bluuebunny/crossref_metadata_2025_split huggingface dataset:
142 Withdrawal Symptom Assessment in an Esketamine Safety Study in Patients with Treatment-resistant Depression
Authors: Aluisio Leah , Yieh Lynn , Wajs Ewa , DiBernardo Allitia , Krystal Andrew , Drevets Wayne , Wu Yun , Gogate Jagadish , Daly Ella , Zannikos Peter , Curran Valerie , Chen Guang , Singh Jaskaran 
Published: April 2020

Abstract:Background:SUSTAIN-2 (NCT02497287) was an open-label, phase III trial evaluating the safety of esketamine (ESK) nasal spray plus a newly initiated oral antidepressant (AD) for up to 1 year in adults with treatment-resistant depression (TRD). ESK is a schedule III drug that acts via glutamate receptor modulation. ESK is rapidly cleared from the plasma, and with intermittent dosing there is no accumulation. Thus, no withdrawal syndrome is expected. The current analysis assessed potential withdrawal symptoms in patients who discontinued ESK after long-term, intermittent use. In the absence of a glutamatergic-specific withdrawal scale, the Physicians Withdrawal Checklist1 (PWC-20) was used. The PWC-20 was designed to assess new or worsening benzodiazepine-like discontinuation symptoms after stopping non-SSRI anxiolytics.Methods:ESK nasal spray was administered two times per week during a 4-week induction phase (IND). Responders entered the optimization/maintenance phase (O/M) where ESK nasal spray was dosed either weekly or every two weeks for up to 48 weeks. Patients entered a 4-week follow up period (F/U) after discontinuation from either phase, during which continuation of the AD was recommended. PWC-20 assessments were conducted at the last ESK dosing (endpoint of IND or O/M) and at weeks 1, 2 and 4 of F/U. Symptoms were rated using a 0-3-point scale (Not present = 0, Mild = 1, Moderate = 2, Severe = 3). To account for worsening of underlying depression, subset calculations were performed for depressive symptoms (PWC-DS: loss of appetite; anxiety or nervousness; irritability; dysphoric mood or depression; insomnia; fatigue, lethargy or lack of energy; restlessness or agitation; headaches; muscle aches or stiffness; weakness; difficulty concentrating or remembering; depersonalization-derealization) and withdrawal symptoms (PWC-WS: nausea and/or vomiting; diarrhea; poor coordination; diaphoresis; tremor or tremulousness; dizziness or light-headedness; increased acuity of sound, smell, or touch; paresthesias).Results:Data on 357 patients entering F/U were included in the analysis (91 completed treatment during the IND phase and 141 were treated during O/M). The mean (SD) PWC-20 total scores (range 0-60) at treatment endpoint, Week 1, 2 and 4 were 7.2 (6.8), 7.5(7.0), 7.4 (7.1) and 7.2 (6.9), respectively. At these same assessment times, mean PWC-WS scores (range 0-24) were 0.9 (1.7), 1.0 (1.7), 1.0 (1.8), and 0.9 (1.8). Mean PWC-DS scores (range 0-36) were 6.3 (5.6), 6.5 (5.7), 6.5 (5.8), and 6.3 (5.7), respectively. Complete analysis of data from the entire SUSTAIN-2 dataset will be presented.Conclusions:No indication of drug-specific withdrawal symptoms was seen after stopping up to 1-year of intermittent treatment with ESK nasal spray for TRD.Funding Acknowledgements:Janssen Research and Development
144 Esketamine Nasal Spray for Management of Treatment-Resistant Depression: Number Needed to Treat, Number Needed to Harm, Likelihood to be Helped/Harmed
Authors: Citrome Leslie , DiBernardo Allitia , Singh Jaskaran 
Published: April 2020

Abstract:Background:Targeting of glutamate receptors is a novel approach for the treatment of major depressive disorder (MDD). This study aimed to review the usefulness for esketamine nasal spray for the management of treatment-resistant depression (TRD) using the tools of evidence-based medicine: number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).Methods:Data sources were four completed Phase 3 randomized, double-blind, placebo-controlled, studies, including two pivotal registration studies of esketamine nasal spray in TRD in non-elderly adults (acute flexible-dose study NCT02418585, maintenance study NCT02493868) Efficacy outcomes included acute response (≥50% decrease from baseline on Montgomery-Asberg Depression Rating Scale [MADRS] total score), acute remission (MADRS scores ≤12; and other thresholds using the MADRS and Clinical Global Impressions-Severity [CGI-S] scales), categorical shifts in MADRS and CGI-S scores, and avoidance of relapse/recurrence (observed relapse rates). NNT, NNH and LLH are calculated for combination of esketamine nasal spray and oral antidepressant (esketamine+AD) vs AD+placebo in patients with TRD.Results:In the acute flexible-dose study of esketamine nasal spray (56-84 mg twice-weekly for 4 weeks), MADRS response with esketamine+AD vs AD+placebo at endpoint (rates 63.4% vs 49.5%, respectively) yielded an NNT value of 8, and MADRS remission at endpoint (48.2% vs 30.3%) resulted in a NNT vs AD+placebo of 6. NNH values vs AD+placebo were <10 for the adverse events (AE) of dissociation (26.1% vs 3.7%), vertigo (26.1% vs 2.8%), nausea (26.1% vs 6.4%), dizziness (20.9% vs 4.6%), and dysgeusia (24.3% vs 11.9%), the NNH values were 5, 5, 6, 7, and 9, respectively. Discontinuation rates due to AE (7.0% vs 0.9%) yielded a NNH of 17. LHH comparing MADRS remission vs discontinuation was 17/6, or approximately 3. The pattern of results was similar for the other acute studies and for the pooled data combining all 3 acute studies. Maintenance use of esketamine (dose 56-84 mg once-weekly or once-every-other-week) plus an oral AD demonstrated NNT values <10 for relapse and/or maintenance of remission in favor of esketamine+AD vs AD+placebo, a NNT of 4 was observed for outcome of relapse in patients with stable response at the time of randomization (relapse rates were 25.8% vs 57.6%, respectively). In the maintenance study, discontinuation rates due to an AE (2.6% vs 2.1%) yielded a non-significant NNH value of 178.Conclusion:The low NNT values <10 for efficacy outcomes suggest potential benefits of esketamine+AD for both acute and maintenance use. LHH was favorable: esketamine+AD was 3 times more likely to result in acute remission vs discontinuation due to an AE.Funding Acknowledgements:Janssen Global Services, LLC
147 Training Forgiveness. A Novel Approach to Reducing Physician Burnout
Authors: Firulescu Lidia , May Ross W. , Fincham Frank D. , Arocha Emelina A. , Sanchez-Gonzalez Marcos A. 
Published: April 2020

Abstract:Study Objective:Psychological risk factors that lead to impaired work performance, negatively impacting mental and physical health, have emerged as a concern across clinical settings. Although depression and anxiety are linked to poor physician mental health, physician burnout characterized by work related stress due to chronic exhaustion from clinical work, cynicism toward meaning of the medical profession, and feelings of inadequacy toward work related accomplishments, may be an even stronger indicator of well-being. Literature suggests that work satisfaction among physicians is rapidly deteriorating owing to high rates of burnout and poor mental health. Although the relationship between work burnout (WB) and negative affectivity has been well documented, the association with positive affect, such as trait forgiveness (TF) has been overlooked. On that note, research shows that lifetime stress severity and lower levels of forgiveness predict worse mental and physical health. Since TF has been linked strongly with healthy workplace relationships, positive occupational outcomes and general well-being, its association with WB remains to be investigated. Therefore, the aim of the present study was to explore the link between TF and WB among physicians. We hypothesized that TF would be associated with reduced levels of burnout.Method:A total of 62 (F=23) medical residents at a Teaching Hospital consented for the study. Residents were administered surveys on WB (Maslach Burnout Inventory), workplace bullying, personal bullying (PB), interpersonal rejection sensitivity (IRS), perceived stress scale (PSS), TF, anxiety, and depression, all of which were anonymously submitted via electronically. Hierarchical multiple regression (HMR) models were used to determine the associations between WB, work environment social factors and TF. A p-value of <0.05 was considered significant.Results:The mean age 33.1 ± SD 4.2 years. HMR analysis using WB as main outcome contained 6 predictors: Model 1 contained depression and anxiety, Model 2 added PB, Model 3 added IRS and PSS, Model 4 added TF. Anxiety and TF were the only significant predictors (p= >0.05) accounting for 10.4% and 17.5% of the variance in WB scores, respectively.Conclusions:The novel finding of the present study is that TF was associated with low levels of burnout. Additionally, WB was found to be linked to anxiety and depression which is in line with previous research. These data suggest that TF could be a potential resolution to the deleterious influence of burnout. Further exploration is needed in order to understand the psychology of forgiveness as a potential adjuvant and/or therapeutic intervention for physicians’ burnout. These results suggest that strategies including forgiveness training aimed at decreasing WB while increasing job satisfaction among physicians warrant further exploration.
151 Confirmed Safety of Deutet.rabenazine for Tardive Dyskinesia in a 3-Year Open-Label Extension Study
Authors: Fernandez Hubert H. , Barkay Hadas , Hauser Robert A. , Factor Stewart A. , Jimenez-Shahed Joohi , Gross Nicholas , Marinelli Leslie , Gordon Mark Forrest , Savola Juha-Matti , Anderson Karen E. 
Published: April 2020

Abstract:Background:Deutetrabenazine (Austedo) is approved by the FDA for treatment of tardive dyskinesia (TD) in adults. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The objective of this study was to evaluate the long-term safety and tolerability of deutetrabenazine in patients with TD at 3 years.METHODS:Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used for calculating AE frequencies. This analysis reports results up to Week 158.RESULTS:A total of 343 patients were enrolled (111 received placebo and 232 received deutetrabenazine in the parent studies). At the time of this analysis, 183 patients were still receiving treatment; 259 completed 1 year, 172 completed 2 years, and 41 completed 3 years. There were 623 patient-years of exposure. More than 40% of patients reached the maximum dose. EAIRs of AEs were comparable to or lower than those observed in the ARM-TD and AIM-TD short-term randomized trials of deutetrabenazine vs. placebo. The frequency of SAEs (EAIR 0.10) was similar to that observed with short-term placebo (0.33) and short-term deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.06), dose reduction (0.10), and dose suspension (0.05) were uncommon.CONCLUSION:These results support the safety outcomes observed in the ARM-TD and AIM-TD parent studies and the safety of deutetrabenazine for long-term use in patients with TD.Funding Acknowledgements: This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel
Inhibitory effects of bioaccessible anthocyanins and procyanidins from apple, red grape, cinnamon on α-amylase, α-glucosidase and lipase
Authors: Ercan Pınar , El Sedef Nehir 
Published: April 2020

Abstract. The goals of this study were to determine and evaluate the bioaccessibility of total anthocyanin and procyanidin in apple (Amasya, Malus communis), red grape (Papazkarası, Vitis vinifera) and cinnamon (Cassia, Cinnamomum) using an in vitro static digestion system based on human gastrointestinal physiologically relevant conditions. Also, in vitro inhibitory effects of these foods on lipid (lipase) and carbohydrate digestive enzymes (α-amylase and α-glucosidase) were performed with before and after digested samples using acarbose and methylumbelliferyl oleate (4MUO) as the positive control. While the highest total anthocyanin content was found in red grape (164 ± 2.51 mg/100 g), the highest procyanidin content was found in cinnamon (6432 ± 177.31 mg/100 g) (p < 0.05). The anthocyanin bioaccessibilities were found as 10.2 ± 1%, 8.23 ± 0.64%, and 8.73 ± 0.70% in apple, red grape, and cinnamon, respectively. The procyanidin bioaccessibilities of apple, red grape, and cinnamon were found as 17.57 ± 0.71%, 14.08 ± 0.74% and 18.75 ± 1.49%, respectively. The analyzed apple, red grape and cinnamon showed the inhibitory activity against α-glucosidase (IC50 544 ± 21.94, 445 ± 15.67, 1592 ± 17.58 μg/mL, respectively), α-amylase (IC50 38.4 ± 7.26, 56.1 ± 3.60, 3.54 ± 0.86 μg/mL, respectively), and lipase (IC50 52.7 ± 2.05, 581 ± 54.14, 49.6 ± 2.72 μg/mL), respectively. According to our results apple, red grape and cinnamon have potential to inhibit of lipase, α-amylase and α-glucosidase digestive enzymes.
The Recovery Process for Individuals With Schizophrenia in the	Context of Evidence-Based Psychotherapy and Rehabilitation
Authors: Rakitzi Stavroula , Georgila Polyxeni , Becker-Woitag Astrid Prabala 
Published: April 2020

Abstract. This systematic review aimed to evaluate the efficacy of Cognitive Behavioral Therapy (CBT), META Cognitive Therapy (MCT), Metacognitive Training (MCTR), Metacognitive Reflection and Insight Therapy (MERIT), of various rehabilitation programs and of recovery programs in schizophrenia. Medline/Pubmed was searched for studies published in English from January 2010 to August 2018, which were screened against inclusion criteria by two reviewers. The methodological quality of the included studies was evaluated by two independent raters, which are the Effective Public Health Practice Project (EPHPP) quality assessment tool for quantitative studies and the fidelity criteria. The study included 41 RCTs and 12 case studies with n = 3,059 persons with schizophrenia. Cognitive Behavioral Therapy (CBT) proved to be superior in terms of the improvement of primary and secondary outcomes. MCT decreased positive symptoms and improved metacognitive capacity and insight. MCTR reduced positive symptoms and socially disruptive behavior. MERIT improved metacognitive capacity and insight. Rehabilitation programs were efficacious in the improvement of cognition, symptoms, and functional outcome. The recovery programs enhanced illness-management knowledge, attitudes toward medication and insights related to negative symptoms. It is recommended to combine the above evidence based psychotherapeutic interventions. Limitations of this systematic review are discussed toward the end of the essay. Some important factors have to be considered in the future have been mentioned.
Profiles of MBL Cloud and Drizzle Microphysical Properties Retrieved From Ground‐Based Observations and Validated by Aircraft In Situ Measurements Over the Azores
Authors: Wu Peng , Dong Xiquan , Xi Baike , Tian Jingjing , Ward Dale M. 
Published: April 2020

AbstractThe profiles of marine boundary layer (MBL) cloud and drizzle microphysical properties are important for studying the cloud‐to‐rain conversion and growth processes in MBL clouds. However, it is challenging to simultaneously retrieve both cloud and drizzle microphysical properties within an MBL cloud layer using ground‐based observations. In this study, methods were developed to first decompose drizzle and cloud reflectivity in MBL clouds from Atmospheric Radiation Measurement cloud radar reflectivity measurements and then simultaneously retrieve cloud and drizzle microphysical properties during the Aerosol and Cloud Experiments in the Eastern North Atlantic (ACE‐ENA) campaign. These retrieved microphysical properties, such as cloud and drizzle particle size (rc and rm,d), their number concentration (Nc and Nd) and liquid water content (LWCc and LWCd), have been validated by aircraft in situ measurements during ACE‐ENA (~158 hr of aircraft data). The mean surface retrieved (in situ measured) rc, Nc, and LWCc are 10.9 μm (11.8 μm), 70 cm−3 (60 cm−3), and 0.21 g m−3 (0.22 g m−3), respectively. For drizzle microphysical properties, the retrieved (in situ measured) rd, Nd, and LWCd are 44.9 μm (45.1 μm), 0.07 cm−3 (0.08 cm−3), and 0.052 g m−3 (0.066 g m−3), respectively. Treating the aircraft in situ measurements as truth, the estimated median retrieval errors are ~15% for rc, ~35% for Nc, ~30% for LWCc and rd, and ~50% for Nd and LWCd. The findings from this study will provide insightful information for improving our understanding of warm rain processes, as well as for improving model simulations. More studies are required over other climatic regions.
Inconsistent Responses of Transpiration of Different Canopy Layers to Simulated Canopy and Understory N Depositions in a Low‐Subtropical Evergreen Broadleaf Forest
Authors: Li Yanqiong , Zhao Ping , Zhang Zhenzhen , Zhu Liwei , Ouyang Lei , Ni Guangyan 
Published: April 2020

AbstractQuantifying transpiration and its response to meteorological factors at a stand scale and different canopy layers of forest is important for understanding the hydrological impact of nitrogen (N) deposition on local water balance. For this purpose, sap flows were measured in three upper (Schima superba, Castanea henryi, and Machilus chinensis) and three lower (Symplocos ramosissima, Ilex ficoidea, and Schefflera octophylla) canopy species based on a manipulative experimental platform with canopy (CN) and understory (UN) N additions in a low‐subtropical evergreen broadleaf forest. Each application included concentrations of 0, 25, and 50 kg·ha−1·a−1 N. Results showed that N addition obviously influenced the sap flux density and such influence varied among different species and between canopy layers. Upper canopy species contributed the most transpiration for the whole forest, and CN25 greatly affected the transpiration in both upper and lower canopy layers. Daily water use (Qd) increased logarithmically with daytime average photosynthetically active radiation and daily average vapor pressure deficit. An appropriate canopy N addition (CN25) promoted the Qd and its sensitivity to micrometeorological factors, whereas UN had a minimal effect. These results suggest a substantial difference in response of transpiration to the N addition ways. CN had more effective influence on the canopy transpiration. Thus, UN could not fully reflect the effects of increased N deposition on the canopy‐associated transpiration, and the response of forest transpiration to N deposition needs to be analyzed beyond species and upscaled to the canopy level in favor of meaningful assessments of N deposition.
Tropical Cyclogenesis From Self‐Aggregated Convection in Numerical Simulations of Rotating Radiative‐Convective Equilibrium
Authors: Carstens Jacob D. , Wing Allison A. 
Published: April 2020

AbstractIn a modeled environment of rotating radiative‐convective equilibrium (RCE), convective self‐aggregation may take the form of spontaneous tropical cyclogenesis. We investigate the processes leading to tropical cyclogenesis in idealized simulations with a three‐dimensional cloud‐permitting model configured in rotating RCE, in which the background planetary vorticity is varied across f‐plane cases to represent a range of deep tropical and near‐equatorial environments. Convection is initialized randomly in an otherwise homogeneous environment, with no background wind, precursor disturbance, or other synoptic‐scale forcing. We examine the dynamic and thermodynamic evolution of cyclogenesis in these experiments and compare the physical mechanisms to current theories. All simulations with planetary vorticity corresponding to latitudes from 10°–20° generate intense tropical cyclones, with maximum wind speeds of 80 m s−1 or above. Time to genesis varies widely, even within a five‐member ensemble of 20° simulations, indicating large stochastic variability. Shared across the 10°–20° group is the emergence of a midlevel vortex in the days leading to genesis, which has dynamic and thermodynamic implications on its environment that facilitate the spin‐up of a low‐level vortex. Tropical cyclogenesis is possible in this model at values of Coriolis parameter as low as that representative of 1°. In these experiments, convection self‐aggregates into a quasicircular cluster, which then begins to rotate and gradually strengthen into a tropical storm, aided by strong near‐surface inflow that is already established days prior. Other experiments at these lower Coriolis parameters instead self‐aggregate into a nonrotating elongated band and fail to undergo cyclogenesis over the 100‐day simulation.
Eurasian Cooling Linked to the Vertical Distribution of Arctic Warming
Authors: He Shengping , Xu Xinping , Furevik Tore , Gao Yongqi 
Published: April 2020

AbstractObservations show that deep Arctic winter warming, extending from surface to mid‐troposphere, has concurred with below‐average temperature over central Eurasia. Modeling studies focusing on the response to Arctic sea ice loss have shown Arctic surface warming but no consistent atmospheric changes at midlatitude. Using a large number of simulations from coupled and uncoupled climate models, we show that Eurasian below‐average temperatures are more frequent in winters with deep warming compared to shallow, near‐surface warming over the Barents‐Kara Seas. Dramatic weakening of the midlatitude jet stream and increase in Ural blocking frequency are more likely to occur in winters with deep Arctic warming. Deep warming is independent of sea ice forcing but follows increased poleward atmospheric energy and moisture advection from the North Atlantic to the Arctic, indicating that internal natural variability and not sea ice is the main driving forcing for deep Arctic warming‐cold Eurasia pattern in historical simulations.
Constraining Global Changes in Temperature and Precipitation From Observable Changes in Surface Radiative Heating
Authors: Dhara Chirag 
Published: April 2020

AbstractChanges in the atmospheric composition alter the magnitude and partitioning between the downward propagating solar and atmospheric longwave radiative fluxes heating the Earth's surface. These changes are computed by radiative transfer codes in Global Climate Models and measured with high precision at surface observation networks. Changes in radiative heating signify changes in the global surface temperature and hydrologic cycle. Here, we develop a conceptual framework using an Energy Balance Model to show that first‐order changes in the hydrologic cycle are mainly associated with changes in solar radiation, while those in surface temperature are mainly associated with changes in atmospheric longwave radiation. These insights are used to explain a range of phenomena including observed historical trends, biases in climate model output, and the intermodel spread in climate change projections. These results may help identify biases in future generations of climate models.