bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Safety and Efficacy of Deutetrabenazine in Younger and Older Patients With Tardive Dyskinesia
Authors: Sajatovic Martha , Wilhelm Amanda , Finkbeiner Stacy , Barkay Hadas , Chaijale Nayla , Gross Nicholas , Gordon Mark Forrest 
Published: May 2021

AbstractBackgroundTardive dyskinesia (TD) is an involuntary movement disorder that is more prevalent in older patients. However, there is limited information on TD treatment for this population. In two 12-week pivotal trials (ARM-TD and AIM-TD), TD patients demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) score with deutetrabenazine versus placebo.MethodsPatients who completed ARM-TD or AIM-TD enrolled in an open-label extension (OLE) study. This post hoc analysis assessed change and percent change from baseline in AIMS score, response rates for ≥50% AIMS improvement, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety in younger (<55 years) and older (≥55 years) patients.ResultsThis analysis included 119 younger and 218 older patients enrolled in the OLE. Data presented at Week 145 (mean±SE): total deutetrabenazine dose was 39.4±1.39mg/day and 39.5±1.04mg/day in younger and older patients, respectively. Changes from baseline in AIMS score were –6.7±0.62 and –6.5±0.47, respectively (percent changes of –61.4%±4.10% and –54.6%±3.01%). The majority of younger and older patients achieved treatment success per CGIC (67% and 76%) and PGIC (64% and 63%) and achieved ≥50% AIMS response (76% and 62%). Deutetrabenazine was generally well tolerated in both groups. Exposure-adjusted incidence rates (incidence/patient-years) were <0.01 and 0.02 for akathisia, 0.07 (both) for somnolence and sedation, 0.04 and 0.11 for parkinson-like events, and 0.06 and 0.09 for depression in younger and older patients, respectively.ConclusionsDeutetrabenazine treatment was associated with sustained improvements in AIMS score and was well tolerated in both younger and older TD patients.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Single-Dose Pharmacokinetics of Amphetamine Extended-Release Oral Suspension (AMPH EROS) in 6–12-Year-Old Children with ADHD
Authors: Pardo Antonio , Childress Ann C. , King Thomas R. , Rafla Eman , Kando Judith C. 
Published: May 2021

AbstractMethodsThis Phase 1, open-label, single-dose, one-period, one-treatment PK study enrolled 12 children 6–12 y with ADHD. PK parameters for d- and l-amphetamine in plasma (Cmax, tmax, AUC0–8, and t1/2) were calculated and expressed as means, geometric means, and standard deviations. The primary endpoint was all objective PK measurements at 28 hours post-dose. PK was evaluated for 2 cohorts (6 pts ages 6–9 y and 6 pts aged 10–12 y). Safety was monitored continuously and assessed based on occurrence of adverse events.ResultsA single dose of 10 mg (4 ml) AMPH EROS (2.5 mg/ml) administered under fasted conditions resulted in a rapid rise in mean plasma concentration in d-amphetamine, reaching maximum concentrations within 5 hours. The overall study population mean (SD) plasma AUC0–8 (d-amphetamine) was 1061.2 (309) h*ng/mL, and for l-amphetamine was 380.5 (112) h*ng/mL. The mean maximum concentration (Cmax) for the overall study population was 54.91 ng/mL and 17.1 (5.2) ng/mL for d- and l-amphetamine, respectively. The overall study population median time to maximum concentrations (Tmax) for d-amphetamine were reached at 3.4 hours, and for l-amphetamine at 4.1 hours. The elimination half-life (t1/2) for the entire study cohort was 10.6 (2.0) hours for d-amphetamine, and 12.5 (3.2) hours for l-amphetamine. Directionally, a higher mean Cmax, AUC0–8, AUCt, and median Tmax were observed in the younger (6 to 9-year-old) age group, and this result was consistent with both the d- and l-amphetamine enantiomers. The mean elimination t1/2 for both d- and l-amphetamine was higher in the older cohort (10–12 years) than in the 6 to 12-year-olds. Study drug was well-tolerated by the subjects in this study. Two TEAEs were reported in one subject TEAEs (diarrhea and rash on legs) occurred approximately 12 hours postdose.ConclusionsThis study confirmed that the PK profile of AMPH EROS in 6 to 12-year-olds provided a consistent, predictable extended-release profile in a highly titratable liquid formulation, and this finding was relatively consistent and directionally predictable between the age groups assessed, with higher maximum concentrations and AUCs and shorter elimination half-lives noted in the younger population, with no anomalous parameters demonstrated, and no untoward or unexpected safety issues noted.FundingTris Pharma, Inc.
Challenges in Treating Tardive Dyskinesia: Assessing the Impact of Virtual Medical Education
Authors: Glazar Amanda , Peterson Cecilia , Lemon Michael , Shah Chirag , Masand Prakash 
Published: May 2021

AbstractIntroductionTardive Dyskinesia (TD) refers to abnormal, involuntary, choreoathetoid movements of the tongue, lips, face, trunk, and extremities and is associated with long-term exposure to dopamine-blocking agents, such as antipsychotic medications. Once established, these movements usually persist. The movements are disfiguring and can bring unwanted attention to affected individuals. When severe, especially if the respiratory muscles are affected, the movements can be disabling, limit activity, and reduce quality of life. The prevalence is 7.2% in individuals on newer antipsychotics who have never been exposed to older neuroleptics. Until recently, there were no effective treatments for TD. In recent years, many new treatments have been investigated for the treatment of TD, including valbenazine, deutetrabenazine, and branched chain amino acids. Valbenazine first, followed by deutetrabenazine are FDA approved to treat TD. A virtual broadcast was developed to assess the ability of continuing medical education (CME) to improve awareness of the recognition and treatment of TD among psychiatrists.MethodsThe virtual broadcast (May 9, 2020) consisted of a two-hour, live-streamed discussion between two expert faculty. Impact of the educational activity was assessed by comparing psychiatrists’ responses to four identical questions presented before and directly after activity participation. A follow-up survey was sent to all participants six-weeks post-activity to measure performance in practice changes. A chi-square test was used to identify significant differences between pre- and post-assessment responses. Cohen’s d was used to calculate the effect size of the virtual broadcast.ResultsActivity participation resulted in a noticeable educational effect among psychiatrists (n=621; d=6.12, P<.001). The following areas showed significant (P<0.05) pre- vs post-educational improvements: recognition of movements in patients with TD, rate of TD in SGA exposed patients, treatment options for TD (on and off-label), and treatment of TD using VMAT inhibitors. Additionally, 54% of psychiatrists reported a change in practice performance as a result of the education received in the activity, including utilization of a standard scale to evaluate movement disorders and educate patients and family members about potential for TD, how to recognize symptoms, and when to treat.ConclusionsThe results indicated that a CME-certified two-hour virtual broadcast was effective at improving knowledge among psychiatrists for the recognition and treatment of TD. This knowledge also resulted in positive changes in practice performance post-activity. Future education should continue to address best practices in the diagnosis, treatment and management of patients with TD, as there remains an increased need for tailored CME among psychiatrists.FundingNeurocrine Biosciences, Inc.
The Incidence and Economic Burden of Extrapyramidal Symptoms in Patients with Schizophrenia Treated with Atypical Antipsychotics
Authors: Kadakia Aditi , Brady Brenna L. , Huang Huan , Dembek Carole , Williams G. Rhys , Kent Justine M. 
Published: May 2021

AbstractObjectiveExtrapyramidal symptoms (EPS), including movement disorders, tremors, and muscle contractions are common side effects of atypical antipsychotic (AAP) drugs in patients with schizophrenia. This study examined the incidence and burden of EPS in patients with schizophrenia initiating AAPs.MethodsPatients with schizophrenia initiating AAPs with no prior EPS were identified in the MarketScan Multi-state Medicaid database from 1/1/2012-12/31/2018. Incidence of EPS (identified via ICD-9/ICD-10 diagnoses and medications) was assessed during the 12-months following AAP initiation. Cohorts with and without EPS were defined. Demographics, clinical characteristics, and healthcare resource use and costs over 12 months following the first EPS claim (EPS) or randomly assigned index date (Non-EPS) were assessed.ResultsA total of 11,642 patients with schizophrenia were identified; 21.2% developed EPS in the 12-months following AAP initiation. EPS and Non-EPS cohorts included 2,295 (mean age 38, 61% male, CCI 0.6) and 5,607 (mean age 39, 57% male, CCI 0.7) patients, respectively. Over the 12-month post-index period, EPS cohort had significantly higher rates of all-cause (30.2% vs. 24.6%, p<0.001) and schizophrenia-related hospitalizations (22.5% vs. 12.9%, p<0.001) and schizophrenia-related emergency room visits (25.5% vs. 16.7%, p<0.001) compared to Non-EPS cohort. All-cause ($25,911 vs. $21,550, p<0.001) and schizophrenia-related healthcare costs ($12,134 vs. $6,230, p<0.001) were significantly higher in EPS vs. Non-EPS cohort.ConclusionsIn the 12 months following AAP initiation, over 20% of schizophrenia patients developed EPS, which was associated with increased healthcare resource utilization and costs. Treatment options that minimize EPS may reduce the economic burden of schizophrenia.FundingSunovion Pharmaceuticals Inc.
Hospitalization Risk Among Adults with Bipolar I Disorder Treated with Oral Atypical Antipsychotics: A Long-Term Data Analysis of Medicaid Claims Data
Authors: Niu Xiaoli , Veeranki Phani , Dennen Syvart , Liu Yanmei , Shafrin Jason , Dembek Carole , Laubmeier Kimberly , Williams G. Rhys 
Published: May 2021

AbstractObjectiveTo compare the risk of hospitalization for adult Medicaid beneficiaries with bipolar I disorder (BPD-I) when treated with lurasidone compared to other atypical antipsychotics (AAPs) as monotherapy.MethodsUsing IBM MarketScan Multi-State Medicaid Claims database, a retrospective cohort study was conducted on adult BPD-I patients who initiated an AAP (index date) between January 1, 2014 and June 30, 2019. Patients were required to be continuously enrolled during the 12-month pre- and 24-month post-index date. Marginal structural models were performed to estimate the risk of hospitalization (all-cause, BPD-I-related, and psychiatric-related) associated with each AAP and the average length of stay.ResultsThe analysis included 8262 adult BPD-I patients, of whom AAP use was divided between lurasidone (14%), aripiprazole (17%), olanzapine (8%), quetiapine (29%), risperidone (10%), no/minimal (1%) or other (21%) during each month of post-index period. The adjusted odds ratios (aORs) for all-cause hospitalization were significantly higher for olanzapine (aOR=1.60, 95% CI=1.09–2.10) and quetiapine (aOR=1.54, 95% CI=1.18–1.89), compared to lurasidone. The aORs for BPD-I-related hospitalization were significantly higher for quetiapine (aOR=1.57, 95% CI=1.10–2.04) and risperidone (aOR=1.80, 95% CI=1.04–2.56) compared to lurasidone. The average length of hospital stay was more than twice as high for quetiapine compared to lurasidone (aRR=2.12, 95% CI=1.32–2.92). The risk of psychiatric-related hospitalization was numerically lower for lurasidone compared to all other AAPs.ConclusionOver a 24-month follow-up period, lurasidone-treated adult BPD-1 patients had significantly lower risk of all-cause hospitalization than those treated with olanzapine and quetiapine, lower risk of BPD-I-related hospitalization than quetiapine and risperidone, and fewer hospital days than quetiapine in a Medicaid population.FundingSunovion Pharmaceuticals Inc.
Could Improved Microcirculation Reverse the Effects of Fetal Alcohol Syndrome? A Review
Authors: Yavari Arman Phillipe 
Published: May 2021

AbstractFetal alcohol spectrum disorders, (FASDs) are a spectrum of neurodevelopmental and cognitive conditions, caused by the consumption of alcohol in varying amounts in utero that affect an estimated 1 - 5% of the general population in the United States. The effects of the spectrum of disorders are lifelong, resulting in often significant learning difficulties, cognitive deficits, and behavioral issues. It is known that blood flow and microcirculation to the brain are affected by the consumption of alcohol in utero, and that microcirculation and neurology are intimately linked, with changes in the former having drastic effects on the latter. The purpose of the current review is to analyze whether improvement in microcirculation in the infant or child with FASDs could affect quality of clinical outcomes in the spectrum of disorders, or lead to the improvement of disorder-related symptoms. Scientific evidence from the literature suggests that, in theory, improving cerebral microcirculation in the infant or young child with FASDs could lead to a corresponding improvement in neurological health, and potentially an improvement in cerebral development, which may in theory lead to a lessening of symptoms. Further review into the connection between microcirculation and neurological health, and correspondingly, clinical outcomes in patients with neurological deficits, is warranted.
Perampanel-Induced Cataplexy in a Young Male with Generalized Epilepsy
Authors: Kenaan Kelsey , Zafar Mohsin , Bond Ronnie , Gracious Barbara 
Published: May 2021

AbstractPerampanel is an anti-epileptic drug reported to exert its effects in the central never system (CNS) by inhibiting post-synaptic glutamate receptors. The most commonly reported neuropsychiatric side effects are affective dysregulation with some reports of psychosis. However, the precise therapeutic mechanism is unknown. We report on a 32-year-old African American male with recurring generalized tonic-clonic (GTC) seizures, who presented to our hospital with onset of mood lability for several months, subsequent to adding perampanel to his antiepileptic medications. On presentation, perampanel administration was temporarily withheld, and subsequently, noted to be coincident with neuropsychiatric symptomatology, including motor weakness in emotional contexts. The mechanisms underlying cataplexy are complex and, in our patient, most likely induced by an interaction between perampanel and the wakeful inhibition of the sublaterodorsal nucleus projections.
Untreated Insomnia in Corrections and Increased Risk of Death
Authors: Collins Caiti , Wallis Richard 
Published: May 2021

AbstractStudy ObjectivesThis review discusses the potential negative consequences of untreated insomnia in correctional settings.MethodsA literature review was conducted on the association between insomnia and negative health outcomes, the best practices for treating insomnia with and without medications, and common practices that prohibit the treatment of insomnia in correctional settings.ResultsUntreated insomnia was associated with increased psychiatric distress, increased risk for suicide, and increased all-cause mortality. Common practices in many correctional institutions impose restrictions on treating insomnia. These practices lead to an increased likelihood for negative health outcomes, including suicide and an increase in all-cause death.ConclusionsPractices that prohibit the treatment of sleep in correctional settings increase the risk of death by suicide and other adverse health outcomes. The practices are often put in place due to pressure from the security staff who have trouble controlling the black-market trade of prescribed medications and other contraband within jails and prisons. Healthcare professionals in the correctional setting must advocate for the importance of treating sleep problems in jails and prisons and work with security staff on ways to overcome the problems of pill diversion and the trade of contraband in order to provide quality healthcare to this protected population.
Evaluation of MADRS Severity Thresholds in Patients With Bipolar Depression
Authors: Thase Michael E. , Harrington Amanda , Calabrese Joseph , Montgomery Stuart , Niu Xiaomeng , Patel Mehul 
Published: May 2021

AbstractIntroductionThe Montgomery-Åsberg Depression Rating Scale (MADRS) is commonly used for the assessment of depressive symptom changes in patients with major depressive disorder (MDD) or bipolar depression. Categories of depression severity that correspond to ranges of MADRS total score have been previously reported in patients with MDD, but it appears that MADRS severity ranges have not been reported for patients with bipolar I disorder. The objective of this study was to evaluate MADRS total score ranges that correspond with different grades of depression severity in patients with bipolar I depression.MethodsData were pooled from 3 randomized, double-blind, placebo-controlled, 6- or 8-week trials of cariprazine in patients with bipolar I depression. MADRS severity ranges were evaluated using an anchor-based approach with the clinician-rated, 7-category Clinical Global Impression-Severity (CGI-S) scale. CGI-S has previously been used to determine severity thresholds in MDD. Correlations between MADRS total score and CGI-S score were assessed in the pooled dataset at week 6; placebo and active treatment arms were pooled together. Youden index from receiver operating characteristic (ROC) curves was used to determine the optimal threshold for MADRS total score corresponding to each CGI-S severity level.ResultsThe pooled dataset included 1523 patients with bipolar depression. Mean CGI-S scores were highly correlated with mean MADRS total scores at week 6 (r=.87; P<.0001), with MADRS total scores increasing with CGI-S severity. Using the ROC curves, MADRS total score ranges corresponding to each CGI-S severity category were estimated as follows: score of 0-6 for “normal, not at all ill”, 7-12 for “borderline mentally ill”, 13-18 for “mildly ill”, 19-23 for “moderately ill”, 24-36 for “markedly ill”, 37-39 for “severely ill”, and 40 or greater for “extremely ill”. Area under the curve (AUC) values for these cutoffs ranged from 0.930 to 0.997, representing outstanding sensitivity and specificity.ConclusionsUtilizing data from 3 recent clinical trials of subjects with bipolar depression, we were able to identify MADRS severity thresholds. These empirical findings may help clinicians to understand and contextualize MADRS results from bipolar clinical research and apply to their patients in practice.FundingAbbVie Inc.
Assessment of iodine nutrition of schoolchildren in Gonda, India, indicates improvement and effectivity of salt iodisation
Authors: Gaurav Kushagra , Yadav Subhash , Kumar Sheo , Mishra Anjali , Godbole Madan M , Singh Uttam , Mishra Saroj K 
Published: May 2021

AbstractObjective:To study the total goitre rate (TGR), urinary iodine concentration (UIC) and salt iodine content among schoolchildren in a previously endemic area for severe iodine deficiency disorder (IDD).Design:Cross-sectional epidemiological study.Setting:The study was carried out in the Gonda district (sub-Himalayan region) of North India.Participants:Nine hundred and seventy-seven schoolchildren (6–12 years) were studied for parameters such as height, weight, UIC and salt iodine content. Thyroid volume (TV) was measured by ultrasonography to estimate TGR.Results:The overall TGR in the study population was 2·8 % (95 % CI 1·8, 3·8). No significant difference in TGR was observed between boys and girls (3·5 % v. 1·9 %, P = 0·2). There was a non-significant trend of increasing TGR with age (P = 0·05). Median UIC was 157·1 μg/l (interquartile range: 94·5–244·9). At the time of the study, 97 % of salt sample were iodised and nearly 86 % of salt samples had iodine content higher than or equal to 15 part per million. Overall, TGR was significantly lower (2·8 % v. 31·0 %, P < 0·001), and median UIC was significantly higher (157·1 v. 100·0 μg/l, P < 0·05) than that reported in the same area in 2009.Conclusions:A marked improvement was seen in overall iodine nutrition in the Gonda district after three and a half decades of Universal Salt Iodisation (USI). To sustainably control IDD, USI and other programmes, such as health education, must be continuously implemented along with putting mechanisms to monitor the programme at regular intervals in place.
An efficient and novel treatment regimen including temozolomide for medulloblastoma: a case study
Authors: Arbabi-Kalati Farshid , Dadras Ali , Nami Mohammad 
Published: May 2021

Abstract

Background:
The central nervous system (CNS) embryonal tumour is a rare malignancy reported in adults and more commonly in children. The most available treatments may cause neurological dysfunctions requiring clinical attention.

Case presented:
A 29-year-old male was referred with ataxia and diplopia, and brain imaging revealed a posterior fossa lesion suggesting medulloblastoma. The tumour and related symptoms were notably alleviated following treatment with dexamethasone. Following the recurrence of tumour, a biopsy and pathology report, the diagnosis of desmoplastic/nodular medulloblastoma was confirmed. The patient underwent 18 fractions of 180 cGy spine and whole-brain radiation therapy (RT). In addition, 5400 cGy irradiation in 12 fractions was given to the posterior fossa together with 2 mg/m2 intravenous vincristine (VCR) weekly over 6 weeks. Following a 3-week break, the patient was scheduled to receive 150 mg/m2/day temozolomide for 5 days, 2 mg VCR and 65 mg/m2/day cisplatin every 3 weeks for 8 cycles.

Conclusion:
The patient gained survival benefit to date (60 months since diagnosis) with favourable life quality. The promising response in this one exemplary case study proposes that a combined chemotherapy regimen including temozolomide, vincristine and cisplatin is an effective treatment choice for CNS embryonal tumours following RT; however, the further evaluation and a randomised clinical trial are needed.
High‐Resolution Numerical Modeling of Barotropic Global Ocean Tides for Satellite Gravimetry
Authors: Sulzbach R. , Dobslaw H. , Thomas M. 
Published: May 2021

AbstractThe recently upgraded barotropic tidal model TiME is employed to study the influence of fundamental tidal processes, the chosen model resolution, and the bathymetric map on the achievable model accuracy, exemplary for the M2 tide. Additionally, the newly introduced pole‐rotation scheme allows to estimate the model’s inherent precision (open ocean rms: 0.90 cm) and enables studies of the Arctic domain without numerical deviations originating from pole cap handling. We find that the smallest open ocean rms with respect to the FES14‐atlas (3.39 cm) is obtained when tidal dissipation is carried out to similar parts by quadratic bottom friction, wave drag, and parametrized eddy‐viscosity. This setting proves versatile to obtaining high accuracy values for a diverse ensemble of additional partial tides. Using the preferred model settings, we show that for certain minor tides it is possible to obtain solutions that are more accurate than results derived with admittance assumptions from data‐constrained tidal atlases. As linear admittance derived minor tides are routinely used for de‐aliasing of satellite gravimetric data, this opens the potential for improving gravity field products by employing the solutions from TiME.