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The Primary Care Companion For CNS... Jun 2024To review the effects of the ketogenic diet on epilepsy in children and adolescents. A literature search was conducted in PubMed with no publication date or language...
To review the effects of the ketogenic diet on epilepsy in children and adolescents. A literature search was conducted in PubMed with no publication date or language restrictions based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. Keywords used included , , , , and . After excluding articles that did not meet the inclusion criteria, such as missing variables of study, adult population, and nonrandomized clinical trials, a total of 12 studies were included in the final review. Data on study design, duration, sample size, population, and type of intervention were collected using a standard template. The ketogenic diet and its modified versions were noted to have beneficial effects in reduction of seizure frequency and severity, with manageable adverse effects such as gastrointestinal disturbances, dehydration, dyslipidemia, hyperuricemia, infection, and metabolic acidosis. Depending on patient compliance and comorbidities, all variations of the ketogenic diet were found to be helpful for seizure treatment, whether as an additive or an alternative treatment option, for children and adolescents with epilepsy. .
Topics: Humans; Diet, Ketogenic; Epilepsy; Child; Adolescent
PubMed: 38954792
DOI: 10.4088/PCC.23r03661 -
PloS One 2024Auditory-verbal hallucinatory experiences (AVH) have a 12% prevalence in the general pediatric population. Literature reports a higher risk of developing AVH in... (Observational Study)
Observational Study
Relationship between social cognition and emotional markers and acoustic-verbal hallucination in youth with post-traumatic stress disorder: Protocol for a prospective, 2-year, longitudinal case-control study.
INTRODUCTION
Auditory-verbal hallucinatory experiences (AVH) have a 12% prevalence in the general pediatric population. Literature reports a higher risk of developing AVH in post-traumatic stress disorder (PTSD). The persistence of AVHs during adolescence represents a risk of evolution into psychotic disorders. Social cognition and emotional markers could be considered prodromes markers of this evolution. The objectives of this prospective observational study are to observe social cognition and emotional markers correlation with the presence and persistence of AVH over two years and with the evolution of PTSD and psychotic diagnosis.
METHODS AND ANALYSIS
This prospective case-control study, longitudinal over two years (with an interim reassessment at six months and one year), will include 40 participants aged 8 to 16 years old with a diagnosis of PTSD and without a diagnosis of psychosis according to the criteria of DSM-5 (K-SADS-PL). Subjects included are divided into two groups with AVH and without AVH matched by gender, age and diagnosis. The primary outcome measure will be the correlation between social cognition and emotional makers and the presence of AVH in the PTSD pediatric population without psychotic disorders. The social cognition marker is assessed with the NEPSY II test. The emotional marker is assessed with the Differential Emotion Scale IV and the Revised Beliefs About Voices Questionnaire. The secondary outcome measures are the correlation of these markers with the persistence of AVH and the evolution of the patient's initial diagnosis two years later.
DISCUSSION
The originality of our protocol is to explore the potential progression to psychosis from PTSD by cognitive biases. This study supports the hypothesis of connections between PTSD and AVH through sensory, emotional and cognitive biases. It proposes a continuum model from PTSD to psychotic disorder due to impaired perception like AVH.
TRIAL REGISTRATION
Clinical trial registration: ClinicalTrials.gov Identifier: NCT03356028.
Topics: Humans; Stress Disorders, Post-Traumatic; Adolescent; Child; Case-Control Studies; Male; Female; Prospective Studies; Longitudinal Studies; Emotions; Hallucinations; Social Cognition; Psychotic Disorders
PubMed: 38954699
DOI: 10.1371/journal.pone.0306338 -
Genetics and Molecular Biology 2024Despite their global prevalence, the mechanisms for mood disorders like bipolar disorder and major depressive disorder remain largely misunderstood. Mood stabilizers and...
Despite their global prevalence, the mechanisms for mood disorders like bipolar disorder and major depressive disorder remain largely misunderstood. Mood stabilizers and antidepressants, although useful and effective for some, do not have a high responsiveness rate across those with these conditions. One reason for low responsiveness to these drugs is patient heterogeneity, meaning there is diversity in patient characteristics relating to genetics, etiology, and environment affecting treatment. In the past two decades, novel induced pluripotent stem cell (iPSC) research and technology have enabled the use of human-derived brain cells as a new model to study human disease that can help account for patient variance. Human iPSC technology is an emerging tool to better understand the molecular mechanisms of these disorders as well as a platform to test novel treatments and existing pharmaceuticals. This literature review describes the use of iPSC technology to model bipolar and major depressive disorder, common medications used to treat these disorders, and novel patient-derived alternative treatment methods for non-responders stemming from past publications, as well as presenting new data derived from these models.
PubMed: 38954533
DOI: 10.1590/1678-4685-GMB-2023-0305 -
Journal of Traumatic Stress Jul 2024The heterogeneity of the core symptoms of posttraumatic stress disorder (PTSD), high rates of comorbid mental and physical health conditions, and substantial impact of...
The heterogeneity of the core symptoms of posttraumatic stress disorder (PTSD), high rates of comorbid mental and physical health conditions, and substantial impact of the disorder on functioning and well-being contribute to complex clinical presentations that can be challenging to treat. Despite these challenges, there are excellent manualized treatments for PTSD with significant empirical support. Although the success of frontline treatments for PTSD is evident, there remains room for improvement as indicated by suboptimal response and attrition rates. To address challenges to optimal therapy outcomes (COTOs), researchers have conducted numerous clinical trials designed to (a) enhance the core structure of treatment protocols to increase flexibility or (b) expand the protocols to address comorbid conditions that inhibit recovery. However, it is implausible to ever conduct the number of enhancement and expansion clinical trials necessary to test manual modifications for the universe of possible COTOs. This conceptual review describes the concept of a personalized model of therapy that leverages a case formulation approach to implementing an evidence-based treatment for PTSD. This personalized approach provides guidance for the clinician in assessing the patient's COTOs, monitoring them throughout treatment, and relying on the patient's idiosyncratic data to inform treatment decisions, including how and when to diverge from treatment when clinically indicated and ensuring a clear path to return to trauma-focused work when the COTO is stabilized. This personalized, case formulation approach to treating PTSD provides guidance for adopting a more flexible approach to treating clinically complex patients while ensuring fidelity to the protocol.
PubMed: 38954530
DOI: 10.1002/jts.23073 -
Sleep Jul 2024The Maintenance of Wakefulness Test (MWT) is a widely accepted objective test used to evaluate daytime somnolence and is commonly used in clinical studies evaluating...
The Maintenance of Wakefulness Test (MWT) is a widely accepted objective test used to evaluate daytime somnolence and is commonly used in clinical studies evaluating novel therapeutics for excessive daytime sleepiness. In the latter, sleep onset latency (SOL) is typically the sole MWT endpoint. Here, we explored microsleeps, sleep probability measures derived from automated sleep scoring, and quantitative electroencephalography (qEEG) features as additional MWT biomarkers of daytime sleepiness, using data from a phase 1B trial of the selective orexin receptor 2 agonist danavorexton (TAK-925) in people with narcolepsy type 1 (NT1) or type 2 (NT2). Danavorexton treatment reduced the rate and duration of microsleeps during the MWT in NT1 (days 1 and 7; p ≤ 0.005) and microsleep rate in NT2 (days 1 and 7; p < 0.0001). Use of an EEG-sleep-staging-derived measure to determine the probability of wakefulness for each minute revealed a novel metric to track changes in daytime sleepiness, which were consistent with the θ/α ratio, a known biomarker of drowsiness. The slopes of line-fits to both the log-transformed sleepiness score or log-transformed θ/α ratio correlated well to (inverse) MWT SOL for NT1 (R = 0.93 and R = 0.83, respectively) and NT2 (R = 0.97 and R = 0.84, respectively), suggesting that individuals with narcolepsy have increased sleepiness immediately after lights-off. These analyses demonstrate that novel EEG-based biomarkers can augment SOL as predictors of sleepiness and its response to treatment and provide a novel framework for the analysis of wake EEG in hypersomnia disorders.
PubMed: 38954525
DOI: 10.1093/sleep/zsae148 -
Clinical Gerontologist Jul 2024This review examines health care team-focused interventions on managing persistent or recurrent distress behaviors among older adults in long-term residential or... (Review)
Review
OBJECTIVES
This review examines health care team-focused interventions on managing persistent or recurrent distress behaviors among older adults in long-term residential or inpatient health care settings.
METHODS
We searched interventions addressing health care worker (HCW) knowledge and skills related to distress behavior management using Ovid MEDLINE, Elsevier Embase, and Ovid PsycINFO from December 2002 through December 2022.
RESULTS
We screened 6,582 articles; 29 randomized trials met inclusion criteria. Three studies on patient-facing HCW interactions (e.g. medication management, diagnosing distress) showed mixed results on agitation; one study found no effect on quality of life. Six HCW-focused studies suggested short-term reduction in distress behaviors. Quality-of-life improvement or decreased antipsychotic use was not evidenced. Among 17 interventions combining HCW-focused and patient-facing activities, 0 showed significant distress reduction, 8 showed significant antipsychotic reduction (OR = 0.79, 95%CI [0.69, 0.91]) and 9 showed quality of life improvements (SMD = 0.71, 95%CI [0.39, 1.04]). One study evaluating HCW, patient-, and environmental-focused intervention activities showed short-term improvement in agitation.
CONCLUSIONS AND CLINICAL IMPLICATIONS
Novel health care models combining HCW training and patient management improve patient quality of life, reduce antipsychotic use, and may reduce distress behaviors. Evaluation of intervention's effects on staff burnout and utilization is needed.
PubMed: 38954524
DOI: 10.1080/07317115.2024.2372424 -
Age and Ageing Jul 2024Anxiety symptoms and disorders are common in older adults and often go undetected. A systematic review was completed to identify tools that can be used to detect anxiety...
BACKGROUND
Anxiety symptoms and disorders are common in older adults and often go undetected. A systematic review was completed to identify tools that can be used to detect anxiety symptoms and disorders in community-dwelling older adults.
METHODS
MEDLINE, Embase and PsycINFO were searched using the search concepts anxiety, older adults and diagnostic accuracy in March 2023. Included articles assessed anxiety in community-dwelling older adults using an index anxiety tool and a gold standard form of anxiety assessment and reported resulting diagnostic accuracy outcomes. Estimates of pooled diagnostic accuracy outcomes were completed.
RESULTS
Twenty-three anxiety tools were identified from the 32 included articles. Pooled diagnostic accuracy outcomes were estimated for the Geriatric Anxiety Inventory (GAI)-20 [n = 3, sensitivity = 0.89, 95% confidence interval (CI) = 0.70-0.97, specificity = 0.80, 95% CI = 0.67-0.89] to detect generalized anxiety disorder (GAD) and for the GAI-20 (n = 3, cut off ≥ 9, sensitivity = 0.74, 95% CI = 0.62-0.83, specificity = 0.96, 95% CI = 0.74-1.00), Beck Anxiety Inventory (n = 3, sensitivity = 0.70, 95% CI = 0.58-0.79, specificity = 0.60, 95% CI = 0.51-0.68) and Hospital Anxiety and Depression Scale (HADS-A) (n = 3, sensitivity = 0.78, 95% CI = 0.60-0.89, specificity = 0.76, 95% CI = 0.60-0.87) to detect anxiety disorders in clinical samples.
CONCLUSION
The GAI-20 was the most studied tool and had adequate sensitivity while maintaining acceptable specificity when identifying GAD and anxiety disorders. The GAI-20, GAI-Short Form and HADS-A tools are supported for use in detecting anxiety in community-dwelling older adults. Brief, self-rated and easy-to-use tools may be the best options for anxiety detection in community-dwelling older adults given resource limitations. Clinicians may consider factors including patient comorbidities and anxiety prevalence when selecting a tool and cut off.
Topics: Humans; Aged; Anxiety; Anxiety Disorders; Geriatric Assessment; Female; Male; Independent Living; Psychiatric Status Rating Scales; Reproducibility of Results; Aged, 80 and over; Age Factors; Predictive Value of Tests
PubMed: 38954435
DOI: 10.1093/ageing/afae122 -
Current Medical Research and Opinion Jul 2024Post-COVID-19 condition (PCC), also known as "long COVID," is characterized by persistent symptoms, negatively affecting the well-being of individuals with PCC....
Post-COVID-19 condition (PCC), also known as "long COVID," is characterized by persistent symptoms, negatively affecting the well-being of individuals with PCC. Anhedonia (i.e., reduced capacity for pleasure) and compromised psychosocial functioning are notable symptoms in those with PCC. We aimed to provide insights to understand the effects of anhedonia and impaired psychosocial functioning of patients with PCC. This post-hoc analysis used data from an 8-week, double-blind, randomized, placebo-controlled trial which evaluated vortioxetine for cognitive deficits in individuals with PCC (Clinicaltrials.gov Identifier: NCT05047952). A total of 147 eligible participants were randomly assigned to receive vortioxetine or matching placebo over eight weeks of double-blind treatment. Our study investigated the relationship between anhedonia, assessed by the Snaith-Hamilton Pleasure Scale (SHAPS), and psychosocial functioning, measured with the Post-COVID Functional Status (PCFS) scale. The analysis was conducted using a generalized linear model, with adjustments for relevant covariates such as age, sex, education, suspected versus confirmed COVID diagnosis, MDD diagnosis, and alcohol consumption. Of the 147 participants, 143 participants had available baseline data for analysis. We observed that baseline PCFS score was statistically significantly positively correlated to baseline SHAPS score (β = 0.070, p = 0.045, 95% CI). Our analysis revealed a significant relationship between measures of anhedonia and psychosocial functioning in adults with PCC. Strategies that aim to improve patient-reported outcomes with PCC need to prioritize the prevention and treatment of hedonic disturbances in patients experiencing PCC.
PubMed: 38954402
DOI: 10.1080/03007995.2024.2374510 -
Journal of General Internal Medicine Jul 2024Primary care (PC) offers an opportunity to treat opioid use disorders (OUD). The Substance Use Symptom Checklist ("Checklist") can assess DSM-5 substance use disorder...
BACKGROUND
Primary care (PC) offers an opportunity to treat opioid use disorders (OUD). The Substance Use Symptom Checklist ("Checklist") can assess DSM-5 substance use disorder (SUD) symptoms in PC.
OBJECTIVE
To test the psychometric properties of the Checklist among PC patients with OUD or long-term opioid therapy (LTOT) in Kaiser Permanente Washington (KPWA).
DESIGN
Observational study using item response theory (IRT) and differential item functioning (DIF) analyses of measurement consistency across age, sex, race and ethnicity, and receipt of treatment.
PATIENTS
Electronic health records (EHR) data were extracted for all adult PC patients visiting KPWA 3/1/15-8/30/2020 who had ≥ 1 Checklist documented and indication of either (a) clinically-recognized OUD (i.e., documented OUD diagnosis and/or OUD medication treatment) or (b) LTOT in the year prior to the checklist.
MAIN MEASURE
The Checklist includes 11 items reflecting DSM-5 criteria for SUD. We described the prevalence of 2 SUD symptoms reported on the Checklist (consistent with mild-severe DSM-5 SUD). Analyses were conducted in the overall sample and in two subsamples (clinically-recognized OUD and LTOT only).
KEY RESULTS
Among 2007 eligible patients, 39.9% endorsed ≥ 2 SUD symptoms (74.3% in the clinically-recognized OUD subsample and 13.1% in LTOT subsample). IRT indicated that a unidimensional model for the 11 checklist items had excellent fit (comparative fit index = 0.998) with high item-level discrimination parameters for the overall sample and both subsamples. DIF across age, race and ethnicity, and treatment was observed for one item each, but had minimal impact on expected number of criteria (0-11) patients endorse.
CONCLUSIONS
The Substance Use Symptom Checklist measured SUD symptoms consistent with DSM-5 conceptualization (scaled, unidimensional) in patients with clinically-recognized OUD and LTOT and had similar measurement properties across demographic subgroups. The Checklist may support symptom assessment in patients with OUD and diagnosis in patients with LTOT.
PubMed: 38954321
DOI: 10.1007/s11606-024-08845-0 -
CNS Drugs Jul 2024TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone that is approved by the United States Food and Drug Administration for the...
BACKGROUND
TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone that is approved by the United States Food and Drug Administration for the treatment of schizophrenia in adults. In the phase 3, randomized, double-blind RIsperidone Subcutaneous Extended-release (RISE) study, TV-46000 once monthly (q1m) and once every 2 months (q2m) significantly prolonged time to impending relapse compared with placebo [5.0-fold (q1m) and 2.7-fold (q2m)]. This phase 3, randomized, double-blind Safety in Humans of TV-46000 subcutaneous INjection Evaluation (SHINE) study was designed to evaluate the long-term safety, tolerability, and exposure of TV-46000 in schizophrenia.
METHODS
Patients who completed RISE without relapse (rollover) or who were newly recruited (de novo) were eligible for the SHINE study. Patients were initially stabilized on oral risperidone for 12 weeks (completed in RISE for rollover, or in SHINE for de novo). Patients in the de novo cohort and patients who received placebo in RISE were randomized 1:1 in SHINE to receive TV-46000 q1m or q2m for up to 56 weeks. Primary endpoint for SHINE was frequency of reported adverse events (AEs); event rates [ER; events per 100 patient-years (PYs)] were calculated for each AE by patients upon general questioning.
RESULTS
Overall, 336 patients were randomized in SHINE [TV-46000 q1m, n = 174; TV-46000 q2m, n = 162; of these, de novo, n = 109 and rollover, n = 227 (n = 172 patients were treated and n = 55 received placebo)]. A total of 334 patients were evaluated for safety [q1m, n = 172 (PY = 97.8); q2m, n = 162 (PY = 104.5)]. Proportions of patients (ER) with ≥ 1 AE and ≥ 1 treatment-related AE were 37% (180.0) and 21% (84.9) for TV-46000 q1m and 46% (157.9) and 20% (70.8) for TV-46000 q2m, respectively. Frequent treatment-related AEs [≥ 3% of patients in either group; proportion of patients (ER)] were injection site pain [q1m, 5% (24.5); q2m, 4% (22.0)] and injection site nodule [q1m, 2% (9.2); q2m, 6% (12.4)]. The proportions of patients with serious AEs was 5% for TV-46000 q1m and 7% for TV-46000 q2m; serious AEs reported for ≥ 2 patients overall were worsening schizophrenia [q1m, n = 1 (< 1%; ER, 1.02); q2m, n = 2 (1%; ER, 1.91)] and hyperglycemia [q1m, n = 1 (< 1%; ER, 1.02); q2m, n = 1 (< 1%; ER, 0.96)]. Of three reported deaths, none were related to treatment. Overall, eight patients discontinued treatment because of AEs. Similar or somewhat lower rates of AEs were reported for patients who rolled over from TV-46000 treatment compared with those who had no prior TV-46000 treatment (de novo and placebo rollover). Most AEs related to injection site reactions were mild; no patient had a severe reaction.
CONCLUSION
Results from this long-term safety study add to the favorable safety profiles of TV-46000 q1m and q2m, consistent with other formulations of risperidone and previous studies with TV-46000.
REGISTRATION
ClinicalTrials.gov, NCT03893825; 27 March 2019.
PubMed: 38954317
DOI: 10.1007/s40263-024-01102-2