A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia.

We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia (CLL) developed using a training-validation model in a series of 1,879 cases from Italy, the United Kingdom and the United States. By means of regression analysis, we identified five prognostic variables with weighting as follows: deletion of the short arm of chromosome 17 and unmutated immunoglobulin heavy chain gene status, 2 points; deletion of the long arm of chromosome 11, trisomy of chromosome 12, and white blood cell count >32.0x103/microliter, 1 point. Low-, intermediate- and high-risk categories were established by recursive partitioning in a training cohort of 478 cases, and then validated in four independent cohorts of 144 / 395 / 540 / 322 cases, as well as in the composite validation cohort. Concordance indices were 0.75 in the training cohort and ranged from 0.63 to 0.74 in the four validation cohorts (0.69 in the composite validation cohort). These findings advocate potential application of our novel prognostic calculator to better stratify early-stage CLL, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 CLL being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemofree era.

Prevalence and intensity of persistent post-surgical pain following breast cancer surgery: a systematic review and meta-analysis of observational studies.

BACKGROUND: The prevalence and intensity of persistent post-surgical pain (PPSP) after breast cancer surgery are uncertain. We conducted a systematic review and meta-analysis to further elucidate this issue. METHODS: We searched MEDLINE, Embase, CINAHL, and PsycINFO, from inception to November 2018, for observational studies reporting persistent pain (≥3 months) after breast cancer surgery. We used random-effects meta-analysis and the Grading of Recommendations, Assessment, Development and Evaluations approach to rate quality of evidence. RESULTS: We included 187 observational studies with 297 612 breast cancer patients. The prevalence of PPSP ranged from 2% to 78%, median 37% (inter-quartile range: 22-48%); the pooled prevalence was 35% (95% confidence interval [CI]: 32-39%). The pooled pain intensity was 3.9 cm on a 10 cm visual analogue scale (95% CI: 3.6-4.2 cm). Moderate-quality evidence supported the subgroup effects of PPSP prevalence for localized pain vs any pain (29% vs 44%), moderate or greater vs any pain (26% vs 44%), clinician-assessed vs patient-reported pain (23% vs 36%), and whether patients underwent sentinel lymph node biopsy vs axillary lymph node dissection (26% vs 43%). The adjusted analysis found that the prevalence of patient-reported PPSP (any severity/location) was 46% (95% CI: 36-56%), and the prevalence of patient-reported moderate-to-severe PPSP at any location was 27% (95% CI: 10-43%). CONCLUSIONS: Moderate-quality evidence suggests that almost half of all women undergoing breast cancer surgery develop persistent post-surgical pain, and about one in four develop moderate-to-severe persistent post-surgical pain; the higher prevalence was associated with axillary lymph node dissection. Future studies should explore whether nerve sparing for axillary procedures reduces persistent post-surgical pain after breast cancer surgery.

A prospective evaluation of thromboelastometry (ROTEM) to identify acute traumatic coagulopathy and predict massive transfusion in military trauma patients in Afghanistan.

BACKGROUND: Hemorrhage is the leading cause of preventable trauma-related mortality and is frequently aggravated by acute traumatic coagulopathy (ATC). Viscoelastic tests such as rotational thromboelastometry (ROTEM) may improve identification and management of ATC. This study aimed to prospectively evaluate changes in ROTEM among combat casualties during the first 24 hours and compare the capabilities of our conventional clotting assay (international normalized ratio [INR], >1.2) to a proposed integrated ROTEM model (INR >1.2 with the addition of tissue factor pathway activation thromboelastometry [EXTEM] A5 ≤35 mm and/or EXTEM LI30 <97% on admission) to identify ATC and predict massive transfusion (MT). STUDY DESIGN AND METHODS: This was a prospective observational study of trauma patients treated in NATO hospitals in Afghanistan between January 2012 and June 2013. ROTEM (EXTEM, functional fibrinogen thromboelastometry, APTEM, EXTEM with the addition of a fibrinolysis inhibitor) was performed on admission and at 6 and 24 hours by a designated research team. Treatment teams did not have access to the ROTEM results. RESULTS: ROTEM values were available for 40 male casualties. The integrated ROTEM model classified 15% more patients with ATC than with INR alone and increased the detection of those that required MT by 22%. The sensitivity of the integrated ROTEM model to predict MT was higher than with INR greater than 1.2 (86% vs. 64%); however, specificity with both definitions for predicting MT was poor (38% vs. 50%, respectively). CONCLUSION: These observations support the importance of early identification of and intervention in ATC. Integrating ROTEM into the definition of ATC would increase detection of those requiring MT arguing for its use as an adjunct to clinical presentation in the ultimate decision to initiate MT.

HIV-Specific Granzyme B-Secreting but Not Gamma Interferon-Secreting T Cells Are Associated with Reduced Viral Reservoirs in Early HIV Infection.

A major barrier to a human immunodeficiency virus type 1 (HIV-1) infection cure is the establishment of a viral reservoir in spite of combined antiretroviral therapy (cART). It is unclear how HIV-specific cytotoxic T lymphocytes (CTLs) influence the size of the reservoir in early HIV infection. Twenty-eight subjects with early HIV infection were recruited to receive cART and followed for 48 weeks. HIV reservoirs in peripheral CD4+ T cells measured by cell-associated proviral DNA and viral outgrowth cultures were determined at baseline and after 48 weeks of cART. At baseline, granzyme B and gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assays were performed with peptides spanning the HIV proteome. All subjects had detectable HIV-specific granzyme B and IFN-γ responses at baseline. The quantity and specificity of granzyme B responses did not correlate with IFN-γ responses. For granzyme B, Tat/Rev was the most dominant whereas for IFN-γ, Gag predominated. HIV-specific granzyme B T cell responses negatively correlated with HIV proviral loads at baseline and at 48 weeks and with replication-competent viral infectious units per million (IUPM) CD4+ T cells at baseline but not significantly at 48 weeks. Tat/Rev-, Env-, Gag-, and Vif-specific granzyme B responses correlated most strongly with reservoir control. There was no correlation of HIV-specific IFN-γ responses with reservoir size at baseline or at 48 weeks. The majority of granzyme B responses were contributed by CD8+ T cells. Thus, our findings suggest that the induction of potent granzyme B-producing CTLs to Tat, Rev, Env, Gag, and Vif during early infection may be able to prevent the establishment of a large viral reservoir, thereby facilitating a reduced HIV burden.IMPORTANCE A major barrier to the cure of human immunodeficiency virus type 1 (HIV-1) infection is the establishment of a viral reservoir that must be significantly reduced or eradicated entirely to enable a cure. Combined antiretroviral therapy (cART) alone is unable to clear this viral reservoir. It has been shown that CD8+ cytotoxic T lymphocytes (CTLs) are important in controlling early HIV infection by reducing plasma viremia. However, it is not known if these HIV-specific CTLs influence the establishment of the viral reservoir in early HIV infection. We show that HIV-specific granzyme B responses targeting HIV Tat/Rev, Env, Gag, and Vif, but not IFN-γ responses, are associated with reduced virus reservoirs at baseline and at 48 weeks of cART. These findings shed light on the nature of the effector CTL response that might limit reservoir size with implications for cure research and HIV vaccines.

Analysis of 36 cases of Blaschkoid dyspigmentation: reading between the lines of Blaschko.

Genetic mosaicism indicated by lines of Blaschko pigmentary changes has been described under a number of different and confusing terms, including hypomelanosis of Ito, linear and whorled nevoid hypermelanosis, nevus depigmentosus, and cutis tricolor. Moreover, extracutaneous findings, particularly serious neurologic defects, have been reported in a large number of these cases. We reviewed the cutaneous and extracutaneous findings in 36 patients referred to the Harriet Lane Pediatric Dermatology Clinic, Johns Hopkins University, from June 12, 2008, to May 24, 2009, for evaluation of macular lesions along the lines of Blaschko. Patients with dyspigmentation along the lines of Blaschko and no history of preceding inflammatory skin lesions were identified for inclusion in a database at their initial visit. Information on age at presentation; sex; age when first diagnosed; type, pattern, and location of the pigmentary anomaly; and extracutaneous abnormalities noted on a review-of-systems questionnaire and physical examination was recorded for each child. Patients were asked to follow up within 6 to 12 months of the initial visit. Patients included 13 boys and 23 girls ages 3 months to 15 years with lesions noted from birth to 12 years. Lesions were hypopigmented in 21 patients and hyperpigmented in 15. No patients presented with hypopigmented and hyperpigmented lesions. Extracutaneous findings were noted in five children (13.9%). Historically, cases of Blaschkoid hypopigmentation and hyperpigmentation have been associated with a high percentage of extracutaneous manifestations, particularly neurologic and neurodevelopmental defects. In our study, only five patients (13.9%) were noted to have extracutaneous abnormalities, and these findings may have been coincidental. We propose the term 'Blaschkoid dyspigmentation' to describe the cutaneous findings. Although serious extracutaneous findings may occur in children with Blaschkoid dyspigmentation and results of careful physical examination and review of systems should direct an evaluation, serious extracutaneous findings occur in a minority of patients.

Seeing Bradycardia: How Ultrasound Improves Medical Decision-Making.

There is a broad differential for new-onset cardiac dysrhythmia, and the rapid identification of the underlying cause of these cardiac emergencies can be lifesaving. Identifying wall motion abnormalities on point-of-care ultrasound (POCUS) is not a core echocardiography application for Emergency Medicine (EM) physicians. However, ruling in a regional wall motion abnormality can expedite patient-centered care and assist the busy EM physician in high-risk cases.

Point of Care Ultrasounds Obtained by Novice Physician Assistant Residents (POCUS ON PAR).

INTRODUCTION: The integration of Point of Care Ultrasound (POCUS) into the care of trauma patients, specifically the E-FAST, has improved the accuracy of initial diagnoses and improved time to surgical intervention in critically ill patients. Physician assistants (PAs) are critically important members of any military trauma resuscitation team and are often team leaders in a pre-hospital setting. They may receive training in ultrasound but there are little data to support their use or evaluate their effectiveness in using POCUS. We designed a study to evaluate the image quality of an E-FAST Exam performed by Emergency Medicine Physician Assistant (EMPA) Fellows and Emergency Medicine (EM) Interns following identical training. Our hypothesis is that image quality obtained by EMPAs will be non-inferior to those images obtained by EM Interns. MATERIALS AND METHODS: This is a prospective single-blinded study comparing the image quality of E-FAST exams performed by first year EM interns and first year EMPA fellows. All participants completed standard POCUS training prior to enrollment in the study. A total of 8 EMPAs and 8 EM first year residents completed 10 recorded E-FAST exams to be used as study images. Participants also viewed a 15-question slide show containing images of positive (6) and negative (9) E-FAST exams and recorded their interpretations. Images were reviewed by expert reviewers who were blinded to which images were collected by which group. An image quality score was recorded for each view as well as an overall image quality score. Image quality was rated on a 1 to 5 image quality scale. RESULTS: For overall image quality, the mean score for EMPAs was 3.6 ± 0.5 and for EM residents was 3.2 ± 0.5 with statistical significance favoring better image quality from the EMPAs. The time to completion for the EFAST exam for EMPAs was 4.8 ± 1.3 minutes and for interns it was 3.4 ± 1.4 minutes (P value = 0.02). There was no difference in image interpretation quiz scores between the groups (mean score 92% among interns and 95% among PAs). CONCLUSIONS: POCUS is an imaging modality which is very portable and relatively inexpensive which makes it ideal for military medicine. PAs are essential members of military trauma teams, and often run an initial trauma resuscitation. Being able to correctly identify patients who have free fluid early in the course of treatment allows for more correct evacuation criteria to ensure the sickest patients get to care the fastest. Although there are limited data to support POCUS use by non-physicians, our data support a growing body of evidence that it is not the profession or baseline medical education that determines an individual's ability to use and incorporate ultrasound into bedside and clinical practice. Our study shows that with training and experience PAs or other members of the military health care team can use the EFAST to better care for trauma patients.

Blinatumomab consolidation post-autologous stem cell transplantation in patients with diffuse large B-cell lymphoma.

ABSTRACT: Outcomes in patients with relapsed diffuse large B-cell lymphoma (DLBCL) who undergo autologous stem cell transplant (auto-SCT) are poor. Blinatumomab is a CD3/CD19 bispecific T-cell engager that directs cytotoxic T cells to CD19+ cells. Here, we performed a pilot study of blinatumomab consolidation after auto-SCT for 14 patients with DLBCL or transformed follicular lymphoma. All patients underwent standard-of-care auto-SCT with carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning followed by 1 cycle (4 weeks continuous infusion) of blinatumomab consolidation starting at day 42 after auto-SCT. All 14 patients treated on study completed BEAM auto-SCT and 1 cycle of posttransplant blinatumomab. Five patients developed grade 1 cytokine release syndrome (CRS), with no grade 2 or higher CRS. Immune effector cell-associated neurotoxicity syndrome was not observed. Patients were followed up for 3 years after auto-SCT, with median follow-up of 37 (range, 12-65) months. One-hundred days after auto-SCT (1 month after blinatumomab consolidation), 12 patients (86%) had achieved complete remission. At 1 year after auto-SCT, 7 patients (50%) remained in CR, and 1 patient had died of progressive disease. Patients who relapsed had a lower CD8:CD4 T-cell ratio before starting blinatumomab than patients who remained in remission. This pilot study demonstrates blinatumomab consolidation after auto-SCT is safe and well tolerated. Strategies to increase the CD8:CD4 ratio and use additional cycles of consolidation in a larger randomized trial are needed to confirm the efficacy of consolidation with blinatumomab after auto-SCT. This trial was registered at www.clinicaltrials.gov as #NCT03072771.

Functional Analysis and Chained Schedule Treatment of Elopement in Teens with Autism Spectrum Disorder.

Elopement is one of the most common forms of problem behavior for individuals with autism spectrum disorder (ASD) and is associated with the greatest probability of a lethal outcome. This study evaluated the effects of a function-based treatment package on elopement for two teenage boys with ASD who eloped frequently from caregivers. Functional analyses (FA) identified the variables that evoked and maintained each teen's elopement. Treatment involved a chained schedule comprised primarily of empirically derived differential reinforcement of other behavior (DRO), functional communication training (FCT), and extinction procedures. The treatment produced clinically significant decreases in elopement for both teens. Decreases in elopement maintained when the treatment evaluation was extended to additional contexts. The current study extends the literature on assessment and treatment of elopement and chained schedule treatments that involve both DRO and FCT.

Vasculopathy related to cocaine adulterated with levamisole: A review of the literature.

BACKGROUND: Recently, there have been numerous case reports and series describing patients presenting with cutaneous vasculopathy that has been linked to the levamisole frequently found in cocaine. OBJECTIVE: The purpose of this study was to review all published case reports and series of patients reported with cutaneous vasculopathic findings of lemavisole induced vasculopathy (LIV) associated with cocaine use. METHODS: A review of PubMed was performed searching the keywords: levamisole, cocaine, in combination with vasculitis, and vasculopathy. Twenty-two case reports and series were available with sufficient data on reported patients to be included. Four patients from the authors' clinical experience are included as well. RESULTS: A number of common clinical and pathological findings are reviewed, including lower extremity (46/55 patients, 84%) and ear involvement (40/55 patients, 73%), and positive anti-neutrophil cytoplasmic antibodies (ANCA) findings (p-ANCA 42/48 patients, 88%; anti human neutrophil elastase 11/11 patients, 100%). Similar numbers of patients were treated with systemic corticosteroids as were treated conservatively; there was comparable improvement on follow up. CONCLUSIONS: There are a number of clinical and laboratory findings that are commonly found in patients with LIV. There is currently insufficient data to recommend treatment with systemic corticosteroids in patients with this condition.

Axicabtagene ciloleucel for the treatment of relapsed or refractory follicular lymphoma.

INTRODUCTION: Axicabtagene ciloleucel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was recently approved for relapsed or refractory follicular lymphoma following progression on two or more lines of therapy including an anti-CD20 monoclonal antibody with an alkylating agent, providing a therapeutic breakthrough in a subset of indolent non-Hodgkin lymphoma associated with poor clinical outcomes. AREAS COVERED: In this article, we outline the drug profile of axicabtagene ciloleucel in comparison to currently approved agents and other CAR T-cell and T-cell redirecting therapies under investigation for the treatment of relapsed or refractory follicular lymphoma. We also review the efficacy, safety, and pharmacokinetic data from the ZUMA-5 phase II trial, which forms the basis of the recent approval of axicabtagene ciloleucel. EXPERT OPINION: Axicabtagene ciloleucel is the first cellular therapy approved for relapsed or refractory follicular lymphoma, demonstrating high rates of durable responses and a manageable toxicity profile in heavily pre-treated patients.

The Potential for Selective Cyclin-Dependent Kinase 4/6 Inhibition in the Therapy for Head and Neck Squamous Cell Carcinoma.

ABSTRACT: Preclinical data support investigation of selective CDK4/6 inhibition as a therapeutic strategy for human papillomavirus (HPV)-unrelated head and neck squamous cell carcinoma (HNSCC). Phase 1 clinical trials established the feasibility of combining palbociclib with cetuximab in patients with recurrent or metastatic HNSCC. Nonrandomized phase II trials showed that palbociclib plus cetuximab resulted in efficacy outcomes better than cetuximab in biomarker-unselected, platinum-resistant or cetuximab-resistant, HPV-unrelated HNSCC. A double-blind, randomized phase II trial (PALATINUS) evaluated the efficacy of palbociclib or placebo and cetuximab in patients with biomarker-unselected, platinum-resistant, cetuximab-naive, HPV-unrelated HNSCC. Palbociclib and cetuximab did not significantly prolong overall survival compared with placebo and cetuximab. However, correlative biomarker analyses identified that trends for better overall survival with palbociclib and cetuximab were observed in certain prespecified subsets; the largest reduction in risk of death with palbociclib versus placebo and cetuximab occurred in the subset with CDKN2A mutations. Several phase II-III trials are underway investigating palbociclib in biomarker-selected patients with HPV-unrelated locally advanced or recurrent or metastatic HNSCC.

Comparing the Sensitivity of a Low Frequency Versus a High Frequency Probe in the Detection of Pneumothorax in a Swine Model.

BACKGROUND: Correct diagnosis of pneumothorax in trauma patients is essential. Under-diagnosis can lead to development of life-threatening tension pneumothorax, but overdiagnosis leads to placement of unnecessary chest tubes with potential related morbidity and pain. It is unclear from previous work if there is a benefit to switching from the phased array (low frequency) probe to the linear (high frequency) probe. Is the improvement in image quality worth the time lost changing probes? METHODS: We compared the sensitivity and specificity of a low frequency and high frequency ultrasound probe for the detection of pneumothorax. Images were obtained using swine models and were interpreted by Emergency Medicine residents, attendings, and physician assistants. RESULTS: We found a specificity of 89% and sensitivity of 99% for the low frequency probe and specificity of 96% and sensitivity of 99% for the high frequency probe. There was a statistically different specificity between the two probes, suggesting that the linear probe may be the superior probe for confirming the presence of pneumothorax. CONCLUSION: We conclude switching to the linear probe for the thoracic portion of the Extended-Focused Assessment in Trauma will lead to more accurate diagnosis of pneumothorax and decreased false-positive exams.

Ultrasound at the Role 1: An Analysis of After-Action Reviews from the Prehospital Trauma Registry.

BACKGROUND: Ultrasound is a portable and adaptable imaging modality used widely in the care of trauma patients. The initial exam, known as the "Focused Assessment in Trauma (FAST) exam focused on the evaluation for hemoperitoneum and hemopericardium. In recent years, the exam has expanded to include evaluate for thoracic pathology, including pneumothorax, and is now known as the "Extended Focused Assessment in Trauma" (E-FAST) exam. METHODS: We reviewed after-action reviews (AAR) from the Joint Trauma System Prehospital Trauma Registry from 2013-2014 in which the use of an ultrasound exam was noted. Given the largely unstructured nature of the AARs, we selected relevant information from the free text available. RESULTS: Our initial dataset contained 705 casualties, of which we identified 45 cases containing the key words with AAR data for review: 39 cases involved the use of the FAST exam, three explicitly described the use of pulmonary ultrasound and they were categorized as E-FAST exams, two cases described the use of point of care echo to evaluate for cardiac standstill, and two cases described the use of ultrasound to evaluate for vascular injury. Of those with vital signs documented, 25% (11) reported at least one episode of tachycardia (≥120/min) and 16% (7) with at least one episode of systolic hypotension (less than 90mmHg). Of the 45 cases reviewed, six were recorded as equivocal, which we interpreted to indicate more training in either performance or interpretation of the exam was needed. CONCLUSIONS: Our findings suggest that training in both the FAST exam and E-FAST has the potential to improve patient care for military trauma patients. A performance improvement system would enable real-time confirmation of findings and feedback for training and quality improvement.

TP53 Mutations with Low Variant Allele Frequency Predict Short Survival in Chronic Lymphocytic Leukemia.

PURPOSE: In chronic lymphocytic leukemia (CLL), TP53 mutations are associated with reduced survival and resistance to standard chemoimmunotherapy (CIT). Nevertheless, the clinical impact of subclonal TP53 mutations below 10% to 15% variant allele frequency (VAF) remains unclear. EXPERIMENTAL DESIGN: Using a training/validation approach, we retrospectively analyzed the clinical and biological features of TP53 mutations above (high-VAF) or below (low-VAF) the previously reported 10.0% VAF threshold, as determined by deep next-generation sequencing. Clinical impact of low-VAF TP53 mutations was also confirmed in a cohort (n = 251) of CLL treated with fludarabine-cyclophosphamide-rituximab (FCR) or FCR-like regimens from two UK trials. RESULTS: In the training cohort, 97 of 684 patients bore 152 TP53 mutations, while in the validation cohort, 71 of 536 patients had 109 TP53 mutations. In both cohorts, patients with the TP53 mutation experienced significantly shorter overall survival (OS) than TP53 wild-type patients, regardless of the TP53 mutation VAF. By combining TP53 mutation and 17p13.1 deletion (del17p) data in the total cohort (n = 1,220), 113 cases were TP53 mutated only (73/113 with low-VAF mutations), 55 del17p/TP53 mutated (3/55 with low-VAF mutations), 20 del17p only, and 1,032 (84.6%) TP53 wild-type. A model including low-VAF cases outperformed the canonical model, which considered only high-VAF cases (c-indices 0.643 vs. 0.603, P < 0.0001), and improved the prognostic risk stratification of CLL International Prognostic Index. Clinical results were confirmed in CIT-treated cases (n = 552) from the retrospective cohort, and the UK trials cohort. CONCLUSIONS: TP53 mutations affected OS regardless of VAF. This finding can be used to update the definition of TP53 mutated CLL for clinical purposes.

Migration defects by DISC1 knockdown in C57BL/6, 129X1/SvJ, and ICR strains via in utero gene transfer and virus-mediated RNAi.

Disrupted-in-Schizophrenia 1 (DISC1) is a promising genetic risk factor for major mental disorders. Many groups repeatedly reported a role for DISC1 in brain development in various strains of mice and rats by using RNA interference (RNAi) approach. Nonetheless, due to the complexity of its molecular disposition, such as many splice variants and a spontaneous deletion in a coding exon of the DISC1 gene in some mouse strains, there have been debates on the interpretation on these published data. Thus, in this study, we address this question by DISC1 knockdown via short-hairpin RNAs (shRNAs) against several distinct target sequences with more than one delivery methodologies into several mouse strains, including C57BL/6, ICR, and 129X1/SvJ. Here, we show that DISC1 knockdown by in utero electroporation of shRNA against exons 2, 6, and 10 consistently results in neuronal migration defects in the developing cerebral cortex, which are successfully rescued by co-expression of full-length DISC1. Furthermore, lentivirus-mediated shRNA also led to migration defects, which is consistent with two other methodologies already published, such as plasmid-mediated and retrovirus-mediated ones. The previous study by Song's group also reported that, in the adult hippocampus, the phenotype elicited by DISC1 knockdown with shRNA targeting exon 2 was consistently seen in both C57BL/6 and 129S6 mice. Taken together, we propose that some of DISC1 isoforms that are feasible to be knocked down by shRNAs to exon 2, 6, and 10 of the DISC1 gene play a key role for neuronal migration commonly in various mouse strains and rats.

Sugammadex in Ontario hospitals: Access and institutional policies.

RATIONALE AND AIMS: Sugammadex is a novel neuromuscular blockade reversal agent which rapidly reverses the effects of rocuronium and vecuronium. Compared with the first-generation neuromuscular blockade reversal agent, neostigmine, sugammadex has a number of superior properties; however, sugammadex is significantly more expensive per dose compared with neostigmine (~CAD$95 vs $4). Given the high cost of sugammadex, many Ontario hospitals either do not stock the drug or have specific policies on when the drug can be administered. This study was designed to determine access to sugammadex in Ontario hospitals, as well as the prevalence and content of institutional policies on its use. METHODS: We designed a survey assessing the availability of sugammadex and institutional policies on its use. We identified 60 Ontario hospitals with surgical services and obtained contact information for 45 of the anaesthesia departments. Surveys were sent to each department chief, and results were collected from July to October 2018. RESULTS: Thirty-four (75.6%) hospitals responded to the survey. Twenty-seven (79.4%) of the 34 respondent hospitals had sugammadex. Of the seven hospitals that did not have sugammadex, six were group B hospitals, and one was a paediatric hospital. Of the 27 hospitals with sugammadex, 16 (59.3%) hospitals had specific policies on when sugammadex may be used. Based on policies, sugammadex was most frequently allowed to be used in emergency situations, especially failed intubations or "can't intubate, can't ventilate" situations where 100% of policies allowed its use. Policies on specific patient populations for sugammadex use were uncommon, with 43.8% of existing hospital policies not specifying any patient populations. CONCLUSIONS: Though most hospitals have sugammadex available, there is a marked heterogeneity in hospital policies on its use. Given the high cost of sugammadex use, it is worthwhile to have evidence-based policies on its use. Judicious use of sugammadex may also have secondary cost-saving benefits, through improved operating room efficiency and decreased complication rates.

Assessment of an Orthopedic Surgery Rotation on Musculoskeletal Competency in Emergency Medicine Residency Training.

OBJECTIVE: To determine baseline knowledge of emergency medicine (EM) residents at 2 different residency training programs and assess if a 4-week orthopedic surgery rotation would improve musculoskeletal (MSK) knowledge as assessed by the basic competency exam (BCE). This study also sought to compare variations of the BCE to determine how emergency physicians would perform on the full 25-question assessment vs a modified 18-question test. DESIGN: Residents from 2 different EM residency training programs were given the BCE to determine baseline MSK knowledge prior to their orthopedic surgery rotations. A postrotation BCE was given to the residents from both EM training programs upon completion of their orthopedic surgery rotation. Both prerotation and postrotation tests were reviewed and scored independently by a panel of experts and later assessed by 2 independent reviewers. SETTING: San Antonio Military Medical Center, SA Tx Level I Trauma, Tertiary Care Center University of Texas Health, SA, Tx, Level 1 Trauma, Tertiary Care Center. PARTICIPANTS: A total of 54 EM residents completed both the prerotation test and pos-rotation test. RESULTS: EM residents at both programs had significantly improved test scores after an orthopedic surgery rotation. Baselines scores of PGY-2 residents were higher than PGY-1 residents. CONCLUSIONS: EM residents can improve their competency in MSK education with a 4-week rotation in orthopedic surgery. Further studies are needed to determine knowledge retention and to identify components of an optimal orthopedic rotation.