Search

Background The incidence of positional plagiocephaly has increased significantly over the last two decades, which has caused a service delivery challenge for pediatric neurosurgeons. As a potential solution to the long waitlists for abnormal head shape, a plagiocephaly clinic was established at BC Children's Hospital (BCCH) in Vancouver, Canada. This clinic was supervised by an occupational therapist who had been trained by a neurosurgeon to independently assess and manage patients with a referring diagnosis of positional plagiocephaly. Objectives To determine the efficiency of the BCCH Plagiocephaly Clinic in the management of positional plagiocephaly patients and to investigate the clinic's ability to appropriately identify and refer patients with craniosynostosis to pediatric neurosurgeons for further assessment. Methods A retrospective chart review was conducted to identify patients who were assessed and managed at the BCCH Plagiocephaly Clinic between 2008 and 2014. Data on patient demographics, head shape measurements, and treatment recommendations were collected, and the BC Children's neurosurgical database was cross-referenced to identify craniosynostosis cases missed by the Plagiocephaly Clinic. A descriptive analysis of the clinic's average wait times, severity of the patients' plagiocephaly, and recommended interventions was conducted. In addition, the sensitivity and specificity of the clinic's ability to appropriately refer craniosynostosis patients to pediatric neurosurgery were calculated. Results Of 1752 patients seen in the BC Children's Plagiocephaly Clinic between 2008 and 2014, 66% of patients received counseling about repositioning, 34% were referred for head banding, 19% were referred to physiotherapy for torticollis, and 1.4% were referred to the BC Children's Pediatric Neurosurgery Clinic for suspicion of craniosynostosis. The mean time from referral to first assessment by the Plagiocephaly Clinic was 41 days, and time from referral by the plagiocephaly clinic to diagnosis of craniosynostosis by a pediatric neurosurgeon was 8 days. Pediatric neurosurgeons requested imaging for 6 of the referred patients (25% ). The sensitivity and specificity of the plagiocephaly clinic for referral of craniosynostosis patients to the Pediatric Neurosurgery Clinic were 100 and 99%, respectively. Conclusion The BC Children's Plagiocephaly Clinic is efficient and safe for the initial evaluation and treatment of patients with positional plagiocephaly. The clinic's model decreases wait times, appropriately manages patients with positional plagiocephaly, screens for craniosynostosis with high sensitivity and specificity, and takes pressure off outpatient neurosurgical clinics. This model for assessment of plagiocephaly could be considered in other medical centers.

Background Although many studies have determined that PD-L1 expression by immunohistochemistry can be somewhat predictive of a response to checkpoint inhibitor the impact of specific genomic changes and smoking history in the context of PD-L1 expression is limited. This single-center study examined clinical and genomic factors beyond STK11 and EGFR in patients with advanced non-small cell lung cancer (NSCLC) to determine which patients benefit from therapy with immune checkpoint inhibitors (ICIs). Methods Clinical and genomic features of patients with NSCLC treated with immunotherapy were compiled into a database. Genomic information collected included gene mutations via next generation sequencing, tumor mutation burden (TMB), and PD-L1 tumor proportional scores. Results A total of 131 patients with advanced NSCLC treated with ICIs were examined. Race was not associated with response. A positive response to immunotherapy was associated with smoke year increase (P=0.042). KRAS mutation and MYC amplification were associated with a positive response to immunotherapy while EGFR, RB1, and NF1 mutations were associated with a lack of response. KRAS mutation (P=0.007) and high TMB (P=0.070) were positively associated with smoking history. EGFR mutation was negatively associated with smoking history (P=0.002) . In multivariate analysis controlling for age and smoking history, MYC amplification continued to be the only predictive genomic marker with a trend toward response to therapy (P=0.092) beyond the smoking history. Conclusions Among the clinical and genomic factors examined in this study, smoking status is the most predictive of response to ICIs. Only MYC amplification continued to predict a trend toward response to immunotherapy when controlling for smoking history. Other genomic predictors such as EGFR and KRAS simply reflect their association with smoking. Detailed smoking history and MYC amplification alone can predict response to ICI.

We report the identification of a de novo GABRA1 (R214C) variant in a child with epileptic encephalopathy (EE), describe its functional characterization and pathophysiology, and evaluate its potential therapeutic options. The GABRA1 (R214C) variant was identified using whole exome sequencing, and the pathogenic effect of this mutation was investigated by comparing wild-type (WT) α1 and R214C α1 GABA

Childhood primary angiitis of the central nervous system (cPACNS) is a rare inflammatory disease of brain vessels. The small vessel subtype is diagnosed on brain biopsy and often presents with cognitive and behavioral changes, headaches, and seizures. However, there are few reported cases of super-refractory status epilepticus in children. We present a case of small vessel cPACNS complicated by super-refractory status epilepticus requiring burst suppression for 4 weeks in addition to multiple antiseizure medications and the ketogenic diet. Our patient was also treated with intravenous and oral steroids, intravenous immunoglobulin, and cyclophosphamide before starting maintenance therapy with mycophenolate mofetil. After prolonged rehabilitation, he recovered almost completely and has a normal neurologic examination with rare epileptiform activity on electroencephalogram (EEG). This is one of the longest cases of status epilepticus in small vessel cPACNS in the literature. We illustrate that super-refractory status epilepticus can be the first manifestation of small vessel cPACNS in previously healthy children and that symptomatic management of seizures with concurrent immunosuppression to treat the underlying pathology resulted in favorable neurologic outcomes.

Background Status epilepticus (SE) is a common pediatric neurological emergency that requires timely treatment to minimize morbidity and mortality, yet administration of rescue medications is often delayed and underdosed. Seizure action plans (SAPs) outline the steps that should be taken by parents and caregivers in case of SE in order to optimize patient outcomes. Our study determined the uptake of SAPs in a pediatric population with epilepsy and assessed parental interest in a SAP mobile application. Methods A survey was distributed to parents of patients with epilepsy aged 1 month to 19 years at British Columbia Children’s Hospital. Following chart review, univariate and multivariate analyses were performed to identify variables that predict whether patients have SAPs. A systematic search of available mobile applications for epilepsy management was conducted. Results Of 192 participants, 62% have SAPs. On univariate analysis, history of prior SE and male gender increased likelihood of SAP. On logistic regression, Nagelkerke R2 was 0.204 and our model correctly predicted 82% of patients with SAPs. 83% of parents were interested in a SAP mobile application. There are currently 40 mobile applications available for epilepsy management, but only 15% of respondents reported using them. Conclusions There is a need to increase the percentage of patients with epilepsy with SAPs, particularly in those at greater risk of SE. Most parents would find a SAP mobile application valuable in their child’s epilepsy management. There is a gap between the high parental interest in mobile applications for epilepsy management and their current use of such applications.

The specialty of anesthesiology will soon adopt the Competence By Design (CBD) approach to residency education developed by the Royal College of Physicians and Surgeons of Canada (RCPSC). A foundational component of CBD is frequent and contextualized assessment of trainees. In 2013, the RCPSC Anesthesiology Specialty Committee assembled a group of simulation educators, representing each of the 17 Canadian anesthesiology residency programs, to form the Canadian National Anesthesiology Simulation Curriculum (CanNASC) Task Force. The goals were to develop, implement, and evaluate a set of consensus-driven standardized mannequin-based simulation scenarios that every trainee must complete satisfactorily prior to completion of anesthesiology residency and certification. Curriculum development followed Kern's principles and was accomplished via monthly teleconferences and annual face-to-face meetings. The development and implementation processes included the following key elements: 1) Curriculum needs assessment: 368 of 958 invitees (38.4%) responded to a national survey resulting in 64 suggested scenario topics. Use of a modified Delphi technique resulted in seven important and technically feasible scenarios. 2) Scenario development: All scenarios have learning objectives from the National Curriculum for Canadian Anesthesiology Residency. Standardized scenario templates were created, and the content was refined and piloted. 3) Assessment: A validated Global Rating Scale (GRS) is the primary assessment tool, informed by using scenario-specific checklists (created via a modified Delphi technique) and the Anesthesia Non-Technical Skills GRS. 4) Implementation: Standardized implementation guidelines, pre-brief/debrief documents, and rater training videos, guide, and commentary were generated. National implementation of the scenarios and program evaluation is currently underway. It is highly feasible to achieve specialty-based consensus on the elements of a national simulation-based curriculum. Our process could be adapted by any specialty interested in implementing a simulation-based curriculum incorporating competency-based assessment on a national scale.

The retinoblastoma gene (RB1) encodes the retinoblastoma (RB) pocket protein that plays an important role in cell cycle progression. Here we determine the frequency and prognostic significance of RB1 mutation in non small cell lung cancer (NSCLC), restricting inclusion to Stage III and IV patients with linked genomic and clinical data. The primary outcome was median overall survival (OS). We identified RB1 mutation in 8.2% of NSCLC patients. The median OS for wild‐type (wt) RB1 was 28.3 months vs 8.3 months for mutant RB1 (Hazard Ratio = 2.59, P = 0.002). Of special interest, RB1 mutation also correlated with lack of response to immunotherapy. Our study focused on RB1 mutation in locally advanced and advanced non small cell lung cancer to better facilitate comparisons with small cell lung cancer (SCLC). In our SCLC cohort, RB1 mutation was identified in 75% of patients and wt RB1 was associated with significantly shorter OS (P = 0.002). The different outcomes of RB1 mutation observed among lung cancer subtypes suggest a more complicated mechanism than simple regulation of cell cycle or response to chemotherapy.

A 3,220-g male infant is born at 34 weeks’ gestation by urgent cesarean delivery because of concerns for fetal well-being to a 33-year-old gravida 3 para 1 now 2 mother with serologies significant for O positive, rubella nonimmune, hepatitis B surface antigen negative, rapid plasma reagin nonreactive, human immunodeficiency virus negative, Group B streptococcus status unknown. Resuscitation of the infant is significant for the need for positive pressure ventilation, intubation, chest compressions for 1 minute and bilateral thoracentesis with no drainage of fluid. Pregnancy was complicated by previous herpes simplex virus infection with negative bright light examination at time of delivery, previous Cesarean delivery, and new-onset hydrops fetalis. One week before delivery, ultrasound of the fetus was significant for bilateral pleural effusions, cardiac enlargement, increased middle cerebral artery Doppler flow, and polyhydramnios with an amniotic fluid index of 40. Initial assessment reveals a large-for-gestational age infant with generalized edema. He is placed on the high-frequency oscillator on admission. His abdominal examination is significant for the liver edge palpated 3 cm below the right costal margin. An initial chest radiograph reveals bilateral pleural effusions, with right greater than left and hazy lung fields (Fig 1). A cardiology consultation is urgently requested after admission, and the initial echocardiogram reveals a small patent foramen ovale, a small midseptal muscular ventricular septal defect both with left to right flow, right ventricular hypertrophy with normal function, and a tiny pericardial effusion. Figure 1. Initial chest and abdomen radiograph on admission to the NICU displaying a small left pleural effusion and moderate right pleural effusion. Cardiac size is normal for gestational age. ### Initial Evaluation Initial arterial blood gas is pH 7.36 mm Hg, pCO2 45 mm Hg, pO2 132 mm Hg, HCO3 26 mmol/L with base deficit of 0.2 mmol/L. His initial complete blood count reveals white blood cell count …

Background The objective of this study was to compare the effect of thoracic paravertebral block (TPVB) and local anesthetic (LA) on persistent postoperative pain (PPP) 1 year following breast cancer surgery. Secondary objectives were to compare the effect on arm morbidity and quality of life. Methods Women scheduled for elective breast cancer surgery were randomly assigned to either TPVB or LA followed by general anesthesia. An NRS value of >3 at rest or with movement 1 year following surgery defined PPP. Blinded interim analysis suggested rates of PPP much lower than anticipated, making detection of the specified 20 % absolute reduction in the primary outcome impossible. Recruitment was stopped, and all enrolled patients were followed to 1 year. Results A total of 145 participants were recruited; 65 were randomized to TPVB and 64 to LA. Groups were similar with respect to demographic and treatment characteristics. Only 9 patients (8 %; 95 % CI 4–14 %) met criteria for PPP 1 year following surgery; 5 were in the TPVB and 4 in the LA group. Brief Pain Inventory severity and interference scores were low in both groups. Arm morbidity and quality of life were similar in both groups. The 9 patients with PPP reported shoulder-arm morbidity and reduced quality of life. Conclusions This study reports a low incidence of chronic pain 1 year following major breast cancer surgery. Although PPP was uncommon at 1 year, it had a large impact on the affected patients’ arm morbidity and quality of life.

Background Autologous or allogeneic hematopoietic stem cell transplant (SCT) is often considered in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) but there are limited data on the use of SCT for the treatment of NHL in the pediatric setting. Procedure To evaluate the role of SCT for children with NHL, we reviewed 36 consecutive pediatric patients with NHL who underwent an allogeneic (n = 21) or autologous (n = 15) SCT at our institution between 1982 and 2004. Pathologic classification included: lymphoblastic lymphoma (n = 12), Burkitt lymphoma (BL) (n = 5), diffuse large B-cell lymphoma (n = 4), anaplastic large cell lymphoma (ALCL) (n = 13), peripheral T cell lymphoma (n = 1), and undifferentiated NHL (n = 1). Donor source for allogeneic-SCT recipients was an HLA-matched related donor (n = 15), a matched unrelated donor (n = 4), or a mismatched donor (related n = 1; unrelated n = 1). Twenty-eight patients (78%) had chemotherapy responsive disease at the time of transplant (either CR or PR). Results Overall survival (OS) and disease-free survival (DFS) were 55% and 53% with a median follow-up of 9.75 years. Outcomes were similar in patients receiving autologous and allogeneic-SCT (DFS 53% in both groups). Patients with ALCL had a DFS of 76.9%. In contrast, of five patients transplanted for BL, none survived. DFS among patients with chemotherapy sensitive disease was 61%, compared with 25% among patients with relapsed/refractory disease (P = 0.019). Conclusions Allogeneic and autologous SCT offer the prospect of durable, disease-free survival for a significant proportion of pediatric patients with relapsed or refractory NHL. Survival is superior among patients with chemotherapy sensitive disease. Pediatr Blood Cancer 2013;60:2018–2024. © 2013 Wiley Periodicals, Inc.

Background Mental practice (MP) is defined as the ‘symbolic rehearsal of a physical activity in the absence of any gross-muscular movements' and has been used in sport and music to enhance performance. In healthcare, MP has been demonstrated to improve technical skill performance of surgical residents. However, its effect on crisis resource management (CRM) skills has yet to be determined. We aimed to investigate the effect of warm-up with MP on CRM skill performance during a simulated crisis scenario. Methods Following ethics board approval, 40 anaesthesia residents were randomized. The intervention group performed 20 min of MP of a script based on CRM principles. The control group received a 20 min didactic teaching session on an unrelated topic. Each subject then managed a simulated cardiac arrest. Two CRM experts rated the video recordings of each performance using the previously validated Ottawa GRS. The time to start chest compressions, administer epinephrine, and give blood was recorded. Results There was no significant difference between the intervention and control groups: total Ottawa GRS score was 24.50 (18.63–28.88 [6.50–34.50]) (median (inter-quartile range [range]) vs 20.50 (13.00–29.13 [6.50–34.50]) (P=0.53); the time to start chest compressions 146.0 s (138.0–231.0 [115.0–323.0]) vs 162.5 s (138.0–231.0 [100.0–460.0]) (P=0.27), the time to epinephrine administration 163.0 s (151.0–187.0 [111.0–337.0]) vs 187.0 s (164.0–244.0 [115.0–310.0]) (P=0.09), and the time to blood administration 220.5 s (130.8–309.0 [92.0–485.0]) vs 252.5 (174.5–398.8 [65.0–527.0]) (P=0.48). Conclusion Unlike technical skills, warm-up with MP does not seem to improve CRM skills in simulated crisis scenarios.

A preoperative machine check is imperative, yet machine faults are missed despite experience. We hypothesized that a simulation training session would improve junior residents’ ability to perform a machine check beyond the level of final year residents who received only didactic training. In 2005, an experiential machine check training session was introduced into residency training at the postgraduate year 1 (PGY-1) level. Three weeks later, the simulation residents were asked to perform a machine check and detect ten preset faults. The control group consisted of PGY-5 residents who had received a didactic anesthesia machine lecture during their residency; these control residents were asked to perform the same machine check as the simulation residents. Data were collected from 2005 to 2008 with each cohort of incoming PGY-1 residents and graduating PGY-5 residents. When the first group of PGY-1 residents became PGY-5 residents in 2009, they were invited to return for a retention test. In all tests, the number of faults detected was recorded, and the machine check was evaluated using a checklist. Thirty-seven simulation residents and 27 control residents participated in the study. Simulation residents had significantly higher checklist scores than the control residents, and they identified more machine faults (both P

OBJECTIVE: To examine the effect of a blended educational intervention (in-class and independent learning modules) developed to enhance Ohio PHN confidence in 25 disaster surge competencies that address the PHN role and skills in Preparedness, Response, and Recovery. DESIGN AND SAMPLE: This was a quasi-experimental one group pre and post design. Participants (N = 54) completed pre- and postintervention surveys to evaluate intervention impact on self-perceived confidence and need for further training in the 25 competencies. MEASURES: Parallel pre and post surveys assessed participant evaluation of confidence and need for further competency training. Paired t tests and repeated measures ANOVA compared pre- and postsurvey results. RESULTS: Confidence in Preparedness, Response, and Recovery PHN disaster surge competencies significantly increased, whereas self-perceived need for further competency training correspondingly significantly decreased. CONCLUSIONS: A blended learning approach to disaster surge training effectively improved PHNs confidence in competency achievement and reduced perceived need for further training. Language: en

T-cell depleted allogeneic hematopoietic stem cell transplants (TCD-HSCT) have demonstrated durable disease-free survival with a low risk of graft vs. host disease (GVHD) in patients with AML. We investigated this approach in 61 patients with primary refractory or relapsed non-Hodgkin lymphoma (NHL), who underwent TCD-HSCT from January 1992 through September 2004. Patients received myeloablative cytoreduction consisting of hyperfractionated total body irradiation, followed by either thiotepa and cyclophosphamide (45 patients) or thiotepa and fludarabine (16 patients). We determined the second-line age-adjusted International Prognostic Index score (sAAIPI) prior to transplant. Median follow-up of surviving patients is 6 years. The 10-year overall (OS) and event-free-survival (EFS) were 50% and 43%, respectively. The relapse rate at 10 years was 21% in patients with chemosensitive disease and 52% in those with resistant disease at time of HSCT. Nine of the 18 patients who relapsed entered a subsequent CR. Overall survival (p=0.01) correlated with the sAAIPI. The incidence of grade II-IV acute GVHD was 18%. We conclude that allogeneic TCD-HSCT can induce high rates of OS and EFS in advanced NHL with a low incidence of GVHD. Furthermore, the sAAIPI can predict outcomes and may be used to select the most appropriate patients for this type of transplant.

Crisis resource management (CRM) skills are a set of nonmedical skills required to manage medical emergencies. There is currently no gold standard for evaluation of CRM performance. A prior study examined the use of a global rating scale (GRS) to evaluate CRM performance. This current study compared the use of a GRS and a checklist as formal rating instruments to evaluate CRM performance during simulated emergencies.First-year and third-year residents participated in two simulator scenarios each. Three raters then evaluated resident performance in CRM using edited video recordings using both a GRS and a checklist. The Ottawa GRS provides a seven-point anchored ordinal scale for performance in five categories of CRM, and an overall performance score. The Ottawa CRM checklist provides 12 items in the five categories of CRM, with a maximum cumulative score of 30 points. Construct validity was measured on the basis of content validity, response process, internal structure, and response to other variables. T-test analysis of Ottawa GRS scores was conducted to examine response to the variable of level of training. Intraclass correlation coefficient (ICC) scores were used to measure inter-rater reliability for both scenarios.Thirty-two first-year and 28 third-year residents participated in the study. Third-year residents produced higher mean scores for overall CRM performance than first-year residents (P0.05), and in all individual categories within the Ottawa GRS (P0.05) and the Ottawa CRM checklist (P0.05). This difference was noted for both scenarios and for each individual rater (P0.05). No statistically significant difference in resident scores was observed between scenarios for both instruments. ICC scores of 0.59 and 0.61 were obtained for Scenarios 1 and 2 with the Ottawa GRS, whereas ICC scores of 0.63 and 0.55 were obtained with the Ottawa CRM checklist. Users indicated a strong preference for the Ottawa GRS given ease of scoring, presence of an overall score, and the potential for formative evaluation.Construct validity seems to be present when using both the Ottawa GRS and CRM checklist to evaluate CRM performance during simulated emergencies. Data also indicate the presence of moderate inter-rater reliability when using both the Ottawa GRS and CRM checklist.

Results of allogeneic hematopoietic stem cell transplantation (HCT) to treat advanced leukemia or myelodysplastic syndrome (MDS) remain poor due to excessive relapse and transplant-related mortality. To improve transplant outcome in this patient population, 43 patients (median age, 46.1 years) with high-risk or advanced lymphoid (n = 5) or myeloid malignancy (n = 38) were prospectively enrolled on a pilot trial of cytoreduction with intravenous busulfan and melphalan followed by an unmodified HLA-A, -B, and –DRβ1–matched related (n = 18) or unrelated (n = 25) HCT. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Thirty-four patients had ≥ 5% blasts at the time of HCT; 12 of these had > 20% blasts. Seventeen patients had unfavorable cytogenetics, 8 patients underwent transplantation for secondary MDS or acute myelogenous leukemia, and 4 patients had relapsed after a previous allogeneic transplantation. Although mucositis was the most significant regimen-related toxicity, requiring the addition of folinic acid rescue and failure to receive all 4 doses of methotrexate in 23 patients, the nonrelapse mortality at 30 and 100 days was low at 0% and 16%, respectively. The cumulative incidence of grade II-IV acute GVHD was 24%, and that of extensive chronic GVHD was 7%. With a minimum follow-up of 18 months, the estimated 3-year overall survival is 37% and the estimated disease-free survival (DFS) is 33%. For 18 patients with MDS (≤ RAEB-2) or high-risk myeloproliferative disorder, the estimated 3 year DFS is 61%. These data demonstrate the curative potential of this regimen in patients with high-risk myeloid malignancies.

We have designed a mobile device application (RRate), to provide an efficient measurement of respiratory rate with clinically acceptable accuracy. The method is based on analysis of multiple consecutive breath intervals. We investigated in this study the difference in measurement variability between breaths as a representative of recording quality. Respiratory rate of 322 children aged 0 - 12 years at a Ugandan rural health centre were recorded using the RRate mobile application, and compared to respiratory rate recordings obtained from 22 volunteers using the RRate application while observing 10 videos of children breathing in a lab setting. The variability of the recorded breaths (confidence) of both groups follow a similar Weibull distribution. However, we observed a trend towards higher variability in the data obtained in the field (median 89.7% confidence) compared to the data obtained in the laboratory setting (median 92.6% confidence). This suggests that it is more difficult to obtain consistent measurements when assessing patients in a clinical setting, and therefore the confidence in the measured respiratory rate is reduced. The mobile device application provided a respiratory rate value up to 6 times faster than the current practice of one minute counting. The measure of variability between individual measured breaths provided a powerful way to display confidence in a measurement.

Antithymocyte globulin (ATG) has been used in allogeneic stem-cell transplantation to prevent graft rejection and graft-versus-host disease (GvHD). Its use, however, has been associated with delayed T-cell reconstitution and prolonged susceptibility to opportunistic infections (OIs) especially in patients undergoing T cell–depleted (TCD) transplantation. Recently, a prospective trial was conducted in 52 adult patients (median age, 47 years) with various hematologic malignancies undergoing TCD transplantation from HLA-matched related donors without the use of ATG. The cytoreductive regimen consisted of hyperfractionated total body irradiation (HFTBI), thiotepa, and fludarabine. The preferred source of the graft was peripheral blood stem cells (PBSCs). No additional graft rejection or GvHD prophylaxis was given. All evaluable patients engrafted without any immune-mediated graft rejections. Disease-free survival (DFS) at 3 years was 61% in all patients, and 70% in patients with standard-risk disease. Acute GvHD was limited to grade 2 in 8% and chronic GvHD in 9% of patients. Life-threatening OIs occurred in 3 of 52 patients and was fatal in 1. This study demonstrates durable engraftment with a low incidence of GvHD despite the lack of ATG, as well as the curative potential of this regimen.

Daclizumab has been shown to have activity in acute GVHD, but appears to be associated with an increased risk of infection. To investigate further the long-term effects of daclizumab, we performed a retrospective review of 57 patients who underwent an allogeneic hematopoietic stem cell transplant from January 1993 through June 2000 and were treated with daclizumab for steroid-refractory acute GVHD. The median number of daclizumab doses given was 5 (range 1-22). GVHD was assessed at baseline, days 15, 29 and 43. By day 43, 54% patients had an improvement in their overall GVHD score, including 76% patients aged < or =18. Opportunistic infections developed in 95% patients. Forty-three patients (75%) died following treatment with daclizumab. The causes of death included active GVHD and infection (79%), active GVHD (5%), chronic GVHD (2%) and relapse (14%). Patients with grade 3-4 GVHD had a significantly shorter median survival than patients with grade 1-2 GVHD (2.0 vs 5.1 months, P=0.001). Daclizumab has no infusion-related toxicity, is active in steroid-refractory GVHD, especially among pediatric patients, but is associated with significant morbidity and mortality due to infectious complications. Careful patient selection and aggressive prophylaxis against viral and fungal infections are recommended.

Resuscitation of critically ill patients requires medical knowledge, clinical skills, and nonmedical skills, or crisis resource management (CRM) skills. There is currently no gold standard for evaluation of CRM performance. The primary objective was to examine the use of high-fidelity simulation as a medium to evaluate CRM performance. Since no gold standard for measuring performance exists, the secondary objective was the validation of a measuring instrument for CRM performance-the Ottawa Crisis Resource Management Global Rating Scale (or Ottawa GRS).First- and third-year residents participated in two simulator scenarios, recreating emergencies seen in acute care settings. Three raters then evaluated resident performance using edited video recordings of simulator performance.A Canadian university tertiary hospital.: The Ottawa GRS was used, which provides a 7-point Likert scale for performance in five categories of CRM and an overall performance score.Construct validity was measured on the basis of content validity, response process, internal structure, and response to other variables. One variable measured in this study was the level of training. A t-test analysis of Ottawa GRS scores was conducted to examine response to the variable of level of training. Intraclass correlation coefficient scores were used to measure interrater reliability for both scenarios. Thirty-two first-year and 28 third-year residents participated in the study. Third-year residents produced higher mean scores for overall CRM performance than first-year residents (p.0001) and in all individual categories within the Ottawa GRS (p = .0019 to p.0001). This difference was noted for both scenarios and for each individual rater (p = .0061 to p.0001). No statistically significant difference in resident scores was observed between scenarios. Intraclass correlation coefficient scores of .59 and .61 were obtained for scenarios 1 and 2, respectively.Data obtained using the Ottawa GRS in measuring CRM performance during high-fidelity simulation scenarios support evidence of construct validity. Data also indicate the presence of acceptable interrater reliability when using the Ottawa GRS.

To report the anesthetic management of an anemic Jehovah's Witness patient presenting for laparoscopic adrenalectomy for pheochromocytoma.A 49-yr-old woman presented with hemodynamic instability progressing to cardiogenic shock and subsequent acute renal failure. Her course was complicated by anemia. An adrenal pheochromocytoma was diagnosed. Preoperatively, alpha- and beta-adrenergic blockade was instituted with phenoxybenzamine and metoprolol therapy and her anemia was treated with erythropoietin. She underwent laparoscopic resection of the adrenal tumour. A cell saver device was employed and attached to the laparoscopic suction-irrigation apparatus to provide salvage capability in the event of a major hemorrhage. The surgical intervention was uneventful and well tolerated. The patient was discharged home and well on follow-up.Cell salvage is the only mechanism currently acceptable to Jehovah's Witnesses which will allow for perioperative salvage and replacement of blood loss. Its use is encouraged in all situations in which surgical hemorrhage is anticipated.

In this trial, we wished to test whether a chemotherapeutic regimen combining myeloablation with busulfan (Bu) and melphalan (Mel) with fludarabine (Flu) and ATG could be used to secure consistent engraftment of T-cell depleted transplants thereby reducing GvHD and regimen-related toxicity without increasing risk of relapse in patients with advanced myeloid malignancies. Between 08/01 and 06/07, sixty two patients with a diagnosis of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) were enrolled on this trial, including 33 males and 29 females of a median age of 54.5 years (range 0.6–71.3 years). Eleven patients had primary AML in CR1 (N=4) or ≥ CR2 (N=7). Thirty two pts had primary (1°) MDS and 19 pts treatment related (2°) MDS/AML. Forty five of the 51 pts with 1° or 2° MDS had ≥ RAEB status at diagnosis and required chemotherapy prior to transplant. The status of MDS pts at the time of SCT included: CR1 (N=14), CR2 (N=3), primary RA (N=6), second RA (N=21), > RA (N=7). Thirteen pts received allografts from HLA-matched related donors, 4 pts from HLA-mismatched related donors, 22 pts from HLA-matched unrelated donors, and 23 pts from HLA-mismatched unrelated donors. Cytoreduction consisted of BU (0.8–1 mg/Kg/dose × 10 doses), MEL (70 mg/Kg/day × 2) and FLU (25 mg/m2/day × 5). Graft rejection prophylaxis included pre-transplant rabbit ATG (Thymoglobulin) (2.5 mg/Kg/day × 2) and no post transplant immunosuppression was administered. Fifty nine pts received G-CSF mobilized peripheral blood stem cell transplants (PBSCT) that were T-cell depleted by positive CD34 selection and sheep-RBC rosetting while three pts received soybean agglutinin E-rosette depleted marrow grafts. For the PBSCT grafts, the median CD34+ cell dose/Kg was 5.0 × 106 (range: 1.3–28.8 × 106) and the median CD3+ cell dose/Kg was 1.1 × 103 (range 0–12 × 103). Median follow-up was 16 months (range 0.7–68.7 mo). Engraftment occurred in 59 of 61 evaluable pts, but two recipients of unrelated donor grafts suffered a graft failure. Acute grade 2–4 GvHD occurred in 7 pts, and chronic GvHD in three of 40 evaluable pts. Twenty two pts died of infection (n=7), organ toxicity (n=6), GvHD (n=3), graft failure (n=1) or relapse (n=5). The two-year probabilities of overall survival (OS) and disease-free survival (DFS) for the entire patient cohort were 62% and 54% respectively with a two-year probability of relapse of 16.2%.The two-year DFS for recipients of HLA-matched related and unrelated grafts was 54% and 57% for recipients of HLA-disparate unrelated grafts. Two-year DFS was 58% for pts with primary AML, 57% for pts with primary MDS and 51% for pts with secondary MDS/AML. Two-year DFS was 60.6% for pts ≤ 50 years and 49.7% for pts > 50 years. In summary, cytoreduction with Bu Mel and Flu and rabbit ATG has secured consistent engraftment of T-cell depleted transplants for both HLA-matched or disparate, related and unrelated donors. The incidence of acute or chronic GvHD and disease relapse were low, with favorable outcomes in this cohort of older patients with high risk myeloid malignancies.

Posttransplant relapse is a major limitation to the success of allogeneic SCT in patients with advanced MDS (refractory anemia with excess blasts (RAEB I and II), refractory anemia in transformation (RAEB-t), and acute myeloid leukemia transformed from MDS). The use of induction chemotherapy prior to transplant to induce remission and thereby to reduce posttransplant relapse in these patients remains controversial. From 1985 to 2004, 47 patients with advanced MDS underwent bone marrow or peripheral blood SCT from HLA identical siblings after myeloablative conditioning with total body irradiation (TBI) and cyclophosphamide alone or in some combined with thiotepa, carboplatinum, diaziquone, or etoposide, or TBI combined with thiotepa and fludarabine. Thirty-six patients received low dose (3 patients) or full induction (33 patients) chemotherapy before conditioning, and 11 patients did not receive any chemotherapy. Prior to transplant, 22 of the 36 treated patients were in hematologic remission (CR) and 4 achieved a second refractory cytopenia phase (RCy2) for a total of 26 responders, and 10 had failed to respond to chemotherapy. Marrow grafts were depleted of T cells using soybean lectin agglutination and then sheep RBC-rosetting (n=32 patients). G-CSF-mobilized peripheral blood stem cell (PBSC) grafts underwent positive CD34 selection and T-cell depletion by sheep RBC-rosetting (n=10 patients). Five patients received a marrow graft followed by a PBSC allograft from the same donor because of low marrow cell dose. Rejection prophylaxis with anti-thymocyte globulin was used in 33 patients. No posttransplant pharmacologic prophylaxis for GvHD was given. The median age was 48 years (range 13–61). Forty-three of the 47 patients in this series engrafted, and 2 had primary graft failure. Two patients died before engraftment. Only 3 patients developed acute GvHD (grades 1 and 3) and 1 chronic GvHD. At 5 years posttransplant, the DFS was 44% for the patients in CR and RCy2 at time of transplant, but no patients in the untreated group or in the chemotherapy failure group survived (p=0.0004). The cumulative incidence (CI) of relapse at 2-years posttransplant for the responders was 27.0%, for the failures 50%, and for the untreated group 45%. The CI for non-relapse mortality at 2-years posttransplant was 19% for the responders, 40% for the failures, and 36% for the untreated patients. All survivors have achieved ≥KPS 90%. These results indicate that patients with advanced MDS who achieve remission or a second refractory anemia phase with chemotherapy before TCD allogeneic SCT can achieve successful long-term remisions. In contrast, the high incidence of posttransplant relapse mitigates against the use of TCD SCT in patients with advanced MDS with active disease (≥5% blasts) prior to transplant. Prospective multicenter randomized studies are needed to validate the value of pre-transplant chemotherapy in patients with advanced MDS undergoing allogeneic SCT.