Accelerating development of simulation-based medical skill training programs : a comparative evaluation research study

A shift in Military utilization of Live Tissue Training (LTT) to Simulation-based Training (SBT) for combat casualty care training programs is currently underway. While each has been reported to be effective, there is little high quality research comparing traditional LTT with SBT learning outcomes. The shift in training methods is partly in response to increased regulatory requirements, higher costs and public sentiments. The benefits of training with a live anesthetized animal are an immediate physiologic feedback to treatment interventions and practice in 'real-world', high-stakes continual patient assessment and decision making. Simulation-based training offers opportunities for deliberate practice and skill mastery without the sense of urgency or 'real-world' life and death outcomes the trainee will face in combat casualty care. The paucity of experimental evidence demonstrating that the two types of training are comparable has contributed to slow adoption of SBT technology for resuscitation procedures, particularly in combat casualty training. This study entails the direct comparison of LTT and SBT in a randomized, pre-test post-test experiment. Changes in trainee knowledge, psychomotor skill, and self-efficacy are assessed using established measures. Stress and emotion are known to play a role in performance and learning. This study also investigated the use of sweat measurement as a possible indicator of a stressful response to the training situation. This was accomplished by measuring changes in skin impedance during didactic and hands-on training. Following completion of the training session, training participants completed a survey regarding perceived value of the training. An independent evaluation of the study was conducted by the University of Central Florida's Institute for Simulation and Training. Statistical analyses showed no significant difference between the training groups in any of the learning measures. The change in electrodermal activity was non-significant between the two training groups. Participant evaluations revealed strong belief among trainees that LTT was of greater value to the training participants, however, participants suggested that LTT should be continued for combat casualty care training while SBT could be useful to other groups of learners. A more limited use of LTT would address the concerns regarding the use of live tissue. The comparison of learning outcomes in this controlled study provides new evidence to support further integration of SBT in combat casualty training. The study results will inform trauma education planning so that the most effective training methods available for military personnel preparing for combat casualty care can be utilized.Includes bibliographical references (pages 139-147)

Adherence to Statin Therapy and Attainment of LDL Cholesterol Targets in an Outpatient Population of Type 2 Diabetes Patients:Analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT)

Objective: To assess adherence to statin therapy and its association with sociodemographic data, medical characteristics, LDLc levels, and LDLc target attainment in real-world T2D patients treated in secondary care.Research Design and Methods: Cross-sectional analyses were performed on baseline data of 393 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT). The medication possession ratio (MPR), calculated with pharmacy dispensing data, was used to determine adherence to statins for an intended period of 24 months. Statins were included in the analyses if they were used for at least six consecutive months with at least three dispenses. Adherence was defined as an MPR >= 80%. Associations with adherence were assessed using descriptive statistics and binary logistic regression.Results: Overall, 80% of the patients had a statin prescription and of those, 89% were adherent. The proportion of patients who reached LDLc targets o

Low Physical Activity in Patients with Complicated Type 2 Diabetes Mellitus Is Associated with Low Muscle Mass and Low Protein Intake

Objective: In order to promote physical activity (PA) in patients with complicated type 2 diabetes, a better understanding of daily movement is required. We (1) objectively assessed PA in patients with type 2 diabetes, and (2) studied the association between muscle mass, dietary protein intake, and PA. Methods: We performed cross-sectional analyses in all patients included in the Diabetes and Lifestyle Cohort Twente (DIALECT) between November 2016 and November 2018. Patients were divided into four groups: = 10,000 steps/day. We studied the association between muscle mass (24 h urinary creatinine excretion rate, CER) and protein intake (by Maroni formula), and the main outcome variable PA (steps/day, Fitbit Flex device) using multivariate linear regression analyses. Results: In the 217 included patients, the median steps/day were 6118 (4115-8638). Of these patients, 48 patients (22%) took 7000-9999 steps/day, 37 patients (17%) took >= 10,000 steps/day, and 78 patients (36%) took = 10,000 steps/day, a higher body mass index (BMI) (33 +/- 6 vs. 30 +/- 5 kg/m(2), p = 0.009), lower CER (11.7 +/- 4.8 vs. 14.8 +/- 3.8 mmol/24 h, p = 0.001), and lower protein intake (0.84 +/- 0.29 vs. 1.08 +/- 0.22 g/kg/day, p < 0.001). Both creatinine excretion (beta = 0.26, p < 0.001) and dietary protein intake (beta = 0.31, p < 0.001) were strongly associated with PA, which remained unchanged after adjustment for potential confounders. Conclusions: Prevalent insufficient protein intake and low muscle mass co-exist in obese patients with low physical activity. Dedicated intervention studies are needed to study the role of sufficient protein intake and physical activity in increasing or maintaining muscle mass in patients with type 2 diabetes

The price of tumor control

Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

Folding and Self-Assembly of the TatA Translocation Pore Based on a Charge Zipper Mechanism

SummaryWe propose a concept for the folding and self-assembly of the pore-forming TatA complex from the Twin-arginine translocase and of other membrane proteins based on electrostatic “charge zippers.” Each subunit of TatA consists of a transmembrane segment, an amphiphilic helix (APH), and a C-terminal densely charged region (DCR). The sequence of charges in the DCR is complementary to the charge pattern on the APH, suggesting that the protein can be “zipped up” by a ladder of seven salt bridges. The length of the resulting hairpin matches the lipid bilayer thickness, hence a transmembrane pore could self-assemble via intra- and intermolecular salt bridges. The steric feasibility was rationalized by molecular dynamics simulations, and experimental evidence was obtained by monitoring the monomer-oligomer equilibrium of specific charge mutants. Similar “charge zippers” are proposed for other membrane-associated proteins, e.g., the biofilm-inducing peptide TisB, the human antimicrobial peptide dermcidin, and the pestiviral ERNS protein

Real-life achievement of lipid-lowering treatment targets in the DIAbetes and LifEstyle Cohort Twente:Systemic assessment of pharmacological and nutritional factors

BACKGROUND/OBJECTIVES: Lowering low-density lipoprotein cholesterol (LDLc) in type 2 diabetes mellitus is of paramount importance in preventing cardiovascular disease. However, treatment targets for LDLc are often not reached. We studied the prevalence of LDLc target achievement in a real-life population of type 2 diabetes mellitus patients in secondary care, and investigated whether in those not on target, there is room for intensifying pharmacological and lifestyle management according to current treatment guidelines. SUBJECTS/METHODS: We performed a cross-sectional analysis in the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1; n = 450, age 63 ± 9 years, 58% men, diabetes duration 11 (7-18) years). At baseline, we determined plasma LDLc concentration, pharmacological treatment (i.e., statin use), and lifestyle (physical activity and dietary intake). Patients were divided according to LDLc < 1.8, LDLc 1.8-2.5, and LDLc > 2.5 mmol/l. Dietary intake was collected from a validated Food Frequency Questionnaire (177 items) and we determined guideline adherence for different food groups. Physical activity was assessed with the Short Questionnaire to ASsess Health enhancing behavior. RESULTS: LDLc data were available in 428 type 2 diabetes mellitus patients. LDLc ≤ 2.5 mmol/l was achieved in 317 patients (76%). In total, 76% of patients used statins, in those with LDLc > 2.5 mmol/l, this was 44%. Adherence to lifestyle guidelines was not different between the LDLc groups and was as follows: body mass index 6%, physical activity 59%, vegetables 7%, fruit 28%, legumes 59%, nuts 14%, dairy 19%, fish 36%, tea 8%, fats 66%, red meat 12%, processed meat 2%, alcohol 71%, sweetened beverages 34%, and sodium 12%. CONCLUSIONS: In type 2 diabetes mellitus patients in secondary health care, the target LDLc is achieved by three quarters of patients. Increasing statin treatment could be a first step to improve LDLc. In addition, there are ample opportunities for lifestyle management through increasing adherence to lifestyle guidelines

PtyNAMi: ptychographic nano-analytical microscope

Ptychographic X-ray imaging at the highest spatial resolution requires an optimal experimental environment, providing a high coherent flux, excellent mechanical stability and a low background in the measured data. This requires, for example, a stable performance of all optical components along the entire beam path, high temperature stability, a robust sample and optics tracking system, and a scatter-free environment. This contribution summarizes the efforts along these lines to transform the nanoprobe station on beamline P06 (PETRA III) into the ptychographic nano-analytical microscope (PtyNAMi