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In ESCAPE-TRD (NCT04338321), a randomized, open-label, rater-blinded, long-term, phase 3b trial, augmentation with esketamine nasal spray (ESK) demonstrated increased probability of achieving meaningful clinical benefit versus quetiapine extended release (QUE XR) in patients (pts) with treatment-resistant depression (TRD). This subgroup analysis of ESCAPE-TRD evaluated the incidence, duration, and impact of treatment-emergent adverse events (TEAEs) on treatment discontinuation in adults with TRD treated with ESK or QUE XR according to US prescribing information.
Methods
Pts aged 18-64 years were randomly assigned to receive flexibly dosed ESK (56 or 84 mg) or QUE XR (150-300 mg), both consistent with US label dosing and in combination with an ongoing oral antidepressant. The incidence and duration of the most commonly occurring TEAEs, as well as the most common TEAEs leading to treatment discontinuation, were summarized descriptively. All randomly assigned participants receiving ≥1 dose of study drug were included in the safety analyses.
Results
Among the 636 pts included in the subgroup analysis, 316 and 320 were randomly assigned to ESK and QUE XR, respectively; 314 and 316 were included in the safety population. In the combined acute and maintenance phases, TEAEs occurred in 92.0% of pts in the ESK group and 78.5% of pts in the QUE XR group. The most commonly reported TEAEs with ESK or QUE XR in the combined acute and maintenance phases were dizziness (47.1% and 7.9%, respectively), headache (25.5% and 13.0%, respectively), somnolence (15.0% and 23.4%, respectively), and nausea (29.9% and 3.2%, respectively). Across all TEAE events reported in >5% of pts in either arm, 91.8% (5831 of 6351) resolved within 1 day in the ESK arm compared to 11.6% (90 of 776) with QUE XR. For specific TEAE events of clinical interest for ESK, same-day resolution rates for increased blood pressure, sedation, and dissociation in the ESK group were 93.5% (116 of 124), 96.2% (127 of 132), and 99.6% (740 of 743), respectively. The majority of TEAEs of clinical interest in the ESK group that occurred on the same day of dosing resolved within the first 2 hours after dosing. For the most frequently reported TEAEs with QUE XR, same-day resolution rates for somnolence, headache, and fatigue were 7.8% (8 of 103), 49.2% (29 of 59), and 9.5% (4 of 42), respectively. Fewer pts treated with ESK discontinued treatment due to TEAEs compared to QUE XR (4.4% versus 10.6%).
Conclusions
Safety data from this subgroup analysis were consistent with the overall study population as well as the known tolerability profile of each treatment. TEAEs were reported at higher incidence with ESK than with QUE XR; however, the majority of TEAEs occurring with ESK were transient in nature and did not result in a higher rate of treatment discontinuation compared to QUE XR.
On February 6, 2023, a strong earthquake (7.8 Richter scale) shook southwestern Türkiye, and also affected areas in northwest Syria, resulting in over 50 000 fatalities and more than 100 000 injured in Türkiye, in addition to the displacement of approximately 3 million people. In response to an international request for assistance from the Turkish government, the United Kingdom (UK) government deployed an Emergency Medical Team (EMT) Type 1 to provide outpatient care. This report describes the type of medical conditions treated at the facility from 1 week to 3 months post-earthquake. Consultations and diagnoses were recorded using standardized UK EMT patient records and reported through the WHO Minimum Data Set (MDS) format. A total of 7048 patient consultations were documented during the deployment.
The majority of cases involved infectious conditions, primarily respiratory illnesses, rather than trauma. Noncommunicable diseases (NCDs), such as cardiovascular diseases and diabetes, were also prevalent, particularly among adults and older patients. The report outlines some recommendations to better adapt data collection in order to improve EMT preparedness for future earthquake responses.
European countries have been important supporters of Ukraine since the 2022 invasion by Russia. Responding to the invasion, however, was not the only challenge facing these countries in 2022. A tough domestic economic situation caused by high inflation and skyrocketing energy prices gave rise to public resentment accusing governments of favoring Ukraine and Ukrainian refugees over their own citizens. Yet, communicating governments’ policies on Ukraine efficiently and having the public on board matters because lack of public support may endanger the countries’ ability to help Ukraine in the war. Given the importance of political communication, we use the case of Czechia to explore the role of empathy in political communication between Ukraine and Ukrainian refugees. We build on existing studies which suggest that empathy in communication has the potential to decrease polarization of public opinion and that candidates using empathetic communication are viewed more positively. First, in a rhetorical analysis, we demonstrate that empathy with citizens’ concerns is not a part of the government’s defense of its refugee policy. Then, in an original survey experiment, we show that contrary to expectations, expressing empathy with citizens’ concerns does not significantly increase public support for help to refugees.
Measuring the aerodynamics and stability characteristics of small unmanned aerial vehicles (sUAVs) operating at Reynolds numbers below $60,000$ is a challenge. Conventional measurement methods can be impractical and costly due to the vehicle’s size and the considerably low forces and moments involved. To overcome these limitations, the current study aims at utilising an existing motion tracking system to conduct off-board aerodynamic measurements of sUAVs. Six sUAVs, with varying wing aspect ratios, are investigated in un-powered, glide flight mode to establish the utility of the motion capture system as an aerodynamic characterisation system and understand the low Reynolds number effects on the flight dynamics. The trajectory tracking system was thoroughly validated through a series of static and dynamic tests to account for uncertainties and errors. Subsequently, flight trajectory data was collected and processed to extract the aircraft’s force and moment characteristics under quasi-steady conditions. The measured lift, drag and moment data compared well with existing literature and theoretical predictions. Longitudinal, lateral and dynamic stability derivatives were also accurately captured. Key findings from the current work included an inverse relationship between the wing aspect ratio and lift curve slope and substantially lower Oswald efficiency factors, both of which were attributed to low Reynolds number effects.
Thomas Schelling argued that “The most spectacular event of the past half century is one that did not occur. We have enjoyed sixty years without nuclear weapons exploded in anger.” To this, he added a question: “Can we make it through another half dozen decades?” Contemporary technological innovation, weapons proliferation, increased modernization efforts, and nuclear saber-rattling have made Schelling's question an urgent one. Recently, there has been an explosion in scholarship attempting to test the resilience of nonuse. These scholars have focused primarily on methodological innovations, generating an impressive body of evidence about the future of nonuse. Yet we argue that this literature is theoretically problematic: it reduces mechanisms of nuclear nonuse to a “rationalist” versus “normative” dichotomy which obscures the distinct pathways to nuclear (non)use within each theoretical framework. With rationalist theories, the current literature commits the sin of conflation, treating what should be distinct mechanisms—cost and credibility—as a single causal story. With normative theories, scholars have committed a sin of omission, treating norms as structural and overlooking mechanisms of norm contestation. We show that teasing out these different causal pathways reveals radically different expectations about the future of nonuse, especially in a world of precision nuclear weapons.
Anhedonia, a multidimensional domain including the reduced ability to experience pleasure, is a core diagnostic symptom of major depressive disorder (MDD) and a common residual symptom. In patients with MDD, anhedonia has been associated with poor treatment outcomes, suicide and reduced functioning and quality of life. This post-hoc analysis of data from a phase 3 trial (NCT03738215) evaluated the efficacy of adjunctive cariprazine (CAR) treatment on anhedonia symptoms in patients with MDD.
Methods
Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to CAR 1.5 mg/d + ADT, CAR 3 mg/d + ADT, or placebo + ADT for 6 weeks of double-blind treatment. Post hoc analyses evaluated the change from baseline to Week 6 in Montgomery–Åsberg Depression Rating Scale (MADRS) total score, MADRS anhedonia subscale score (items: 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]), and MADRS anhedonia item 8 in the overall modified intent-to-treat (mITT) population and in subgroups of patients with baseline MADRS anhedonia item 8 score of ≥4 or baseline anhedonia subscale score of ≥18. Least square (LS) mean change from baseline to Week 6 was analyzed using a mixed-effects model for repeated measures.
Results
There were 751 patients in the mITT population (CAR + ADT: 1.5 mg/d=250, 3 mg/d=252; placebo + ADT=249). At baseline, 508 (67.6%) patients had MADRS anhedonia item 8 scores ≥4, and 584 (77.8%) had MADRS anhedonia subscale scores ≥18. In the overall mITT population, LS mean change from baseline to Week 6 in anhedonia subscale score was significantly greater for CAR 1.5 mg/d + ADT (-8.4) and CAR 3 mg/d + ADT (-7.9) than for placebo + ADT (-6.8; both P<.05). The LS mean change from baseline in MADRS individual item 8 was also significantly greater for CAR 1.5 mg/d + ADT (-1.7) vs placebo + ADT (-1.3; P=.0085). In both subgroups of patients with baseline anhedonia, CAR 1.5 mg/d + ADT was associated with significantly greater reduction in MADRS total score, MADRS anhedonia subscale score, and MADRS item 8 score compared with placebo + ADT (all P<.05). In the CAR 3 mg/d + ADT group, significantly greater reductions vs placebo + ADT were observed for MADRS total score and MADRS anhedonia subscale score in the subgroup of patients with baseline anhedonia subscale scores ≥18 (both P<.05).
Importance
Adjunctive treatment with CAR was associated with a reduction in symptoms of anhedonia relative to adjunctive placebo in patients with MDD and inadequate response to ADT alone. In subgroups of patients with moderate-to-severe anhedonia at baseline, CAR + ADT demonstrated greater improvements than placebo + ADT in overall depressive symptoms and symptoms of anhedonia. These results suggest that adjunctive CAR treatment may be effective for improving symptoms of anhedonia in patients with MDD who have symptoms of anhedonia.
Long-acting injectable antipsychotics (LAIs) have demonstrated better rates of adherence among patients with schizophrenia than oral antipsychotics (OAs). While LAIs often cost more than OAs, better adherence can lead to cost offsets in other areas.
Objective
The purpose of this LAI Cost-Offset Value Calculator (LCVC) model is to provide an evidence-based model that estimates total costs and total cost offsets for a hypothetical population of adult patients with schizophrenia treated with atypical LAIs relative to second-generation oral antipsychotics (SGOAs) in the United States.
Methods
The model was derived based on studies included in a recent meta-analysis of patients who relapsed while taking an SGOA and were either switched to an atypical LAI or continued an SGOA. User inputs to the model include population size and payer archetype. The model then estimates the difference in adherence rates, relapse rates, hospitalizations, hospital days, hospital costs, emergency department (ED) visits, ED costs, and pharmacy costs, as well as cost offsets overall and by source (ie, hospitalization, ED, pharmacy).
Results
In the base case, representing a hypothetical cohort of 1000 adult patients with schizophrenia in the United States and a composite payer archetype, 1-year pharmacy costs were higher for patients who switched to an LAI relative to patients who continued taking an SGOA ($14,561,971 vs $7,203,142). However, cost offsets were observed for other dimensions of direct costs, including lower ED costs ($1,664,808 vs $2,241,483) and substantially lower hospital costs ($23,623,612 vs $44,195,100) due to fewer relapses (409 vs 508). For some payer archetypes (ie, Medicare and Veteran Affairs), the cost offsets completely covered the higher pharmacy costs for LAIs; for others (ie, Commercial and Medicaid), the cost offsets partially covered the higher pharmacy costs for LAIs, though sometimes substantially.
Conclusion
Despite potential higher pharmacy costs for LAIs, this model supports the conclusion that those costs could be mitigated by cost offsets in other areas, with varying results depending on payer archetype. The LCVC model, parameterized using real-world data extracted from a recent systematic review and meta-analysis, may be helpful for payers in understanding the potential cost offsets of switching patients with schizophrenia who have relapsed while taking OAs to LAIs. To our knowledge, there are no similar studies for schizophrenia that calculate cost offsets based solely on empirical evidence of patients who failed on OAs.
Late-onset mania presents as a diagnostic challenge given the interplay between psychiatry and neurology. Neurocognitive disorders, especially the behavioral subtype of Frontotemporal Dementia (FTD), are among one of the differential diagnoses in patients presenting later in life with manic-like symptoms. Here we discuss a case of new-onset manic symptoms in an elderly patient with no prior history of bipolar disorder and conduct a comprehensive literature review to assist with the diagnostic challenges of late-onset mania and dementia with behavioral disturbances.
Case
Mrs. X is a 67-year-old female with bipolar disorder diagnosed 2 months prior to admission who presented to the hospital after a mechanical fall and witnessed seizure-like activity thought to be due to benzodiazepine withdrawal. She was found to have new atrial fibrillation that was stabilized, and clonazepam was resumed. Psychiatry was consulted to assist with manic behaviors. On initial evaluation, Mrs. X presented as anxious, distractible, tangential with pressured speech, increased psychomotor activity, and paranoid towards her husband. She was treated for a urinary tract infection but otherwise workup was unremarkable. Head imaging demonstrated gray matter volume loss that appeared more prominent in the temporal and frontal lobes. Once transferred to the inpatient psychiatry unit, she presented with elevated mood, excessive jocularity, disinhibition, and poor insight. SLUMS of 18 noted poor attention, processing, and short-term recall. She was started on divalproex sodium titrated to 1500 mg daily (VPA level 108 mcg/mL) and olanzapine 25 mg daily. Observations throughout this time included minimal change in affect, elevated mood, memory deficits and social disinhibition. She did have less aggression, minimal paranoia towards her husband and circumstantial thought process although noted with confabulation.
Methods
We completed a comprehensive literature review utilizing PubMed and Google Scholar. Search terms included combinations of “late-onset”, “bipolar disorder”, “mania”, “neurocognitive disorder”, “dementia”, “frontotemporal”, “behavioral disturbances”.
Discussion
Once Mrs. X’s initial delirium resolved, she remained with manic-like symptoms. Collateral, brain imaging of reduced gray matter volume in the frontal and temporal lobes, and lack of response to high doses of a mood stabilizer and antipsychotic favor a probable neurocognitive disorder with behavioral disturbances. Literature reviewed helped to narrow down the differential diagnosis for Mrs. X and allowed for a more comprehensive treatment plan.
Conclusion
Diagnostic elucidation of late-onset mania relies on a comprehensive investigation into psychiatric and non-psychiatric etiologies, a detailed collateral history, and a neuropsychiatric lens. Neurocognitive disorders remain an important differential diagnosis.
Solving a decision theory problem usually involves finding the actions, among a set of possible ones, which optimize the expected reward, while possibly accounting for the uncertainty of the environment. In this paper, we introduce the possibility to encode decision theory problems with Probabilistic Answer Set Programming under the credal semantics via decision atoms and utility attributes. To solve the task, we propose an algorithm based on three layers of Algebraic Model Counting, that we test on several synthetic datasets against an algorithm that adopts answer set enumeration. Empirical results show that our algorithm can manage non-trivial instances of programs in a reasonable amount of time.
The crisis that now grips the ‘living earth’ establishes an intersection of climate and finance which entails questions of time: what does temporality mean in the context of both climate emergency and the processes of financialisation? In this paper, I intervene in these debates by reflecting on the reconstruction of time as a concrete legal object in the space of international investor-state arbitration. Over the past decade, international arbitration settlements, often using the accounting technique of discounted cash flow (DCF) analysis, have increasingly relied on a conception of investor-oriented time that offers an expansive future, a time of long-term unbroken integrity. I trace the complex but often uneven shifts in arbitration practices through which the future is reconfigured not as a proximate and conditional object but as a category, encoded in DCF, which is endlessly expansive. The time of the unbroken asset, I argue, is in urgent disjuncture with the time of transition.
Forecasting international migration is a challenge that, despite its political and policy salience, has seen a limited success so far. In this proof-of-concept paper, we employ a range of macroeconomic data to represent different drivers of migration. We also take into account the relatively consistent set of migration policies within the European Common Market, with its constituent freedom of movement of labour. Using panel vector autoregressive (VAR) models for mixed-frequency data, we forecast migration in the short- and long-term horizons for 26 of the 32 countries within the Common Market. We demonstrate how the methodology can be used to assess the possible responses of other macroeconomic variables to unforeseen migration events—and vice versa. Our results indicate reasonable in-sample performance of migration forecasts, especially in the short term, although with varying levels of accuracy. They also underline the need for taking country-specific factors into account when constructing forecasting models, with different variables being important across the regions of Europe. For the longer term, the proposed methods, despite high prediction errors, can still be useful as tools for setting coherent migration scenarios and analysing responses to exogenous shocks.
Ebstein’s anomaly represents 40% of congenital tricuspid valve abnormalities. Studies about paediatric Ebstein’s anomaly patients are limited.
Aim:
To evaluate clinical characteristics, treatment (medical/arrhythmia ablation/surgical) results, and outcome of Ebstein’s anomaly patients, and to determine factors affecting arrhythmia presence and mortality.
Methods:
Clinical data, echocardiography, treatment results, and outcomes of patients followed in our centre between 2000 and 2017 were retrospectively evaluated.
Results:
A total of 79 patients (61 children, median diagnosis age: 1.5 years [1 day–24 years]) were included. Eight patients (10.1%) were deceased during the study period. Common associated anomalies were atrial septal defect/patent foramen ovale (56.9%), mitral regurgitation (25.3%), pulmonary stenosis/atresia (17.7%), and ventricular septal defect (16.5%). Genetic diseases/congenital anomalies were present in 5/3.8%. Tricuspid regurgitation was present in 75.9%, and severe in 50%. Arrhythmias were detected in 30.4%, and accessory pathway-mediated re-entrant tachycardia was the most common (67%). Wolff-Parkinson-White syndrome was present in 12.7%. Twenty-one ablation procedures (radiofrequency ablation [85.7%]/cryoablation [14.3%]) were performed in 16 patients (median age: 13.3 years [4.9–17]). Acute success/recurrence rates: 87.5/25%. Surgery was performed in 31.6% (median age: 6.5 years [4 days–29 years]), 7.6% were operated during the first month, and 12.6% during the first year. Second surgery was required in 28%. Perioperative mortality rate was 12%, and median mortality age was 25 days (1 day–17 years). Median follow-up period was 5.3 years (1 day–32 years). Older diagnosis age (p = 0.005) and mild-moderate mitral regurgitation (p = 0.036) were associated with arrhythmias. Younger age at diagnosis (p = 0.012), younger age at first surgery (p = 0.004), surgery before age three years (p = 0.037), and presence of pulmonary atresia (p = 0.000014) were associated with mortality. Gender, diagnosis age, congenital anomalies/genetic disorders, tricuspid regurgitation, arrhythmias, and surgery history did not have an independent effect on survival.
Conclusions:
In children and young adults presenting with Ebstein’s anomaly, younger age at presentation and at surgery, surgery before age three years, pulmonary atresia were associated with death. Ablation procedures can be successfully performed but recurrence rate is still high.
To examine the effectiveness of short-term progressive muscle relaxation therapy in reducing symptoms of depression, anxiety, and aggression/agitation, in patients on an inpatient psychiatric unit. Additionally, to determine the impact of clinical and sociodemographic factors on its effectiveness.
Methods
Psychiatric inpatients at a private, community-based psychiatric hospital were invited to participate in a progressive muscle relaxation activity and filled out pre- and post-activity surveys querying symptoms of depression, anxiety, and aggression/agitation, using a created Likert scale.
Results
The 57 participants in this study showed an average decrease in every symptom domain, including -0.93 in agitation/aggressive symptoms (p<0.001), -2.14 in depressive symptoms (p<0.001), and -1.81 in anxiety symptoms (p<0.001). While diagnosis did not appear to be significantly related to change in score, patients with different primary diagnoses had changes in different symptom domains, with patients with Bipolar Disorder having statistically significant changes in aggression (-1.57, p=0.012) and depression (-2.36, p<0.001), but not in anxiety. Patients with Depression had significant changes in depression (-2.08, p<0.001) and anxiety (-1.96, p<0.001) but not in aggression/agitation, while patients with a Schizophrenia spectrum illness had changes in depression alone (-2.33, p=0.008). Sociodemographic variables had no significant impact.
Conclusions
The findings in this study indicate that a short-term progressive muscle relaxation intervention can lead to statistically and clinically significant changes across various symptom domains and in patients with a variety of psychiatric diagnoses, and support the implementation of this non-invasive and budget-friendly exercise.
This case discusses a 33-year-old transgender Army Veteran, diagnosed with co-occurring Bipolar Disorder Type 1 (Bipolar I) and Post-Traumatic Stress Disorder (PTSD), both with psychotic features. The patient exhibited recurrent mood swings, delusions, auditory hallucinations, and passive suicidal thoughts. Concurrent symptoms, such as disrupted sleep, irritability, and intrusive thoughts, complicated diagnosis and treatment. The patient’s medical history included migraines, chronic pain, medication-induced seizures, traumatic brain injury (TBI), and Borderline Personality Disorder.
During the assessment, the patient displayed mood fluctuations, cognitive issues, and intermittent tearfulness. They were averse to sedative medications and preferred non-pharmacological approaches. The Alpha-Stim (Cranial Electrical Stimulator – CES) was recommended for anxiety, depression, insomnia, and chronic pain.
Medication options (Aripiprazole, Lurasidone, and Risperidone) were discussed, and the patient chose Aripiprazole. The treatment plan included Dialectical Behavior Therapy for Borderline Personality Disorder and potential polysomnography to evaluate sleep disorders.
This case underscores the management challenges of co-occurring Bipolar I and PTSD with psychotic features, emphasizing the need for further research on their interplay, impact on functioning, and optimal treatments. It also explores CES as a potential intervention for psychosis during mood episodes.
Was Jackson Pollock “Jack the dripper” with paintings “that a dog or cat could have done better,” or did Pollock insert Polloglyphs – images that are encrypted that tell a story about Pollock’s inner being - into his paintings and then disguise them with drippings? On the one hand, some - especially art critics - have emphasized the formal elements of Pollock’s work, arguing that no images are present and the viewer can find whatever they are looking for because such images are artefacts of the “fractal” fuzzy edges to the drippings and are just fooling the eyes. Thus, maybe Pollock’s paintings are just a massive set of new Rorschach inkblots to provoke the viewer to project their own emotions onto the painting, whereas there is actually nothing at all in the painting from the artist. On the other hand, from a psychiatric point of view, given that Pollock had bipolar disorder, painted when he was euthymic or manic and not intoxicated nor depressed, had extensive exposure to Rorschach ink blots during his own psychiatric treatment, had visual images and hallucinations of images, clearly incorporated images into his pre-drip paintings (e.g., see Troubled Queen), and used repeatedly the same images in multiple drip paintings (e.g., booze bottles, images of himself, monkeys, clowns, elephants and more), the alternate point of view is that Pollock either consciously or unconsciously encrypted images in his drip paintings. His remarkable ability to do this with Polloglyphs hiding in plain sight may be part of Pollock’s creative genius and could have been enhanced by the endowment of extraordinary visual spatial skills that have been described in some bipolar patients. If so, painting could have been Pollock’s way to rapidly unspool his images and to do this onto canvas. Pollock himself stated that consciously “I try to stay away from any recognizable image; if it creeps in, I try to do away with it.” However, he also admitted “recognizable images are always there in the end.” If coming from his deep unconscious creativity and genius, such images may have appeared in spite of himself. Pollock thus may indeed not have been mindful of creating Polloglyphs as he stated “When I am in my painting, I’m not aware of what I am doing.” He painted in air, letting gravity make the picture, and dripping became not just another way of obscuring images but as well a new way of creating them. Ultimately, we may never know if there are Polloglyphs present in Jackson Pollock’s famous drip paintings, nor can we know for sure whether they are merely in the mind of the beholder or put there consciously or unconsciously by the artist. In the meantime, it can be fun and enlightening to view Pollock’s works and decide for yourself.
Although many patients respond equally well to both stimulant and nonstimulant medications for ADHD, some patients respond preferentially to one class over another. Currently, most patients receive a stimulant as first-line therapy; however, nonstimulants present fewer obstacles for prescribers and patients and have low abuse/misuse potential. Still, when patients have suboptimal response to stimulants, physicians may be reticent to switch to a nonstimulant medication due to concerns that the nonstimulant response will be less robust or less preferable for patients. Viloxazine ER (viloxazine extended-release capsules; Qelbree®) is a nonstimulant, FDA-approved treatment for ADHD in children (≥6 years) and adults. This post-hoc analysis of adult Phase 3 trial data (NCT04016779) evaluates response to viloxazine ER (200-600 mg/day) based on whether or not patients reported a history of previous stimulant use.
Methods
For patients randomized to viloxazine in this Phase 3, double-blind, placebo-controlled trial, the change from baseline (CFB) in Adult ADHD Investigator Symptom Rating Scale (AISRS) score (primary trial outcome) was analyzed for prior stimulant users vs. nonusers using MMRM. Prior stimulant use was based on patient-reported medication history recorded upon enrollment. Subjects using stimulants at the time of study screening were required to undergo a ≥1-week washout period prior to randomization.
Results
Of 372 patients treated, 189 received viloxazine ER. Of the patients who received viloxazine ER, 40 reported prior stimulant use and 149 did not. Mean (SD) baseline AISRS scores for prior stimulant users and nonusers were 38.5 (7.40) and 38.3 (6.44), respectively. Response appeared similar in both patient groups. At Week 6/End of Study (EOS) the least squares (LS) mean (SE) CFB AISRS scores for prior stimulant users and nonusers were -15.8 (2.51) and -15.6 (1.08)]; treatment difference -0.2 (2.41); P=0.93. Though not significant, prior stimulant users showed a larger magnitude of improvement on the AISRS at early timepoints compared to those without prior stimulant use [Week 1, LS mean (SE) CFB AISRS Total scores: -9.2 (1.40) vs. -6.8 (0.70), respectively; treatment difference: -2.4 (1.56); P=0.12.]
Conclusions
A history of prior stimulant use did not appear to influence the magnitude of ADHD symptom response to viloxazine ER in this preliminary analysis of Phase 3 trial data in adults. Rather, subjects with prior stimulant use showed numerically larger reductions in AISRS scores at early timepoints that were not significantly different from those without prior stimulant use. Additional analysis should be undertaken to evaluate patterns of response in the pediatric population.
Cable-guiding mechanisms (CGMs) and the stiffness characteristics directly influence the dynamic features of the cable-driven upper limb rehabilitation robot (PCUR), which will affect PCUR’s performance. This paper introduces a novel CGM design. Given the precision and movement stability considerations of the mechanism, an analytical model is developed. Using this model, we analyze the error of the CGM and derive velocity and acceleration mappings from the moving platform to the cables. Continuity of cable trajectory and tension is rigorously demonstrated. Subsequently, a mathematical model for PCUR stiffness is formulated. Utilizing MATLAB/Simscape Multibody, simulation models for the CGM and stiffness characteristics are constructed. The feasibility of the proposed CGM design is validated through simulation and experimentation, while the influence of stiffness characteristics on PCUR motion stability is comprehensively analyzed.
Rates of attention deficit hyperactivity disorder (ADHD) have increased among adults, and barriers to treatment (e.g., medication shortages; inaccessibility of behavioral treatments) underscore need for novel, scalable interventions. There is a particular need for treatments for inattentive symptoms, which are the most frequently endorsed ADHD symptoms in adults. AKL-T01 (EndeavorRx®) is an FDA-authorized digital therapeutic, currently approved for attention in children ages 8-12 with inattentive or combined-type ADHD and a demonstrated attention issue. This study evaluated the efficacy and safety of AKL-T01 in adults.
Methods
STARS-ADHD-Adults (NCT05183919) was a multicenter, single-arm trial at 14 US sites. Enrolled patients were 18 or older, had a diagnosis of ADHD (combined or inattentive), and demonstrated attentional impairment with a Test of Variables of Attention (TOVA) Attention Comparison Score (ACS) ≤ -1.8. Treatment involved using AKL-T01 at home 25 minutes/day, 5 days/week, for 6 weeks. The primary endpoint was change in TOVA-ACS. Secondary endpoints were changes in the ADHD Rating Scale-IV (ADHD-RS-IV) inattention subscale and total score, and Adult ADHD Quality of Life (AAQoL) total score. Safety, tolerability, and compliance were assessed.
Results
Of 440 participants screened, 221 were enrolled, and 153 (M age = 39.9, 70% female; 39% current stimulant use) had sufficient data for analysis. TOVA-ACS significantly improved from baseline to study day 42, M change = 6.46, SD = 6.95, t(152) = 11.49, p <.0001. There was significant improvement across all secondary endpoints (ps <.0001). In exploratory responder analyses, 36.6% moved into the normative range on TOVA (ACS>0), and 27.1% had ADHD-RS-IV improvement ≥ 30%. The treatment was well-tolerated (5% reported ADEs; none serious), and compliance was high (M = 81.1%).
Conclusions
Results support the efficacy of AKL-T01 in adults, and the magnitude of TOVA change in adults was nearly 7x the change reported in pediatric trials. Given the increasing rates of ADHD in adults, the barriers to accessing evidence-based treatments, and the centrality of inattentive symptoms as ADHD patients develop into adulthood, AKL-T01 holds promise as a scalable, targeted treatment for attention in adult ADHD with impacts to real-world symptoms.
Deprivation of national citizenship is one of the strategies used to counter the phenomenon of foreign terrorist fighters, that is, individuals traveling abroad for the purpose of terrorism. This Article begins with a short overview of the case-law of the European Court of Human Rights on the deprivation of citizenship. In these cases, the contestation of the deprivation of citizenship was based on the infringement of the rights to private and family life. We then turn to the limits imposed by EU law on decisions made by national authorities of Member States concerning citizenship deprivation of foreign terrorist fighters. Focusing on recent cases of the Court of Justice of the European Union (CJEU) concerning the European citizenship, we address the evolving role that EU law plays in the assessment of the proportionality of Member States’ decisions to strip individuals of national citizenship. We also consider the national practice, focusing on a recent decision in Denmark. In addition, we consider legal issues arising from the repatriation of Foreign Terrorist Fighters and their children. We argue that EU citizenship thus offers a further layer of protection against the deprivation of citizenship and that Member States are under a positive obligation to repatriate EU citizens who are the children of Foreign Terrorist Fighters on account of the case-law stemming from the Ruiz-Zambrano and X (Thai national) cases. For the moment, no common approach to repatriation of foreign fighters, or their children, is taken by EU member States in the context of the EU.
Rasoul Namazi's Leo Strauss and Islamic Political Thought is a wonderful tour through, well, Leo Strauss's reading of medieval Islamic political philosophy (as well as, or including, the Arabian Nights) and much of the secondary literature surrounding both the reception of Strauss's ideas and methods and the obstruction of such a reception on the part of mainstream historical and philological scholarship. One of the many great virtues and contributions of Namazi's book is that it resists the traditional insularity of Straussian and non-Straussian schools alike, seeking to read with an open mind non- and anti-Straussian scholars while modestly yet confidently making a case for why non-Straussians should read Strauss on Islamic political philosophy.