bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and characterization of colistin-resistant E. coli and K. pneumoniae isolated from Lower Himalayan Region of India
Authors: Singh Avinash , Keshri Anand Kumar , Rawat Suraj Singh , Swami Deepak , Uday Kala Venkata , Prasad Amit
Published: May 2021

Multidrug resistance is one of the worldwide public health concerns. Water represents the most suitable environment, for the exchange of antibiotic resistance genes among pathogenic to non-pathogenic bacteria. Therefore, we aimed to screen the presence of blaNDM-1, blaTEM, blaSHV, blaCTX-M and mcr1–5 genes among water samples from different locations of Lower Himachal Pradesh. We examined the genotypic incidences of blaNDM-1, blaTEM, blaSHV, blaCTXM and mcr1–5 by polymerase chain reaction. Survivability assay, fitness cost assay and biofilm assay were performed for phenotypic characterization. The presence of blaNDM-1 and its related variants were analysed and confirmed by sequencing-based approaches. A total of 73 bacterial strains were identified on M-lauryl sulphate agar medium. Out of 73 colistin-resistant isolates, 34 were E. coli and 39 were K. pneumoniae. Out of 34 samples, 2 (5.8%), 2 (5.8%), 5 (14.7%), 5 (14.7%) and 4 (11.76%) E. coli were blaTEM, blaSHV,blaCTXM-1, blaCTXM-2 and blaCTXM-15 positive, respectively. Among 39 K. pneumoniae, 15 (38.4%), 6 (15.3%), 10 (25.6%), 9 (23.07%) and 10 (25.6%) were blaTEM, blaSHV, blaCTXM-1, blaCTXM-2 and blaCTXM-15 positive, respectively. Interestingly, we observed one E. coli (HG4) isolate with both blaNDM-1 and mcr-1 gene. Further analysis showed HG4 isolate has lesser survivability on the cotton swab, long lag phase and less biofilm production compared to colistin-sensitive isolates. Detection of E. coli with blaNDM-1 and mcr-1 in this geographical region is an alarming signal for tourists, community, health workers and policymakers. Hence, it is utmost important to take appropriate measures to control the dissemination of antibiotic resistance gene in such pristine locations.
Mechanical and durability assessment of cement-based and alkali-activated coating mortars in an aggressive marine environment
Authors: Lashkari Salar , Yazdipanah Farzad , Shahri Mahyar , Sarker Prabir
Published: May 2021

Coatings are used as practical solutions against the intrusion of corrosive ions into concrete structures, particularly, in the harsh marine environment. In the present study, the effectiveness of using cement-based and geopolymer-based coatings produced using by-product materials has been evaluated. Silica fume and GGBFS at their optimum dosages were incorporated into mortar mixtures as a cement replacement, and mixtures of NaOH or KOH and sodium silicate solutions were used in the alkali-activated mortars. Shrinkage test, RCMT, and capillary absorption test as common experiments for durability analysis, as well as tests related to the mechanical and bonding properties including compressive strength test, pull-off test, and shear bonding strength test were carried out on the specimens. According to the results, both geopolymer and cement-based mortars improved the compressive and bonding strengths, and chloride diffusion resistance of coatings compared to the OPC mortar. Silica fume was found to be more effective in the strength development of mortars at young ages, while GGBFS was more responsible for acting as a filler and producing further gel in the older ages. The major drawback with geopolymer mortars is the high rate of water absorption and shrinkage coefficient in the early hours, which shows the importance of curing of these mortars at young ages. Overall, the mix design produced with 30% GGBFS and 7.5% silica fume showed the highest durability and mechanical properties and proved to be more compatible with the harsh environment of the Persian Gulf.
Significance of cutting plane in liquid metal embrittlement severity quantification
Authors: DiGiovanni C. , He L. , Hawkins C. , Zhou N. Y. , Biro E.
Published: May 2021

The automotive industry is turning to advanced high strength steels (AHSS) to reduce vehicle weight and increase fuel efficiency. However, the zinc coating on AHSS can cause liquid metal embrittlement (LME) cracking during resistance spot welding. To understand the problem, the severity of the cracking must be measured. Typically, this is done from the weld cross-section. Currently, there is no standard procedure to determine which plane through the weld must be examined to gauge cracking severity, leading to a variety of practices for choosing a cutting plane. This work compares the magnitude and variability of LME severity measured from the plane of exhibiting the most severe surface cracking to arbitrarily chosen planes. The plane exhibiting the most severe cracks had more and longer cracks on the cross-section than the arbitrarily chosen plane, resulting in a higher crack severity measurement. This higher absolute measurement increased the relative accuracy of the examination, allowing for fewer welds to be examined to precisely determine the effect of LME mitigation methods on cracking severity, how welding parameters affect LME cracking severity and the predicted LME affected strength of a particular weld.
Force Generation Profiles of Para-Nordic Sit-Skiers Representing Different Physical Impairments
Authors: Karczewska-Lindinger Magdalena , Linnamo Vesa , Rosso Valeria , Gastaldi Laura , Rapp Walter , Vanlandewijck Yves , Lindinger Stefan
Published: May 2021

Purpose

To biomechanically profile force generation connected to the complex role of the trunk in double poling in a representative sample of Para-Nordic sit-skiers.

Methods

Twelve male World Cup Para-Nordic sit-skiers (sport classes: LW10–12) were skiing on flat snow terrain at submaximal speed of 4.5 m/s (~ 73% maximum speed). 2D video (50 Hz) and pole force analyses (1000 Hz) were performed synchronously, examining angle, force and cycle characteristics to analyse the role of the trunk in generating propulsion.

Results

LW10–11.5 skiers lost between 21% and 4% propulsive force versus LW12 athletes only due to different geometrics of the trunk and pole angle at an equal axial pole force. While LW10–11 skiers indicated trunk extension or position maintenance during pole thrust, LW11.5–12 skiers showed strong trunk flexion combined with smaller pole angles to the ground. Hence, LW11.5–12 skiers could create larger propulsive forces and therefore greater cycle lengths at lower cycle rates at the same speed. Maximum speed increased from LW10 to LW12 and was significantly correlated to trunk flexion range of motion (r = 0.63) and cycle length (r = 0.59). Trunk flexion ROM showed a significant relationship to the impulse of propulsive force (r = 0.63) and pole angle to the ground (r = − 0.76) (allP < 0.05).

Conclusion

The impact of impairment on the force production profiles and its physiological-biomechanical consequences need further investigation also in other terrains and at wider spectrums of skiing speeds. The evident problem of low numbers of LW10–11 skiers in World Cup needs creative future solutions for research.
Aspergillus fumigatusand aspergillosis: From basics to clinics
Authors: Arastehfar A. , Carvalho A. , Houbraken J. , Lombardi L. , Garcia-Rubio R. , Jenks J.D. , Rivero-Menendez O. , Aljohani R. , Jacobsen I.D. , Berman J. , Osherov N. , Hedayati M.T. , Ilkit M. , Armstrong-James D. , Gabaldón T. , Meletiadis J. , Kostrzewa M. , Pan W. , Lass-Flörl C. , Perlin D.S. , Hoenigl M.
Published: May 2021

The airborne fungusAspergillus fumigatusposes a serious health threat to humans by causing numerous invasive infections and a notable mortality in humans, especially in immunocompromised patients. Mould-active azoles are the frontline therapeutics employed to treat aspergillosis. The global emergence of azole-resistantA.fumigatusisolates in clinic and environment, however, notoriously limits the therapeutic options of mould-active antifungals and potentially can be attributed to a mortality rate reaching up to 100 %. Although specific mutations inCYP51Aare the main cause of azole resistance, there is a new wave of azole-resistant isolates with wild-typeCYP51Agenotype challenging the efficacy of the current diagnostic tools. Therefore, applications of whole-genome sequencing are increasingly gaining popularity to overcome such challenges. Prominent echinocandin tolerance, as well as liver and kidney toxicity posed by amphotericin B, necessitate a continuous quest for novel antifungal drugs to combat emerging azole-resistantA.fumigatusisolates. Animal models and the tools used for genetic engineering require further refinement to facilitate a better understanding about the resistance mechanisms, virulence, and immune reactions orchestrated againstA.fumigatus. This review paper comprehensively discusses the current clinical challenges caused byA.fumigatusand provides insights on how to address them.
On the Epistemological Similarities of Market Liberalism and Standpoint Theory
Authors: Pils Raimund , Schoenegger Philipp
Published: May 2021

In this paper, we draw attention to the epistemological assumptions of market liberalism and standpoint theory and argue that they have more in common than previously thought. We show that both traditions draw on a similar epistemological bedrock, specifically relating to the fragmentation of knowledge in society and the fact that some of this knowledge cannot easily be shared between agents. We go on to investigate how market liberals and standpoint theorists argue with recourse to these similar foundations, and sometimes diverge, primarily because of normative pre-commitments. One conclusion we draw from this is that these similarities suggest that market liberals ought to, by their own epistemological lights, be more attentive towards various problems raised by feminist standpoint theorists, and feminist standpoint theorists ought to be more open to various claims made by market liberals.
“Wholly an Australian Industry”? Establishing British Multinational Manufacture at the Bryant & May Empire Works, 1909–1914
Authors: Robertson Emma , Fahey Charles
Published: May 2021

The Bryant & May company is well known for its operations in Britain. Historians have paid less attention to the actions of the company overseas. The opening of a new Australian subsidiary factory in 1909 marked an early venture in multinational manufacturing within the British Empire. This article uses business records and newspapers from both the British and Australian archives to examine the day-to-day operations of this multinational, with a particular focus on the human dimension of the interactions between London and Melbourne. The Bryant & May case study reveals the evolving, sometimes tense, relationship between the “home” and “subsidiary” branches in the context of British imperialism and Australian federation in the years preceding World War I. Business, personal, and imperial relationships intertwined. While business historians have developed theoretical frameworks to understand why companies embark on multinational operations, work remains to be done on the longer-term operations of companies in particular political, social, and cultural contexts. We examine the building of the Empire Works match factory in Melbourne, the nature of transnational management, labor relations, and key production challenges up to the Interstate Commission of 1914. We reveal how Melbourne managers, sometimes against the inclinations of the London directors, were prepared to drive a hard bargain with local politicians and workers. Bryant & May successfully, and sometimes controversially, gained competitive advantage as a “local” company with access to preferential tariffs. This placed the firm in an ideal position to prosper when international trade was disrupted during World War I.
Relationship among social tactics, job embeddedness, and affective commitment in newcomers: the moderating effect of workplace spirituality
Authors: Huang Hsien-Long , Cheng Li-Keng , Sun Pi-Chuan , Jiang Yi Shiuan , Lin Hsin Hua
Published: May 2021

The cost of recruitment and training of newcomers can be a burden for enterprises, causing adverse effects on human resources management. Although much research has addressed employee turnover, less attention has been paid to methods of improving the retention of new hires. This study is an empirical examination of the increase in predictive strength of antecedents of affective commitment for comparing newcomers’ workplace spirituality. The results of an employee survey completed by 237 newcomers with under two years of work experience indicate that socialization tactics have a direct impact on job embeddedness, which in turn has a direct effect on affective commitment. Workplace spirituality has a significant moderating effect on the relationship between socialization tactics and job embeddedness. Also, workplace spirituality has a significant moderating effect on the relationship between job embeddedness and affective commitment.
Work–family conflict and job performance: mediating role of work engagement in healthcare employees
Authors: Şahin Safiye , Yozgat Uğur
Published: May 2021

This study aims to examine the mediating role of work engagement in the effect of work interfering with the family (WIF) and family interfering with the work (FIW) on employees' employee-rated and supervisor-rated contextual and task performance, drawing on Job Demands and Job Resources model. The sample of the study consisted of 432 healthcare employees and 61 supervisors working for public hospitals in Turkey. We found support for a mediational model such that the relationship between FIW and employee-rated job performance (contextual and task) was mediated by work engagement. Although some studies examined how work–family conflict affects job performance, our knowledge on how these relationships can be mediated through work engagement is still limited. This study further investigates the underlying mechanism in the relationship between WFC and job performance.
Mood symptoms Associated with CADASIL Syndrome: A Case Report
Authors: Shaikh Asad , Idowu Joel
Published: May 2021

Objective

To discuss the psychiatric symptoms that are associated with CADASIL syndrome Abstract Cerebral:

Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare type of hereditary disease involving the small cerebral vessels. The clinical symptoms are various and include recurrent ischemic strokes, migraine with aura, seizures with epilepsy, psychiatric problems such as mood disturbances, and progressive cognitive decline leading to dementia. This disease needs awareness amongst the psychiatrists even though it is discussed much more in neurology literature. Psychiatric symptoms are seen in 20–41% of patients with CADASIL syndrome (1, 2). Psychiatric symptoms are actually the initial presentation in 15% of the cases. (3) The psychiatric disturbance most reported are mood disturbances (9–41%) especially depression. Here a 42-year-old African American female was brought to the hospital emergency room after she was found wandering in the streets. Psychiatry was consulted for altered mental status. Upon evaluation by the psychiatric consult service she was only oriented to person, depressed, anxious and complaining of headaches. Initial CT scan showed marked small vessel disease and old lacunar infarcts in the basal ganglia and right corona radiata. Magnetic Resonance Imaging (MRI) of the brain showed acute infarcts in the right posterior frontal and right parietal lobes along with old infarcts. Her symptoms and findings on imaging were consistent with CADASIL syndrome. Once the diagnosis was confirmed and prior records were obtained patient was resumed on an antidepressant and anxiolytic.

Conclusion

The purpose of this case report was to discuss psychiatric symptoms associated with CADASIL syndrome. Although there has been research showing a relationship between vascular disease and depression, a review of the literature suggests that there needs to be more research done to explore other psychiatric disturbances that may be seen with this syndrome. Psychiatric symptoms that are untreated can have the potential to further impact the quality of life therefore psychiatrists need to be aware of this syndrome in order to treat these patients promptly.

References

1 https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0778-8 2 http://dx.doi.org/10.32474/OJNBD.2018.01.000101 3 https://pdfs.semanticscholar.org/47f6/5952ee3c5dcf2a61345f704914b17fa8dc0d.pdf
The Dilemma, Conversion Disorder or Stiff Person Syndrome, a Case Report
Authors: Jahan Sultana
Published: May 2021

Study Objectives

The main objectives of this case study are 1. Clinicians facing symptoms that are difficult to interpret should exercise caution in diagnosing conversion disorder. 2. Increasing awareness about rare neurological conditions may appear as psychogenic illnesses. 3. Clinicians be advocate for their patients.

Introduction

Conversion disorder is a mental condition in which a person present with one or more symptoms of altered voluntary motor or sensory function, or other neurologic symptoms that cannot be explained by medical evaluation. Stiff person syndrome (SPS) is a disabling autoimmune central nervous system disorder characterized by progressive muscle rigidity, gait impairment, with superimposed painful spasms. SPS is commonly associated with high anti-glutamic acid decarboxylase (GAD) antibody titers. The dominant antigen recognized by these antibodies is the GABA-synthesizing enzyme GAD.

Method

Patient X, a 17-year-old Hispanic American female who presented to the Child and Adolescent Psychiatry Clinic with the complaint of ataxia & aphasia associated with anxiety. Patient was referred by the neurology clinic after they could not establish any organic cause of her ataxia or aphasia. After thorough evaluation at the child psychiatry clinic she was given the diagnosis of anxiety secondary to ataxia and aphasia and r/o Conversion Disorder. She was initiated treatment with sertraline for her anxiety. Her sertraline dose was increased gradually up to 100 mg daily. From the beginning the patient also received counseling & physical therapy. With these combination of treatments, patient’s symptoms did not get any better. Her symptoms actually got worse over time. At this point, the Child Psychiatry Clinic sent a message to the neurology clinic for further evaluation of patient due to her progressive gait and speech impairments.

Results

The neurology clinic saw the patient again and did further testing. The patient was positive for high titers of anti-glutamic acid decarboxylase antibodies (Anti-GAD). At this point, the patient was given the diagnosis of Stiff Person Syndrome. Patient was admitted to the hospital for further management. She was treated with benzodiazepines, IV immune globulin, & steroid. Soon after discharge from the hospital, the patient was seen at the Child Psychiatric Clinic. The patient’s mother reported, after the in-patient treatment, the patient’s symptoms improved.

Discussion

It is essential for clinicians to look for neurologic & other general medical conditions while evaluating a patient with possible conversion disorder. A systematic review of 27 studies found that among 1466 patients initially diagnosed with conversion symptoms, the frequency of misdiagnosis was approximately 4 percent.

References. BMJ. 2005;331(7523):989. Epub Oct 13. Childhood onset of stiff-man syndrome. JAMA Neurol. 2013;70(12):1531. J Neurol Neurosurg Psychiatry. 2015 Aug; 86(8):840–8. Epub 2014 Dec 15.
Onset and Resolution of Key Adverse Events in Valbenazine-Treated Patients with Tardive Dyskinesia: Pooled Analyses from Two Long-Term Clinical Trials
Authors: Marder Stephen R. , Lindenmayer Jean-Pierre , Shah Chirag , Carmack Tara , Angelov Angel S. , Lundt Leslie
Published: May 2021

Objective

Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Long-term safety of the approved TD medication, valbenazine, was demonstrated in 2 clinical trials (KINECT 3 [NCT02274558], KINECT 4 [NCT02405091]). Data from these trials were analyzed post hoc to evaluate the onset and resolution of adverse events (AEs).

Methods

Participants in KINECT 3 and KINECT 4 received up to 48 weeks of once-daily valbenazine (40 or 80 mg). Data from these studies were pooled and analyzed to assess the incidence, time to first occurrence, and resolution for the following AEs of potential clinical interest: akathisia, balance disorder, dizziness, parkinsonism, somnolence/sedation, suicidal behavior/ideation, and tremor.

Results

In the pooled population (N=314), all AEs of potential clinical interest occurred in <10% of participants, with somnolence (9.6%), suicidal behavior/ideation (6.4%), and dizziness (5.7%) being the most common AEs. Mean time to first occurrence ranged from 36 days (akathisia [n=9]) to 224 days (parkinsonism [n=2]). By end of study (or last study visit), resolution of AEs was as follows: 100% (suicidal ideation/behavior, parkinsonism); >85% (somnolence/sedation, dizziness); >70% (akathisia, balance disorder, tremor).

Conclusions

In long-term clinical trials, the incidence of AEs of potential clinical interest was low (<10%) and most were resolved by end of treatment (>70–100%). All patients taking valbenazine should be routinely monitored for AEs, particularly those that may exacerbate the motor symptoms associated with TD.

Funding

Neurocrine Biosciences, Inc.
Using Item 8 of the Abnormal Involuntary Movement Scale (AIMS) to Assess Improvement in Patients with Tardive Dyskinesia
Authors: Citrome Leslie , Lundt Leslie , Shah Chirag , Carmack Tara
Published: May 2021

Objective

The Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1–7) is usually the primary efficacy measure in tardive dyskinesia (TD) clinical trials. However, item 8 of the AIMS (clinician’s global impression of severity) might also be an appropriate assessment in real-life healthcare settings. To explore the potential of item 8 as a clinical measure, post hoc analyses were conducted using data from a long-term study of valbenazine, an approved TD medication.

Methods

In KINECT 4 (NCT02405091), adults with TD received once-daily valbenazine (40 or 80 mg) for 48 weeks. Analyses included two sets of AIMS item 8 scores: based on investigators ratings of item 8 using protocol-defined descriptors; and based on investigators highest scores from items 1–7 (analyzed post hoc). Shift analyses included an improvement from score =3 at baseline (moderate or severe) to score =2 at Week 48 (none to mild).

Results

At baseline in all participants (N=163), AIMS item 8 mean scores were 3.2 (protocol) and 3.3 (post hoc). In participants with a score =3 at baseline per investigators ratings using protocol-defined descriptors, 95.9% [94/98] shifted to a score =2 by Week 48. A similar result (93.9% [93/99]) was found when item 8 was based on investigators highest scores from items 1–7.

Conclusion

Shift analyses using AIMS item 8 scores indicated that most participants in KINECT 4 had a clinically meaningful improvement after 48 weeks of once-daily treatment with valbenazine. AIMS item 8 may be an appropriate clinical measure for assessing changes in TD severity.

Funding

Neurocrine Biosciences, Inc.
Disease Prevalence, Comorbid Conditions, and Medication Utilization Among Patients with Schizophrenia in the United States
Authors: Roy Brittany , Shah Ankitaben , Bloomgren Gary , Wenten Made , Li Jianheng , Lally Cathy
Published: May 2021

Objective

Disease prevalence, comorbid conditions, and pharmacological treatments were examined in a large population of US commercial- or Medicaid-insured individuals with schizophrenia.

Methods

This retrospective, cross-sectional claims analysis sourced data from the IBM MarketScan Commercial and Medicare Supplemental Databases and the Multi-state Medicaid Database (01Jan2009 to 30Jun2016). Cases were defined by =1 diagnostic claim (ICD-9-CM/ICD-10-CM) for schizophrenia during the study period. Comorbidities (=1 ICD-9-CM/ICD-10-CM diagnosis code) were grouped according to Clinical Classifications Software (CCS) level 2 categories. For the per-database analysis of comorbidities, schizophrenia cases were matched with controls by demographic characteristics. Case-control comorbidity comparisons were performed using prevalence rate ratios (PRRs) and 95% CIs. Per-database medication exposure (=1 National Drug Code in outpatients grouped by Redbook classification) was also assessed.

Results

Schizophrenia prevalence was 0.11% and 0.99% in commercially and Medicaid-insured patients, respectively. In both databases, comorbidity prevalence was higher among schizophrenia cases versus controls in approximately =80% of the CCS level 2 categories assessed. Common top categories of comorbidities for schizophrenia cases were mood disorders, anxiety disorders, other connective tissue disease, and diseases of the heart. Comorbidities with the highest case-control PRRs included personality disorders, suicide and intentional self-inflicted injury, and impulse control disorders. Across databases, the most commonly prescribed medications in cases were antipsychotics, antidepressants, and analgesics/antipyretics opiate agonists; the most highly prescribed antipsychotics were risperidone, quetiapine, aripiprazole, and olanzapine.

Conclusions

This large-scale analysis quantifies the high prevalence of medical and psychiatric comorbidity burden in patients with schizophrenia, highlighting the importance of integrated medical and psychiatric care.

Funding

Alkermes, Inc.
Effect of Deutetrabenazine on Metabolic Parameters in the Treatment of Tardive Dyskinesia
Authors: Jimenez-Shahed Joohi , Barkay Hadas , Anderson Karen E. , Fernandez Hubert H. , Factor Stewart A. , Hauser Robert A. , Wieman Maria , Gordon Mark Forrest , Savola Juha-Matti
Published: May 2021

Background

Deutetrabenazine, a novel vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved by the FDA for treatment of tardive dyskinesia (TD) in adults. Dopamine-receptor antagonists (DRAs) are associated with worsening of metabolic parameters, including weight gain, hyperlipidemia, and elevated blood glucose. This post hoc analysis assessed the short- and long-term effects of deutetrabenazine treatment on weight and metabolic parameters in individuals treated for TD.

Methods

Two 12-week, randomized placebo-controlled trials (RCTs) of deutetrabenazine for patients with TD evaluated either fixed dosing (AIM-TD; 12, 24, or 36 mg) or dose titration (ARM-TD; max dose, 48 mg/day). Patients completing ARM-TD or AIM-TD were included in an open-label extension (OLE) study, in which all patients underwent response-driven titration of deutetrabenazine from 12 mg/day up to a maximum total dose of 48 mg/day. Weight, body mass index (BMI), serum glucose, serum total cholesterol, and serum triglycerides were evaluated at baseline and during treatment in the RCTs and in the OLE.

Results

In the RCTs, 282 and 133 patients received deutetrabenazine or placebo. At baseline, 77% of patients used DRAs. At Week 12, no meaningful changes in weight were observed, with mean (standard error) weight changes of 0.9–1.2 (0.3–0.5) and 0.2 (0.3) kg in the deutetrabenazine and placebo groups, respectively, and mean BMI changes of 0.3–0.5 (0.1–0.2) and 0.1 (0.1) kg/m2. 337 patients were included in the analysis of the OLE study. No meaningful changes were observed in weight (mean change: 0.4 [0.4] kg at Week 54, –0.5 [0.6] kg at Week 106, and –1.1 [0.6] kg at Week 145) or BMI (mean change: 0.1 [0.2] kg/m2 at Week 54, –0.2 [0.2] kg/m2 at Week 106, and –0.3 [0.2] kg/m2 at Week 145). Across the studies, no meaningful changes were observed in triglyceride, cholesterol, or glucose levels.

Conclusion

Deutetrabenazine does not affect common metabolic parameters in patients with TD, even during long-term exposure.

Funding

Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Othello Syndrome: Delusional Disorder - Jealous Type ≠ Violence
Authors: Ahn Elizabeth Soyeon , Hobbs Jacqueline A.
Published: May 2021

Background

Othello syndrome, also known as morbid jealousy, pathological jealousy, and conjugal paranoia, is a rare delusional disorder related to partner’s infidelity. There are no large scale or comprehensive studies on delusional jealousy, and only few case reports and cases series leave delusional disorder jealous type (DDJT) largely unknown. Herein, we report a case of DDJT, its possible etiology and describe its characteristics, comorbidities, and interventions.

Case Description

A 65-year-old married, retired, and disabled Caucasian male with a history of closed traumatic brain injury and chronic pain presented for outpatient care accompanied by his wife with a chief complaint of paranoid delusions. The patient was a car racer when he sustained over 25% total body surface area burns after his motor vehicle crashed at the speed of almost 160 mph. The patient was in a coma for more than nine weeks, coded three times, and was resuscitated each time. Per imaging, the patient suffered subarachnoid hemorrhage to the right outer parietal and left front parietal lobes. The patient developed chronic pain from the extensive burns and has been on opioids for many years until he gradually tapered himself off about six years ago. For the last couple of years, the patient has experienced cognitive decline associated with disorientation and memory deficit. The patient has been perseverative on his wife’s trip two years ago during which the patient believed that she had an affair with one of their mutual acquaintances. The patient denied visual or auditory hallucinations and continued to express his love and affection toward his wife. Although his wife has continually provided reassurance, and multiple family members confirmed her faithfulness, the patient had minimal insight into his delusion and expressed disappointment in loss of sexual intimacy between him and his wife. The patient has been prescribed duloxetine 60mg and trazodone 150mg, and his mood, anxiety, and sleep have been stable. The patient has also started taking pimozide 1mg nightly since beginning of this year with good response.

Discussion

The DSM estimates the prevalence of DDJT to be less than 1%. At least a third of cases show neurological basis involving frontal lobe dysfunction associated with strokes, Parkinson’s disease, brain trauma and tumors, neurodegenerative disorder, encephalitis, multiple sclerosis, and even normal pressure hydrocephalus. Association with alcohol, amphetamine, cocaine, and dopamine therapy (pergolide, ropinirole, levodopa, amantadine, and pramipexole) were reported. Finally, DDJT is known to be a risk factor of violent crimes including homicide. Treatment with pimozide shows the strongest evidence, and most patients show improvement with any antipsychotic medication along with CBT. Continued research and further clinical trials are warranted for DDJT considering patients’ positive response to interventions, and because DDJT can become a dangerous condition in forensic situations.
Long-Term Deutetrabenazine Treatment Is Associated With Continued Improvement in Tardive Dyskinesia in the Completed 3-Year Open-Label Extension Study
Authors: Hauser Robert A. , Barkay Hadas , Fernandez Hubert H. , Factor Stewart A. , Jimenez-Shahed Joohi , Gross Nicholas , Marinelli Leslie , Wilhelm Amanda , Gordon Mark Forrest , Savola Juha-Matti , Anderson Karen E.
Published: May 2021

Background

The 12-week ARM-TD and AIM-TD studies in tardive dyskinesia (TD) patients showed statistically significant improvements in TD symptoms with deutetrabenazine. The completed open-label extension (OLE) study (SD-809-C−20) evaluated long-term efficacy and safety of deutetrabenazine in TD.

Methods

Patients who completed ARM-TD or AIM-TD enrolled in the OLE study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in Abnormal Involuntary Movement Scale (AIMS) score was assessed by local site raters. Treatment success was evaluated locally as patients being “much improved” or “very much improved” on Clinical Global Impression of Change (CGIC).

Results

343 patients enrolled in the OLE study; 6 patients were excluded from analyses. At Week 54 (n=249; dose [mean±SE]: 38.7±0.66mg/day), mean change from baseline in AIMS score was –4.8±0.28; 66% of patients experienced treatment success. At Week 106 (n=194; dose: 39.3±0.75mg/day), mean change from baseline in AIMS score was –5.4±0.33; 65% of patients experienced treatment success. At Week 145 (n=160; dose: 39.4±0.83mg/day), mean change from baseline in AIMS score was –6.6±0.37; 73% of patients experienced treatment success. Treatment was generally well tolerated across 723 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) for akathisia/restlessness were 0.01, somnolence/sedation were 0.07, and symptoms which may represent parkinsonism or depression were 0.08 each.

Conclusions

Patients who received long-term treatment with deutetrabenazine achieved sustained improvement in AIMS scores. Findings from this open-label trial with response-driven dosing suggest the possibility of increasing benefit over time.

Funding

Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Long-Term Efficacy and Safety of Deutetrabenazine for Chorea in Huntington’s Disease: Results From the ARC-HD Open-label Study
Authors: Frank Samuel , Testa Claudia M. , Stamler David , Kayson Elise , Oakes David , Vaughan Christina , Goldstein Jody , Whaley Jacquelyn , Davis Mat D. , Gordon Mark Forrest , Savola Juha-Matti ,   on behalf of the Huntington Study Group ARC-HD Investigators
Published: May 2021

Background

Chorea is a prominent motor dysfunction in Huntington’s disease (HD). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is FDA-approved for the treatment of chorea in HD. In the pivotal, 12-week First-HD trial, deutetrabenazine treatment reduced the Unified Huntington’s Disease Rating Scale (UHDRS) total maximal chorea (TMC) score versus placebo. ARC-HD, an open-label extension study, evaluated long-term safety and efficacy of deutetrabenazine dosed in a response-driven manner for treatment of HD chorea.

Methods

Patients who completed First-HD (Rollover) and patients who converted overnight from a stable dose of tetrabenazine (Switch) were included. Safety was assessed over the entire treatment period; exposure-adjusted incidence rates (EAIRs; adverse events [AEs] per person-year) were calculated. A stable, post-titration time point of 8 weeks was chosen for efficacy analyses.

Results

Of 119 patients enrolled (Rollover, n=82; Switch, n=37), 100 (84%) completed ≥1 year of treatment (mean [SD] follow-up, 119 [48] weeks). End of study EAIRs for patients in the Rollover and Switch cohorts, respectively, were: any AE, 2.6 and 4.3; serious AEs, 0.13 and 0.14; AEs leading to dose suspension, 0.05 and 0.04. Overall, 68% and 73% of patients in Rollover and Switch, respectively, experienced a study drug–related AE. Most common AEs possibly related to study drug were somnolence (17% Rollover; 27% Switch), depression (23%; 19%), anxiety (9%; 11%), insomnia (10%; 8%), and akathisia (9%; 14%). Rates of AEs of interest include suicidality (9%; 3%) and parkinsonism (6%; 11%). In both cohorts, mean UHDRS TMC score and total motor score (TMS) decreased from baseline to Week 8; mean (SD) change in TMC score (units) was –4.4 (3.1) and –2.1 (3.3) and change in TMS was –7.1 (7.3) and –2.4 (8.7) in Rollover and Switch, respectively. While receiving stable dosing from Week 8 to 132 (or end of treatment), patients showed minimal change in TMC score (0.9 [5.0]), but TMS increased compared to Week 8 (9.0 [11.3]). Upon drug withdrawal, there were no remarkable AEs and TMC scores increased 4.4 (3.7) units compared to end of treatment.

Conclusions

The type and severity of AEs observed in long-term deutetrabenazine exposure are consistent with the previous study. Efficacy in reducing chorea persisted over time. There was no unexpected worsening of HD or chorea associated with HD upon deutetrabenazine withdrawal.

Funding

Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel
Overcoming the Challenges of the Mental Health Care System in United States in the Aftermath of COVID-19
Authors: Radfar Amir , Caceres Maria Mercedes Ferreira , Sosa Juan Pablo , Filip Irina
Published: May 2021

Study Objective(s)

The impact of pandemic events such as the coronavirus (COVID-19) pandemic led to an economic crisis worldwide as well as an increase of mental health problems. In the United States, the gaps in the mental health care system struggle to meet the needs of vulnerable populations and have caused a major public health problem. We aim to increase the awareness of health care professionals, psychiatrists, and policy makers regarding failures and gaps in the mental health care system and suggest new ideas to overcome the growing burden of mental disorders.

Method

We utilized data from PubMed, Science Direct, Cochrane, Embase and Clinicaltrials.gov databases to analyze available information on the US mental health system. We included any relevant articles addressing the prevalence of mental diseases, disparities and the gaps for an accessible and affordable mental health system, as well as the psychological impact of COVID-19 pandemic.

Keywords

‘COVID-19’, ‘Coronavirus’, ‘SARS-CoV-2’, ‘mental health’, ‘Health, Mental’ were used.

Results

Following scoping review of several studies we noticed that while prevalence of mental health problems in the US varies between states and socio-demographic groups, it is among the top 10 causes of premature death and disability in adults. We noticed that mental health problems are currently one of the costliest public health issues in the healthcare system. Tracking Poll from one of the studies in our scoping review suggested that financial inequities are magnified by the COVID-19 pandemic and that psychological distress was substantially larger among respondents with lower income (33%), Hispanics (28%) and Blacks (26%). Furthermore, in another poll 62% of US population are shown to be anxious due to COVID-19. We observed that the prevalence of reported symptoms of psychological distress among US adults increased when compared to 2018. Common barriers such as failure of accessibility, insufficient funding, insufficient psychiatric beds, limited insurance access and economic burden, clinician shortages, fragmented care, insufficient mental health care policies and insufficient education and awareness about mental illness become more prominent during the COVID-19 pandemic era.

Conclusions

The impact of COVID-19 on mental health is alarming, which affects public health and has made the health care system more vulnerable. Pandemic events not only cause acute negative impact, they also result in long-lasting health problems, isolation and stigma. The COVID-19 pandemic threatens the mental health of the population and its long-term consequences can lead to a secondary pandemic. The outcomes of the COVID-19 pandemic on mental health emphasize the need for policies and strategies to support and strengthen a concerted effort to address its burden on the US mental health care system. In addition, it magnifies the need for high quality and well-funded research for future pandemics.
A Multiparametric MRI Protocol for Evaluation of Cognitive Insufficiency, Dementia and Traumatic Brain Injury (TBI): A Case Series
Authors: Sherman John L. , Kutz Christen F. , Szymczak Mitchell S. , York Deborah , Adams Laurence J.
Published: May 2021

Background

The purpose of this work was to determine the extent to which a multiparametric magnetic resonance imaging (MRI) approach to patients with dementia and/or traumatic brain injury (TBI) can help to determine the most likely diagnosis and the prognosis of these patients.

Objective

Volumetric brain MRI alone is recognized as a useful imaging tool to differentiate behavioral variant frontotemporal dementia (bvFTD) from the more common Alzheimer’s disease (AD). Our objective is to create a protocol that will provide additional non-standard, objective imaging data that can be utilized clinically to distinguish common and uncommon forms of dementia and TBI. As patients with these diseases are increasingly presenting to clinical practice, our ability to combine multiple parameters within the standard 30-minute or 45-minute (pre- and post-contrast) MRI exams has high potential to affect current and future clinical practice.

Methods

All MRI studies were performed on 1.5 T MRI GE 450w or GE HDx imagers. All patients were seen clinically in outpatient practices. All techniques are FDA approved. The 30 minute protocol utilized T2w FSE 3 mm, 2.5 mm SWAN, 3D T1 sagittal 1.2 mm, DWI 5 mm, 3D FLAIR 1.2 mm, 2.5 mm SWAN (susceptibility sensitive), 3D T1 sagittal 1.2 mm, arterial spin labeling perfusion, posterior cingulate single voxel PRESS MR spectroscopy and NeuroQuant automated volumetric analysis and LesionQuant automated lesion detection and measurement. The 45-minute TBI protocol added diffusion tensor imaging, MR spectroscopy (MRS) of normal appearing frontal white matter and 3D gadolinium enhanced technique.

Results

The combination of multiparametric data together with standard imaging and clinical information allowed radiologic interpretation that was able to focus on 1–2 specific diagnoses and to indicate those patients in which a combination of pathologies was most likely. Neurologists, gerontologists, neuropsychologists and psychiatric specialists used these data and our summary conclusions to develop more specific diagnoses, treatments and prognoses.

Conclusions

Readily available MRI techniques can be added to standard imaging to markedly improve the usefulness of the radiologic opinion in cases of subjective cognitive insufficiency, clinical mild cognitive insufficiency, behavioral pathologies, dementia and post-traumatic brain syndromes.
The Effectiveness of a Neighbor-to-Neighbor Get-Out-the-Vote Program: Evidence from the 2017 Virginia State Elections
Authors: Handan-Nader Cassandra , Ho Daniel E. , Morantz Alison , Rutter Tom A.
Published: May 2021

We analyze the results of a neighbor-to-neighbor, grassroots get-out-the-vote (GOTV) drive in Virginia, in which unpaid volunteers were encouraged to contact at least three nearby registered voters who were likely co-partisans yet relatively unlikely to vote in the 2017 state election. To measure the campaign’s effectiveness, we used a pairwise randomization design whereby each volunteer was assigned to one randomly selected member of the most geographically proximate pair of voters. Because some volunteers unexpectedly signed up to participate outside their home districts, we analyze the volunteers who adhered to the original hyper-local program design separately from those who did not. We find that the volunteers in the original program design drove a statistically significant 2.3% increase in turnout, which was concentrated in the first voter pair assigned to each volunteer. We discuss implications for the study and design of future GOTV efforts.
Biogeochemical Responses to Nutrient Fluxes in the Open South China Sea: A 3‐D Modeling Study
Authors: Shuai Yiping , Li Qian P. , Wu Zhengchao
Published: May 2021

Recent Bio‐Argo observations revealed a spatial difference of seasonal chlorophyll‐a pattern in the South China Sea (SCS) with permanent subsurface chlorophyll‐a maximum layer in the central SCS (CSCS) but intense winter chlorophyll‐a bloom in the northern SCS (NSCS). A three‐dimensional physical‐biogeochemical model was used to simulate the temporal change of upper ocean physics and biogeochemistry of the open SCS following the trajectories of the two Bio‐Argo floats to explore mechanisms driving the difference between the two very contrasting marine ecosystems. The model reasonably reproduced the Bio‐Argo vertical observations in both regions. In the model, high nitrate fluxes had supported a strong winter chlorophyll‐a and productivity in the NSCS, while low nitrate fluxes in the CSCS leading to a stable subsurface chlorophyll‐a layer throughout the year. We found that nitrate fluxes in the north were controlled by diffusion during the early winter but by advection during the late winter. Both buoyancy and wind forcing contributed to increased diffusive nutrient fluxes by mixing nutrients below the nutricline in the early winter of the NSCS. A strong upwelling during the late winter in the north was supported by eddy‐Ekman pumping, particularly the nonlinear effect induced by eddy vorticity gradient. The finding is consistent with the change of vertical advection in both directions and magnitudes in the north throughout the year. The eddy‐driven difference in advection between the two regions was further confirmed by substantially larger eddy kinetic energies and eddy activities in the north.
Toward Entrainment Thresholds in Fluvial Plucking
Authors: Hurst A. A. , Anderson R. S. , Crimaldi J. P.
Published: May 2021

Plucking of blocks is an important, but understudied component of erosion in steep bedrock rivers. With the goal of developing realistic entrainment thresholds for use in bedrock channel evolution models, we re‐formulate the block entrainment problem. We derive the force and torque balances representing sliding and toppling of blocks occupying backward‐facing steps in the channel floor. We employ a computational fluid dynamics package to calculate the pressures and shear stresses on all faces of such a block, therefore explicitly representing the horizontally directed drag force and vertically directed lift force. We find that the pressure difference between the upstream and downstream block faces can significantly impact the force and torque balances. At typical flows, downstream pressure becomes ∼1%–2% lower than total upstream pressure, reflecting the reduction in fluid pressures in the recirculation zone. This pressure difference scales with the block Reynolds number squared and dramatically increases if the block protrudes above the plane of the upstream ledge. The resulting net downstream‐directed force both adds to the forces promoting sliding and provides a torque about the lower downstream corner of the block. Armed with the full set of forces on a block, we explore the roles of block geometry, flow velocity and depth, toppling pivot point location, and bed slope in facilitating sliding and toppling. Incorporating the small pressure difference between upstream and downstream faces greatly lowers the threshold for plucking, and suggests that blocks on river channel floors should move at lower and hence more frequent discharges than previously thought.