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Background: Adaptive clinical trials use accumulating data from enrolled subjects to alter trial conduct in pre-specified ways based on quantitative decision rules. In this research, we sought to characterize the perspectives of key stakeholders during the development process of confirmatory-phase adaptive clinical trials within an emergency clinical trials network and to build a model to guide future development of adaptive clinical trials. Methods: We used an ethnographic, qualitative approach to evaluate key stakeholders’ views about the adaptive clinical trial development process. Stakeholders participated in a series of multidisciplinary meetings during the development of five adaptive clinical trials and completed a Strengths–Weaknesses–Opportunities–Threats questionnaire. In the analysis, we elucidated overarching themes across the stakeholders’ responses to develop a conceptual model. Results: Four major overarching themes emerged during the analysis of stakeholders’ responses to questioning: the perceived statistical complexity of adaptive clinical trials and the roles of collaboration, communication, and time during the development process. Frequent and open communication and collaboration were viewed by stakeholders as critical during the development process, as were the careful management of time and logistical issues related to the complexity of planning adaptive clinical trials. Conclusion: The Adaptive Design Development Model illustrates how statistical complexity, time, communication, and collaboration are moderating factors in the adaptive design development process. The intensity and iterative nature of this process underscores the need for funding mechanisms for the development of novel trial proposals in academic settings.

Background Protocol deviations before and after tissue plasminogen activator (tPA) treatment for ischemic stroke are common. It is unclear if patient or hospital factors predict protocol deviations. We examined predictors of protocol deviations and the effects of protocol violations on symptomatic intracerebral hemorrhage (sICH). Methods We used data from the Increasing Stroke Treatment through Interventional Behavior Change Tactics trial, a cluster-randomized, controlled trial evaluating the efficacy of a barrier assessment and educational intervention to increase appropriate tPA use in 24 Michigan community hospitals, to review tPA treatments between 2007 and 2010. Protocol violations were defined as deviations from the standard tPA protocol, both before and after treatment. Multilevel logistic regression models were fitted to determine if patient and hospital variables were associated with pretreatment or post-treatment protocol deviations. Results During the study, 557 patients (mean age 70, 52% male, median National Institutes of Health Stroke Scale score 12) were treated with tPA. Protocol deviations occurred in 233 (42%) patients: 16% had pretreatment deviations, 35% had post-treatment deviations, and 9% had both. The most common protocol deviations included elevated post-treatment blood pressure, antithrombotic agent use within 24 hours of treatment, and elevated pretreatment blood pressure. Protocol deviations were not associated with sICH, stroke severity, or hospital factors. Older age was associated with pretreatment protocol deviations (adjusted odds ratio [OR], .52; 95% confidence interval [CI], .30-.92). Pretreatment deviations were associated with post-treatment deviations (adjusted OR, 3.20; 95% CI, 1.91-5.35). Conclusions Protocol deviations were not associated with sICH. Aside from age, patient and hospital factors were not associated with protocol deviations.

Objectives Intracranial hemorrhage (ICH) after acute stroke thrombolysis is associated with poor outcomes. Previous investigations of the relationship between preexisting antiplatelet use and the safety of intravenous (IV) thrombolysis have been limited by low event rates. The objective of this study was to determine whether preexisting antiplatelet therapy increased the risk of ICH following acute stroke thrombolysis. The primary hypothesis was that antiplatelet use would not be associated with radiographic evidence of ICH after controlling for relevant confounders. Methods Consecutive cases of thrombolysis patients treated in the emergency department (ED) were identified using multiple methods. Retrospective data were collected from four hospitals from 1996 to 2004 and 24 other hospitals from 2007 to 2010 as part of a cluster-randomized trial. The same chart abstraction tool was used during both time periods, and data were subjected to numerous quality control checks. Hemorrhages were classified using a prespecified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow-up imaging (primary outcome). Symptomatic ICH (sICH) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to postthrombolysis ICH. Sensitivity analyses were conducted where the unadjusted and adjusted results from this study were combined with those of previously published external studies on this topic via meta-analytic techniques. Results There were 830 patients included, with 47% having documented preexisting antiplatelet treatment. The mean (± standard deviation [SD]) age was 69 (±15) years, and the cohort was 53% male. The unadjusted proportion of patients with any ICH was 15.1% without antiplatelet use and 19.3% with antiplatelet use (absolute risk difference = 4.2%, 95% confidence interval [CI] = −1.2% to 9.6%); for sICH this was 6.1% without antiplatelet use and 9% with antiplatelet use (absolute risk difference = 3.1%, 95% CI = −1% to 6.7%). After adjusting for confounders, antiplatelet use was not significantly associated with radiographic ICH (odds ratio [OR] = 1.1, 95% CI = 0.8 to 1.7) or sICH (OR = 1.3, 95% CI = 0.7 to 2.2). In patients 81 years and older, there was a higher risk of radiographic ICH (absolute risk difference = 11.9%, 95% CI = 0.1% to 23.6%). The meta-analyses combined the findings of this investigation with previous similar work and found increased unadjusted risks of radiographic ICH (absolute risk difference = 4.9%, 95% CI = 0.7% to 9%) and sICH (absolute risk difference = 4%, 95% CI = 2.3% to 5.6%). The meta-analytic adjusted OR of sICH for antiplatelet use was 1.6 (95% CI = 1.1 to 2.4). Conclusions The authors did not find that preexisting antiplatelet use was associated with postthrombolysis ICH or sICH in this cohort of community treated patients. Preexisting tobacco use, younger age, and lower severity were associated with lower odds of sICH. The meta-analyses demonstrated small, but statistically significant increases in the absolute risk of radiographic ICH and sICH, along with increased odds of sICH in patients with preexisting antiplatelet use. Resumen ?Influye el Tratamiento Antiagregante Previo en la Hemorragia Intracraneal tras la Trombolisis en los Pacientes con Ictus Isquemicos Tratados en la Comunidad? Un Estudio Observacional Objetivos La hemorragia intracraneal (HIC) tras la trombolisis de un ictus agudo se asocia con malos resultados. Los estudios previos de la relacion entre el uso de antiagregantes y la seguridad de la trombolisis intravenosa (IV) han estado limitados por los porcentajes bajos de sucesos. El objetivo de este estudio fue determinar si el tratamiento antiagregante previo esta asociado con la evidencia radiologica de HIC tras el control por los factores de confusion relevantes. Metodologia Se identificaron los casos consecutivos de pacientes tratados con trombolisis en el SU de multiples formas. Se recogieron los datos de forma retrospectiva de cuatro hospitales de 1996 a 2004 y de 24 hospitales distintos de 2007 a 2010 como parte de un ensayo clinico aleatorizado en racimos. Se utilizo la misma tabla resumen de historia clinica durante ambos periodos de tiempo y los datos fueron sometidos a numerosos controles de calidad. Las hemorragias se clasificaron siguiendo una metodologia preestablecida: la HIC se definio como la presencia de hemorragia en las interpretaciones radiologicas de las imagenes de seguimiento (resultado primario); y la HIC sintomatica (HICs) se definio como la HIC radiologica asociada con un empeoramiento clinico. Se construyo un modelo multivariable de regresion logistica para ajustar los factores clinicos previamente identificados como relacionados con un la HIC tras la trombolisis. Los analisis de sensibilidad se realizaron mediante tecnicas de metanalisis y se combinaron los resultados ajustados y no ajustados de esta investigacion con los estudios externos previamente publicados en este tema. Resultados Se incluyeron 830 pacientes, de los cuales el 47% tenia documentado tratamiento antiagregante previo. La media de edad fue de 69 anos, y el 53% eran varones. La proporcion no ajustada de pacientes con cualquier tipo de HIC fue del 15,1% sin toma de antiagregante y del 19,3% con la toma de antiagregante (diferencia del riesgo absoluto 4,2%, IC 95% = −1,2% a 9,6%); y para las HICs fue del 6,1% sin toma de antiagregantes y del 9% con la toma de antiagregantes (diferencia absoluta del riesgo 3,1%, IC 95% = −1% a 6,7%). Tras ajustar por los factores de confusion, la toma de antiagregantes no se asocio de forma significativa con la HIC radiologica (OR 1,1, IC 95% = 0,8 a 1,7]) o HICs (OR 1,3, IC 95% = 0,7 a 2,2). En los pacientes de 81 anos o mas, hubo mayor riesgo de HIC radiologica (diferencia de riesgo absoluta 11,9%, IC 95% = 0,1% a 23,6%). El metanalisis que combino los hallazgos de esta investigacion con los trabajos similares previos encontro un riesgo no ajustado incrementado para la HIC radiologica (diferencia absoluta del riesgo 4,9%, IC 95% = 0,7% a 9%) y de HICs (diferencia absoluta del riesgo 4%, IC 95% = 2,3% a 5,6%). La odds ratio ajustada del metanalisis de HICs para los pacientes con tratamiento de antigregantes fue de 1,6 (IC 95% = 1,1 a 2,4). Conclusiones Los autores no encontraron que la toma previa de antigregantes se asocie con la HIC o la HICs tras la trombolisis en esta cohorte de pacientes tratados en la comunidad. El consumo previo de tabaco, la edad mas joven y la menor gravedad se asociaron con odds ratio menores de HICs. El metanalisis demostro un incremento bajo, aunque estadisticamente significativo, de riesgo absoluto de HIC radiologica o de HICs, con una odds ratio aumentada de HICs en los pacientes con toma previa de antiagregantes.

Objectives: The objective was to evaluate safety of intravenous (IV) tissue plasminogen activator (tPA) delivered without dedicated thrombolytic stroke teams. Methods: This was a retrospective, observational study of patients treated between 1996 and 2005 at four southeastern Michigan hospital emergency departments (EDs) with a prospectively defined comparison to the National Institute of Neurological Disorders and Stroke (NINDS) tPA stroke study cohort. Main outcome measures were mortality, intracerebral hemorrhage (ICH), systemic hemorrhage, neurologic recovery, and guideline violations. Results: A total of 273 consecutive stroke patients were treated by 95 emergency physicians (EPs) using guidelines and local neurology resources. One-year mortality was 27.8%. Unadjusted Cox model relative risk (RR) of mortality compared to the NINDS tPA treatment and placebo groups was 1.20 (95% confidence interval [CI] = 0.87 to 1.64) and 1.04 (95% CI = 0.76 to 1.41), respectively. The rate of significant ICH by computed tomography (CT) criteria was 6.6% (odds ratio [OR] = 1.03, 95% CI = 0.56 to 1.90 compared to the NINDS tPA treatment group). The proportions of symptomatic ICH by two other prespecified sets of clinical criteria were 4.8 and 7.0%. The rate of any ICH within 36 hours of treatment was 9.9% (RR = 0.94, 95% CI = 0.58 to 1.51 compared to the NINDS tPA group). The occurrence of major systemic hemorrhage (requiring transfusion) was 1.1%. Functional recovery by the modified Rankin Scale score (mRS = 0 to 2) at discharge occurred in 38% of patients with a premorbid disability mRS

Background and Purpose— The objective of this study was to determine the baseline proportion of emergency physicians with favorable attitudes and beliefs toward intravenous tissue plasminogen activator (tPA) use in a cohort of randomly selected Michigan hospitals. Methods— Two hundred seventy-eight emergency physicians from 24 hospitals were surveyed. A confidential, self-administered, pilot-tested survey assessing demographics, practice environment, attitudes, and beliefs regarding tPA use in stroke was used. Main outcome measures assessed belief in a legal standard of care, likelihood of use in an ideal setting, comfort in use without a specialist consultation, and belief that science on tPA use is convincing. ORs with robust 95% CIs (adjusted for clustering) were calculated to quantify the association between responses and physician- and hospital-level characteristics. Results— One hundred ninety-nine surveys completed (gross response rate 71.6%). Ninety-nine percent (95% CI: 97.8 to 100) indicated use of tPA in eligible patients represented either acceptable or ideal patient care. Twenty-seven percent (95% CI: 21.7 to 32.3) indicated use of tPA represented a legal standard of care. Eighty-three percent (95% CI: 78.5 to 87.5) indicated they were “likely” or “very likely” to use tPA given an ideal setting. When asked about using tPA without a consultation, 65% (95% CI: 59.3 to 70.7) indicated they were uncomfortable. Forty-nine percent (95% CI: 43.0 to 55.0) indicated the science regarding use of tPA in stroke is convincing with 30% remaining neutral. Characteristics associated with favorable attitudes included non-emergency medicine board certification; older age, and a smaller hospital practice environment. Conclusions— In this cohort, emergency physician attitudes and beliefs toward intravenous tPA use in stroke are considerably more favorable than previously reported.

Background and Purpose— We evaluated the hypothesis that consultation with neurology would be associated with fewer protocol deviations in tissue plasminogen activator-treated patients with stroke. Methods— A retrospective analysis of consecutive tissue plasminogen activator-treated patients with acute patients was performed. Using χ 2 tests, the proportion of patients with a protocol deviation was calculated and compared between those with evidence of a neurology consultation and those without. Logistic regression was then used to determine the OR for protocol deviation at the same time as controlling for clinical presentation covariates. Results— Two hundred seventy-three subjects were included. Protocol deviation rates did not significantly differ between those with (44%) and those without (41%) a consultation. The adjusted OR for deviation comparing any consultation versus nonconsultation was 1.25 (95% CI: 0.58 to 2.68). There was no statistically significant difference between symptomatic intracranial hemorrhage and in-hospital mortality rates between the groups. The proportion of patients with pretreatment deviations not related to timing was low in both the consultation (9.7%) and nonconsultation groups (8.1%). Conclusions— Neurological consultation was not found to be associated with decreased protocol deviations in this cohort, although the high proportion of deviations with and without consultation suggests that quality improvement is needed. Most observed pretreatment deviations were attributable to timing. As acute stroke care becomes more efficient and additional methods in reducing door-to-treatment times are sought, models in which emergency physicians direct the initial phase of treatment may merit further consideration.

Kirsch NL, de Leon MB, Maio RF, Millis SR, Tan-Schriner CU, Frederiksen S. Characteristics of a mild head injury subgroup with extreme, persisting distress on the Rivermead Postconcussion Symptoms Questionnaire. Objective To examine baseline variables and identify characteristics of participants with extremely high reports of symptoms (ie, outliers) 12 months after mild head injury (MHI). Design A prospective cohort study of MHI with and without loss of consciousness (LOC) and/or posttraumatic amnesia (PTA) recruited from and interviewed at the emergency department (ED), with a follow-up telephone interview at 12 months. Setting Level II community hospital ED. Participants Participants (n=58) with MHI and LOC less than or equal to 30 minutes and/or PTA less than 24 hours and participants (n=173) with MHI but no PTA/LOC. Inclusion criteria: age greater than or equal to 18 years, less than or equal to 24 hours after injury, Glasgow Coma Scale score greater than or equal to 13, and discharge from the ED. Fourteen (6%) participants had extremely high scores on the Rivermead Postconcussion Symptoms Questionnaire (RPQ). Main Outcome Measures RPQ and questions on health services use and litigation. Results Characterizing the outlier cases are prior head injury, preinjury disability, history of substance use, unemployment, and elevated somatic symptoms at the ED. At 12 months, outliers had higher use of health services and litigation. Conclusions The existence of a subgroup with a distinctive pattern of baseline characteristics in combination with elevated somatic symptoms at the time of presentation to the ED suggests that further taxonomic distinctions may be warranted for the MHI population, each requiring appropriately targeted interventions for addressing symptomatic complaints.

de Leon MB, Kirsch NL, Maio RF, Tan-Schriner CU, Millis SR, Frederiksen S, Tanner CL, Breer ML. Baseline predictors of fatigue 1 year after mild head injury. Objective To compare reports of fatigue 12 months after minor trauma by participants with mild head injury (MHI) with those with other injury, and identify injury and baseline predictors of fatigue. Design An inception cohort study of participants with MHI and other nonhead injuries recruited from and interviewed at the emergency department (ED), with a follow-up telephone interview at 12 months. Setting Level II community hospital ED. Participants Participants (n=58) with MHI and loss of consciousness (LOC) of 30 minutes or less and/or posttraumatic amnesia (PTA) less than 24 hours, 173 with MHI but no PTA/LOC, and 128 with other mild nonhead injuries. Inclusion criteria: age 18 years or older, within 24 hours of injury, Glasgow Coma Scale score of 13 or higher, and discharge from the ED. Interventions Not applicable. Main Outcome Measure Medical Outcomes Study 36-Item Short-Form Health Survey Vitality subscale. Results Significant predictors of fatigue severity at 12 months were baseline fatigue, having seen a counselor for a mental health issue, medical disability, marital status, and in some stage of litigation. Injury type was not a significant predictor. Conclusions Fatigue severity 12 months after injury is associated with baseline characteristics and not MHI. Clinicians should be cautious about attributing persisting fatigue to MHI without comprehensive consideration of other possible etiologic factors.

Background Adaptive designs have been increasingly used in the pharmaceutical and device industries, but adoption within the academic setting has been less widespread — particularly for confirmatory phase trials. We sought to understand perceptions about understanding, acceptability, and scientific validity of adaptive clinical trials (ACTs). Methods We used a convergent mixed methods design using survey and mini-focus group data collection procedures to elucidate attitudes and opinions among “trial community” stakeholders regarding understanding, acceptability, efficiency, scientific validity, and speed of discovery with adaptive designs. Data were collected about various aspects of ACTs using self-administered surveys (paper or Web-based) with visual analog scales (VASs) with free text responses and with mini-focus groups of key stakeholders. Participants were recruited as part of an ongoing NIH/FDA-funded research project exploring the incorporation of ACTs into an existing NIH network that focuses on confirmatory phase clinical trials in neurological emergencies. “Trial community” representatives, namely, clinical investigators, biostatisticians, NIH officials, and FDA scientists involved in the planning of four clinical trials, were eligible to participate. In addition, recent and current members of a clinical trial-oriented NIH study section were also eligible. Results A total of 76 stakeholders completed the survey (out of 91 who were offered it, response rate 84 %). While the VAS attitudinal data showed substantial variability across respondents about acceptability and understanding of ACTs by various constituencies, respondents perceived clinicians to be less likely to understand ACTs and that ACTs probably would increase the efficiency of discovery. Textual and focus group responses emerged into several themes that enhanced understanding of VAS attitudinal data including the following: acceptability of adaptive designs depends on constituency and situation; there is variable understanding of ACTs (limited among clinicians, perceived to be higher at FDA); views about the potential for efficiency depend on the situation and implementation. Participants also frequently mentioned a need for greater education within the academic community. Finally, the empiric, non-quantitative selection of treatments for phase III trials based on limited phase II trials was highlighted as an opportunity for improvement and a potential explanation for the high number of neutral confirmatory trials. Conclusions These data show considerable variations in attitudes and beliefs about ACTs among trial community representatives. For adaptive trials to be fully considered when appropriate and for the research enterprise to realize the full potential of adaptive designs will likely require extensive experience and trust building within the trial community. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1493-z) contains supplementary material, which is available to authorized users.

Background In an adaptive clinical trial (ACT), key trial characteristics may be altered during the course of the trial according to predefined rules in response to information that accumulates within the trial itself. In addition to having distinguishing scientific features, adaptive trials also may involve ethical considerations that differ from more traditional randomized trials. Better understanding of clinical trial experts’ views about the ethical aspects of adaptive designs could assist those planning ACTs. Our aim was to elucidate the opinions of clinical trial experts regarding their beliefs about ethical aspects of ACTs. Methods We used a convergent, mixed-methods design employing a 22-item ACTs beliefs survey with visual analog scales and open-ended questions and mini-focus groups. We developed a coding scheme to conduct thematic searches of textual data, depicted responses to visual analog scales on box-plot diagrams, and integrated findings thematically. Fifty-three clinical trial experts from four constituent groups participated: academic biostatisticians (n = 5); consultant biostatisticians (n = 6); academic clinicians (n = 22); and other stakeholders including patient advocacy, National Institutes of Health, and U.S. Food and Drug Administration representatives (n = 20). Results The respondents recognized potential ethical benefits of ACTs, including a higher probability of receiving an effective intervention for participants, optimizing resource utilization, and accelerating treatment discovery. Ethical challenges voiced include developing procedures so trial participants can make informed decisions about taking part in ACTs and plausible, though unlikely risks of research personnel altering enrollment patterns. Conclusions Clinical trial experts recognize ethical advantages but also pose potential ethical challenges of ACTs. The four constituencies differ in their weighing of ACT ethical considerations based on their professional vantage points. These data suggest further discussion about the ethics of ACTs is needed to facilitate ACT planning, design and conduct, and ultimately better allow planners to weigh ethical implications of competing trial designs. Electronic supplementary material The online version of this article (doi:10.1186/s12910-015-0022-z) contains supplementary material, which is available to authorized users.

Study objective We determine whether the use of an emergency medical services (EMS) protocol for selective spine immobilization would result in appropriate immobilization without spinal cord injury associated with nonimmobilization. Methods A 4-year prospective study examined EMS and hospital records for patients after the implementation of an EMS protocol for selective spine immobilization. EMS personnel were trained to perform and document a spine injury assessment for out-of-hospital trauma patients with a mechanism of injury judged sufficient to cause a spine injury. The assessment included these clinical criteria: altered mental status, evidence of intoxication, neurologic deficit, suspected extremity fracture, and spine pain or tenderness. The protocol required immobilization for patients with a positive assessment on any of those criteria. Outcome characteristics included the presence or absence of spine injury and spine injury management. Results The study collected data on 13,483 patients; 126 of the patients were subsequently excluded from the study because of incomplete data, leaving a study sample of 13,357 patients with complete data. Spine injuries were confirmed in the hospital records for 3% (n=415) of patients, including 50 patients with cord injuries and 128 patients with cervical injuries. Sensitivity of the EMS protocol was 92% (95% confidence interval [CI] 89.4 to 94.6%) resulting in nonimmobilization of 8% of the patients with spine injuries (33 of 415). None of the nonimmobilized patients sustained cord injuries. The specificity was 40% (95% CI 38.9 to 40.5%). Conclusion The use of our selective immobilization protocol resulted in spine immobilization for most patients with spine injury without causing harm in cases in which spine immobilization was withheld.

Objective. To determine the feasibility of prehospital pain measurement among patients 13 years of age or older using a verbal and numeric rating scale and to assess the severity of pain in a prehospital patient population. Methods. Retrospective cross-sectional study of emergency medical services (EMS) run sheets after the adoption of a universal prehospital pain assessment protocol. Data were abstracted from a sequential (1:4) sample of run sheets from the first three months after adoption of the protocol. Verbal rating scale (VRS) and numeric rating scale (NRS) pain assessment information was obtained, along with demographic, location, and call information. Run sheets without pain assessment underwent structured review and classification according to predefined protocol. Descriptive statistics and 95% confidence intervals were calculated. Results. A total of 1,227 run sheets were reviewed, 582 (47%) of patients were male, and 452 (36%) were 65 years of age or older. A total of 907 (75%) were nontrauma ...

A tremendous amount of public resources are focused on improving cardiac arrest (OHCA) survival in public places, yet most OHCAs occur in private residences.A prospective, observational study of patients transported to seven urban and suburban hospitals and the individuals who called 911 at the time of a cardiac arrest (bystander) was performed. Bystanders (N=543) were interviewed via telephone beginning 2 weeks after the incident to obtain data regarding patient and bystander demographics, including cardiopulmonary resuscitation (CPR) training. Of all arrests 80.2% were in homes. Patients who arrested in public places were significantly younger (63.2 vs. 67.2, P0.02), more often had an initial rhythm of VF (63.0 vs. 37.7%, P0.001), were seen or heard to have collapsed by a bystander (74.8 vs. 48.1%, P0.001), received bystander CPR (60.2 vs. 28.6%, P0.001), and survived to DC (17.5 vs. 5.5%, P0.001). Patients who arrested at home were older and had an older bystander (55.4 vs. 41.3, P0.001). The bystander was less likely to be CPR trained (65.0 vs. 47.4%, P0.001), less likely to be trained within the last 5 years (49.2 vs. 17.9, P0.001), and less likely to perform CPR if trained (64.2 vs. 30.0%, P0.001). Collapse to shock intervals for public versus home VF patients were not different.Many important characteristics of cardiac arrest patients and the bystander differ in public versus private locations. Fundamentally different strategies are needed to improve survival from these events.

Background: Spine immobilization is one of the most frequently performed prehospital procedures. If trauma patients without significant risk for spine injury complications can be identified, spine immobilization could be selectively performed. The purpose of this study was to evaluate five prehospital clinical criteria—altered mental status, neurologic deficit, spine pain or tenderness, evidence of intoxication, or suspected extremity fracture—the absence of which identify prehospital trauma patients without a significant spine injury. Methods: Prospectively collected emergency medical services data items included the above-listed criteria. Outcome data include spine fracture or cord injury, and also the level and management of injuries. Results: A total of 295 patients with spine injuries were present in 8,975 (3.3%) cases. Spine injury was identified by the prehospital criteria in 280 of 295 (94.9%) injured patients. The criteria missed 15 patients. Thirteen of 15 had stable injuries, the majority of which were stable compression or vertebral process injuries. The remaining two would have been captured by more accurate prehospital evaluation. Conclusion: Absence of the study criteria may form the basis of a prehospital protocol that could be used to identify trauma patients who may safely have rigid spine immobilization withheld. Evaluation of such a protocol in practice should be performed.

Objectives Cluster randomized trials (CRTs) are increasingly used to evaluate quality improvement interventions aimed at health care providers. In trials testing emergency department (ED) interventions, migration of emergency physicians (EPs) between hospitals is an important concern, as contamination may affect both internal and external validity. We hypothesized that geographically isolating EDs would prevent migratory contamination in a CRT designed to increase ED delivery of tissue plasminogen activator (tPA) in stroke (the INSTINCT trial). Methods INSTINCT was a prospective, cluster randomized, controlled trial. Twenty-four Michigan community hospitals were randomly selected in matched pairs for study. Contamination was defined at the cluster level, with substantial contamination defined a priori as greater than 10% of EPs affected. Nonadherence, total crossover (contamination + nonadherence), migration distance, and characteristics were determined. Results Three hundred seven EPs were identified at all sites. Overall, 7 (2.3%) changed study sites. One moved between control sites, leaving 6 (2.0%) total crossovers. Of these, 2 (0.7%) moved from intervention to control (contamination); and 4 (1.3%) moved from control to intervention (nonadherence). Contamination was observed in 2 of 12 control sites, with 17% and 9% contamination of the total site EP workforce at follow-up, respectively. Average migration distance was 42 miles for all EPs moving in the study and 35 miles for EPs moving from intervention to control sites. Conclusion The mobile nature of EPs should be considered in the design of quality improvement CRTs. Increased reporting of contamination in CRTs is encouraged to clarify thresholds and facilitate CRT design.

UNLABELLED Stroke teams are advocated for the rapid treatment of patients who have acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rt-PA). An alternate model uses existing ED resources with specialist consultation as needed. OBJECTIVES To evaluate the treatment of AIS with rt-PA in this alternate ED model. METHODS A retrospective observational review was performed of consecutive patients with AIS treated with rt-PA at four hospitals affiliated with an emergency medicine residency. Emergency physicians (EPs) were directly responsible for the treatment of all patients according to predefined guidelines. Records were evaluated from the implementation of the guidelines through December 15, 1997. RESULTS 37 patients with AIS received rt-PA. Mean age+/-SD was 63+/-16 years (range 22-87), with 25 (68%) male. Patients presented 67+/-29 minutes after stroke onset. After ED arrival, they were seen by the EP in 14+/-13 minutes, had CT in 46+/-22 minutes, and were treated in 97+/-35 minutes. Neurologist consultation occurred in the department for nine patients (24.3%), and by telephone for 14 (37.8%). Symptomatic intracerebral hemorrhage (ICH) occurred in four (10.8%, 95% CI = 0.8% to 20.8%). There were two deaths, neither associated with ICH. Neurologic outcome at discharge compared with presentation in survivors was normal for four patients (11.4%), improved for 16 (45.7%), unchanged for ten (28.6%), and worse for five (14.3%). CONCLUSIONS In this analysis, EPs, with specialty consultation as required, successfully identified patients with AIS and delivered rt-PA with satisfactory outcomes. Important elements of this model include early patient identification, preestablished protocols, and rapid access to CT scanning and interpretation.

Traditional EMS teaching identifies mechanism of injury as an important predictor of spinal injury. Clinical criteria to select patients for immobilization are being studied in Michigan and have been implemented in Maine. Maine requires automatic immobilization of patients with "a positive mechanism" clearly capable of producing spinal injury.To determine whether mechanism of injury affects the ability of clinical criteria to identify patients with spinal injury.In this multicenter prospective cohort study, EMS personnel completed a check-off data sheet for prehospital spine-immobilized patients. Data included mechanism of injury and yes/no determinations of the clinical criteria: altered mental status, neurologic deficit, evidence of intoxication, spinal pain or tenderness, and suspected extremity fracture. Hospital outcome data included confirmation of spinal injury and treatment required. Mechanisms of injury were tabulated and rates of spinal injury for each mechanism were calculated. The patients were divided into three different high-risk and low-risk groups.Data were collected for 6,500 patients. There were 209 (3.2%) patients with spinal injuries identified. There were 1,058 patients with 100 (9.4%) injuries in the first high-risk mechanism group, and 5,423 patients with 109 (2%) injuries in the first low-risk group. Criteria identified 97 of 100 (97%) injuries in the high-risk group and 102 of 109 (94%) in the low-risk group. Two additional data divisions yielded identical results.Mechanism of injury does not affect the ability of clinical criteria to predict spinal injury in this population.

See related editorial, p 168. Study objective: To determine whether emergency patients with acute chest pain and low suspicion of acute myocardial infarction (AMI) can be managed cost-effectively and safely in a dedicated chest pain center (CPC) that incorporates mandatory stress testing. Methods: We assembled a prospective observational case series of consecutive adult patients transferred from the emergency department to a nine-bed, 23-hour CPC in a 564-bed community hospital from January 13 through May 31, 1994. In our institution, all emergency patients with acute nontraumatic chest pain of unclear origin, suggestive of myocardial ischemia but with a low probability of AMI, are transferred to the CPC for further evaluation. All patients in whom AMI is ruled out undergo individually appropriate cardiac diagnostic testing in accordance with CPC clinical guidelines. Patients with end-stage coronary artery disease transferred to the CPC for a "rule-out" protocol only did not undergo further diagnostic testing. Admitted and discharged patients were followed through chart review and telephone survey, respectively. Results: Of the 502 patients transferred to the CPC, 477 (95%) completed follow-up at 14 days. Four hundred ten (86%) were discharged home. Those discharged after diagnostic evaluation yielded negative findings had 100% survival and zero diagnosis of AMI at 5-month follow-up. Overall mortality and incidence of AMI on long-term follow-up for all patients transferred to the CPC were .4% and .2%, respectively. Sixty-seven patients (13%) were admitted from the CPC, of whom 44 (66%) had a final diagnosis of ischemic heart disease (IHD) or AMI. Twenty-four patients with IHD (55%; 6% of stress-tested group) were identified only on further stress testing. Of these patients, seven underwent percutaneous transluminal coronary angioplasty or coronary artery bypass grafting during hospitalization. All were discharged home without major morbidity. Four hundred twenty-four patients (84%) underwent stress testing. The cost of mandatory stress testing to identify one patient with IHD after AMI was ruled out was $3,125. An average cost-per-case savings of 62% was achieved for each patient transferred to the CPC who would have been hospitalized before the inception of the CPC. Conclusion: Mandatory stress testing is a safe, cost-effective, and valuable diagnostic and prognostic tool in CPC patients. [Mikhail MG, Smith FA, Gray M, Britton C, Frederiksen SM: Cost-effectiveness of mandatory stress testing in chest pain center patients. Ann Emerg Med January 1997;29:88-98.]

Introduction: Emergency physician (EP) turnover is a significant issue that can have strong economic impact on hospital systems, as well as implications on research efforts to test and improve clinical practice. This work is particularly important to researchers planning randomized trials directed toward EPs because a large degree of turnover within a physician group would attenuate the effectiveness of the desired intervention. We sought to determine the incidence and factors associated with EP workforce changes. Methods: In an attempt to determine EP turnover and workforce change, data from the INSTINCT (INcreasing Stroke Treatment through INterventional behavior Change Tactics) trial were used. The INSTINCT trial is a prospective, cluster-randomized, controlled trial evaluating a targeted behavioral intervention to increase appropriate use of tissue plasminogen activator in acute ischemic stroke. Individual EPs staffing each of the study hospitals were identified at baseline and 18 months. Surveys were sent to EPs at both intervals. Models were constructed to investigate relationships between physician/hospital characteristics and workforce change. Results: A total of 278 EPs were identified at baseline. Surveys were sent to all EPs at baseline and 18 months with a response rate of 72% and 74%, respectively. At 18 months, 37 (15.8%) had left their baseline hospital and 66 (26.3%) new EPs were working. Seven EPs switched hospitals within the sample. The total number of EPs at 18 months was 307, a 10.8% overall increase. Among the 24 hospitals, 6 had no EP departures and 5 had no new arrivals. The median proportion of EP workforce departing by hospital was 16% (interquartile range [IQR] ¼ 4%–25%; range ¼ 0%–73%), and the median proportion added was 21% (IQR ¼ 7%–41%; range ¼ 0%–120%). None of the evaluatedcovariates investigating relationships between physician/hospital characteristics and workforce change were significant. Conclusion: EP workforce changes over an 18-month period were common. This has implications for emergency department directors, researchers, and individual EPs. Those planning research involvinginterventions upon EPs should account for turnover as it may have an impact when designing clinical trials to improve performance on healthcare delivery metrics for time-sensitive medical conditions suchas stroke, acute myocardial infarction, or trauma. [West J Emerg Med. 2013;14(1):16–22.]

Summary Background Use of alteplase improves outcome in some patients with stroke. Several types of barrier frequently prevent its use. We assessed whether a standardised, barrier-assessment, multicomponent intervention could increase alteplase use in community hospitals in Michigan, USA. Methods In a cluster-randomised controlled trial, we selected adult, non-specialty, acute-care community hospitals in the Lower Peninsula of Michigan, USA. Eligible hospitals discharged at least 100 patients who had had a stroke per year, had less than 100 000 visits to the emergency department per year, and were not academic comprehensive stroke centres. Using a computer-generated randomisation sequence, we selected 12 matched pairs of eligible hospitals. Within pairs, the hospitals were allocated to intervention or control groups with restricted randomisation in January, 2007. Between January, 2007, and December, 2007, intervention hospitals implemented a multicomponent intervention that included qualitative and quantitative assessment of barriers to alteplase use and ways to address the findings, and provided additional support. The primary outcome was change in alteplase use in patients with stroke in emergency departments between the pre-intervention period (January, 2005, to December, 2006) and the post-intervention period (January, 2008, to January, 2010). Physicians in participating hospitals and the coordinating centre could not be masked to group assignment, but were masked to progress made in paired control hospitals. External medical reviewers who were masked to group assignment assessed outcomes. We did intention-to-treat (ITT) and target-population (without one pair that was excluded after randomisation) analyses. This trial is registered at ClinicalTrials.gov, number NCT00349479. Findings All 24 hospitals completed the study. Overall, 745 of 40 823 patients with stroke received intravenous alteplase treatment. In the ITT analysis, the proportion of patients with stroke who were admitted and treated with alteplase increased between the pre-intervention and post-intervention periods in intervention hospitals (89 [1·25%] of 7119 patients to 235 [2·79%] of 8419) to a greater extent than in control hospitals (99 [1·25%] of 7946 to 194 [2·10%] of 9222), but the difference between groups was not significant (relative risk [RR] 1·37, 95% CI 0·96–1·93; p=0·08). In the target-population analysis, the increase in alteplase use in intervention hospitals (59 [1·00%] of 5882 to 191 [2·62%] of 7288) was significantly greater than in control hospitals (65 [1·09%] of 5957 to 120 [1·72%] of 6989; RR 1·68, 95% CI 1·09–2·57; p=0·02), but was still clinically modest. Interpretation The intervention did not significantly increase alteplase use in patients with ischaemic stroke. The increase in use of alteplase in the target population was significant, but smaller than the effect to which the study was powered. Additional strategies to increase acute stroke treatment are needed. Funding National Institutes of Health National Institute of Neurological Disorders and Stroke.

Background and Purpose— Identifying modifiable tissue plasminogen activator treatment delays may improve stroke outcomes. We hypothesized that prethrombolytic antihypertensive treatment (AHT) may prolong door-to-treatment time (DTT). Methods— We performed an analysis of consecutive tissue plasminogen activator–treated patients at 24 randomly selected community hospitals in the Increasing Stroke Treatment through Interventional Behavior Change Tactics (INSTINCT) trial between 2007 and 2010. DTT among stroke patients who received prethrombolytic AHT were compared with those who did not receive prethrombolytic AHT. We then calculated a propensity score for the probability of receiving prethrombolytic AHT using logistic regression with demographics, stroke risk factors, home medications, stroke severity (National Institutes of Health Stroke Scale), onset-to-door time, admission glucose, pretreatment blood pressure, emergency medical service transport, and location at time of stroke as independent variables. A paired t test was performed to compare the DTT between the propensity-matched groups. Results— Of 534 tissue plasminogen activator–treated stroke patients analyzed, 95 received prethrombolytic AHT. In the unmatched cohort, patients who received prethrombolytic AHT had a longer DTT (mean increase, 9 minutes; 95% confidence interval, 2–16 minutes) than patients who did not. After propensity matching, patients who received prethrombolytic AHT had a longer DTT (mean increase, 10.4 minutes; 95% confidence interval, 1.9–18.8) than patients who did not receive prethrombolytic AHT. Conclusion— Prethrombolytic AHT is associated with modest delays in DTT. This represents a potential target for quality-improvement initiatives. Further research evaluating optimum prethrombolytic hypertension management is warranted.

Randomized clinical trials, which aim to determine the efficacy and safety of drugs and medical devices, are a complex enterprise with myriad challenges, stakeholders, and traditions. Although the primary goal is scientific discovery, clinical trials must also fulfill regulatory, clinical, and ethical requirements. Innovations in clinical trials methodology have the potential to improve the quality of knowledge gained from trials, the protection of human subjects, and the efficiency of clinical research. Adaptive clinical trial methods represent a broad category of innovations intended to address a variety of long-standing challenges faced by investigators, such as sensitivity to previous assumptions and delayed identification of ineffective treatments. The implementation of adaptive clinical trial methods, however, requires greater planning and simulation compared with a more traditional design, along with more advanced administrative infrastructure for trial execution. The value of adaptive clinical trial methods in exploratory phase (phase 2) clinical research is generally well accepted, but the potential value and challenges of applying adaptive clinical trial methods in large confirmatory phase clinical trials are relatively unexplored, particularly in the academic setting. In the Adaptive Designs Accelerating Promising Trials Into Treatments (ADAPT-IT) project, a multidisciplinary team is studying how adaptive clinical trial methods could be implemented in planning actual confirmatory phase trials in an established, National Institutes of Health–funded clinical trials network. The overarching objectives of ADAPT-IT are to identify and quantitatively characterize the adaptive clinical trial methods of greatest potential value in confirmatory phase clinical trials and to elicit and understand the enthusiasms and concerns of key stakeholders that influence their willingness to try these innovative strategies.

Background/Purpose: Increased time to tPA treatment is associated with worse outcomes. Thus, identifying modifiable treatment delays may improve stroke outcomes. We hypothesized that pre-thrombolytic anti-hypertensive treatment (AHT) may prolong door to treatment time (DTT). Methods: Secondary data analysis of consecutive tPA-treated patients at 24 randomly selected Michigan community hospitals in the INSTINCT trial. DTT among stroke patients who received pre-thrombolytic AHT were compared to those that did not receive pre-thrombolytic AHT. We then calculated a propensity score for the probability of receiving pre-thrombolytic AHT using a logistic regression model with covariates including demographics, stroke risk factors, antiplatelet or beta blocker as home medication, stroke severity (NIHSS), onset to door time, admission glucose, pretreatment systolic and diastolic blood pressure, EMS usage and location at time of stroke. A paired t-test was then performed to compare the DTT between the propensity matched groups. A separate generalized estimating equations (GEE) approach was also used to estimate the differences between patients receiving pre-thrombolytic AHT and those that did not while accounting for within hospital clustering. Results: A total of 557 patients were included in INSTINCT, however onset, arrival or treatment times were not able to be determined in 23, leaving 534 patients for this analysis. The unmatched cohort consisted of 95 stroke patients who received pre-thrombolytic AHT and 439 stroke patients who did not receive AHT from 2007-2010 ( table ). In the unmatched cohort, patients who received pre-thrombolytic AHT had a longer DTT (mean increase 9 minutes; 95% confidence interval (CI) 2-16 minutes) than patients who did not receive pre-thrombolytic AHT. After propensity matching (table), patients who received pre-thrombolytic AHT had a longer DTT (mean increase 10.4 minutes, 95% CI 1.9 - 18.8) than patients who did not receive pre-thrombolytic AHT. This effect persisted and its magnitude was not altered by accounting for clustering within hospitals. Conclusion: Pre-thrombolytic AHT is associated with modest delays in DTT. This represents a feasible target for physician educational interventions and quality improvement initiatives. Further research evaluating optimum hypertension management pre-thrombolytic treatment is warranted.

Background and purpose Protocol deviations (PDs) before and immediately after IV thrombolysis for acute ischemic stroke are common. Patient and hospital factors associated with PDs are not well described. We aimed to determine which patient or hospital factors were associated with pre- and post-treatment PDs in a cohort of community treated thrombolysis patients. Methods The INSTINCT (Increasing Stroke Treatment through Interventional Behavior Change Tactics) study was a multicenter, cluster-randomized controlled trial in 24 Michigan community hospitals evaluating the efficacy of a barrier assessment and educational intervention to increase appropriate tPA use. PDs were defined based on 2007 AHA guidelines with the addition of the 3-4.5 hour treatment window, for which the ECASS III criteria were applied. PDs were categorized as pre-treatment (Pre-PDs), post-treatment (Post-PDs) or both. Multi-level logistic regression models were fitted to determine whether patient and hospital variables were associated with Pre-PDs or Post-PDs. The models included all variables specified a priori to be potentially clinically relevant; Pre-PD was included as a covariate in the model for Post-PD. Results During the study, 557 patients (mean age 70; 52% male; median NIHSS 12) were treated with IV tPA. PDs occurred in 233 (42%) patients: 26% had only Post-PDs, 7% had only Pre-PDs, and 9% had both. The most common PDs included failure to treat post-treatment hypertension (131, 24%), antiplatelet agent within 24 hours of treatment (61, 11%), pre-treatment blood pressure over 185/110 (39, 7%), anticoagulant agent within 24 hours of treatment (31, 6%), and treatment outside the time window (29, 5%). Symptomatic intracranial hemorrhage (SICH) was observed in 7.3% of patients with PDs and 6.5% of patients without any PD. In-hospital case fatality was 12% with and 10% without a PD. The differences in SICH and case fatality were not statistically significant. In the fully adjusted model, older age was significantly associated with Pre-PDs ( Table ). When Post-PDs were evaluated with adjustment for Pre-PDs, age was not associated with PDs; however, Pre-PDs were associated with Post-PDs. Conclusion Older age was associated with increased odds of Pre-PDs in Michigan community hospitals. Pre-PDs were associated with Post-PDs. SICH and in-hospital case fatality were not associated with PDs; however, the low number of such events limited our ability to detect a difference. Stroke severity and hospital factors were not associated with PDs.

Background: Post-thrombolysis ICH is associated with poor outcomes. Previous investigations have attempted to determine the relationship between pre-existing anti-platelet (AP) use and the safety of intravenous thrombolysis, but have been limited by low event rates thus decreasing the precision of estimates. Our objective was to determine whether pre-existing AP therapy increases the risk of ICH following thrombolysis. Methods: Consecutive cases of ED treated thrombolysis patients were identified using multiple methods, including active and passive surveillance. Retrospective data were collected from 4 hospitals from 1996-2005, and 24 distinct hospitals from 2007-2010 as part of a cluster randomized trial. The same chart abstraction tool was used during both time periods and data was subjected to numerous quality control checks. Hemorrhages were classified using a pre-specified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow up imaging (primary outcome). Symptomatic ICH (secondary outcome) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to post-thrombolysis ICH. The models included: pre-existing AP use, age*, NIHSS*, pre-treatment systolic blood pressure, onset to treatment interval, pre-treatment blood glucose*, tobacco use, presence of post-treatment protocol violations (*variable classified by quartile). As there were fewer SICH events, the multivariable model was constructed similarly, except that variables divided into quartiles in the primary analysis were dichotomized at the median. Results: There were 830 patients included, with 47% having documented pre-existing AP treatment. The mean age was 69 years, the cohort was 53% male, and the median NIHSS was 12. The unadjusted proportion of patients with any ICH was 15.1% without AP and 19.3% with AP (difference 4.2% [95% CI: -1.2% - 9.6%]); for SICH this was 6.1% without AP and 9% with AP (difference 3.1% [95%CI: -1-6.7%]). No significant association between pre-existing AP treatment with radiographic or symptomatic ICH was observed ( table ). Conclusions: We did not find that AP treatment was associated with post-thrombolysis ICH or SICH in this cohort of community treated patients. Pre-existing tobacco use, younger age, and lower severity were associated with lower odds of SICH. An association between AP therapy and SICH may still exist - further research with larger sample sizes is warranted in order to detect smaller effect sizes.

Introduction: Prior work demonstrates substantial economic benefit from tPA use. We hypothesized a T2 knowledge translation (KT) program to increase community tPA treatment would provide a cost-effective method to increase tPA use in AIS. Methods: Data were utilized from the INcreasing Stroke Treatment through INterventional behavior Change Tactics (INSTINCT) trial, a prospective, cluster randomized, controlled trial involving 24 randomly selected acute care community hospitals in matched pairs. Within pairs, hospitals were randomly assigned to receive a barrier assessment-interactive educational intervention (BA-IEI) or no intervention (control). Cost analyses were conducted from a societal perspective for 2 cases: 1) using the total trial research costs and 2) using the intervention costs alone (without research overhead) as an estimate of the costs of generalization of the results. Total trial costs were calculated by combining direct and indirect INSTINCT funding with the opportunity costs of local health professionals attending study events. Savings attributable to increased tPA use were determined by applying published stroke economic data, adjusted for inflation, to the study cohorts. These data were integrated in a Markov model to determine the long-term economic impact of the INSTINCT BA-IEI program versus no intervention. Results: The total INSTINCT trial cost (US)$3.3 million. In the intervention and post-intervention phases, the intervention sites treated 2.30% (244/10,627) of stroke patients with tPA compared to 1.59% (160/10,071) at control sites (per protocol analysis). This increase in tPA use resulted in a direct medical cost savings of approximately $540,000 due to reduced LOS and use of rehab and nursing facilities in the model. In addition, the increased usage resulted in an estimated additional 81 quality adjusted life years (QALY), with an incremental cost-effectiveness ratio of $34,000/QALY. Using $50,000 as a conservative estimate of societal value per QALY, this provided an additional societal benefit of $4,100,000, or a net economic societal benefit of $1.3 million for the trial. Generalizing the intervention in a similar population (excluding the cost of research overhead) would cost an estimated $680,000 and provide a net economic benefit of $3.9 million, assuming similar intervention effectiveness and treatment outcomes. Conclusions: Due to the underlying cost-effectiveness of tPA, community knowledge translation efforts which show modest absolute gains in tPA usage demonstrate substantial societal economic returns and are considered good value when compared to spending on other health interventions.

The objective was to evaluate safety of intravenous (IV) tissue plasminogen activator (tPA) delivered without dedicated thrombolytic stroke teams.This was a retrospective, observational study of patients treated between 1996 and 2005 at four southeastern Michigan hospital emergency departments (EDs) with a prospectively defined comparison to the National Institute of Neurological Disorders and Stroke (NINDS) tPA stroke study cohort. Main outcome measures were mortality, intracerebral hemorrhage (ICH), systemic hemorrhage, neurologic recovery, and guideline violations.A total of 273 consecutive stroke patients were treated by 95 emergency physicians (EPs) using guidelines and local neurology resources. One-year mortality was 27.8%. Unadjusted Cox model relative risk (RR) of mortality compared to the NINDS tPA treatment and placebo groups was 1.20 (95% confidence interval [CI] = 0.87 to 1.64) and 1.04 (95% CI = 0.76 to 1.41), respectively. The rate of significant ICH by computed tomography (CT) criteria was 6.6% (odds ratio [OR] = 1.03, 95% CI = 0.56 to 1.90 compared to the NINDS tPA treatment group). The proportions of symptomatic ICH by two other prespecified sets of clinical criteria were 4.8 and 7.0%. The rate of any ICH within 36 hours of treatment was 9.9% (RR = 0.94, 95% CI = 0.58 to 1.51 compared to the NINDS tPA group). The occurrence of major systemic hemorrhage (requiring transfusion) was 1.1%. Functional recovery by the modified Rankin Scale score (mRS = 0 to 2) at discharge occurred in 38% of patients with a premorbid disability mRS2. Guideline deviations occurred in the ED in 26% of patients and in 25% of patients following admission.In these EDs there was no evidence of increased risk with respect to mortality, ICH, systemic hemorrhage, or worsened functional outcome when tPA was administered without dedicated thrombolytic stroke teams. Additional effort is needed to improve guideline compliance.

Rationale Hyperglycaemia is associated with adverse outcomes in some studies of acute ischaemic stroke. Aims We hypothesised that in thrombolytic-treated stroke patients, hyperglycaemia would be independently associated with haemorrhagic transformation and unfavourable outcome. Design Consecutive rt-PA-treated acute ischaemic stroke patients presenting to four emergency departments were analysed. Associations of initial blood glucose and survival to hospital discharge, symptomatic intracerebral haemorrhage, any form of intracerebral haemorrhage, and disability at hospital discharge were determined. Potentially confounding factors of age, National Institutes of Health Stroke Scale, and smoking were analysed by univariate logistic regression and those with PStudy Outcome In 268 patients, initial glucose values ranged from 62 to 507mg/dl (mean 131). Elevated glucose at arrival was not significantly associated with any adverse clinical outcomes. A trend towards higher mortality in hyperglycae-mic patients (odds ratio 1·71 per 100mg/dl increase in glucose, 95% confidence interval 0·92–3·13, P = 0·08) was seen, but is of unclear significance, and was not corroborated by effects on discharge disability, symptomatic intracerebral haemorrhage or intracerebral haemorrhage. Conclusions Thrombolytic-treated stroke patients with hyperglycaemia at presentation did not have significantly worse outcomes than others in this cohort. These data fail to confirm previously described associations seen in similarly sized studies. Further study of these associations and their magnitude are necessary to better define the relationship between serum glucose and outcome in thrombolytic-treated acute ischaemic stroke.

Background Comparing patterns of resource utilization between hospitals is often complicated by biases in community and patient populations. Stroke patients treated with tissue plasminogen activator (tPA) provide a particularly homogenous population for comparison because of strict eligibility criteria for treatment. We tested whether resource utilization would be similar in this homogenous population between two hospitals located in a single Midwestern US community by comparing use of diagnostic testing and associated outcomes following treatment with t-PA. Methods Medical records from 206 consecutive intravenous t-PA-treated stroke patients from two teaching hospitals (one university, one community-based) were reviewed. Patient demographics, clinical characteristics and outcome were analyzed, as were the frequency of use of CT, MRI, MRA, echocardiography, angiography, and EEG. Results Seventy-nine and 127 stroke patients received t-PA at the university and community hospitals, respectively. The two patient populations were demographically similar. There were no differences in stroke severity. All outcomes were similar at both hospitals. Utilization of CT scans, and non-invasive carotid and cardiac imaging studies were similar at both hospitals; however, brain MR, TEE, and catheter angiography were used more frequently at the university hospital. EEG was obtained more often at the community hospital. Conclusions Utilization of advanced brain imaging and invasive diagnostic testing was greater at the university hospital, but was not associated with improved clinical outcomes. This could not be explained on the basis of stroke severity or patient characteristics. This variation of practice suggests substantial opportunities exist to reduce costs and improve efficiency of diagnostic resource use as well as reduce patient exposure to risk from diagnostic procedures.

Objective Postconcussion (PC) syndrome etiology remains poorly understood. We sought to examine predictors of persistent PC symptoms after minor injury. Methods Health status, symptom, and injury information were obtained on a sample of patients presenting to the emergency department after minor injury. Postconcussion and cognitive symptoms were assessed at 1, 3, and 12 months. Results Among 507 patients enrolled, 339 had head injury. Repeated-measures logistic regression modeling of PC and cognitive symptom presence across time indicated that baseline mental health status and physical health status were most predictive of persistent symptoms. In contrast, head injury presence did not predict persistent PC syndrome. Discussion Baseline mental health status and physical health status were associated with persistent PC syndrome after minor injury, but head injury status was not. Further studies of PC syndrome pathogenesis are needed.

Patient care practices often lag behind current scientific evidence and professional guidelines. The failure of such knowledge translation (KT) efforts may reflect inadequate assessment and management of specific barriers confronting both physicians and patients at the point of treatment level. Effective KT in this setting may benefit from the use of qualitative methods to identify and overcome these barriers. Qualitative methodology allows in-depth exploration of the barriers involved in adopting practice change and has been infrequently used in emergency medicine research. The authors describe the methodology for qualitative analysis within the INcreasing Stroke Treatment through INteractive behavioral Change Tactics (INSTINCT) trial. This includes processes for valid data collection and reliable analysis of the textual data from focus group and interview transcripts. INSTINCT is a 24-hospital, randomized, controlled study that is designed to evaluate a system-based barrier assessment and interactive educational intervention to increase appropriate tissue plasminogen activator (tPA) use in ischemic stroke. Intervention hospitals undergo baseline barrier assessment using both qualitative as well as quantitative (survey) techniques. Investigators obtain data on local barriers to tPA use, as well as information on local attitudes, knowledge, and beliefs regarding acute stroke treatment. Targeted groups at each site include emergency physicians, emergency nurses, neurologists, radiologists, and hospital administrators. Transcript analysis using NVivo7 with a predefined barrier taxonomy is described. This will provide both qualitative insight on thrombolytic use and importance of specific barrier types for each site. The qualitative findings subsequently direct the form of professional education efforts and system interventions at treatment sites.

To determine the feasibility of prehospital pain measurement among patients 13 years of age or older using a verbal and numeric rating scale and to assess the severity of pain in a prehospital patient population.Retrospective cross-sectional study of emergency medical services (EMS) run sheets after the adoption of a universal prehospital pain assessment protocol. Data were abstracted from a sequential (1:4) sample of run sheets from the first three months after adoption of the protocol. Verbal rating scale (VRS) and numeric rating scale (NRS) pain assessment information was obtained, along with demographic, location, and call information. Run sheets without pain assessment underwent structured review and classification according to predefined protocol. Descriptive statistics and 95% confidence intervals were calculated.A total of 1,227 run sheets were reviewed, 582 (47%) of patients were male, and 452 (36%) were 65 years of age or older. A total of 907 (75%) were nontrauma transports and 27 (2%) were unconscious. Among conscious patients, pain was assessed using the protocol in 1,002 of 1,200 (84% [range, 81%-86%]). Among patients reporting pain, 104 of 518 (20% [range, 17%-24%] completed a VRS but not an NRS. The greatest risk factor for no pain assessment was altered mental status (39% of patients not assessed). Forty-eight percent (23 of 48) of patients with altered mental status reporting pain completed a VRS only. Thirty-one percent (range, 28%-34%) of all patients in the sample reported moderate or severe pain.Prehospital pain assessment using a VRS and NRS was feasible in this patient population. Further studies are needed to confirm this finding in other settings. Moderate or severe pain was present in approximately 31% of patients.

Background and Purpose— The emergency department (ED), as the point of first medical contact for many complaints referable to atrial fibrillation (AF) and a common source of primary care, occupies a unique position to identify AF patients at risk of stroke. This study evaluates that potential by determining the prevalence of AF in an ED population and assessing antithrombotic use in those patients with recurrent AF. Methods— This was a multicenter, retrospective, cross-sectional study of consecutive records of ED patients with AF identified by ECG between January and June 1998. American Heart Association and modified Stroke Prevention in Atrial Fibrillation criteria established high-risk patients and contraindications to anticoagulation, respectively. Results— We identified 866 records with ECG-proven AF in 78 787 patient visits for an estimated prevalence of 1.10% (95% CI, 1.03 to 1.17). We found that 556 records had a prior history of AF; of these, 221 (40%) used warfarin alone, 155 (28%) had antiplatelet therapy alone, 28 (5%) used both, and 152 (27%) had no antithrombotic therapy identified. Sixty-eight patients (12%; 95% CI, 0.10 to 0.15) were warfarin eligible and without antithrombotic therapy. An additional 64 (12%; 95% CI, 0.09 to 0.14) had antiplatelet therapy alone. In warfarin-eligible patients, no differences were identified between the anticoagulated and nonanticoagulated groups on the basis of age, sex, or race. Of patients on warfarin with a measured international normalized ratio, 61% (95% CI, 0.55 to 0.67) were outside the AHA-recommended range of 2.0 to 3.0. Conclusions— AF is a common finding in an ED population. Many are warfarin eligible and untreated or undertreated. Methods to increase anticoagulant use in this at-risk population warrant further investigation.

Previous studies have reported inadequate pain control in the emergency department (ED). The primary purpose of this study was to determine the proportion of ED patients with acute fractures who actually wanted pain medication given in the ED. A convenience sample of 107 adults with acute long-bone fractures seen in a community hospital ED were surveyed on the pain level they had on ED presentation, the pain level desired at ED discharge, and their preferences for administration of analgesia in the ED. Eighty-eight percent of the patients wanted pain medication given in the ED and 77% actually received it. Sixty-nine percent were comfortable with a nurse administering pain medication before physician evaluation. Seventy percent wanted pain control without being sedated and 25% wanted complete pain relief even if sedation was necessary to achieve it. Sixty percent were either slightly concerned or not concerned about potential medication side effects.

The objective of this study was to identify clinical findings that are associated with spinal fracture and/or spinal cord injuries in prehospital trauma patients.A retrospective chart review was performed at three tertiary referral centers in Southeastern Michigan. All charts of patients with spinal fractures or spinal cord injuries during 1992 and 1993 were reviewed. Patients with available prehospital records were included in the study analysis. Prehospital data points included documentation of head injury; altered mental status; neurologic deficit; evidence of intoxication; cervical, thoracic, and lumbar pain or tenderness; nonspecified back pain or tenderness; and a narrative for all other documented injuries. Hospital data collected included type and level of spinal injury and age and sex of the patient.Of 867 injury patients identified, 536 were excluded, leaving 346 analyzable fractures in 331 patients. The 346 spinal fractures/spinal cord injuries were distributed as: 100 (29%) cervical, 83 (24%) thoracic, 128 (37%) lumbar, and 35 (10%) sacral. Prehospital documentation of altered mental status, neurologic deficit, evidence of intoxication, spinal pain, or suspected extremity fracture was found for every patient with a cervical injury, 82/83 patients with thoracic injuries (99%), and 124/128 patients with lumbar injuries (97%). All five patients who were not documented as having one of the predictors had stable injuries.Prehospital clinical findings of altered mental status, neurologic deficit, evidence of intoxication, spinal pain, and suspected extremity fracture were documented for all patients with significant spinal injuries in this series. These findings may be useful to identify patients who require prehospital spinal immobilization.

Objective: Traditional EMS teaching identifies mechanism of injury as an important predictor of spine injury. Clinical criteria to select patients for immobilization are being studied in Michigan and have been implemented in Maine. Maine requires automatic immobilization of patients with “a positive mechanism” clearly capable of producing spine injury. The purpose of this study is to determine if mechanism of injury effects the ability of clinical criteria to select patients with spine injury.Design: Multicenter Prospective Cohort.Methods: EMS personnel completed a check-off data sheet on out-of-hospital spine immobilized patients. Data included mechanism of injury and yes/no determinations of the clinical criteria: altered mental status, neurologic deficit, evidence of intoxication, spinal pain or tenderness, and suspected extremity fracture. Hospital outcome data included confirmation of spine injury and treatment required. Mechanisms of injury were tabulated and rates of spine injury for each mechanism was calculated. The patients were divided into high-risk and low-risk groups.Results: Data was collected on 6,500 patients. There were 213 (3.3%) patients with spine injuries identified. There were 1,065 patients with 100 (9.4%) injuries in the high-risk mechanism group, and 5435 patients with 113 (2%) injuries in the low-risk group. Clinical criteria identified 96 of 100 (96%) injuries in the high risk mechanism group and 106 of 113 (94%) in the low-risk group.

Background Only 1-3% of ischemic stroke patients receive thrombolytic therapy. Provider barriers to adhering with guidelines recommending tPA delivery in acute stroke are not well known. The main objective of this study was to describe barriers to thrombolytic use in acute stroke care. Methods Twenty-four hospitals were randomly selected and matched into 12 pairs. Barrier assessment occurred at intervention sites only, and utilized focus groups and structured interviews. A pre-specified taxonomy was employed to characterize barriers. Two investigators independently assigned themes to transcribed responses. Seven facilitators (three emergency physicians, two nurses, and two study coordinators) conducted focus groups and interviews of emergency physicians (65), nurses (62), neurologists (15), radiologists (12), hospital administrators (12), and three others (hospitalists and pharmacist). Results The following themes represented the most important external barriers: environmental and patient factors. Important barriers internal to the clinician included familiarity with and motivation to adhere to the guidelines, lack of self-efficacy and outcome expectancy. The following themes were not substantial barriers: lack of awareness of the existence of acute stroke guidelines, presence of conflicting guidelines, and lack of agreement with the guidelines. Conclusions Healthcare providers perceive environmental and patient-related factors as the primary barriers to adherence with acute stroke treatment guidelines. Interventions focused on increasing physician familiarity with and motivation to follow guidelines may be of highest yield in improving adherence. Improving self-efficacy in performing guideline concordant care may also be useful. Trial Registration ClinicalTrials.gov identifier: NCT00349479