bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudo-Wellens Syndrome: Demonstrating the Importance of Electrocardiogram in Emergency Psychiatric Patients
Authors: Berhane Asmeret , Hashemi Ava , Imtiaz Ayyub , Elahi Adil , Zaidi Muhammad 
Published: January 2025

IntroductionPseudo-Wellens syndrome (PWS) is a rare but clinically significant condition characterized by electrocardiogram (ECG) abnormalities that mimic acute ST-segment elevation myocardial infarction (STEMI) in the absence of obstructive lesions on coronary angiography. The occurrence of PWS should be on the differential for any patient who visits the Emergency Room (ER) with known and/or suspected drug overdose. This will avoid the potential for inappropriate invasive diagnostic modalities in otherwise cardiac healthy individuals. This literature review aims to explore the ECG changes in patients diagnosed with PWS in the context of drug intoxication presenting to the ER.MethodsSpecific keywords such as "Pseudo-Wellens Syndrome," "ECG/EKG,” and "substance abuse," were used to search PubMed, Google Scholar, and PsycInfo. Articles on PWS that were not on patients presenting with substance use or not in English were removed. We extracted substance use history, ECG parameters, and their clinical presentations to the ER for review.ResultsWe found cases of PWS in patients presenting with cannabis, PCP, methamphetamine, opioid, and cocaine intoxication, either in combination or singularly. The most common ECG finding across the cases was biphasic T wave inversion in V2 and V3 with involvement in the anterior leads. The authors were unable to find any characteristic ECG changes associated with individual substances. This might be attributed by the small number of patients in the studies and due to the use of multiple drugs by patients at presentation to the ER, especially with drugs known to cause ECG abnormalities such as opioids. While PWS typically resolves spontaneously in most cases, this review revealed a concerning trend. Patients who consumed cocaine were at a higher risk of developing life-threatening cardiac conditions, including myocardial infarction. This finding underscores the importance of considering the pretest probability of acute coronary syndromes and avoiding misinterpretation of PWS as a less severe entity. For those patients presenting with a suspicious diagnosis and high pretest probability indicating an interruption of coronary blood flow, a comprehensive work up should be done to investigate any other possible life-threatening cardiac conditions.ConclusionsPWS has ST segment and T wave abnormalities, which are ECG abnormalities that are already very common in psychiatric patients seen in-hospital. Recognizing the specific ECG findings in PWS is of utmost importance for clinicians to prevent unnecessary interventions and potential harm to patients. For further understanding, more comprehensive analysis of ECG findings with larger sample sizes while considering comorbid conditions and contributing factors to the patient presentation should be conducted.FundingNo Funding
Pollock’s Abstract Images in Paintings Prior to His Drip Paintings
Authors: Morrissette Debbi Ann , Stahl Stephen M. , Gates Jon A. 
Published: January 2025

Although Jackson Pollock is most famous for his drip drawings, these occurred late in his career, starting around 1947. Prior to that he produced some “surrealist inflected” paintings and “gestural abstraction.” Troubled Queen in 1945 is considered Pollock’s masterful transitional work from the regionalist figurative paintings of his early years to the passionate “drip paintings” for which he is best known. As stated by Elliot Bostwick Davis et al (mfashop.com/9020398034), “As Troubled Queen shows, Pollock had begun to work in a very large scale by this time; his paint was dragged over, dripped on, and flung at the canvas. His subject matter was no less highly wrought: emerging from the churning coils and jagged lines of this life-sized canvas are two facelike forms, one a leering mask, the other a one-eyed diamond shape. Their nightmarish presences reflect not only Pollock’s agitated psyche but also the years of violence that had torn the world apart through war.” Thus, Troubled Queen shows that Pollock included images in his painting prior to his “drip paintings,” rendering it feasible that he continued to include images in his “drip paintings” using that new technique. We have coined the term “Polloglyphs TM” to name the images that are encrypted in his “drip paintings” and that tell a story about Pollock’s inner being, camouflaged yet hiding in plain sight.Here, in order to establish the basis for Polloglyphs in his later “drip paintings,” we have deconstructed the multiple images in Troubled Queen by first showing the image on a white background and then transposing it upon the painting. In this way, the observer can begin to see how images were incorporated into Pollock’s pre-drip paintings. These are not Rorschach ink blots with fractal edges that are fooling the eyes and only in the mind of the viewer, but images purposely put on canvas as the observer can see. Clearly, there is a “troubled queen” in Troubled Queen. Beyond that there are images of war possibly inspired by Picasso’s famous Guernica painted in 1937 and first seen by Pollock in 1939. A character is also seen to her left. Pollock had a trick that can be used to better visualize and uncover his images by rotating this painting 90 degrees counterclockwise. In this case, a small angel of mercy with her sword can be seen in the upper left quadrant. Another character, possibly a soldier with a hatchet and gun with bullet in the barrel can also be seen. Several other images can also be deciphered including a Picasso-like rooster and many others. Together, these images suggest a theme of war during the midst of World War II and may have triggered Pollock’s long standing feelings of inadequacy as his psychiatrist and his draft board found him unfit to serve as a soldier and he was exempted from serving. We encourage the observer to look carefully at Troubled Queen and to develop an opinion on which if any of the images are seen and to ponder as well what they may mean.FundingNo Funding
IDgenetix-Guided Medication Management for Major Depressive Disorder: Confirmation of Randomized Controlled Trial Outcomes by Real-World Evidence
Authors: Cao Feng , Hanson Andrea , Cook Robert 
Published: January 2025

IntroductionIDgenetix is an advanced multi-gene pharmacogenomic (PGx) test that incorporates drug-gene interactions, drug-drug interactions, and lifestyle factors to guide medication management for patients diagnosed with major depressive disorder (MDD), anxiety, or other mental illnesses. In a previously published randomized controlled trial (RCT), IDgenetix significantly improved patient response and remission rates (Bradley et al., 2018). In this analysis, we aimed to compare the clinical outcome results from the RCT with real-world evidence from an open-label study (Cao et al., 2023).MethodsSubjects with moderate to severe MDD at baseline per their HAM-D17 or PHQ-9 scores were included in the analysis for the RCT (n=261) and real-world data (n=242). In both studies, 8-week response and remission rates were analyzed for patients using IDgenetix-guided medication management (Guided) compared to patients receiving standard of care (Unguided).ResultsPatient response and remission rates strongly aligned between both studies. Response rates for the IDgenetix-guided participants in the RCT were 49% compared to 58% in the real-world data. Remission rates in the Guided group were 31% in both the RCT and real-world study compared to 22% and 19%, respectively, for participants in the Unguided group.ConclusionsComparing the clinical outcome results from the RCT with real-world data demonstrated the consistent impact of IDgenetix on patient response and remission rates. This study provides robust evidence-based research that supports the clinical use of IDgenetix to guide medication management in patients with MDD.FundingCastle Biosciences (Friendswood, TX)
Centanafadine Sustained Release Is Efficacious in Patients with Adult ADHD, Regardless of Their Treatment History
Authors: Mattingly Greg , Cutler Andrew J , Zhang Zhen , Ward Caroline , McDonough Jessica 
Published: January 2025

IntroductionCentanafadine (CTN) is a potential first-in-class norepinephrine/dopamine/serotonin triple reuptake inhibitor (NDSRI) that has demonstrated efficacy, safety, and tolerability vs placebo (PBO) in adults with ADHD in 2 pivotal phase 3 trials (Adler LA, et al. J Clin Psychopharmacol. 2022;42:429-39).MethodsPooled data from 2 double-blind, multicenter, PBO-controlled trials enrolling adults (18–55 years) meeting DSM-5 ADHD criteria were analyzed. Patients were randomized 1:1:1 to CTN sustained release (SR) 200 mg or 400 mg total daily dose (TDD) or matching PBO if Adult ADHD Investigator Symptom Rating Scale (AISRS) score was ≥28 at screening (if not receiving pharmacologic ADHD treatment) or ≥22 at screening and ≥28 at baseline (if receiving treatment). Having had no prior benefit from ≥2 ADHD therapies of different classes, use of prohibited medications, and positive alcohol/drug screens were exclusionary. Studies had 4 periods: (1) screening and washout (≤28 days), (2) single-blind PBO run-in (1 week), (3) double-blind treatment (6 weeks), and (4) follow-up (10 days after last dose). Patients with ≥30% Adult ADHD Self-report Scale (ASRS) improvement from start to end of screening were screen failures; those with ≥30% ASRS improvement from start to end of PBO run-in were terminated early. A mixed model for repeated measures analysis evaluated CTN SR vs PBO based on ADHD treatment history; least squares mean (LSM) change from baseline (BL) in AISRS at day 42 was the outcome of interest.ResultsIn total, 859 patients were analyzed (CTN SR 200 mg TDD, n=287; 400 mg TDD, n=287; PBO, n=285). LSM change from BL in AISRS score was significant at day 42 for each CTN SR TDD group (both, P<0.001) in the overall population vs PBO. Among patients with prior stimulant/nonstimulant treatment (n=542), LSM change from BL was significant at day 42 vs PBO in the CTN SR 200 mg (P=0.016) and 400 mg (P=0.008) TDD groups. Although cohort size was limited (n=47), LSM change from baseline with CTN SR 400 mg TDD was significant (P<0.05) from days 14 to 42 in those who took 2 prior stimulant/nonstimulant treatments, with P=0.030 at day 42. In those with no prior stimulant/nonstimulant treatment (n=317), LSM change from BL was significant at day 42 for the CTN SR 200 mg (P=0.007) and 400 mg (P=0.008) TDD groups vs PBO. When analyzed by history of any past stimulant use, LSM change from BL was significant at day 42 for CTN 200 mg (n=179; P=0.013) and 400 mg (n=166; P=0.006), with significance (P<0.05) noted at day 7 (200 mg TDD) and at day 21 (400 mg TDD), remaining significant to day 42.ConclusionsThis pooled analysis suggests that CTN SR treatment is efficacious in adults with ADHD, regardless of prior treatments, an encouraging finding given reported adult ADHD treatment patterns.Study Registration: NCT03605680, NCT03605836FundingOtsuka
The Use of Carbamazepine in the Management of Psychogenic Nonepileptic Seizures (PNES)
Authors: Golembeski Gregory , Kalaga Manisha , Said Khaled 
Published: January 2025

Psychogenic nonepileptic seizures (PNES) is a conversion disorder subtype that cause motor, sensory, autonomic, and cognitive symptoms that superficially resemble ictal epileptiform activity but without the electroencephalographic (EEG) activity that defines epilepsy. While 10-20% of patients referred to epilepsy centers are estimated to have PNES (1), diagnosing the condition is labor intensive as it requires seizure-like behavior observed during EEG monitoring. However, accurate diagnosis is essential as psychopharmacologic interventions have been shown to have limited utility in reducing seizure-like activity in PNES (2). Instead, case reports and small randomized clinical control trials have shown cognitive behavioral therapy (CBT) effective (3), and it is considered main stay of treatment.We present the case of a 37-year-old woman who presented to our clinic with symptoms of depression including hypersomnia and anhedonia. Her most distressing symptoms were episodes of abnormal movements and shaking without loss of consciousness. She has a past medical history notable for EEG-confirmed PNES, major depressive disorder with psychotic features, generalized anxiety disorder, clipped-intracranial aneurysm. She had been taking Duloxetine for major depressive disorder and fibromyalgia, and Carbamazepine was initiated to manage abnormal movements and her depressive symptoms. She reported improvement in the frequency and severity of abnormal movements after initiating Carbamazepine. Unfortunately, her depression worsened, and she was admitted to the inpatient unit for suicidal ideation and auditory and visual hallucinations commanding her to end her life. She was initiated on Aripiprazole. She was admitted for four days and was discharged after she demonstrated improvement in mood and severity of auditory hallucinations.FundingNo Funding
Efficacy of Viloxazine ER (Qelbree) for ADHD in Adults Based on Prior Stimulant Exposure
Authors: Mattingly Greg , Young Joel , Earnest Jami , Koch Jennifer , Qin Peibing , Rubin Jonathan 
Published: January 2025

IntroductionAlthough many patients respond equally well to both stimulant and nonstimulant medications for ADHD, some patients respond preferentially to one class over another. Currently, most patients receive a stimulant as first-line therapy; however, nonstimulants present fewer obstacles for prescribers and patients and have low abuse/misuse potential. Still, when patients have suboptimal response to stimulants, physicians may be reticent to switch to a nonstimulant medication due to concerns that the nonstimulant response will be less robust or less preferable for patients. Viloxazine ER (viloxazine extended-release capsules; Qelbree®) is a nonstimulant, FDA-approved treatment for ADHD in children (≥6 years) and adults. This post-hoc analysis of adult Phase 3 trial data (NCT04016779) evaluates response to viloxazine ER (200-600 mg/day) based on whether or not patients reported a history of previous stimulant use.MethodsFor patients randomized to viloxazine in this Phase 3, double-blind, placebo-controlled trial, the change from baseline (CFB) in Adult ADHD Investigator Symptom Rating Scale (AISRS) score (primary trial outcome) was analyzed for prior stimulant users vs. nonusers using MMRM. Prior stimulant use was based on patient-reported medication history recorded upon enrollment. Subjects using stimulants at the time of study screening were required to undergo a ≥1-week washout period prior to randomization.ResultsOf 372 patients treated, 189 received viloxazine ER. Of the patients who received viloxazine ER, 40 reported prior stimulant use and 149 did not. Mean (SD) baseline AISRS scores for prior stimulant users and nonusers were 38.5 (7.40) and 38.3 (6.44), respectively. Response appeared similar in both patient groups. At Week 6/End of Study (EOS) the least squares (LS) mean (SE) CFB AISRS scores for prior stimulant users and nonusers were -15.8 (2.51) and -15.6 (1.08)]; treatment difference -0.2 (2.41); P=0.93. Though not significant, prior stimulant users showed a larger magnitude of improvement on the AISRS at early timepoints compared to those without prior stimulant use [Week 1, LS mean (SE) CFB AISRS Total scores: -9.2 (1.40) vs. -6.8 (0.70), respectively; treatment difference: -2.4 (1.56); P=0.12.]ConclusionsA history of prior stimulant use did not appear to influence the magnitude of ADHD symptom response to viloxazine ER in this preliminary analysis of Phase 3 trial data in adults. Rather, subjects with prior stimulant use showed numerically larger reductions in AISRS scores at early timepoints that were not significantly different from those without prior stimulant use. Additional analysis should be undertaken to evaluate patterns of response in the pediatric population.FundingSupernus Pharmaceuticals, Inc.
Viloxazine Extended-Release Capsules in Children and Adolescents with ADHD: Final Results of a Long-Term, Phase 3, Open-Label Extension Study
Authors: Findling Robert L. , Fry Nicholas , Katic Alain , Liebowitz Michael , Maldonado-Cruz Zulane , Qin Peibing , Waxmonsky James G. , Yarullina Ilmiya , Rubin Jonathan 
Published: January 2025

IntroductionViloxazine ER (extended-release capsules; Qelbree®) is a nonstimulant medication, FDA-approved for ADHD in children (≥6 years) and adults. Efficacy and safety for children and adolescents were evaluated in one phase 2 [NCT02633527]and four phase 3 [NCT03247517, NCT03247556, NCT03247530, and NCT03247543], double-blind (DB), placebo-controlled trials that fed into a long-term, open-label extension (OLE) trial [NCT02736656]. Here we report the findings from this OLE trial.MethodsParticipants completing the DB trials were eligible for the OLE. Viloxazine ER was initiated at 100 mg/day (children) or 200 mg/day (adolescents) and adjusted (if needed) over a 12-week Dose-Optimization Period (up to 400 mg/day [children] or 600 mg/day [adolescents]). Maintenance treatment then continued up to 72 months. Safety assessments included adverse events (AEs), clinical laboratory tests, vital signs, ECG (12-lead), and the Columbia Suicide Severity Rating Scale (C-SSRS). Efficacy assessments included the ADHD Rating Scale, 4th (Phase 2) or 5th (Phase 3) Edition (ADHD-RS-IV/5), and the Clinical Global Impression-Improvement (CGI-I) scale. Efficacy was assessed relative to DB baseline at study visits ˜ 3 months apart. Two response measures, 50% improvement in ADHD-RS-IV/5 Total score and CGI-I score of 1-2, were also evaluated.Results1100 individuals (646 children; 454 adolescents; 66.5% male/33.5% female) received treatment. Median (range) exposure to viloxazine ER was 260 (1 to 1896) days. AEs were reported by 57.3% participants, most commonly (≥5%) nasopharyngitis (9.7%), somnolence (9.5%), headache (8.9%) decreased appetite (6.0%), and fatigue (5.7%). AEs were mostly mild or moderate in severity (3.9% reported any severe AE); AEs led to viloxazine ER discontinuation for 8.2%. The mean (SD) changes from DB baseline in ADHD-RS IV/5 Total score were -17.0 (14.18) (viloxazine ER) and -11.2 (13.19) (placebo) at the last DB study visit, 24.3 (11.96) at OLE Month 3, and 22.4 (13.62) at participants’ last OLE study visit. ADHD-RS-IV/5 and CGI-I responder rates each exceeded 65% at all OLE visits following Dose-Optimization.ConclusionsThe safety and efficacy of viloxazine ER were maintained with long-term use in children and adolescents with ADHD. No new safety concerns emerged, and efficacy results suggested potential for continued improvement over that seen during DB treatment.FundingSupernus Pharmaceuticals, Inc.
Long-term Safety, Tolerability, and Effectiveness of TV-46000, a Long-Acting Subcutaneous Antipsychotic (LASCA), in Patients With Schizophrenia (SHINE)
Authors: Kane John M. , Citrome Leslie , Harary Eran , Tohami Orna , Eshet Roy , Merenlender-Wagner Avia , Sharon Nir , Elgart Anna , Knebel Helena , Davis Glen L. , Mychaskiw Marko A. , Suett Mark , Franzenburg Kelli R. , Correll Christoph U. 
Published: January 2025

IntroductionIn RISE, TV46000 once monthly (q1m) or once every 2 months (q2m) significantly extended time to impending schizophrenia relapse. The current study (SHINE, NCT03893825) evaluated the long-term safety, tolerability, and effect of TV46000.MethodsPatients completing RISE without relapse (rollover) or newly recruited (de novo) were eligible. The de novo and placebo rollover cohorts were randomized 1:1 to q1m or q2m for ≤56 weeks; the TV46000 rollover cohort continued assigned regimen. Exploratory efficacy endpoints included time to impending relapse and patient centered outcomes (PCOs) including Schizophrenia Quality of Life Scale (SQLS).Results334 patients were randomized and received TV46000 q1m (n=172) or q2m (n=162), for 202.3 patient-years [PY] of TV-46000 treatment. Treatment-emergent adverse events (AEs) reported for ≥5% of patients were: overall–injection site pain (event rate/100 PY, n [%]; 23.23, 16 [5%]); de novo (n=109)–injection site pain (56.10, 11 [10%]), injection site nodule (16.03, 6 [6%]), blood creatine phosphokinase increased (16.03, 8 [7%]), urinary tract infection (10.69, 7 [6%]); placebo rollover (n=53)–tremor (18.50, 5 [9%]); TV46000 rollover (n=172)–headache (7.97, n=8 [5%]). Serious AEs reported for ≥2 patients were worsening schizophrenia and hyperglycemia. Kaplan– Meier estimates for remaining relapse-free at week 56 were 0.98 (2% risk; q1m) and 0.88 (12%; q2m). SQLS improved for q1m (least-squares mean change [SE], − 2.16 [0.98]) and q2m (− 0.43 [0.98]); other PCOs (5Level EuroQoL 5Dimensions Questionnaire, Personal and Social Performance Scale, Drug Attitudes Inventory 10-item version) remained stable.ConclusionsTV-46000 had a favorable long-term benefit–risk profile in patients with schizophrenia.FundingTeva Branded Pharmaceutical Products R&D Inc.Study Registration Number: NCT03893825
Evaluation of Dermal Irritation with the Dextroamphetamine Transdermal System (d-ATS) in Healthy Adults and Patients with ADHD
Authors: Meeves Suzanne , Komaroff Marina , Haj-Ibrahim Houda , Castelli Mariacristina , Khan Mahwish , Balakrishnan Kanan 
Published: January 2025

BackgroundThe d-ATS patch was developed as an alternative to oral amphetamine formulations for attention-deficit hyperactivity disorder (ADHD). The US Food & Drug Administration (FDA) recommends evaluating irritation of transdermal patches under intended (rotating application sites) and exaggerated use (repeated application to one site). These studies assessed irritation after d-ATS application.MethodsIntended Use: In Study 1, adults with ADHD, d-ATS was applied daily (9-hour application) for 4 weeks rotated between 5 sites (left/right: hip, flank, chest, upper arm, upper back), with irritation assessed on Days 1, 7, 14, 27, and 28. In Study 2, children and adolescents with ADHD, d-ATS was applied daily (9 hours) for 5 weeks to the hip (left or right), with irritation assessed daily.Exaggerated Use: In Study 3, adults with ADHD, d-ATS was applied daily (9 hours) to the hip (repeated application to one site) for 4 weeks, with irritation assessed daily. In Study 4, healthy adults, 1 d-ATS and 1 placebo patch were applied daily (24 hours) for 21 days to the back (repeated application to 1 site), with irritation assessed daily.Irritation was assessed by a trained evaluator 30-60 min after patch removal using Berger and Bowman Dermal Response (0-7, with 7 being the worst reaction) and Other Effects (0-3, with 3 being the worst reaction) scores. Dermal Response and Other Effects scores were added together for the combined score. A combined score of ≥3 was considered clinically meaningful irritation.ResultsIntended Use: In Study 1 (N=15), meaningful irritation after patch removal was reported in 9/15 subjects (60%). The mean (SD) combined score was 1.05 (0.21), with no treatment-emergent adverse events at the application site. In Study 2 (N=110), all combined irritation scores were ≤3 for d-ATS, with a combined score of 3 reported by 2% of patients. There were no discontinuations due to dermal reactions in either study.Exaggerated Use: In Study 3 (N=20), meaningful irritation was reported in 19/20 subjects (95%). The mean (SD) combined score was 1.63 (0.78). In Study 4, mean (SD) combined scores were 2.1 (0.73) for d-ATS and 1.3 (0.69) for placebo (N=206 for both), with no discontinuations due to dermal reactions.ConclusionsThese results support previous findings that d-ATS is safe and well tolerated for ADHD. After intended use, irritation was minimal and did not cause study discontinuations.FundingNoven Pharmaceuticals, Inc.