Cost-Effectiveness of Virtual Reality Cognitive Behavioral Therapy for Psychosis:Health-Economic Evaluation Within a Randomized Controlled Trial

Background: Evidence was found for the effectiveness of virtual reality-based cognitive behavioral therapy (VR-CBT) for treating paranoia in psychosis, but health-economic evaluations are lacking. Objective: This study aimed to determine the short-term cost-effectiveness of VR-CBT. Methods: The health-economic evaluation was embedded in a randomized controlled trial evaluating VR-CBT in 116 patients with a psychotic disorder suffering from paranoid ideation. The control group (n=58) received treatment as usual (TAU) for psychotic disorders in accordance with the clinical guidelines. The experimental group (n=58) received TAU complemented with add-on VR-CBT to reduce paranoid ideation and social avoidance. Data were collected at baseline and at 3 and 6 months postbaseline. Treatment response was defined as a pre-post improvement of symptoms of at least 20% in social participation measures. Change in quality-adjusted life years (QALYs) was estimated by using Sanderson et al's conversion factor to map a change in the standardized mean difference of Green's Paranoid Thoughts Scale score on a corresponding change in utility. The incremental cost-effectiveness ratios were calculated using 5000 bootstraps of seemingly unrelated regression equations of costs and effects. The cost-effectiveness acceptability curves were graphed for the costs per treatment responder gained and per QALY gained. Results: The average mean incremental costs for a treatment responder on social participation ranged between €8079 and €19,525, with 90.74%-99.74% showing improvement. The average incremental cost per QALY was €48,868 over the 6 months of follow-up, with 99.98% showing improved QALYs. Sensitivity analyses show costs to be lower when relevant baseline differences were included in the analysis. Average costs per treatment responder now ranged between €6800 and €16,597, while the average cost per QALY gained was €42,030. Conclusions: This study demonstrates that offering VR-CBT to patients with paranoid delusions is an economically viable approach toward improving patients' health in a cost-effective manner. Long-term effects need further research. Trial Registration: International Standard Randomised Controlled Trial Number (ISRCTN) 12929657; http://www.isrctn.com/ISRCTN12929657

Adaptation strategies of the Icelandic horse with induced forelimb lameness at walk, trot and tölt

Background and objective Lameness assessment in the gaited Icelandic horse is complex. We aimed to describe their kinematic and temporal adaptation strategies in response to forelimb lameness at walk, trot and tolt.Study designIn vivo experiment.Methods Ten clinically non-lame Icelandic horses were measured before and after reversible forelimb lameness induction. Upper body and limb kinematics were measured using 11 inertial measurement units mounted on the poll, withers, pelvis (tubera sacrale) and all four limbs and hoofs (Equimoves (R), 500 Hz). Horses were measured on a straight line at walk and trot in-hand and at walk, trot and tolt while ridden. Linear mixed models were used to compare baseline and lame conditions (random factor = 'horse'), and results are presented as the difference in estimated marginal means or percentage of change.Results Lameness induction significantly (p < 0.05) increased head vertical movement asymmetry at walk (HDmin/HDmaxHAND: 18.8/5.7 mm, HDmin/HDmaxRIDDEN: 9.8/0.3 mm) and trot (HDmin/HDmaxHAND: 18.1/7.8 mm, HDmin/HDmaxRIDDEN: 24.0/9.3 mm). At the tolt, however, HDmin did not change significantly (1.1 mm), but HDmax increased by 11.2 mm (p < 0.05). Furthermore, pelvis vertical movement asymmetry (PDmax) increased by 4.9 mm, sound side dissociation decreased (-8.3%), and sound diagonal dissociation increased (6.5%). Other temporal stride variables were also affected, such as increased stance duration of both forelimbs at walk, tolt and in-hand trot.Main limitations Only one degree of lameness (mild) was induced with an acute lameness model.Conclusions Classical forelimb lameness metrics, such as vertical head and withers movement asymmetry, were less valuable at tolt compared to walk and trot, except for HDmax. Therefore, it is advised to primarily use the walk and trot to detect and quantify forelimb lameness in the Icelandic horse

Adaptation strategies of the Icelandic horse with induced forelimb lameness at walk, trot and tölt

Background and objective: Lameness assessment in the gaited Icelandic horse is complex. We aimed to describe their kinematic and temporal adaptation strategies in response to forelimb lameness at walk, trot and tölt. Study design: In vivo experiment. Methods: Ten clinically non-lame Icelandic horses were measured before and after reversible forelimb lameness induction. Upper body and limb kinematics were measured using 11 inertial measurement units mounted on the poll, withers, pelvis (tubera sacrale) and all four limbs and hoofs (Equimoves®, 500 Hz). Horses were measured on a straight line at walk and trot in-hand and at walk, trot and tölt while ridden. Linear mixed models were used to compare baseline and lame conditions (random factor = ‘horse’), and results are presented as the difference in estimated marginal means or percentage of change. Results: Lameness induction significantly (p < 0.05) increased head vertical movement asymmetry at walk (HDmin/HDmaxHAND: 18.8/5.7 mm, HDmin/HDmaxRIDDEN: 9.8/0.3 mm) and trot (HDmin/HDmaxHAND: 18.1/7.8 mm, HDmin/HDmaxRIDDEN: 24.0/9.3 mm). At the tölt, however, HDmin did not change significantly (1.1 mm), but HDmax increased by 11.2 mm (p < 0.05). Furthermore, pelvis vertical movement asymmetry (PDmax) increased by 4.9 mm, sound side dissociation decreased (−8.3%), and sound diagonal dissociation increased (6.5%). Other temporal stride variables were also affected, such as increased stance duration of both forelimbs at walk, tölt and in-hand trot. Main limitations: Only one degree of lameness (mild) was induced with an acute lameness model. Conclusions: Classical forelimb lameness metrics, such as vertical head and withers movement asymmetry, were less valuable at tölt compared to walk and trot, except for HDmax. Therefore, it is advised to primarily use the walk and trot to detect and quantify forelimb lameness in the Icelandic horse

Thyrotrophin and thyroxine support immune homeostasis in humans

The endocrine and the immune systems interact by sharing receptors for hormones and cytokines, cross-control and feedback mechanisms. To date, no comprehensive study has assessed the impact of thyroid hormones on immune homeostasis. By studying immune phenotype (cell populations, antibody concentrations, circulating cytokines, adipokines and acute-phase proteins, monocyte-platelet interactions and cytokine production capacity) in two large independent cohorts of healthy volunteers of Western European descent from the Human Functional Genomics Project (500FG and 300BCG cohorts), we identified a crucial role of the thyroid hormone thyroxin (T4) and thyroid-stimulating hormone (TSH) on the homeostasis of lymphocyte populations. TSH concentrations were strongly associated with multiple populations of both effector and regulatory T cells, whereas B-cell populations were significantly associated with free T4 (fT4). In contrast, fT4 and TSH had little impact on myeloid cell populations and cytokine production capacity. Mendelian randomization further supported the role of fT4 for lymphocyte homeostasis. Subsequently, using a genomics approach, we identified genetic variants that influence both fT4 and TSH concentrations and immune responses, and gene set enrichment pathway analysis showed enrichment of fT4-affected gene expression in B-cell function pathways, including the CD40 pathway, further supporting the importance of fT4 in the regulation of B-cell function. In conclusion, we show that thyroid function controls the homeostasis of the lymphoid cell compartment. These findings improve our understanding of the immune responses and open the door for exploring and understanding the role of thyroid hormones in the lymphocyte function during disease

Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study

The Burden of Obstructive Lung Disease (BOLD) study was established to assess the prevalence of chronic airflow obstruction, a key characteristic of chronic obstructive pulmonary disease, and its risk factors in adults (≥40 years) from general populations across the world. The baseline study was conducted between 2003 and 2016, in 41 sites across Africa, Asia, Europe, North America, the Caribbean and Oceania, and collected high-quality pre- and post-bronchodilator spirometry from 28 828 participants. The follow-up study was conducted between 2019 and 2021, in 18 sites across Africa, Asia, Europe and the Caribbean. At baseline, there were in these sites 12 502 participants with high-quality spirometry. A total of 6452 were followed up, with 5936 completing the study core questionnaire. Of these, 4044 also provided high-quality pre- and post-bronchodilator spirometry. On both occasions, the core questionnaire covered information on respiratory symptoms, doctor diagnoses, health care use, medication use and ealth status, as well as potential risk factors. Information on occupation, environmental exposures and diet was also collected

The bii4africa dataset of faunal and floral population intactness estimates across Africa’s major land uses

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species’ population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate ‘intactness scores’: the remaining proportion of an ‘intact’ reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region’s major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/ taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems

The bii4africa dataset of faunal and floral population intactness estimates across Africa’s major land uses

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species’ population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate ‘intactness scores’: the remaining proportion of an ‘intact’ reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region’s major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems

Extrarenal effects on the pathogenesis and relapse of idiopathic nephrotic syndrome in Buffalo/Mna rats

Buffalo/Mna rats spontaneously develop a focal segmental glomerulosclerosis with a histological pattern similar to the human disease. In this study, we investigated the potential of recurrence of the disease by transplantation of normal kidneys into Buffalo/Mna recipients. Kidneys from healthy LEW.1W rats were grafted into proteinuric 6-month-old Buffalo/Mna rats without or with specific tolerance induction following donor-specific transfusion (DST) aimed at controlling host anti-donor immune responses. The inverse combination was carried out to determine whether a proteinuric Buffalo/Mna kidney can recover its permselectivity in a normal environment. As a control, LEW.1W kidneys were grafted into Wistar Furth recipients. After transplantation without DST, recurrence of proteinuria in LEW.1W kidneys appeared at approximately 10 days, possibly associated with rejection of the graft. In the same combination with DST, proteinuria occurred after 20 days, and the attendant glomerular damage suggested that the initial kidney disease had recurred. Transplanted control animals remained free of proteinuria. In the opposite combination, the proteinuria and the lesions of Buffalo/Mna kidneys regressed after transplantation into healthy LEW.1W rats. The recurrence of proteinuria after transplantation in Buffalo/Mna and the remission of lesions in Buffalo/Mna kidneys transplanted into normal hosts suggests that Buffalo/Mna rats express circulating albuminuric factors, which may be relevant to the relapse of idiopathic nephrotic syndrome in humans

Induction of T Regulatory Cells Attenuates Idiopathic Nephrotic Syndrome

Buffalo/Mna rats spontaneously develop FSGS and nephrotic syndrome as a result of an immune disorder. Similar to some humans with FSGS, the disease recurs after renal transplantation, suggesting the involvement of a circulating factor. Here, we tested the effect of several immunosuppressive treatments on these rats. Although corticosteroids, cyclosporin A, and anti–T cell receptor treatment reduced proteinuria, only the deoxyspergualin derivative LF15-0195 led to a rapid and complete normalization of proteinuria. Furthermore, this compound led to the regression of renal lesions during both the initial disease and posttransplantation recurrence. The frequency of splenic and peripheral CD4+CD25+FoxP3+ T lymphocytes significantly increased with remission. Moreover, the transfer of purified LF15-0195–induced CD4+CD25+ T cells to irradiated Buff/Mna rats significantly reduced their proteinuria compared with the transfer of untreated control cells, suggesting that LF15-0195 induces regulatory T cells that are able to induce regression of rat nephropathy. These data suggest that idiopathic nephrotic syndrome/FSGS disease can be regulated by cellular transfer, but how this regulation leads to the reorganization of the podocyte cytoskeleton remains to be determined