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Learning How to Improve the Treatment of Persecutory Delusions: Using a Principal Trajectories Analysis to Examine Differential Effects of Two Psychological Interventions (Feeling Safe, Befriending) in Distinct Groups of Patients.
BACKGROUND: A theory-driven cognitive therapy (Feeling Safe) has produced much better outcomes for patients with persecutory delusions. There are four distinct response classes: very high delusion conviction with large improvement, very high delusion conviction with no response, high delusion conviction with large improvement, and high delusion conviction with modest improvement. Our objective was to apply principal trajectories analysis, a novel statistical method, to original trial data to estimate whether these groups may have responded differently to a different intervention: befriending. DESIGN: One hundred and thirty patients with persistent persecutory delusions were randomised to six months of Feeling Safe or befriending. Baseline assessments were used to assign patients allocated to befriending (who did not receive Feeling Safe) into the four Feeling Safe response classes. The treatment effect, including on potential mediators, was then estimated for these classes. RESULTS: Patients in two treatment response classes (Very high conviction/large improvement, High conviction/large improvement) benefited more from Feeling Safe, patients in one group (Very high conviction/no improvement) benefited more from befriending, and patients in the remaining group (High conviction/moderate improvement) benefited equally from the interventions. Mechanism differences were detected when Feeling Safe was superior to befriending, but not when befriending was superior. CONCLUSIONS: There may be patients with psychosis who benefit more from one type of therapy than another, likely due to different change mechanisms. The application of principal trajectories has generated testable hypotheses and a potential step toward personalised treatment. We recommend an investigation of whether sequential provision of the treatment types could enhance patient outcomes. Keywords: persecutory, delusions, outcome trajectories, psychosis, cognitive therapy.
Anatomic Relationship Between the Greater Occipital Nerve and the Axis: Is It Possible to Safely Insert a Percutaneous C2 Screw Without Causing Occipital Neuralgia?
BACKGROUND AND OBJECTIVES: Harms' technique is a widely used method for atlantoaxial stabilization. In recent years, minimally invasive surgery (MIS) using various robotic systems for percutaneous C1 to C2 screw insertion has started to be used. However, MIS raises concerns about the precision required to avoid injury to vascular and neural structures. The greater occipital nerve (GON) primarily arises from the C2 spinal root, located between the posterior arch of the C1 vertebra and the lamina of the C2 vertebra. The first bend of the GON could potentially overlay the lateral aspect of the C2 vertebra, specifically between the superior and inferior facets, ie, the interarticular part (IAP), making it susceptible to injury during C2 pedicle screw insertion causing the occipital neuralgia. That is why the aim of our study is to investigate the relationship of the GON to the axis and to assess the risk of its violation during C2 pedicle screw insertion. METHODS: Eight cadaveric specimens, embalmed in classical formaldehyde solution, were dissected to describe the position of the GON in relation to the axis. RESULTS: The apex of the first GON bend was localized 3.9 ± 2.2 mm from the lateral margin of the C2 IAP, 10.5 ± 2.7 mm caudal from the superior facet joint of the axis. The apex of the first bend was 3.5 ± 2.0 mm above the surface of the C2 IAP. The width of the C2 IAP was 14.2 ± 3.8 mm while the height was 15.9 ± 1.3 mm. CONCLUSION: The GON overlaid the cranial two-thirds of the IAP surface and can cross the entry point of the C2 screw. Therefore, we recommend using the most caudal entry point as possible, with steeper cranial angle controlled with navigation, to avoid the GON injury during MIS.
A cross-sectional investigation of the ophthalmological impact of loiasis in Cameroon, Central Africa
Background Current knowledge of ocular manifestations of loiasis is limited to the transient subconjunctival passage of the adult filaria and anecdotal reports of posterior segment lesions. Therefore, the ocular burden of loiasis is likely underestimated since it has never been systematically assessed at the population level. We aimed to evaluate the relationship of Loa loa microfilaremia and recent eye worm passage with chronic ocular lesions identified through comprehensive ophthalmological assessment in an endemic area. Methodology/principal findings Subjects aged ≥ 15 years, residing in Akonolinga for ≥ 5 years, without filaricidal treatment for ≥3 years, were screened for filariases. After excluding participants with onchocerciasis lesions, a subset of randomly selected participants was assessed by ophthalmologists blinded to blood test results then allocated to four groups defined by microfilarial load (MFL) on calibrated thick blood film: G1 (Loa MFL = 0), G2 (MFL < 8000/mL), G3 (MFL ≥ 8000/mL), G4 (co-infestation with Mansonella MFL > 100/mL). The ophthalmological assessment comprised distance visual acuity, examination of the anterior segment with a slit lamp, and fundoscopy. The primary analysis consisted of univariable comparisons of the frequency of abnormal findings across four groups (G1 – 4) or two groups defined by history of eye worm passage. The secondary analysis consisted of a multivariable logistic regression analysis of the relationship of high Loa MFL (≥8000/mL) with chorioretinitis and eye worm passage with unilateral ametropia, adjusting for confounders. Of 1511 subjects screened, 200 underwent ophthalmological assessment, including 65, 69, 35, and 16 in G1 to 4. History of eye worm passage in the previous year was reported by 121 participants (65.4%). Unilateral ametropia was more prevalent in people with history of eye worm passage in the previous year (26.5% versus 10.9%, p = 0.014). Chorioretinitis was the most frequent posterior segment lesion (n = 11, 6.1%) and was most prevalent in G3 (14.3%). The frequency of chorioretinitis was higher in participants with moderate-to-severe visual impairment (27.3% versus 4.4%, p = 0.002). High Loa MFL was an independent predictor of chorioretinitis (adjusted OR=5.28; p = 0.01). History of eye worm passage in the previous year was independently associated with unilateral ametropia (adjusted OR=3.27, p = 0.0088). Conclusions/significance This study has, for the first time, provided evidence of independent association between history of eye worm passage and unilateral ametropia, and between high Loa MFL and severe chorioretinal lesions. This suggests that loiasis should be classified as a neglected tropical disease.
Academia in the throes of faceless bureaucracy
Pansieri et al. argue that bureaucracy is suffocating research, as an ever increasing administrative burden consumes researchers’ time and diverts focus from discovery to compliance. They highlight ways in which red tape delays progress, wastes funding, and drives researchers out of academia, and call for systemic change.
Submaximal 2-day cardiopulmonary exercise testing to assess exercise capacity and post-exertional symptom exacerbation in people with long COVID.
Long COVID has a complex pathology and a heterogeneous symptom profile that impacts quality of life and functional status. Post-exertional symptom exacerbation (PESE) affects one-third of people living with long COVID, but the physiological basis of impaired physical function remains poorly understood. Sixty-eight people (age (mean ± SD): 50 ± 11 years, 46 females (68%)) were screened for severity of PESE and completed two submaximal cardiopulmonary exercise tests separated by 24 h. Work rate was stratified relative to functional status and was set at 10, 20 or 30 W, increasing by 5 W/min for a maximum of 12 min. At the first ventilatory threshold (VT1), V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ was 0.73 ± 0.16 L/min on Day 1 and decreased on Day 2 (0.68 ± 0.16 L/min; P = 0.003). Work rate at VT1 was lower on Day 2 (Day 1 vs. Day 2; 28 ± 13 vs. 24 ± 12 W; P = 0.004). Oxygen pulse on Day 1 at VT1 was 8.2 ± 2.2 mL/beat and was reduced on Day 2 (7.5 ± 1.8 mL/beat; P = 0.002). The partial pressure of end tidal carbon dioxide was reduced on Day 2 (Day 1 vs. Day 2; 38 ± 3.8 vs. 37 ± 3.2 mmHg; P = 0.010). Impaired V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ is indicative of reduced transport and/or utilisation of oxygen. V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ at VT1 was impaired on Day 2, highlighting worsened function in the 24 h after submaximal exercise. The data suggest multiple contributing physiological mechanisms across different systems and further research is needed to investigate these areas.
Prior Expectations of Volatility Following Psychotherapy for Delusions: A Randomized Clinical Trial.
IMPORTANCE: Persecutory delusions are common, distressing, and difficult to treat. Testing computational neuroscience models of delusions can identify new therapeutic targets. OBJECTIVE: To determine whether change in delusion severity is associated with a corresponding change in volatility priors and brain activation estimated during a belief updating task. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted from April 9, 2021, to December 5, 2023, within the Vanderbilt University Medical Center Psychiatric Hospital and at a community mental health center in Nashville, Tennessee. Participants were adults (aged between 18 and 65 years) with schizophrenia spectrum or delusional disorder and an active, persistent (≥3 months) persecutory delusion with strong conviction (>50%). Participants were randomly assigned 1:1 to either cognitive behavioral therapy for psychosis (CBTp)-based intervention or befriending therapy. Intention-to-treat analysis was performed from June 1 to October 31, 2024. INTERVENTION: The CBTp was a manualized intervention targeting persecutory delusions. The befriending therapy involved engaging in conversations and activities focused on neutral topics. Both interventions were provided in person, lasted for 8 weeks, and included standard care. Standard care consisted of medication management and ancillary services. MAIN OUTCOMES AND MEASURES: Primary outcomes were volatility priors (ie, prior expectations of volatility) derived from a 3-option probabilistic reversal learning task; persecutory delusion severity measured by the Psychotic Symptom Rating Scales (PSYRATS delusion subscale; score range: 0-16, with the highest score indicating severe preoccupation, distress, conviction, and functioning impact); and brain activation in the striatum and prefrontal cortex measured by blood oxygenation level-dependent signal change. Associations between volatility priors, clinical improvement, and change in neural activation were examined. RESULTS: Sixty-two participants (median [range] age, 31 [19-63] years; 38 males [61%]) were randomly assigned to the CBTp (n = 32) or befriending therapy (n = 30) arms. A subgroup of 35 participants (57%) completed functional magnetic resonance imaging. Volatility priors decreased following treatment (F1,112 = 7.7 [P = .006]; Cohen d = 0.52 [95% CI, 0.15-0.90]), as did delusion severity (F1,112 = 59.7 [P
Validation of the “Patient‐Acceptable Symptom State” Question as Outcome Measure in AChR Myasthenia Gravis: A Multicentre, Prospective Study
ABSTRACTIntroductionPatient Acceptable Symptom State (PASS) is emerging as a valuable subjective measure of the overall myasthenia gravis (MG)‐related burden. This study aimed at identifying PASS‐positive thresholds for the most used clinical scales, investigating whether PASS and MGFA post‐intervention status capture different aspects of the disease outcome, and identifying clinical variables associated with PASS=YES response.MethodsAdult AChR‐MG patients were prospectively enrolled at two Italian Centres (Rome: index cohort; Florence: validation cohort). PASS thresholds for MG‐ADL, QMG, and MG‐QOL15r were defined in the index cohort by ROC analysis and validated in the validation cohort; predictors of favorable PASS were identified by multivariable analysis.ResultsThis study included 173 patients (44% females, median age at onset: 53 years). PASS=YES patients had significantly lower median MG‐ADL, QMG, and MG‐QOL15r scores, with the following thresholds for PASS=YES: MG ADL ≤ 2, QMG ≤ 8 and MG‐QOL15r ≤ 6. The MG‐ADL (OR = 0.46, 95% CI = 0.36–0.60, p < 0.001), QMG (OR = 0.72, 95% CI = 0.64–0.81, p < 0.001) and MG‐QOL15r (OR = 0.76, 95% CI = 0.70–0.84, p < 0.001), were independently associated with a favorable PASS. The degree of ocular involvement in each scale was the strongest negative determinant of PASS=YES.ConclusionsThis study validates the PASS question and highlights the relevance of ocular complaints in patients' perception of MG burden.
Postural sway variability in young adults presents higher complexity during morning compared to evening hours while in older adults remains the same
Human movement variability reflects the adaptive capacity of the nervous system, yet how it is influenced by aging and circadian rhythms remain unclear. Therefore, the purpose of this study was to investigate postural sway variability as a function of aging and time of day. Nineteen young and nineteen older adults completed one 60-s quite stance trial with eyes open while standing on a force platform, at 12 p.m. and 12 a.m. Postural sway variability was evaluated regarding both its magnitude (total travel distance and interquartile range) and the complexity (a exponent using Detrended Fluctuation Analysis) of its temporal structure using the center of pressure time series. A two-way ANOVA (2 age groups × 2 times of day) was used. Correlation analysis was also performed to further investigate the relationship between circadian regulation and postural sway complexity. Complexity was higher for the young compared to the older group independently of the time of day. Furthermore, young adults presented higher values during the morning as compared to evening, while older adults did not reveal significant differences within the day. Finally, a strong correlation was found but only for young adults. In general, our results suggested that complexity of postural sway variability is affected both by age and time of day. Aging impacts postural control by reducing the complexity of sway variability and diminishing its sensitivity to circadian influences. Future work will address the effect of chronotype, sleep, and arousal levels on these novel findings and assess their impact on overall health.
Sleep-related hypermotor epilepsy in a patient with myelin-oligodendrocyte-glycoprotein antibody disease
Unusual seizure phenotypes in myelin-oligodendrocyte-glycoprotein (MOG) seropositive patients have previously been reported, although so far, no cases of sleep-related hypermotor epilepsy (SHE). In our case, a patient with a diagnosis of MOG antibody-associated disease (MOGAD) began reporting unusual sleep disturbances; video-audio documentation was in keeping with the clinical diagnosis of SHE. MRI brain was normal at the time of the assessment for seizures. Symptoms responded to antiepileptic drugs (AEDs). These unusual seizure events were thought to be indicative of the underlying autoimmune condition, suggesting that the clinical spectrum of MOGAD is wider than previously thought.
The relationship between TMS measures of functional properties and DTI measures of microstructure of the corticospinal tract
Background: Recently, a link between resting motor threshold (RMT) and local tissue microstructure, as indexed by fractional anisotropy (FA), was demonstrated in large parts of white matter. However, regions showing such correlations were generally found outside of the corticospinal tract (CST). Therefore, the question arises whether other electrophysiologic measurements could be more locally related to microstructural properties of the CST. In this study, we explored the relationship between such measurements and regional FA in a group of healthy volunteers. Objective/Hypothesis: We hypothesized that RMT might be more related to an overall susceptibility of white matter to TMS, whereas other electrophysiologic markers might be more specifically related to properties of the CST only. Methods: Thirty-seven subjects were included. We studied RMT, active motor threshold (AMT), intensity to evoke a motor-evoked potential (MEP) of 1 mV (S1mV), MEP input-output curve (IO-curve), and central motor conduction time (CMCT) using transcranial magnetic stimulation, and FA of the corticospinal tract using diffusion tensor magnetic resonance imaging. We performed voxel-wise and TBSS correlation analysis between these electrophysiologic measurements and FA. In addition, we tested for significant correlation between these parameters and mean diffusivity (MD). Results: On voxel-wise analysis, we did not detect significant correlations between any electrophysiologic parameter (RMT, AMT, S1mV, IO curve slope, CMCT) and FA. With TBSS, we detected correlations between FA and bilateral AMT, as well as left-hemispheric S1mV, but these correlations were found in locations unlikely to contribute to motor pathways. Conclusions: Although a relationship between structure and function has been shown in many other regions of the brain, it seems to be much more challenging to demonstrate such a relationship in the CST of healthy subjects. © 2012 Elsevier Inc. All rights reserved.
Spatiotemporal dynamics of bimanual integration in human somatosensory cortex and their relevance to bimanual object manipulation
Little is known about the spatiotemporal dynamics of cortical responses that integrate slightly asynchronous somatosensory inputs from both hands. This study aimed to clarify the timing and magnitude of interhemispheric interactions during early integration of bimanual somatosensory information in different somatosensory regions and their relevance for bimanual object manipulation and exploration. Using multi-fiber probabilistic diffusion tractography and MEG source analysis of conditioning-test (C-T) median nerve somatosensory evoked fields in healthy human subjects, we sought to extract measures of structural and effective callosal connectivity between different somatosensory cortical regions and correlated them with bimanual tactile task performance. Neuromagnetic responses were found in major somatosensory regions, i.e., primary somatosensory cortex SI, secondary somatosensory cortex SII, posterior parietal cortex, and premotor cortex. Contralateral to the test stimulus, SII activity was maximally suppressed by 51% at C-T intervals of 40 and 60 ms. This interhemispheric inhibition of the contralateral SII source activity correlated directly and topographically specifically with the fractional anisotropy of callosal fibers interconnecting SII. Thus, the putative pathway that mediated inhibitory interhemispheric interactions in SII was a transcallosal route from ipsilateral to contralateral SII. Moreover, interhemispheric inhibition of SII source activity correlated directly with bimanual tactile task performance. These findings were exclusive to SII. Our data suggest that early interhemispheric somatosensory integration primarily occurs in SII, is mediated by callosal fibers that interconnect homologous SII areas, and has behavioral importance for bimanual object manipulation and exploration. © 2012 the authors.