Emergency research without prior consent in the United States, Canada, European Union and United Kingdom: How regulatory differences affect study design and implementation in cardiac arrest trials.

Aim: A major barrier to performing cardiac arrest trials is the requirement for prospective informed consent, which is often infeasible during individual medical emergencies. In an effort to improve outcomes, some governments have adopted legislation permitting research without prior consent (RWPC) in these circumstances. We aimed to outline key differences between legislation in four Western locations and explore the effects of these differences on trial design and implementation in cardiac arrest research. Data sources: We performed a narrative review of RWPC legislation in the United States (US), Canada, the European Union (EU) and the United Kingdom (UK). Results: The primary criteria required to perform RWPC was similar across locations: the study must involve an individual medical emergency during which neither the prospective subject nor their authorized representative can provide informed consent. The US regulations were unique in their requirements for performing Community Consultation and Public Disclosure in the communities in which the research takes place. Another major difference was the requirement for consent for ongoing participation in Canada, the EU and the UK, while only notification of enrollment and the opportunity to discontinue participation are required in the US. Additionally, only Canada and the EU explicitly state that the subject or their representative may request withdrawal of their data. Conclusion: Regulations governing RWPC in the US, Canada, the EU and the UK have similar goals and protections for vulnerable populations during medical emergencies. Differences in the qualifying criteria and implementation procedures exist across locations and may affect study design.

Implementation and facilitation of post-resuscitation debriefing: a comparative crossover study of two post-resuscitation debriefing frameworks.

BACKGROUND: Post-resuscitation debriefing (PRD) is the process of facilitated, reflective discussion, enabling team-based interpersonal feedback and identification of systems-level barriers to patient care. The importance and benefits of PRD are well recognized; however, numerous barriers exist, preventing its practical implementation. Use of a debriefing tool can aid with facilitating debriefing, creating realistic objectives, and providing feedback. OBJECTIVES: To assess utility of two PRD tools, Debriefing In Situ Conversation after Emergent Resuscitation Now (DISCERN) and Post-Code Pause (PCP), through user preference. Secondary aims included evaluating differences in quality, subject matter, and types of feedback between tools and implications on quality improvement and patient safety. METHODS: Prospective, crossover study over a 12-month period from February 2019 to January 2020. Two PDR tools were implemented in 8 week-long blocks in acute care settings at a tertiary care children's hospital. Debriefings were triggered for any intubation, resuscitation, serious/unanticipated patient outcome, or by request for distressing situations. Post-debriefing, team members completed survey evaluations of the PDR tool used. Descriptive statistics were used to analyze survey responses. A thematic analysis was conducted to identify themes that emerged from qualitative responses. RESULTS: A total of 114 debriefings took place, representing 655 total survey responses, 327 (49.9%) using PCP and 328 (50.1%) using DISCERN. 65.2% of participants found that PCP provided emotional support while only 50% of respondents reported emotional support from DISCERN. PCP was found to more strongly support clinical education (61.2% vs 56.7%). There were no significant differences in ease of use, support of the debrief process, number of newly identified improvement opportunities, or comfort in making comments or raising questions during debriefs between tools. Thematic analysis revealed six key themes: communication, quality of care, team function & dynamics, resource allocation, preparation and response, and support. CONCLUSION: Both tools provide teams with an opportunity to reflect on critical events. PCP provided a more organized approach to debriefing, guided the conversation to key areas, and discussed team member wellbeing. When implementing a PRD tool, environmental constraints, desired level of emotional support, and the extent to which open ended data is deemed valuable should be considered.

Applications of Postresuscitation Debriefing Frameworks in Emergency Settings: A Systematic Review.

OBJECTIVES: Postresuscitation debriefing (PRD) is a valuable educational tool in emergency medicine. It is recommended by international resuscitation guidelines, has been shown to improve both patient outcomes and resuscitation team performance, and is frequently requested by medical learners. However, there is limited research comparing standardized debriefing frameworks. Not only does this hinder the ability of interested emergency departments (EDs) to adopt PRD, but it limits the quality of future debriefing research. We sought to identify and compare existing PRD frameworks to inform the implementation of effective PRD in emergency medicine. METHODS: We conducted a systematic review following PRISMA standards to identify debriefing frameworks used in the ED and other acute care settings for further analysis. Identified frameworks were analyzed and compared based on a method previously described in the literature. RESULTS: Our search identified six frameworks, which ranged from simple tools for immediate feedback to complex, hospital-wide systems engineering-based approaches to quality improvement. Key findings were the importance of ensuring debriefing facilitators are properly selected and trained and of tailoring framework design to specific organizational targets. However, there is limited validation data for these frameworks, and more study is needed to identify and validate true best practices in PRD. CONCLUSIONS: All six identified frameworks seem to be effective methods of debriefing. Given the breadth in debriefing methods and goals identified, this suggests that there may not be a one-size-fits-all approach to PRD and that organizations should instead identify their own unique needs and barriers and adopt the debriefing framework that best addresses those needs. Other findings were the importance of well-trained debriefing facilitators and the use of clear roles in organizing debriefings. Further research is needed to assess the effectiveness of postresuscitation frameworks with regard to both team performance and patient outcomes.

Fast I(n)dentification of Pathogens in Neonates (FINDPATH-N): protocol for a prospective pilot cohort study of next-generation sequencing for pathogen identification in neonates with suspected sepsis.

INTRODUCTION: Sepsis is a major source of morbidity and mortality in neonates; however, identification of the causative pathogens is challenging. Many neonates have negative blood cultures despite clinical evidence of sepsis. Next-generation sequencing (NGS) is a high-throughput, parallel sequencing technique for DNA. Pathogen-targeted enrichment followed by NGS has the potential to be more sensitive and faster than current gold-standard blood culture. In this pilot study, we will test the feasibility and pathogen detection patterns of pathogen-targeted NGS in neonates with suspected sepsis. Additionally, the distribution and diagnostic accuracy of biomarkers cell-free DNA and protein C levels at two time points will be explored. METHODS AND ANALYSIS: We will conduct a prospective, pilot observational study. Neonates over 1 kg with suspected sepsis from a single tertiary care children's hospital will be recruited for the study. Recruitment will be censored at 200 events or 6 months' duration. Two blood study samples will be taken: the first simultaneous to the blood culture (time=0 hour, for NGS and biomarkers) via an exception to consent (deferred consent) and another 24 hours later after prospective consent (biomarkers only). Neonates will be adjudicated into those with clinical sepsis, culture-proven sepsis and without sepsis based on clinical criteria. Feasibility parameters (eg, recruitment) and NGS process time will be reported.For analysis, NGS results will be described in aggregate, compared with the simultaneous blood culture (sensitivity and specificity) and reviewed via expert panel for plausibility. Pilot data for biomarker distribution and diagnostic accuracy (sensitivity and specificity) for distinguishing between septic and non-septic neonates will be reported. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Hamilton Integrated Research Ethics Board. We will seek publication of study results in peer-reviewed journals.

A trial to determine whether septic shock-reversal is quicker in pediatric patients randomized to an early goal-directed fluid-sparing strategy versus usual care (SQUEEZE): study protocol for a pilot randomized controlled trial.

BACKGROUND: Current pediatric septic shock resuscitation guidelines from the American College of Critical Care Medicine focus on the early and goal-directed administration of intravascular fluid followed by vasoactive medication infusions for persistent and fluid-refractory shock. However, accumulating adult and pediatric data suggest that excessive fluid administration is associated with worse patient outcomes and even increased risk of death. The optimal amount of intravascular fluid required in early pediatric septic shock resuscitation prior to the initiation of vasoactive support remains unanswered. METHODS/DESIGN: The SQUEEZE Pilot Trial is a pragmatic, two-arm, parallel-group, open-label, prospective pilot randomized controlled trial. Participants are children aged 29 days to under 18 years with suspected or confirmed septic shock and a need for ongoing resuscitation. Eligible participants are enrolled under an exception to consent process and randomly assigned via concealed allocation to either the Usual Care (control) or Fluid Sparing (intervention) resuscitation strategy. The primary objective of this pilot trial is to determine feasibility, based on the ability to enroll participants and to adhere to the study protocol. The primary outcome measure by which success will be determined is participant enrollment rate ("pass" defined as at least two participants/site/month, recognizing that enrollment may be slower during the run-in phase). Secondary objectives include assessing (1) appropriateness of eligibility criteria, and (2) completeness of clinical outcomes to inform the endpoints for the planned multisite trial. To support the nested translational study, SQUEEZE-D, we will also evaluate the feasibility of describing cell-free DNA (a procoagulant molecule with prognostic utility) in blood samples obtained from children enrolled into the SQUEEZE Pilot Trial at baseline and at 24 h. DISCUSSION: The optimal degree of fluid resuscitation and the timing of initiation of vasoactive support in order to achieve recommended therapeutic targets in children with septic shock remains unanswered. No prospective study to date has examined this important question for children in developed countries including Canada. Recruitment for the SQUEEZE Pilot Trial opened on 6 January 2014. Findings will inform the feasibility of the planned multicenter trial to answer our overall research question. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01973907 , registered on 23 October 2013.

Exploring the experiences of substitute decision-makers with an exception to consent in a paediatric resuscitation randomised controlled trial: study protocol for a qualitative research study.

INTRODUCTION: Prospective informed consent is required for most research involving human participants; however, this is impracticable under some circumstances. The Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS) outlines the requirements for research involving human participants in Canada. The need for an exception to consent (deferred consent) is recognised and endorsed in the TCPS for research in individual medical emergencies; however, little is known about substitute decision-maker (SDM) experiences. A paediatric resuscitation trial (SQUEEZE) (NCT01973907) using an exception to consent process began enrolling at McMaster Children's Hospital in January 2014. This qualitative research study aims to generate new knowledge on SDM experiences with the exception to consent process as implemented in a randomised controlled trial. METHODS AND ANALYSIS: The SDMs of children enrolled into the SQUEEZE pilot trial will be the sampling frame from which ethics study participants will be derived. DESIGN: Qualitative research study involving individual interviews and grounded theory methodology. PARTICIPANTS: SDMs for children enrolled into the SQUEEZE pilot trial. SAMPLE SIZE: Up to 25 SDMs. Qualitative methodology: SDMs will be invited to participate in the qualitative ethics study. Interviews with consenting SDMs will be conducted in person or by telephone, taped and professionally transcribed. Participants will be encouraged to elaborate on their experience of being asked to consent after the fact and how this process occurred. ANALYSIS: Data gathering and analysis will be undertaken simultaneously. The investigators will collaborate in developing the coding scheme, and data will be coded using NVivo. Emerging themes will be identified. ETHICS AND DISSEMINATION: This research represents a rare opportunity to interview parents/guardians of critically ill children enrolled into a resuscitation trial without their knowledge or prior consent. Findings will inform implementation of the exception to consent process in the planned definitive SQUEEZE trial and support development of evidence-based ethics guidelines.

Evaluating the test re-test reliability and inter-subject variability of Health Care Provider manual fluid resuscitation performance.

BACKGROUND: Health Care Providers (HCPs) report that manual techniques of intravascular fluid resuscitation are commonly used during pediatric shock management. The optimal pediatric fluid resuscitation technique is currently unknown. We sought to determine HCP test-retest reliability (repeatability) and inter-subject variability of fluid resuscitation performance outcomes to inform the design of future studies. METHODS: Fifteen consenting HCPs from McMaster Children's Hospital, in Hamilton, Canada participated in this single-arm interventional trial. Participants were oriented to a non-clinical model representing a 15 kg toddler, which incorporated a 22-gauge IV catheter. Following a standardization procedure, participants administered 600 mL (40 mL/kg) of saline to the simulated child under emergency conditions using prefilled 60-mL syringes. Each participant completed 5 testing trials. All testing was video recorded, with fluid administration time outcome data (in seconds) extracted from trial videos by two blinded outcome assessors. Data describing catheter dislodgement events, volume of saline effectively delivered, and participant demographics were also collected. The primary outcome of fluid administration time test-retest reliability was analyzed by one-way analysis of variance (ANOVA) and intra-class correlation (ICC), with good reliability defined as ICC > 0.70. RESULTS: Differences in HCP fluid administration times are attributable to inter-subject variability rather than intra-subject variability based on one-way ANOVA analysis, F (14,60) = 43.125; p < 0.001. Test-retest reliability of subjects was excellent with ICC = 0.97 (95% CI: 0.95-0.99); p < 0.001. CONCLUSIONS: Findings demonstrate excellent test-retest reliability of HCP fluid resuscitation performance in a setting involving a non-clinical model. Investigators can justify a single evaluation of HCP performance in future studies.

Rapid paediatric fluid resuscitation: a randomised controlled trial comparing the efficiency of two provider-endorsed manual paediatric fluid resuscitation techniques in a simulated setting.

OBJECTIVES: Manual techniques of intravascular fluid administration are commonly used during paediatric resuscitation, although it is unclear which technique is most efficient in the hands of typical healthcare providers. We compared the rate of fluid administration achieved with the disconnect-reconnect and push-pull manual syringe techniques for paediatric fluid resuscitation in a simulated setting. METHODS: This study utilised a randomised crossover trial design and enrolled 16 consenting healthcare provider participants from a Canadian paediatric tertiary care centre. The study was conducted in a non-clinical setting using a model simulating a 15 kg child in decompensated shock. Participants administered 900 mL (60 mL/kg) of normal saline to the simulated patient using each of the two techniques under study. The primary outcome was the rate of fluid administration, as determined by two blinded independent video reviewers. We also collected participant demographic data and evaluated other secondary outcomes including total volume administered, number of catheter dislodgements, number of technical errors, and subjective and objective measures of provider fatigue. RESULTS: All 16 participants completed the trial. The mean (SD) rate of fluid administration (mL/s) was greater for the disconnect-reconnect technique at 1.77 (0.145) than it was for the push-pull technique at 1.62 (0.226), with a mean difference of 0.15 (95% CI 0.055 to 0.251; p=0.005). There was no difference in mean volume administered (p=0.778) or participant self-reported fatigue (p=0.736) between techniques. No catheter dislodgement events occurred. CONCLUSIONS: The disconnect-reconnect technique allowed for the fastest rate of fluid administration, suggesting that use of this technique may be preferable in situations requiring rapid resuscitation. These findings may help to inform future iterations of paediatric resuscitation guidelines. TRIAL REGISTRATION NUMBER: This trial was registered at ClinicalTrials.gov [NCT01774214] prior to enrolling the first participant.

Identifying significant and relevant events during pediatric transport: a modified Delphi study.

OBJECTIVES: Children must often be transported to dedicated pediatric centers to receive specialized medical and surgical care, which places them at risk for significant deterioration and life-threatening events. Studies designed to identify and mitigate these events have been limited by variability in the selection and definition of significant events. The objective of this study was to identify and evaluate indicators that represent significant events during the transport of pediatric patients and are relevant to future research initiatives in transport medicine. DESIGN: We conducted a modified Delphi study consisting of four iterations. SETTING: The expert panel included Canadian, interdisciplinary healthcare providers with transport experience. INTERVENTIONS: In the first Delphi iteration, experts suggested indicators for consideration and evaluated proposed indicators from the literature and introduced by the study steering committee. In subsequent iterations, respondents reevaluated all indicators that had not yet achieved a priori-defined consensus; group comments and aggregate scores for each indicator from previous iterations were provided. MEASUREMENTS AND MAIN RESULTS: The expert panel consisted of 16 physicians and 17 nonphysician healthcare providers from 10 Canadian institutions. In total, the panel evaluated 57 indicators, including 26 not previously presented in the literature. The expert panel determined 52 were significant and relevant to future studies in pediatric transport. The final indicator list includes trigger tools (interventions, physiological markers, and laboratory values) and team member safety and process issues. CONCLUSIONS: Using a systematic, modified Delphi approach, we developed an inclusive list of indicators for application to pediatric transport-related quality improvement and clinical research projects.

Factors affecting pediatric isotonic fluid resuscitation efficiency: a randomized controlled trial evaluating the impact of syringe size.

BACKGROUND: Goal-directed therapy guidelines for pediatric septic shock resuscitation recommend fluid delivery at speeds in excess of that possible through use of regular fluid infusion pumps. In our experience, syringes are commonly used by health care providers (HCPs) to achieve rapid fluid resuscitation in a pediatric fluid resuscitation scenario. At present, it is unclear which syringe size health care providers should use when performing fluid resuscitation to achieve maximal fluid resuscitation efficiency. The objective of this study was therefore to determine if an optimal syringe size exists for conducting manual pediatric fluid resuscitation. METHODS: This 48-participant parallel group randomized controlled trial included 4 study arms (10, 20, 30, 60 mL syringe size groups). Eligible participants were HCPs from McMaster Children's Hospital, Hamilton, Canada blinded to the purpose of the trial. Consenting participants were randomized using a third party technique. Following a standardization procedure, participants administered 900 mL (60 mL/kg) of isotonic saline to a simulated 15 kg child using prefilled provided syringes of the allocated size in rapid sequence. Primary outcome was total time to administer the 900 mL and this data was collected through video review by two blinded outcome assessors. Sample size was predetermined based upon a primary outcome analysis using one-way ANOVA. RESULTS: 12 participants were randomized to each group (n=48) and all completed trial protocol to analysis. Analysis was conducted according to intention to treat principles. A significant difference in fluid resuscitation time (in seconds) was found between syringe size group means: 10 mL, 563s [95% CI 521; 606]; 20 mL, 506s [95% CI 64; 548]; 30 mL, 454s [95% CI 412; 596]; 60 mL, 455s [95% CI 413; 497] (p<0.001). CONCLUSIONS: The syringe size used when performing manual pediatric fluid resuscitation has a significant impact on fluid resuscitation speed, in a setting where fluid filled syringes are continuously available. Greatest efficiency was achieved with 30 or 60 mL syringes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01494116.

Sodium bicarbonate use in shock and cardiac arrest: attitudes of pediatric acute care physicians.

OBJECTIVES: To evaluate the preferences and self-reported practices of pediatric acute care physicians with respect to sodium bicarbonate administration to infants and children in shock or cardiac arrest. DESIGN: National survey study utilizing a self-administered questionnaire. SETTING: Thirteen Canadian pediatric tertiary care centers. SUBJECTS: Canadian pediatric critical care physicians, pediatric emergency physicians, and trainees in these subspecialties. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Survey items were evaluated based on Yes/No responses, frequency responses, and Likert scales. Overall response rate was 53% (151/284) with 49.0% (74/151) citing pediatric critical care as their primary practice. 82.0% of respondents (123/150) indicated they would administer sodium bicarbonate as part of ongoing resuscitation for septic shock, whereas 58.3% (88/151) would administer sodium bicarbonate in a cardiac arrest scenario (p=0.004). 47.3% (71/150) selected a pH threshold at or below which they would administer sodium bicarbonate (mean, 6.94±0.013; median, 7.00; range, 6.50-7.20; interquartile range, 6.90-7.00), whereas 20.5% (31/151) selected a base excess threshold (mean, -15.62±0.78; median, -16; range, -20 to -4; interquartile range, -20 to -14). Both pH and duration of resuscitation were strongly associated with the decision to administer sodium bicarbonate (p<0.0001). Respondents' perceptions regarding a colleague's likelihood of administering sodium bicarbonate to the same patient under the same circumstances reflect an acknowledgment of disparate practices with respect to sodium bicarbonate use. 53.0% (79/149) felt current American Heart Association guidelines help them in deciding whether to administer sodium bicarbonate to critically ill patients, and 84% would support a randomized trial. CONCLUSION: Differences of opinion exist among pediatric acute care physicians with respect to the timing and appropriateness of sodium bicarbonate administration during resuscitation. Most indicated they would support moving forward with a clinical trial.

Translating resuscitation guidelines into practice: health care provider attitudes, preferences and beliefs regarding pediatric fluid resuscitation performance.

INTRODUCTION: Children who require fluid resuscitation for the treatment of shock present to tertiary and non-tertiary medical settings. While timely fluid therapy improves survival odds, guidelines are poorly translated into clinical practice. The objective of this study was to characterize the attitudes, preferences and beliefs of health care providers working in acute care settings regarding pediatric fluid resuscitation performance. METHODS: A single-centre survey study was conducted at McMaster Children's Hospital from January to May, 2012. The sampling frame (n = 115) included nursing staff, physician staff and subspecialty trainees working in Pediatric Emergency Medicine (PEM) or Pediatric Critical Care Medicine (PCCM). A self-administered questionnaire was developed and assessed for face validity prior to distribution. Eligible participants were invited at 0, 2, and 4 weeks to complete a web-based version of the survey. A follow-up survey administration phase was conducted to improve the response rate. RESULTS: Response rate was 72.2% (83/115), with 83% (68/82) self-identifying as nursing staff and 61% (50/82) as PCCM providers. Resuscitation experience, frequency of shock management, and years in specialty, were similar between PCCM and PEM responders. Physicians and nurses had differing opinions regarding the most effective method to achieve rapid fluid resuscitation in young children presenting in shock (p<0.001). Disagreement also existed regarding the age and size of patients in whom rapid infuser devices, such as the Level-1 Rapid Infuser, should be used (p<0.001). Providers endorsed a number of potential concerns related to the use of rapid infuser devices in children, and only 14% of physicians and 55% of nursing staff felt that they had received adequate training in the use of such devices (p = 0.005). CONCLUSIONS: There is a lack of consensus among health care providers regarding how pediatric fluid resuscitation guidelines should be operationalized, supporting a need for further work to define best practices.

Study protocol for a randomised controlled trial comparing the efficiency of two provider-endorsed manual paediatric fluid resuscitation techniques.

INTRODUCTION: Paediatric shock is a life-threatening condition with many possible causes and a global impact. Current resuscitation guidelines require rapid fluid administration as a cornerstone of paediatric shock management. However, little evidence is available to inform clinicians how to most effectively perform rapid fluid administration where this is clinically required, resulting in suboptimal knowledge translation of current resuscitation guidelines into clinical practice. OBJECTIVES: This study aims to determine which of the two commonly used techniques for paediatric fluid resuscitation (disconnect-reconnect technique and push-pull technique) yields a higher fluid administration rate in a simulated clinical scenario. Secondary objectives include determination of catheter dislodgement rates, subjective and objective measures of provider fatiguability and descriptive information regarding any technical issues encountered with performance of each method under the study. METHODS AND ANALYSIS: This study will utilise a randomised crossover trial design. Participants will include consenting healthcare providers from McMaster Children's Hospital. Each participant will administer 900 ml (60 ml/kg) of normal saline to a simulated 15 kg infant as quickly as possible on two separate occasions using the manual fluid administration techniques under the study. The primary outcome, rate of fluid administration, will be evaluated using a paired two-tailed Student t test. ETHICS AND DISSEMINATION: This protocol has been approved by the Hamilton Health Sciences Research Ethics Board. RESULTS: These will be published in a peer-reviewed scientific journal and presented at one or more scientific conferences. PROTOCOL REGISTRATION: Protocol Registered on ClinicalTrials.gov NCT01774214.

Prospective evaluation of direct approach with a tablet device as a strategy to enhance survey study participant response rate.

BACKGROUND: Investigators conduct survey studies for a variety of reasons. Poor participant response rates are common, however, and may limit the generalizability and utility of results. The objective of this study was to determine whether direct approach with a tablet device enhances survey study participant response rate and to assess participants' experiences with this mode of survey administration. FINDINGS: An interventional study nested within a single center survey study was conducted at McMaster Children's Hospital. The primary outcome was the ability to achieve of a survey study response rate of 70% or greater. Eligible participants received 3 email invitations (Week 0, 2, 4) to complete a web-based (Survey Monkey) survey. The study protocol included plans for a two-week follow-up phase (Phase 2) where non-responders were approached by a research assistant and invited to complete an iPad-based version of the survey. The Phase 1 response rate was 48.7% (56/115). Phase 2 effectively recruited reluctant responders, increasing the overall response rate to 72.2% (83/115). On a 7-point Likert scale, reluctant responders highly rated their enjoyment (mean 6.0, sd 0.83 [95% CI: 5.7-6.3]) and ease of use (mean 6.7, sd 0.47 [95% CI: 6.5-6.9]) completing the survey using the iPad. Reasons endorsed for Phase 2 participation included: direct approach (81%), immediate survey access (62%), and the novelty of completing a tablet-based survey (54%). Most reluctant responders (89%) indicated that a tablet-based survey is their preferred method of survey completion. CONCLUSIONS: Use of a tablet-based version of the survey was effective in recruiting reluctant responders and this group reported positive experiences with this mode of survey administration.

Rapid, easy, and cheap randomization: prospective evaluation in a study cohort.

BACKGROUND: When planning a randomized controlled trial (RCT), investigators must select randomization and allocation procedures based upon a variety of factors. While third party randomization is cited as being among the most desirable randomization processes, many third party randomization procedures are neither feasible nor cost-effective for small RCTs, including pilot RCTs. In this study we present our experience with a third party randomization and allocation procedure that utilizes current technology to achieve randomization in a rapid, reliable, and cost-effective manner. METHODS: This method was developed by the investigators for use in a small 48-participant parallel group RCT with four study arms. As a nested study, the reliability of this randomization procedure was prospectively evaluated in this cohort. The primary outcome of this nested study was the proportion of subjects for whom allocation information was obtained by the Research Assistant within 15 min of the initial participant randomization request. A secondary outcome was the average time for communicating participant group assignment back to the Research Assistant. Descriptive information regarding any failed attempts at participant randomization as well as costs attributable to use of this method were also recorded. Statistical analyses included the calculation of simple proportions and descriptive statistics. RESULTS: Forty-eight participants were successfully randomized and group allocation instruction was received for 46 (96%) within 15 min of the Research Assistant placing the initial randomization request. Time elapsed in minutes until receipt of participant allocation instruction was Mean (SD) 3.1 +/- 3.6; Median (IQR) 2 (2,3); Range (1-20) for the entire cohort of 48. For the two participants for whom group allocation information was not received by the Research Assistant within the 15-min pass threshold, this information was obtained following a second request at 18 and 20 min, respectively. The method described here produced an email audit trail, which proved useful to the primary study. CONCLUSIONS: We report a method of third party randomization that uses current technology to operationalize randomization and allocation in a rapid, easy, and cost-effective manner. Other investigators may find this method useful, particularly for small RCTs, including pilot RCTs, on a tight budget.

Predictors of major intervention in infants with bronchiolitis.

OBJECTIVE: We sought to identify predictors of the major medical intervention (MMI) in infants with bronchiolitis in the Emergency Department (ED) to recognize those in need of hospitalization versus the candidates for discharge. PATIENTS AND METHODS: We conducted an analysis of data from a prospective cohort study of previously healthy infants 2-23 months presenting to our ED with first episode of wheeze and respiratory distress. Infants were divided into those with at least one MMI defined as oxygen administration for saturation of <90%, intravenous (IV) fluids of 20 ml/kg, apnea management, or critical care unit (CCU) admission (MMI group) versus those without (no-MMI group). The primary outcome was the association between the MMI versus no-MMI groups and potential risk factors for these outcomes. RESULTS: Of 312 study infants, 52 experienced MMI--all received oxygen for saturation <90%, four also received IV fluids and none required apnea management or CCU care. The following four risk factors were associated with MMI: baseline accessory muscle score >or=6/9 [OR 2.44, 95% CI 1.29; 4.62], oxygen saturation or=60 [OR 1.85, 95% CI 0.97; 3.54], and poor fluid intake [OR 2.65, 95% CI 1.12; 6.26]. Of the 148 infants without predictors 11 (7.4%) received MMI, 145 required either no MMI or oxygen for