bluuebunny/crossref_metadata_2025 huggingface dataset:
117 RE-KINECT: Real-World Dyskinesia Screening Study and Registry in Patients Taking Antipsychotic Agents: Interim Baseline Burden of Illness Results
Authors: Cutler Andrew , Caroff Stanley , Tanner Caroline , Lenderking William R. , Yeomans Karen , Shalhoub Huda , Pagé Véronique , Yonan Chuck
Published: June 2018

Background

Tardive dyskinesia (TD) is associated with prolonged exposure to dopamine receptor blockers including antipsychotics. This registry describes the prevalence and impact of involuntary movements (possible TD) in a real-world population of patients taking antipsychotics.

Methods

RE-KINECT (NCT03062033) aims to enroll 1,000 patients from 70 US psychiatric practices. Adults with ≥3 months lifetime exposure to antipsychotic(s) and ≥1 psychiatric disorder are eligible for two-tier screening: informal observation, and then clinician observation of abnormal involuntary movements in general body regions (head/face, neck/trunk, upper/lower limbs) and confirmation of possible TD. Based on clinician assessment, patients are assigned to Cohort 1 or Cohort 2 (without or with abnormal involuntary movements, respectively). In both cohorts, the following baseline assessments are included: clinician’s assessment of clinical psychiatric severity, patient perceived health‐related quality of life (EuroQOL 5-Dimensions), social burden/disability questionnaire (Sheehan Disability Scale), and 12-month retrospective chart review ofmedical and treatment history. Cohort 2 also participate in 12-month longitudinal evaluation. Interim baseline data are available from four sites.

Results

Baseline data are currently available for 116 patients—mean age, 49.6 years; female, 60.3%; schizophrenia/schizoaffective disorder, 32.8%; at least 1 mood disorder, 84.5%, and 10.4 years mean cumulative lifetime exposure to antipsychotic(s). The most concerning health condition for both cohorts is their mental health (69.0%), followed by physical activity and nutrition (33.6%). 32.8% of subjects had clinician confirmation of possible TD.

Conclusion

This novel registry aims to evaluate the real-world potential impact/burden of TD. Preliminary analyses suggest that TD is common in patients with schizophrenia and mood disorders taking antipsychotics. Further analyses will explore the burden of illness in this population.

Funding Acknowledgements

This study was funded by Neurocrine Biosciences, Inc.
118 Demographics and Real World Healthcare Cost and Utilization for Patients With Probable Tardive Dyskinesia
Authors: Polson Michael , Yonan Chuck , Williams Ted
Published: June 2018

Background

Tardive dyskinesia (TD) is a movement disorder associated with prolonged exposure to antipsychotics. The current study was designed to describe demographics and comorbidities for patients with a dyskinesia diagnosis as probable TD (cohort 1), patients likely to have undiagnosed/uncoded TD (cohort 2), and a control population.

Methods

This retrospective study analyzed Medicaid claims data from July 2013-March 2017. For a pool of patients with a history of 3 months or more of taking an antipsychotic, three cohorts were evaluated: cohort 1 (ICD-9/10 codes for dyskinesia); cohort 2 (propensity score matching to cohort 1); and cohort 3 (patients withschizophrenia, major depressive disorder [MDD], and/or bipolar disorder [BD] and history of ≤2 antipsychotic medications). Outcomes included patient characteristics, Charlson Comorbity Index (CCI) and healthcare utilization (pre-and post [12-month] period).

Results

Cohort sizes and characteristics were: cohort 1 (n=1,887; female, 68%; mean age, 42 years; MDD, 17%; BD, 48%); cohort 2 (n=1,572; female, 58%; mean age, 39 years; MDD, 22%; BD, 48%); cohort 3 (n=25,949; female, 67%; mean age, 40 years; MDD, 11%; BD, 49%). Cohorts 1 and 2 had higher comorbidity burden than cohort 3 (mean pre-index CCIs: 0.68, 0.79, and 0.47, respectively; p<0.001 for each cohort). After 12 months, mean per member per year healthcare costs were higher in cohort 1 and2 compared to cohort 3 ($21,293, $18,988, and $11,522, respectively), as were mean claims per member per year (185, 138, and 109, respectively).

Conclusion

In the study population, patients likely suffering from TD, ICD-9/10 code-confirmed or unconfirmed, have a higher overall comorbidity burden and healthcareutilization than those who probably do not have TD.

Funding Acknowledgements

This study was funded by Neurocrine Biosciences, Inc.
122 Use of Pimavanserin in Patients With Parkinson’s Disease Psychosis: Subgroup Analysis of Efficacy and Safety in Patients With and Without Cognitive Impairment
Authors: Weintraub Daniel , Norton James , Coate Bruce , Andersson Candace , Fredericks Doral , Ballard Clive
Published: June 2018

Objective

A planned subgroup analysis of a phase 3 study was performed to evaluate the efficacy and safety of pimavanserin (PIM) in Parkinson’s disease psychosis (PDP) patients withglobal cognitive impairment.

Background

PDP is frequent, distressing, a leading cause of institutionalization, complicates PD management and is linked to increased morbidity, incident dementia and mortality. PIM, a selective serotonin receptor (5-HT2A) inverse agonist/antagonist, is newly FDA-approved for the treatment of hallucinations and delusions associated with PDP.

Methods

In Study 020, a 6-week FDA registration study, 199 patients with baseline Mini-Mental State Examination (MMSE) score ≥21, moderate-severe psychosis, and on stable PD meds, were randomized to PIM (34 mg/day) or placebo (PBO) for 6 weeks. This subgroup analysis evaluates efficacy and safety between two groups: those with MMSE total score ≥21 but <25 (cognitively impaired; equivalent to Montreal Cognitive Assessment [MoCA] score 15-19) and those with score ≥25 (cognitively normal; equivalent to MoCA score 20-30). Safety assessments were performed on the full safety dataset (i.e., three 6-week placebo-controlled studies) including 614 subjects (PIM=382, PBO=231).

Results

Overall, patients in the PIM group experienced a statistically significant improvement in SAPS-PD scores from baseline to Day 43 compared with PBO (-5.79 vs. -2.73; p=0.001). In the subgroup analysis stratifying by baseline MMSE score, the change from baseline to Day 43 compared with PBO in the cognitively-impaired group (N=50) was numerically larger (-7.11 vs. -0.47; p=0.002). In the full safety dataset examining cognitively impaired patients, there were no between-group (PIM vs. PBO) differences in any treatment-emergent adverse event (TEAE) (57.6% vs. 56.1%) or serious TEAE (6.8% vs. 5.3%). The most common TEAEs occurring at ≥5% in either group were fall (7.4% vs.10.5%), confusional state (6.5% vs.1.8%), and orthostatic hypotension (0.0% vs. 8.8%).

Conclusions

In this subgroup analysis of PDP patients, the treatment effect of PIM on SAPS-PD was larger in the cognitively-impaired group, with similar TEAE and serious TEAE rates. These results hold promise for cognitively-impaired patients that will be further elucidated in future studies.

Funding Acknowledgements

Clinical study was funded by ACADIA Pharmaceuticals Inc.
125 Short Duration Monoballismus
Authors: Dhillon Davinder , Batta Priya , Hirsch Alan R.
Published: June 2018

Study Objective

While monoballismus has been reported to be associated with hemorrhagic lesions in the subthalamic nucleus (Ohnishi, 2009) and multiple sclerosis (MS) (Rosa, 2011), the duration has been reported to be at least six days (Soysal, 2012). A patient with epochs of monoballismus lasting for 45 minutes is presented.

Methods

Case Study: A 57 year old right handed female with attention deficit hereditary disorder predominantly inattentive on amphetamine sulphate, presented with two years of memory loss. For instance, after ordering food in restaurants, by the time the food arrives, she could not recall what she ordered. At the onset of this symptom, she noted three epochs of her left arm jerking for 45 minutes. The jerking would begin with low amplitude and low frequency and rapidly progress to the forearm and arm of greater magnitude and low frequency. With her right hand she would try to hold down her left arm without success. There was no associated paresis, sensory phenomena, headaches, dizziness, presyncope, loss of consciousness, or strong emotions. She admitted to frequent jamais vu.

Results

Abnormalities: Neurological Examination: Mental Status Examination: Memory: Immediate Recall: 5 digits forward and 2 digits backwards. Cranial Nerve (CN) Examination: CN I: Alcohol Sniff Test 8 (hyposmia). CN XII: tongue tremor on protrusion. Motor Examination: Drift Test: positive right pronator drift. Gait Examination: Tandem Gait: unstable. Reflexes: 0-1 throughout. Neuropsychiatric Examination: Go-No-Go Test: 6/6 (normal). Animal Fluency Test: 15 (normal). Clock Drawing Test: 3 (abnormal). Center for Neurologic Study Lability Scale: 16 (pseudobulbar affect). Other: MRI with and without infusion: normal.

Conclusion

Transient tonic-clonic movements of one limb have been described with focal epilepsy associated with diabetic non-ketotic hyperglycemia (Grant, 1985). A metabolic abnormality such as transient hypoglycemia or hyperkalemia can cause a focal dystonia (Soysal, 2012), which theoretically could manifest with monoballismus. This could be a somatic manifestation of underlying conflict, conversion disorder, or as a result of a physical manifestation of panic attack with hyperventilation and tetany (Mihai, 2008). This may be the first manifestation of a generalized cerebral disorder associated with chorea or ballismus such as Wilson’s disease, or Huntington’s Chorea (Mihai, 2008). It is possible that this is a variant of Alien Hand Syndrome with parietal lobe involvement (Shrestha, 2015). But this is unlikely given the absence of hemineglect or hemiagnosia. It is possible that amphetamines may have induced a monochorea. Chronic amphetamine use has been demonstrated to cause chorea (Klawans, 1974) and it theoretically could have caused ballismus movements in this case. In patients who present with short duration monoballismus, evaluation for subthalamic nuclei function, seizure disorders and other origins of ballismus are warranted.

Funding Acknowledgements

Smell & Taste Treatment and Research Foundation
133 Cognitive Impairment Following Overdose on Lamotrigine
Authors: Chandrashekar Geetha , Ash David , Singh Garima
Published: June 2018

Objective

To generate hypotheses, accumulate scientific data about rare presentations, and serve as a major educational tool.

Method

This is a retrospective case report of a patient in inpatient unit.

Introduction

Lamotrigine is a mood stabilizer with unique mechanisms of action. At therapeutic levels, it has been reported that Lamotrigine is neuroprotective and improves cognition. In this case, we present a patient who suffered significant cognitive slowing following overdose on Lamotrigine.

Case

A 17yo white male with a diagnosis of Autism spectrum disorder and Bipolar disorder type 1 was admitted for bizarre behavior and profound cognitive impairment. His past psychiatric history was significant for two suicide attempts - first by overdose on baby aspirin and second by overdose on Lamotrigine, both of which had occurred about six months prior to his presentation and had each required an inpatient hospitalization. His family reported that since his overdose on Lamotrigine, he had been withdrawn, aloof, and appeared depressed. His school teachers had noticed significant decline in his memory, attention and concentration, and there had been noticeable impairment in his ability to follow commands or complete a task. On assessment, he was noted to have significant psychomotor slowing, latency in speech and thought blocking. At the time of his presentation, he was on Lithium 300mg BID. A careful review of his previous medical records revealed that he had been on a combination of Seroquel, Lamotrigine and Lithium prior to his overdose attempt on Lamotrigine. During this hospitalization, Seroquel was restarted. Patient tolerated the medication well. There were no safety concerns and he was deemed safe to discharge under 24hr supervision of his family. He has since been followed up in clinic. Although he continues to have some cognitive slowing, overall, he has demonstrated slow but steady improvement.

Discussion

Lamotrigine acts by blocking voltage sensitive sodium channels. It also reduces release of glutamate, a major excitatory neurotransmitter in the central nervous system. Glutamate modulates synaptic plasticity, a property thought to be vital for memory and learning. While too much glutamate causes over activation of NMDA receptors resulting in increased intracellular oxidative stress and eventually apoptosis, too little glutamate may lead to decreased glutamate mediated postsynaptic excitation of neural cells and thus impacting memory formation, learning and cognition. At therapeutic levels (2.5- 15mcg/ml), it has been reported that Lamotrigine is neuroprotective and improves cognition. At the time of overdose, our patient had a Lamotrigine level of 21.5mcg/ml. There is limited literature on cognitive effect of supra-thrapeutic levels of Lamotrigine. As such, a causal relationship cannot be determined from a single care report. Also in differentials to consider are schizophrenia and seizures from lamotrigine withdrawal.

Funding Acknowledgements

No funding.
142 The Burden of Tardive Dyskinesia Secondary to Antipsychotic Medication Use Among Patients With Mental Disorders
Authors: McEvoy Joseph , Park Tyson , Schilling Traci , Terasawa Emi , Ayyagari Rajeev , Carroll Benjamin
Published: June 2018

Introduction

Extrapyramidal symptoms (EPS), including tardive dyskinesia (TD), may result from exposure to antipsychotics. TD is often irreversible, may be debilitating, and cause additional burden to patients with underlying psychiatric conditions.

Objective

To assess the impact of developing TD, both with and without other EPS, on healthcare resource utilization (HRU).

Methods

Data on patients receiving antipsychotics who had schizophrenia, major depressive disorder, or bipolar disorder were extracted from a Medicaid claims database. Patients from the TD cohorts (TD+EPS and TD non-EPS) were matched to those in the non-TD/EPS cohort at ∼1:5 ratio. HRU outcomes associated with TD were assessed.

Results

TD+EPS (n=289) and TD non-EPS (n=394) cohorts were matched with 1398 and 1922 control patients, respectively. The percentage of patients with all-cause and mental disorder-related inpatient admissions increased from baseline to follow-up in the TD+EPS (12.8% and 12.5%, respectively) and TD non-EPS (16.0% and 13.5%) cohorts, in contrast with slight decreases (∼3%) in matched controls. A higher percentage of patients in the TD cohorts had medical admissions/visits and claims for drugs that might be used to address TD or EPS than their matched controls at baseline and follow-up. The within-cohort change from baseline to follow-up in the use of potential drugs for TD or EPS was similar between the TD cohorts and their matched controls; however, both TD cohorts exhibited a larger increase in crisis–non-specific psychotherapy services versus matched controls.

Conclusions

Results demonstrated increased HRU in TD patients with or without other pre-existing EPS, compared with matched controls.

Presented at: Psych Congress; September 16–19, 2017; New Orleans, Louisiana, USA.

Funding Acknowledgements

This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
150 Estimation of an MCID for AIMS Total Score Change in Tardive Dyskinesia
Authors: Sajatovic Martha , Cutler Andrew J. , Farahmand Khodayar , Burke Joshua , Siegert Scott , Liang Grace S.
Published: June 2018

Background

The efficacy of valbenazine (INGREZZA) in tardive dyskinesia (TD) was demonstrated in placebo-controlled clinical trials, based on the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1-7). In these trials, mean changes in the AIMS total score were significantly greater with valbenazine 80 mg than with placebo. Currently, no minimal clinically important difference (MCID) has been established for the AIMS total score in patients with TD. Using valbenazine trial data, analyses were conducted to establish a MCID for AIMS total score in TD.

Methods

Data were pooled from three 6-week trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), KINECT 3 (NCT02274558). Using the Clinical Global Impression ofChange (CGI-TD) as an anchor comparison, AIMS total score changes from baseline to Week 6 were summarized for all study participants (pooled valbenazine and placebo groups) with a “minimal” CGI-TD score of ≤3 (minimally improved or better) or “robust” ≤2 (much improved or better) at Week 6.

Results

In the pooled population (N=373), 72% and 29% of all participants had CGI-TD scores of ≤3 and ≤2, respectively. The median (maximum, minimum) change from baseline in AIMS total score at Week 6 was -2 (-13, 8) in participants with CGI-TD score ≤3 and -3 ( 13, 8) in participants with a score ≤2.

Conclusion

Pooled data from 3 randomized, double-blind, placebo-controlled trials suggest that a 2 point decrease in AIMS total score may represent the minimal clinically meaningful improvement. Larger AIMS score improvements were associated with “much improved” or “very much improved” CGI TD assessments.

Funding Acknowledgements

This study was funded by Neurocrine Biosciences, Inc.
151 Improving the Systematic Use of Pharmacogenetic Testing for Depression Prescribing
Authors: Hughes Lauren Thomann
Published: June 2018

Study Objectives

The purpose of this project was to systematize the use of pharmacogenetic testing (PGT) among psychiatric prescribers. The use of PGT in clinical practice is inconsistent despite the evidence supporting its efficacy (Burke, Love, Jones, & Fife, 2016). The question to be answered is: In patients with major depressive disorder (MDD), how is PGT currently used in clinical practice compared to use after implementation of practice change interventions?

Method

This study was conducted among 4 psychiatric prescribers in a behavioral health clinic. 3 interventions were utilized to change practice. An educational in-service was delivered to address the PGT knowledge gap. A protocol for identifying patients that may benefit from PGT was developed, indicating PGT was warranted for patients with non-remitting moderate to severe MDD and at least 2 medication failures from 2 different classes. Next, a medication failure documentation template and the PGT report were integrated into the EHR. A baseline survey was administered before the in-service, assessing prescriber PGT perceptions and current parameters and barriers for use. Follow-up surveys were administered 3 months post-implementation. Project processes were measured by assessing the rate of medication failure template usage, as well as thePGT EHR upload rate.

Results

A comparison of baseline and follow-up surveys indicated there was little change in prescriber view of test utility, receptiveness, and likelihood of use. This may be attributed to previous experience with testing and to PGT manufacturer education. View of parameters and barriers for use did change. Key parameter for use changes included patient experience of adverse reaction (increase) and only 2 medication failures from the same class (decrease). Key barrier to use changes included time to results (decrease). 3 PGT were completed during the project. All patients met the protocol criteria for testing. None of these patients had medication failures documented using theEHR template; all of the patients did have documentation using each prescriber’s preferred method. 2 of the 3 tests were uploaded to the EHR. The first test completed was not integrated, likely due to support staff becoming accustomed to the new workflow. 117 historical PGT were also integrated into the EHR.

Conclusions

While 16 to 20% of the population meets the criteria for MDD, available treatments achieve symptom remission only 40% of the time (Singh, 2014). Patients who do not achieve remission experience relapse more quickly and are more likely to develop chronic non-remitting MDD (Gaynes, 2016). While the PGT evidence base is still evolving, its use in clinical practice has the potential to improve depression treatment outcomes. This study highlighted continued barriers to PGT use in a practice setting, while implementing key interventions, including PGT use guidelines and EHR integration, to improve its systematic and appropriate use.

Funding Acknowledgements

No funding.
155 Improvement of VIIIth Cranial Nerve Function With Cariprazine
Authors: Philobos Maximous K. , Hirsch Alan R.
Published: June 2018

Introduction

Cariprazine an atypical antipsychotic which acts as a dopamine D3-prefering partial agonist at dopamine D2/D3 receptors, as an antagonist at over stimulated dopamine receptors, as a partial agonist at serotonin 5-HT1A receptors, and as an antagonist of 5-HT2A receptors (Citrome, 2016; Kiss, 2010). While indicated for the treatment of schizophrenia and bipolar disorder, it has never been described to improve disorders of cranial nerve VIII. A patient with hearing loss associated with tinnitus, responsive to cariprazine, is reported.

Methods

Case Study: A 34 year old right handed married male 5 years prior to presentation developed bilateral auditory hallucinations of whispers, and one male disparaging voice. Approximately 6 months later it began belittling him, whereupon he was diagnosed with schizoaffective disorder, attention deficit hyperactivity disorder, and obsessive-compulsive disorder.

Three months prior to presentation he developed sepsis and became comatose. Upon awakening he experienced constant tinnitus, AS more than AD high pitched, without diurnal variation, which has been unrelenting. Coincident with the tinnitus was decreased hearing AS more than AD. Within a few days of treatment with cariprazine at 1.5 mg a day, the tinnitus transiently resolved and after raising the cariprazine to 3 mg per day the tinnitus abruptly stopped and his hearing returned to normal after 2 months. One and a half days after discontinuing the cariprazine the tinnitus and hearing loss returned. After reinstating the cariprazine to 3 mg a day the tinnitus and hearing loss resolved again.

Results

Psychiatric evaluation: Disheveled with postural tremor of both upper extremities. Pharyngeal dysarthria. Irritable and with expansive and labile affect. Severely impaired attention. Slow tangential thoughts, preoccupied with paranoia and suspiciousness. Paranoid delusions. Mental status examination: Memory testing: Immediate recall: 5 digits forwards and 3 digits backwards. Able to recall none of 4 objects in 3 minutes and 1 with reinforcement. Unable to spell the word “world.” Similarities interpreted concretely. Calculation ability poor.

Discussion

In the cochlea, as an inhibitory neurotransmitter, dopamine reduces sensitivity to auditory sensation (Langguth, 2009). Since ambient sounds are known to reduce tinnitus (masking), an antagonist at overstimulated dopamine receptors, cariprazine may act to reduce dopamine’s effectiveness, reducing inhibition and thus enhancing perceived external sound. It may act as a 5-HT1A serotonin agonist, directly reducing tinnitus. With reduced tinnitus there is less of a distraction and thus enhanced hearing. Or its function may be through its neuroleptic effects; the tinnitus could be a manifestation of auditory hallucinations, through reduction of this noise cariprazine secondarily causes enhanced hearing. Further investigation into the use of cariprazine in those with intractable tinnitus is worthwhile.

Funding Acknowledgements

No funding.
160 Optimizing TMS Treatment for Depression - The 19 Minute Dash™ Protocol
Authors: Mina Miriam , Brock David G. , Pascual-Leone Alvaro , Demitrak Mark A.
Published: June 2018

Title

Optimizing TMS treatment for Depression - The 19 Minute Dash™ protocol

Objective

NeuroStar transcranial magnetic stimulation (TMS) is an effective treatment for patients with major depressive disorder. Due to the treatment session duration, a reduced treatment time would promote patients’ comfort and convenience. Also, shorter treatment sessions of retained efficacy and safety would increase access to treatment. This reduction could be accomplished by decreasing the time between TMS pulse sequences, the intertrain interval (ITI).

Methods

Meta-analysis of TMS delivered using varying treatment parameters, particularly the ratio of train duration (“on-time”) to ITI (“off-time”). PubMed and SCOPUS databases were searched through March 30, 2015 using the terms: “transcranial magnetic stimulation”, “TMS”, “rTMS”, “inter-train interval”, “inter-stimulus interval”, and “cortical spread”. Three hundred and one articles were identified comprising a total of 3359 patients. Clinical outcomes were reported as the proportion of patients achieving response defined as 50% reduction in baseline score on the primary outcome measure in each study. Treatment risk was assessed by the frequency of adverse events reported, and specifically considering the incidence of seizures.

Results

This analysis confirms prior reports that the variables which impact treatment efficacy are the number of treatmentsessions, the number of pulses per session and the percent motor threshold. Varying the train duration/ITI (on-time/off-time) ratio over a broad range from 2.0 to 14 did not impact efficacy or safety.

Conclusions

Shortening the ITI to 11 seconds does not impact the safety and antidepressant effectiveness of the NeuroStar TMS and would result in shortening of each treatment session from approximately 37.5 to 19 minutes.

Funding Acknowledgements

Neuronetics, Inc.
161 The NeuroStar Outcomes Registry
Authors: Mina Miriam , Brock David G. , West W. Scott , Hutton Todd , Pages Kenneth P. , Kane Timothy J.
Published: June 2018

The NeuroStar Outcomes Registry

Objective

NeuroStar transcranial magnetic stimulation (TMS) is an effective acute treatment for patients with major depressive disorder (MDD). In order to further understand use of the NeuroStar in a clinical setting, Neuronetics has established a patient treatment and outcomes registry to collect and analyze utilization information on patients receiving treatment with the NeuroStar.

Methods

Individual NeuroStar providers are invited to participate in the registry and agree to provide their de-identified patient treatment data. The NeuroStar has an integrated electronic data management system (TrakStar) which allows for the data collection to be automated. The data collected for the registry include Demographic Elements (age, gender), Treatment Parameters, and Clinical Ratings. Clinical assessments are: Clinician Global Impression - Severity of Illness (CGI-S) and thePatient Health Questionnaire 9-item (PHQ-9). De-identified patient data is uploaded to Registry server; an independent statistical service then creates final data reports.

Results

Over 500 patients have entered the NeuroStar Outcomes Registry since Sept 2016. Mean patient age: 48.0 (SD±16.0); 64% Female. Baseline PHQ-9, mean 18.8 (SD±5.0.) Response/Remission Rate, PHQ-9: 61%/33% CGI-S: 78%/59%.

Conclusions

For the initial 500 patients in the Outcomes Registry, approximately 2/3 patients achieve respond and 1/3 patients achieve remission with an acute course of NeuroStar. These treatment outcomes consistent with NeuroStar open-label study data (Carpenter, 2012). The TrakStar data management system makes large scale data collection feasible. The NeuroStarOutcomes Registry is ongoing, and expected to reach 6000 outpatients from more than 47 clinical sites in 36 months.

Funding Acknowledgements

Neuronetics, Inc.
176 The Influence of Chronic Stress on the Development of Psychiatric Conditions
Authors: Phyu Pwint , Dumenigo Rhaisa , Oms Juan D. , Gunaseelan Luxhman , Foroughi Golbon , Rizvi Syed A. A.
Published: June 2018

A 20-year-old woman with a history of bipolar disorder (BD), posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD) presented to the emergency department with suicidal ideation. This report compares her clinical course with that of her twin brother, who also had received a BD diagnosis but grew up in a less stressful environment than his sister. It also describes the possible genetic and environmental etiologic factors associated with BD, PTSD, BPD, and other psychiatric conditions. Chronic stress is strongly associated with the development of these conditions; pathologic processes involving the effect of stress hormones and neurotransmitters on the brain and central nervous system are described, along with pharmacologic and nonpharmacologic approaches to reducing chronic stress in persons with BD and other psychological disorders.

Funding Acknowledgements

No funding.
187 Buprenorphine/Naloxone (Suboxone and Bunavail)-Induced Glycolimia, an Indication of Undermedication?
Authors: Kress Stefany , Hirsch Alan
Published: June 2018

INTRODUCTION

Buprenorphine/Naloxone combination drugs such as Suboxone and Bunavail have not been reported to induce glycolimia. Two such cases are presented.

METHODS

CASE STUDY: Case 1: A 30-year-old, right-handed, white female with a history of opioid abuse was started on 4.2 mg buprenorphine/0.7 mg naloxone (Bunavail) BID and began sweet cravings and consumption of sweet foods. In a typical day she would eat 16 strawberry pop-tarts and 2 boxes of Little Debbie cookies. This may have provoked the 10 pound weight augmentation in the first two weeks of treatment. She denied any craving for opioids and no evidence of opioid withdrawal was present. Her Clinical Opiate Withdrawal Scale (COWS) score =4 (normal).

Case 2: A 51-year-old, right-handed, male with opiate dependence, four days following the initiation of Suboxone (8 mg buprenorphine/2 mg naloxone) BID, developed strong cravings for sugary foods including donuts and ice cream, of which he was previously never inclined to eat and gained 10 pounds in one month. His COWS score= 7 (mild symptoms).

DISCUSSION

There are myriad mechanisms that may be acting to induce sugar cravings with buprenorphine/naloxone. Humans and rats acutely withdrawing from opiates, such as heroin, develop strong urges for consumption of sugary substances (Lieblich et al., 1991; Sapira, 1968; Weiss, 1982). Glycolimia in the above cases may reflect early or subclinical withdrawal, which if becoming more severe, would manifest as opioid craving. If the value of the reward system induced by sweets doesn’t meet the threshold invoked by the opioid stimulation, this “withdrawal” may lead to further sugar cravings in an attempt to reach the same reward level. In animals, certain foods and drugs share the same neurological pathway involved in the “reward system” potentially explaining why opioids influence food palatability in humans (Pelchat, 2002).

Alternatively, it is possible that buprenorphine induces hypoglycemia at high doses (Bullingham et al., 1981) such that hypoglycemia may paradoxically act to enhance sugar craving similar to the Somogyi effect in insulin dependent diabetics. Another possible mechanism of action is that since buprenorphine acts to decrease glucose metabolism in the brain (Walsh et al., 1994), this may lead to a neural compensatory response by increasing sugar access to the brain behaviorally via glycolimiaand somatically reducing insulin release, thus explaining the high hemoglobin A1c observed in opioid addicts (Giugliano, 1984). Given the above presentation, complaints of sugar craving may indicate consideration to increase buprenorphine dosing and trial of this in those with glycolimia without opioid dependence may be warranted.

Funding Acknowledgements

No funding.
189 Emetophobia: The Specific Phobia of Vomiting: 2 Case Studies With 1-Year Follow-up
Authors: Jahan Sultana , Bysani Sailaja
Published: June 2018

EDUCATIONAL OBJECTIVES

At the conclusion of the session, the participant should be able: 1) To recognize emetophobia & how it can lead to significant impairment & reduce quality of life; 2) To appreciate the prevalence of emetophobia among the general population, 3) To learn that the selective serotonin reuptake inhibitor sertraline can be effective for emetophobia; 4)Need for more research.

INTRODUCTION

Emetophobia is an intense, irrational fear of vomiting. The prevalence rate of emetophobia in a community sample has been estimated to 8.8 % with a female to male ratio 4:1: It can occur at any age and can have a chronic course affecting one’s academic/career, family, and social life.

METHODS

Case 1: B. was a 7 year old female referred by her pediatrician for psychiatric evaluation for her intense fear ofvomiting. Mother shared that B’s overwhelming fear of vomiting started when she was 6 years old and it may have stemmed from an incident when one of B’s cousins threw up inside their van. At school, B constantly monitored whether or not anybody was getting sick around her. If she found out, someone was sick she began screaming and crying. B’s academic performance was negatively affected due to her intense irrational fear.

Case 2: P was a 12 year male patient referred by his pediatrician for psychiatric evaluation after receiving 4 days inpatient treatment on the pediatric unit for dehydration. Patient reported that he was afraid of vomiting and gradually stopped eating and drinking & became so dehydrated that he was hospitalized. Several months prior to his hospitalization he had suffered from theflu & during that time he had intense vomiting and since then he has been fearful of a recurrence of the vomiting.

After a complete psychiatric evaluation, a diagnosis of emetophobia was established for each patient. Both patients were treated with sertraline.

RESULTS

B and P both started with initial dose of sertraline 12.5mg daily and then increased gradually over a period of next few months. They responded well with sertraline. B and P continued sertraline 50mg daily and 25mg daily as a maintenance treatment respectively. At 1 year follow up visit both of them were symptoms free.

CONCLUSIONS

Emetophobia is a common and chronic debilitating mental illness. Still there are no treatment protocols and randomized controlled trials for the treatment of emetophobia. CBT/Exposure-based therapies are the most commonly used approaches for emetophobia per literature. More studies are needed for a better understanding of eremophobia, which is relatively deserted illness although it can cause as much suffering as other major psychiatric disorders do and any patient presenting with these symptoms deserve to be evaluated an managed with scientific understanding and guideline.

Funding Acknowledgements

No funding.
191 Multi-Watt Near Infrared Phototherapy as a Treatment for Traumatic Brain Injury
Authors: Henderson Theodore , Morries Larry D.
Published: June 2018

Background

Depression treatment is hampered by low efficacy of antidepressant medications and concerns about alternative modalities. Animal studies of treatment with low-level (0.5 Watt or less) near infrared (NIR) light from diodes has shown some benefit in models of traumatic brain injury (TBI) with evidence of reduced lesion size, increased neurotrophin production, synaptogenesis, fewer apoptotic cells, and improved neurological function. Two small case series have demonstrated transient clinical improvement with low-level NIR treatment given on a daily basis over several weeks. We have previously shown marked and persistent clinical improvement in a case series of patients with chronic mild-to-moderate (m-MTBI) after treatmentwith NIR at a power of 9 Watts or greater. We also have published a review of the potential for application of NIR for the treatment of depression. The current study explores NIR efficacy in a proof-of-concept study as a treatment for depression.

Methods

Thirty-nine sequential patients treated for TBI between March 2013 and May 2017 provided depression self-assessment data and/or were administered the Hamilton Depression Rating Scale. Each completed the Quick Inventory of Depression Symptomatology-Self Reports (QIDS) before and after treatment. Patients received transcranial multi-Watt near-infrared light treatment (NILT) using near-infrared lasers (810/980 nm at 8-15 Watts) applied to forehead and temporal regions bilaterally for 9-12 minutes to each area.

Results

For 36 of the 39 patients, after 16.82 + 6.26 treatments, QIDS scores indicated a robust response (decrease of QIDS total score by > 50%). For 32 of 39 patients post-treatment QIDS scores indicated a remission from depression (decrease of QIDS total score < 5). Overall, the QIDS score fell from 14.10 + 3.39 to 3.44 + 3.39 SD (p=6.29 X 10-19). With 12 or fewer treatments, QIDS score dropped from 14.83 + 2.55 to 4.17 + 3.93. Patients receiving 13 or more treatments showed a change in QIDS score from 13.67 + 3.64 to 3.11 + 3.14. Those (N=15) who received the entire treatment course within 8 weeks or less (5.33 + 1.72 weeks) showed a change in QIDS score from 13.86 + 3.14 to 4.5 + 3.94. Suicidal ideation resolved in all, but two patients. The non-responsive patients are described in detail. Patients remained in remission for up to 55 months after a single course of treatment.

Conclusion

This is the first report of high-powered NILT showing efficacy for depression. Patients saw benefit often within 4 treatments and some had resolution of depressive symptoms in as little as 4 weeks. These data raise an intriguing possibility – that NILT may be a safe, effective, and rapid treatment for depression. A double-blind, placebo controlled trial is warranted to verify these proof-of-concept data.

Funding Acknowledgements

Neuro-Laser Foundation
195 Current Use and Trends in the Management of Tardive Dyskinesia: Role of VMAT2 Inhibitors
Authors: Sreeram Venkatesh , Shagufta Shanila , Kagadkar Faisal , Qureshi Mustafa
Published: June 2018

Objectives

Tardive Dyskinesia (TD) is a debilitating condition that requires prompt care and intervention. Studies demonstrated the probable role of Vesicular Monoamine Transport 2 (VMAT2) in the pathogenesis of TD and use of VMAT2inhibitors in managing TD. Our aim is to provide available data on the management of TD and to determine the efficacy ofvarious VMAT2 inhibitors for independent use. Also, to identify their use in combination and assess if there, any change inoutcome with early intervention.

Methods

We did a pivotal search of the scientific literature by querying PubMed and Google Scholar for studies on treatment modalities of TD including atypical antipsychotics and VMAT2 inhibitors. Also, references from publications were accessed for review.

Results

Early detection and prevention are of paramount importance in managing TD. Cessate the antipsychotic been using andother dopamine blocking agents that probably implicated in causing the symptoms. Certain studies showed the use of new atypical antipsychotics like Paliperidone, Quetiapine in small titrated dose resolving the symptoms. According to the available data, using benzodiazepines, botulinum toxin injections and VMAT2 inhibitors like Valbenazine, Tetrabenazine, andDeutetrabenazine also managed TD with efficacy. Valbenazine has breakthrough global approval in resolving the symptoms. Although other VMAT2 inhibitors were used for TD earlier and showed to be effective in managing TD, larger trials are required showing their safety and reliability in efficacy.

Conclusions

VMAT2 inhibitors were tested as efficacious in managing TD. Valbenazine and recently deutetrabenazine has been approved by US Food and Drug Administration (FDA) to treat TD. However, Tetrabenazine is yet to be approved by FDA. More clinical trials are required exploring their efficacy by comparing them or using them in combination. Our review also suggests timely detection and earlier intervening, especially if witnessed in children and adolescents would differ the outcome of TD.

Funding Acknowledgements

No funding.
Projecting future demand for informal care among older people in China: the road towards a sustainable long-term care system
Authors: Hu Bo
Published: June 2018

The long-term care system in China relies heavily on informal care provided by family members. This study makes projections on the demand for informal care among Chinese older people between 2015 and 2035 and quantifies the level of long-term care resources needed to meet their needs. The data come from longitudinal information in a nationally representative sample, China Health and Retirement Longitudinal Survey 2011 and 2013. The macrosimulation approach (PSSRU model) and the Markov approach are integrated into one Bayesian modelling framework. The Monte Carlo simulation technique is used to capture parameter uncertainty. We project that the demand for informal care will increase from 41.3 million people (95% CI: 39.9–42.7) in 2015 to 82.6 million people (95% CI: 78.3–86.9) in 2035. The long-term care system faces unbalanced pressure of demand for informal care from different groups of older people. The projected demand is sensitive to changes in older people’s disability trajectory and the availability of formal care provided by the government, but less sensitive to an increase in singleton households in the future. We discuss possible policy measures to alleviate the mounting pressure on the demand for informal care.
Adult Self-Esteem and Family Relationships
Authors: El Ghaziri Nahema , Darwiche Joëlle
Published: June 2018

Abstract. We conducted a literature review to examine the effects of self-esteem in the family context, selecting 40 studies exploring the associations between self-esteem, coparental relationship, parent-child relationship, and global family functioning. The research focused primarily on self-esteem and the parent-child relationship. The evidence indicates that parents with high self-esteem experience enhanced satisfaction with their children and exhibit more positive interactions with them. It was also found that parents’ high self-esteem is associated with less physical abuse and child neglect. Studies focusing on coparenting and family functioning are still rare, and more evidence is needed to establish robust conclusions.
Subjektive Theorien von Lehrpersonen über schwierige Unterrichtssituationen
Authors: Lauth-Lebens Morena , Lauth Gerhard W. , Rietz Christian
Published: June 2018

Zusammenfassung. Lehrkräfte richten ihre pädagogischen Handlungsentscheidungen im komplexen und voraussetzungsreichen Unterrichtsalltag vielfach an ihren subjektiven Theorien aus. Darunter werden erfahrungsgebundene und nahezu ausschließlich über den Dialog zugängliche Kognitionen mit zumeist impliziten Wissensstrukturen sowie einer handlungsleitenden Funktion subsummiert. Insofern vereinen subjektive Theorien strukturelle Wissens- und prozessuale Konstrukte; sie vermitteln zwischen Situation und Reaktion. Allgemein wird zwischen subjektiven Theorien geringer, mittlerer und hoher Reichweite unterschieden, was sich nach dem Wirkumfang der darin enthaltenen Erklärungen bemißt. In der vorliegenden explorativen und hypothesengenerierenden Untersuchung werden subjektive Theorien mit geringer Reichweite untersucht. Diese zeichnen sich dadurch aus, dass sie auf einer konkreten Handlungsebene wirksam werden. Untersucht wird die noch eher unterrepräsentierte Frage nach den subjektiven Theorien über schwierige Unterrichtssituationen (z.B. Konfliktsituationen, Disziplinprobleme). Mithilfe eines halbstrukturierten Erhebungsbogens wurden diese in einer Stichprobe (N = 30) von überwiegend in Klassenlehrerfunktion tätigen Grundschullehrkräften erhoben. Sie sollten eine exemplarische Problemsituation aus den letzten zwei Monaten ihres Schulalltags schildern, deren Entstehung erklären sowie die daraufhin von ihnen ergriffene Maßnahme beschreiben und in ihrem Erfolg bewerten. Im Ergebnis nennen die Lehrkräfte mehrheitlich personeninterne oder kontextuelle und nur selten interaktionelle Merkmale als ursächliche Problembedingungen (z.B. Absichten und Motive, Beeinträchtigungen der Schulkinder, familiäre Bedingungen). Sie führen tendenziell ereignisferne Erklärungen als ursächlich an. Mit ihren Maßnahmen erzielen sie nach eigener Einschätzung kaum Erfolge. Erfolg und Misserfolg der ergriffenen Maßnahmen sind kaum vorhersagbar. Infolgedessen findet kein generalisierbares Erfolgslernen statt. Angesichts dessen ist es nicht illegitim, negative Auswirkungen auf die Selbstwirksamkeitserwartungen und den Fertigkeitserwerb der Lehrkräfte anzunehmen.
Modeling the Chemical Impact and the Optical Emissions Produced by Lightning‐Induced Electromagnetic Fields in the Upper Atmosphere: The case of Halos and Elves Triggered by Different Lightning Discharges
Authors: Pérez‐Invernón F. J. , Luque A. , Gordillo‐Vázquez F. J.
Published: June 2018

Halos and elves are transient luminous events produced in the lower ionosphere as a consequence of lightning‐driven electromagnetic fields. These events can influence the upper atmospheric chemistry and produce optical emissions. We have developed different two‐dimensional self‐consistent models that couple electrodynamical equations with a chemical scheme to simulate halos and elves produced by vertical cloud‐to‐ground lightning discharges, compact intracloud discharges and energetic in‐cloud pulses. The optical emissions from radiative relaxation of excited states of molecular and atomic nitrogen and oxygen have been calculated. We have upgraded previous local models of halos and elves to calculate for the first time the vibrationally detailed optical spectra of elves triggered by compact intracloud discharges and energetic in‐cloud pulses. According to our results, the optical spectra of elves do not depend on the type of parent lightning discharge. Finally, we have quantified the local chemical impact in the upper atmosphere of single halos and elves. In the case of the halo, we follow the cascade of chemical reactions triggered by the lightning‐produced electric field during a long‐time simulation of up to 1 s. We obtain a production rate of NO molecules by single halos and elves of 1016 and 1014 molecules/J, respectively. The results of these local models have been used to estimate the global production of NO by halos and elves in the upper atmosphere at ∼10−7 Tg N/year. This global chemical impact of halos and elves is 7 orders of magnitude below the production of NO in the troposphere by lightning discharges.
Statistical Interpolation of Groundwater Hydrographs
Authors: Peterson Tim J. , Western Andrew W.
Published: June 2018

Groundwater observation bores are often monitored irregularly and infrequently. The resulting groundwater hydrographs are consequently less informative for understanding groundwater level trends, seasonality, flow directions, drawdown, and recovery. This paper presents an approach to temporally interpolate a groundwater hydrograph that has an irregular observation frequency to daily time steps. The approach combines nonlinear transfer function noise modeling with temporal kriging of the model residuals to produce an interpolated hydrograph that honors all water level observations input to the modeling and accounts for meteorological forcing between the observations. The reliability of the approach was evaluated using six observation bores having extended periods of daily data and by resampling them to six observation frequencies ranging from weekly to annually. The analysis showed that for weekly to monthly resampled data, >90% of the observed daily variability can be simulated at four of six bores. The performance declined with observation step size, as expected, but even at a biannual time step the error corrected interpolation can explain >70% of the variance at three of six bores. Additionally, an application shows that (1) the probability of a water level depth being exceeded can be estimated from quarterly resampled data and (2) the median annual water level range can be estimated from monthly resampled data. Supplementing less frequent observations with 6 and 12 months of daily data was also examined, with the addition of a 12‐month period significantly improving interpolation results at three of the four analyzed bores. The approach has been incorporated into theHydroSighttoolboxhttp://peterson‐tim‐j.github.io/HydroSight/.
AGU Launches Its Centennial Celebration
Authors: McEntee Chris
Published: June 2018

For the next 18 months, AGU will amplify stories of achievement in the Earth and space sciences, build connections with society, and mobilize scientists to communicate their science.