Effects of a focused training on first-year osteopathic medical students' ability to incorporate point-of-care ultrasound in assessment of the anterior knee.

CONTEXT: Patients frequently present to the outpatient clinic, urgent care, or emergency department with a painful, swollen knee. Differentiating the underlying etiology can be a challenge for both medical students and seasoned clinicians alike. Because this scenario can represent a time-sensitive emergency, developing skills to diagnose the underlying cause quickly and accurately is essential for proper management, whether the patient would benefit from osteopathic manipulation, prompt administration of antibiotics, or a more invasive procedure like joint aspiration or surgery. OBJECTIVES: The objectives are to determine the effects of a focused ultrasound training on first-year osteopathic medical students' ability to identify normal sonographic anatomy of the anterior knee and to differentiate between three common pathologies: joint effusion, prepatellar bursitis, and cellulitis. METHODS: First-year osteopathic medical students voluntarily participated in this cross-sectional study. The study protocol included a focused ultrasound training (online materials, brief didactic and single hands-on sessions) followed by a hands-on assessment. A written test and 5-point Likert scale questionnaire were administered before and after the focused training. Nine weeks later, students completed a follow-up written test. The proportion of students who correctly identified common pathologies on written tests before (pretest) and after (posttest) training and on the follow-up written test were compared utilizing the Fisher's exact test. A t test was utilized to compare data from the pretraining and posttraining questionnaires. RESULTS: Of 101 students completing the written pretest and pretraining questionnaire, 95 (94.1 %) completed the written posttest and posttraining questionnaire, and 84 (83.2 %) completed the follow-up written test. Students had limited previous experience with ultrasound; 90 (89.1 %) students had performed six or fewer ultrasound examinations before the focused ultrasound training. On written tests, students accurately identified joint effusion (22.8 % [23/101] pretest, 65.3 % [62/95] posttest, 33.3 % [28/84] follow-up test), prepatellar bursitis (14.9 % [15/101] pretest, 46.3 % [44/95] posttest, 36.9 % [31/84] follow-up test), and cellulitis (38.6 % [39/101] pretest, 90.5 % [86/95] posttest, 73.8 % [62/84] follow-up test). Differences were found between pretest and posttest for identification of all three pathologies (all p<0.001) and between the pretest and 9-week follow-up test for identification of prepatellar bursitis and cellulitis (both p≤0.001). For questionnaires, (where 1=strongly agree, 5=strongly disagree), the mean (standard deviation [SD]) confidence for correctly identifying normal sonographic anatomy of the anterior knee was 3.50 (1.01) at pretraining and 1.59 (0.72) at posttraining. Student confidence in the ability to differentiate joint effusion, prepatellar bursitis, and cellulitis utilizing ultrasound increased from 4.33 (0.78) at pretraining to 1.99 (0.78) at posttraining. For the hands-on assessment, 78.3 % (595 correct/760 aggregated responses) of the time students correctly identified specific sonographic landmarks of the anterior knee. When the evaluation combined real-time scanning with a prerecorded sonographic video clip of the anterior knee, 71.4 % (20/28) accurately identified joint effusion, 60.9 % (14/23) correctly diagnosed prepatellar bursitis, 93.3 % (28/30) recognized cellulitis, and 47.1 % (8/17) diagnosed the normal knee. CONCLUSIONS: Our focused training was effective at immediately increasing basic knowledge, as well as confidence of first-year osteopathic medical students when assessing the anterior knee with point-of-care ultrasound. However, spaced repetition and deliberate practice may be useful for learning retention.

Assessing Competency in Family Medicine Residents Using the Osteopathic Manipulative Medicine Mini-Clinical Evaluation Exercise.

CONTEXT: The Mini-Clinical Evaluation Exercise (Mini-CEX) is one example of a direct observation tool used for workplace-based skills assessment. The Mini-CEX has been validated as a useful formative evaluation tool in graduate medical education. However, no Mini-CEX has been reported in the literature that specifically assesses the osteopathic manipulative medicine (OMM) skills of family medicine residents. Therefore, the authors created and studied an OMM Mini-CEX to fill this skills assessment gap. OBJECTIVE: To determine whether the OMM Mini-CEX is perceived as an effective evaluation tool for assessing the OMM core competencies of family medicine residents. METHODS: Faculty and residents of The Wright Center for Graduate Medical Education National Family Medicine Residency program participated in the study. Each resident was evaluated at least once using the OMM Mini-CEX. Surveys were used to assess faculty and resident perceptions of the usefulness and effectiveness of the OMM Mini-CEX for assessing OMM competencies. RESULTS: Eighty-one responses were received during 2 survey cycles within a 7-month period. The internal consistency of the survey responses had a high reliability (Cronbach α=0.93). Considering respondents who agreed that they had a clear understanding of the general purpose of a Mini-CEX, the perceived effectiveness score for the OMM Mini-CEX was higher among those who agreed that a Mini-CEX was a useful part of training than among those who disagreed or were unsure of its usefulness (median score, 4.0 vs 3.4, respectively; P=.047). CONCLUSIONS: The results suggest the OMM Mini-CEX can be a useful direct observation evaluation tool to assess OMM core competencies in family medicine residents. Additional research is needed to determine its perceived effectiveness in other clinical specialties and in undergraduate medical education.

Licence to swill: James Bond's drinking over six decades.

OBJECTIVES: To describe the patterns of alcohol use in James Bond movies over six decades. DESIGN: Film content analysis. SETTING: Wide range of international locations in 24 James Bond movies (Eon Productions series, 1962-2015). MAIN OUTCOME MEASURES: Drinking episodes for Bond and major female characters; alcohol product placement in films; peak estimated blood alcohol concentrations; features relevant to DSM-5 criteria for alcohol use disorder. RESULTS: Bond has drunk heavily and consistently across six decades (109 drinking events; mean, 4.5 events per movie). His peak blood alcohol level was estimated to have been 0.36 g/dL, sufficient to kill some people. We classified him as having severe alcohol use disorder, as he satisfied six of 11 DSM-5 criteria for this condition. Chronic risks for Bond include frequently drinking prior to fights, driving vehicles (including in chases), high stakes gambling, operating complex machinery or devices, contact with dangerous animals, extreme athletic performance, and sex with enemies, sometimes with guns or knives in the bed. Notable trends during the study period included a decline in using alcohol as a weapon (P = 0.023) and an increase in the number of alcohol products in his environment (for alcohol-related product placement: P < 0.001), but his martini consumption has been steady. Drinking by lead female characters and a random selection of 30 of his sexual partners was fairly stable over time, but also occasionally involved binges. CONCLUSIONS: James Bond has a severe chronic alcohol problem. He should consider seeking professional help and find other strategies for managing on-the-job stress.

Teaching Medical Students About Health Systems Science and Osteopathic Principles and Practice Using a Virtual World: The Envision Community Health Center.

Medical education technology initiatives can be used to prepare osteopathic medical students for modern primary care practice and to provide students with training to serve vulnerable populations. Over academic years 2014 through 2017, the authors designed and implemented 26 case studies using patient simulations through a virtual community health center (CHC). First-year students, who were preparing for clinical training in CHCs, and second-year students, who were training in CHCs, completed the simulation case studies, gaining practice in clinical reasoning, Health Systems Science, and applied osteopathic principles and practice. This article explains the project, illustrates an alignment with Health Systems Science and osteopathic competencies, and highlights findings from previous research studies.

Effectiveness of osteopathic manipulative treatment for carpal tunnel syndrome: a pilot project.

CONTEXT: Osteopathic manipulative treatment (OMT) has been recognized as a management option for carpal tunnel syndrome (CTS), although limited research exists to substantiate its effectiveness. OBJECTIVE: To evaluate the effectiveness of OMT in the management of CTS. METHODS: This single-blinded quasi-controlled trial was conducted at an academic institution. Participants with CTS underwent weekly OMT sessions for 6 consecutive weeks. The main outcome measures were the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ), a sensory symptom diagram (SSD), patient estimate of overall change, electrophysiologic testing of the median nerve (trans-carpal tunnel motor and sensory nerve conduction velocity and amplitude ratio), and carpal tunnel ultrasound imaging of the cross-sectional area of the median nerve and transverse carpal ligament length and bowing. All outcome measures were administered to participants before the first OMT session. Immediately after the first session, electrophysiologic testing of the median nerve and ultrasound imaging of the carpal tunnel were repeated. After 6 weeks of OMT, all outcome measures were readministered. RESULTS: Results of the BCTQ revealed statistically significant improvements in symptoms and function after 6 weeks of OMT (F=11.0; P=.004), and the improvements tended to be more pronounced on the treated side. The drop in SSD scores after 6 weeks of treatment was statistically significant (F=4.19; P=.0002). Patient estimate of overall improvement of symptoms was statistically significant for the treated side. No statistically significant changes in electrophysiologic function of the median nerve, cross-sectional area of the median nerve, or transverse carpal ligament bowing were observed. After treatment, the increase in transverse carpal ligament length was statistically significant, but no side-to-side difference was detected. CONCLUSION: Osteopathic manipulative treatment resulted in patient-perceived improvement in symptoms and function associated with CTS. However, median nerve function and morphology at the carpal tunnel did not change, possibly indicating a different mechanism by which OMT acted, such as central nervous system processes.

Assessment of skin blood flow following spinal manual therapy: a systematic review.

Skin blood flow (SBF) indexes have been used to describe physiological mechanisms associated with spinal manual therapy (SMT). The aims of the current review were to assess methods for data collection, assess how investigators interpreted SBF changes, and formulate recommendations to advance manual medicine research. A database search was performed in PubMed, Cochrane Library, the Physiotherapy Evidence Database, and the Cumulative Index to Nursing and Allied Health Literature through April 2014. Articles were included if at least 1 outcome measure was changes in 1 SBF index following SMT. The database search yielded 344 records. Two independent authors applied the inclusion criteria. Twenty studies met the inclusion criteria. Selected studies used heterogeneous methods to assess short-term post-SMT changes in SBF, usually vasoconstriction, which was interpreted as a general sympathoexcitatory effect through central mechanisms. However, this conclusion might be challenged by the current understanding of skin sympathetic nervous activity over local endothelial mechanisms that are specifically controlling SBF. Evaluation of SBF measurements in peripheral tissues following SMT may document physiological responses that are beyond peripheral sympathetic function. Based on the current use of SBF indexes in clinical and physiological research, 14 recommendations for advancing manual medicine research using laser Doppler flowmetry are presented.

Use of real-time physiologic parameter assessment to augment osteopathic manipulative treatment training for first-year osteopathic medical students.

CONTEXT: The first 2 years of osteopathic medical school involve training in osteopathic principles and practice, including understanding the tenets of osteopathic medicine and developing palpatory skills for clinical application. Although this training emphasizes the link between somatic dysfunction and physiologic function, it does not include the opportunity for students to quantitatively assess the physiologic effect of osteopathic manipulative treatment (OMT) using physiologic measurements. OBJECTIVE: To evaluate an approach for integrated OMT training coupled with physiologic measurements of relevant parameters, whereby first-year osteopathic medical students assess the quantitative, real-time changes in specific physiologic signals during instruction. METHODS: During mandatory musculoskeletal and cardiovascular demonstration laboratories at a single osteopathic medical school, students were divided into small groups and performed OMT on each other while recording real-time measurements of physiologic functions such as maximum clench force, time to fatigue for the forearm flexor muscles, heart rate, and peripheral vascular flow. After data were collected, students analyzed pre- and post-OMT measurements and discussed underlying physiologic principles in a large group format. At the end of the sessions, students completed a brief survey on the usefulness of the integrated laboratories. RESULTS: Overall, 13 of 28 student groups (46.4%) measured a pre- to post-OMT increase in maximum clench force, and 16 (57.1%) observed an increase in time to fatigue for the forearm flexor muscles. Twenty-three of 27 student groups (85.2%) observed a reduction in heart rate and 19 (70.4%) measured an increase in peripheral vascular flow after OMT. Student satisfaction was generally favorable, with overall mean (SD) ratings of 6.38 (1.86) for the musculoskeletal laboratory and 7.81 (1.69) for the cardiovascular laboratory out of a maximum of 10 points. In open-ended comments, students deemed the combined laboratories as clinically applicable but desired more time for completing the laboratories. CONCLUSION: Measurement of specific physiologic musculoskeletal and cardiovascular parameters before and after OMT enabled quantification of physiologic responses to OMT. Students' favorable feedback indicated that the quality of learning in the laboratories was enhanced by the addition of physiologic measurements.

Somatic dysfunction and use of osteopathic manual treatment techniques during ambulatory medical care visits: a CONCORD-PBRN study.

CONTEXT: Osteopathic manual treatment (OMT) of somatic dysfunction is a unique approach to medical care that may be studied within a practice-based research network. OBJECTIVE: To measure patient characteristics and osteopathic physician practice patterns within the Consortium for Collaborative Osteopathic Research Development-Practice-Based Research Network (CONCORD-PBRN). DESIGN: Cross-sectional card study. SETTING: Eleven member clinics within the CONCORD-PBRN coordinated by The Osteopathic Research Center. PATIENTS: A total of 668 patients seen between January and March 2013. MAIN STUDY MEASURES: Patient age and sex; primary diagnoses; somatic dysfunction as manifested by tenderness, asymmetry, restricted motion, or tissue texture changes; and use of 14 OMT techniques. Results were stratified by anatomical region and adjusted for clustering within member clinics. Clustering was measured by the intracluster correlation coefficient. RESULTS: Patient ages ranged from 7 days to 87 years (adjusted mean age, 49.2 years; 95% confidence interval [CI], 43.3-55.1 years). There were 450 females (67.4%) and 508 patient visits (76.0%) involved a primary diagnosis of disease of the musculoskeletal system and connective tissue. Structural examination was performed during 657 patient visits (98.4%), and 649 visits (97.2%) involved OMT. Restricted motion and tenderness were the most and least common palpatory findings, respectively. Cranial (1070 [14.5%]), myofascial release (1009 [13.7%]), muscle energy (1001 [13.6%]), and counterstrain (980 [13.3%]) techniques were most commonly used, accounting for more than one-half of the OMT provided. Pediatric patients were more likely than adults to receive OMT within the head (adjusted odds ratio [OR], 9.53; 95% CI, 1.28-71.14). Geriatric patients were more likely than adults to receive a structural examination (adjusted OR, 1.83; 95% CI, 1.09-3.07) and OMT (adjusted OR, 1.62; 1.02-2.59) within the lower extremity. Females were more likely than males to receive a structural examination (adjusted OR, 2.44; 95% CI, 1.44-4.16) and OMT (adjusted OR, 2.11; 95% CI, 1.26-3.52) within the sacrum and OMT within the pelvis (adjusted OR, 1.79; 95% CI, 1.12-2.88). Intracluster correlation coefficients for the 4 most commonly used OMT techniques ranged from 0.34 to 0.72. CONCLUSION: This study provides proof of concept of the feasibility of studying osteopathic medical practice on a national level by developing and growing the CONCORD-PBRN.

Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma.

Multiple myeloma (MM) is associated with the development of osteolytic bone disease, mediated by increased osteoclastic bone resorption and impaired osteoblastic bone formation. Dickkopf-1 (Dkk1), a soluble inhibitor of wingless/int (Wnt) signaling and osteoblastogenesis, is elevated in patients with MM and correlates with osteolytic bone disease. In this study, we investigated the effect of inhibiting Dkk1 on the development of osteolytic lesions in the 5T2MM murine model of myeloma. We showed that Dkk1 is expressed by murine 5T2MM myeloma cells. Injection of 5T2MM cells into C57BL/KaLwRij mice resulted in the development of osteolytic bone lesions (p < 0.05), mediated by increased osteoclast numbers (p < 0.001) and a decrease in osteoblast numbers (p < 0.001) and mineralizing surface (p < 0.05). Mice bearing 5T2MM cells were treated with an anti-Dkk1 antibody (BHQ880, 10 mg/kg, IV, twice weekly for 4 wk) from time of paraprotein detection. Anti-Dkk1 treatment prevented 5T2MM-induced suppression of osteoblast numbers (p < 0.001) and surface (p < 0.001). Treatment increased mineralizing surface by 28% and bone formation rate by 25%; however, there was no change in mineral apposition rate. Inhibiting Dkk1 had no effect on osteoclast numbers. muCT analysis showed that anti-Dkk1 treatment significantly protected against 5T2MM-induced trabecular bone loss (p < 0.05) and reduced the development of osteolytic bone lesions (p < 0.05). Treatment had no significant effect on tumor burden. These data suggest that inhibiting Dkk1 prevents the suppression of bone formation and in doing so is effective in preventing the development of osteolytic bone disease in myeloma, offering an effective therapeutic approach to treating this clinically important aspect of myeloma.

An osteoprotegerin-like peptidomimetic inhibits osteoclastic bone resorption and osteolytic bone disease in myeloma.

Multiple myeloma is a B-cell malignancy characterized by the uncontrolled growth of plasma cells in the bone marrow and the development of osteolytic bone disease. Myeloma cells express the receptor activator of nuclear factor kappaB ligand (RANKL), induce RANKL expression in the bone marrow, and down-regulate expression of the decoy receptor osteoprotegerin, thereby promoting bone resorption. Targeting this system in myeloma has clear therapeutic potential. However, osteoprotegerin also binds tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and prevents TRAIL-induced apoptosis of myeloma cells. Whether or not osteoprotegerin can bind TRAIL and prevent apoptosis in vivo and the relative importance of osteoprotegerin binding to TRAIL and RANKL are unclear. In the present study, we have investigated the ability of an osteoprotegerin-like peptidomimetic (OP3-4), designed to block the RANKL/RANK interaction, to inhibit osteoclastic bone resorption and TRAIL-induced apoptosis in vitro and myeloma bone disease in vivo. OP3-4 inhibited osteoclast formation (P < 0.01) and bone resorption (P < 0.01) in vitro. However, OP3-4 had no effect on TRAIL-induced apoptosis of RPMI 8226 myeloma cells. Treatment of 5T2MM myeloma-bearing mice with OP3-4 decreased osteoclast number and the proportion of bone surface covered by osteoclasts (P < 0.05). Treatment also prevented the tumor-induced decrease in cancellous bone area and the development of osteolytic lesions (P < 0.05). OP3-4 also reduced tumor burden when compared with the control (P < 0.05). These data suggest that OP3-4 and the selective inhibition of RANKL, but not TRAIL activity, are effective in preventing myeloma bone disease and offer a novel therapeutic approach to treating this aspect of myeloma. [Cancer Res 2007;67(1):202-8].

Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma.

The effect of bortezomib on bone remodelling was evaluated in 34 relapsed myeloma patients. At baseline, patients had increased serum concentrations of dickkopf-1 (DKK-1), soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), sRANKL/osteoprotegerin ratio, C-telopeptide of type-I collagen (CTX) and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b); bone-alkaline phosphatase and osteocalcin were reduced. Serum DKK-1 correlated with CTX and severe bone disease. Bortezomib administration significantly reduced serum DKK-1, sRANKL, CTX, and TRACP-5b after four cycles, and dramatically increased bone-alkaline phosphatase and osteocalcin, irrespective of treatment response. This is the first study showing that bortezomib reduces DKK-1 and RANKL serum levels, leading to the normalisation of bone remodelling in relapsed myeloma.

Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation.

Dickkopf-1 (DKK-1) protein, a soluble inhibitor of Wnt signalling, has been implicated in the pathogenesis of myeloma bone disease through the suppression of osteoblast differentiation. In this study, serum concentrations of DKK-1 were measured in 50 myeloma patients (32 at diagnosis and 18 before and after autologous stem cell transplantation (ASCT), 18 patients with monoclonal gammopathy of undetermined significance (MGUS), and 22 healthy controls. Serum DKK-1 levels were increased in MM at diagnosis compared with MGUS (mean +/- SD: 67 +/- 54 ng/mL vs. 38 +/- 13 ng/mL; p = 0.006) and controls (31 +/- 11 ng/mL; p = 0.02), while there was no difference between MGUS patients and controls. Although patients with stage 2 and 3 myeloma had higher DKK-1 values than stage 1 patients (79 +/- 63 vs. 40 +/- 13; p = 0.005), no significant correlation between serum DKK-1 and myeloma bone disease was observed. Myeloma patients before ASCT also had increased levels of DKK-1 (63 +/- 77 ng/mL; p = 0.03) compared with controls, supporting the notion that DKK-1 may be responsible for the suppressed osteoblast activity even in patients with low tumor burden. After ASCT, there was a sustained decrease in DKK-1 levels over time, while bone formation markers elevated, suggesting that the reduction of DKK-1 levels after ASCT may correlate with the normalization of osteoblast function. These results could provide the basis for developing agents that block DKK-1, thus restoring osteoblast function and counteracting the increased osteoclastogenesis observed in myeloma.

Expression profiling and functional analysis of wnt signaling mechanisms in mesenchymal stem cells.

Through their broad differentiation potential, mesenchymal stem cells (MSCs) are candidates for a range of therapeutic applications, but the precise signaling pathways that determine their differentiated fate are not fully understood. Evidence is emerging that developmental signaling cues may be important in regulating stem cell self-renewal and differentiation programs. Here we have identified a consistent expression profile of Wnt signaling molecules in MSCs and provide evidence that an endogenous canonical Wnt pathway functions in these cells. Wnts bind to Frizzled (Fz) receptors and subsequent canonical signaling inhibits glycogen synthase kinase-3beta (GSK-3beta), causing beta-catenin translocation into the nucleus to induce target gene expression. In human MSCs isolated from bone marrow of different donors, we appear to have identified a common Wnt/Fz expression profile using reverse transcriptase polymerase chain reaction (RT-PCR). Associated Wnt signaling components, including low-density lipoprotein receptor-related protein-5 (LRP-5), kremen-1, dickkopf-1 (Dkk-1), secreted Frizzled-related peptide (sFRP)-2, sFRP3, sFRP4, Disheveled (Dvl), GSK-3beta, adenomatous polyposis coli (APC), beta-catenin,T-cell factor (TCF)-1, and TCF-4, were also identified. Nuclear beta-catenin was observed in 30%-40% of MSCs, indicative of endogenous Wnt signaling. Exposure to both Wnt3a and Li+ ions, which promotes canonical Wnt signaling by inhibiting GSK-3beta, reduced phosphorylation of beta-catenin in MSCs and increased beta-catenin nuclear translocation approximately threefold over that of the controls. Our findings indicate that autocrine Wnt signaling operates in primitive MSC populations and supports previous evidence that Wnt signaling regulates mesenchymal lineage specification. The identification of a putative common Wnt/Fz molecular signature in MSCs will contribute to our understanding of the molecular mechanisms that regulate self-renewal and lineage-specific differentiation.

Involvement of tissue transglutaminase in the stabilisation of biomaterial/tissue interfaces important in medical devices.

Tissue transglutaminase (tTG) has recently been established as a novel cell surface adhesion protein that binds with high affinity to fibronectin in the pericellular matrix. In this study, we have made use of this property to enhance the biocompatibility of poly(epsilon-caprolactone) (PCL), a biomaterial currently used in bone repair. Poly(epsilon-caprolactone) discs were first coated with fibronectin and then tTG. The surface localisation of the two proteins was confirmed using ELISA and the tTG shown to be active on the surface by incorporation of biotin cadaverine into the fibronectin coating. When human osteoblasts (HOBs) were seeded onto the coated polymer surfaces in serum free medium, the surface coated with fibronectin and then tTG showed an increase in the spreading of the cells as compared to the surface coated with fibronectin alone, when analysed using environmental scanning electron microscopy. The presence of tTG had no effect on HOB cell differentiation when analysed by determining alkaline phosphatase activity. The use of tTG as a novel adhesion protein in this way may therefore have considerable potential in forming a stable tissue/biomaterial interface for application in medical devices.