The Effect of miRNA-Modified Exosomes in Animal Models of Spinal Cord Injury: A meta-Analysis

Background: Spinal cord injury (SCI) is currently not completely curable. Exosomes have been widely used in preclinical studies of spinal cord injury. Here, in this meta-analysis, we focused on evaluating the overall efficacy of therapies based on miRNA-modified exosomes on functional recovery in animal models of SCI.Methods: PubMed, embase and Web of Science library databases were searched. Relevant literature was included, and the random effects model was used to assess the overall effect of the intervention, with outcomes expressed as SMD. The primary outcome included motor function scores. Risk of bias (ROB) was assessed using the ROB tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). R version 4.1.1software and Review Manager software were used for meta-analysis.Results: A total of 11 preclinical studies were included. The meta-analysis revealed that miRNA-modified exosome therapy was effective in improving motor function scores compared with exosomes alone or control therapy (standardized mean difference: 4.21; 95% confidence interval: 3.39–5.04). There was significant asymmetry in the funnel plot, and trim-and-fill analysis revealed four unpublished studies of motor scores. The quality of all included studies was evaluated with SYRCLE’s ROB tool. The SCI model, administration time and dose had an impact on the effect of the treatment.Conclusion: MiRNA-modified exosomes have shown great potential in the treatment of SCI. Moreover, the efficacy of miRNA-modified exosomes was superior to that of exosomes alone.

The AEQ-S: A short version of the Achievement Emotions Questionnaire

The Achievement Emotions Questionnaire (AEQ) is a well-established instrument for measuring achievement emotions in educational research and beyond. Its popularity rests on the coverage of the component structure of various achievement emotions across different academic settings. However, this broad conceptual scope requires the administration of 6 to 12 items per scale (Mdn = 10), which limits the applicability of the AEQ in empirical studies that necessitate brief administration times. We therefore developed the AEQ-S, a short version of the AEQ, with only 4 items per scale that nevertheless maintain the conceptual scope of the instrument. We validated the AEQ-S based on a reanalysis of Pekrun, Goetz, Frenzel, Barchfeld, and Perry's (2011) dataset (N = 389 university students) and by administering them to a new and independent validation sample (N = 471 university students). Despite their brevity, the AEQ-S scales achieved satisfactory reliability and correlated substantially with the original AEQ scales. Moreover, structural relationships and intercorrelations between the scales and their relations with external measures of antecedents and outcomes of achievement emotions were highly similar for the AEQ-S and AEQ scales. These findings suggest that the AEQ-S is a suitable substitute for the AEQ when administration time is limited.

Evaluation of electronic medication management systems on inpatient omitted dose rates at 2 acute metropolitan hospitals

Rationale, aim and objectives: Medication error is common and the most common form of administration error is omission. Implementation of Electronic Medication Management systems (eMMS) has been hypothesized to decrease the rate of omitted doses due to the creation of a number of forcing functions and decision support tools however there is limited evidence currently available in the literature to support this assumption. This study therefore aims to ascertain if implementation of eMMS at 2 acute metropolitan hospitals reduces the rate of omitted doses Method: A retrospective cohort study was undertaken pre and post implementation of eMMS. Patients meeting eligibility criteria had all medication charts from their admission reviewed and an omitted dose rate calculated. For each omitted dose identified; medication name, imprest availability, dispensing history, administration time and frequency were recorded. Results: 386 patients met eligibility criteria for this study (11,796 opportunities for omission). The implementation of eMMS was associated with a significant reduction in omitted doses (3.6% vs 1.8% p<0.01). Benefit was not consistent among subgroups. eMMS implementation at the hospital with the higher baseline omitted dose rate was associated with a significant reduction in omitted doses (5.8% vs 0.9% p<0.01) but not at the hospital with a lower baseline rate (2.7% vs 2.4% p=0.3). The most common times for an omitted dose to occur were 0800 (33%) and 2000 (18%). The most common frequencies for an omitted dose were daily (35%) and twice daily (32%). Conclusion: The introduction of eMMS was associated with a decrease rate of omitted doses. Greatest benefit is likely to occur in areas with a high baseline rate of omission.

Strain-, Sex-, and Time-Dependent Antidepressant-like Effects of Cannabidiol

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behavior. Moreover, only a few studies investigated the effect of CBD in female rodents. Therefore, we aimed to (i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects and (ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect 1 h post injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at 1 h and decreasing it at 2 h. In conclusion, strain, sex, and administration time affect CBD’s behavioral response to rodents exposed to tests predictive of antidepressant effects.

Delayed Administration of Nafamostat Mesylate Inhibits Thrombin-Mediated Blood-Spinal Cord Barrier Breakdown During Acute Spinal Cord Injury in Rats

Background: Nafamostat mesylate (NM), an FDA-approved serine protease inhibitor, exerts anti-neuroinflammation and neuroprotective effect on rat spinal cord injury (SCI). However, the time window for NM administration after SCI as well as its underlying mechanism remains unclear. Methods: A series of different first administration time points of NM was tested on rat contusive SCI model. The optimal time window of NM was screened by evaluating hindlimb locomotion and electrophysiology. We performed western blot and immunofluorescence to evaluate the drug target thrombin as well as its downstream Protease activated receptor 1 (PAR-1), and matrix metalloproteinase-9 (MMP9). Enzyme activity assay was used to test thrombin activity. The permeability of blood-spinal cord barrier (BSCB) was assessed by Evans Blue leakage. The infiltration of peripheral inflammatory cell was observed by immunofluorescence.Results: The optimal administration time window of NM was 2-12 h. The thrombin specific inhibitor, Argatroban, had similar pattern. The temporal expression pattern of thrombin peaked at 12 hours and returned to normal level at 7 days post SCI. PAR-1, the thrombin receptor, was observed a significant upregulation after SCI. MMP9, downstream of PAR-1, was also increased along with thrombin and PAR1. The most significant increase of thrombin expression was detected in vascular endothelial cells (ECs). NM significantly downregulated the thrombin and MMP9 expression as well as thrombin activity in the spinal cord, especially in ECs. NM administration at 2-12 h after SCI could inhibit the leakage of Evans blue in the epicenter and upregulate tight junction proteins (TJPs) expression. 8 h administration of NM effectively inhibited the infiltration of peripheral macrophages in the acute SCI. Conclusions: Our study provided preclinical data of NM administration time window in SCI model, which is clinically relevant in the acute SCI. We elucidated the protective mechanism of NM through BSCB protection and anti-neuroinflammation via thrombin intervention.

A size and space structured model of tumor growth describes a key role for protumor immune cells in breaking equilibrium states in tumorigenesis

Switching from the healthy stage to the uncontrolled development of tumors relies on complicated mechanisms and the activation of antagonistic immune responses, that can ultimately favor the tumor growth. We introduce here a mathematical model intended to describe the interactions between the immune system and tumors. The model is based on partial differential equations, describing the displacement of immune cells subjected to both diffusion and chemotactic mechanisms, the strength of which is driven by the development of the tumors. The model takes into account the dual nature of the immune response, with the activation of both antitumor and protumor mechanisms. The competition between these antagonistic effects leads to either equilibrium or escape phases, which reproduces features of tumor development observed in experimental and clinical settings. Next, we consider on numerical grounds the efficacy of treatments: the numerical study brings out interesting hints on immunotherapy strategies, concerning the role of the administered dose, the role of the administration time and the interest in combining treatments acting on different aspects of the immune response. Such mathematical model can shed light on the conditions where the tumor can be maintained in a viable state and also provide useful hints for personalized, efficient, therapeutic strategies, boosting the antitumor immune response, and reducing the protumor actions.

Evaluation of Available Cognitive Tools Used to Measure Mild Cognitive Decline: A Scoping Review

Cognitive decline is a broad syndrome ranging from non-pathological/age-associated cognitive decline to pathological dementia. Mild cognitive impairment MCI) is defined as the stage of cognition that falls between normal ageing and dementia. Studies have found that early lifestyle interventions for MCI may delay its pathological progression. Hence, this review aims to determine the most efficient cognitive tools to discriminate mild cognitive decline in its early stages. After a systematic search of five online databases, a total of 52 different cognitive tools were identified. The performance of each tool was assessed by its psychometric properties, administration time and delivery method. The Montreal Cognitive Assessment (MoCA, n = 15), the Mini-Mental State Examination (MMSE, n = 14) and the Clock Drawing Test (CDT, n = 4) were most frequently cited in the literature. The preferable tools with all-round performance are the Six-item Cognitive Impairment Test (6CIT), MoCA (with the cut-offs of ≤24/22/19/15.5), MMSE (with the cut-off of ≤26) and the Hong Kong Brief Cognitive Test (HKBC). In addition, SAGE is recommended for a self-completed survey setting whilst a 4-point CDT is quick and easy to be added into other cognitive assessments. However, most tools were affected by age and education levels. Furthermore, optimal cut-off points need to be cautiously chosen while screening for MCI among different populations.

Clinical Administration Characteristics of Subcutaneous and Intravenous Administration of Daratumumab in Multiple Myeloma Patients at Mayo Clinic

Introduction: Daratumumab is approved across lines of therapy for multiple myeloma (MM) by subcutaneous administration (DARA SC) or by intravenous administration (DARA IV). In clinical studies, the administration time ranges from 3-5 minutes for DARA SC versus 3-7 hours for DARA IV, and DARA SC is associated with reduced rates of administration-related reactions (ARRs). These characteristics of DARA SC are associated with benefits for clinics in terms of safety and clinic time. We previously reported DARA administration characteristics at Mayo Clinic infusion centers: DARA SC had shorter total clinic and total chair times compared with DARA IV, and DARA SC was associated with very low rates of ARR-related events (Soefje S, et al. EHA Library. 2021). Based upon this analysis, the treatment plan was modified to reduce the mandated observation time for DARA SC to improve clinic efficiency. Here, we describe updated clinical administration characteristics for DARA SC at Mayo Clinic infusion centers before and after the reduction in procedure-mandated observation time, versus DARA IV, using a novel empirical data extraction approach from Electronic Health Records (EHR). Methods: Patients ≥18 years of age with an ICD-9/10 diagnosis code of MM and a first DARA treatment between April 5, 2017 and June 22, 2021 were identified in Mayo Clinic's EHR database. Data were extracted using a scheduling and pharmacy software that tracked patient movement through appointments at a Mayo Clinic infusion center. On May 3, 2021, the Mayo treatment plan was amended to shorten the mandated post-administration observation time for DARA SC from 4 to 2 hours for Dose 1 and from 1 hour to 30 minutes for Doses 2 and 3, with no mandated observation time for Doses 4+. In this analysis, data were captured for patients initiating DARA IV throughout the defined treatment window. For DARA SC, data were captured for patients starting DARA SC therapy on the initial treatment plan (before May 3, 2021; DARA SC initial) and after the change to shorten the mandated post-administration observation time for DARA SC (after May 3, 2021; DARA SC shortened). Time-based measures included: total clinic time (check-in time through patient check-out); total chair time (time from infusion room entry to infusion room exit or check-out time, including order review, pharmacy preparation time, and post-administration observation time); and observation time (time from the end of medication administration to infusion room exit or patient check-out). The medication administration time documented for DARA SC was 0 minutes due to the default duration for SC injections in the EHR. Results: In total, 755 (DARA IV, n=586; DARA SC initial, n=145; DARA SC shortened, n=24) patients received DARA treatment for MM. For all doses combined, the median total clinic time was 2.9 hours shorter for DARA SC compared with DARA IV (DARA IV, 4.9 hrs; DARA SC initial, 2.0 hrs). The median total clinic time for DARA SC and DARA IV was highest at Dose 1 (DARA IV, 9.5 hrs; DARA SC initial, 6.1 hrs; DARA SC shortened, 4.4 hrs) and lower for subsequent doses (Dose 4+: DARA IV, 4.6 hrs; DARA SC initial, 1.7 hrs; DARA SC shortened, 1.6 hrs; Figure). Similarly, the median total chair time was 2.7 hours shorter in the DARA SC group compared with the DARA IV group for all doses combined (DARA IV, 4.1 hrs; DARA SC initial, 1.4 hrs). The median total chair time for DARA SC and DARA IV was highest at Dose 1 (DARA IV, 8.8 hrs; DARA SC initial, 5.6 hrs; DARA SC shortened, 3.9) and lower for subsequent doses (Dose 4+: DARA IV, 3.7 hrs; DARA SC initial, 1.1 hrs; DARA SC shortened, 1.1 hrs). Conclusion: Marked reductions in the amount of time spent both in clinic and in chair were observed with DARA SC compared with DARA IV, with additional time savings observed following the Mayo procedure change to reduce the DARA SC mandated observation time. These favorable DARA SC administration characteristics may indicate a reduction in the burden on both clinical resources and patients in Mayo Clinic infusion centers. These results add to the growing body of evidence supporting the use of DARA SC as an efficient and convenient treatment administration option for patients with MM. Figure 1 Figure 1. Disclosures Soefje: Beigene: Consultancy; Pfizer: Speakers Bureau; Janssen: Consultancy, Research Funding. Carpenter: nference Inc.: Current Employment; Janssen: Consultancy. Carlson: nference Inc.: Current Employment; Janssen: Consultancy. Awasthi: nference Inc.: Current Employment, Current holder of individual stocks in a privately-held company; Janssen: Consultancy. Lin: Janssen: Current Employment. Kaila: Janssen Scientific Affairs, LLC: Current Employment. Kayal: nference Inc.: Current Employment; Janssen: Consultancy. Kirkup: nference Inc.: Current holder of individual stocks in a privately-held company, Ended employment in the past 24 months; Path AI: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Wagner: nference Inc.: Current Employment; Janssen: Consultancy. Gray: Janssen Scientific Affairs, LLC: Current Employment, Current holder of individual stocks in a privately-held company. Kumar: Oncopeptides: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Antengene: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Bluebird Bio: Consultancy; Beigene: Consultancy; Tenebio: Research Funding; Roche-Genentech: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding.

Assessment of knowledge of drug-food interactions among healthcare professionals in public sector hospitals in eThekwini, KwaZulu-Natal

Background Foods and the nutrients they contain can interact with drugs and thereby interfere with their therapeutic safety and efficacy. Adequate knowledge of healthcare professionals (HCPs) about drug-food interactions can help in preventing potential drug-food interactions among patients. This study aimed to assess the knowledge of HCPs about common drug-food interactions. Methods A cross-sectional study was carried out among 459 HCPs from three public hospitals in eThekwini district, KwaZulu-Natal between November 2018, and January 2019. Informed consent was obtained from the HCPs, and a structured questionnaire was thereafter administered. Data were analysed using SPSS® version 25. Factors associated with knowledge of the HCPs were determined using logistic regression analysis. Results Of the 459 participants, 22.2% (n = 102) were doctors, 11.3% (n = 52) pharmacists, 63.8% (n = 293) nurses and 2.6% (n = 12) dietitians. Most of the HCPs were females 79.7% (n = 366), the mean age of the HCPs was 38.61±0.48. The knowledge score of the HCPs was 22.66±0.25 out of an overall score of 46. The HCPs poorly identified food types that interact with drugs and correct administration time of drugs relative to meals. Being a pharmacist (OR: 14.212, CI: 4.941–40.879, p<0.001), doctor (OR: 5.223, CI: 2.146–12.711, p<0.001), or a dietitian (OR: 5.476, CI: 1.103–27.191, p = 0.038) was associated with higher knowledge of drug-food interactions. Conclusion The HCPs in this survey had low drug-food interaction knowledge. These findings suggest the need for additional training and educational courses for the HCPs on drug-food interactions.