Influence of systemic fluoroquinolone administration on the presence of Pasteurella multocida in the upper respiratory tract of clinically healthy calves

The influence of enrofloxacin administration (5 mg/kg) for five consecutive days on the occurrence of Pasteurella multocida in the upper respiratory tract of two healthy calves was monitored over a 10-day period. From nasal swabs of two additional healthy control calves, which received a placebo saline administration, P. multocida was isolated throughout the study period. In the enrofloxacin treated calves, P. multocida was not demonstrated in the nasopharynx from 48 h after the first injection until two days after the last administration, when P. multocida reappeared and proved to be clonal in nature to the original isolates. During the experiment, no change in minimal inhibitory concentration for enrofloxacin of the P. multocida isolates was detected (MIC ≤ 0.015 μg/mL). Enrofloxacin concentrations were determined in the plasma by a high-performance liquid chromatography method with fluorescence detection. The PK/PD indices AUC/MIC and Cmax/MIC ratio were calculated and found to be 1157.7 and 129.8, respectively. Remarkably, the respiratory pathogen Arcanobacterium pyogenes became the predominant recovered organism in the nasopharynx of one animal following enrofloxacin therapy throughout the remaining of the experiment

Outcomes of cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after the acute phase

© 2022 American Heart Association, Inc.Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0–2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94–194). Two patients died during follow-up (3% [95% CI, 1%–11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%–94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.This study was funded by the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10430072110005), the Dr. C.J. Vaillant Foundation, and Hospital District of Helsinki and Uusimaa (grant TYH2022223).info:eu-repo/semantics/publishedVersio

Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination

Objective Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. Methods We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. Results Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). Conclusions In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022Peer reviewe

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19

Introduction: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. Patients and methods: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. Results: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28–54) vs 45 (28–56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28–79) vs 68 (30–125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19–62) vs 53 (20–92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. Discussion and conclusions: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.</p

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19

Introduction: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. Patients and methods: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. Results: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28–54) vs 45 (28–56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28–79) vs 68 (30–125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19–62) vs 53 (20–92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. Discussion and conclusions: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.</p

Developing a Research Protocol to Investigate Stress, Workload, and Driving Apprehension during Driving Lessons in Young Adults with an Autism Spectrum Disorder: A Feasibility Study

Background: Autism Spectrum Disorders (ASD) are known to impact quality-of-life (QoL). Driving can increase autonomy and QoL by enabling maintenance of work and social contacts. Research suggests people with ASD experience difficulties in complex driving situations. These difficulties may induce increased stress, workload, and driving apprehension (i.e., fear or worry), discouraging the pursuit of licensure and potentially interfering with safely learning to drive. Driver instructors can be seen as key players in the development of safe driving skills, already during the learning phase. Internationally, attention went to the development of educational modules for driver instructors to learn how to deal with ASD learner drivers. Especially in the Netherlands, and recently in Belgium, several driving schools adopt a distinct approach for ASD learner drivers. However, effect evaluations often lack, neither has it been investigated whether these approaches lead to less stress, workload, and driving apprehension. Moreover, to avoid extra stress, too demanding research protocols are best avoided. Objectives: We conducted a feasibility study with wearable technology and questionnaires to determine levels of stress, workload, and driving apprehension during driving lessons. To this end, we developed a research protocol and asked a pilot sample to evaluate the procedure. Methods: The protocol included Q-sensor wristbands to indicate levels of stress and workload during driving lessons via measurement of electrodermal activity. We also included the Rating Scale of Mental Effort (RSME), together with the Driving Attitude Scale Parent-Report (DAS-PR) & Self-Report (DAS-SR) from Cox and colleagues as indicators for signs of apprehensive driving. Participants wore Q-sensors during each lesson and completed the RSME after each lesson, as their instructors also did. After the first, middle, and final driving lesson, participants and their parents completed the DAS questionnaires. Besides that, we included questionnaires to determine baseline levels of anxiety and ASD characteristics. We followed a similar procedure for participants that took a driving test. The pilot sample included 4 ASD diagnosed (1 male) and 2 control (1 male) learner drivers, age 18-25. Participants received the instructions once, at reception of the materials. Results: Procedures and measures were evaluated positively. However, to avoid incomplete or unusable data, special attention should go to clear enough instruction of the correct procedure. For instance, two participants wore sensors on the upper instead of the lower wrist, leading to unusable data. Furthermore, questionnaires were not always completed consistently. The non-parametric group comparison tests were not significant, probably due to the limited sample size. Only one ASD learner driver completed the driving exam during the study (i.e., one academic year). Conclusions: The developed protocol was evaluated positively and therefore can be used to investigate levels of stress, workload, and driving apprehension during driving lessons. However, sufficient attention to the instructions is warranted (e.g., inclusion of practice sessions and reminders). Finally, to include the driving exam, sufficient time allocation to the study is required