bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved MOCA Scores While on Clozapine Gains Insight into HIV
Authors: Seamon Amanda , Shashank Reddy 
Published: April 2022

AbstractIntroductionMany patients suffer from comorbid HIV and Schizophrenia diagnoses. Patients with schizophrenia and other psychosis are at increased risk of contracting HIV due to numerous psychosocial factors including increased frequency of drug use, increased rates of victimization, and increased propensity for high-risk sexual behaviors. In addition to deficits in functioning related to psychiatric illness, patients with HIV also suffer from virus-related neurocognitive insults. It is quite possible that inflammation associated with an untreated HIV infection could compound the pre-existing neurocognitive decline seen in patients with schizophrenia and other psychosis, creating poor outcomes and treatment-resistant pathology. The benefit of clozapine treatment for schizophrenia patients with comorbid HIV extends beyond just symptomatic control. Long-term and consistent treatment of schizophrenia can be a stepping-stone for the improvement of many psychosocial aspects of life. Patients with well-controlled schizophrenia can lead relatively unaffected lives with improved insight and self-care. Improved insight allows patients to better understand their illness, treatment regimen, and follow-up needs. Improved self-care contributes to increased adherence to treatment regimens and overall health. It is likely that patients who are consistently treated for their schizophrenia will have an increased capacity to understand their HIV diagnosis. With gained understanding, these patients may be more likely to adhere to HAART therapy for HIV and to attend follow-up appointments with infectious disease or primary care. Furthermore, with adherence to HAART therapy, patients can enjoy an improved quality and duration of life by raising CD4 counts and preventing progression to AIDS or succumbing to AIDS-related opportunistic infections.MethodsA patient with schizophrenia and HIV diagnosis was monitored and interviewed with repeated MOCA scoring over a lengthy hospitalization period. During this time, he was titrated to an effective dose of clozapine totaling 400 mg at bedtime. His MOCA scores were compared over this period.ResultsIn this case, we have observed that starting a patient on clozapine with therapeutic levels for adequate period has improved MOCA scores. Low MOCA scores could be due to untreated HIV, untreated underlying psychosis. Improved MOCA scores have led the patient to gain insight into his HIV diagnosis. For the first time, he felt the need to be on antiretroviral medication and understood the chronic nature of his illness.ConclusionsIn conclusion, this case describes a patient with untreated HIV and comorbid schizophrenia who is started on clozapine to gain insight into his medical conditions and become more adherent with HIV HAART. The patient shows improvement in PANSS and MOCA scores, supporting an increased awareness of his illness and an increased ability to remain on treatment.FundingNo funding
Anosmia as an Enantiopathy for Migraines
Authors: Singh Amrinder , Rubani Sidhu , Ribeiro Estevao , Kaur Vikram Preet , Hirsch Alan 
Published: April 2022

AbstractIntroductionElimination of olfactory sensory perception with a reduction in odor-induced migraine has not heretofore been reported.MethodsCase study: A 64-year-old right-handed woman presented with a history of common migraines since childhood. The headaches were bilateral, throbbing, pulsatile, and without aura and were associated with lightheadedness, photophobia, sonophobia, nausea, and vomiting. They would be precipitated by ambient aromas, such as perfumes and bath products, and she became agoraphobic, fearful of going out of her domicile and being exposed to odors. She avoided stores, perfume counters, and public places; scared that it would initiate a disabling headache. Twenty-five years prior to presentation, the patient fell on ice, striking her head and causing a transient loss of consciousness and persistent absence of smell and taste. From that point forwards, while she would have an occasional headache independent of an odor, she no longer experienced odor-induced headaches. Her agoraphobia had resolved. Since the head trauma, her smell remained at 10% to 20%. Her taste remained at 30% of normal.ResultsAbnormalities on neurological examination: Motor examination: Drift testing: Right pronator drift with right abductor digiti minimi sign. Cerebellar examination: Bilateral finger-to-nose dysmetria. Rapid alternating movements: decreased in the left upper extremity. Reflexes: Bilateral upper extremity 3+. Absent bilateral ankle jerks. Bilateral palmomental and Hoffmann reflexes present. Chemosensory testing: Olfaction: Brief Smell Identification Test (B-SIT): 7 (hyposmia), Alcohol Sniff Test: 0 (anosmia). Retronasal Olfaction: Retronasal Smell Index: 4 (hyposmia). Gustation: Propylthiouracil Disc Taste Test: 10 (normogeusia). While performing the B-SIT and sniffing the aroma of rose, the patient noted the sudden onset of a headache, even though she could not detect any odor present.DiscussionThe temporal relationship between loss of sense of smell and elimination of odor-induced migraines suggests a causal relationship. Conscious recognition of odor may induce a stimulus-response paradigm, whereby migraine occurs. Head trauma-induced anosmia, by elimination of conscious perception of the odor, may thus be the modality whereby her headaches resolved. Alternatively, odors may induce an autonomic response, and conscious recognition of such autonomic response may induce a headache. To tergiversate, that the rose aroma in the B-SIT induced a headache, without any conscious detection of the odor, implies that either unconscious perception is enough to precipitate a headache or that these odors act not as odorants, but rather as an exogenous ambient chemical inducing headaches. Possibly the production of temporary anosmia by use of nose clips may be utilized as a prophylactic device for those with odor-induced migraines. Further investigation into this is warranted.FundingNo funding
A Structured Benefit-Risk Assessment to Evaluate a Combination of Olanzapine and Samidorphan for the Treatment of Schizophrenia and Bipolar I Disorder
Authors: Roy Brittany D. , McDonnell David , Yu Bei , Graham Christine , Jiang Ying , Yagoda Sergey , Bhupathi Vasudev , DiPetrillo Lauren 
Published: April 2022

AbstractBackgroundA combination of olanzapine and samidorphan (OLZ/SAM) that provides the efficacy of olanzapine while mitigating weight gain was recently approved by the FDA for the treatment of schizophrenia and bipolar I disorder. To improve communication of the OLZ/SAM benefit-risk profile, a structured framework was utilized.MethodsThe Benefit-Risk Action Team framework was used to evaluate OLZ/SAM, with analyses completed for each pivotal study. ENLIGHTEN-1 evaluated antipsychotic efficacy and safety. ENLIGHTEN-2 evaluated the weight profile of OLZ/SAM vs olanzapine. Benefit-risk outcomes were selected based on study outcome parameters, known risks of olanzapine and samidorphan, and public health importance. A subset of opioid antagonist risks was not assessed due to clinical trial exclusions; however, they were factored into the overall evaluation. Risk differences and confidence intervals were analyzed.ResultsIn ENLIGHTEN-1, OLZ/SAM had a lower risk of psychiatric discontinuation and nonresponse to treatment compared with placebo; higher risks of hyperprolactinemia, weight gain (≥7%), sedation, and worsening of fasting triglycerides and glucose, and no difference for fasting total and LDL cholesterol, neutropenia, orthostatic hypotension, and movement disorders. In ENLIGHTEN-2, OLZ/SAM had reduced risks of weight gain and waist circumference increase compared to olanzapine along with similar risks of relapse and psychiatric discontinuation and no difference in metabolic worsening, neutropenia, hyperprolactinemia, orthostatic hypotension, sedation, and movement disorders.DiscussionBased on this assessment, OLZ/SAM has comparable efficacy and a safety profile consistent with olanzapine, with reduced weight gain. A structured approach to assessing the benefit-risk profile of a product facilitates transparent evaluation and communication.FundingAlkermes, Inc.
Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose Study to Evaluate the Efficacy and Safety of the Amphetamine Extended-Release Tablet in Adults with Attention-Deficit/Hyperactivity Disorder
Authors: Cutler Andrew J. , Childress Ann C. , Pardo Antonio , Rafla Eman , Duhoux Stephanie , Kando Judith C. , Dansie Lori 
Published: April 2022

AbstractBackgroundAttention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by pervasive impairment in symptoms of inattention, hyperactivity, and impulsivity. Psychopharmacologic treatment is targeted at the management of symptoms of ADHD, and evidence exists that ADHD persists into adulthood. Clinical practice guidelines recommend a combination of behavior therapy and psychostimulant medication for the treatment of ADHD in children, adolescents, and adults. Psychostimulants are often prescribed for ADHD in adults, and amphetamine long has been considered a mainstay of treatment for this population. As adult patients seek relief from ADHD symptoms early in the workday and into the early evening hours, with fewer required doses, extended-release formulations with an early onset of efficacy and an extended duration of effect are considered very desirable. The amphetamine-extended release tablet (AMPH ER TAB) was developed to provide a portable, easy-to-use amphetamine tablet dosage option that can be chewed or swallowed whole.ObjectivesTo evaluate the efficacy and safety of an Amphetamine Extended-Release Tablet (AMPH ER TAB) in adults with ADHD aged 18 to 60 years. Methods: In a 5-week forced dose-titration phase, eligible subjects were randomized to either oral double-blind AMPH ER TAB 5 mg starting dose or matching placebo, once daily in the morning beginning the day after the Baseline Visit. Subjects were titrated up (5 mg increments) each week. Safety and efficacy assessments were done weekly. After Visit 3, subjects received 20 mg for 14 (3) days before Visit 5 (V5). Subjects who could not tolerate study drugs discontinued. A Permanent Product Measure of Performance (PERMP) placement test was done at Screening or Baseline. At V5, efficacy assessments included the administration of serial PERMPs predose, 0.5, 1, 2, 4, 8, 10, 12, 13, and 14 hours postdose. The primary efficacy endpoint was the mean PERMP-T score across postdose time points during the Visit 5 serial PERMPs. Safety was monitored by AEs assessed at each visit, C-SSRS, vital signs, weight, and assessment of sleep, appetite, mood, and psychotic AEs.ResultsThe mean postdose PERMP-T score over all postdose time points at V5 was statistically significantly higher in the AMPH ER TAB group vs placebo (302.8 vs 279.6; P = .0043). Common adverse events were decreased appetite, insomnia, and dry mouth. The majority of TEAEs were mild to moderate in severity, and no SAEs were reported.ConclusionThe AMPH ER TAB demonstrated efficacy in the treatment of symptoms of ADHD in adults, with an anticipated safety profile.FundingTris Pharma, Inc.
Social Cognition and Behavioral Variant of Frontotemporal Dementia: Evaluative Utility for the Health and Forensic Field
Authors: Mazzoglio y Nabar Martin J. , Leidi Terren Emmanuel E. , Silva Daniel H. 
Published: April 2022

AbstractIntroductionThe behavioral variant of frontotemporal dementia presents clinical specificities and difficulties for its early diagnosis in the initial stages due to the overlap of symptoms with other psychiatric pathologies. The delay in diagnosis places the subject in a state of vulnerability because the treatment will not be adequate and the alteration in the psycho-functional capacity can expose him to risks.ObjectiveThe objective of this research was to describe the importance at the forensic and health level of the neuropsychological evaluation of social cognition in people with behavioral variant frontotemporal dementia and to correlate the results with the clinical manifestations of the patients.Materials and MethodsForty-five patients with behavioral variant frontotemporal dementia were studied with social cognition tests (Reading the Mind in the Eyes and Faux Pas Tests) and staged with standardized scales (CDR [Clinical Dementia Rating], GDS [Global Deterioration Scale], and the FTD-FRS [Frontotemporal Dementia Rating Scale]). The results were analyzed with descriptive and inferential statistical tests and the current ethical-legal requirements were met (requirement of informed consent, reservation of the identity of the participants, compliance with the GCP-Good clinical practice-, ANMAT provision 6677/10 and adherence to the Ethical Principles derived from the Declaration of Helsinki).ResultsWe found a significant prevalence of alterations in social cognition tests, mainly in Faux Pas Test, from the initial stages of the disease, which were correlated with the clinical stage of the patient.ConclusionsThe behavioral variant of frontotemporal dementia is a condition with significant diagnostic complexity in its initial stages that affects decision-making, the type of treatment to be instituted and presents the consequences for the subject and their environment. Early detection with a deep assessment of social tools will provide clinical tools for pharmacological treatment, as well as to know the capacity and safeguard the rights of the subject and implement the necessary support measures. It was confirmed that the alterations in the social cognition tests were correlated with the clinical stage in the FTD-FRS scale and high implication in the results of the Faux Pas Test mainly, and secondarily in the Reading the Mind in the Eyes Test.FundingNo funding
Efficacy, Tolerability, and Safety of Atypical Antipsychotics in East Asian Ethnicity
Authors: Hina Mehwish , Sultana Tania , Youn Sophia 
Published: April 2022

AbstractBackgroundA number of intrinsic (age, gender, physical comorbidities, genetic factors, and ethnicity), and extrinsic factors (diet, concomitant medications, alcohol use, and smoking) influence an individual’s response to psychotropic medications. Data suggest that ethnicity may affect medication efficacy, tolerability, and safety through different pharmacokinetics and pharmacodynamics. Asians have been found to have a high frequency of reduced function of CYP2D6 allele (CYP2D6*10), which contributes to the slower metabolism of some medications compared to other ethnic groups. The previous study has shown East Asians appear to have a clinically relevant decrease in clozapine clearance compared with Caucasians. This review will explore the magnitude of the impact of ethnicity, especially the East Asian population on psychotropic medications such as atypical antipsychotics.ObjectiveTo understand the efficacy, safety, and tolerability of atypical antipsychotics in East Asian ethnicity. To emphasize the importance of ethnicity in clinical practice while offering/prescribing atypical antipsychotic medications.DiscussionSeveral previous studies reported the diverse response to the antipsychotics among different ethnicities secondary to differences in pharmacokinetics and pharmacodynamics. One study revealed White Europeans may require higher doses of therapeutic antipsychotics than Asians and Hispanics. Aripiprazole in Asians had a relatively higher rate of akathesia, and a significantly increased risk of tremor compared to placebo. A significantly increased risk of weight gain and fasting total cholesterol from olanzapine were observed in Japanese patients. Olanzapine was also associated with somnolence and dizziness. Quetiapine XR was associated with a significant increase risk of somnolence and dizziness in Chinese patients.ConclusionIt is indicated from previous studies antipsychotics respond in various ways in different ethnicity in terms of metabolism, clearance, and adverse effects. Further research could be beneficial on what is clinically most effective dosing of different antipsychotics among different populations including East Asians.FundingNo funding
Long-Term Efficacy and Safety of Deutetrabenazine in Patients with Tardive Dyskinesia by Concomitant Dopamine-Receptor Antagonist Use
Authors: Hauser Robert A. , Barkay Hadas , Fernandez Hubert H. , Factor Stewart A. , Jimenez-Shahed Joohi , Gross Nicholas , Marinelli Leslie , Wilhelm Amanda , Gordon Mark Forrest , Savola Juha-Matti , Anderson Karen E. 
Published: April 2022

AbstractIntroductionTardive dyskinesia (TD) is an involuntary movement disorder that can result from exposure to dopamine-receptor antagonists (DRAs). Deutetrabenazine demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores in the 12-week pivotal trials (ARM-TD/AIM-TD). This post hoc analysis assessed the long-term efficacy and safety of deutetrabenazine by baseline DRA use.MethodsPatients who completed ARM-TD or AIM-TD enrolled in the 3-year, open-label extension (OLE) study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in total motor AIMS score, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and adverse event (AE) rates were analyzed in subgroups by baseline DRA use.ResultsOf 337 patients in the OLE study, 254 were taking DRAs at baseline (mean age, 56 years; 48% male; 6.0 years since diagnosis) and 83 were not (mean age, 60 years; 31% male; 4.9 years since diagnosis). Mean ± SE dose at week 145 was 39.9 ± 1.0 mg/day in patients taking DRAs (n = 108) and 38.5 ± 1.5 mg/day in patients not taking DRAs (n = 53). At week 145, mean ± SE change from baseline in AIMS score was −6.1 ± 0.43 and −7.5 ± 0.71; 64% and 62% achieved PGIC treatment success; and 69% and 81% achieved CGIC treatment success, respectively. Overall AE incidence was low (exposure-adjusted incidence rates [incidence/patient-years]: any, 1.08 and 1.97; serious, 0.10 and 0.12; leading to discontinuation, 0.06 and 0.05).ConclusionThis analysis suggests that deutetrabenazine for long-term treatment of TD is beneficial, with a favorable safety profile, regardless of concomitant DRA use.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel
The Rey Auditory Verbal Learning Test: Cross-validation of Mayo Normative Studies (MNS) demographically corrected norms with confidence interval estimates
Authors: Loring David W. , Saurman Jessica L. , John Samantha E. , Bowden Stephen C. , Lah James J. , Goldstein Felicia C. 
Published: April 2022

AbstractObjective:The Mayo Normative Studies (MNS) represents a robust dataset that provides demographically corrected norms for the Rey Auditory Verbal Learning Test. We report MNS application to an independent cohort to evaluate whether MNS norms accurately adjust for age, sex, and education differences in subjects from a different geographic region of the country. As secondary goals, we examined item-level patterns, recognition benefit compared to delayed free recall, and derived Auditory Verbal Learning Test (AVLT) confidence intervals (CIs) to facilitate clinical performance characterization.Method:Participants from the Emory Healthy Brain Study (463 women, 200 men) who were administered the AVLT were analyzed to demonstrate expected demographic group differences. AVLT scores were transformed using MNS normative correction to characterize the success of MNS demographic adjustment.Results:Expected demographic effects were observed across all primary raw AVLT scores. Depending on sample size, MNS normative adjustment either eliminated or minimized all observed statistically significant AVLT differences. Estimated CIs yielded broad CI ranges exceeding the standard deviation of each measure. The recognition performance benefit across age ranged from 2.7 words (SD = 2.3) in the 50–54-year-old group to 4.7 words (SD = 2.7) in the 70–75-year-old group.Conclusions:These findings demonstrate generalizability of MNS normative correction to an independent sample from a different geographic region, with demographic adjusted performance differences close to overall performance levels near the expected value of T = 50. A large recognition performance benefit is commonly observed in the normal aging process and by itself does not necessarily suggest a pathological retrieval deficit.
An Outstanding Claim: The Ryukyu/Okinawa Peoples’ Right to Self-Determination under International Human Rights Law
Authors: ABE Ai 
Published: April 2022

AbstractThis paper aims to examine the legitimacy of Ryukyuans/Okinawans’1right to self-determination (RSD) under international human rights law. To this end, it first details the evolution of the RSD from the traditional right to independence for colonial peoples, to the continuing right to self-governance for wider groups of peoples, which is followed by an analysis of holders of the RSD. The paper then turns to Ryukyu/Okinawa to discuss the RSD of its peoples. Three historical events, the Disposition of Ryukyu, the Treaty of San Francisco, and the reversion of Okinawa to Japan, are analysed from a legal perspective, followed by an examination of the peoplehood of Ryukyuans/Okinawans. These lead to the conclusion that the Ryukyuans/Okinawans may legitimately claim that they possess the “unexercised” RSD as a quasi-non-self-governing people, and that they are entitled to claim the RSD as a “people” under the International Covenant on Civil and Political Rights, International Covenant on Economic, Social, and Cultural Rights, and other United Nations declarations.
Influence of the South American Low‐Level Jet on the Austral Summer Precipitation Trend in Southeastern South America
Authors: Varuolo‐Clarke A. M. , Williams A. P. , Smerdon J. E. , Ting M. , Bishop D. A. 
Published: April 2022

AbstractAustral summer precipitation increased by 27% from 1902 to 2020 over southeastern South America (SESA), one of the largest centennial precipitation trends observed globally. We assess the influence of the South American low‐level jet on the SESA precipitation trend by analyzing low‐level moisture fluxes into SESA in two reanalysis datasets from 1951 to 2020. Increased moisture flux through the jet accounts for 20%–45% of the observed SESA precipitation trend. While results vary among reanalyzes, both point to increased humidity as a fundamental driver of increased moisture flux and SESA precipitation. Increased humidity within the jet is consistent with warming sea surface temperatures driven by anthropogenic forcing, although additional natural climate variations also may have played a role. The jet's velocity also increased, further enhancing precipitation, but without a clear connection to anthropogenic forcing. Our findings indicate the SESA precipitation trend is partly attributable to jet intensification arising from both natural variability and anthropogenic forcing.