at 13 days (interquartile range 9-21) and enrolled the first subjects 64 days (interquartile range 13-154) after study launch. The recruitment milestone was reached 4 months ahead of schedule, with no safety concerns identified. Overall recruitment in this ongoing trial remains on target. CONCLUSIONS: The Therapeutic Hypothermia after Pediatric Cardiac Arrest vanguard phase proved beneficial for the investigators and funding agency. Because complex multicenter trials are rarely ready to launch when grant funds are received, the vanguard allowed time to refine the protocol and recruitment approaches. Competition for vanguard positions led to expedient Institutional Review Board and subcontract completion. Early success and sustained momentum contributed to recruitment at or above goals. Financial risks to the sponsor were minimized by tying funding for the full trial to achieving prespecified milestones. A vanguard phase may be a desirable strategy for the successful conduct of other complex clinical trials.

Reaching emergency medical services providers: is one survey mode better than another?

OBJECTIVES: To determine which mode of completing a survey yields the highest response rate among emergency medical services (EMS) providers, examine rural and urban differences, and determine the completeness of questions by mode of response. METHODS: A random sample of EMS providers was mailed one of the following: 1) a paper survey, with instructions to return it via the enclosed self-addressed, stamped envelope; 2) a letter, with instructions to complete the survey at the provided URL (Web address); or 3) a paper survey with a self-addressed, stamped envelope and a URL, with the option of choosing the mode of response. We compared response rates based on the three different modes. We conducted analysis of the number of skipped multiple-choice and open-ended questions by mode and content analysis of the open-ended questions. RESULTS: The paper-only option resulted in the highest response rate (40.4%, p = 0.003) compared with the response rates from Web-only and choice of mode. Overall, rural EMS providers responded at a higher rate than urban EMS providers (40.3% vs. 31.6%, respectively [p = 0.0002]). Web respondents were more likely to complete all the open-ended questions (p = 0.003). Almost a fourth (22.8%) of the paper respondents skipped multiple-choice questions. There was a pattern of more complete responses for open-ended questions among the Web-based participants, but this was not significant (p = 0.17). CONCLUSION: EMS providers seem to prefer a more traditional mode (paper) when responding to a survey. Rural providers are more likely to respond. Mode of response influences the number of skipped questions but does not impact the quality of open-ended answers.