bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Syndrome in Bipolar Depression with Lumateperone (ITI-007): A Post Hoc Analysis of 2 Randomized, Placebo-Controlled Trials
Authors: Correll Christoph U , Kozauer Susan G , Lands Micah , Huo Jason , Durgam Suresh 
Published: April 2023

AbstractIntroductionTreatments for bipolar disorder are often associated with increased rates of metabolic syndrome (MetSy). MetSy is defined as meeting 3 of the following 5 criteria: waist circumference >40in (men) or >35in (women), triglycerides ≥150mg/dL, high density lipoprotein cholesterol <40mg/dL (men) or <50mg/dL (women), systolic blood pressure (BP) ≥130mmHg or diastolic BP ≥85mmHg, fasting glucose ≥100mg/dL.MetSy elevates the risk of developing type II diabetes, cardiovascular disease, and premature morbidity. Lumateperone (LUMA), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. This distinct pharmacological profile has been associated with favorable tolerability and a low risk of adverse metabolic effects in clinical trials.LUMA 42-mg monotherapy was evaluated in 2 randomized, double-blind, placebo (PBO)-controlled studies (Study 401 [NCT02600494]; Study 404 [NCT03249376]) in patients with a major depressive episode (MDE) associated with bipolar I or bipolar II disorder. This post hoc pooled analysis of these studies compares rates of MetSy with LUMA 42 mg and PBO in the treatment of bipolar depression.MethodsThe incidence and shift in MetSy were analyzed in data pooled from 2 studies that recruited patients aged 18–75 years with a confirmed diagnosis of bipolar I or bipolar II disorder who were experiencing an MDE (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score ≥20 and Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score ≥4). Patients in these studies were randomized 1:1 to LUMA or PBO and treated for 6 weeks.ResultsThe safety population comprised 746 patients (LUMA, 372; PBO, 374). Rates of MetSy were similar between groups at baseline (LUMA, 20.7%; PBO, 22.2%) and at the end of treatment (EOT, LUMA, 21.8%; PBO, 23.8%). More LUMA patients (36.4%) compared with PBO patients (30.1%) improved from having MetSy at baseline to no longer meeting MetSy criteria at EOT. The individual criteria that shifted the most from meeting MetSy criteria at baseline to no longer meeting criteria at EOT was BP for LUMA (46.8%) and glucose for PBO (43.2%). The rate of MetSy developed during treatment was similar for LUMA (10.8%) and PBO (10.7%) with approximately half of these patients (LUMA, 43.8%; PBO, 45.2%) shifting due to a change in ≥2 criteria.ConclusionIn this post hoc analysis of 2 randomized, PBO-controlled trials in patients with a MDE associated with bipolar I or bipolar II disorder, LUMA 42 mg had similar rates of MetSy compared with PBO. These results suggest that LUMA 42 mg is a promising new treatment for bipolar depression with a favorable metabolic profile.FundingIntra-Cellular Therapies, Inc.
IVIG for Treatment-Resistant Psychosis For a Child with Turner Syndrome
Authors: Perdomo Monica , Silverman Daniel , Hamilton Celine 
Published: April 2023

AbstractPsychosis is defined as the presence of false beliefs or false perceptions. In children some causes of psychosis include psychiatric diagnosis such as schizophrenia and autism. However, it may also be secondary to medical conditions like various forms of encephalitis. Studies have shown that IVIG has been efficacious in the treatment of psychosis in the setting of autoimmune encephalitis.A 9-year-old girl with a past medical history of Turner Syndrome, developmental delay, epilepsy, growth hormone deficiency, metabolic bone disease, and autism (ASD) presented with auditory and visual hallucinations that began June 2020. She began with her hearing voices that repeated the word “dead” and told her that she would not live. The hallucination later took the form of a man that would mock her, laugh about her parents dying, and tell her to kill them. The patient had associated symptoms of insomnia, anxiety, sadness, and increased anger. On her initial admission, CSF studies including culture and gram strain were unremarkable. NMDA, VHKC, and GAD65 antibodies were negative. At this time the hallucinations were thought to be due to ASD and she was prescribed Risperdal 0.25mg twice a day. Unfortunately, this did not improve her symptoms and from the time period of June 2020 to May 2021 she subsequently underwent trials of Risperdal, Zyprexa, Invega, Abilify, Thorazine, Haldol, and Clozaril. However, the symptoms persisted. Zoloft was prescribed, which was efficacious for anger and dysphoria. Trazodone, melatonin, and Remeron were tried for the treatment of insomnia, but did not cause enough improvement to continue the medications. Due to progression of command hallucinations with “the man” instructing her to hurt others, the patient was admitted July 2021 for administration of IVIG. Repeat CSF studies and brain MRI were unremarkable. From July 29, 2021 to August 1, 2021 she received three doses of IVIG which resulted in improvement of psychosis. Prior to administration, she was seeing “the man” throughout the day every single day, was sleeping only 3–4 hours a night, and having nightmares everyday. On evaluation 2 weeks after IVIG, she was only seeing “the man” 1–2 time a day, sleeping 6–8 hours a night, having nightmares 1–2 times a week, and her mood had improved.This case illustrates the potential use of IVIG for the treatment of treatment-resistant psychosis. Although the cause of this patient’s symptoms remains unclear, there were clear benefits from the administration of IVIG that were not seen with trials of antipsychotics.FundingNo Funding
Health-Related Quality of Life and Healthcare Resource Use: Comparison of Patients with Bipolar I Disorder and Potentially Misdiagnosed Depression
Authors: Culpepper Larry , Higa Sara , Martin Ashley , Parikh Mousam , Harrington Amanda 
Published: April 2023

AbstractBackgroundBipolar I disorder (BP-I) is associated with a high humanistic and economic burden. Evidence suggests that BP-I is often misdiagnosed as major depressive disorder (MDD), but the unmet needs associated with BP-I misdiagnosis are unknown. This study compares socioeconomic, healthcare-related quality of life (HRQoL), and healthcare resource utilization (HRU) burdens of participants diagnosed with BP-I vs participants who screened as probable for BP-I but were diagnosed only with MDD.MethodsUsing responses to the 2020 National Health and Wellness Survey, respondents were categorized into cohorts of potentially misdiagnosed BP-I (i.e., self-reported physician diagnosis of MDD but screened as probable BP-I [mBP-I]) or BP-I (i.e., self-reported physician diagnosis of BP-I, stratified by BP-I severity). Baseline characteristics were evaluated using bivariate analyses. HRQoL (Short Form-36v2 Health Survey [SF36v2] mental and physical component scores, EuroQol Five-Dimension Visual Analogue Scale [EQ-5D VAS]), HRU, were evaluated using multivariable analyses adjusting for key baseline differences.ResultsThere were 302 respondents in the mBP-I cohort and 818 in the BP-I cohort (mild=336, moderate=285, severe=197). Adults with mBP-I were similar in age and level of depression and anxiety to those with moderate and severe BP-I. With respect to HRQoL, the mBP-I cohort had significantly worse SF36v2 mental component scores and EQ-5D VAS scores vs the mild BP-I cohort (31.3 vs 40.3 [P<.001] and 60.6 vs 69.4 [P=.01], respectively) and statistically similar scores vs the moderate BP-I cohort. SF36v2 physical component scores were statistically similar to those of the mild BP-I cohort. Respondents with mBP-I reported similar rates of provider (5.5 vs 6.1 [P=.63]) and ER visits (.34 vs .40 [P=.59]) to patients with mild BP-I (but significantly fewer hospitalizations: .08 vs .19 [P=.03]).ConclusionsRespondents with mBP-I exhibited similar HRQoL scores to those with mild to moderate BP-I. As expected for patients without a formal BP-I diagnosis, HRU was lower for mBP-I patients than moderate or severe BP-I, but comparable with mild BP-I. These results suggest that patients with potentially misdiagnosed BP-I may experience considerable HRQoL and HRU burdens akin to those of patients with mild to moderate BP-I.FundingAbbVie
Stimulant Use for ADHD in a Cardiac Transplant Recipient: A Case Report
Authors: Iverson Olivia , Sinha Shirshendu , Schneekloth Terry , Hardaway Brian , Martin Kari 
Published: April 2023

AbstractIntroductionMethylphenidate is a central nervous system stimulant used as first-line treatment for attention-deficit/hyperactivity disorder (ADHD). CNS stimulant use is associated with increased risk of cardiovascular events such as increased resting heart rate and blood pressure, sudden cardiac death, arrhythmia, and stroke. Its safety profile in recipients of cardiovascular transplants is unknown, and more research is warranted to determine the risk of adverse cardiac events due to stimulant medication in this population.MethodsClinical case report, n=1Results/Clinical CaseA 19-year-old female with a history of restrictive cardiomyopathy, cardiac arrest, and orthotopic cardiac transplant has been treated with methylphenidate for ADHD for approximately 2 years without incident. The patient was diagnosed with ADHD between the ages of 8 and 10 and historically was treated with stimulant medication. At age 13, she experienced a cardiac arrest after a volleyball game with 4–6 minutes of pulselessness. She was successfully resuscitated and underwent defibrillator placement. It was concluded that the patient had restrictive cardiomyopathy undetected at birth, leading to the need for orthotopic cardiac transplantation at age 16. After her cardiac arrest, the patient’s memory and cognition worsened, and approximately 1 year after her transplant, she was prescribed amantadine. The patient remained untreated for her ADHD until approximately 1.5 years after her cardiac transplant, at which time she underwent neuropsychological testing that showed findings consistent with attention deficit disorder, and was restarted on stimulant medication. Her transplant cardiologist and psychiatrist have collaborated in her ongoing treatment with methylphenidate 40 mg daily and monitoring symptom response and cardiac stability. Because the patient had previously been stable on stimulant medication for many years, it is reasonable to conclude that stimulant medication did not lead to her cardiac arrest. The patient reports that methylphenidate has been helpful in improving her functioning as a college student, through reduction of her ADHD symptoms. The patient’s blood pressure and heart rate remain within an acceptable range and she has not experienced any adverse cardiac events to date while taking methylphenidate.ConclusionThis case sheds light on the potential to treat cardiac transplant recipients with stimulant medication for ADHD. Although a careful evaluation of risk factors must be undertaken in cooperation with cardiology and other specialists, a role exists for the safe use of stimulant medications in the cardiac transplant population.FundingNo Funding
A Review of Current Strategies in Treatment-Resistant Schizophrenia: Considering Paliperidone Palmitate LAI With and Without Olanzapine as an Alternative to Clozapine
Authors: Malik Raghav , Zaidi Muhammad 
Published: April 2023

AbstractBackgroundSchizophrenia is a debilitating mental illness that affects patient’s function and quality of life. Estimates indicate a lifetime prevalence of 0.48%, causing up to 13.4 million years of life burdened by disability. 30% of these patients are deemed as having treatment-resident schizophrenia (TRS), a subset of which do not respond to clozapine, the medication designated for TRS. Those that do not respond to clozapine are deemed to have clozapine-resistant schizophrenia (CRS), requiring further augmentation or multiple antipsychotics.Current limitationsClozapine only has limited formulations available (oral [PO] and dissolving [ODT]) and has a substantial side effect burden. Most serious among these side effects includes agranulocytosis, which in some cases can cause severe infections such as septicemia. Regular blood draws monitoring for this are vital to prevent this dangerous consequence, but place further burden on patients, requiring weekly to monthly lab work and visits. Other common and burdensome side effects include tachycardia, hypotension, sialorrhea, weight gain, and metabolic syndrome, to name a few. However, treatment for TRS is still needed, and further alternatives must be explored.Proposed alternativesAmong studies done on clozapine, few compare second-generation antipsychotics head-to-head, and those that do find similar improvement in overall symptom burden among multiple antipsychotics, especially olanzapine and paliperidone (in particular, paliperidone palmitate). Due in part to the improved receptor profile of these medications (especially 5-HT2A, 6, and 7) compared to clozapine, they can have similar or superior effect in patients with TRS without substantial patient side effect and functional burden. Paliperidone palmitate formulations are developing that can be spaced further and further apart, allowing for minimal impact on patient’s livelihood, while demonstrating similar overall effect with improved side effect profile. However, onset of action is slow, and an effective adjunct strategy may be to initially administer olanzapine for the first 6 months until peak effect is expected from paliperidone palmitate, at which point monotherapy with paliperidone is preferred.ConclusionsAlternative therapies for patients with TRS may be more functional with fewer side effects, and this work indicates a particularly effective strategy may be to pursue paliperidone palmitate monotherapy long-term while utilizing the unique combination of paliperidone and olanzapine in the short-term (first 6 months) while awaiting peak efficacy.FundingNo Funding
Ketamine in the Treatment of Delusions: A Review of the Evidence
Authors: Costa Renzo , Guieb John , Imtiaz Ayyub , Zaidi Muhammad 
Published: April 2023

AbstractIntroductionDelusions are defined as fixed false beliefs that are not within normal parameters of society, culture, or religion that can be part of psychotic or mood disorders. They can be difficult to treat and, for some inpatient individuals, persistent delusions can make safe discharge impossible. Ketamine is a dissociative agent that has shown promise in treating mood disorders. Despite this, clinicians hesitate to prescribe this when a patient presents with any type of psychotic symptom. There is proof that ketamine is safe to use with psychotic symptoms, and there is growing evidence that it may be a suitable treatment alternative for delusions resistant to other psychopharmacology.MethodsA literature review using articles from multiple databases was conducted to gather supporting evidence on the use of ketamine in the context of psychosis. Since there has not been a reported conducted study specifically for ketamine and delusions, a look into its use for psychosis was done to find links between the neurobiology of delusions and the mechanism of action of ketamine.ResultsCurrent literature does not demonstrate that ketamine within a therapeutic setting exacerbates psychotic symptoms in those with depression or bipolar disorder, regardless of the presence of psychotic features, nor does it reveal that predisposed patients experience lasting psychotic effects. Furthermore, although ketamine is often used to model schizophrenia, brain connectivity seen during ketamine-induced delusions is opposite to the connectivity seen in delusions in the context of chronic schizophrenia. Regardless of connectivity patterns, ketamine appears to act upon many of the same mechanisms that underlie delusions. There is evidence delusions are characterized by low belief flexibility, high prediction error, and high aberrant salience. An animal model of stress-induced cognitive dysfunction found that ketamine corrected the cognitive flexibility deficits. Ketamine has been shown to alter prediction error in those suffering from major depressive disorder, resulting in greater optimism bias when patients update maladaptive beliefs post-ketamine administration. In respect to aberrant salience, neural networks affecting this include midbrain dopaminergic neurons and their projections to striatal and frontal cortical regions. Studies have shown this effect was reduced by ketamine-induced plasticity in the orbitofrontal cortex.ConclusionPsychotic symptoms may not be an absolute contraindication for ketamine treatment. In fact, ketamine could be beneficial in the treatment of various mental illnesses with psychotic features that are not amenable to classical treatment. The dissociative properties may jump-start treatment while waiting for antipsychotics to work. This could significantly reduce hospital stays, especially for patients in long-term facilities.FundingNo Funding
Practical Pharmacotherapy for Opioid Use Disorder in the Age of Fentanyl
Authors: Pyo Subin , Kim Jungjin 
Published: April 2023

AbstractOpioid use disorder (OUD) is a serious public health threat. Pharmacotherapy, commonly known as medications for opioid use disorder (MOUD), is established as the cornerstone of OUD treatment. MOUDs reduce likelihood of relapse, promote recovery, and save lives. However, many clinicians are still reluctant to use these medications, in part due to inadequate training and experience. In light of the ongoing opioid overdose epidemic, it has become ever more important for clinicians to confidently and thoughtfully deploy these medications to help patients struggling with OUD. To aid busy clinicians, we have put together a review of the extant literature on three FDA-approved pharmacotherapy options—methadone, buprenorphine, and extended-release naltrexone—with a heavy focus on practical clinical application. We discuss how to effectively engage patients with OUD and initiate them on MOUDs—especially when their primary misused drug is fentanyl. We also review novel strategies, such as buprenorphine microinduction, as well as suggested best practice to effectively transition between MOUDs. Finally, we synthesize our review and recommendations in an algorithmic flowchart to provide visually compelling information.FundingNo Funding
Who benefits from the social democratic march to the middle?
Authors: Polacko Matthew 
Published: April 2023

AbstractSocial democratic parties have experienced considerable electoral decline recently, which has often been attributed to their rightward policy movement. This paper advances this literature by examining who benefits from this moderation strategy and who is abandoning the social democrats. It does so by analyzing aggregate-level election results and individual-level Comparative Study of Electoral Systems data, on a sample of 21 advanced democracies, over 327 elections, from 1965 to 2019. I find little support for the assertion that social democrats are defecting to one party. However, in agreement with the spatial theory of party competition, results reveal that the radical left increasingly and significantly benefit from social democratic economic rightward positions, which is magnified when combined with rightward sociocultural positions. This predominantly occurs because left-leaning voters migrate to the radical left. The findings provide notable ramifications for party strategy and contribute to explanations for the rise of challenger parties, at the expense of mainstream parties.
Hydrogen and Silicon Effects on Hexagonal Close Packed Fe Alloys at High Pressures: Implications for the Composition of Earth's Inner Core
Authors: Fu Suyu , Chariton Stella , Prakapenka Vitali B. , Shim Sang‐Heon 
Published: April 2023

AbstractHexagonal close‐packed (hcp) structured Fe‐Ni alloy is believed to be the dominant phase in the Earth's inner core. This phase is expected to contain 4%–5% light elements, such as Si and H. While the effects of individual light element candidates on the equation of state (EoS) of the hcp Fe metal have been studied, their combined effects remain largely unexplored. In this study, we report the equations of state for two hcp‐structured Fe‐Si‐H alloys, namely Fe0.83Si0.17H0.07 and Fe0.83Si0.17H0.46, using synchrotron X‐ray diffraction measurements up to 125 GPa at 300 K. These alloys were synthesized by cold compression of Fe‐9wt%Si in either pure H2 or Ar‐H2 mixture medium in diamond‐anvil cells. The volume increase caused by a H atom in hcp Fe‐Si‐H alloys is approximately eight times greater than that by a Si atom. We used the improved data set to develop a composition‐dependent EoS that covers a wide range of compositions. Our calculated density and bulk sound velocity of hcp Fe‐Si‐H alloys suggest a large trade‐off between Si and H contents in fitting the seismic properties of the inner core. Combining our new EoS with geophysical and geochemical constraints, we propose 1.6–3 wt% Si and 0.15–0.6 wt% H in the Earth's inner core.
Projected 21st Century Wind‐Wave Climate of Bass Strait and South‐East Australia: Comparison of EC‐Earth3 and ACCESS‐CM2 Climate Model Forcing
Authors: Liu Jin , Meucci Alberto , Young Ian R. 
Published: April 2023

AbstractThis study analyses the past and future wave climate of Bass Strait and south‐east Australia by comparing two high‐resolution regional wave climate models (RWCMs), respectively forced by the surface wind speed of EC‐Earth3 and ACCESS‐CM2 global circulation models (GCMs) under two emission scenarios (SSP1‐2.6 and SSP5‐8.5). The two RWCMs are verified against long‐term buoy and satellite observations as well as hindcast model data. The comparison with long‐term satellite altimeter observations shows good agreement between the long‐term model climate and the observations. Both RWCMs project a future increase in swell, approaching the coast of Tasmania and mainland Australia, generated from distant storms in the Southern Ocean. However, different projected wave height spatial distributions are found in the coastal regions, affected by local synoptic weather events and by the coarse resolution of the GCMs winds. We also show that the long‐term wave climate in the domain is impacted by the Southern Annular Mode. As low‐pressure systems are projected to move southward, especially in the SSP5‐8.5 scenario, the swells approaching south‐east Australia are projected to be longer and more energetic in the future. The combination of more energetic swell systems and a counterclockwise rotation in peak wave direction, projected by both RWCMs, may influence the coastal equilibrium, impacting critical coastal locations.