bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of the Community Earth System Model in human dimensions climate research and applications
Authors: Laidlaw Emily K. , O'Neill Brian C. , Harp Ryan D.
Published: March 2019

Earth system models (ESMs) are the primary tool used to understand and project changes to the climate system. ESM projections underpin analyses of human dimensions of the climate issue, yet little is known about how ESMs are used in human dimensions research. Such foundational information is necessary for future critical assessments of ESMs. We review applications of a leading ESM, the National Center for Atmospheric Research (NCAR) Community Earth System Model (CESM), to human dimensions topics since 2004. We find that this research has grown substantially over this period, twice as fast as CESM research overall. Although many studies have primarily addressed long‐term impacts on physical systems with societal relevance, applications to managed, societal, and ecological systems have grown quickly and now make up more than half of CESM human dimensions work. CESM applications focused nearly equally on global and regional analyses, most often using multimodel ensembles, although the use of single simulations remains prevalent. Downscaling and bias correction of output was infrequent and most common for regional studies. U.S.‐based, university‐affiliated authors primarily drove human dimensions work using CESM, with only 12% of authors based at NCAR. Our findings identify important questions that warrant further investigation, such as reasons for the infrequent use of downscaling and bias correction techniques; motivations to continue to use older model versions after newer model versions have been released; and model development needs for improved human dimensions applications. Additionally, our synthesis provides a baseline and framework that enables continued tracking of CESM and other ESMs.

This article is categorized under:

Assessing Impacts of Climate Change > Evaluating Future Impacts of Climate Change
Aβ and tau structure‐based biomarkers for a blood‐ and CSF‐based two‐step recruitment strategy to identify patients with dementia due to Alzheimer's disease
Authors: Nabers Andreas , Hafermann Henning , Wiltfang Jens , Gerwert Klaus
Published: March 2019

Introduction

Alzheimer's disease (AD) diagnosis requires invasive CSF analysis or expensive brain imaging. Therefore, a minimal‐invasive reliable and cost‐effective blood test is requested to power large clinical AD trials at reduced screening failure.

Methods

We applied an immuno‐infrared sensor to measure the amyloid‐β (Aβ) and tau secondary structure distribution in plasma and CSF as structure‐based biomarkers for AD (61 disease controls, 39 AD cases).

Results

Within a first diagnostic screening step, the structure‐based Aβ blood biomarker supports AD identification with a sensitivity of 90%. In a second diagnostic validation step, the combined use of the structure‐based CSF biomarkers Aβ and tau excluded false‐positive cases which offers an overall specificity of 97%.

Discussion

The primary Aβ‐based blood biomarker funnels individuals with suspected AD for subsequent validation of the diagnosis by structure‐based combined analysis of the CSF biomarkers Aβ and tau. Our novel two‐step recruitment strategy substantiates the diagnosis of AD with a likelihood of 29.
Differences in cognitive performance and cognitive decline across European regions: a population-based prospective cohort study
Authors: Formanek Tomas , Kagstrom Anna , Winkler Petr , Cermakova Pavla
Published: March 2019

Background:

A large variation in cognitive performance exists between European regions. However, it is unclear how older Europeans differ in the rate of cognitive decline.

Methods:

We analysed data from 22 181 individuals (54% women; median age 71) who participated in the Survey on Health, Ageing and Retirement in Europe. Cognition was measured using tests on verbal fluency, immediate and delayed recall. We used linear regression and linear mixed effects regression to examine regional differences in the level of cognitive performance and the rate of cognitive decline.

Results:

Scandinavians had the highest baseline cognitive scores (mean standardized overall cognitive score 0.3), followed by Western Europeans (mean 0.2), Central and Eastern Europeans (mean 0.1) and individuals from Mediterranean countries (mean -0.4). These differences persisted even after adjustment for sociodemographic and clinical characteristics. The annual cognitive decline in Scandinavia (0.59%) was approximately two times greater than in Western Europe (0.28%), Central and Eastern Europe (0.25%) and Mediterranean countries (0.23%).

Discussion:

There are substantial differences in cognitive performance as well as rates of cognitive decline among the elderly throughout European regions. This might be explained by differing levels of cognitive reserve.
On nonlinear strain theory for a viscoelastic material model and its implications for calving of ice shelves
Authors: CHRISTMANN JULIA , MÜLLER RALF , HUMBERT ANGELIKA
Published: March 2019

In the current ice-sheet models calving of ice shelves is based on phenomenological approaches. To obtain physics-based calving criteria, a viscoelastic Maxwell model is required accounting for short-term elastic and long-term viscous deformation. On timescales of months to years between calving events, as well as on long timescales with several subsequent iceberg break-offs, deformations are no longer small and linearized strain measures cannot be used. We present a finite deformation framework of viscoelasticity and extend this model by a nonlinear Glen-type viscosity. A finite element implementation is used to compute stress and strain states in the vicinity of the ice-shelf calving front. Stress and strain maxima of small (linearized strain measure) and finite strain formulations differ by ~ 5% after 1 and by ~ 30% after 10 years, respectively. A finite deformation formulation reaches a critical stress or strain faster, thus calving rates will be higher, despite the fact that the exact critical values are not known. Nonlinear viscosity of Glen-type leads to higher stress values. The Maxwell material model formulation for finite deformations presented here can also be applied to other glaciological problems, for example, tidal forcing at grounding lines or closure of englacial and subglacial melt channels.
ON A METRIC GENERALIZATION OF THE tt-DEGREES AND EFFECTIVE DIMENSION THEORY
Authors: KIHARA TAKAYUKI
Published: March 2019

In this article, we study an analogue of tt-reducibility for points in computable metric spaces. We characterize the notion of the metric tt-degree in the context of first-level Borel isomorphism. Then, we study this concept from the perspectives of effective topological dimension theory and of effective fractal dimension theory.
Sin Ŏnjun (1904–1938) and Lu Xun's Image in Korea: Colonial Korea's Nationalist Transnationalism
Authors: Tikhonov Vladimir
Published: March 2019

Throughout the Japanese colonial period, Korea's reading public paid close attention to Chinese revolutions against Japanese and Western empires. Korean nationalists viewed China's revolutionary struggles as important for liberating Korea from Japan, a stance that reveals a transnational basis of Korean nationalism in the colonial era. One such nationalist was Sin Ŏnjun (1904–38),Tong'a Ilbo’s Shanghai-based correspondent, who played a critical role in conveying the momentous events in contemporary China to colonized Koreans. Drawing on Sin's example, this article shows how Sino-Korean transnationalism constituted Korea's left-wing, progressive nationalism in the 1930s. Although Sin Ŏnjun was a nationalist rather than a communist, he highlighted the communist struggles in China in his dispatches. He saw communism as the only viable way of solving China's internal and external problems, although he, at the same time, disapproved of Chinese communists’ “terrorist methods.” This article argues that this position also reflected his stance in favor of a broad communist-nationalist alliance in the Korean independence movement. He saw Korea's liberation agenda as closely related to the revolutionary events in China, thus accomplishing a synthesis between Korean nationalistic and social aspirations and an East Asia–wide transnational paradigm of a universal emancipatory struggle.
The Transition to the Knowledge Economy, Labor Market Institutions, and Income Inequality in Advanced Democracies
Authors: Hope David , Martelli Angelo
Published: March 2019

The transition from Fordism to the knowledge economy in the world’s advanced democracies was underpinned by the revolution in information and communications technology (ict). The introduction and rapid diffusion ofictpushed up wages for college-educated workers with complementary skills and allowed top managers and CEOs to reap greater rewards for their own talents. Despite these common pressures, income inequality did not rise to the same extent everywhere; income in the Anglo-Saxon countries remains particularly unequally distributed. To shed new light on this puzzle, the authors carry out a panel data analysis of eighteenoecdcountries between 1970 and 2007. Their analysis stands apart from the existing empirical literature by taking a comparative perspective. The article examines the extent to which the relationship between the knowledge economy and income inequality is influenced by national labor market institutions. The authors find that the expansion of knowledge employment is positively associated with both the 90/10 wage ratio and the income share of the top 1 percent, but that these effects are mitigated by the presence of strong labor market institutions, such as coordinated wage bargaining, strict employment protection legislation, high union density, and high collective bargaining coverage. The authors provide robust evidence against the argument that industrial relations systems are no longer important safeguards of wage solidarity in the knowledge economy.
How do Latino Immigrants Perceive the Current Sociopolitical Context? Identifying Opportunities to Improve Immigrant Health in the United States
Authors: LEE JANE J. , ZHOU YUANJIN
Published: March 2019

Migration is an important social determinant of health for immigrants in the United States. Increased attention on Latino immigrants in recent years has sparked interest in policies that affect this population. While prior research has assessed the potential health impact of specific immigration policies, there is limited understanding of how the overall sociopolitical context shapes the health of Latino immigrants. This study examines the potential mechanisms that link the sociopolitical context and health among Latino immigrants. Specifically, we explore how perceptions of the sociopolitical context are implicated in this relationship. Qualitative interviews with community gatekeepers (n=13) and Latino immigrants (n=34) in New York City revealed general perceptions about the overall sociopolitical context, which were characterized by discrimination towards immigrants, unpredictable and mercurial circumstances, and confusion and lack of information. These perceptions influenced participants’ psycho-emotional health and health-related behaviors. Findings suggest the importance of integrating immigrants’ perceptions of the sociopolitical context into health promotion efforts. Furthermore, findings demonstrate the need for paradigm shifts in developing policy-related actions to integrate immigrants’ perspectives. We propose an integrated, multi-level framework to guide future research and practice regarding social determinants of immigrant health.
Modernizing China's Tertiary Education Sector: Enhanced Autonomy or Governance in the Shadow of Hierarchy?
Authors: Jian Hu , Mols Frank
Published: March 2019

The Chinese government has acknowledged that in order to turn Chinese universities into world class institutions, it will have to grant them a greater degree of autonomy. However, the reforms that have been introduced to achieve this goal run counter to a long tradition of central government oversight. The question now presenting itself is how much actual control government has devolved to universities. The qualitative evidence presented in this paper, obtained through interviews with university presidents and Party secretaries, not only confirms that, as one might expect, Chinese universities continue to operate “in the shadow of hierarchy,” but also and more importantly that formal efforts to devolve authority are being rendered ineffective by informal pressures and control mechanisms. Discussion reflects on the state of play in Chinese public administration studies, and urges public policy researchers examining devolution in China to account for both formal reforms and everyday “lived experiences.”
5 Clinical Evaluation of the Abuse Potential of Buprenorphine/Samidorphan Combination
Authors: Cutler Andrew J. , Mathew Sanjay J. , DeBakey Michael E. , Setnik Beatrice , Nangia Narinder , Stanford Arielle D. , Pathak Sanjeev
Published: March 2019

Introduction

Buprenorphine (BUP)/samidorphan (SAM) combination is an opioid system modulator being investigated as an adjunctive treatment for major depressive disorder (MDD). BUP/SAM is a fixed-dose combination of BUP, a partial µ-opioid receptor agonist and κ-opioid receptor antagonist, and SAM, a µ-opioid receptor antagonist added to address the abuse and dependence potential of BUP.1,2

Study Objective

We assessed the effects of SAM on the abuse potential of BUP in the BUP/SAM combination in two ways: (1) a human abuse potential (HAP) study in volunteers; and (2) an evaluation of the clinical experience across studies of patients with MDD.

Methods

Study 212 (ClinicalTrials.gov ID: NCT02413281) was a HAP study in nondependent, recreational, adult opioid users. Following a qualification period, participants were randomized to 6 treatments in a blinded, crossover design: placebo (PBO), BUP/SAM at the target therapeutic dose (BUP/SAM 2mg/2mg), at 8mg/8mg and 16mg/16mg , and BUP alone (8mg and 16mg). The primary endpoint was maximum effect (Emax) for “At The Moment” Drug Liking Visual Analog Scale (VAS).

The clinical program for BUP/SAM included 4 PBO-controlled studies of patients with MDD (n=961). Pooled safety data were evaluated for adverse events (AEs) that may be associated with abuse, dependence, or withdrawal, as well as for objective signs of withdrawal with the Clinical Opioid Withdrawal Scale (COWS).

Results

In Study 212 (n=38), Emax Drug Liking VAS scores for the BUP/SAM 2mg/2mg dose were similar to those for PBO (median within-subject difference [90% CI]: 2.5 [0.0–9.0]). Emax Drug Liking VAS scores for all BUP/SAM dose groups, including supratherapeutic doses, were significantly lower than those observed for either of the BUP doses. The supratherapeutic doses of BUP/SAM (8mg/8mg and 16mg/16mg) had higher Emax Drug Liking VAS scores than PBO, but the differences were small.

In the MDD controlled studies, the incidence of euphoria-related AEs was low for BUP/SAM 2mg/2mg and PBO (1.6% vs 0.2%, respectively) and there was no evidence of abuse or dependence behavior. Euphoria-related events typically occurred with treatment initiation and resolved with continued treatment. There was minimal evidence of withdrawal by reported AEs or COWS assessment.

Conclusions

These findings indicate that SAM mitigates the abuse potential of BUP in the BUP/SAM combination.

Funding Acknowledgements: Alkermes, Inc.
11 Therapeutic Equivalences in Long-term Antipsychotics
Authors: Gómez Sánchez-Lafuente C.
Published: March 2019

Study Objectives

The 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).

Method

The 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).

Results

The results will be shown in a 8x8 table.

Conclusions

DDD 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

BACKGROUND/METHOD

Wearable 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.

RESULTS

All 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.

CONCLUSIONS

Data 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

Study objective

Patient-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.

Methods

We 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).

Results

Patients 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.

Conclusion

Patients 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

Objective

Valbenazine (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.

Methods

Key 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”]).

Results

160 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%).

Conclusions

A 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

Study Objectives

1. To assess the effectiveness, functionality and tolerability of Aripiprazole long-acting injectable (ALAI) in patients with stable schizophrenia

2. Compare hospitalizations and emergency assists during 18-month period before (retrospective period) and after (prospective period) switch to ALAI

Method

The 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 assists

The 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.

Results

a) 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 insomnia

c) 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 study

d) 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 afterswitch

e) Treatment compliance: shown in Table 1.

Conclusions

ALAI 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

Study Objectives

To 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).

Method

A 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 test

Working memory (W.M): Digit sequencing task

Motor speed (M.S): Token motor task

Verbal fluency (V.F): Semantic or category fluency

Attention (A): Symbol coding

Executive function (E.F): Tower of London

The 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).

Results

In 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.

Conclusions

In 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

Study Objectives

We 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).

Method

In 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).

Results

All 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.

Conclusion

AR19 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

Title

“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

Objectives

Report 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.

Methods

Males 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.

Results

For 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.

Conclusion

AMPH 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.
88 The Efficacy and Safety of Amphetamine Extended-Release Oral Suspension (AMPH EROS) in Children with Attention-Deficit/Hyperactivity Disorder
Authors: Kando Judith C. , King Thomas , Pardo Antonio , Herman Barry K.
Published: March 2019

OBJECTIVES

To determine the efficacy and safety of amphetamine extended-release oral suspension (AMPH EROS) in the treatment of attention-deficit/hyperactivity disorder (ADHD) compared with placebo in a dose-optimized, randomized, double-blind study.

METHODS

The efficacy of AMPH EROS was evaluated in a laboratory classroom study conducted in 108 pediatric patients (aged 6–12 years) with ADHD. The study began with an open-label dose optimization (5weeks) with an initial AMPH EROS dose of 2.5 or 5mg once daily in the morning. The dose could be titrated every 4–7 days in increments of 2.5–10mg until an optimal dose or the maximum dose of 20mg/day was reached. Subjects were required to tolerate a minimal dose of 10mg/day. Subjects then entered a 1-week randomized, double-blind treatment phase with the individually optimized dose or placebo. At the end of the week, raters evaluated the attention and behavior of the subjects in a laboratory classroom using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP-C) rating scale. SKAMP-C is a 13-item teacher-rated scale that assesses manifestations of ADHD in a classroom setting.

The primary efficacy endpoint was change from pre-dose in the SKAMP-C score at 4hours post dose. The key secondary endpoint efficacy parameters were onset and duration of clinical effect. The change scores from pre-dose SKAMP-C scores at post dose time points (1, 2, 6, 8, 10, 12 and 13hours) were used to evaluate the key secondary efficacy endpoints.

RESULTS

More boys (68.7%) than girls participated in the study. The study population was 55.6% white, most patients had inattentive or combined type ADHD presentations. The primary efficacy endpoint, the change from pre-dose SKAMP-C score at 4hours post dose was statistically significantly improved (p<0.0001) compared with placebo. Each of the secondary efficacy endpoints were also significantly improved (p<0.0001 at each time point) compared with placebo. Adverse events reported (frequency >5%) reported during the dose optimization phase were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings, and headache.

CONCLUSIONS

AMPH EROS was effective in reducing symptoms or ADHD from 1 to 13hours after dosing. Adverse events reported were consistent with those of other amphetamine products.

Funding Acknowledgements: This study was supported by Tris Pharma, Inc.
Implementation of stepped care for patients with chronic fatigue syndrome in community-based mental health care: outcomes at post-treatment and long-term follow-up
Authors: Janse Anthonie , van Dam Arno , Pijpers Coby , Wiborg Jan F. , Bleijenberg Gijs , Tummers Marcia , Twisk Jos , Nikolaus Stephanie , Knoop Hans
Published: March 2019

Background:

Cognitive behavioural therapy (CBT) is an evidence-based treatment for chronic fatigue syndrome (CFS). Stepped care for CFS, consisting of a minimal intervention followed by face-to-face CBT, was found efficacious when tested in a CFS specialist centre. Stepped care implemented in a community-based mental health centre (MHC) has not yet been evaluated.

Aims:

(1) To test the effectiveness of stepped care for CFS implemented in a MHC at post-treatment and at long-term follow-up; and (2) compare post-treatment outcomes of implemented stepped care with treatment outcomes of a CFS specialist centre.

Method:

An uncontrolled study was used to test effectiveness of stepped care implemented in a MHC (n = 123). The outcomes of implemented care were compared with the outcomes of specialist care reported in previous studies (n = 583). Data on outcomes from implemented stepped care were gathered at post-treatment and at long-term follow-up. Mixed models were used as method of analysis.

Results:

Fatigue decreased and physical functioning increased significantly following implemented stepped care (both p < .001). The follow-up was completed by 94 patients (78%) within 1–6 years after treatment. Treatment effects were sustained to follow-up. Patients in the MHC showed less improvement directly following stepped care compared with patients in a CFS specialist centre (p < .01).

Conclusion:

Implemented stepped care for CFS is effective with sustained treatment gains at long-term follow-up. There is room for improvement when compared with outcomes of a CFS specialist centre. Some suggestions are made on how to improve stepped care.
Public health and the ultra-processed food and drink products industry: corporate political activity of major transnationals in Latin America and the Caribbean
Authors: Mialon Mélissa , Gomes Fabio da Silva
Published: March 2019

Objective

To identify examples of the ‘corporate political activity’ (CPA) of the industry producing and selling ultra-processed food and drink products (UPP) in Latin America and the Caribbean.

Design

Searches were conducted on the national websites and social media accounts of large industry actors. Coding was deductive and based on a framework for classifying the CPA of the food industry.

Setting

Fifteen countries in Latin America and the Caribbean.

Participants

Twelve members of the International Food and Beverage Alliance (IFBA) and major trade associations and chambers of commerce in the region.

Results

During the current pilot study, more than 200 examples of CPA were found in Latin America and the Caribbean. The UPP industry lobbied governments during the development of national health policies. UPP companies tried to build alliances with health professionals, but also with communities where they operated and with policy makers. In addition, the UPP industry fought against regulation in court and proposed weaker alternatives to public health policies, such as self-regulation.

Conclusions

Food systems in low- and middle-income countries, including in Latin America and the Caribbean, are increasingly penetrated by the UPP industry. These countries are at risk of being influenced by the CPA strategies described in the present study. There is a need to further identify, monitor and evaluate the impact of these CPA strategies on public health policies and public opinion in the region, in order to develop mechanisms to effectively prevent such interference.
Spurensuche
Authors: Leue Christina
Published: March 2019

Zusammenfassung. Bedarfsmedikation ist seit langem ein Bestandteil der psychiatrischen Behandlung. Die Festlegung ist aus dem psychiatrischen Alltag nicht mehr wegzudenken. Es scheint keine Schwierigkeit darin zu bestehen, den Begriff zu definieren, sondern zu eruieren, welche Aspekte bei der Vergabe von Bedarfsmedikation bedacht werden sollten und welche rechtlichen Grundlagen erfüllt sein müssen, um eine Arzneimitteltherapiesicherheit zu gewähren.
Weg von der Compliance und hin zur Adherence
Authors: Redzinski Kerstin
Published: March 2019

Zusammenfassung. Häufig werden die Begriffe Compliance und Adherence in einem Atemzug genannt und als Synonym verwendet. Jedoch sind dies zwei unterschiedliche Behandlungskulturen, wobei Compliance der Ursprung war und sich nach mehreren Jahren Adherence entwickelt hat, besonders im Bereich der psychiatrischen Erkrankungen. Während bei einer Non-Compliance stets vom Versagen des Patienten die Rede war, wird bei einer niedrigen Adherence mit dem Patienten gemeinsam hingeschaut, warum sie vorliegt und einen langfristigen Therapieerfolg verhindert. Ein praktisches Beispiel der Förderung der Adherence zeigt ein Medikamententraining, das in der Gerontopsychiatrie angewendet wird.
Damit das Innere wachsen kann
Authors: Menne Martina
Published: March 2019

Zusammenfassung. In der Psychiatrie begegnen wir dem Phänomen der Selbstvernachlässigung in verschiedenen Ausrichtungen: bei der Körperpflege, in der Ernährung, bei der Ordnung und Sauberkeit der Wohnung, sowie im Sammeln bestimmter Gegenstände, so dass durch unverhältnismässiges Anhäufen dieser Dinge eine „Messi“-Situation entsteht.