Ten Years of Experience Training Non-Physician Anesthesia Providers in Haiti.

Surgery is increasingly recognized as an effective means of treating a proportion of the global burden of disease, especially in resource-limited countries. Often non-physicians, such as nurses, provide the majority of anesthesia; however, their training and formal supervision is often of low priority or even non-existent. To increase the number of safe anesthesia providers in Haiti, Médecins Sans Frontières has trained nurse anesthetists (NAs) for over 10 years. This article describes the challenges, outcomes, and future directions of this training program. From 1998 to 2008, 24 students graduated. Nineteen (79%) continue to work as NAs in Haiti and 5 (21%) have emigrated. In 2008, NAs were critical in providing anesthesia during a post-hurricane emergency where they performed 330 procedures. Mortality was 0.3% and not associated with lack of anesthesiologist supervision. The completion rate of this training program was high and the majority of graduates continue to work as nurse anesthetists in Haiti. Successful training requires a setting with a sufficient volume and diversity of operations, appropriate anesthesia equipment, a structured and comprehensive training program, and recognition of the training program by the national ministry of health and relevant professional bodies. Preliminary outcomes support findings elsewhere that NAs can be a safe and effective alternative where anesthesiologists are scarce. Training non-physician anesthetists is a feasible and important way to scale up surgical services resource limited settings

Proactive behavior in voice assistants: A systematic review and conceptual model

Voice assistants (VAs) are increasingly integrated into everyday activities and tasks, raising novel challenges for users and researchers. One emergent research direction concerns proactive VAs, who can initiate interaction without direct user input, offering unique benefits including efficiency and natural interaction. Yet, there is a lack of review studies synthesizing the current knowledge on how proactive behavior has been implemented in VAs and under what conditions proactivity has been found more or less suitable. To this end, we conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. We searched for articles in the ACM Digital Library, IEEExplore, and PubMed, and included primary research studies reporting user evaluations of proactive VAs, resulting in 21 studies included for analysis. First, to characterize proactive behavior in VAs we developed a novel conceptual model encompassing context, initiation, and action components: Activity/status emerged as the primary contextual element, direct initiation was more common than indirect initiation, and suggestions were the primary action observed. Second, proactive behavior in VAs was predominantly explored in domestic and in-vehicle contexts, with only safety-critical and emergency situations demonstrating clear benefits for proactivity, compared to mixed findings for other scenarios. The paper concludes with a summary of the prevailing knowledge gaps and potential research avenues

International practice patterns and factors associated with non-conventional hemodialysis utilization

<p>Abstract</p> <p>Background</p> <p>The purpose of our study was to determine characteristics that influence the utilization of non-conventional hemodialysis (NCHD) therapies and its subtypes (nocturnal (NHD), short daily (SDHD), long conventional (LCHD) and conventional hemodialysis (CHD) as well as provider attitudes regarding the evidence for NCHD use.</p> <p>Methods</p> <p>An international cohort of subscribers of a nephrology education website <url>http://www.nephrologynow.com</url> was invited to participate in an online survey. Non-conventional hemodialysis was defined as any forms of hemodialysis delivered > 3 treatments per week and/or > 4 hours per session. NHD and SDHD included both home and in-centre. Respondents were categorized as CHD if their centre only offered conventional thrice weekly hemodialysis. Variables associated with NCHD and its subtypes were determined using multivariate logistic regression analysis. The survey assessed multiple domains regarding NCHD including reasons for initiating and discontinuing, for not offering and attitudes regarding evidence.</p> <p>Results</p> <p>544 surveys were completed leading to a 15.6% response rate. The final cohort was limited to 311 physicians. Dialysis modalities utilized among the respondents were as follows: NCHD194 (62.4%), NHD 83 (26.7%), SDHD 107 (34.4%), LCHD 81 (26%) and CHD 117 (37.6%). The geographic regions of participants were as follows: 11.9% Canada, 26.7% USA, 21.5% Europe, 6.1% Australia/New Zealand, 10% Africa/Middle East, 10.9% Asia and 12.9% South America. Variables associated with NCHD utilization included NCHD training (OR 2.47 CI 1.25-4.16), government physician reimbursement (OR 2.66, CI 1.11-6.40), practicing at an academic centre (OR 2.28 CI 1.25-4.16), higher national health care expenditure and number of ESRD patients per centre. Hemodialysis providers with patients on NCHD were significantly more likely to agree with the statements that NCHD improves quality of life, improves nutritional status, reduces EPO requirements and is cost effective. The most common reasons to initiate NCHD were driven by patient preference and the desire to improve volume control and global health outcomes.</p> <p>Conclusion</p> <p>Physician attitudes toward the evidence for NCHD differ significantly between NCHD providers and conventional HD providers. Interventions and health policy targeting these areas along with increased physician education and training in NCHD modalities may be effective in increasing its utilization.</p

Rapid Intradermal Delivery of Liquid Formulations Using a Hollow Microstructured Array

Purpose The purpose of this work is to demonstrate rapid intradermal delivery of up to 1.5 mL of formulation using a hollow microneedle delivery device designed for self-application. Methods 3M’s hollow Microstructured Transdermal System (hMTS) was applied to domestic swine to demonstrate delivery of a variety of formulations including small molecule salts and proteins. Blood samples were collected after delivery and analyzed via HPLC or ELISA to provide a PK profile for the delivered drug. Site evaluations were conducted post delivery to determine skin tolerability. Results Up to 1.5 mL of formulation was infused into swine at a max rate of approximately 0.25 mL/min. A red blotch, the size of the hMTS array, was observed immediately after patch removal, but had faded so as to be almost indistinguishable 10 min post-patch removal. One-mL deliveries of commercial formulations of naloxone hydrochloride and human growth hormone and a formulation of equine anti-tetanus toxin were completed in swine. With few notable differences, the resulting PK profiles were similar to those achieved following subcutaneous injection of these formulations. Conclusions 3M’s hMTS can provide rapid, intradermal delivery of 300–1,500 µL of liquid formulations of small molecules salts and proteins, compounds not typically compatible with passive transdermal delivery. KEY WORDS transdermal drug delivery. microneedles. intradermal. hollow microstructures. MT

A new implicit review instrument for measuring quality of care delivered to pediatric patients in the emergency department

BackgroundThere are few outcomes experienced by children receiving care in the Emergency Department (ED) that are amenable to measuring for the purposes of assessing of quality of care. The purpose of this study was to develop, test, and validate a new implicit review instrument that measures quality of care delivered to children in EDs.MethodsWe developed a 7-point structured implicit review instrument that encompasses four aspects of care, including the physician's initial data gathering, integration of information and development of appropriate diagnoses; initial treatment plan and orders; and plan for disposition and follow-up. Two pediatric emergency medicine physicians applied the 5-item instrument to children presenting in the highest triage category to four rural EDs, and we assessed the reliability of the average summary scores (possible range of 5-35) across the two reviewers using standard measures. We also validated the instrument by comparing this mean summary score between those with and without medication errors (ascertained independently by two pharmacists) using a two-sample t-test.ResultsWe reviewed the medical records of 178 pediatric patients for the study. The mean and median summary score for this cohort of patients were 27.4 and 28.5, respectively. Internal consistency was high (Cronbach's alpha of 0.92 and 0.89). All items showed a significant (p &lt; 0.005) positive correlation between reviewers using the Spearman rank correlation (range 0.24 to 0.39). Exact agreement on individual items between reviewers ranged from 70.2% to 85.4%. The Intra-class Correlation Coefficient for the mean of the total summary score across the two reviewers was 0.65. The validity of the instrument was supported by the finding of a higher score for children without medication errors compared to those with medication errors which trended toward significance (mean score = 28.5 vs. 26.0, p = 0.076).ConclusionThe instrument we developed to measure quality of care provided to children in the ED has high internal consistency, fair to good inter-rater reliability and inter-rater correlation, and high content validity. The validity of the instrument is supported by the fact that the instrument's average summary score was lower in the presence of medication errors, which trended towards statistical significance

Construction of a Mean Square Error Adaptive Euler--Maruyama Method with Applications in Multilevel Monte Carlo

A formal mean square error expansion (MSE) is derived for Euler--Maruyama numerical solutions of stochastic differential equations (SDE). The error expansion is used to construct a pathwise a posteriori adaptive time stepping Euler--Maruyama method for numerical solutions of SDE, and the resulting method is incorporated into a multilevel Monte Carlo (MLMC) method for weak approximations of SDE. This gives an efficient MSE adaptive MLMC method for handling a number of low-regularity approximation problems. In low-regularity numerical example problems, the developed adaptive MLMC method is shown to outperform the uniform time stepping MLMC method by orders of magnitude, producing output whose error with high probability is bounded by TOL>0 at the near-optimal MLMC cost rate O(TOL^{-2}log(TOL)^4).Comment: 43 pages, 12 figure

Event-Related Potentials Dissociate Effects of Salience and Space in Biased Competition for Visual Representation

BACKGROUND: Selective visual attention is the process by which the visual system enhances behaviorally relevant stimuli and filters out others. Visual attention is thought to operate through a cortical mechanism known as biased competition. Representations of stimuli within cortical visual areas compete such that they mutually suppress each others' neural response. Competition increases with stimulus proximity and can be biased in favor of one stimulus (over another) as a function of stimulus significance, salience, or expectancy. Though there is considerable evidence of biased competition within the human visual system, the dynamics of the process remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used scalp-recorded electroencephalography (EEG) to examine neural correlates of biased competition in the human visual system. In two experiments, subjects performed a task requiring them to either simultaneously identify two targets (Experiment 1) or discriminate one target while ignoring a decoy (Experiment 2). Competition was manipulated by altering the spatial separation between target(s) and/or decoy. Both experimental tasks should induce competition between stimuli. However, only the task of Experiment 2 should invoke a strong bias in favor of the target (over the decoy). The amplitude of two lateralized components of the event-related potential, the N2pc and Ptc, mirrored these predictions. N2pc amplitude increased with increasing stimulus separation in Experiments 1 and 2. However, Ptc amplitude varied only in Experiment 2, becoming more positive with decreased spatial separation. CONCLUSIONS/SIGNIFICANCE: These results suggest that N2pc and Ptc components may index distinct processes of biased competition--N2pc reflecting visual competitive interactions and Ptc reflecting a bias in processing necessary to individuate task-relevant stimuli

Differential protein profiling as a potential multi-marker approach for TSE diagnosis

Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177This "proof of concept" study, examines the use of differential protein expression profiling using surface enhanced laser desorption and ionisationtime of flight mass spectrometry (SELDI-TOF) for the diagnosis of TSE disease. Spectral output from all proteins selectively captured from individual murine brain homogenate samples, are compared as "profiles" in groups of infected and non-infected animals. Differential protein expression between groups is thus highlighted and statistically significant protein "peaks" used to construct a panel of disease specific markers. Studies at both terminal stages of disease and throughout the time course of disease have shown a disease specific protein profile or "disease fingerprint" which could be used to distinguish between groups of TSE infected and uninfected animals at an early time point of disease. Results Our results show many differentially expressed proteins in diseased and control animals, some at early stages of disease. Three proteins identified by SELDI-TOF analysis were verified by immunohistochemistry in brain tissue sections. We demonstrate that by combining the most statistically significant changes in expression, a panel of markers can be constructed that can distinguish between TSE diseased and normal animals. Conclusion Differential protein expression profiling has the potential to be used for the detection of disease in TSE infected animals. Having established that a "training set" of potential markers can be constructed, more work would be required to further test the specificity and sensitivity of the assay in a "testing set". Based on these promising results, further studies are being performed using blood samples from infected sheep to assess the potential use of SELDI-TOF as a pre-mortem blood based diagnostic.https://doi.org/10.1186/1471-2334-9-1889pubpub

Design and Synthesis of Potent in Vitro and in Vivo Anticancer Agents Based on 1-(3′,4′,5′-Trimethoxyphenyl)-2-Aryl-1H-Imidazole

A novel series of tubulin polymerization inhibitors, based on the 1-(3',4',5'-trimethoxyphenyl)-2-aryl-1H-imidazole scaffold and designed as cis-restricted combretastatin A-4 analogues, was synthesized with the goal of evaluating the effects of various patterns of substitution on the phenyl at the 2-position of the imidazole ring on biological activity. A chloro and ethoxy group at the meta- and para-positions, respectively, produced the most active compound in the series (4o), with IC50 values of 0.4-3.8 nM against a panel of seven cancer cell lines. Except in HL-60 cells, 4o had greater antiproliferative than CA-4, indicating that the 3'-chloro-4'-ethoxyphenyl moiety was a good surrogate for the CA-4 B-ring. Experiments carried out in a mouse syngenic model demonstrated high antitumor activity of 4o, which significantly reduced the tumor mass at a dose thirty times lower than that required for CA-4P, which was used as a reference compound. Altogether, our findings suggest that 4o is a promising anticancer drug candidate that warrants further preclinical evaluation