Search

Abstract Background Healthcare curricula need summative assessments relevant to and representative of clinical situations to best select and train learners. Simulation provides multiple benefits with a growing literature base proving its utility for training in a formative context. Advancing to the next step, “the use of simulation for summative assessment” requires rigorous and evidence-based development because any summative assessment is high stakes for participants, trainers, and programs. The first step of this process is to identify the baseline from which we can start. Methods First, using a modified nominal group technique, a task force of 34 panelists defined topics to clarify the why, how, what, when, and who for using simulation-based summative assessment (SBSA). Second, each topic was explored by a group of panelists based on state-of-the-art literature reviews technique with a snowball method to identify further references. Our goal was to identify current knowledge and potential recommendations for future directions. Results were cross-checked among groups and reviewed by an independent expert committee. Results Seven topics were selected by the task force: “What can be assessed in simulation?”, “Assessment tools for SBSA”, “Consequences of undergoing the SBSA process”, “Scenarios for SBSA”, “Debriefing, video, and research for SBSA”, “Trainers for SBSA”, and “Implementation of SBSA in healthcare”. Together, these seven explorations provide an overview of what is known and can be done with relative certainty, and what is unknown and probably needs further investigation. Based on this work, we highlighted the trustworthiness of different summative assessment-related conclusions, the remaining important problems and questions, and their consequences for participants and institutions of how SBSA is conducted. Conclusion Our results identified among the seven topics one area with robust evidence in the literature (“What can be assessed in simulation?”), three areas with evidence that require guidance by expert opinion (“Assessment tools for SBSA”, “Scenarios for SBSA”, “Implementation of SBSA in healthcare”), and three areas with weak or emerging evidence (“Consequences of undergoing the SBSA process”, “Debriefing for SBSA”, “Trainers for SBSA”). Using SBSA holds much promise, with increasing demand for this application. Due to the important stakes involved, it must be rigorously conducted and supervised. Guidelines for good practice should be formalized to help with conduct and implementation. We believe this baseline can direct future investigation and the development of guidelines.

ObjectiveRheumatoid Arthritis (RA) is a progressive and systemic autoimmune disorder associated with chronic and destructive joint inflammation. The hallmarks of joint synovial inflammation are cellular proliferation, extensive neoangiogenesis and infiltration of immune cells, including macrophages. In vitro approaches simulating RA synovial tissue are crucial in preclinical and translational research to evaluate novel diagnostic and/or therapeutic markers. Two-dimensional (2D) settings present very limited in vivo physiological proximity as they cannot recapitulate cell-cell and cell-matrix interactions occurring in the three-dimensional (3D) tissue compartment. Here, we present the engineering of a spheroid-based model of RA synovial tissue which mimics 3D interactions between cells and pro-inflammatory mediators present in the inflamed synovium.MethodsSpheroids were generated by culturing RA fibroblast-like-synoviocytes (RAFLS), human umbilical vein endothelial cells (ECs) and monocyte-derived macrophages in a collagen-based 3D scaffold. The spheroids were cultured in the presence or absence of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (bFGF) or RA synovial fluid (SF). Spheroid expansion and cell migration were quantified for all conditions using confocal microscopy and digital image analysis.ResultsA novel approach using machine learning was developed to quantify spheroid outgrowth and used to reexamine the existing spheroid-based model of RA synovial angiogenesis consisting of ECs and RAFLS. A 2-fold increase in the spheroid outgrowth ratio was demonstrated upon VEGF/bFGF stimulation (p

Unmanned aerial vehicles (UAVs) provide a cost-effective way to fill in gaps between surface in situ observations and remotely sensed data from space. In this study, a novel portable CO2 measuring system suitable for operations on board small-sized UAVs has been developed and validated. It is based on a low-cost commercial nondispersive near-infrared (NDIR) CO2 sensor (Senseair AB, Sweden), with a total weight of 1058 g, including batteries. The system performs in situ measurements autonomously, allowing for its integration into various platforms. Accuracy and linearity tests in the lab showed that the precision remains within ± 1 ppm (1σ) at 1 Hz. Corrections due to temperature and pressure changes were applied following environmental chamber experiments. The accuracy of the system in the field was validated against a reference instrument (Picarro, USA) on board a piloted aircraft and it was found to be ± 2 ppm (1σ) at 1 Hz and ± 1 ppm (1σ) at 1 min. Due to its fast response, the system has the capacity to measure CO2 mole fraction changes at 1 Hz, thus allowing the monitoring of CO2 emission plumes and of the characteristics of their spatial and temporal distribution. Details of the measurement system and field implementations are described to support future UAV platform applications for atmospheric trace gas measurements.

Background: Cephalosporins are the cornerstone of cardiac device infection prophylaxis. Owing to fears of cross-reactivity, penicillin-allergic patients are exposed to potentially more-toxic drugs, with decreased efficacy. We evaluated the safety of a cefazolin test dose (CTD) in self-reported penicillin-allergic patients. Methods: In this single-centre study, we evaluated consecutive patients with chart documentation of penicillin allergy undergoing cardiac device implantation, over a 2-year period. A CTD was performed if no cephalosporin allergy or severe anaphylactic reaction to penicillin had been documented. Patients were given 2 doses of 100 mg IV cefazolin, and if no allergic reaction occurred after 5 minutes, the full dose (1800 mg) was administered in the electrophysiology laboratory just before the implantation procedure. Results: A total of 2200 patients were included. The frequency of reported penicillin allergy was 9.3% (n = 204). In 80% of cases, the type of allergic reaction was not reported in medical notes or was unknown by the patient. A CTD was performed in 67.6% of patients with a penicillin allergy (n = 138). A total of 5 adverse events occurred (3.6% of patients [95% confidence interval, 1.1%-6.1%]) — 4 skin rashes and 1 tongue edema. These 5 patients became asymptomatic after antihistaminic and corticosteroid IV treatment. Even if the test dose was negative, 79% of patients also were administered vancomycin before the procedure, as it requires a 1-hour infusion prior to the CTD in the implantation procedure room. Conclusion: A CTD in most penicillin-allergic patients appears to be safe and allows its use per recommended guidelines. Résumé: Contexte: Les céphalosporines sont la pierre angulaire de la prophylaxie des infections des dispositifs cardiaques. En raison du risque appréhendé de réactivité croisée, les patients allergiques à la pénicilline se trouvent exposés à des médicaments potentiellement plus toxiques, qui s’avèrent aussi moins efficaces. Nous avons évalué l’innocuité d’une dose d’essai de céfazoline chez des patients qui s’étaient dits allergiques à la pénicilline. Méthodologie: Dans cette étude monocentrique, nous avons suivi pendant deux ans des patients consécutifs dont le dossier médical faisait état d’une allergie à la pénicilline et chez qui un dispositif cardiaque devait être implanté. Une dose d’essai de céfazoline a été administrée aux patients sans antécédents documentés d’allergie aux céphalosporines ou de réaction anaphylactique sévère à la pénicilline. Deux doses de 100 mg de céfazoline ont été administrées par voie intraveineuse. En l’absence de réaction allergique après cinq minutes, les patients recevaient la dose complète (1 800 mg) au laboratoire d’électrophysiologie juste avant l’implantation du dispositif cardiaque. Résultats: Au total, 2 200 patients ont été inscrits à l’étude. Le taux de signalement de l’allergie à la pénicilline était de 9,3 % (n = 204). Dans 80 % des cas, le type de réaction allergique n’a pas été précisé dans les notes médicales ou était inconnu du patient. Une dose d’essai de céfazoline a été administrée à 67,6 % des patients allergiques à la pénicilline (n = 138). Au total, cinq événements indésirables se sont produits (3,6 % des patients [intervalle de confiance à 95 % : 1,1-6,1 %]) – quatre éruptions cutanées et un œdème de la langue. Les cinq patients touchés par ces événements sont devenus asymptomatiques après avoir reçu un antihistaminique et un corticostéroïde par voie intraveineuse. Même en l’absence de réaction allergique à la dose d’essai, 79 % des patients ont reçu de la vancomycine avant l’intervention, cet agent devant être administré par perfusion durant une heure avant la dose d’essai de céfazoline dans la salle d’intervention. Conclusion: Chez la plupart des patients allergiques à la pénicilline, une dose d’essai de céfazoline semble sans danger et permet d’avoir recours à ce médicament conformément aux lignes directrices.

Growth and destruction are central components of the neuronal injury response. Injured axons that are capable of repair, including axons in the mammalian peripheral nervous system and in many invertebrate animals, often regenerate and degenerate on either side of the injury. Here we show that TIR-1/dSarm/SARM1, a key regulator of axon degeneration, also inhibits regeneration of injured motor axons. The increased regeneration in tir-1 mutants is not a secondary consequence of its effects on degeneration, nor is it determined by the NADase activity of TIR-1. Rather, we found that TIR-1 functions cell-autonomously to regulate each of the seemingly opposite processes through distinct interactions with two MAP kinase pathways. On one side of the injury, TIR-1 inhibits axon regeneration by activating the NSY-1/ASK1 MAPK signaling cascade, while on the other side of the injury, TIR-1 simultaneously promotes axon degeneration by interacting with the DLK-1 mitogen-activated protein kinase (MAPK) signaling cascade. In parallel, we found that the ability to cell-intrinsically inhibit axon regeneration is conserved in human SARM1. Our finding that TIR-1/SARM1 regulates axon regeneration provides critical insight into how axons coordinate a multidimensional response to injury, consequently informing approaches to manipulate the response toward repair.

Abstract Background Sharing anonymized/de-identified clinical trial data and publishing research outcomes in scientific journals, or presenting them at conferences, is key to data-driven scientific exchange. However, when data from scientific publications are linked to other publicly available personal information, the risk of reidentification of trial participants increases, raising privacy concerns. Therefore, we defined a set of criteria allowing us to determine and minimize the risk of data reidentification. We also implemented a review process at Takeda for clinical publications prior to submission for publication in journals or presentation at medical conferences. Methods Abstracts, manuscripts, posters, and oral presentations containing study participant information were reviewed and the potential impact on study participant privacy was assessed. Our focus was on direct (participant ID, initials) and indirect identifiers, such as sex, age or geographical indicators in rare disease studies or studies with small sample size treatment groups. Risk minimization was sought using a generalized presentation of identifier-relevant information and decision-making on data sharing for further research. Additional risk identification was performed based on study participant/personnel parameters present in materials destined for the public domain. The potential for participant/personnel identification was then calculated to facilitate presentation of meaningful but de-identified information. Results The potential for reidentification was calculated using a risk ratio of the exposed versus available individuals, with a value above the threshold of 0.09 deemed an unacceptable level of reidentification risk. We found that in 13% of Takeda clinical trial publications reviewed, either individuals could potentially be reidentified (despite the use of anonymized data sets) or inappropriate data sharing plans could pose a data privacy risk to study participants. In 1/110 abstracts, 58/275 manuscripts, 5/87 posters and 3/58 presentations, changes were necessary due to data privacy concerns/rules. Despite the implementation of risk-minimization measures prior to release, direct and indirect identifiers were found in 11% and 34% of the analysed documents, respectively. Conclusions Risk minimization using de-identification of clinical trial data presented in scientific publications and controlled data sharing conditions improved privacy protection for study participants. Our results also suggest that additional safeguards should be implemented to ensure that higher data privacy standards are met.

Western central Africa is atypical of the equatorial domain as the main dry season is cloudier than the rainy seasons. To understand this cloud cover's diurnal evolution, we set up an infrared camera and acquired measurements of the total cloud cover fraction (TCF) and cloud optical depth at Bambidie, Gabon (0°44′30.5″S, 12°58′12.4″E), from May to October 2022. Diurnal variations in TCF can be summarized into four types, mostly discretized through the timing and duration of clouds clearing in the afternoon [early afternoon clearing (EaC), late afternoon clearing (LaC), and clear night (CNi)], while one type [no clearing (NoC)] shows overcast conditions all day long. Meteorological measurements show that NoC days record 50 W m−2 less shortwave incoming surface radiation, resulting in daytime temperatures 1°C lower than the seasonal norm, but 20% more diffuse light and 0.5 mm day−1 less ETo. Conversely, EaC days record 50 W m−2 more shortwave incoming surface radiation, leading to temperatures 1.5°C higher than the seasonal norm, but 40% more direct light. The larger water demand (0.5 mm day−1 more ETo) is partly compensated by more frequent rainfall at nighttime. The satellite estimates of Satellite Application Facilities for supporting Nowcasting and very short-range Forecasting (SAFNWC) capture the TCF variations for most of the four types well. They confirm that TCF is dominated by very low and low clouds whose dissipation in the afternoon and evolution into fractional and cumuliform convective clouds explains the clearings on EaC and LaC days. Satellite estimates also show that the four types of days extracted at Bambidie are representative of a larger-scale cloud cover evolution in western central Africa, with a west–east gradient in the timing of afternoon cloud dissipation. [ABSTRACT FROM AUTHOR]

Aim: The diagnosis of hypertrophic cardiomyopathy (HCM) with moderate hypertrophy is challenging. Hypertensive heart disease (HHD) is the most common differential diagnosis that mimics the LVH of HCM. The aim of this study was to compare the QRS duration in HCM and HHD to create a novel diagnostic tool to identify primary HCM. Methods and results: We conducted an international retrospective multicentre study enrolling patients with true HCM and HHD. A total of 547 individuals with HCM and 139 with HHD were included. The median QRS duration was significantly shorter in HCM than in HHD (88 ms [80–94] vs. 98 ms [88–108]; P < 0.01). Multivariable logistic regression identified for the novel diagnostic HCM (D‐HCM) score: absence of antihypertensive drugs (+2); family history of unexplained sudden death (+2); QRS duration [<95 ms] = +1; maximum wall thickness (mm) [≥17] = +1. A cumulative QRS‐HCM score ≥2 supports the diagnostic certainty of true HCM with a sensitivity of 79%, specificity of 99%, negative predictive value (NPV) of 55%, and positive predictive value (PPV) of 99%. Conclusion: The QRS duration in patient with HCM is significantly shorter compared with patients with HHD‐related LVH. QRS duration can be used as a diagnosis marker to distinguish between HCM and HHD. The D‐HCM score is a novel, simple, and accurate diagnosis tool for HCM patients with mild to moderate phenotypes. [ABSTRACT FROM AUTHOR]

Background: Skin biorevitalization involves multiple intradermal injections to enhance skin quality, but precise dermal targeting can be challenging due to variations in skin thickness smaller, less painful needles with fewer skin reactions are attractive options. Aims: This study evaluates a new Micro‐Needle device's performance and safety in comparison with the classic needle used in skin biorevitalization. Patients/Methods: Subjects with facial and neck skin aging were enrolled. Safety outcomes, including immediate and local tolerability, were assessed. Performance outcomes measured skin radiance, wrinkles and photoaging grade, hydration, subepidermal low echogenic band, dermis thickness, and skin elasticity. Both subjects and investigators recorded Global Aesthetic Improvement Scale scores. Results: Micro‐Needle injections demonstrated superior performance compared to the classic needle, influenced by the specific skin zones and thickness. Micro‐Needle was superior for skin wrinkles at D49 for periorbital zone and nasolabial folds by −14.5% (p = 0.01) and −15% (p = 0.004), respectively, and for neck by 9.6% (p = 0.0008). The Nanosoft device showed a faster improvement for skin hydration at D42 for the cheek zone (p = 0.04) and at D75 for the neck area (p = 0.01); and for skin radiance at D75 (p = 0.03) and at D120 (p = 0.0098). Ex vivo studies confirmed the Micro‐Needle's accuracy in product placement in the dermis. Adverse events were milder with Micro‐Needle and no serious adverse events occurred. Conclusions: Both needles significantly improved skin quality, but Micro‐Needle enhanced the outcomes of skin biorevitalization procedures, particularly in terms of skin wrinkle reduction, elasticity, and overall skin hydration. [ABSTRACT FROM AUTHOR]

Background: Microfracture is one surgical treatment strategy for osteochondral lesions of the talus (OLTs) but results in fibrocartilage repair tissue, which has inferior mechanical properties to native hyaline cartilage. Biological regulation of microfracture has been suggested to improve the quality of cartilage repair in patients. Purpose: To determine if administration of losartan, fisetin, or losartan and fisetin combined can enhance microfracture-mediated cartilage repair of OLTs in a rabbit model. Study Design: Controlled laboratory study. Methods: Four-month-old female rabbits were divided into the following groups (8 rabbits per group): microfracture only (microfracture), microfracture plus losartan (losartan), microfracture plus fisetin (fisetin), and microfracture plus losartan and fisetin (losartan+fisetin). A 2.7-mm osteochondral defect and 4 microfracture holes were created in the talar dome cartilage. The rabbits were administered losartan (10 mg/kg/day), fisetin (20 mg/kg/day), or losartan and fisetin orally until euthanized 12 weeks after surgery. Gross evaluation, micro–computed tomography, histology, and immunohistochemistry evaluations of the osteochondral defects were performed as well as quantitative polymerase chain reaction of capsule tissue and enzyme-linked immunosorbent assay of serum. Results: The losartan and fisetin groups had increased International Cartilage Regeneration & Joint Preservation Society macroscopic scores with improved cartilage repair and enhanced subchondral bone healing compared with the microfracture group. However, the losartan+fisetin group did not show a synergistic effect. O'Driscoll histology scores were higher in the losartan and fisetin groups compared with the microfracture group, while the losartan+fisetin group had a lower score than the losartan, fisetin, and microfracture groups. Collagen type 2 staining revealed organized chondrocytes in the losartan and fisetin groups, but the losartan+fisetin group did not show improvement when compared with other groups. Fisetin treatment decreased catalase and transforming growth factor-β1–activated kinase 1 expression in capsular tissue. Conclusion: Concomitant microfracture and biological regulation, using oral administration of either losartan or fisetin, may improve cartilage healing of OLTs; however, losartan and fisetin combined in the current drug administration regimen does not appear to provide synergistic effects. Clinical Relevance: Oral intake of losartan or fisetin may result in beneficial effects on microfracture-mediated cartilage repair of OLTs. [ABSTRACT FROM AUTHOR]

Conduction disturbances (CDs) are common after transcatheter aortic valve replacement. Continuous improvements in preprocedural planification, implant techniques, and device design have markedly reduced periprocedural complications. However, CDs rate remains in the double-digit range. Because CDs after TAVR are associated with poorer outcomes, seeking a reduction in their occurrence is paramount. Several nonmodifiable and modifiable factors are associated with an increased risk of CDs. Previous right bundle branch block has been shown to have a strong association with pacemaker implant after TAVR. Among the modifiable factors, a lower implantation depth seems to be associated with a higher risk of CDs, and several implant strategies aiming to obtain a higher implant depth have shown promising results. This literature review provides a detailed description of updated evidence about the epidemiology, impact, and preventive and management strategies of CDs after TAVR. Also, based on these updated data, a fast-track protocol CDs management is proposed. [Display omitted] • Conduction disturbances are a frequent adverse event after TAVR, with only a few studies showing permanent pacemaker rates in the 1-digit frame. • Permanent pacemaker implantation and new-onset persistent left bundle branch block are associated with impaired outcomes, including a higher risk of long-term mortality and heart failure hospitalization. • The identification of modifiable factors associated with a higher risk of conduction disturbance appearance has led to the development of refined implantation techniques (high implant depth), leading to a significant reduction of permanent pacemaker implantation. • Future studies are warranted to reduce the incidence of conduction disturbances and also to reduce the burden associated with permanent pacemaker implantation such as the use of conduction system pacing. [ABSTRACT FROM AUTHOR]

Background: Labral repair has become the preferred method for the arthroscopic treatment of acetabular labral tears that are associated with femoroacetabular impingement (FAI) resulting in pain and dysfunction. Labral reconstruction is performed mainly in revision hip arthroscopy but can be utilized in the primary setting for absent or calcified labra. The purpose of this study was to compare the minimum 2-year patient-reported outcomes (PROs) and risk of revision or conversion to arthroplasty between primary labral reconstruction and primary labral repair. Methods: Patients with FAI who underwent primary hip arthroscopy with labral repair or reconstruction performed by the senior author between 2006 and 2018 were identified from a prospectively enrolled patient outcome registry. Exclusion criteria included confounding injuries, dysplasia, prior ipsilateral hip surgery, or a joint space of <2 mm. Patients who were 18 to 80 years old were eligible for inclusion. Multiple regression with inverse propensity score weighting was conducted to estimate the average treatment effect in the treated (ATT) for labral reconstruction versus labral repair with respect to postoperative PROs and the likelihood of subsequent surgery (revision hip arthroscopy or conversion to arthroplasty). PROend points included theHip Outcome Score Activities of Daily Living subscale (HOS-ADL), modified Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index total score (WOMAC), 12-Item Short Form Health Survey Physical Component Summary score (SF-12 PCS), and patient satisfaction. Results: A total of 150 hips undergoing primary labral reconstruction and 998 hips undergoing primary labral repair were included. The median follow-up time was 5.3 years in the reconstruction group and 5.8 years in the repair group. Compared with labral repair, labral reconstruction was associated with a higher risk of conversion to total hip arthroplasty (THA) (20% versus 7%; adjusted odds ratio, 3.2; 95% confidence interval [CI], 1.2 to 8.8; p = 0.024). Inverse propensity score-weighted multiple regression estimated a significant negative effect of labral reconstruction, relative to labral repair, on the postoperative values for the HOS-ADL (ATT, 23.3; 95% CI, 25.8 to 20.7; p = 0.012) and WOMAC (ATT, 2.6; 95% CI, 0.1 to 5.2; p = 0.044). Conclusions: Compared with primary labral reconstruction, primary labral repair resulted in better postoperative HOS-ADL and WOMAC values and decreased conversion to THA. These findings were demonstrated in both the unadjusted group comparisons and multivariable modeling. These data support the use of labral repair in the primary setting of labral tears and the reservation of labral reconstruction for more advanced labral pathology or for revision cases. [ABSTRACT FROM AUTHOR]