bluuebunny/crossref_metadata_2025_split huggingface dataset:
11 Therapeutic Equivalences in Long-term Antipsychotics
Authors: Gómez Sánchez-Lafuente C. 
Published: March 2019

AbstractStudy ObjectivesThe concept of dose equivalence is very useful when it comes to using drugs. In the case of antipsychotics, the first comparison was established by Davis in 1974, called the classical comparison method. Subsequently, other methods have appeared, such as the minimum effective dose method, the dose response method, the consensus among experts such as consensus method by Gardner, and the Daily Dose method of the World Health Organization. In 2016, Leucht et al performed the meta-analysis comparing the equivalence by the alternative methods of second-generation antipsychotics orally, based on Olanzapine. However, therapeutic equivalences between injectable antipsychotics have not yet been made.The objective of the study is to establish a pattern of therapeutic equivalences between long-acting antipsychotics, based on the method of the Defined Daily Dose (DDD).MethodThe DDD is the dose of the maintenance medium of a drug for its main indication in adults of 70kg. In the case of antipsychotics, psychosis is the most important indication. DDDs are different for each route of administration, especially if the bioavailability of the drug varies between one route and another. To establish the DDD of a drug, 3 measures are taken: firstly, the dose ranges of the drug approved by at least 1 major regulatory authority. Secondly, doses used in clinical trials. Thirdly, post marketing data on dose used in clinical practice when the drug is commercialized. Depot formulations are usually assigned the same DDDs as the ordinary oral dosage form. Based on the DDD according to the WHO classification at http://www.whocc.no/.For comparison, Olanzapine 210mg was used as the main drug and equivalences were established from it. Therapeutic deposit of Aripiprazole (ARI), Flufenazine decanoate (FLU), Haloperidol Decanoate (HAL) Olanzapine pamoate (OLA), Paliperidone palmitate (PAL), Risperidone depot (RIS), and Zuclopenthixol decanoate (ZUC).ResultsThe results will be shown in a 8x8 table.ConclusionsDDD is available for almost all antipsychotics and is an accepted method as well as a clinical level as a researcher. They are based on a wide variety of data from different sources. Several studies have found a strong correlation between this method and other methods of equivalence. This method also has limitations. First, the DDDs were not established for the purpose of therapeutic equivalences. Secondly, the daily dose can be applied mainly to the efficacy of the drug, when the dose could cause some adverse effects.The establishment of therapeutic equivalences may help when a clinician needs to change one long-term antipsychotic. This could reduce psychotic relapses. It may enhance therapeutic adherence avoiding undesirable side effects. On the other hand, long-acting antipsychotics have corroborated the adherence and decrease of relapses, which is why it is increasingly used as a good alternative to oral drugs.
15 Feasibility of Using Wearable Sensors to Detect Agitation in Persons with Dementia
Authors: Nesbitt Christianne , Gupta Ajay , Maly Kurt , Okhravi Hamid Reza , Jain Shubham 
Published: March 2019

AbstractBACKGROUND/METHODWearable sensors have become increasingly accurate in measuring various aspects of health monitoring in humans. Persons with dementia (PWD) often experience problematic behavioral and psychological symptoms of dementia (BPSD). These behaviors can include kicking, hitting, biting, screaming, pushing and are stressful and dangerous for the PWD as well as for caregivers both formal paid caregivers and informal family caregivers. There are many proven methods to intervene during agitated behavior outburst and the earlier these methods are used the better the results. Such methods include redirection, one-on-one socialization, music therapy, pet assisted therapy, etc. These types of effective methods are preferred over routine or as needed medications to control the behaviors. The medications currently used have well documented adverse side effects, especially in aging adults.This IRB approved study used a convenience sample of eight PWD who had a history of BPSD in an assisted living facility specializing in the care of PWD. We evaluated the use of off-the-shelf smart watch technology to measure limb movements, vocalizations, heart rate and location in a facility. The research goal was to determine the feasibility of using this technology to accurately measure patient data which in turn will allow clinicians to promptly detect agitation and provide early intervention. Output data from the watch was compared to data recorded by trained observers using the Cohen-Mansfield Agitation Inventory (CMAI). Data was collected in four-hour blocks of time over a two-day period.RESULTSAll the participants wore the devices without difficulty. Observations were then compared to the information obtained from the smart watch technology. Limb movements and heart rate increases correlated well with observers’ measurements of agitation. True positive measures were greater than 60% (data streams from devices correlated with observations). The voice measures of tone, volume and words used did not correlate well due to background noise in this communal environment.CONCLUSIONSData streams did correlate with observations. This technology could be useful in quickly identifying, and potentially anticipate, agitation in PWD. Further research is pending that will fine tune our software developed to measure the data streams and enhance accuracy. Also, improvements are being made in the ability to use voice recognition technology to capture the vocalizations associated with agitation. This technology can be used to quickly identify and prevent escalation of some BPSD by allowing early application of non-pharmacologic methods to treat agitation. Further study will also evaluate the impact this may have on the quality of life for caregivers and PWD.Funding Acknowledgements: Old Dominion University Office of Research, $2,500
21 Patient Preferences Concerning the Efficacy and Side-effect Profile of Schizophrenia Medication: A Survey of Patients Living with Schizophrenia
Authors: Achtyes Eric D , Simmons Adam , Skabeev Anna , Jiang Ying , Marcy Patricia , Levy Nikki , Weiden Peter J 
Published: March 2019

AbstractStudy objectivePatient-reported outcomes and preferences rely on reports of the status of a patient’s health condition that comes directly from the patient, without interpretation or qualification by clinicians or investigators. Patient-reported outcomes and preferences have become an accepted approach in drug development. As part of this effort, we assessed the relative importance to patients with schizophrenia of trying a new antipsychotic that might improve symptoms in the context of common antipsychotic side effects, especially weight gain. Information from surveys such as this one can provide pilot guidance about what might be acceptable versus unacceptable trade-offs when considering new therapies for schizophrenia.MethodsWe prospectively administered a cross-sectional survey to 250 patients with clinical diagnoses of schizophrenia or schizoaffective disorder, aged ≥18 years, from five US outpatient community clinics, regarding the importance of efficacy and side effects on treatment decisions involving medications. Sixty-four percent (n=160) of the patients were male; mean age was 43 years (range: 18–72 years); mean weight was 91 kg (range: 49–182 kg); and mean body mass index was 30.3 kg/m2 (range: 15.3–63.3 kg/m2).ResultsPatients rated both efficacy and side effects as important attributes of medication for schizophrenia treatment, with 88.5% identifying the ability to think more clearly as an important property of their medication. Patients identified efficacy and side effects as important drivers to take their prescribed medicine (endorsed as very or most important by 94.3% and 84.0% of patients, respectively). Patients identified weight gain, physical restlessness and somnolence as significant side effects of current treatments for schizophrenia (very/most important by 61.5%, 60.4%, and 58.9%, respectively). When asked about willingness to change antipsychotics, anticipated weight gain had a strong negative influence on willingness to try a new antipsychotic, with 44.9% of patients declining to try a medication that would lead to a weight gain of 3–5 kg, and 70.8% of patients declining for an anticipated weight gain of 5–9kg.ConclusionPatients living with schizophrenia or schizoaffective disorder are influenced by many factors when considering whether to take their prescribed medication, including efficacy and side effects. It is important for clinicians to assess patient-specific concerns and develop a comprehensive treatment plan to maximize adherence to prescribed therapies.Funding Acknowledgements: This study was funded by Alkermes, Inc.
38 Global Improvement and Patient Satisfaction: Results from a Long-term, Open-label, Rollover Study of Valbenazine in Tardive Dyskinesia
Authors: Verghese Cherian , Lindenmayer Jean-Pierre , Marder Stephen R. , Burke Joshua , Jimenez Roland , Yonan Chuck , Farahmand Khody , Siegert Scott 
Published: March 2019

AbstractObjectiveValbenazine (VBZ) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved to treat tardive dyskinesia (TD) in adults. It has been evaluated in 2 long-term studies (KINECT 3, KINECT 4) in which participants received VBZ (40 or 80mg) for up to 48weeks. This long-term rollover study (NCT02736955) was conducted to evaluate global TD improvement and patient satisfaction with once-daily VBZ.MethodsKey eligibility criteria: age 18 to 85 years; completion of KINECT 3 or KINECT 4; maintenance medications (for schizophrenia, schizoaffective disorder, or mood disorder) at stable doses; Brief Psychiatric Rating Scale score <50; no significant risk of active suicidal ideation or behavior. Following washout of prior VBZ treatment (Weeks 48 to 52 of KINECT 3 and KINECT 4), participants were re-initiated at 40mg (4weeks) and escalated to 80mg based on tolerability and clinical assessment of TD; dose was reduced to 40mg if 80mg was not tolerated (80/40mg). If unable to tolerate the 40mg dose, the participant was discontinued. Participants received open-label VBZ for up to 72weeks or until commercial availability. Assessments included Clinical Global Impression of Severity-TD (CGIS-TD: range, 1[“normal, not at all ill”] to 7[“among the most extremely ill patient”]) and Patient Satisfaction Questionnaire (PSQ: range, 1[“very satisfied”] to 5[“very dissatisfied”]).Results160 participants with available data were included in analyses (40mg =35; 80mg =117; 80/40mg =8); 138 were receiving treatment when VBZ became commercially available. The percentages of participants who completed visits at Wks 12, 24, 36, and 48 were 96.3%, 78.1%, 56.9% and 35.0%, respectively. Few reached Wk 60 (n=4) or Wk 72 (n=0) due to commercial availability. The percentage of participants with CGIS-TD score ≤2 (“normal, not at all ill” or “borderline ill”) increased from baseline (before restarting VBZ) (40mg, 5.7%; 80mg, 18.1%) to Wk 48 (40mg , 41.7%; 80mg , 74.4%). At baseline, almost all participants rated their prior VBZ experience with a PSQ score ≤2 (“very satisfied” or “somewhat satisfied”) (40mg , 100%, 80mg , 99.1%). Similar results were seen at the Wk 48 visit, with most participants continuing to express satisfaction with VBZ (40mg , 100%; 80mg , 97.4%).ConclusionsA clinician-based global assessment indicated ongoing, meaningful TD improvements in adults who received once-daily VBZ in the current study. In participants treated for >1 year, continued patient satisfaction rates with VBZ were high.Funding Acknowledgements: Neurocrine Biosciences, Inc.
64 Aripiprazole Long-acting Injectable in Schizophrenia. An 18-month Follow-up and Mirror-image Study
Authors: García de Diego Beatriz-Oda Plasencia , Guillena Samuel-Leopoldo Romero 
Published: March 2019

AbstractStudy Objectives1. To assess the effectiveness, functionality and tolerability of Aripiprazole long-acting injectable (ALAI) in patients with stable schizophrenia2. Compare hospitalizations and emergency assists during 18-month period before (retrospective period) and after (prospective period) switch to ALAIMethodThe study sample involved 18 patients with stable schizophrenia (DSM 5 criteria) who started treatment with ALAI between January-December 2016.Variables: age, gender, psychopharmacological treatment.- Follow-up study: Prospective assessments were performed at baseline and at 3, 6, 9, 12, 15 and 18 months:∙ Brief Psychiatric rating Scale (BPRS)∙ Global Clinical Impression Scale (ICG-SI)∙ Personal and social Performance (PSP)∙ Side effects reported- Mirror-image study: 18-month before and afters witch∙ Number of hospitalizations and emergency assistsThe study was performed in accordance with the Declaration of Helsinki and all the participants provided written consent for participation.Student’s t-test and Chi-square test were used to assess differences between baseline evaluation and subsequent visits. For mirror-image analysis test Z and MacNemar was used.Resultsa) Efficacy and functionality: At the end of the study we observed:∙ A statistically significant: reduction in the total score of ICG-SI, and increase in the total score of PSP∙ A reduction in the total score of BPRS.There is an indirect correlation between age and changes in the score on: BPRS and ICG-SI (p<0.05) and PSP scale (p<0.05)b) Tolerability: The most frequent side effect with an incidence of 22% was transient mild insomniac) Psychopharmacological treatment: The percentage of patients on monotherapy increased from 39.6% baseline to 66.6%, and treatment with Biperidene decreased from 27.5% to 5.5% at the end of the studyd) Number of hospitalizations and emergency assist:∙ 12 hospital admission during 18-month period before switch to ALI, and 3 hospital admission 18-month after switch∙ 24 emergency assist during 18-month period before switch to ALI, and 7 emergency assist 18-month afterswitche) Treatment compliance: shown in Table 1.ConclusionsALAI can be effective therapy for the treatment of patients with schizophrenia: improves psychopathological symptoms, functionality and can prevent hospitalizations and emergency visits. In addition, ALAI is well tolerated, achieving a high percentage of patients in monotherapy.
68 Cognitive Impairment in Schizophrenia. First-generation Long-acting Antipsychotics versus Aripiprazole Long-acting Injectable
Authors: Guillena Samuel-Leopoldo Romero , García de Diego Beatriz-Oda Plasencia 
Published: March 2019

AbstractStudy ObjectivesTo assess differences in cognitive impairment in a group of patients with schizophrenia receiving first-generation long-acting antipsychotics (FG-LAI) versus Aripiprazole long-actinginjectable (ALAI).MethodA descriptive, cross-sectional, multi-centerstudy.Study sample: 28 outpatients with stable schizophrenia (18 men and 10 women) with ages ranging from 22 to 64years.Inclusion criteria were: Clinically stable patients with a diagnosis of schizophrenia (according to DSM-5 criteria) and without any changes to their antipsychotic or antidepressant therapy in the last six months.Simple stratified sampling was performed to collect data from patients with schizophrenia receiving FG-LAI (n=14) versus patients with schizophrenia receiving Aripiprazole long-acting injectable (ALAI) (n=14)Groups were matched by age, gender, years of evolution of the disease, and years on formal education.Functionality in the different cognitive domains was evaluated based on the Brief Assessment of cognition in Schizophrenia (BACS.), a hetero-applied instrument, which Spanish version has been validated. BACS evaluates the following cognitive domains:Verbal memory (V.M): Word list testWorking memory (W.M): Digit sequencing taskMotor speed (M.S): Token motor taskVerbal fluency (V.F): Semantic or category fluencyAttention (A): Symbol codingExecutive function (E.F): Tower of LondonThe data obtained were analyzed using the SPSS 22.0 statistical package Differences between the means of quantitative variables were assessed using the independent-sample Student-t test. Individual test scores were converted into standardized (T and Z) scores and composite scores that were corrected for age and gender.Informed consent was obtained from all patients according to the Declaration of Helsinki (World Medical Association).ResultsIn the group receiving ALAI, the most severely impaired cognitive domain was attention, whereas motor speed was barely affected. In contrast, verbal memory was most impaired, whereas motor speed was the least impaired cognitive domain in the group receiving FG-LAI.Patients with schizophrenia taking ALAI showed a better cognitive function in all domains (except for motor speed and attention) than patients receiving FG-LAI.Summarized results in Table1.ConclusionsIn our study, patients with schizophrenia receiving Aripiprazole long-acting injectable have better cognitive function than patients receiving first-generation long-acting antipsychotics.
81 Bioequivalence of a Manipulation-Resistant Immediate-Release Amphetamine Sulfate Formulation Compared with Reference Standard
Authors: Caras Steve , Sharpe Terrilyn 
Published: March 2019

AbstractStudy ObjectivesWe compared the bioavailability of racemic amphetamine (d-amphetamine and l-amphetamine) from a manipulation-resistant immediate-release (IR) amphetamine sulfate capsule (AR19) versus amphetamine sulfate IR tablets (reference).MethodIn this open-label, randomized, two-period, two-treatment, two-sequence, crossover study, 36 healthy volunteers aged 18–45 received a single dose (20-mg capsule) of AR19 in one period and a single dose (2 x 10-mg tablets) of reference in another period, after a 10-hour overnight fast. Each drug administration was separated by a washout period of at least 6days. Bioequivalence for d- and l-amphetamine was assessed using time to peak concentration (Tmax), peak concentration in plasma (Cmax), and area under the plasma concentration–time curve from time-zero to the time of the last quantifiable concentration (AUClast) and extrapolated to infinity (AUCinf).ResultsAll 36 volunteers completed both treatment sequences. Mean (standard deviation; SD) Tmax for d- and l-amphetamine was similar for AR19 (2.84[1.05]; 3.05[1.22], respectively) and reference (2.52[0.75]; 2.75[1.00], respectively). The geometric least-squares mean ratios and 90% confidence intervals were within the boundary of 80%–125% for bioequivalence for Cmax (d-amphetamine, 98.35% [96.12–100.64]; l-amphetamine, 98.82% [96.42–101.28]), AUClast (d-amphetamine, 99.45% [96.92–102.05]; l-amphetamine, 99.29% [96.55–102.10]), and AUCinf (d-amphetamine, 99.50%[96.77–102.30]; l-amphetamine, 99.23% [96.06–102.50]). A total of 13 mild adverse events were reported by 7 volunteers (AEs; AR19, n=5; reference, n=8). No serious AEs were reported.ConclusionAR19 was well tolerated and was bioequivalent to reference when administered as a 20-mg dose in healthy volunteers.Funding Acknowledgements: This study was funded by Arbor Pharmaceuticals, LLC.
86 Hyperfamiliarity for Unknown Faces in a Patient with Lewy Body Dementia
Authors: Uga Aghaegbulam , Ibilah Terngu 
Published: March 2019

AbstractTitle“I know everybody here”Hyperfamiliarity for unknown faces, a delusion of misidentification, is a rare disorder.We present a 67-year-old female admitted with worsening cognitive impairment and poor self-care associated with parkinsonian symptoms of one-year duration. During evaluation, she was noted to relate to strangers with familiar gestures like people she already knew causing distress for family and care givers.Workup revealed significant cognitive impairment, MOCA of 9/30 and neuroimaging showing diffuse temporal lobe volume loss predominantly on the left.Assessment was Lewy body dementia with hyperfamiliarity for unknown faces.This rare presentation reflects the need for detailed examination and workup during evaluation.
87 Efficacy Measures in an Open-label Dose-Optimization of an Amphetamine Extended-Release Oral Suspension in Children with Attention-Deficit/Hyperactivity Disorder
Authors: Cutler Andrew , Pardo Antonio , King Thomas R. , Kando Judith C. , Herman Barry K. 
Published: March 2019

AbstractObjectivesReport the efficacy of open-label amphetamine extended-release oral suspension (AMPH EROS) for the treatment of children with ADHD.AMPH EROS has a 1-hr onset of effect and a duration of action of 13hours and was approved by FDA for treatment of ADHD in children aged 6–17 years based on a double-blind, placebo-controlled efficacy and safety study in children aged 6–12 years with ADHD. A significant treatment difference in change from pre-dose SKAMP-combined score was observed at the primary endpoint of 4hours post-dose (p<0.0001) and each post-dose time point assessed (1, 2, 4, 6, 8, 10, 12, 13hours).Data reported here are from the 5-week, open-label dose optimization period. These efficacy data support the primary endpoint result.MethodsMales and females aged 6 to 12 years with ADHD enrolled and began open-label treatment with 2.5 mg or 5mg/day of AMPH EROS titrated in 2.5–10mg/day increments until optimal dose (maximum 20mg/day). Doses could be decreased for tolerability. Subjects took morning AMPH EROS for 5weeks. Other efficacy outcomes during the open-label dose optimization phase: ADHD-RS (ADHD-Rating Scale), CGI-S (Clinical Global Impression of Severity), CGI-I (CGI-of Improvement) and CPRS (Conners’ Parent Rating Scale). All subjects were assessed for safety.ResultsFor the ITT population (n=99): treatment with AMPH EROS was associated with a mean change in ADHD-RS-IV (baseline to end of the open-label dose optimization; week 6) of 28.2 (±9.03) (Baseline score = 41.3±7.95). 90.9% of subjects had a change from baseline to open-label week 6 of ≥50% in the ADHD-RS-IV total score and were defined as responders. The CGI-S scores decreased continuously from baseline, with a high 4.8 at baseline to a low of 2.0 at open-label week 6. The percentage of subjects classified as moderately ill or greater correspondingly decreased from 97% at Baseline to 1% at open-label week 6. The decrease in the CGI-I over the study was similar to the change in CGI-S scores. CPRS for most categories decreased continuously from Baseline to open-label week 6. Mean change from baseline to open-label week 6 on the CPRS inattention T-score subscale was –25.3 (±14.38) and –24.4 (±13.87).Adverse events (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings and headache.ConclusionAMPH EROS was effective in reducing symptoms of ADHD in this open-label dose optimization. The AE profile of AMPH EROS was consistent with those of other amphetamine products.Funding Acknowledgements: This work was funded by Tris Pharma, Inc.