bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital Health Technologies in Mental Health Care: Changing Perspectives of Health Care Professionals from 2019 to 2021
Authors: Tacelosky Mark , Sadat Fatima , Meyer Chip , McKinley Tara , Pikul Dana , Carlton Tarolyn , Rohman Patricia , Singh Surinder , Moghadam Reza 
Published: April 2023

AbstractIntroductionDemand for digital mental health tools has risen since the start of the COVID-19 pandemic; however, their evolving use in mental health care is not well understood. We surveyed mental health care professionals (HCPs) before and after the onset of the pandemic and assessed how use of and attitudes about digital technology changed.MethodsWe distributed a digital health survey to HCPs in the United States in 2019 (pre-pandemic; N = 141) and in 2021 (during the pandemic; N = 151). Both surveys recorded the respondents’ perceived barriers to integrating new digital health technologies and the tools they currently used in their practice.ResultsHCP use of telemedicine increased from 47% of respondents in 2019 to 81% in 2021, as did the use of mHealth sensors (2% vs 10%). Patient comfort with technology remained one of the biggest barriers to implementing new digital tools (40% vs 43%), while difficulty integrating digital tools into clinical practice became less common (40% vs 32%). Data management (19% vs 10%) and patient acceptability (19% vs 13%) were cited less often as barriers in 2021. Respondents’ thoughts on what can be most improved by digital technology shifted substantially, with increased access to care rising from 27% of responses in 2019 to 46% in 2021.ConclusionsThe pandemic has changed how HCPs perceive digital health technologies and how they implement these tools in clinical practice. A growing number of HCPs believe increased access to care is the outcome that technology can most improve.FundingOtsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA
Long-Term Safety and Effectiveness of Lurasidone in Adolescents and Young Adults With Schizophrenia: Pooled Post-hoc Analyses of Two 12-month Extension Studies
Authors: Calisti Fabrizio , Tocco Michael , Mao Yongcai , Pikalov Andrei , Goldman Robert 
Published: April 2023

AbstractIntroductionEarlier onset of schizophrenia, which occurs more commonly in males, is characterized by greater illness severity, chronicity, and functional impairment with a less favorable prognosis than later-onset schizophrenia. The aim of this pooled analysis was to evaluate the long-term safety and effectiveness of lurasidone in the treatment of schizophrenia in adolescents (13–17 years) and young adults (18–25 years).MethodsThe 2 pooled studies used similar designs and outcome measures. Patients (13–25 years) with schizophrenia completed an initial double-blind 6-week trial of lurasidone (40 and 80 mg/d), and (80 and 160 mg/d) in the young adult trial. In the open-label long-term trials, adolescent patients were treated with 20-80 mg/d of lurasidone, and adults were treated with 40–160 mg/d of lurasidone. Efficacy was evaluated based on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Scale (CGI-S).ResultsThe safety population consisted of 306 patients (mean age, 16.2 years; 208 patients (68.0%) who completed 12 months of treatment; 8.2% discontinued by 12 months due to an adverse event. Mean (SD) change in the PANSS total score from extension Baseline to Months 6 and 12 was -11.8 (13.9) and -15.3 (15.0), respectively (OC); and mean (SD) change in the CGI-S score was -0.8 (1.0) and -1.0 (1.1), respectively (OC). The most frequent adverse events were headache (17.6%), anxiety (11.4%), schizophrenia (9.8%), and nausea (9.8). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin.ConclusionsIn adolescents and young adults with schizophrenia, treatment with lurasidone was generally well-tolerated and effective. Long-term treatment was associated with continued reduction in symptoms of schizophrenia. Long-term treatment was associated with minimal effects on weight, metabolic parameters, and prolactin.FundingAngelini Pharma S.p.A. and Sunovion Pharmaceuticals Inc.
Hyperammonemia and First-Degree Atrio-Ventricular Block in Adult Male from Valproic Acid Toxicity
Authors: Wilson Nicholas 
Published: April 2023

AbstractIntroductionThe purpose of this case study is to review the clinical presentation and medical work of an adult male who experienced symptomatic hyperammonemia and first-degree atrio-ventricular block in the setting of valproic acid toxicity.MethodThis case involves a 28-year-old African American male with a past psychiatric history of bipolar 1 disorder with psychotic features, antisocial personality disorder, PTSD, and ASD, who was psychiatrically hospitalized for mania and psychosis at a large midwestern university hospital. At the time of evaluation in the emergency department, the patient endorsed suicidal ideation, religious/persecutory delusions, and auditory hallucinations of demons. Zyprexa Zydis was started and titrated to 20 mg every 12 hours, which did not sufficiently improve symptoms. Depakote EC/DR 1000 mg every 12 hours was then added for treatment of mania. Approximately 1 week later, the patient was observed to be somnolent and complained of malaise, nausea, and vomiting.ResultsLabs were collected which showed an elevated ammonia level of 336 umol/L and free valproic acid level of 13.3 mcg/ml. An EKG was performed which showed first-degree atrio-ventricular block with fusion complexes. The patient’s baseline EKG displayed sinus bradycardia with no evidence of atrio-ventricular block. The patient’s CMP was unremarkable except total bilirubin of 1.5 mg/dL and glucose of 104 mg/dL. His lactate was elevated at 1.95 mmol/L. The patient’s troponin and CRP were unremarkable. The patient was medically transferred for management of hyperammonemia and EKG changes. Depakote was discontinued and lactulose 20 g TID was initiated. Patient was placed on telemetry and the first-degree atrio-ventricular block resolved within 24 hours after discontinuation of Depakote. Daily ammonia level, chem 7, and magnesium were collected. Ammonia decreased to 79 and 59 umol/L on consecutive days. Sodium was mildly elevated at 144 on day 2 of medical admission. Poison control was contacted and L-carnitine 990 TID was started for suspected carnitine deficiency. The patient medically recovered after several days and was readmitted to the psychiatric hospital for further psychiatric management.ConclusionsThe patient’s presentation of hyperammonemia and first-degree atrio-ventricular block were likely due to valproic acid toxicity. We suspect that carnitine deficiency contributed to the patient’s valproic acid toxicity at lower-than-expected blood levels. Although antipsychotics can cause prolonged QTc interval, conduction disorders are not typical abnormalities. Caution should be taken when prescribing Depakote to individuals at higher risk of developing toxicity, including those with potential nutritional deficiencies as well as those with limited self-advocacy abilities secondary to psychiatric illness. Rapid identification of side effects, such as valproic acid toxicity, remain crucial for favorable patient outcomes.FundingNo Funding
Safety and Tolerability of Cariprazine for the Adjunctive Treatment of Major Depressive Disorder: A Pooled Analysis of Phase 2B and 3 Clinical Trials
Authors: Thase Michael E. , Yeung Paul P. , Hankinson Arlene , Liu Meng , Rekeda Ludmyla , Earley Willie R. 
Published: April 2023

AbstractBackgroundCariprazine has been shown to be efficacious in placebo-controlled clinical trials. In this pooled analysis, the safety of cariprazine in patients with major depressive disorder (MDD) with inadequate response to antidepressants was evaluated using data from placebo-controlled studies of up to 8 weeks’ duration and a long-term open-label safety study.MethodsThe safety, tolerability, and efficacy of cariprazine as an adjunctive treatment for patients with MDD with inadequate response to antidepressant alone was assessed in five placebo-controlled studies (two 6-week fixed-dose studies [NCT03738215; NCT03739203] and three 8-week flexible-dose studies [NCT00854100; NCT01715805; NCT01469377]) and one 26-week open-label flexible-dose study (NCT01838876). Fixed doses of cariprazine 1.5 and 3 mg/d and flexible doses of 0.1-4.5 mg/d were evaluated. Safety assessments included adverse event (AE) reporting, clinical laboratory tests, weight and other vital signs, and suicide evaluation with Columbia-Suicide Severity Rating Scale (C-SSRS). Pooled analyses of the incidence of safety endpoints overall and within each treatment arm were performed using the most frequent (modal) daily dose taken by patients during the study.ResultsA total of 2,222 MDD patients with an ongoing antidepressant received treatment with cariprazine, representing 370 patient-years of exposure in placebo-controlled and open-label studies. In the placebo-controlled studies, 1,969 patients were randomized to cariprazine (dose range, 0.1–4.5 mg/d) and 1,108 patients were randomized to placebo. Overall, treatment-emergent AEs occurred in 61% of cariprazine- and 48% of placebo-treated patients; discontinuation due to an AE occurred with 6% of cariprazine- and 2% of placebo-treated patients. The 2 AEs that occurred in at least 5% of cariprazine-treated patients and at a rate at least twice the rate in placebo-treated patients were akathisia (cariprazine=11%; placebo=2%) and restlessness (cariprazine=6%; placebo=2%). Changes in metabolic parameters, including shifts in fasting glucose and lipid parameters, were similar in cariprazine- and placebo-treated patients. In the long-term safety study, mean weight change was 1.6 kg over 6 months. In the placebo-controlled and long-term studies, other safety endpoints including laboratory and C-SSRS assessments of suicidality were generally consistent with the safety profile of cariprazine in approved indications of bipolar disorder and schizophrenia.ConclusionCariprazine is generally safe and well-tolerated in MDD patients with inadequate response to antidepressant monotherapy. Safety analysis of 2,222 cariprazine-treated patients with MDD revealed no new safety signals, and the data is consistent with the currently approved prescribing information.FundingAbbVie
TAAR1 Agonist Ulotaront Improves Glycemic Control and Reduces Body Weight in Rodent Models of Diabetes, Obesity, and Iatrogenic Weight Gain
Authors: Dedic Nina , Jones Philip G. , Hajos-Korcsok Eva , Synan Colleen , Wu Serena , Anacker Christoph , Vickers Steve P. , Hecksher-Sørensen Jacob , Zeni Courtney , Milanovic Snezana , Hopkins Seth C. , Bristow Linda J. , Koblan Kenneth S. 
Published: April 2023

AbstractIntroductionPreclinical evidence has identified the trace amine-associated receptor 1 (TAAR1) as a novel regulator of metabolic control. Ulotaront is a TAAR1 and 5-HT1A agonist currently in Phase 3 clinical trials for the treatment of schizophrenia. Here we summarize preclinical results assessing the effects of ulotaront on weight and metabolic parameters.MethodsEffects of ulotaront administration were evaluated on oral glucose tolerance (oGTT), gastric emptying, and in rodent models of weight gain (high-fat diet [HFD]-, corticosterone-, and olanzapine-induced).ResultsFollowing 15-day oral administration of ulotaront, rats on HFD showed dose-dependent reduction in body weight, food intake, and liver triglyceride content compared to controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in rats switched to ulotaront (vs. vehicle). Consistent with weight-lowering effects in rats, chronic ulotaront treatment normalized corticosterone-induced weight gain in mice. Assessment of oGTT showed a dose-dependent reduction of glucose excursion in response to acute ulotaront administration in naive and diabetic db/db mice. Ulotaront administration also delayed gastric emptying in mice—a likely mechanism driving reductions in glucose excursions during the oGTT. Whole-brain c-fos imaging of ulotaront-treated mice revealed increased neuronal activity in several brain regions associated with regulation of food intake and metabolic signals.ConclusionsThe data indicate that ulotaront not only lacks metabolic liabilities typically associated with antipsychotics but can reduce body weight and improve glucose tolerance in rodent models. The underlying mechanisms may include TAAR1-mediated peripheral effects on glucose homeostasis and/or direct modulation of homeostatic and hedonic neurocircuits regulating energy balance. The beneficial metabolic effects of ulotaront may suggest a substantially improved risk-benefit profile compared to established antipsychotics.FundingSunovion Pharmaceuticals Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc.
Acute Emergence of Suicidal Thoughts Following Lemborexant Initiation: An Adverse Reaction Case Report
Authors: Roberts Thomas , Stryker Homer , Nagalla Madhavi Latha 
Published: April 2023

AbstractThis is a case report highlighting the side effect of suicidal ideation with lemborexant, a novel agent approved for the treatment of insomnia. A 22-year-old man received care at an outpatient psychiatrist for the treatment of major depressive disorder, persistent depressive disorder, generalized anxiety disorder, social phobia, and insomnia. The patient also has a diagnosis of Loeys-Dietz syndrome, a connective tissue disorder. Following numerous medication trials for both depression and insomnia that resulted in partial remission of mood symptoms without improvement in sleep, he was initiated on lemborexant to address insomnia. He was noted to be denying suicidal ideation at the appointment when lemborexant was prescribed. The patient did not take lemborexant until three days after the appointment, at which time he took the recommended dose of 5 mg at bedtime for insomnia. The patient experienced drowsiness immediately following taking this dose; however, he woke up two hours later with new-onset suicidal ideation. The patient was brought to the hospital for this complaint, and the following evening had attempted suicide by hanging in his hospital room. Laboratory investigations showed normal findings in blood chemistries, complete blood count, thyroid stimulating hormone, vitamin B12 level, vitamin D level, and urine illicit drug screening. Differential diagnosis includes acute reaction to insomnia, medication-induced side effect, and major depressive disorder. He had completed trials for insomnia with zolpidem, hydroxyzine, quetiapine, nortriptyline, and trazodone prior to beginning lemborexant. The patient had no history of suicide attempts in the past, but did experience suicidal ideation following a trial of nortriptyline. In the hospital, the lemborexant was discontinued, and clonidine and clonazepam were initiated at bedtime to address insomnia and ruminative thoughts. The patient was discharged with follow-up at his outpatient psychiatrist after his suicidal ideation was in remission, as well as noted improvement in insomnia. This case highlights new-onset suicidal ideation with subsequent suicide attempt after first use of lemborexant in a patient with major depressive disorder. This case is important given lemborexant is a new medication with limited information about its efficacy and safety in major psychiatric disorders.FundingNo Funding
Assessing the Unmet Clinical Need and Opportunity for Digital Therapeutic Intervention in Schizophrenia: Perspective From People With Schizophrenia
Authors: Campellone Tim , Carretta Carrie , Davidson Charlie , Lakhan Shaheen , Sand Michael 
Published: April 2023

AbstractIntroductionRecent research has highlighted the increasing ubiquity of smartphone ownership as well as the feasibility of digital interventions within schizophrenia. Digital therapeutics, a subset of digital interventions, have established standards for efficacy and safety and are subject to regulatory oversight as Software as a Medical Device. Here, we present data from a survey that assessed the opportunity and expectations that people with schizophrenia have for a digital therapeutic designed to be delivered on top of antipsychotic pharmacotherapy.MethodsSeventy-five people with schizophrenia completed a 10-item survey. Participants were between 22 and 55 years of age, reported no hospitalizations or medication changes within the past 3 months, and were currently seeing a psychiatrist. For each question, participants were asked to rank responses to provide a clear understanding of their preferences.ResultsPatients with schizophrenia reported the survey items that most impacted their daily life were: difficulty meeting new people (17%) and difficulty setting goals/completing activities in daily life and not being productive in their free time (both at 13%). The greatest unmet treatment needs reported by people with schizophrenia were: improving social skills (19%); reducing distress related to disease (19%); and being more productive in their free time (13%). In terms of expectations for what a digital therapeutic would include, the items reported as most important were: sharing progress with providers (13%); teaching ways to deal with symptoms (13%); and helping to set and achieve goals (12%).ConclusionMany of the top unmet needs that people with schizophrenia identified can be uniquely targeted by a digital therapeutic that augments their ongoing standard of care.FundingBoehringer Ingelheim International GmbH and CLICK Therapeutics, Inc.
Lemborexant and Daridorexant for the Treatment of Insomnia: An Indirect Comparison, Using Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed
Authors: Citrome Leslie , Juday Timothy , Lundwall Christie 
Published: April 2023

AbstractBackgroundTo describe lemborexant and daridorexant for insomnia treatment using number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).MethodsDichotomous outcomes were identified from the two registrational daridorexant randomized controlled trials. Analogous data were then extracted for lemborexant from the two lemborexant registration studies.ResultsUsing pooled dosage data, lemborexant had a clinically relevant magnitude of therapeutic effect, as evidenced by NNT values versus placebo <10, and NNH values for lemborexant versus placebo were >10, suggesting that lemborexant is relatively tolerable. When comparing response versus discontinuation because of an adverse event (AE) for Month 3, the LHH ranges 5.2 to 10.4 for lemborexant pooled 5 mg and 10 mg doses (a favorable result). For daridorexant, the efficacy outcomes for pooled 25 mg and 50 mg doses generally result in NNT values versus placebo ≥10; in all instances, doses of 50 mg yield more robust NNT estimates than for the 25 mg dose. The rate of discontinuation because of an AE at Month 3 was higher for placebo than for daridorexant, rendering favorable LHH calculations for daridorexant despite the less robust NNT estimates, with an LHH in the range of 90.9 to 125 for Month 3 when comparing response versus discontinuation because of an AE (a favorable result).ConclusionsBenefit-risk ratio for lemborexant and daridorexant is favorable as measured by NNT, NNH, and LHH. Indirect comparisons suggest an efficacy advantage for lemborexant and a tolerability advantage for daridorexant.FundingEisai Inc.
Imaging and Molecular Annotation of Xenographs and Tumours (IMAXT): High throughput data and analysis infrastructure
Authors: González-Solares Eduardo A. , Dariush Ali , González-Fernández Carlos , Küpcü Yoldaş Aybüke , Molaeinezhad Alireza , Al Sa’d Mohammad , Smith Leigh , Whitmarsh Tristan , Millar Neil , Chornay Nicholas , Falciatori Ilaria , Fatemi Atefeh , Goodwin Daniel , Kuett Laura , Mulvey Claire M. , Páez Ribes Marta , Qosaj Fatime , Roth Andrew , Vázquez-García Ignacio , Watson Spencer S. , Windhager Jonas , Aparicio Samuel , Bodenmiller Bernd , Boyden Ed , Caldas Carlos , Harris Owen , Shah Sohrab P. , Tavaré Simon ,   CRUK IMAXT Grand Challenge Team, Bressan Dario , Hannon Gregory J. , Walton Nicholas A. 
Published: April 2023

Abstract
With the aim of producing a 3D representation of tumors, imaging and molecular annotation of xenografts and tumors (IMAXT) uses a large variety of modalities in order to acquire tumor samples and produce a map of every cell in the tumor and its host environment. With the large volume and variety of data produced in the project, we developed automatic data workflows and analysis pipelines. We introduce a research methodology where scientists connect to a cloud environment to perform analysis close to where data are located, instead of bringing data to their local computers. Here, we present the data and analysis infrastructure, discuss the unique computational challenges and describe the analysis chains developed and deployed to generate molecularly annotated tumor models. Registration is achieved by use of a novel technique involving spherical fiducial marks that are visible in all imaging modalities used within IMAXT. The automatic pipelines are highly optimized and allow to obtain processed datasets several times quicker than current solutions narrowing the gap between data acquisition and scientific exploitation.
The Forest Resistance to Droughts Differentiated by Tree Height in Central Europe
Authors: Li Tiewei , Guo Lanlan , He Bin , Liu Lianyou , Yuan Wenping , Chen Xiuzhi , Hao Xingming , Liu Xuebang , Zheng Hao , Zheng Huan , Wang Rui 
Published: April 2023

AbstractMore frequent droughts are altering the dynamics and function of the European forest ecosystem, which is deeply connected to the global carbon cycle. Tree height is an important structural feature of forests; however, how it regulates the response of forests to droughts remains controversial. By comprehensively examining the variations of satellite‐based vegetation greenness with drought evolution and the legacy effect of drought indicated by radial growth, we observed apparent height‐dependence forests' resistance to drought. Short forests showed lower resistance to drought than taller forests, demonstrating earlier and larger negative vegetation greenness anomalies. Additionally, larger reductions in radial growth after the drought year were also observed for shorter trees, implying an apparent legacy effect of drought on tree growth. The observed resistance differences can be attributed to the differences in the capacity for water absorption and regulation among forests of different heights. Our results provide an integrated explanation of tree‐level function that will be critical in understanding the response of forests and vegetation‐climate feedbacks in more widespread, prolonged, and extreme drought in the future.