A 10-Step Process to Align Problem-Based Learning With Accreditation Expectations for Self-Directed and Lifelong Learning.

OBJECTIVE: Self-directed and lifelong learning (SDLL) skills are essential skillsets in both undergraduate and graduate medical education (UME and GME). Hence, medical schools' accreditation bodies emphasize the requirements to acquire these skills in their accreditation standards. For example, in the United States, the Liaison Committee on Medical Education (LCME) clearly defines the components of the SDLL process in Element 6.3 of Accreditation Standard Six. Among the active learning pedagogies, problem-based learning (PBL) provides ample learning opportunities where SDLL skills are effectively applied. The aim of this article is to streamline the process of developing, delivering, and evaluating PBL sessions in line with the SDLL accreditation requirements through a 10-step design and implementation process. METHODS: Our 10-step process, detailed in the article, starts with developing learning objectives that inform the content of the PBL case and the required embedded learning triggers. The process carefully addresses the components of the SDLL process and other aspects of the accreditation needs within the framework of PBL. The approach to implementation, feedback, assessment, and evaluation is explicitly described to meet the regulatory expectations. DISCUSSION: In addition to the essential role in UME and GME, SDLL skills are vital requisites for continuing medical education of all physicians. Instilling this skillset early in medical students helps to cultivate their ability to apply these skills in their future professional roles. Using accreditation standards as a foundation for creating learning experiences, for example, PBL, requires careful content development and sequencing. Such a process needs explicit standardized steps that should not only be feasible, but also transferable for usage by different medical schools. CONCLUSION: Our streamlined 10-step process of designing and delivering an SDLL-oriented PBL experience can easily be adopted by other medical schools to address the SDLL skills acquisition as well as meeting the accreditation requirements.

PharmaMemory: an interactive, animated web application for learning autonomic physiology and pharmacology.

Medical students face challenging but important topics they must learn in short periods of time, such as autonomic pharmacology. Autonomic pharmacology is difficult in that it requires students to synthesize detailed anatomy, physiology, clinical reasoning, and pharmacology. The subject poses a challenge to learn as it is often introduced early in medical school curricula. To ease the difficulty of learning autonomic pharmacology, we created a free web application, PharmaMemory (www.pharmamemory.com), that interactively depicts the effects of high-yield autonomic drugs on the human body. PharmaMemory provides users with the opportunity to read and quiz themselves on the mechanisms, side effects, indications, and contraindications of these drugs while interacting with the application. We provided PharmaMemory to first-year medical students for three consecutive years of quality improvement and assessed the application's perceived effects on learning via user surveys. Survey feedback showed that users viewed PharmaMemory favorably and self-reported increased knowledge and confidence in the subject of autonomic pharmacology. Comments revealed that users liked the website's visuals, opportunity for challenged recall, and conciseness. PharmaMemory utilizes challenged recall, visual stimulation, and interactive learning to provide users with a multifaceted learning tool. Preliminary data suggest that students find this method of learning beneficial. Further studies are needed to assess PharmaMemory compared with more traditional learning methods such as PowerPoint or text-based learning. Additionally, further research is needed to quantitatively assess reduction in cognitive load.NEW & NOTEWORTHY PharmaMemory (www.pharmamemory.com) is a free web application that interactively depicts the effects of high-yield autonomic drugs on the human body.

A dynamic systems theory of intrateam conflict contagion.

Recognizing the challenges that conflict poses, organizational researchers have invested considerable energy toward investigating the processes by which conflict occurs and spreads within a team. However, current theoretical frameworks of conflict contagion posit a static growth trajectory in which members become engaged in conflict and stay in conflict. While this trajectory is certainly possible, the broader conflict literature outside of the organizational sciences has shown evidence for a more varied set of potential trajectories of conflict contagion. To advance theory on team conflict, we integrate conflict research from micro-level (interpersonal) to macro-level (interstate) perspectives into a formal theory of intrateam conflict contagion. Drawing from conflict stage and social contagion theory, we theorize that team members move through three stages of conflict (disengaged, at-risk, engaged) at rates determined by four process mechanisms (faultlines, forgiveness, frustration, integration) such that disengaged individuals become at-risk of engaging in conflict, engage in conflict, then disengage, only to potentially become at risk of reengaging at a later point in time. Using computational modeling, we demonstrate the generative sufficiency of our theory to account for conflict trajectories observed in the broader conflict literature. To facilitate the interpretation of such trajectories, we present a typology of contagion trajectories, discuss the dynamic properties of these trajectories (e.g., stability, bifurcations), and provide implications for future theory building and practice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Does monoclonal antibody treatment for COVID-19 impact short and long-term outcomes in a large generalisable population? A retrospective cohort study in the USA.

OBJECTIVES: To explore whether monoclonal antibodies (MAb) administered to high-risk patients with COVID-19 during the first week of illness prevent postacute sequelae of SARS-CoV-2 infection. DESIGN: Retrospective cohort study. SETTING: USA. PARTICIPANTS: A sample of 3809 individuals who received MAbs and a matched one-to-one comparison group from a set of 327 079 eligible patients who did not receive MAb treatment were selected from a deidentified administrative data set from commercial and Medicare Advantage health plan enrollees in the USA, including claims and outpatient laboratory data. RESULTS: Individuals who received MAb were 28% less likely to be hospitalised (HR=0.72, 95% CI 0.58 to 0.89) and 41% less likely to be admitted to the intensive care unit (HR=0.59, 95% CI 0.38 to 0.89) 30 days from SARS-CoV-2 diagnosis compared with individuals who did not receive MAb. A higher proportion of individuals given MAb therapy received care for clinical sequelae in the postacute phase (p=0.018). CONCLUSIONS: While MAb therapy was associated with benefits in the acute period, the benefit of therapy did not extend into the postacute period and did not reduce risk for clinical sequelae.

Comparative effectiveness of the sars-CoV-2 vaccines during delta dominance.

Background: Several vaccines with demonstrated efficacy for coronavirus disease 2019 (Covid-19) are available. The purpose of this study was to evaluate the COVID mRNA based and adenovector based vaccines' differential effectiveness during the time of circulation of the Delta variant and determine what impact this would have on population health and cost effectiveness. Methods: We used de-identified claims in a research database that included vaccination status and Covid-positivity status. Individuals ≥18 years, fully vaccinated with Ad26.COV2·S/J&J/Janssen, mRNA-1273/Moderna, or BNT162b2/Pfizer-BioNTech by September 30, 2021, were included. Outcomes were SARS-CoV-2-infection, emergency department visits, outpatient visits, inpatient hospitalizations, intensive care unit (ICU) transfers, death, and hospice transfers through September 30, 2021. Results: Among ∼6.5 million fully vaccinated individuals in the UHC Medicare Advantage and our commercially insured research database, mRNA-1273 performed better than BNT162b2 for infection, composite-hospitalization (hospitalization/ICU transfer/hospice transfer/death), and composite-ICU transfer (ICU transfer/hospice transfer/death) caused by B.1.612.7 (delta) variant infection. 26 CE.COV2.S performed worse than BNT162b2 for infection, composite-hospitalization, and composite-ICU transfers. The number needed to vaccinate (NNV) with mRNA1273 to prevent one hospitalization at 90 days was 3130 compared to 26 CE.COV2·S and 15,472 compared to BNT162b2. The NNV with mRNA1273 to prevent one ICU transfer at 90 days was 6358 compared to 26 CE.COV2·S and 34,279 compared to BNT162b2. For every one million individuals vaccinated with BNT162b compared to mRNA-1273, the approximate incremental inpatient cost would be $405,000 and the approximate incremental ICU cost would be $662,000. Conclusions: The two-dose mRNA vaccines' effectiveness significantly exceeded the single-dose Ad26.COV2·S vaccine's effectiveness from population health and cost-effectiveness perspectives. The mRNA1273 vaccine showed slightly more effectiveness than the BNT162b vaccine.

Brain-Derived Neurotrophic Factor Val66Met Genotype Modulates Latent Inhibition: Relevance for Schizophrenia.

BACKGROUND AND HYPOTHESIS: Latent inhibition (LI) is a measure of selective attention and learning relevant to Schizophrenia (SZ), with 2 abnormality poles: Disrupted LI in acute SZ, thought to underlie positive symptoms, and persistent LI (PLI) in schizotypy and chronic SZ under conditions where normal participants fail to show LI. We hypothesized that Brain-Derived Neurotrophic Factor (BDNF)-Met genotype shifts LI toward the PLI pole. STUDY DESIGN: We investigated the role of BDNF-Val66Met polymorphism and neural activation in regions involved in LI in mice, and the interaction between the BDNF and CHL1, a gene associated with SZ. STUDY RESULTS: No LI differences occurred between BDNF-wild-type (WT) (Val/Val) and knock-in (KI) (Met/Met) mice after weak conditioning. Chronic stress or stronger conditioning disrupted LI in WT but not KI mice. Behavior correlated with activation in infralimbic and orbitofrontal cortices, and nucleus accumbens. Examination of LI in CHL1-KO mice revealed no LI with no Met alleles (BDNF-WTs), PLI in CHL1-WT mice with 1 Met allele (BDNF-HETs), and PLI in both CHL1-WTs and CHL1-KOs with 2 Met alleles (BDNF-KIs), suggesting a shift to LI persistence with the number of BDNF-Met alleles in the CHL1 model of acute SZ. CONCLUSIONS: Results support a role for BDNF polymorphisms in gene-gene and gene-environment interactions relevant to SZ. BDNF-Met allele may reduce expression of some acute SZ symptoms, and may increase expression of negative symptoms in individuals with chronic SZ. Evaluation of (screening for) SZ phenotypes associated with mutations at a particular locus (eg, CHL1), may be masked by strong effects at different loci (eg, BDNF).

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis for patients with COVID-19: March 2022 update on the use of anticoagulation in critically ill patients.

BACKGROUND: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for patients with COVID-19. METHODS: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing systematic evidence reviews (up to January 2022). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 and May 2021 as part of the living phase of these guidelines. RESULTS: The panel made 1 additional recommendation: a conditional recommendation for the use of prophylactic-intensity over therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of thrombotic and bleeding risk. CONCLUSIONS: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation for patients with COVID-19-related critical illness.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: January 2022 update on the use of therapeutic-intensity anticoagulation in acutely ill patients.

BACKGROUND: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation in patients with COVID-19. METHODS: ASH formed a multidisciplinary guideline panel that included patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process and performed systematic evidence reviews (through November 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 as part of the living phase of these guidelines. RESULTS: The panel made one additional recommendation. The panel issued a conditional recommendation in favor of therapeutic-intensity over prophylactic-intensity anticoagulation in patients with COVID-19-related acute illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of risk of thrombosis and bleeding. The panel also noted that heparin (unfractionated or low molecular weight) may be preferred because of a preponderance of evidence with this class of anticoagulants. CONCLUSION: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19-related acute illness.

Application of the Milan System for Reporting Salivary Gland Cytopathology in pediatric patients: An international, multi-institutional study.

BACKGROUND: Pediatric salivary gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a small proportion of malignancies. This international, multi-institutional cohort evaluated the application of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and the risk of malignancy (ROM) for each diagnostic category. METHODS: Pediatric (0- to 21-year-old) salivary gland FNA specimens from 22 international institutions of 7 countries, including the United States, England, Italy, Greece, Finland, Brazil, and France, were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. Cytology-histology correlation was performed where available, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The cohort of 477 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 10.3%; nonneoplastic, 34.6%; AUS, 5.2%; benign neoplasm, 27.5%; SUMP, 7.5%; SM, 2.5%; and malignant, 12.4%. Histopathologic follow-up was available for 237 cases (49.7%). The ROMs were as follows: nondiagnostic, 5.9%; nonneoplastic, 9.1%; AUS, 35.7%; benign neoplasm, 3.3%; SUMP, 31.8%; SM, 100%; and malignant, 100%. Mucoepidermoid carcinoma was the most common malignancy (18 of 237; 7.6%), and it was followed by acinic cell carcinoma (16 of 237; 6.8%). Pleomorphic adenoma was the most common benign neoplasm (95 of 237; 40.1%). CONCLUSIONS: The MSRSGC can be reliably applied to pediatric salivary gland FNA. The ROM of each MSRSGC category in pediatric salivary gland FNA is relatively similar to the ROM of each category in adult salivary gland FNA, although the reported rates for the different MSRSGC categories are variable across institutions.

The dynamic nature of interpersonal conflict and psychological strain in extreme work settings.

Humanity will mount interplanetary exploration missions within the next two decades, supported by a growing workforce operating in isolated, confined, and extreme (ICE) conditions of space. How will future space workers fare in a closed social world while subjected to persistent stressors? Using a sample of 32 participants operating in ICE conditions over the course of 30-45 days, we developed and tested a dynamic model of conflict and strain. Drawing on conservation of resources (COR) theory, we investigated reciprocal relationships between different forms (i.e., task and relationship) of conflict, and between conflict and strain. Results demonstrated evidence for a resource threat feedback loop as current-day task conflict predicted next-day relationship conflict and current-day relationship conflict predicted next-day task conflict. Additionally, results indicated support for a resource loss feedback loop as current-day relationship conflict predicted next-day strain, and current-day strain predicted next-day relationship conflict. Moreover, we found that job conditions affected these associations as current-day relationship conflict was more associated with next-day task conflict when next-day workload was high, but not when next-day workload was low. Similarly, current-day relationship conflict was more associated with next-day strain when next-day workload was high; however, this association decreased when next-day workload was low. Therefore, the results suggest that workload plays a critical role in weakening the effect of these spirals over time, and suggests that targeted interventions (e.g., recovery days) can help buffer against the negative impact of relationship conflict on strain and decrease the extent that relationship conflict spills over into task disputes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: July 2021 update on postdischarge thromboprophylaxis.

BACKGROUND: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19 who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the grading of recommendations assessment, development, and evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation against the use of outpatient anticoagulant prophylaxis in patients with COVID-19 who are discharged from the hospital and who do not have suspected or confirmed VTE or another indication for anticoagulation. CONCLUSIONS: This recommendation was based on very low certainty in the evidence, underscoring the need for high-quality randomized controlled trials assessing the role of postdischarge thromboprophylaxis. Other key research priorities include better evidence on assessing risk of thrombosis and bleeding outcomes in patients with COVID-19 after hospital discharge.

Inclusive LGBTQIA+ healthcare: An interprofessional case-based experience for cultural competency awareness.

Introduction: Lesbian, Gay, Bi-sexual, Transgender, Questioning, Intersex, and Asexual (LGBTQIA+) patients report experiences of discrimination within healthcare settings due to a lack of provider knowledge and biases of healthcare workers. There is an identified need among all health professions to provide more culturally competent healthcare for this community. Early interventions during healthcare profession training programs may be effective to address this need. The overall goal of this study was to assess the educational impact of an active learning session that was specifically designed to enhance LGBTQIA+ cultural competency awareness using an interprofessional setting. Methods: This 2-year study involved students from 16 healthcare professional programs joining virtually to form interprofessional teams. A small group case-based learning approach was used and included pre/post-activity surveys to measure the change in student attitude and confidence, as well as the change in perception of the importance of the activity. Results: Results indicate an increase in perception of importance (p < 0.005) and in overall level of confidence (p < 0.001) with respect to LGBTQIA+ issues post-session. Key themes established through the session represent an overall recognition of the importance of interprofessional education and awareness of LGBTQIA+ healthcare needs. Discussion: The results demonstrate the effectiveness of a case-based approach for enhancing cultural competency awareness across different healthcare professions programs. This session also provided an interprofessional learning environment to allow multiple healthcare professions program students to interact and share perspectives. The positive impact of this intervention in a highly collaborative virtual learning environment also highlights that this immersive active learning approach that can be adopted across different programs and institutions.

Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48.

Dysregulated mitochondrial function is a hallmark of immune-mediated inflammatory diseases. Cytochrome c oxidase (CcO), which mediates the rate-limiting step in mitochondrial respiration, is remodeled during development and in response to changes of oxygen availability, but there has been little study of CcO remodeling during inflammation. Here, we describe an elegant molecular switch mediated by the bifunctional transcript C15orf48, which orchestrates the substitution of the CcO subunit NDUFA4 by its paralog C15ORF48 in primary macrophages. Expression of C15orf48 is a conserved response to inflammatory signals and occurs in many immune-related pathologies. In rheumatoid arthritis, C15orf48 mRNA is elevated in peripheral monocytes and proinflammatory synovial tissue macrophages, and its expression positively correlates with disease severity and declines in remission. C15orf48 is also expressed by pathogenic macrophages in severe coronavirus disease 2019 (COVID-19). Study of a rare metabolic disease syndrome provides evidence that loss of the NDUFA4 subunit supports proinflammatory macrophage functions.

Attitudes and Knowledge of Medical Students Towards Healthcare for Lesbian, Gay, Bisexual, and Transgender Seniors: Impact of a Case-Based Discussion With Facilitators From the Community.

BACKGROUND:  Lesbian, gay, bisexual, and transgender (LGBT) seniors are generally a medically underserved population that faces unique healthcare challenges. When compared to younger patients, LGBT seniors are at a greater risk for social isolation and have higher rates of smoking, disability, physical and mental distress, and lack of access to healthcare services. They are often reluctant to discuss their sexual orientations and gender identities with healthcare providers due to fear of discrimination and receiving inferior care based on prior unsatisfactory experiences with untrained or insensitive healthcare providers. Furthermore, recent research has revealed that only about 50% of primary care providers indicated confidence in providing culturally competent LGBT healthcare, highlighting the need for more LGBT proficiency training in medical school curricula. OBJECTIVES: The aim of this study was to provide early intervention training to first-year medical students regarding best practices for equitable healthcare for LGBT seniors through integrative, small group, case-based discussions. The impact of this activity on the knowledge and attitudes of medical students regarding LGBT healthcare was also assessed. METHODS: First-year medical students participated in a two-hour small group, case-based discussion. Each group consisted of seven to eight students with one of seven facilitators who were invited members of the LGBT community. Students were provided with two clinical case scenarios related to treatment of LGBT senior patients. Students were given a pre/post-session knowledge and attitude survey to assess the impact of the session on their attitudes and understanding of the importance of providing equitable healthcare to LGBT patients. A rubric was also used by facilitators to evaluate level of student engagement and professionalism. RESULTS: A total of 51 first-year medical students attended the session and 38 (74.5%) completed the pre/post surveys. There was diverse representation in our student demographic with 5.2% of respondents identifying as LGBT. Survey results showed a significant increase in knowledge confidence and attitudes following the session. Students' attitudes regarding determinants of health status changed significantly for nine of the 13 (69%) survey items. In addition, their confidence in knowledge regarding healthcare barriers, health issues, and practices for LGBT culturally competent care significantly increased post-session. Data from our assessment rubrics also show that students were highly professional and engaged with the LGBT facilitators. CONCLUSION: Our study provides some evidence that case-based training of medical students regarding issues that affect health of LGBT seniors can improve attitudes and sensitize them to the unique needs of this population. Through this activity, the students indicated their desire to learn more about the topics covered and to receive further training in this field of study. While the study was somewhat limited by a small participant number, the significance of the data demonstrates the effectiveness of the approach involving members of the LGBT community as facilitators. Future work with these students as part of a longitudinal curriculum will include additional LGBT proficiency training to be offered in the subsequent blocks of instruction. Additionally, this intervention could potentially be adapted by other medical schools.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate-intensity anticoagulation in critically ill patients.

BACKGROUND: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021. RESULTS: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. CONCLUSIONS: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk.

Three-Dimensional Modeling of the Structural Microenvironment in Post-Traumatic War Wounds.

BACKGROUND: The development of post-traumatic heterotopic ossification (HO) is a common, undesirable sequela in patients with high-energy (war-related) extremity injuries. While inflammatory and osteoinductive signaling pathways are known to be involved in the development and progression of post-traumatic HO, features of the structural microenvironment within which the ectopic bone begins to form remain poorly understood. Thus, increasing our knowledge of molecular and structural changes within the healing wound may help elucidate the pathogenesis of post-traumatic HO and aid in the development of specific treatment and/or prevention strategies. METHODS: In this study, we performed high-resolution microscopy and biochemical analysis of tissues obtained from traumatic war wounds to characterize changes in the structural microenvironment. In addition, using an electrospinning approach, we modeled this microenvironment to reconstitute a three-dimensional type I collagen scaffold with non-woven, randomly oriented nanofibers where we evaluated the performance of primary mesenchymal progenitor cells. RESULTS: We found that traumatic war wounds are characterized by a disorganized, densely fibrotic collagen I matrix that influences progenitor cells adhesion, proliferation and osteogenic differentiation potential. CONCLUSION: Altogether, these results suggest that the structural microenvironment present in traumatic war wounds has the potential to contribute to the development of post-traumatic HO. Our findings may support novel treatment strategies directed towards modifying the structural microenvironment after traumatic injury.

Incidence and Risk Factors of Acute Patellar Tendon Rupture, Repair Failure, and Return to Activity in the Active-Duty Military Population.

BACKGROUND: Patellar tendon ruptures have a reported incidence of 0.68 per 100,000 person-years in the general population. The epidemiology of surgically treated patellar tendon ruptures in the US military has yet to be reported, which would provide opportunity for identification of risk factors for these otherwise healthy and active patients. PURPOSE: To determine the incidence of patellar tendon rupture in the Military Health System (MHS) population and to analyze demographic patterns, surgical fixation methods, and rerupture rates. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: We utilized the MHS Data Repository (MDR) to identity active-duty military servicemembers surgically treated for patellar tendon rupture between 2010 and 2015. Records were reviewed for demographic information, injury characteristics, fixation technique, and occurrence of rerupture. Risk factors for rupture were calculated using Poisson regression based on population counts and demographic data obtained in the MDR. Risk factors for rerupture and return to duty were analyzed via univariate analysis and multivariate regression. RESULTS: A total of 504 operatively treated primary patellar tendon repairs in 483 patients were identified, with an overall incidence of 6 per 100,000 person-years. Mean age was 33.6 years (range, 17-54 years) and 98% of patients were male. Fixation method was 81% bone tunnels and 7% suture anchors, and 12% were unknown. Black race had a higher relative rate ratio for rupture compared with the race categories White (9.21; P < .0001) and Other (3.27; P < .0001). The rupture rate was higher in 35- to 44-year-old patients compared with those aged 18 to 24 years (P < .0001), 25 to 34 years (P < .0001), and 45 to 64 years (P = .004). Return to full previous level of activity occurred in 75.8% of patients, 14.6% returned to activity with limitations, and 9.5% were medically separated. The rerupture rate was 3%. Fixation method, tobacco usage, body mass index, and race were not significant risk factors for rerupture. CONCLUSION: The incidence of patellar tendon rupture in the US military population is substantially higher than has been reported in the civilian population. Among military personnel, men, Black servicemembers, and those aged 35 to 44 years were at highest risk for patellar tendon rupture. Three-quarters of patients were able to return to full activity without limitations. The rerupture rate was low and unaffected by fixation method.

Compliance with American College of Chest Physicians (ACCP) recommendations for thromboembolic prophylaxis in the intensive care unit: a level I trauma center experience.

BACKGROUND: Recommendations are for nearly universal venous thromboembolism (VTE) prophylaxis in critically ill hospitalized patients because of their well-recognized risks. In those intensive care units (ICUs) where patient care is more uniformly directed, it may be expected that VTE prophylaxis would more closely follow this standard over units that are less uniform, such as open-model ICUs. METHODS: This was a retrospective cohort study on all patients aged 18+ admitted to an open ICU between 6/1/2017 and 5/31/2018. Patients were excluded if they had instructions to receive comfort measures only or required therapeutic anticoagulant administration. Prophylaxis administration practices, including administration of mechanical and/or pharmacologic prophylaxis and delayed (≥48 h post-ICU admission) initiation of pharmacologic prophylaxis, were compared between patients admitted to the ICU by the trauma service versus other departments. Root causes for opting out of pharmacological prophylaxis were documented and compared between the two study groups. RESULTS: One-hundred two study participants were admitted by the trauma service, and 98 were from a non-trauma service. Mechanical (98% trauma vs. 99% non-trauma, P = 0.99) and pharmacologic (54% vs. 44%, P = 0.16) prophylaxis rates were similar between the two admission groups. The median time from ICU admission to pharmacologic prophylaxis initiation was 53 h for the trauma service and 10 h for the non-trauma services (P ≤ 0.01). In regression analyses, trauma-service admission (odds ratio (OR) = 2.88, 95% confidence interval (CI) 1.21-6.83) and increasing ICU length of stay (OR = 1.13, 95% CI 1.05-1.21) were independently associated with pharmacologic prophylaxis use. Trauma-service admission (OR = 8.30, 95% CI 2.18-31.56) and increasing hospital length of stay (OR = 1.15, 95% CI 1.03-1.28) were independently associated with delayed prophylaxis initiation. CONCLUSIONS: Overall, the receipt of VTE prophylaxis of any type was close to 100%, due to the nearly universal use of mechanical compression devices among ICU patients in this study. However, when examining pharmacologic prophylaxis specifically, the rate was considerably lower than is currently recommended: 54% among the trauma services and 44% among non-trauma services.

Identifying optimal COVID-19 testing strategies for schools and businesses: Balancing testing frequency, individual test technology, and cost.

BACKGROUND: COVID-19 test sensitivity and specificity have been widely examined and discussed, yet optimal use of these tests will depend on the goals of testing, the population or setting, and the anticipated underlying disease prevalence. We model various combinations of key variables to identify and compare a range of effective and practical surveillance strategies for schools and businesses. METHODS: We coupled a simulated data set incorporating actual community prevalence and test performance characteristics to a susceptible, infectious, removed (SIR) compartmental model, modeling the impact of base and tunable variables including test sensitivity, testing frequency, results lag, sample pooling, disease prevalence, externally-acquired infections, symptom checking, and test cost on outcomes including case reduction and false positives. FINDINGS: Increasing testing frequency was associated with a non-linear positive effect on cases averted over 100 days. While precise reductions in cumulative number of infections depended on community disease prevalence, testing every 3 days versus every 14 days (even with a lower sensitivity test) reduces the disease burden substantially. Pooling provided cost savings and made a high-frequency approach practical; one high-performing strategy, testing every 3 days, yielded per person per day costs as low as $1.32. INTERPRETATION: A range of practically viable testing strategies emerged for schools and businesses. Key characteristics of these strategies include high frequency testing with a moderate or high sensitivity test and minimal results delay. Sample pooling allowed for operational efficiency and cost savings with minimal loss of model performance.

Automated solubility screening platform using computer vision.

Solubility screening is an essential, routine process that is often labor intensive. Robotic platforms have been developed to automate some aspects of the manual labor involved. However, many of the existing systems rely on traditional analytic techniques such as high-performance liquid chromatography, which require pre-calibration for each compound and can be resource consuming. In addition, automation is not typically end-to-end, requiring user intervention to move vials, establish analytical methods for each compound and interpret the raw data. We developed a closed-loop, flexible robotic system with integrated solid and liquid dosing capabilities that relies on computer vision and iterative feedback to successfully measure caffeine solubility in multiple solvents. After initial researcher input (<2 min), the system ran autonomously, screening five different solvent systems (20-80 min each). The resulting solubility values matched those obtained using traditional manual techniques.