An Animal-Assisted Intervention Study in the Nursing Home: Lessons Learned

AAI studies in the nursing home pose a specific set of challenges. In this article the practical and ethical issues encountered during a Dutch psychogeriatric nursing home AAI study are addressed with the aim of sharing our experiences for future researchers as well as AAI practitioners in general. In our study we compared three groups of clients with dementia who participated in group sessions of either visiting dog teams, visiting FurReal Friend robot animals, or visiting students (control group) and monitored the effect on social interaction and neuropsychiatric symptoms through video analysis and questionnaires. We encountered the following four categories of challenges during our study. Participant-related challenges include the legal implications of working with vulnerable patients, the practical implications of a progressive neurodegenerative disease with accompanying memory loss and behavioral problems, and the ethical implications of the use of robot animals for people with diminished cognitive functions. A very important challenge involves the selection of the participating dogs and ensuring animal welfare during the study. We partnered with a local university of applied sciences to help us successfully address these issues. The nursing home setting poses several practical challenges due to its inherent organizational structure, the high workload of nursing home staff, and an often suboptimal environment for a controlled randomized trial, especially when comparing nonpharmacological interventions. Balancing the desire for scientifically sound procedures with the practical limitations of a nursing home setting is often difficult and requires specific considerations

Latent classes of DSM-5 acute stress disorder symptoms in children after single-incident trauma: findings from an international data archive

Background: After a potentially traumatic event (PTE), children often show symptoms of acute stress disorder (ASD), which may evolve into posttraumatic stress (PTS) disorder. A growing body of literature has employed latent class analysis (LCA) to disentangle the complex structure underlying PTS symptomatology, distinguishing between homogeneous subgroups based on PTS presentations. So far, little is known about subgroups or classes of ASD reactions in trauma-exposed children. Objective: Our study aimed to identify latent classes of ASD symptoms in children exposed to a single-incident PTE and to identify predictors of class membership (gender, age, cultural background, parental education, trauma type, and trauma history). Method: A sample of 2287 children and adolescents (5–18 years) was derived from the Prospective studies of Acute Child Trauma and Recovery (PACT/R) Data Archive, an international archive including studies from the USA, UK, Australia, and Switzerland. LCA was used to determine distinct subgroups based on ASD symptoms. Predictors of class membership were examined using a three-step approach. Results: Our LCA yielded a three-class solution: low (42%), intermediate (43%) and high (15%) ASD symptom severity that differed in terms of impairment and number of endorsed ASD symptoms. Compared to the low symptoms class, children in the intermediate or high severity class were more likely to be of female gender, be younger of age, have parents who had not completed secondary education, and be exposed to a road traffic accident or interpersonal violence (vs. an unintentional injury). Conclusions: These findings provide new information on children at risk for ASD after single-incident trauma,

Indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2 activity and severe course of COVID-19

COVID-19 is a pandemic with high morbidity and mortality. In an autopsy cohort of COVID-19 patients, we found extensive accumulation of the tryptophan degradation products 3-hydroxy-anthranilic acid and quinolinic acid in the lungs, heart, and brain. This was not related to the expression of the tryptophan-catabolizing indoleamine 2,3-dioxygenase (IDO)-1, but rather to that of its isoform IDO-2, which otherwise is expressed rarely. Bioavailability of tryptophan is an absolute requirement for proper cell functioning and synthesis of hormones, whereas its degradation products can cause cell death. Markers of apoptosis and severe cellular stress were associated with IDO-2 expression in large areas of lung and heart tissue, whereas affected areas in brain were more restricted. Analyses of tissue, cerebrospinal fluid, and sequential plasma samples indicate early initiation of the kynurenine/aryl-hydrocarbon receptor/IDO-2 axis as a positive feedback loop, potentially leading to severe COVID-19 pathology

Anti-C5a antibody vilobelimab treatment and the effect on biomarkers of inflammation and coagulation in patients with severe COVID-19: a substudy of the phase 2 PANAMO trial

We recently reported in the phase 3 PANAMO trial that selectively blocking complement 5a (C5a) with vilobelimab led to improved survival in critically ill COVID-19 patients. C5a is an important contributor to the innate immune system and can also activate the coagulation system. High C5a levels have been reported in severely ill COVID-19 patients and correlate with disease severity and mortality. Previously, we assessed the potential benefit and safety of vilobelimab in severe COVID-19 patients. In the current substudy of the phase 2 PANAMO trial, we aim to explore the effects of vilobelimab on various biomarkers of inflammation and coagulation. Between March 31 and April 24, 2020, 17 patients with severe COVID-19 pneumonia were enrolled in an exploratory, open-label, randomised phase 2 trial. Blood markers of complement, endothelial activation, epithelial barrier disruption, inflammation, neutrophil activation, neutrophil extracellular trap (NET) formation and coagulopathy were measured using enzyme-linked immunosorbent assay (ELISA) or utilizing the Luminex platform. During the first 15 days after inclusion, change in biomarker concentrations between the two groups were modelled with linear mixed-effects models with spatial splines and compared. Eight patients were randomized to vilobelimab treatment plus best supportive care (BSC) and nine patients were randomized to BSC only. A significant decrease over time was seen in the vilobelimab plus BSC group for C5a compared to the BSC only group (p < 0.001). ADAMTS13 levels decreased over time in the BSC only group compared to the vilobelimab plus BSC group (p < 0.01) and interleukin-8 (IL-8) levels were statistically more suppressed in the vilobelimab plus BSC group compared to the BSC group (p = 0.03). Our preliminary results show that C5a inhibition decreases the inflammatory response and hypercoagulability, which likely explains the beneficial effect of vilobelimab in severe COVID-19 patients. Validation of these results in a larger sample size is warranted

Neurofilament light increases over time in severe COVID-19 and is associated with delirium

Neurological monitoring in sedated Intensive Care Unit patients is constrained by the lack of reliable blood-based biomarkers. Neurofilament light is a cross-disease biomarker for neuronal damage with potential clinical applicability for monitoring Intensive Care Unit patients. We studied the trajectory of neurofilament light over a month in Intensive Care Unit patients diagnosed with severe COVID-19 and explored its relation to clinical outcomes and pathophysiological predictors. Data were collected over a month in 31 Intensive Care Unit patients (166 plasma samples) diagnosed with severe COVID-19 at Amsterdam University Medical Centre, and in the first week after emergency department admission in 297 patients with COVID-19 (635 plasma samples) admitted to Massachusetts General hospital. We observed that Neurofilament light increased in a non-linear fashion in the first month of Intensive Care Unit admission and increases faster in the first week of Intensive Care Unit admission when compared with mild-moderate COVID-19 cases. We observed that baseline Neurofilament light did not predict mortality when corrected for age and renal function. Peak neurofilament light levels were associated with a longer duration of delirium after extubation in Intensive Care Unit patients. Disease severity, as measured by the sequential organ failure score, was associated to higher neurofilament light values, and tumour necrosis factor alpha levels at baseline were associated with higher levels of neurofilament light at baseline and a faster increase during admission. These data illustrate the dynamics of Neurofilament light in a critical care setting and show associations to delirium, disease severity and markers for inflammation. Our study contributes to determine the clinical utility and interpretation of neurofilament light levels in Intensive Care Unit patients