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This is a copy of the slides presented at the meeting but not formally written up for the volume.
One proposed approach to reduce the spread of HIV is to prevent transmission of the virus through the use of a topical microbicide. One microbicide strategy is a charge inhibition based approach using polyanionic compounds designed to interfere with the process of HIV-1 attachment to potential target cells. This strategy however, is predicated on further understanding the charge characteristics of whole virions and the relative contribution of viral and host-cell proteins to such charge. Electrokinetic methods (i.e. ζ-potential) provide information on the surface structure of biological cells without producing significant alteration of the cellular organization. Electrophoretic fingerprinting (EF) is obtained from 3D templates of the mean electrophoretic mobility (the raw data from which ζ-potential is calculated) of a given particle versus pH and solution conductivity at a fixed temperature. The EF thus represents a surface, described by isomobility lines, over all pertinent electrochemical conditions. These initial electrophoretic analyses have been performed using human CD4+ T cell lines. The cell lines are derived from human white blood cells which are the principle targets of the HIV-1 virus. Tissue culture work was carried out under Class II aseptic conditions. Cell types were maintained in RPMI growth medium supplemented with 10% heat inactivated foetal calf serum, 2mM glutamine, 100 i.u./ml penicillin and 100 μg/ml streptomycin at 37°C in a humidified 5% CO2 incubator. The cells were routinely passaged every 3-4 days in 75 cm3 fillter cap tissue culture flasks, by the addition of 4 mls of cells to 16 mls of fresh growth medium.Electrophoretic mobility (ζ-potential) was measured as a function of pH and ionic strength over a range chosen to cover that known for fluids found in the lower female reproductive tract, including vaginal fluid and semen. Measurements were made using a Malvern ZetaSizer NanoZS operating in the fast field reversal mode (PALS). Data was analyzed using SURFER™ software and the results validated from the covariance matrix of the linear fit. Challenges in the measurement and characterization of the cells include the difficulty of the cell preparation, cleanliness of the samples and sample handling required to maintain cell vitality.Overall, the EF’s analyzed under environments characteristic of physiological conditions for each CD4 T cell line resulted in similar zwitterionic surface charge features. These results suggest that the best candidate for a microbicide active needs, itself, to be zwitterionic so as to be able to mirror-image the shift in sign of surface charge as the pH of the vaginal tract changes. Current results suggest that HIV interaction with target cells is enhanced by physiological fluids. The data provides core information on the physico-chemical properties of model cellular targets for HIV-1 infection and pave the way for rational development of charge-based intervention strategies.
After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.
The association between dietary patterns and CVD risk factors among non-Hispanic whites has not been fully studied. Data from 650 non-Hispanic white adults who participated in one of two clinical sub-studies (about 2 years after the baseline) of the Adventist Health Study-2 (AHS-2) were analysed. Four dietary patters were identified using a validated 204-item semi-quantitative FFQ completed at enrolment into AHS-2: vegans (8·3 %), lacto-ovo-vegetarians (44·3 %), pesco-vegetarians (10·6 %) and non-vegetarians (NV) (37·3 %). Dietary pattern-specific prevalence ratios (PR) of CVD risk factors were assessed adjusting for confounders with or without BMI as an additional covariable. The adjusted PR for hypertension, high total cholesterol and high LDL-cholesterol were lower in all three vegetarian groups. Among the lacto-ovo-vegetarians the PR were 0·57 (95 % CI 0·45, 0·73), 0·72 (95 % CI 0·59, 0·88) and 0·72 (95 % CI 0·58, 0·89), respectively, which remained significant after additionally adjusting for BMI. The vegans and the pesco-vegetarians had similar PR for hypertension at 0·46 (95 % CI 0·25, 0·83) and 0·62 (95 % CI 0·42, 0·91), respectively, but estimates were attenuated and marginally significant after adjustment for BMI. Compared with NV, the PR of obesity and abdominal adiposity, as well as other CVD risk factors, were significantly lower among the vegetarian groups. Similar results were found when limiting analyses to participants not being treated for CVD risk factors, with the vegans having the lowest mean BMI and waist circumference. Thus, compared with the diet of NV, vegetarian diets were associated with significantly lower levels of CVD risk factors among the non-Hispanic whites.
A significant portion of patients with Clostridium difficile infections (CDI) experience recurrence, and there is little consensus on its treatment. With the availability of newer agents for CDI and the added burdens of recurrent disease, a cost-effectiveness analysis may provide insight on the most efficient use of resources.
A decision-tree analysis was created to compare the cost-effectiveness of 3 possible treatments for patients with first CDI recurrence: oral vancomycin, fidaxomicin, or bezlotoxumab plus vancomycin. The model was performed from a payer’s perspective with direct cost inputs and a timeline of 1 year. A systematic review of literature was performed to identify clinical, utility, and cost data. Quality-adjusted life years (QALY) and incremental cost-effectiveness ratios were calculated. The willingness-to-pay (WTP) threshold was set at $100,000 per QALY gained. The robustness of the model was tested using one-way sensitivity analyses and probabilistic sensitivity analysis.
Vancomycin had the lowest cost ($15,692) and was associated with a QALY gain of 0.8019 years. Bezlotoxumab plus vancomycin was a dominated strategy. Fidaxomicin led to a higher QALY compared to vancomycin, at an incremental cost of $500,975 per QALY gained. Based on our WTP threshold, vancomycin alone was the most cost-effective regimen for treating the first recurrence of CDI. Sensitivity analyses demonstrated the model’s robustness.
Vancomycin alone appears to be the most cost-effective regimen for the treatment of first recurrence of CDI. Fidaxomicin alone led to the highest QALY gained, but at a cost beyond what is considered cost-effective.
Introduction: Deliberate practice (DP) is the evolution of practice using continually challenging and focused practice on a particular task. DP involves immediate feedback, time for problem-solving and evaluation, and opportunities for repeated performance. Microskills training breaks down larger tasks into multiple smaller subtasks and then adds opportunities for feedback and adjustment for each subtask. Microskills training is routinely used to achieve excellence in competitive sports, martial arts, military operations, and music. Surgical cricothyrotomy is a rarely performed safety critical task. Methods: Two doctors and three nurses developed stepwise team microskills checklists from case review, simulations and published evidence. The checklist was tested, evaluated and developed during four days of simulation faculty team training. The final 30 item checklist was used to facilitate skills training for doctors, nurses, respiratory therapists and ACPs in one level 2, and two level 3 trauma centers from April 2017 to October 2017. Commonly available airway trainers were retrofitted with the 3-D printed larynx. The microskills checklist was used in four phases: 1. Group discussion of each microskill step; 2. Groups of three team members; operator, assistant and microskill facilitator (using the checklist) to enable the deliberate analysis of the teams current performance. Each subtask is performed with immediate peer and where necessary faculty feedback - changes are recorded; 3. Total task run through without interruption - changes are recorded; 4. Repetition and feedback using different team members, manikins, including time pressure. User satisfaction surveys were collected after the skills training session Results: Teams were composed of Registered Nurses (8), Physicians (9), and Respiratory Therapists (2). All of the teams experienced a change in practice. The median number of microskills changed for MDs 12/21, RNs 6/12. The commonest changes in practice were equipment preparation (all teams). All professions agreed strongly that the approach produces a positive change in practice (median score 5/5). Conclusion: Microskills checklists facilitate cricothyrotomy skill development in interprofessional teams in this provisional analysis.
Introduction: Situational awareness (SA) is the team understanding patient stability, presenting illness and future clinical course. Losing SA has been shown to increase safety-critical events in multiple industries. SA can be measured by the previously validated Situational Awareness Global Assessment Tool (SAGAT). Checklists are used in many safety-critical industries to reduce errors of omission and commission. An RSI checklist was developed from case review and published evidence.The New Brunswick Trauma Program supports an inter-professional simulation-based medical education program Methods: Simulations were facilitated in three hospitals in New Brunswick from April 2017 to October 2017. Learner profiles were collected. The SAGAT tool was completed by a research nurse at the end of each scenario. SAGAT scores were non-normally distributed, so results were expressed as medians and interquartile ranges. Mann Whitney U tests were used to calculate statistical significance. To understand the effect of the of an RSI checklist a comparison was made between SAGAT scores at baseline in scenario 1, and the same first scenario completed after a washout period. A Poisson regression analysis will be used to account for the effect of confounding variables in further analyses. Results: The group was composed of Registered Nurses (8), Physicians (7), and Respiratory Therapists (2). Situational awareness increased significantly with the use of an RSI checklist after 1 day of 4 simulations. The washout period ranged between 5 weeks and 8 weeks. The baseline situational awareness of the whole group during scenario 1 was 9 +/− 0.5 (median, IQR), and with the RSI checklist was 12 +/−1 (median, IQR). The difference was highly statistically significant, p=< 0.001. This level of situational awareness using checklist is comparable to the SAGAT scores after 10 scenarios. Conclusion: In this provisional analysis, the use of an RSI checklist was associated with an increase in measured situational awareness. Higher levels of situational awareness are associated with greater patient safety. A Poisson regression model will be used to understand the confounding effects of user expertise and the likely interaction with simulation exposure.
Introduction: Deliberate practice (DP) is the evolution of practice using continually challenging and focused practice on a particular task. DP involves immediate feedback, time for problem-solving and evaluation, and opportunities for repeated performance. Mircroskills training breaks down larger tasks into multiple smaller subtasks and then adds opportunities for feedback and adjustment for each subtask. Microskills training is routinely used to achieve excellence in competitive sports, martial arts, military operations, and music. Endotracheal intubation is a complex task with a clinically significant complication and failure rate. Methods: Two doctors and three nurses developed stepwise team microskills checklist from case review, simulations and published evidence. The checklist was tested, evaluated and developed during four days of simulation faculty team training. The final 36 item checklist was used to facilitate skills training for doctors, nurses, respiratory therapists and ACPs in one level 2, and two level 3 trauma centers from April 2017 to October 2017. The microskills checklist was used in four phases: 1. Group discussion of each microskill step 2. Groups of three team members; operator, assistant and microskill facilitator (using the checklist) to enable the deliberate analysis of the teams current performance. Each subtask is performed with immediate peer and where necessary faculty feedback. Changes are recorded. 3. Total task run though without interruption. Changes are recorded. 4. Repetition and feedback using different team members, manikins, including time pressure. User satisfaction surveys were collected after the skills training session Results: Results. Teams were composed of Registered Nurses (8), Physicians (9), and Respiratory Therapists (2). All of the teams experienced a change in practice. The median number of microskills changed for MDs 13/30, RNs 7/16. The commonest changes in practice were patient positioning (all teams). All professions agreed strongly that the approach produces a positive change in practice (median score 4.8/5). Conclusion: Microskills checklist facilitate endotracheal intubation with a bougie skill development in interprofessional teams in this provisional analysis.
This study sought to assess the effectiveness of ultrasound simulation as a component of high-fidelity trauma simulation, in training diagnostic capabilities of resident and attending physicians participating in simulated trauma scenarios.
Twelve residents and 20 attending physicians participated in 114 trauma simulations. Participants generated a ranked differential diagnosis list after a physical exam and subsequently after a simulated extended focused assessment with sonography for trauma (E-FAST) ultrasound scan. We compared reports to determine whether the addition of ultrasound improved diagnostic performance.
The primary diagnosis accuracy improved significantly with the addition of simulated ultrasound (p<0.0001). Median diagnostic ranking scores also improved (p<0.0001). Further, participants reported a higher confidence in their diagnoses (p<0.0001) and narrowed their differential diagnosis list (p<0.0001).
We demonstrated that a low-cost ultrasound simulator can be successfully integrated into trauma simulations, resulting in an associated improvement in measures of diagnostic accuracy, confidence, and precision for participating resident and attending physicians.
Objectives: There are no current established pathognomonic diagnostic features for uterine leiomyosarcomas in the pre- or perioperative setting. Recent inadvertent upstaging of this rare malignancy during laparoscopic morcellation of a presumed fibroid has prompted widespread debate among clinicians regarding the safety of current surgical techniques for management of fibroids. This study aims to conduct a systematic review investigating significant diagnostic features in magnetic resonance imaging (MRI) of uterine leiomyosarcomas.
Methods: A comprehensive database search was conducted guided by PRISMA recommendations for peer-reviewed publications to November 2017. Parameters available in MRI were compared for reliability and accuracy of diagnosis of leiomyosarcomas. A decision tree algorithm classifier model was constructed to investigate whether T1 and T2 MRI signal intensities are useful indicators.
Results: Nine eligible studies were identified for analysis. There appears to be a significant relationship between histopathological type and T1 and T2 intensity signals (p < .05). A decision tree model analyzing T1 and T2 signal intensity readings supports this trend, with a diagnostic specificity of 77.78 percent for uterine leiomyosarcomas. The apparent diffusion coefficient (ADC) values were not observed to have a significant relationship with tumor pathology (p = .18).
Conclusions: Various studies have investigated pre- and perioperative techniques in differentiating uterine leiomyosarcoma from benign fibroids. Given the rarity of the malignancy and lack of pathognomonic diagnostic parameters, there is difficulty in establishing definitive criteria. A decision tree model is proposed to aid diagnosis based on MRI signal intensities.
Dyspnea is a common presenting problem that creates a diagnostic challenge for physicians in the emergency department (ED). While the differential diagnosis is broad, acute decompensated heart failure (ADHF) is a frequent cause that can be challenging to differentiate from other etiologies. Recent studies have suggested a potential diagnostic role for emergency lung ultrasound (US). The objective of this systematic review was to assess the accuracy of early bedside lung US in patients presenting to the ED with dyspnea.
A systematic search of EMBASE, PubMed, and the Cochrane Library was performed in addition to a grey literature search. We selected prospective studies that reported on the sensitivity and specificity of B-lines from early lung ultrasound in dyspneic patients presenting to the ED. Selected studies underwent quality assessment using the Critical Appraisal and Skills Program (CASP) questionnaire.
Data Extraction and Synthesis
The search yielded 3674 articles; seven studies met inclusion criteria and fulfilled CASP requirements for a total of 1861 patients. Summary statistics from the meta-analysis showed that as a diagnostic test for ADHF, bedside lung US had a pooled sensitivity of 82.5% (95% confidence interval [CI]=66.4% to 91.8%) and a pooled specificity of 83.6% (95% CI=72.4% to 90.8%).
Our results suggest that in patients presenting to the ED with undifferentiated dyspnea, B-lines from early bedside lung US may be reliably used as an adjunct to current diagnostic methods. The incorporation of lung US may lead to more appropriate and timely diagnosis of patients with undifferentiated ADHF.
Survey results suggest that prolonged administration of prophylactic antibiotics is common after mastectomy with reconstruction. We determined utilization, predictors, and outcomes of postdischarge prophylactic antibiotics after mastectomy with or without immediate breast reconstruction.
Commercially insured women aged 18–64 years coded for mastectomy from January 2004 to December 2011 were included in the study. Women with a preexisting wound complication or septicemia were excluded.
Predictors of prophylactic antibiotics within 5 days after discharge were identified in women with 1 year of prior insurance enrollment; relative risks (RR) were calculated using generalized estimating equations.
Overall, 12,501 mastectomy procedures were identified; immediate reconstruction was performed in 7,912 of these procedures (63.3%). Postdischarge prophylactic antibiotics were used in 4,439 procedures (56.1%) with immediate reconstruction and 1,053 procedures (22.9%) without immediate reconstruction (P<.001). The antibiotics most commonly prescribed were cephalosporins (75.1%) and fluoroquinolones (11.1%). Independent predictors of postdischarge antibiotics were implant reconstruction (RR, 2.41; 95% confidence interval [CI], 2.23–2.60), autologous reconstruction (RR, 2.17; 95% CI, 1.93–2.45), autologous reconstruction plus implant (RR, 2.11; 95% CI, 1.92–2.31), hypertension (RR, 1.05; 95% CI, 1.00–1.10), tobacco use (RR, 1.07; 95% CI, 1.01–1.14), surgery at an academic hospital (RR, 1.14; 95% CI, 1.07–1.21), and receipt of home health care (RR, 1.11; 95% CI, 1.04–1.18). Postdischarge prophylactic antibiotics were not associated with SSI after mastectomy with or without immediate reconstruction (both P>.05).
Prophylactic postdischarge antibiotics are commonly prescribed after mastectomy; immediate reconstruction is the strongest predictor. Stewardship efforts in this population to limit continuation of prophylactic antibiotics after discharge are needed to limit antimicrobial resistance.
To evaluate a central line care maintenance bundle to reduce central line–associated bloodstream infection (CLABSI) in non–intensive care unit settings.
Before-after trial with 12-month follow-up period.
A 1,250-bed teaching hospital.
Patients with central lines on 8 general medicine wards. Four wards received the intervention and 4 served as controls.
A multifaceted catheter care maintenance bundle consisting of educational programs for nurses, update of hospital policies, visual aids, a competency assessment, process monitoring, regular progress reports, and consolidation of supplies necessary for catheter maintenance.
Data were collected for 25,542 catheter-days including 43 CLABSI (rate, 1.68 per 1,000 catheter-days) and 4,012 catheter dressing observations. Following the intervention, a 2.5% monthly decrease in the CLABSI incidence density was observed on intervention floors but this was not statistically significant (95% CI, −5.3% to 0.4%). On control floors, there was a smaller but marginally significant decrease in CLABSI incidence during the study (change in monthly rate, −1.1%; 95% CI, −2.1% to −0.1%). Implementation of the bundle was associated with improvement in catheter dressing compliance on intervention wards (78.8% compliance before intervention vs 87.9% during intervention/follow-up; P<.001) but improvement was also observed on control wards (84.9% compliance before intervention vs 90.9% during intervention/follow-up; P=.001).
A multifaceted program to improve catheter care was associated with improvement in catheter dressing care but no change in CLABSI rates. Additional study is needed to determine strategies to prevent CLABSI in non–intensive care unit patients.
Almost 100 years have passed since J.M. Swaine, the assistant entomologist in charge of Forest Insect Investigations, wrote, “Canadian bark-beetles: a preliminary classification, with an account of the habits and means of control”. The goal was to “put into the hands of practical foresters information of inestimable practical value… to prevent the continued loss of timber now being destroyed” by “the most insidious enemies of the forest”. In this paper, we celebrate Swaine’s pioneering work by summarising the foundational aspects of his early treatise of 1918: the “general habits” of bark beetles, classifications of their behaviour, causes of population increase, and mitigation tactics. In the founding text, Swaine identified all major Dendroctonus Erichson (Coleoptera: Curculionidae) bark beetles found in Canada, although details on life histories were scarce. We summarise current knowledge of the life histories and population dynamics of the spruce beetle, D. rufipennis Kirby; the Douglas-fir beetle, D. pseudotsugae Hopkins; the eastern larch beetle, D. simplex; and address the current range expansion of mountain pine beetle, D. ponderosae Hopkins. We review how aspects of global change, such as invasive species, have altered the population dynamics of certain bark beetles. Finally, we conclude with lessons from two of the many past contributors to bark beetle ecology in Canada, J.M. Swaine and H.A. Richmond.