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Deutetrabenazine is a vesicular monoamine transporter type 2 inhibitor (VMAT2i) for treatment of adults with tardive dyskinesia (TD) and Huntington disease (HD)-related chorea. A 4-week patient titration kit was launched (July 2021) to assist patients in titrating to optimal deutetrabenazine dosages.
Methods
START is an ongoing, routine-care, 2-cohort (TD and HD) study evaluating deutetrabenazine dosing patterns, effectiveness, and treatment satisfaction when initiated using a 4-week patient titration kit, with further titration allowed based on effectiveness and tolerability. Patient satisfaction with the kit was assessed via questionnaire at week 8. Results from the first 50 patients enrolled in the TD cohort are presented in this interim analysis.
Results
50 patients in the TD cohort were included (mean age, 58.7 years, 66% female, 74% White, mean baseline Abnormal Involuntary Movement Scale [AIMS] total motor score, 13.8). 39 of 50 (78%) patients successfully completed the titration kit (completed within 5 weeks or reached optimal dose [≥24 mg/day] within 4 weeks; mean [SE] days, 27.5 [0.32]). Mean (SE) time to reach optimal dosage for the 38 (76%) patients who reached it was 46.3 (5.48) days. Mean (SE) deutetrabenazine dosages were 27.7 (0.92) mg/day at week 4, 32.5 (1.00) mg/day at week 8, and 32.8 (1.18) mg/day at week 12. After completion of the kit, mean (SE) dosage was 31.8 (1.24) mg/day, and 95% of patients reaching week 12 had a maintenance dosage ≥24 mg/day. Mean (SE) adherence with the kit was 97.2% (1.39%). 22% of patients had an adverse event (AE); AEs led to dose reduction for 2%, drug interruption for 2%, and study discontinuation for 6% of patients. Serious and treatment-related adverse events were reported for 2% and 6% of patients. 24 of 49 (49%)23 of 49 patients achieved treatment success (“much”/“very much” improved) at week 12 per Clinical Global Impression of Change (GIC); 23 or 49 (47%) per Patient GIC. Total motor AIMS scores were reduced by 4.8 points at week 12. Among the 39 (78%) patients who responded to the questionnaire, 72% found it easy to understand when/which dosage to take, 77% easy to remember to take their medication, 74% easy to change the dose weekly, 69% easy to follow kit instructions, and 77% easy to use the kit overall.
Conclusions
78% of patients with TD successfully completed the 4-week titration kit in approximately 4 weeks, with adherence rates of 97.2%. 95% of patients reaching week 12 had a maintenance dosage ≥24 mg/day. 49% of patients achieved treatment success based on Clinical GIC. Patients reported high levels of satisfaction with the titration kit and 77% found it easy to use. The 4-week patient titration kit enabled patients to titrate DTBZ to an optimal dosage and experience effectiveness similar to the pivotal clinical trials.
Valbenazine and deutetrabenazine (vesicular monoamine transporter 2 inhibitors) are approved for tardive dyskinesia (TD) treatment in adults. To prevent potential drug-drug interactions (DDIs), valbenazine labeling recommends doses 40 mg/day when taking strong CYP3A4 or CYP2D6 inhibitors and avoidance of strong CYP3A4 inducers and monoamine oxidase inhibitors (MAOIs). Deutetrabenazine labeling recommends doses ≤36-mg/day when taking strong CYP2D6 inhibitors and avoidance of MAOIs. This study estimated proportions of patients with TD at risk of DDIs with valbenazine/deutetrabenazine in real-world practice.
Methods
Patients aged ≥18 years with TD and ≥1 antipsychotic claim(s) and no valbenazine/ deutetrabenazine claims ≥3 months prior and ≥12 months after diagnosis were identified in the Symphony Health Sciences database (US-based medical, hospital, and pharmacy claims database). Proportions of patients meeting valbenazine/deutetrabenazine concomitant medication labeling restrictions were summarized descriptively.
Results
14,264/66,046 patients with TD met inclusion criteria. Proportions of patients at potential risk of DDIs were lower with deutetrabenazine ≤36 mg/day (0.2%) and >36 mg/day (21%) versus valbenazine 40 mg/day (4.4%; 22-times difference) and >40 mg/day (28%; 1.3-times difference). Across age groups, underlying conditions (major depressive, mood, and bipolar disorders; schizophrenia), and payer types, proportions of patients at potential risk of DDIs were lower with deutetrabenazine ≤36 mg/day (0.0%– 0.5%) and >36 mg/day (14%– 30%) versus valbenazine 40 mg/day (3%– 5%; 8.0- to >40.0times difference) and >40 mg/day (22%– 35%; 1.2- to >1.5-times difference).
Conclusions
Estimated proportions of patients with TD at potential risk of DDIs was lower with deutetrabenazine versus valbenazine overall and across age, underlying conditions, and payer types.
The European Union receives thousands of unaccompanied irregular migrant minors every year, but little is known about their life experiences during the migration process. The aim of this study is to describe their experiences as minors when they arrived in Spain in small boats, which will help to understand their psychosocial and health needs. A descriptive qualitative study was undertaken. In-depth interviews were conducted with 18 unaccompanied irregular migrants (15 men and 3 women) from different African countries with a mean age of 20.05 years (SD = 2.77). Thematic analysis was used to analyse the data. Three main themes emerged such as (1) unaccompanied irregular migrant minors: risking it all for a better life; (2) redefining your identity as a means of adaptation and (3) obtaining legal status to avoid deportation. Unaccompanied migrant minors risk their lives on the migration journey, but do not always find better conditions in the destination country. The unaccompanied irregular migrant minors are forced to rebuild their lives at a high cost; they experience rejection from the host society and their culture of origin, which has a negative impact on their physical and psychological health over time.
Psychedelics are a group of psychoactive substances that alter consciousness and produce marked shifts in sensory perception, cognition, and mood. Although psychedelics have been used by indigenous communities for centuries, they have only recently been investigated as an adjunctive therapeutic tool in psychotherapy. Since the early twentieth century, psychedelic-assisted psychotherapy has been explored for the treatment of several neuropsychiatric conditions characterized by rigid thought patterns and treatment resistance. However, this rapidly emerging field of neuroscience has evolved alongside opposition in several areas, including the affiliation with mid-twentieth century counterculture movements, media sensationalization, legislative restriction, and scientific criticisms such as “breaking the blind” and “excessive enthusiasm.” This perspective article explores the historical opposition to psychedelic research and the implications for the credibility of the field. In the midst of psychedelic drug policy reform, drawing lessons from historical events will contribute to clinical research efforts in psychiatry.
The choice of tree species planted with cacao trees is essential for ensuring the efficiency and sustainability of cacao farming systems. This raises the question of the long-term impact of associated tree legumes (ATLs) on cacao bean yields and biomass accumulation. This study was carried out in accordance with four-block randomised experimental design in Divo (Ivory Coast, West Africa). The study involved cacao-Albizia lebbeck (Cacao-Alb) and cacao-Acacia mangium (Cacao-Aca) intercrops and unshaded cacao plots (Control). After 20 years of intercropping, we assessed cacao dendrometry (height, circumference, biomass, and biomass C-stock) and production (number of pods per tree and bean yield at the plot level) as well as soil fertility (soil organic matter (SOM) concentration) at various distances from ATLs (D1:0–1.75 m; D2:3.25–5 m; D3:7–9 m). The distance from the ATLs had no significant effect on the measured cacao dendrometric parameters, except for cacao height. In contrast, the Cacao-Aca association had a negative impact on the SOM concentration (−22%), cacao tree height (−6.15%), and productivity parameters (biomass: −12.4%; bean yield: −43%). However, Cacao-Alb and the Control had no significant differences in terms of SOM, tree biomass, or bean production. Intercropping cacao with the tested tree legumes did not enhance cacao productivity and, in some cases, hindered it, depending on the ATL species. This study highlighted the importance of identifying appropriate shade tree legume species that could be promoted in cacao-based agroforestry systems.
To evaluate the use of a single-lead electrocardiography (1L-ECG) device and digital cardiologist consultation platform in diagnosing arrhythmias among general practitioners (GPs).
Background:
Handheld 1L-ECG offers a user-friendly alternative to conventional 12-lead ECG in primary care. While GPs can safely rule out arrhythmias on 1L-ECG recordings, expert consultation is required to confirm suspected arrhythmias. Little is known about GPs’ experiences with both a 1L-ECG device and digital consultation platform for daily practice.
Methods:
We used two distinct methods in this study. First, in an observational study, we collected and described all cases shared by GPs within a digital cardiologist consultation platform initiated by a local GP cooperative. This GP cooperative distributed KardiaMobile 1L-ECG devices among all affiliated GPs (n = 203) and invited them to this consultation platform. In the second part, we used an online questionnaire to evaluate the experiences of these GPs using the KardiaMobile and consultation platform.
Findings:
In total, 98 (48%) GPs participated in this project, of whom 48 (49%) shared 156 cases. The expert panel was able to provide a definitive rhythm interpretation in 130 (83.3%) shared cases and answered in a median of 4 min (IQR: 2–18). GPs responding to the questionnaire (n = 43; 44%) thought the KardiaMobile was of added value for rhythm diagnostics in primary care (n = 42; 98%) and easy to use (n = 41; 95%). Most GPs (n = 36; 84%) valued the feedback from the cardiologists in the consultation platform. GPs experienced this project to have a positive impact on both the quality of care and diagnostic efficiency for patients with (suspected) cardiac arrhythmias. Although we lack a comprehensive picture of experienced impediments by GPs, solving technical issues was mentioned to be helpful for further implementation. More research is needed to explore reasons of GPs not motivated using these tools and to assess real-life clinical impact.
Childhood maltreatment is associated with wide-ranging psychopathology at all stages of life. In the current study, we investigated whether posttraumatic stress disorder (PTSD) severity mediated the association between childhood maltreatment and internalizing and externalizing disorders among 262 South African trauma-exposed adolescents (aged 12–18 years). Childhood maltreatment and PTSD symptom severity were assessed using the Childhood Trauma Questionnaire and the Child PTSD Checklist, respectively. Psychiatric disorders were assessed utilizing the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version and were grouped into internalizing or externalizing disorders. Hierarchal logistic regression was used to assess the association of childhood maltreatment subtype with internalizing and externalizing disorders, controlling for age and gender, with PTSD symptom severity added to the final model. We found that sexual abuse was significantly associated with internalizing disorders, although this effect was no longer significant when PTSD was added to the model demonstrating that PTSD mediated the association between sexual abuse and internalizing disorders. Physical abuse, but not PTSD, was associated with externalizing disorders. Physical abuse, emotional neglect, and PTSD were associated with comorbid internalizing and externalizing disorders. These findings have implications for intervention and prevention strategies targeted at trauma-exposed adolescents with a history of childhood maltreatment.
This rejoinder takes up some of the points that have been raised by the reviews of Capital and Time in this forum. It engages the question of how political economy should position itself vis-à-vis concerns about the dangers of essentialism and teleological explanation. It argues that a proper theorization of the logic of ‘leverage’ is key to the development of a political economy that appropriates the insights of post-foundational theory but is still able to account for the reality of power and inequality.
Neither external nor internal to finance, the financial imagination marks out a space where the theoretical and practical aspects of finance come together in the inner life of the subject. That means there is something about financial subjectivity that escapes a functional view on the imagination. The purpose of this forum is to probe the contours of the financial imagination in terms of its perimeters and blind spots, its fantasies and delusions.
For some decades now, progressively minded social scientists have argued that markets are too important to leave to economists — indeed, entire new subfields have formed in response to this concern. But this engagement with economic life has often been somewhat half-hearted. Particularly telling in this respect is the fact that these new fields have organized themselves centrally around the rejection of ‘economism’ — the idea that markets have self-regulatory properties. Scholars in fields such as political economy and economic sociology have devoted a great deal of energy to normative critiques of the market, but they have displayed much less interest in rethinking the core categories and principles of economic life itself. What the books considered here have in common, and what sets them apart from established ways of thinking, is a willingness to tarry with the paradoxes of money.
The interface of political economy with arts and literature has become dominated by a particular image: capital's Grinch-like theft of the future. But this image overlooks the peculiar temporal structure of neoliberalism, which renews its broken promises by making up ever more excuses for the past. Contemporary bailout society requires a form of critique that acknowledges these dynamics, that targets the way capital reconstructs our relationship to the past.
Coronavirus disease (COVID-19) lockdowns disproportionately affect older people where most suffer from social isolation and loneliness, which translate into higher rates of depression and anxiety. This study aimed to explore the accessibility, outcomes, and challenges of social technology use among community-dwelling older adults, older adults in long-term care, older adults with neurocognitive disorder, and older adults with pre-frailty and frailty, to help guide future research in this area. A rapid review was conducted, and articles were retrieved from four online databases, including Medline, AgeLine, EconLit and CINAHL, and grey literature from Google Scholar. Of the 131 articles retrieved, 24 were included in this review. The positive outcomes of social technology use include improved mental and physical health, reduced health disparities, and increased autonomy. Adverse outcomes include furthering the digital divide. More research surrounding the economic impacts of social technologies is warranted.
Depression can be understood as a complex dynamic system, where depressive symptoms can directly affect each other. Knowledge on this symptom-symptom interaction is still scarce and is likely to differ between individuals. The hypothalamic-pituitary-adrenal (HPA) axis is often implicated in depression, with hypercortisolism and impaired glucocorticoid receptor-mediated feedback inhibition being commonly reported. High salivary cortisol levels may reflect a reaction to symptoms, or may rather be a cause, effectively ‘binding’ symptoms.
Objectives
We aimed to analyze the temporal interplay between salivary cortisol and emotions in depressed patients and controls by using the novel Dynamic Time Warp analysis (DTW) approach.
Methods
The ‘Mood and movement in daily life’ (MOOVD) study consisted of 30 pair-matched (15 depressed and 15 control) participants. Salivary cortisol was collected three times a day for 30 days, resulting in 90 measurements per individual. At the same moments, participants completed questionnaires on an electronic diary, which included different momentary positive (PA) and negative (NA) affect items. The dynamic interplay between salivary cortisol and affect were analyzed by DTW, which extends momentarily associations to include one earlier and one later time point, in both undirected and directed analyses.
Results
Individual networks differed substantially within groups. At the group level, undirected and directed network analyses showed differences between depressed patients and controls. In undirected analysis, connectivity of PA items was comparable between depressed patients and controls, but the NA items showed a less dense network in depressed patients. Directed DTW analyses indicated (p = 0.07) that increases in salivary cortisol preceded that of some NA items (e.g., tiredness) in controls, but tended to follow upon NA item increase (e.g., not feeling appreciated) in depressed patients.
Conclusions
At the group level, connectiveness between NA items was substantially weaker in depressed patients compared to controls. As in complex systems strong internal connectivity facilitates “critical transitions” to different states, this may reflect (or explain) the persistence of a chronically depressed state. We preliminary conclude that high salivary cortisol in depression may be a consequence of NA, rather than a cause. Replication of these first exploratory findings are needed.
Professional athletes such as soccer players are expected to be in better health than the average member of their age cohort, if only because of the very demands imposed on them by their profession. Moreover, during their active career, their health is monitored on a regular basis. However, whenever a (former) well-known athlete dies, such an event is publicised widely. Perceived mortality among athletes may be distorted. In this article, we examine medium-term mortality of professional soccer players in The Netherlands. More specifically, we answer two questions. First, we examine if the mortality of soccer players is significantly different from mortality in the general population. Second, we assess whether mortality varies by team. We find that mortality among soccer players is significantly lower than in the general population, with no significant between teams variation. The methodology used in this article is easily extended to examine atypical mortality among other groups of athletes.
Bipolar disorder (BD) is a potentially chronic mental disorder marked by recurrent depressive and manic episodes, circadian rhythm disruption, and changes in energetic metabolism. “Metabolic jet lag” refers to a state of shift in circadian patterns of energy homeostasis, affecting neuroendocrine, immune, and adipose tissue function, expressed through behavioral changes such as irregularities in sleep and appetite. Risk factors include genetic variation, mitochondrial dysfunction, lifestyle factors, poor gut microbiome health and abnormalities in hunger, satiety, and hedonistic function. Evidence suggests metabolic jet lag is a core component of BD pathophysiology, as individuals with BD frequently exhibit irregular eating rhythms and circadian desynchronization of their energetic metabolism, which is associated with unfavorable clinical outcomes. Although current diagnostic criteria lack any assessment of eating rhythms, technological advancements including mobile phone applications and ecological momentary assessment allow for the reliable tracking of biological rhythms. Overall, methodological refinement of metabolic jet lag assessment will increase knowledge in this field and stimulate the development of interventions targeting metabolic rhythms, such as time-restricted eating.
Deep brain stimulation (DBS) is effective for refractory obsessive-compulsive disorder (OCD). Post-operative cognitive behavioral therapy (CBT) may augment the effects of DBS, but previous results are conflicting. Here, we investigated whether CBT augments the effect of DBS for OCD.
Method
Patients with and without CBT following DBS of the ventral anterior limb of the internal capsule were included. First, we analyzed Yale–Brown Obsessive-Compulsive Scale (Y-BOCS) and Hamilton Depression Rating Scale (HAM-D) scores before, during and after CBT in all patients with CBT. Second, we matched patients with and without CBT based on clinical baseline variables and initial response to DBS and compared the course of Y-BOCS and HAM-D scores over the same timeframe.
Results
In total, 36 patients with and 16 patients without CBT were included. Average duration of CBT was 10.4 months (s.d. 6.4). In the 36 patients with CBT, Y-BOCS scores decreased on average by 3.8 points (14.8%) from start until end of CBT (p = 0.043). HAM-D scores did not decrease following CBT. Second, 10 patients with CBT were matched to 10 patients without CBT. In both groups, Y-BOCS scores decreased equally from start until end of CBT or over a similar timeframe (10% in CBT group v. 13.1% in no-CBT group, p = 0.741).
Conclusions
Obsessive-compulsive symptoms decreased over time in patients with and without post-operative CBT. Therefore, further improvement may be attributed to late effects of DBS itself. The present study emphasizes the need for prospective randomized controlled studies, examining the effects of CBT.
Conservation action plans need to be devised and implemented if we are to reduce the extinction risk faced by globally threatened plants. However, most plant species categorized as threatened globally on the IUCN Red List lack conservation action plans. In West Africa, Guinea is one of the most diverse countries in terms of botanical species. In total, 273 plant species in Guinea have been assessed as being threatened globally, reflecting increasing pressure from the extractive industry and a growing population requiring food and fuel. In parallel with the implementation of an Important Plant Area programme in Guinea, we developed conservation action plans for 20 threatened plant species through a pilot study. We outline the methods we used and demonstrate the importance of adopting a collaborative approach and having up-to-date field information. The need for such plans is urgent, with recent estimates suggesting that one-third of African plants are threatened with extinction. Based on our experience with the first 20 conservation action plans for Guinea species, we suggest that the preparation of multi-species conservation action plans would be an efficient use of the limited resources available for species conservation.
Cet article s’efforce de démontrer que la détermination de l’objet du différend par la Cour internationale de Justice (CIJ) est une constante dans l’appréciation de sa compétence ratione materiae dans le contentieux des mesures conservatoires. D’une part, l’objet du différend fonde la compétence ratione materiae de l’organe judiciaire principal de l’Organisation des Nations Unies (ONU), à travers la clause compromissoire contenue dans le traité liant les parties au différend, et d’autre part, cette compétence conditionne la détermination de l’objet du différend. L’influence réciproque des deux notions en fait des notions clefs du contentieux des mesures conservatoires devant la CIJ. Par ailleurs, l’interprétation de son pouvoir d’indication des mesures conservatoires au titre de l’article 41, paragraphe 1, du Statut de la Cour internationale de Justice confère à la cour la possibilité d’en indiquer aux fins de non-aggravation du différend, dont le sens et la portée soulèvent de sérieuses interrogations. Au-delà des questionnements portant sur leur possible “déconnection” de l’objet du différend et de la fonction des mesures conservatoires, les mesures conservatoires indiquées aux fins de non-aggravation du différend participeraient d’une certaine manière des buts et principes de l’ONU et plus précisément du maintien de la paix et de la sécurité internationales.
Mood disorders, including depressive and bipolar disorders, represent a multidimensional and prevalent group of psychiatric illnesses characterized by disturbances in emotion, cognition and metabolism. Maladaptive eating behaviors in mood disorders are diverse and warrant characterization in order to increase the precision of diagnostic criteria, identify subtypes and improve treatment strategies. The current narrative review synthesizes evidence for Eating Behavioral Phenotypes (EBP) in mood disorders as well as advancements in pathophysiological conceptual frameworks relevant to each phenotype. Phenotypes include maladaptive eating behaviors related to appetite, emotion, reward, impulsivity, diet style and circadian rhythm disruption. Potential treatment strategies for each phenotype are also discussed, including psychotherapeutic, pharmacological and nutritional interventions. Maladaptive eating behaviors related to mood disorders are relevant from both clinical and research perspectives, yet have been somewhat overlooked thus far. A better understanding of this aspect of mood disorders holds promise to improve clinical care in this patient group and contribute to the subtyping of these currently subjectively diagnosed and treated disorders.