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This chapter provides the reader with a succinct review surround the issues with uncontrolled pain and provides methods for non-pharmacologic treatment in children. The chapter discusses the sequalae of untreated pain and provides the reader with a detailed explanation of the theory behind distraction techniques. The various distraction techniques are discussed based on age appropriate selection.
To assess the safety of, and subsequent allergy documentation associated with, an antimicrobial stewardship intervention consisting of test-dose challenge procedures prompted by an electronic guideline for hospitalized patients with reported β-lactam allergies.
Retrospective cohort study.
Large healthcare system consisting of 2 academic and 3 community acute-care hospitals between April 2016 and December 2017.
We evaluated β-lactam antibiotic test-dose outcomes, including adverse drug reactions (ADRs), hypersensitivity reactions (HSRs), and electronic health record (EHR) allergy record updates. HSR predictors were examined using a multivariable logistic regression model. Modification of the EHR allergy record after test doses considered relevant allergy entries added, deleted, and/or specified.
We identified 1,046 test-doses: 809 (77%) to cephalosporins, 148 (14%) to penicillins, and 89 (9%) to carbapenems. Overall, 78 patients (7.5%; 95% confidence interval [CI], 5.9%–9.2%) had signs or symptoms of an ADR, and 40 (3.8%; 95% CI, 2.8%–5.2%) had confirmed HSRs. Most HSRs occurred at the second (ie, full-dose) step (68%) and required no treatment beyond drug discontinuation (58%); 3 HSR patients were treated with intramuscular epinephrine. Reported cephalosporin allergy history was associated with an increased odds of HSR (odds ratio [OR], 2.96; 95% CI, 1.34–6.58). Allergies were updated for 474 patients (45%), with records specified (82%), deleted (16%), and added (8%).
This antimicrobial stewardship intervention using β-lactam test-dose procedures was safe. Overall, 3.8% of patients with β-lactam allergy histories had an HSR; cephalosporin allergy histories conferred a 3-fold increased risk. Encouraging EHR documentation might improve this safe, effective, and practical acute-care antibiotic stewardship tool.
The response to the 2010 Deepwater Horizon oil spill was impacted by heat. We evaluated the association between environmental heat exposure and self-reported heat-related symptoms in US Coast Guard Deepwater Horizon disaster responders.
Utilizing climate data and postdeployment survey responses from 3648 responders, we assigned heat exposure categories based on both wet bulb globe temperature (WBGT) and heat index (HI) measurements (median, mean, maximum). We calculated prevalence ratios (PRs) and 95% confidence intervals (CIs) via adjusted Poisson regression models with robust error variance to estimate associations with reported heat-related symptoms. We also evaluated the association between use of personal protective equipment (PPE) and heat-related symptoms.
Those in the highest WBGT median–based heat exposure category had increased prevalence of heat-related symptoms compared to those in the lowest category (PR=2.22 [95% CI: 1.61, 3.06]), and there was a significant exposure-response trend (P<.001). Results were similar for exposure categories based on WBGT and HI metrics. Analyses stratified by use of PPE found significantly stronger associations between environmental heat exposure and heat-related symptoms in those who did not use PPE (PR=2.23 [95% CI: 1.10, 4.51]) than in those who did (PR=1.64 [95% CI: 1.14, 2.36]).
US Coast Guard Deepwater Horizon disaster responders who experienced higher levels of environmental heat had higher prevalences of heat-related symptoms. These symptoms may impact health, safety, and mission effectiveness. As global climate change increases the frequency of disasters and weather extremes, actions must be taken to prevent heat-related health impacts among disaster responders. (Disaster Med Public Health Preparedness. 2019;13:561-569)
Background: External ventricular drain (EVD) insertion is a common neurosurgical procedure performed in patients with life-threatening conditions, but can be associated with complications. The objectives of this study are to evaluate data on national practice patterns and complications rates in order to optimize clinical care Methods: The Canadian Neurosurgery Research Collaborative conducted a prospective multi-centre registry of patients undergoing EVD insertions at Canadian residency programs Results: In this interim analysis, 4 sites had recruited 46 patients (mean age: 53.9 years, male:female 2:1). Most EVD insertions occurred outside of the operating theatre, using free-hand technique, and performed by junior neurosurgery residents (R1-R3). The catheter tip was in the ipsilateral frontal horn or body of the lateral ventricle in 76% of cases. Suboptimally placed catheters did not have higher rates of short-term occlusion. EVD-related hemorrhage occurred in 6.5% (3/45) with only 1 symptomatic patient. EVD-related infection occurred in 13% (6/46) at a mean of 6 days and was associated with longer duration of CSF drainage (P=0.039; OR: 1.13) Conclusions: Interim results indicate rates of EVD-related complications may be higher than previously thought. This study will continue to recruit patients to confirm these findings and determine specific risk factors associated with them
Current standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Most tumors recur within a year from diagnosis and median survival for recurrent GBM (rGBM) is 3-9 months. Unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance, exhibited by most GBM patients. VAL-083 is a DNA-targeting agent with a mechanism-of-action that is independent of MGMT. VAL-083 overcomes temozolomide-resistance in GBM cell-lines, cancer stem cells, and in vivo models. VAL-083 readily crosses the blood-brain barrier and accumulates in brain-tumor tissue. We recently completed a VAL-083 dose-escalation trial in temozolomide- and bevacizumab-refractory rGBM and determined that 40mg/m2/day given intravenously on days 1,2,3 of a 21-day cycle is generally well-tolerated. This dosing regimen was selected for subsequent GBM trials, including an ongoing single-arm, biomarker-driven Phase 2 trial (N=48) in temolozomide-refractory, bevacizumab-naïve rGBM , MGMT-unmethylated (Clinicaltrials.gov:NCT02717962). The primary objective of this study is to determine if VAL-083 improves OS compared to a historical control of 7.15 months for MGMT-unmethylated rGBM patients treated with lomustine (EORTC26101). In addition, another single-arm, biomarker-driven, Phase 2 study (N=25) of VAL-083 in combination with radiotherapy in newly diagnosed GBM, MGMT-unmethylated is ongoing (Clinicaltrials.gov:NCT03050736). This trial aims to determine a dose for further study of VAL-083 in combination with radiotherapy and explore if VAL-083 improves PFS and OS compared to historical results in newly diagnosed GBM. Enrollment and safety data updates will be provided at the meeting. The results of these studies, if successful, may support VAL-083 as part of a new chemotherapeutic treatment paradigm for GBM.
Background: Neurosurgical residents face a unique combination of challenges, including long duty hours, technically challenging cases, and uncertain employment prospects. We sought to assess the demographics, interests, career goals, self-rated happiness, and overall well-being of Canadian neurosurgery residents. Methods: A cross-sectional survey was developed and sent through the Canadian Neurosurgery Research Collaborative to every resident enrolled in a Canadian neurosurgery program as of April 1, 2016. Results: We analyzed 76 completed surveys of 146 eligible residents (52% response rate). The median age was 29 years, with 76% of respondents being males. The most popular subspecialties of interest for fellowship were spine, oncology, and open vascular neurosurgery. The most frequent self-reported number of worked hours per week was the 80- to 89-hour range. The majority of respondents reported a high level of happiness as well as stress. Sense of accomplishment and fatigue were reported as average to high and overall quality of life was low for 19%, average for 49%, and high for 32%. Satisfaction with work-life balance was average for 44% of respondents and was the only tested domain in which significant dissatisfaction was identified (18%). Overall, respondents were highly satisfied with their choice of specialty, choice of program, surgical exposure, and work environment; however, intimidation was reported in 36% of respondents and depression by 17%. Conclusions: Despite a challenging residency and high workload, the majority of Canadian neurosurgery residents are happy and satisfied with their choice of specialty and program. However, work-life balance, employability, resident intimidation, and depression were identified as areas of active concern.
Thorium dioxide (thoria, ThO2) is used in refractory applications and as nuclear fuel. Its melting temperature, the highest of any binary oxide, makes it a difficult system to process. Here we report on the effects of flash sintering on the densification of thoria. We found 95% of theoretical density is obtained at ~950 °C (~30% of the melting temperature) with an electric field of 800 V/cm. Variation in power density had a minimal effect on the densification. Scanning electron microscopy images show the effects of flash sintering on grain size as a function of electric field.
Inadvertent hyperthermia during anaesthesia is a rare but life-threatening complication. We have encountered several cases of severe hyperthermia in paediatric patients undergoing anaesthesia for cochlear implantation.
This study aimed to describe the clinical characteristics of children who developed hyperthermia while undergoing cochlear implantation, and to explore possible mechanisms and predisposing factors. The anaesthetic charts of all patients aged under 18 years who underwent cochlear implantation, or mastoid or ophthalmic surgery, between 1 January 2006 and 31 December 2009, at Soroka Medical Center in Beer Sheva, Israel, were reviewed. Patients undergoing mastoid and ophthalmic surgical procedures were used as controls.
A larger percentage of patients who underwent cochlear implant surgery (10 per cent) developed hyperthermia compared to controls (0.7 per cent, p < 0.05). In five of the seven cases, hyperthermia appeared in combination with tachycardia and hypercapnia, adhering to the clinical triad of malignant hyperthermia.
Patients undergoing cochlear implantation are susceptible to developing intra-operative hyperthermia. This article describes the hyperthermic events that occur during paediatric cochlear implantation, and attempts to identify potential triggers of hyperthermia.
Policy-makers and practitioners have a need to assess community resilience in disasters. Prior efforts conflated resilience with community functioning, combined resistance and recovery (the components of resilience), and relied on a static model for what is inherently a dynamic process. We sought to develop linked conceptual and computational models of community functioning and resilience after a disaster.
We developed a system dynamics computational model that predicts community functioning after a disaster. The computational model outputted the time course of community functioning before, during, and after a disaster, which was used to calculate resistance, recovery, and resilience for all US counties.
The conceptual model explicitly separated resilience from community functioning and identified all key components for each, which were translated into a system dynamics computational model with connections and feedbacks. The components were represented by publicly available measures at the county level. Baseline community functioning, resistance, recovery, and resilience evidenced a range of values and geographic clustering, consistent with hypotheses based on the disaster literature.
The work is transparent, motivates ongoing refinements, and identifies areas for improved measurements. After validation, such a model can be used to identify effective investments to enhance community resilience. (Disaster Med Public Health Preparedness. 2018;12:127–137)
Clinician education and prospective audit and feedback interventions, deployed separately and concurrently, did not reduce antimicrobial use errors or rates compared to a control group of general medicine inpatients at our public hospital. Additional research is needed to define the optimal scope and intensity of hospital antimicrobial stewardship interventions.
Background: No standardized method of resident operative-case logging exists. Our study sought to develop a standardized form used by residents to log operative-cases. Methods: Members of the Canadian Neurosurgery Research Collaborative (CNRC), a national resident-led research organization have created a standardized document based on the current Royal College objectives for operative procedures (section 5). Modifications to structure and content will be guided via consensus from Canadian neurosurgery program-directors. Results: Program directors in each CNRC collaborative institution will be asked to modify the standardized form. The CNRC currently involves thirteen of the fourteen Canadian neurosurgery residency programs. Additional consensus, if necessary, can be reached at the Royal College meeting for program directors of neurosurgery March 20th 2017. Conclusions: A standardized operative-case log represents the first step in a prospective study towards compiling operative volume of all Canadian neurosurgical residents over one academic year. Such data will be essential to guide informed decisions with regard to Royal College requirements as Canadian neurosurgical programs transition to a competency based framework.
Background: Communicating with senior neurosurgical colleagues during residency necessitates a reliable and versatile smartphone. Smartphones and their apps are commonplace. They enhance communication with colleagues, provide the ability to access patient information and results, and allow access to medical reference applications. Patient data safety and compliance with the Personal Health Information Protection Act (PHIPA, 2004) in Canada remain a public concern that can significantly impact the way in which mobile smartphones are utilized by resident physicians Methods: Through the Canadian Neurosurgery Research Collaborative (CNRC), an online survey characterizing smartphone ownership and utilization of apps among Canadian neurosurgery residents and fellows was completed in April 2016. Results: Our study had a 47% response rate (80 surveys completed out of 171 eligible residents and fellows). Smartphone ownership was almost universal with a high rate of app utilization for learning and facilitating the care of patients. Utilization of smartphones to communicate and transfer urgent imaging with senior colleagues was common. Conclusions: Smartphone and app utilization is an essential part of neurosurgery resident workflow. In this study we characterize the smartphone and app usage within a specialized cohort of residents and suggest potential solutions to facilitate greater PHIPA adherence
Background: The Canadian Neurosurgery Research Collaborative (CNRC) was founded in November 2015 as a resident-led national network for multicentre research. We present an annual report of our activities. Methods: CNRC meetings and publications were reviewed and summarized. The status of ongoing and future studies was collected from project leaders. Results: In its first year, the CNRC produced two papers accepted for publication in the Canadian Journal of Neurological Sciences: A CNRC launch letter and a study of operative volume at Canadian neurosurgery residency programs. Three manuscripts are in preparation: 1) a study of the demographics of Canadian neurosurgery residents, 2) an assessment of mobile devices usage patterns and 3) a validation study of the most utilized neurosurgery mobile apps. In addition, protocols for two multi-centre studies are currently undergoing national Research Ethics Board review: A retrospective study of the incidence and predictors of cerebellar mutism and a prospective registry of external ventricular drain procedures and complications. The network is now a registered not-for-profit organization endorsed by the Canadian Neurosurgical Society. Conclusions: The CNRC is a feasibile, relevant and productive resident-led national research network. As the CNRC matures, we look forward to expanding the scope and impact of its projects.
Background Currently, the literature lacks reliable data regarding operative case volumes at Canadian neurosurgery residency programs. Our objective was to provide a snapshot of the operative landscape in Canadian neurosurgical training using the trainee-led Canadian Neurosurgery Research Collaborative. Methods: Anonymized administrative operative data were gathered from each neurosurgery residency program from January 1, 2014, to December 31, 2014. Procedures were broadly classified into cranial, spine, peripheral nerve, and miscellaneous procedures. A number of prespecified subspecialty procedures were recorded. We defined the resident case index as the ratio of the total number of operations to the total number of neurosurgery residents in that program. Resident number included both Canadian medical and international medical graduates, and included residents on the neurosurgery service, off-service, or on leave for research or other personal reasons. Results: Overall, there was an average of 1845 operative cases per neurosurgery residency program. The mean numbers of cranial, spine, peripheral nerve, and miscellaneous procedures were 725, 466, 48, and 193, respectively. The nationwide mean resident case indices for cranial, spine, peripheral nerve, and total procedures were 90, 58, 5, and 196, respectively. There was some variation in the resident case indices for specific subspecialty procedures, with some training programs not performing carotid endarterectomy or endoscopic transsphenoidal procedures. Conclusions: This study presents the breadth of neurosurgical training within Canadian neurosurgery residency programs. These results may help inform the implementation of neurosurgery training as the Royal College of Physicians and Surgeons residency training transitions to a competence-by-design curriculum.
Glioblastoma (GBM) is the most common brain cancer. Most GBM tumors have unmethylated promoter status for O6-methylguanine-DNA-methyltransferase (MGMT); a validated biomarker for MGMT protein-expression and ensuing temozolomide-resistance. Second-line treatment with bevacizumab has not improved overall survival (OS). Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent targeting N7-Guanine, thus MGMT-independently inducing interstrand cross-links, DNA double-strand breaks and cell-death in GBM cell-lines and cancer stem cells. VAL-083 is currently in Phase I/II clinical trial for recurrent GBM, post-TMZ and post-bevacizumab. In this Phase II clinical trial, the main goal is to assess the 9-month OS in MGMT-unmethylated, recurrent, bevacizumab-naive GBM. RATIONALE: The vast majority of GBM patients experience recurrent/progressive disease within a year from initial diagnosis and median survival after recurrence is 3-9 months. Chemotherapy regimens for these patients are lacking and there is a significant unmet medical need. Given VAL-083’s novel alkylating mechanism, promising clinical benefit, and favorable safety profile, a trial studying VAL-083 in MGMT-unmethylated recurrent GBM is warranted. METHOD: Randomized, non-comparative biomarker-driven Phase II clinical trial in MGMT-unmethylated GBM patients at first recurrence/progression, prior to bevacizumab. 48 patients will be randomized to receive VAL-083 or “standard-of-care” salvage drug lomustine. 32 patients will receive VAL-083 40mg/m2/day on days 1,2,3 of a 21-day cycle. 16 patients will receive lomustine 90 mg/m2/day on day 1 of a 42-day cycle. Patients will be followed until death or for at least 9 months from enrollment, whichever occurs earlier. Survival will be compared to the BELOB trial for recurrent MGMT-unmethylated GBM patients treated with lomustine.
Glioblastoma (GBM) is the most common brain cancer. Resistance to front-line systemic therapy with temozolomide (TMZ) is correlated with O6-methylguanine-DNA-methyltransferase (MGMT) expression. Second-line treatment with bevacizumab has not improved overall survival. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent that has MGMT-independent cell-kill activity against GBM cell-lines and cancer stem cells in vitro. VAL-083 crosses the blood-brain barrier and showed promise against CNS tumors in prior NCI-sponsored clinical trials. The goal of this clinical trial is to determine appropriate VAL-083 dosing for advancement to Phase III trials as a new treatment for recurrent GBM. METHODS: Patients must have recurrent GBM following surgery, radiation, TMZ and bevacizumab. Phase I: Open-label, single-arm, dose-escalation study. Patients received VAL-083 on days 1,2,3 of a 21-day cycle, until reaching MTD. Phase II: Additional patients enrolled at MTD to further assess safety and outcomes. RESULTS: Phase I: 29 patients were enrolled across 9 dose cohorts (1.5-50 mg/m2/d). 40mg/m2/d was confirmed as MTD. Myelosuppression was mild; no drug-related serious adverse events were reported at doses up to 40mg/m2/d. Dose limiting G4 thrombocytopenia was observed at higher doses. Platelet nadir occurred around day 20 and resolved rapidly and spontaneously. A dose-related survival improvement was observed. Pharmacokinetic analyses show 1-2h plasma terminal half-life; average Cmax 781ng/mL at 40mg/m2/d. Phase II: 14 patients were enrolled at 40mg/m2/d. To date, safety observations in Phase II are consistent with Phase I. CONCLUSIONS: VAL-083 at 40mg/m2/d exhibits a favorable safety profile and dose-related trend toward clinically meaningful improved survival in refractory GBM patient