Anesthesia Practice and Perioperative Outcomes at Two Tertiary Care Hospitals in Freetown, Sierra Leone.

BACKGROUND: Anesthesia in West Africa is associated with high mortality rates. Critical shortages of adequately trained personnel, unreliable electrical supply, and lack of basic monitoring equipment are a few of the unique challenges to surgical care in this region. This study aims to describe the anesthesia practice at 2 tertiary care hospitals in Sierra Leone. METHODS: We conducted an observational study of anesthesia care at Connaught Hospital and Princess Christian Maternity Hospital in Freetown, Sierra Leone. Twenty-five percent of the anesthesia workforce in Sierra Leone, resident at both hospitals, was observed from June 2012 to February 2013. Perioperative assessments, anesthetic techniques, and intraoperative clinical and environmental irregularities were noted and analyzed. The postoperative status of observed cases was ascertained for morbidity and mortality. RESULTS: Between the 2 hospitals, 754 anesthesia cases and 373 general anesthetics were observed. Ketamine was the predominant IV anesthetic used. Both hospitals experienced infrastructural and environmental constraints to the delivery of anesthesia care during the observation period. Vital sign monitoring was irregular and dependent on age and availability of monitors. Perioperative mortality during the course of the study was 11.9 deaths/1000 anesthetics. CONCLUSIONS: We identified gaps in the application of internationally recommended anesthesia practices at both hospitals, likely caused by lack of available resources. Mortality rates were similar to those in other resource-limited countries.

Human Factors Evaluation of the Universal Anaesthesia Machine: Assessing Equipment with High-Fidelity Simulation Prior to Deployment in a Resource-Constrained Environment.

BACKGROUND: Anesthesia providers in low- and middle-income countries face many challenges, including poor availability of functioning equipment designed to meet their environmental, organizational, and resource constraints. These are serious global health disparities which threaten access to care and patient safety for those who receive surgical care. In this study, we conducted a simulation-based human factors analysis of the Universal Anaesthesia Machine (UAM®), a device designed to support anesthesia providers in austere medical settings. Our team anticipated the introduction of the UAM® to the two major referral hospitals in Freetown, Sierra Leone. A prior observational study had identified these two hospitals as having environmental conditions consistent with an austere environment: an unstable electrical grid, as well as limited access to compressed oxygen, biomedical support, and consumables. Although the Baltimore simulation environment cannot reproduce all of the challenges present in a resource-constrained environment such as Sierra Leone, the major impediments to standard anesthesia machine functionality and human factors-associated use can be reproduced with the use of high-fidelity simulation. Using anesthesia care providers who have limited UAM® familiarity, this study allowed for the examination of machine-user issues in a controlled environment in preparation for further field studies concerning equipment introduction, training and device deployment in Sierra Leone. The goals of this study were: 1. to assess the usability of the UAM® (machine-user interface, simulated patient use, symbology, etc.) across different provider user groups during simulation of use in scenarios depicting routine use in healthy patients, use in clinically challenging patients and use in environmentally-challenging scenarios in a controlled setting devoid of patient risk, and 2. To gather feedback on available UAM manuals and cognitive aides and UAM usability issues in order to guide development of curricula for training providers on use of the UAM® in the intended austere clinical environments. METHODS: Residents, fellows, attending physician anesthesiologists, student nurse anesthetists, and nurse anesthetists participated in a variety of simulations involving the Universal Anaesthesia Machine® at the Johns Hopkins Medicine Simulation Center between September 2012 and July 2013. Data collected included participant demographics, performance during simulation scenarios captured with critical action checklists, workload ratings captured with the National Aeronautics and Space Administration Task Load Index (NASA TLX), and participant reactions to UAM® use captured through a post-session survey and semi-structured usability debriefing. The scenarios were: 1. normal use (machine check, induction, and maintenance of an uneventful case), 2. use in a challenging clinical condition (acute onset of bronchospasm) and 3.use in an adverse environmental event (power failure). Critical action checklists and workload ratings were analyzed by Analysis of Covariance (ANCOVA) to control for participant demographics. Usability debriefings were analyzed qualitatively. RESULTS: Thirty-five anesthesia providers participated in the study. Overall participant ratings, observations of performance in simulation scenarios, and usability debriefings indicated a high level of usability for the UAM®. Mean participant ratings were high for ease of use (5.4 ± 0.96) and clarity of instruction (6.2 ± 0.87) on a 7-point scale in which higher ratings indicate more positive perceptions. After adjusting for clinical experience, workload ratings were significantly higher in the bronchospasm scenario than in the normal/routine use (P = 0.046; 95% CI, 0.33-34.7) or power failure scenarios (P = 0.012; 95% CI, 5.24-37.9). Thirty-two specific usability issues were identified and grouped into five themes: device design and labeling, machine use during simulation scenarios, user-anticipated errors or hazards, curriculum issues, and overall impressions of the UAM®. CONCLUSIONS: The UAM® design addresses many of the key challenges facing anesthesia providers in resource-constrained settings. The simulation-based human factors evaluation described here successfully identified opportunities for continued refinement of the initial device design as well as issues to be addressed in future curricula and cognitive aides.

Identification of ATP-binding regions in the RyR1 Ca²âº release channel.

ATP is an important modulator of gating in type 1 ryanodine receptor (RyR1), also known as a Ca²âº release channel in skeletal muscle cells. The activating effect of ATP on this channel is achieved by directly binding to one or more sites on the RyR1 protein. However, the number and location of these sites have yet to be determined. To identify the ATP-binding regions within RyR1 we used 2N3ATP-2',3'-Biotin-LC-Hydrazone (BioATP-HDZ), a photo-reactive ATP analog to covalently label the channel. We found that BioATP-HDZ binds RyR1 specifically with an IC50 = 0.6±0.2 mM, comparable with the reported EC50 for activation of RyR1 with ATP. Controlled proteolysis of labeled RyR1 followed by sequence analysis revealed three fragments with apparent molecular masses of 95, 45 and 70 kDa that were crosslinked by BioATP-HDZ and identified as RyR1 sequences. Our analysis identified four glycine-rich consensus motifs that can potentially constitute ATP-binding sites and are located within the N-terminal 95-kDa fragment. These putative nucleotide-binding sequences include amino acids 699-704, 701-706, 1081-1084 and 1195-1200, which are conserved among the three RyR isoforms. Located next to the N-terminal disease hotspot region in RyR1, these sequences may communicate the effects of ATP-binding to channel function by tuning conformational motions within the neighboring cytoplasmic regulatory domains. Two other labeled fragments lack ATP-binding consensus motifs and may form non-canonical ATP-binding sites. Based on domain topology in the 3D structure of RyR1 it is also conceivable that the identified ATP-binding regions, despite their wide separation in the primary sequence, may actually constitute the same non-contiguous ATP-binding pocket within the channel tetramer.

Alteration of chromosome 9p21 and/or p16 in benign and dysplastic nevi suggests a role in early melanoma progression (United States).

OBJECTIVE: The importance of p16 alterations in the pathogenesis of dysplastic nevi and sporadic melanoma remains controversial. The goal of this work was to discover if p16/9p21 alterations occur early in precursor lesions as well as related sporadic melanomas. METHODS: DNA was microdissected from 44 cutaneous melanomas, 14 dysplastic nevi, and six nevi without atypia as part of a study of melanoma. Alteration of the p16 region on 9p21 was measured by loss of heterozygosity (LOH) analysis as well as detection of homozygous deletions for p16 exon 2. RESULTS: This analysis revealed that LOH in 9p21 directly surrounding p16 occurred in approximately 40% (17/44) of melanoma tumors representing all Clark levels. LOH was also discovered in 64% (9/14) of dysplastic nevi, and 50% (3/6) of benign nevi. Homozygous deletion of p16 was found in 29% (4/14) of dysplastic nevi but never in benign nevi. CONCLUSIONS: These studies reveal that LOH and homozygous deletion can affect 9p21 and the p16 locus early in putative precursor lesions of melanoma, even prior to the establishment of cytologically evident aberrant histology. Comparison of alterations in nevi and melanomas from the same individual revealed a pattern of progressive but heterogeneous events suggesting that systemic processes may affect this region of 9p21 at various times during melanoma progression.