Limitations of split-night polysomnography for the diagnosis of nocturnal hypoventilation and titration of non-invasive positive pressure ventilation in amyotrophic lateral sclerosis.

Split-night polysomnography is performed at our centre in all patients with ALS who require assessment for nocturnal hypoventilation and their response to non-invasive ventilation. The purpose of this study was to determine how successful this practice has been, reflected by whether a complete assessment was achieved by a single split-night polysomnogram. We undertook a systematic, retrospective review of all consecutive split-night polysomnograms in ALS patients between 2005 and 2012. A total of 47 cases were reviewed. Forty-three percent of patients had an incomplete test, resulting in a recommendation to repeat the polysomnogram. Poor sleep efficiency and absence of REM sleep in the diagnostic portion of the study were strongly associated with incomplete studies. Clinical variables that reflect severity of ALS (FVC, PaCO2, ALSFRS-R) and use of REM-suppressing antidepressants or sedative-hypnotics were not associated with incomplete split-night polysomnogram. In conclusion, a single, split-night polysomnogram is frequently inconclusive for the assessment of nocturnal hypoventilation and complete titration of non-invasive positive pressure ventilation in patients with ALS. Poor sleep efficiency and absence of REM sleep are the main limitations of split-night polysomnography in this patient population.

Home mechanical ventilation: a Canadian Thoracic Society clinical practice guideline.

Increasing numbers of patients are surviving episodes of prolonged mechanical ventilation or benefitting from the recent availability of userfriendly noninvasive ventilators. Although many publications pertaining to specific aspects of home mechanical ventilation (HMV) exist, very few comprehensive guidelines that bring together all of the current literature on patients at risk for or using mechanical ventilatory support are available. The Canadian Thoracic Society HMV Guideline Committee has reviewed the available English literature on topics related to HMV in adults, and completed a detailed guideline that will help standardize and improve the assessment and management of individuals requiring noninvasive or invasive HMV. The guideline provides a disease-specific review of illnesses including amyotrophic lateral sclerosis, spinal cord injury, muscular dystrophies, myotonic dystrophy, kyphoscoliosis, post-polio syndrome, central hypoventilation syndrome, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease as well as important common themes such as airway clearance and the process of transition to home. The guidelines have been extensively reviewed by international experts, allied health professionals and target audiences. They will be updated on a regular basis to incorporate any new information.

Assessment and learning curve evaluation of endobronchial ultrasound skills following simulation and clinical training.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound is a revolutionary diagnostic pulmonary procedure. The use of a computer endobronchial ultrasound simulator could improve trainee procedural skills before attempting to perform procedures on patients. This study aims to compare endobronchial ultrasound performance following training with simulation versus conventional training using patients. METHODS: A prospective study of pulmonary medicine and thoracic surgery trainees. Two cohorts of trainees were evaluated using simulated cases with performance metrics measured by the simulator. Group 1 received endobronchial ultrasound training by performing 15 cases on an endobronchial ultrasound simulator (n=4). Group 2 received endobronchial ultrasound training by doing 15-25 cases on patients (n=9). RESULTS: Total procedure time was significantly shorter in group 1 than group 2 (15.15 (±1.34) vs 20.00 (±3.25) min, P<0.05). The percentage of lymph nodes successfully identified was significantly better in group 1 than group 2 (89.8 (±5.4) vs 68.1 (±5.2), P < 0.05). There was no difference between group 1 and group 2 in the percentage of successful biopsies (100.0 (±0.0) vs 90.4 (±11.5), P=0.13). The learning curves for simulation trained fellows did not show an obvious plateau after 19 simulated cases. CONCLUSIONS: Using an endobronchial ultrasound simulator leads to more rapid acquisition of skill in endobronchial ultrasound compared with conventional training methods, as assessed by an endobronchial ultrasound simulator. Endobronchial ultrasound simulators show promise for training with the advantage of minimizing the burden of procedural learning on patients.

Validation of an endobronchial ultrasound simulator: differentiating operator skill level.

BACKGROUND: Endobronchial ultrasound (EBUS) is a revolutionary diagnostic procedure. There is currently no accepted method of assessing EBUS technical skill or competency. OBJECTIVES: This study aimed to validate a computer EBUS simulator in differentiating between operators of varying clinical EBUS experience. METHODS: A convenience sample (n = 22) of bronchoscopists was separated into four cohorts based on previous bronchoscopy experience: group A = novice bronchoscopists, no EBUS experience (n = 4), group B = expert bronchoscopists, no EBUS experience (n = 5), group C = basic clinical EBUS training (n = 9), group D = EBUS experts (n = 4). After a standardized introduction session on the EBUS simulator, participants performed 2 simulated cases on an EBUS simulator with performance metrics measured by the simulator. RESULTS: Significant differences between groups were noted for total procedure time, percentage of lymph nodes identified and percentage of successful biopsies (p < 0.05, ANOVA). Group D performed significantly better than all other groups for total procedure time and percentage of lymph nodes identified (p < 0.05). Group C performed significantly better than groups A and B for total procedure time, percentage of lymph nodes identified and percentage of successful biopsies (p < 0.05, ANOVA). CONCLUSIONS: An EBUS simulator can accurately discriminate between operators with different levels of clinical EBUS experience. EBUS simulators show promise as a tool for assessing training and evaluating competency.

Synthesis, in vitro and in vivo antimalarial assessment of sulfide, sulfone and vinyl amide-substituted 1,2,4-trioxanes prepared via thiol-olefin co-oxygenation (TOCO) of allylic alcohols.

Thiol-Olefin Co-Oxygenation (TOCO) methodology has been applied to the synthesis of a small library of weak base and polar 1,2,4-trioxanes. The 1,2,4-trioxane units synthesised exhibit remarkable stability as they survive base catalysed hydrolysis and mixed anhydride/amine coupling reactions. This unique stability feature has enabled a range of novel substitution patterns to be incorporated within the spiro 1,2,4-trioxane unit. Selected analogues express potent in vitro nM antimalarial activity, low cytotoxicity and oral activity in the Plasmodium berghei mouse model of malaria.

Synthesis, antimalarial activity, and preclinical pharmacology of a novel series of 4'-fluoro and 4'-chloro analogues of amodiaquine. Identification of a suitable "back-up" compound for N-tert-butyl isoquine.

On the basis of a mechanistic understanding of the toxicity of the 4-aminoquinoline amodiaquine (1b), three series of amodiaquine analogues have been prepared where the 4-aminophenol "metabolic alert" has been modified by replacement of the 4'-hydroxy group with a hydrogen, fluorine, or chlorine atom. Following antimalarial assessment and studies on mechanism of action, two candidates were selected for detailed ADME studies and in vitro and in vivo toxicological assessment. 4'-Fluoro-N-tert-butylamodiaquine (2k) was subsequently identified as a candidate for further development studies based on potent activity versus chloroquine-sensitive and resistant parasites, moderate to excellent oral bioavailability, low toxicity in in vitro studies, and an acceptable safety profile.

Two-step synthesis of achiral dispiro-1,2,4,5-tetraoxanes with outstanding antimalarial activity, low toxicity, and high-stability profiles.

A rapid, two-step synthesis of a range of dispiro-1,2,4,5-tetraoxanes with potent antimalarial activity both in vitro and in vivo has been achieved. These 1,2,4,5-tetraoxanes have been proven to be superior to 1,2,4-trioxolanes in terms of stability and to be superior to trioxane analogues in terms of both stability and activity. Selected analogues have in vitro nanomolar antimalarial activity and good oral activity and are nontoxic in screens for both cytotoxicity and genotoxicity. The synthesis of a fluorescent 7-nitrobenza-2-oxa-1,3-diazole (NBD) tagged tetraoxane probe and use of laser scanning confocal microscopy techniques have shown that tagged molecules accumulate selectively only in parasite infected erythrocytes and that intraparasitic formation of adducts could be inhibited by co-incubation with the iron chelator desferrioxamine (DFO).

An efficient route into synthetically challenging bridged achiral 1,2,4,5-tetraoxanes with antimalarial activity.

Here we present an efficient route into synthetically challenging bridged 1,2,4,5-tetraoxanes. The key to the success of this route is the use of H(2)O(2) and catalytic I(2) to form the gem-dihydroperoxide followed by a Ag(2)O mediated alkylation using 1,3-diiodopropane. Using this methodology a range of bridged tetraoxanes which display good in vitro antimalarial activity were synthesized.

Is your patient ready for transport? Developing an ICU patient transport decision scorecard.

Transport of patients from the intensive care unit (ICU) to another area of the hospital can pose serious risks if the patient has not been assessed prior to transport. Recently, the Department of Critical Care Medicine, Calgary Health Region, experienced two adverse events during transport. A subgroup of the Department's Patient Safety and Adverse Events team developed an ICU patient transport decision scorecard. This tool was tested through Plan-Do-Study-Act cycles and further revised using human factors principles. Staff, especially novice nurses, found the tool extremely useful in determining patient preparedness for transport.

Spontaneous empyema and overwhelming septic shock due to Pasteurella multocida.

Invasive Pasteurella multocida infection, although uncommon, has been recognized to occur more frequently among patients with hepatic cirrhosis. This study reports a fatal case of bacteremic P. multocida empyema without pneumonia associated with refractory septic shock in a patient with both cirrhosis and asplenia.