bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term follow-up after bypass surgery or coronary stenting in elderly with multivessel disease
Authors: Gimbel M. E. , Willemsen L. M. , Daggelders M. C. , Kelder J. C. , Oirbans T. , Beukema K. F. , Daeter E. J. , ten Berg J. M.
Published: April 2020

Background

We sought to compare long-term follow-up of coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) in elderly patients with left main or multivessel disease, hypothesising that completeness of revascularisation and severity of coronary artery disease are predictors of adverse outcomes.

Methods

Patients aged ≥75 years with multivessel disease or left main disease who underwent PCI or CABG between 2012–2016 were included in this retrospective cohort study. Baseline characteristics from the index procedure were collected. Severity of coronary artery disease and completeness of revascularisation were assessed. Primary outcome was all-cause mortality, in addition we captured major adverse cardiac and cerebral events, bleedings, recurrent angina and new onset atrial fibrillation.

Results

A total of 597 patients were included. Median follow-up was 4 years (interquartile range 2.8–5.3 years). At baseline, patients in the PCI group more often had a previous medical history of CABG and more frequently underwent an urgent procedure compared with patients in the CABG group. Mortality at 5‑year follow-up was significantly higher in patients who underwent PCI compared with CABG (39.9% vs 25.4%, p < 0.001). Furthermore, acute coronary syndrome (ACS), repeat revascularisation and recurrent angina occurred more frequently after PCI, while occurrence of bleedings and new onset atrial fibrillation were more frequent after CABG. Neither completeness of revascularisation nor severity of coronary artery disease was a predictor for any of the outcomes.

Conclusion

Long-term mortality was higher in elderly patients with multivessel disease undergoing PCI compared with CABG. In addition, patients undergoing PCI had a higher risk of ACS, repeat revascularisation and recurrent angina.
Perceptions of the Importance of Sleep in Common Cold—Two Online Questionnaire-Based Surveys
Authors: Phillipson Gill , Aspley Sue , Fietze Ingo
Published: April 2020

Sleep deprivation affects the immune system and can render subjects more susceptible to symptoms associated with the common cold. The aim of this research was to investigate cold sufferers’ and doctors’ perceptions of the role of sleep in recovery from cold/flu. An online survey of 4000 adults who had suffered from cold/flu in the previous 12 months was conducted in eight countries and an online survey of 150 doctors was conducted in Germany. Responses were collected to questions regarding aspects of life affected by, and concerns while suffering from, cold/flu symptoms including nighttime awakening and actions taken to aid recovery. Responses were also collected to questions regarding advice given to cold/flu patients and the importance of sleep. Ability to sleep well was widely reported as negatively impacted by cold/flu (mean 46.1% of respondents across eight countries), especially in Western Europe, and inability to sleep well was a frequently reported concern associated with suffering from cold/flu (21.8%). To sleep more than usual was a frequently reported action taken to feel better (40.5%). Ninety-four percent of respondents reported waking up at night because of symptoms, cough being the most frequently reported symptom to awaken respondents. There was evidence of a possible relationship between sleep quality and medication taken at night for symptom relief. Countries with the highest proportions of respondents who reported sleep to be the aspect of life most negatively affected by a cold (France, Germany and Italy) were also those with the lowest proportions of respondents who reported that taking medications at night was the most effective way of getting back to sleep after waking due to cold symptoms. The majority of doctors believed sleep helped cold/flu patients to recover faster and that a good night’s sleep was important. Sleep is widely considered to be important in promoting recovery from cold/flu. Hence, the relief of symptoms that disrupt sleep is also likely to be important for a faster recovery.
Impulsgeberin und Anstifterin: Die Deutsche Stiftung Friedensforschung im Lichte der Evaluation
Authors: Schneckener Ulrich , Held Thomas
Published: April 2020

Der Beitrag bewertet die Evaluation durch den Wissenschaftsrat aus Sicht der Deutschen Stiftung Friedensforschung (DSF). Er stellt die Rolle der DSF für das Forschungsfeld dar und diskutiert die wichtigsten Empfehlungen des Wissenschaftsrates für die Profilierung und die Weiterentwicklung der DSF. Außerdem macht der Artikel deutlich, welche Perspektiven sich für die Förderung der Friedens- und Konfliktforschung ergeben – dies betrifft sowohl Förderstrukturen und Förderformate als auch die künftige finanzielle Ausstattung der DSF.
Therapeutic Targeting of Hepatic Macrophages
Authors: Nijland Hilde , Bansal Ruchi
Published: April 2020

Purpose of Review

This review outlines the current knowledge about hepatic macrophages and provides an overview of therapeutic approaches to target hepatic macrophages for the treatment of liver diseases.

Recent Findings

In recent years, it has been increasingly recognized that hepatic macrophages (resident macrophages, Kupffer cells, or circulating bone marrow monocyte-derived macrophages) are implicated in liver homeostasis as well as in disease progression and resolution. More recently, different populations of hepatic macrophages with distinct phenotypes and functions have been identified that have shown to play distinct roles in the pathogenesis of various acute and chronic liver diseases. The understanding of the role of hepatic macrophages in initiation, progression, and resolution of liver diseases has given rise to the development of therapeutics that can target different phenotypes of hepatic macrophages. Innovative strategies comprises of microRNA (miRNA), small interfering RNA (siRNA), therapeutic proteins, and small-molecule inhibitors.

Evidence from recent in vitro and in vivo studies support the fact that hepatic macrophages can be efficiently targeted using miRNA/siRNA-based approaches, protein-based approaches, and small-molecule inhibitors for the treatment of liver diseases. However, more in-depth understanding underlying the roles of distinct macrophage phenotypes in different liver diseases is required for the translation of novel targeted therapeutics to the clinic.
Virtual application of in situ simulation during a pandemic
Authors: Hanel Erich , Bilic Monika , Hassall Kelly , Hastings Mary , Jazuli Farah , Ha Michael , Trotter Brendon , Fraser Cory , Rutledge Greg
Published: April 2020

The coronavirus disease 2019 (COVID-19) pandemic introduced challenges to the use of simulation, including limited personal protective equipment and restricted time and personnel. Our use of video for in situ simulation aimed to circumvent these challenges and assist in the development of a protocol for protected intubation and simultaneously educate emergency department (ED) staff. We video-recorded a COVID-19 respiratory failure in situ simulation event, which was shared by a facilitator both virtually and in the ED. The facilitator led discussions and debriefs. We followed this with in situ run-throughs in which staff walked through the steps of the simulation in the ED, handling medications and equipment and becoming comfortable with use of isolation rooms. This application of in situ simulation allowed one simulation event to reach a wide audience, while allowing participants to respect social distancing, and resulted in the education of this audience and successful crowdsourcing for a protocol amidst a pandemic.
Unveiling the Natural History of Category 4 Tropical Cyclones: The Puerto Rico Trauma Hospital Experience after Hurricane Maria
Authors: Ramos-Meléndez Ediel O. , Nieves-Plaza Mariely , López-Maldonado Julio , Ramírez-Martínez Laura , Guerrios Lourdes , Rodríguez-Ortiz Pablo
Published: April 2020

Objectives:

The hazardous environmental conditions hurricanes create might increase injury incidence almost 7 times. Therefore, a cohort study was performed at the Puerto Rico Trauma Hospital to compare morbidity and mortality patterns of patients after Hurricane Maria with a control period.

Methods:

Admissions from September 20, 2017, through January 20, 2018, constituted the post-Maria period (473 patients); the corresponding months of the previous year comprised the pre-Maria period (439 patients). Comparisons were done using Pearson’s chi-square or Mann-Whitney U-tests, as appropriate. A logistic regression was performed to assess the association between mortality and the study period.

Results:

Postlandfall admissions among patients aged 40-64 y increased by 6.6%, while among subjects between ages 18 and 39 y dropped by 7.0% (P = 0.03). Falls, gunshots, and burns were the injury mechanisms that varied the most across the exposure period. The median Injury Severity Score (13 vs 12; P = 0.05) and the frequency of Glasgow Coma Scale scores ≤8 (17.1% vs 10.9%; P = 0.03) were higher among poststorm patients. Moreover, a 2-fold (odds ratio = 1.93; 95% CI: 1.07-3.47) increase in mortality was observed after Maria, when adjusting for covariates.

Conclusions:

Following a hurricane, trauma centers might expect an older population, with more severe injuries and a 2-fold increased mortality risk.
Bernoulliness of when is an irrational rotation: towards an explicit isomorphism
Authors: LEURIDAN CHRISTOPHE
Published: April 2020

Let $\unicode[STIX]{x1D703}$ be an irrational real number. The map $T_{\unicode[STIX]{x1D703}}:y\mapsto (y+\unicode[STIX]{x1D703})\!\hspace{0.6em}{\rm mod}\hspace{0.2em}1$ from the unit interval $\mathbf{I}= [\!0,1\![$ (endowed with the Lebesgue measure) to itself is ergodic. In a short paper [Parry, Automorphisms of the Bernoulli endomorphism and a class of skew-products. Ergod. Th. & Dynam. Sys.16 (1996), 519–529] published in 1996, Parry provided an explicit isomorphism between the measure-preserving map $[T_{\unicode[STIX]{x1D703}},\text{Id}]$ and the unilateral dyadic Bernoulli shift when $\unicode[STIX]{x1D703}$ is extremely well approximated by the rational numbers, namely, if $$\begin{eqnarray}\inf _{q\geq 1}q^{4}4^{q^{2}}~\text{dist}(\unicode[STIX]{x1D703},q^{-1}\mathbb{Z})=0.\end{eqnarray}$$ A few years later, Hoffman and Rudolph [Uniform endomorphisms which are isomorphic to a Bernoulli shift. Ann. of Math. (2)156 (2002), 79–101] showed that for every irrational number, the measure-preserving map $[T_{\unicode[STIX]{x1D703}},\text{Id}]$ is isomorphic to the unilateral dyadic Bernoulli shift. Their proof is not constructive. In the present paper, we relax notably Parry’s condition on $\unicode[STIX]{x1D703}$: the explicit map provided by Parry’s method is an isomorphism between the map $[T_{\unicode[STIX]{x1D703}},\text{Id}]$ and the unilateral dyadic Bernoulli shift whenever $$\begin{eqnarray}\inf _{q\geq 1}q^{4}~\text{dist}(\unicode[STIX]{x1D703},q^{-1}\mathbb{Z})=0.\end{eqnarray}$$ This condition can be relaxed again into $$\begin{eqnarray}\inf _{n\geq 1}q_{n}^{3}~(a_{1}+\cdots +a_{n})~|q_{n}\unicode[STIX]{x1D703}-p_{n}|<+\infty ,\end{eqnarray}$$ where $[0;a_{1},a_{2},\ldots ]$ is the continued fraction expansion and $(p_{n}/q_{n})_{n\geq 0}$ the sequence of convergents of $\Vert \unicode[STIX]{x1D703}\Vert :=\text{dist}(\unicode[STIX]{x1D703},\mathbb{Z})$. Whether Parry’s map is an isomorphism for every $\unicode[STIX]{x1D703}$ or not is still an open question, although we expect a positive answer.
Investigating a self-reference effect in musical aesthetics
Authors: Kasdan Anna , Belfi Amy M.
Published: April 2020

Previous work on aesthetic experience suggests that aesthetic judgments are self-referential. The self-reference effect (SRE) is the tendency for individuals to show improved memory for items that are judged in relation to themselves. The current study sought to understand if the SRE exists for aesthetic judgments of music. Participants heard musical excerpts (classical, jazz, and electronic) and rated either a) how much they liked the music (Self condition), b) how much a close relative or friend would like the music (Other condition), or c) the genre of the music (Genre condition). After a retention interval, participants completed a recognition memory task for the musical excerpts. Participants did not show improved memory for musical excerpts encoded in the Self condition. These results extend the concept of the SRE into the domain of aesthetic judgments, but do not provide support for a memory advantage when making aesthetic judgments in relation to the self.
ON THE IRREDUCIBLE COMPONENTS OF SOME CRYSTALLINE DEFORMATION RINGS
Authors: BARTLETT ROBIN
Published: April 2020

We adapt a technique of Kisin to construct and study crystalline deformation rings of

$G_{K}$

for a finite extension

$K/\mathbb{Q}_{p}$

. This is done by considering a moduli space of Breuil–Kisin modules, satisfying an additional Galois condition, over the unrestricted deformation ring. For

$K$

unramified over

$\mathbb{Q}_{p}$

and Hodge–Tate weights in

$[0,p]$

, we study the geometry of this space. As a consequence, we prove that, under a mild cyclotomic-freeness assumption, all crystalline representations of an unramified extension of 

$\mathbb{Q}_{p}$

, with Hodge–Tate weights in

$[0,p]$

, are potentially diagonalizable.
The shape of and solutions to the MTurk quality crisis
Authors: Kennedy Ryan , Clifford Scott , Burleigh Tyler , Waggoner Philip D. , Jewell Ryan , Winter Nicholas J. G.
Published: April 2020

Amazon's Mechanical Turk is widely used for data collection; however, data quality may be declining due to the use of virtual private servers to fraudulently gain access to studies. Unfortunately, we know little about the scale and consequence of this fraud, and tools for social scientists to detect and prevent this fraud are underdeveloped. We first analyze 38 studies and show that this fraud is not new, but has increased recently. We then show that these fraudulent respondents provide particularly low-quality data and can weaken treatment effects. Finally, we provide two solutions: an easy-to-use application for identifying fraud in the existing datasets and a method for blocking fraudulent respondents in Qualtrics surveys.
RADIOCARBON RESERVOIR AGES IN THE HOLOCENE DEAD SEA
Authors: Weber Nurit , Lazar Boaz , Stern Ofra , Burr George , Gavrieli Ittai , Roberts Mark , Kurz Mark D , Yechieli Yoseph , Stein Mordechai
Published: April 2020

The sources and fate of radiocarbon (14C) in the Dead Sea hypersaline solution are evaluated with 14C measurements in organic debris and primary aragonite collected from exposures of the Holocene Ze’elim Formation. The reservoir age (RA) is defined as the difference between the radiocarbon age of the aragonite at time of its precipitation (representing lakeʼs dissolved inorganic carbon [DIC]) and the age of contemporaneous organic debris (representing atmospheric radiocarbon). Evaluation of the data for the past 6000 yr from Dead Sea sediments reveal that the lakeʼs RA decreased from 2890 yr at 6 cal kyr BP to 2300 yr at present. The RA lies at ~2400 yr during the past 3000 yr, when the lake was characterized by continuous deposition of primary aragonite, which implies a continuous supply of freshwater-bicarbonate into the lake. This process reflects the overall stability of the hydrological-climate conditions in the lakeʼs watershed during the late Holocene where bicarbonate originated from dissolution of the surface cover in the watershed that was transported to the Dead Sea by the freshwater runoff. An excellent correlation (R2=0.98) exists between aragonite ages and contemporaneous organic debris, allowing the estimation of ages of various primary deposits where organic debris are not available.
Breaking down long-term chronic aggression within a forensic hospital system
Authors: Rose Benjamin , Broderick Charles , Delgado Darci , Kornbluh Rebekah , Stahl Stephen M.
Published: April 2020

Objective.

Historically, patients with multiple acts of aggression, or chronic aggressors, have been studied as one large group. It was our objective to subdivide this group into those patients who engage in physical aggression consistently over multiple years and see if common characteristics of chronic aggressors could classify patients into an aggressive or nonaggressive group.

Method.

Within a forensic hospital system, patients who had committed 5 acts of physical aggression, per year, for 3 years (2010 and 2015) were reviewed. Data was collected on clinical and demographic characteristics that have shown to be associated with chronically aggressive patients and compared to nonaggressive matched controls. Data collection and analysis were completed to determine if the variables could classify patients into an aggressive or nonaggressive group.

Results.

Analysis showed that 2 variables, the presence of a cognitive disorder and a history of suicidal behaviors were significant in the univariate and multivariate analyses. The 2 variables were able to correctly classify 76.7% of the cases.

Conclusion.

A cognitive disorder, a history of suicidal behavior, and increased age were factors associated with this subgroup of aggressive patients. Clinicians may want to explore treatment programs aimed at these clinical factors including cognitive rehabilitation and social cognition treatments, which have been shown to reduce aggression in cognitively impaired populations.
107 Examining Real World Treatment Pathways in Parkinson Disease Psychosis: Initial Findings from the INSYTE Observational Study
Authors: Goldman Jennifer G. , Fox Susan H. , Coate Bruce , LoVerme Jesse , Larsen Niccole J. , Trotter Jeff , Shim Andrew
Published: April 2020

Study Objectives:

The INSYTE study provides an understanding of the management of Parkinson disease psychosis (PDP) in actual practice settings, including use of antipsychotic (APs) and their impact on clinical, economic, and humanistic outcomes. Treatment paradigms or the benefits/consequences of various “real world” PDP treatment strategies have not been evaluated. Thus, providers may be using a wide range of AP treatment strategies that contrast with consensus recommendations.

Method:

The INSYTE study is enrolling up to 750 patients from up to 100 sites in the US. Data are compiled at the baseline (BL) visit and from standard-of-care follow up visits over 3 years. PDP treatment pathways are defined from 3 BL cohorts reflecting (1) no AP medication, (2) use of pimavanserin (PIM), or (3) other AP treatment. Information about APs used is collected at each follow-up visit: history, duration, dose, adjustment, and rationale for adjustment of treatment. Outcomes assessments (clinical, quality of life, disease burden) by the physician, patient, and caregiver are also collected. AP medication and outcomes data are analyzed for patients completing a BL and 1 follow up visit (FU1).

Results:

For 404 patients with BL and FU1 visits (mean 120.7 days from BL), 56.8% used no AP medications, 26.0% used PIM, and 13.6% used other APs at BL. The No Medication group was noted to be less severe in key BL disease parameters. Considering primary PDP treatments at BL and FU1 (including no treatment), 26 distinct pathways were being employed. 12.6% of patients had AP medication adjustments between BL and FU1 visits, most frequently from the non-PIM group. Adjustments of APs occurred in many forms: introduction of a single AP (64.7%%), introduction of multiple APs (5.9%), switching to another AP (3.9%), decreasing the number of APs (5.9%), and discontinuation (19.6%).

Conclusions:

Multiple, divergent AP treatment strategies for PDP exist in actual practice. No identifiable BL characteristics correlated with the broad range of AP treatment pathways. The numerous distinct AP treatment pathways utilized (n=26) reflect discordance with the updated 2019 MDS evidence-based recommendations, which recognize only 2 APs as “efficacious” and “clinically useful”: pimavanserin and clozapine. Education of healthcare professionals remains a priority for PDP management.

Funding Acknowledgements:

ACADIA Pharmaceuticals Inc.
110 Implementation of Personalized Medicine in a Community Psychiatry Practice
Authors: Umbreit Audrey , Sinha Shirshendu , Holm Emily
Published: April 2020

Objective:

To describe the initial results of implementing pharmacogenomics testing in a community-based psychiatry practice and potential impacts on medication management.

Method:

Retrospective chart review of prospectively maintained medical records of all adult patients with pharmacogenomics results from 9/01/2017 to 6/30/2019 under the care of psychiatrist and clinical pharmacist.

Results:

A total of 51 patients met inclusion criteria. A total of 7 pharmacokinetic genes and, due to changes in the test report over time, a range of 6-10 pharmacodynamic genes relevant to psychotropic medications were evaluated per patient. Every patient had genetic variations, with an average of 6.1 per patient (range 3-9; SD= 1.5). Patients were taking an average of 3.6 (range 1-8; SD=1.7) psychiatric medications at the time of the genetic test, to treat an average of 5 psychiatric conditions (range 1-9; SD=2.2). An average of 1.2 (range 0-4; SD=1.0) gene-drug interactions were uncovered per patient. Following review by psychiatrist and pharmacist, medication adjustments resulted in patients remaining on an average of 3.6 psychiatric medications, but decreasing the average number of gene-drug interactions per patient to 0.8 (range 0-3, SD=0.8).

Discussion:

The large number of genetic variations observed per patient is consistent with previous findings 1-2. The decrease in number of gene-drug interactions following testing demonstrates the practical utility of pharmacogenomics information to guide medication therapy. This study did not examine outcomes such as improvement in psychiatric condition or reduction in medication adverse effects; however, these endpoints have been evaluated in other trials 3-4.

Conclusions:

Pharmacogenomics testing presents an opportunity for a personalized medicine approach in a community-based psychiatry practice.
111 Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (P301) Assessing Efficacy and Safety of Extended-Release Viloxazine in Children with ADHD
Authors: Nasser Azmi , Hull Joseph T. , Chowdhry Fatima A. , Adewole Toyin , Liranso Tesfaye , Schwabe Stefan
Published: April 2020

Study Objective:

SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) in development as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This Phase 3, randomized, double-blind study (P301) evaluated the efficacy and safety of once-daily SPN-812 at doses of 100 and 200 mg compared to placebo in children ages 6-11yrs with ADHD.

Method:

Inclusion criteria required subjects have a confirmed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) ADHD diagnosis, ADHD-Rating Scale-5 (ADHD-RS-5) score ≥28, a Clinical Global Impression-Severity score ≥4, and be free of ADHD medication ≥1 week before randomization. This investigation was conducted at 34 study sites in the United States. Subjects (N=477) were randomized 1:1:1 to placebo:100 mg SPN-812:200 mg SPN-812. The 6-week treatment period included up to 1 week of titration and 5 weeks of maintenance (intent-to-treat population: N=460; placebo=155, 100 mg=147, 200 mg=158). The primary efficacy endpoint was the change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) scores at EOS, and CFB at EOS in Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and in Weiss Functional Impairment Rating Scale-Parent Version (WFIRS-P) total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical exams, electrocardiograms, and the Columbia-Suicide Severity Rating Scale.

Results:

Compared to placebo, a significantly greater improvement in ADHD-RS-5 total score was observed in the 100 mg and 200 mg SPN-812 treatment groups beginning at week 1 (p=0.0004, p=0.0244; respectively) through EOS (p=0.0004, p<0.0001; respectively). Significant improvement at EOS for both 100 mg and 200 mg SPN-812 compared to placebo was also observed in CGI-I score (p=0.0020, p<0.0001; respectively), Connors 3-PS Composite T-score (p=0.0003, p=0.0002; respectively), and in WFIRS-P total average score (p=0.0019, p=0.0002, respectively). The most common (≥5%) treatment-related AEs reported were somnolence, decreased appetite, and headache.

Conclusions:

In this study, SPN-812 at 100 mg and 200 mg doses met the primary and secondary objectives with statistical significance. AE-related dropouts were ≤5%, indicating SPN-812 treatment was well tolerated.

This study is an encore of a poster presentation at the 2019 Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP).

Funding Acknowledgements:

This research was funded by Supernus Pharmaceuticals, Inc., Rockville, MD.
115 An Experimental Study to Assess the Professional and Social Consequences of Mild-to-Moderate Tardive Dyskinesia
Authors: Ayyagari Rajeev , Goldschmidt Debbie , Mu Fan , Caroff Stanley N. , Carroll Benjamin
Published: April 2020

Study Objective:

To Evaluate the impact of mild-to-moderate orofacial tardive dyskinesia (TD) symptoms on the people and social lives of people with TD.

Background:

TD, a movement disorder affecting the face and extremities, may arise in patients taking antipsychotics. The impact of stigma on the professional and social lives of people with moderate-to-severe TD was previously examined, but has not been investigated in those with mild-to-moderate TD.

Methods:

This study is an experimental, randomized digital survey of a general population sample. Three component surveys corresponding to employment, dating, and friendship domains were adopted from a prior study. For each domain, participants were randomized 1:1 into either a test group (who viewed a video of a scripted interview with an actor depicting mild-to-moderate TD movements) or a control group (who viewed the same actor but without TD movements) and asked about their impressions of the video subject. Actor simulations of the TD symptoms were validated by physicians familiar with TD and rehearsed to simulate orofacial movements with a total Abnormal Involuntary Movement Scale (AIMS) score of 3–6. Statistical comparison was made using Wilcoxon signed-rank or chi-squared tests for continuous and categorical variables.

Results:

A total of 800 respondents completed each survey. In all domains, respondents had more negative perceptions of actors portraying mild-to-moderate TD movements than of the same actors without movements. For employment, 41% fewer respondents in the test group versus the control group agreed that the actor would be suitable for client-facing jobs (P<0.001). For dating, the proportions of respondents who agreed that they would like to continue talking to the actor and who would be interested in meeting them for a coffee/drink were 23.2% and 26.0% lower, respectively, in the test group than in the control group (P<0.001). For friendship, the proportions of respondents who rated the actor as interesting and who would be interested in friendship with them were 13.0% and 12.2% lower in the test group than in the control group (P<0.001).

Conclusions:

This study addresses the stigma faced by those with mild-to-moderate TD in professional and social situations. Consistent with previous results for moderate-to-severe TD, actors simulating mild-to-moderate orofacial TD movements were perceived to be less likely to move forward in a job interview, be considered as a potential romantic partner, or be a new friend.

Funding Acknowledgements:

This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel.
118 Use of Patient Health Questionnaire to Predict Relapses in Patients with Treatment-resistant Depression Treated With Esketamine + Oral Antidepressant
Authors: Jamieson Carol , Li Nan , Daly Ella , Janik Adam , Lane Rosanne , Singh Jaskaran
Published: April 2020

Objective:

To assess the Patient Health Questionnaire (PHQ-9) as a predictor of relapse of depressive symptoms in treatment-resistant depression (TRD).

Method:

Analysis included maintenance phase data from SUSTAIN-1 (NCT02493868), a randomized, double-blind, active-controlled study in TRD patients that evaluated efficacy of intranasal esketamine (ESK) + oral antidepressant (AD) vs AD + intranasal placebo in delaying relapse of depressive symptoms. A ≥50% reduction in initial symptom score and total score of ≤12 were considered as response and remission, respectively, using the Montgomery-Asberg Depression Rating Scale. PHQ-9 total score (range, 0–27), PHQ-2 total score (0–6), and individual items of the PHQ-9 (0–3) were examined as predictors of relapse. Data were collected every 2 weeks. Association between time-varying PHQ-9 and event of depression relapse was evaluated in Andersen-Gill Cox model.

Results:

Of 176 stable remitters, 63 had a relapse event (ESK+AD [n=24]; AD+placebo [n=39]). Of 121 stable responders, 50 had a relapse event (ESK+AD [n=16]; AD+placebo [n=34]). Among stable remitters, PHQ-9 total score (HR; 95% CI [1.12; 1.04–1.21]) and PHQ-2 total score (1.58; 1.25–1.99) were associated with relapse risk. PHQ-9 items #1 (loss of pleasure, 2.07; 1.38–3.09), #2 (feeling down, 2.18; 1.51–3.15), #4 (feeling tired, 1.54; 1.13–2.11), and #6 (negative self-view, 2.27; 1.41–3.66) were associated with relapse risk. PHQ-2 total scale yielded the smallest Akaike’s Information Criterion among stable remitters and responders.

Conclusion:

PHQ-9, PHQ-2 total scores or individual items may be useful for predicting relapse of depressive symptoms among stable TRD patients.

Funding Acknowledgements:

This study was sponsored by Janssen Research and Development, LLC.
121 Oviposit Dysgeusia; Head Trauma Induced Chemosensory Noisome Egg Dysgeusia: The Miasma of Dante’s Inferno-When Eggs Become Rotten
Authors: Winchester Chevelle , Hirsch Alan
Published: April 2020

Introduction:

Post-traumatic dysgeusia with conversion of the taste of eggs rotten eggs has not heretofore been described.

Method:

Case Report: A 60 year old right handed female 6 months prior to presentation sustained head trauma. Three days later she noted reduced taste and smell dysgeusia to eggs. Eggs tasted distorted, like rotten eggs. Raw egg whites had no smell or taste. Cooked egg whites had faint sulfur smell for 2-3 seconds and the taste of sulfur. Yolk of soft-boiled eggs, had no smell or taste. The white had no smell but an unbearable sulfur taste. Raw eggs had no smell. The yolk of hardboiled eggs had no smell and taste, the whites smelled and tasted like sulfur. Sunny side up eggs with yolk and white segregated had no smell but tasted, as they should. Sunny side up eggs with yolk and white mixed together has no smell but strong sulfur taste. Scrambled eggs had no smell but mild sulfur taste, which changed over time to a rotten egg smell and taste. With nose clips, scrambled eggs had 0/10 taste, without the nose clips the smell of sulfur was 3/10.

Results:

Olfaction: Normosmia to threshold and Retronasal Smell Index: 2 (abnormal): Gustatation : Normogeusia to all. Mild hypogeusia to sodium chloride. MRI: Multiple foci of periventricular and deep white matter demyelization.

Discussion:

Rotten egg smell maybe mediated through retro-nasal pathways, since nasal obstruction eliminated the rotten egg taste. Eggs can possibly be developed as a home device to assess chemosensory function.
124 Reframing the Approach to the Diagnosis and Treatment of Borderline Personality Disorder in Adolescents
Authors: Matthews Dan
Published: April 2020

Background:

Using the same DSM-5 criteria as in adults, BPD in adolescents is defined as a 1-year pattern of immature personality development with disturbances in at least 5 of the 9 domains listed in the DSM-5. BPD can now be reliably diagnosed as young as 13 using one of several standardized clinician, or self-rated diagnostic instruments. Unfortunately published US and Canadian positions regarding pharmacological treatment have been, With regard to evidence-based studies, pharmacological treatment is not recommended and, if ultimately required, should be limited to second-generation antipsychotics. Fortunately, the last decade s extensive advancements in brain-mapping have provided more clarity about the various brain dysfunctions underlying the symptoms/traits presenting in BPD, providing new opportunities to address these primarily Fronto-Limbic dysfunctions neuropharmacologically and potentially, significantly ameliorate. Thus, in turn, likely enhancing the effectiveness of the newer available therapies.

Objectives:

The current study explores the feasibility of more effectively managing BPD symptoms/traits with a unique medication protocol consisting of two medications; an anticonvulsant (oxcarbazepine) and a dopaminergic (amantadine HCl), without use of an antipsychotic medication.

Methods:

Subjects were 147 females, ages 13-16, with the diagnosis of BPD treated with the described medication protocol in a residential facility. Positive outcome was described as achievement and maintenance of greater than 50% improvement from baseline admission state of functioning for 1 year. They were discharged when stable and having achieved greater than 50% improvement from baseline. Outpatient prescribers were requested to be compliant with the treatment protocol. However, some were non-compliant, substituting antipsychotic medication instead. Care givers were surveyed at 6 months and 1 year to determine whether their child was maintaining greater than 50% improvement.

Results:

The percent maintaining greater than 50% improvement was calculated for those whose caregivers reported continuation of the medications as prescribed, versus those whose prescribers changed the medications to the Community Standard. Of those compliant with the medication protocol, 61 of 86 (71%) maintained >50% improvement. Of those moved to the Community Standard approach, 19 of 61 (31%) maintained >50% improvement. Using Chi Square analysis, there was a significant relationship between maintenance of improvement and medication protocol compliance. Chi Square, Fisher’s exact test = p<0.001.

Conclusion:

The results indicate that, for adolescents 1 year post-discharge from residential treatment for BPD, continuation of the above described medication protocol provides significantly higher rates of maintenance of achieved symptom improvement. Further controlled studies are needed.

Funding:

None.
128 Factors Associated with Cost Savings Following Use of a Pharmacogenetic Assay in Individuals with Mood and Anxiety Disorders
Authors: Edwards Alison M , Perlis Roy H , Krause David S
Published: April 2020

Background:

In a study conducted in the database of a large commercial healthcare insurer, we previously demonstrated that use of a commercial pharmacogenetic assay for individuals with mood disorders was associated with decreased resource utilization and cost in the 6 month period following use compared to propensity-score matched controls. We conducted a post hoc analysis to understand variables associated with high cost savings.

Methods:

The results and methods of the initial study have previously been described. Cases were individuals with mood and anxiety disorders who received a commercial pharmacogenetic assay (Genomind, King of Prussia PA) to inform pharmacotherapy. 817 tested individuals (cases) with mood and/or anxiety disorders were matched to 2745 controls. Overall costs were estimated to be $1,948 lower in the tested group. The differences were largely the result of lesser emergency room and inpatient utilization for cases. In the present analysis, cost difference for cases compared to their matched controls was rank ordered by decile. High cost savers were arbitrarily defined a priori as the top 20% of savers. Using multivariable modeling techniques, an ordinal logistic regression model was generated in which baseline or follow-up variables were statistically tested for independent associations with high, low, and no cost savings.

Results:

606 (74%) of cases were net cost savers compared to their controls (cost difference <0). High cost savers (n=121) saved on average $10,690 compared to their matched controls. They were statistically more likely to have been diagnosed with bipolar disorder (n=33/121) than low cost savers (n=57/485) or non-savers (n=31/211), and had a lower Charlson Comorbidity index. High cost savers had fewer mean number of antidepressants in the baseline period (mean=3.16) compared to non-savers (3.73) but more than low cost savers (2.72) (p<0.05 across groups). In a multivariable model, bipolar, count of antidepressants, outpatient visits, and inpatient visits were statistically associated with being a high cost saver; antidepressant count and all-cause inpatient and outpatient visits in the baseline period were inversely associated with cost savings.

Conclusions:

Use of a pharmacogenetic assay was associated with cost-savings in the database of a large commercial insurer. Patients with bipolar disorder were more likely to be high cost savers than individuals with other mood and anxiety disorders.

Funding Acknowledgements:

Genomind
129 Medication Assisted Treatment Protocol
Authors: Mathis David Michael
Published: April 2020

This article describes a protocol to be able to utilize medication assisted treatment options for patients dependent on opioids. The first step is using a 15-day Klonopin taper for effect detox of acute opioid withdrawal. Once detoxed, the patient can be started on low dose methadone or low dose Buprenorphine. Titration above 40 mg of Methadone, or 8 mg of buprenorphine will usually not be needed. Buprenorphine is utilized as the mono product, Subutex. Avoiding Suboxone eliminates the risk of reemergence of acute opioid withdrawal symptoms.

A description of how to transition to Naltrexone is provided. There are some differences between Methadone and Buprenorphine in the transition to Naltrexone. Once the patient is transitioned to Naltrexone, the stage is set for the patient to be able to get off medication assisted treatment.
141 Moderating Perspectives of Long Acting Injectable Use of Antipsychotics: A Literature Review
Authors: Riedford Kathy
Published: April 2020

Long acting injectable (LAI) antipsychotics are indicated for individuals suffering from schizophrenia, delusional disorder, schizoaffective disorder and bipolar disorder. Even though LAIs have traditionally been used for a subgroup of patients who were not compliant with oral treatments or who were a high risk to others, current trends are changing with increased options and availability of these treatments. A number of factors are implicated in the reversal of this trend including perspectives of patients and perspectives of providers. There is not abundant literature available regarding robust studies to examine these perspectives, but this presentation provides a current summary of available literature.

Some factors that influence perspectives of both patients and providers include knowledge about LAIs, cost of LAIs and the traditional views of these agents as being used under coercive circumstances. Altering perspectives has been a primary barrier to increase the use of these agents. Evidence clearly supports the use of early intervention for individuals with first episode psychosis, and poor medication compliance results in poorer treatment outcomes. With the potential improvement in quality of life and potentially decreasing the cost burden of this illness in society, this avenue for treatment must be a strong consideration for all involved in the treatment of the aforementioned disorders.
148 Sustainability of a Benzodiazepine Deprescribing Intervention with Primary Care Providers in a University-Based Community Clinic
Authors: Platt Lois M. , Savage Teresa A.
Published: April 2020

Study Objectives:

In light of the opioid crisis, less attention has been focused on the long-term misuse of benzodiazepines (BZD) for anxiety and sleep disorders. The purpose of this study was to determine the sustainability of positive results (an 80% decrease in BZD prescribing) following a deprescribing intervention with primary care providers working with a low-income population at a Midwestern university-based community clinic.

Method:

All de-identified BZD prescriptions written by providers at the community clinic were captured using the electronic medical record. A BZD equivalency chart was used to compare the relative potencies of BZD commonly prescribed by the clinic. Each prescription was converted to a single number: the diazepam equivalent (DE). This number takes into account the potency of the drug (using diazepam as the standard), the dose of the drug, number of tablets dispensed and number of refills. The number of DE prescribed was tallied every 30 days for 6 months following the completion of a quality improvement BZD deprescribing intervention. The original intervention was implemented in 2018, with the goal of decreasing the prescription of BZD by clinic primary care providers to outpatients for insomnia or anxiety. The brief intervention combined academic detailing and pharmaceutical company detailing with a deprescribing message. Providers were given current evidence about alternatives to BZD, deprescribing schedules, and brain-storming opportunities about the management of patient concerns and resistance to change. Posters with alternatives to BZD were hung in the main provider office at the clinic. Food and “No Benzo” logo merchandise (mugs, pens) were provided to attendees of the intervention and clinic nurses. Thirty days after the intervention, the number of DE prescribed decreased by 80%.

Results:

Benzodiazepine prescribing (measured in DE) continued to decrease every 30 days for six months to 92-93% of pre-intervention numbers.

Conclusions:

Follow up of a 2018 intervention revealed sustainability of the effect of a significant decrease in benzodiazepine (BZD) prescribing in a community clinic. A brief BZD deprescribing intervention using a combination of academic detailing and pharmaceutical company detailing designed to persuade prescribers to change their behavior was effective in influencing providers to decrease the amount of BZD they prescribe. The desired result (an 80% decrease in BZD prescribing) was achieved following the original 30-day intervention. Prescription numbers continued to decrease over the next six months (to 92-93% of pre-intervention numbers), which indicates that the deprescribing intervention may have had a sustainable positive effect on provider prescribing behavior. This intervention is easy to implement and may decrease BZD prescribing, which addresses the overuse/misuse of BZD, a significant public health concern in the United States.

Funding Acknowledgements: Personal funds only
158 Open-label Study of Pimavanserin Patients with Comorbid Parkinson’s Disease and Depression
Authors: Guskey Michael T. , Alva Gustavo , Aldred Jason L. , Coate Bruce , DeKarske Daryl , Cantillon Marc , Norton James C.
Published: April 2020

Study Objectives:

Depression occurs in ~50% of Parkinson’s disease (PD) patients, increases in severity and duration as the disease progresses, and is associated with increased morbidity. Improvement of depression in PD patients is correlated with reduced physical disability and improved quality of life. We are assessing use of pimavanserin (PIM) for treatment of depression in adults with PD.

Method:

A Phase-2, 8-week, open-label, single-arm study is being conducted to evaluate the safety and efficacy of PIM as an adjunct to SSRI/SNRI or as monotherapy in adults with both PD and symptoms of depression (baseline Hamilton Depression Scale [17-items] total score [HAMD-17] ≥15). The primary endpoint of the study is change from Baseline to Week 8 in the HAMD-17. Secondary measures included the Clinical Global Impression (CGI) scales (improvement and severity) and Scales of Outcomes in PD-Sleep (SCOPA).

Results:

Interim results based on the first 34 of 40 planned patients have been evaluated: 55.9% of patients were male, and average age was 68.1 years, with 19 patients on adjunctive therapy and 15 on monotherapy. At baseline, patients had a mean (SE) HAMD-17 of 19.8(0.6). Change from Baseline to Week 8 (least squares mean [LSM] [SE]) in the HAMD-17 was –10.7(1.0) (95% CI; –12.7,–8.7; P<0.001), with significant improvement seen as early as Week 2 (–8.4[1.0]; 95% CI; –10.5,–6.4; P<0.001). Significant improvement was seen for both adjunctive treatment and monotherapy: 45.2% of patients responded to treatment (≥50% improvement on the HAMD-17) at Week 8, and 35.5% reached remission (HAMD-17 ≤7). On the Clinical Global Impressions–Improvement scale, 54.8% were much/very much improved at Week 8. Significant improvement was seen in change from Baseline to Week 8 SCOPA–Global Sleep Quality, –Nighttime Sleep, and –Daytime Sleepiness: –1.0(0.4) (95% CI; –1.7,–0.3; P=0.010), –2.1(0.7) (95% CI; –3.6,–0.6; P=0.008), –2.1(0.4) (95% CI; –3.0,–1.2; P<0.001) respectively. Twenty-one of the 34 enrolled patients have completed the study to date, and another 7 are still continuing. Thirteen patients reported adverse events, the most common being falls, UTI, diarrhea, and nausea.

Conclusions:

These interim data suggest that PIM as adjunctive treatment or monotherapy is associated with early improvement of depressive symptoms in patients with PD and is well tolerated. This is consistent with recently reported data of PIM in major depressive disorder. Final data will be shared at the time of this presentation. However, additional placebo-controlled data will be needed to determine fully the efficacy of PIM in patients with comorbid PD and depression.

Funding Acknowledgements:

ACADIA Pharmaceuticals Inc.