Learning curves and long-term outcome of simulation-based thoracentesis training for medical students

<p>Abstract</p> <p>Background</p> <p>Simulation-based medical education has been widely used in medical skills training; however, the effectiveness and long-term outcome of simulation-based training in thoracentesis requires further investigation. The purpose of this study was to assess the learning curve of simulation-based thoracentesis training, study skills retention and transfer of knowledge to a clinical setting following simulation-based education intervention in thoracentesis procedures.</p> <p>Methods</p> <p>Fifty-two medical students were enrolled in this study. Each participant performed five supervised trials on the simulator. Participant's performance was assessed by performance score (PS), procedure time (PT), and participant's confidence (PC). Learning curves for each variable were generated. Long-term outcome of the training was measured by the retesting and clinical performance evaluation 6 months and 1 year, respectively, after initial training on the simulator.</p> <p>Results</p> <p>Significant improvements in PS, PT, and PC were noted among the first 3 to 4 test trials (p < 0.05). A plateau for PS, PT, and PC in the learning curves occurred in trial 4. Retesting 6 months after training yielded similar scores to trial 5 (p > 0.05). Clinical competency in thoracentesis was improved in participants who received simulation training relative to that of first year medical residents without such experience (p < 0.05).</p> <p>Conclusions</p> <p>This study demonstrates that simulation-based thoracentesis training can significantly improve an individual's performance. The saturation of learning from the simulator can be achieved after four practice sessions. Simulation-based training can assist in long-term retention of skills and can be partially transferred to clinical practice.</p

Potent New Small-Molecule Inhibitor of Botulinum Neurotoxin Serotype A Endopeptidase Developed by Synthesis-Based Computer-Aided Molecular Design

Botulinum neurotoxin serotype A (BoNTA) causes a life-threatening neuroparalytic disease known as botulism. Current treatment for post exposure of BoNTA uses antibodies that are effective in neutralizing the extracellular toxin to prevent further intoxication but generally cannot rescue already intoxicated neurons. Effective small-molecule inhibitors of BoNTA endopeptidase (BoNTAe) are desirable because such inhibitors potentially can neutralize the intracellular BoNTA and offer complementary treatment for botulism. Previously we reported a serotype-selective, small-molecule BoNTAe inhibitor with a Kiapp value of 3.8±0.8 µM. This inhibitor was developed by lead identification using virtual screening followed by computer-aided optimization of a lead with an IC50 value of 100 µM. However, it was difficult to further improve the lead from micromolar to even high nanomolar potency due to the unusually large enzyme-substrate interface of BoNTAe. The enzyme-substrate interface area of 4,840 Å2 for BoNTAe is about four times larger than the typical protein-protein interface area of 750–1,500 Å2. Inhibitors must carry several functional groups to block the unusually large interface of BoNTAe, and syntheses of such inhibitors are therefore time-consuming and expensive. Herein we report the development of a serotype-selective, small-molecule, and competitive inhibitor of BoNTAe with a Ki value of 760±170 nM using synthesis-based computer-aided molecular design (SBCAMD). This new approach accounts the practicality and efficiency of inhibitor synthesis in addition to binding affinity and selectivity. We also report a three-dimensional model of BoNTAe in complex with the new inhibitor and the dynamics of the complex predicted by multiple molecular dynamics simulations, and discuss further structural optimization to achieve better in vivo efficacy in neutralizing BoNTA than those of our early micromolar leads. This work provides new insight into structural modification of known small-molecule BoNTAe inhibitors. It also demonstrates that SBCAMD is capable of improving potency of an inhibitor lead by nearly one order of magnitude, even for BoNTAe as one of the most challenging protein targets. The results are insightful for developing effective small-molecule inhibitors of protein targets with large active sites

Cytoskeletal protein kinases: titin and its relations in mechanosensing

Titin, the giant elastic ruler protein of striated muscle sarcomeres, contains a catalytic kinase domain related to a family of intrasterically regulated protein kinases. The most extensively studied member of this branch of the human kinome is the Ca2+–calmodulin (CaM)-regulated myosin light-chain kinases (MLCK). However, not all kinases of the MLCK branch are functional MLCKs, and about half lack a CaM binding site in their C-terminal autoinhibitory tail (AI). A unifying feature is their association with the cytoskeleton, mostly via actin and myosin filaments. Titin kinase, similar to its invertebrate analogue twitchin kinase and likely other “MLCKs”, is not Ca2+–calmodulin-activated. Recently, local protein unfolding of the C-terminal AI has emerged as a common mechanism in the activation of CaM kinases. Single-molecule data suggested that opening of the TK active site could also be achieved by mechanical unfolding of the AI. Mechanical modulation of catalytic activity might thus allow cytoskeletal signalling proteins to act as mechanosensors, creating feedback mechanisms between cytoskeletal tension and tension generation or cellular remodelling. Similar to other MLCK-like kinases like DRAK2 and DAPK1, TK is linked to protein turnover regulation via the autophagy/lysosomal system, suggesting the MLCK-like kinases have common functions beyond contraction regulation

Patient Preferences for Care by General Internists and Specialists in the Ambulatory Setting

OBJECTIVE: To investigate patients' preferences for care by general internists and specialists for common medical conditions. DESIGN: Telephone interview. SETTING: A convenience sample of general internal medicine practices at 10 eastern academic medical centers. PATIENT/PARTICIPANTS: A probability sample of 314 participants who had at least one visit with their primary care physician during the preceding 2 years. MEASUREMENTS AND MAIN RESULTS: Items addressed patients' attitudes concerning continuity of care, preferences for care by general internists or specialists for common medical problems, and perceptions about the competency of general internists and specialists to manage these problems. Continuity was important to participants, with 63% reporting they preferred having one doctor. Respondents were willing to wait 3 or 4 days to see their regular doctor (85%) and wanted their doctor to see them in the emergency department (77%) and monitor their care while in the hospital (94%). A majority (>60%) preferred care from their regular doctor for a variety of new conditions. Though respondents valued continuity, 84% felt it was important to be able to seek medical care from any type of physician without a referral, and 74% responded that if they needed to see a specialist, they were willing to pay out-of-pocket to do so. Although most participants (98%) thought their regular doctor was able to take care of usual medical problems, the majority thought that specialists were better able to care for allergies (79%) and better able to prescribe medications for depression (65%) and low-back pain (72%). CONCLUSIONS: Participants preferred to see their general internist despite their perceptions that specialists were more competent in caring for the conditions we examined. However, they wanted unrestricted access to specialists to supplement care provided by general internists

Confidence of Graduating Internal Medicine Residents to Perform Ambulatory Procedures

OBJECTIVE: To evaluate the training of graduating internal medicine residents to perform 13 common ambulatory procedures, 3 inpatient procedures, and 3 screening examinations. DESIGN: Self-administered descriptive survey. SETTING: Internal medicine training programs associated with 9 medical schools in the eastern United States. PARTICIPANTS: Graduating residents (N = 128); response rate, 60%. MEASUREMENTS AND MAIN RESULTS: The total number of procedures performed during residency, importance for primary care physicians to perform these procedures, confidence to perform these procedures, and helpfulness of rotations for learning procedures were assessed. The majority of residents performed only 2 of 13 outpatient procedures 10 or more times during residency: simple spirometry and minor wound suturing. For all other procedures, the median number performed was 5 or fewer. The percentage of residents attributing high importance to a procedure was significantly greater than the percentage reporting high confidence for 8 of 13 ambulatory procedures; for all inpatient procedures, residents reported significantly higher confidence than importance. Continuity clinic and block ambulatory rotations were not considered helpful for learning ambulatory procedures. CONCLUSIONS: Though residents in this sample considered most ambulatory procedures important for primary care physicians, they performed them infrequently, if at all, during residency and did not consider their continuity clinic experience helpful for learning these skills. Training programs need to address this deficiency by modifying the curriculum to ensure that these skills are taught to residents who anticipate a career in primary care medicine