Calcium channel blockers for antipsychotic-induced tardive dyskinesia (review)

BackgroundSchizophrenia and related disorders affect a sizable proportion of any population. Antipsychotic medications are the primary treatment for these disorders. Antipsychotic medications are associated with a variety of adverse effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil, flunarizine) have been among these experimental treatments. ObjectivesTo determine the effects of calcium channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic‐induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses. Search methodsWe searched the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017), inspected references of all identified studies for further trials and contacted authors of trials for additional information. Selection criteriaWe selected randomised controlled trials comparing calcium channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness who remained on their antipsychotic medication. Data collection and analysisWe independently extracted data and estimated risk ratios of dichotomous data or mean differences (MD) of continuous data, with 95% confidence intervals (CI). We assumed that people who left the trials early had no improvement. We also created a 'Summary of findings' table using GRADE. Main resultsPrevious versions of this review included no trials. From the 2015 search, we identified three cross‐over trials that could be included. The 2017 search found no new studies relevant to this review. The included trials randomised 47 inpatients with chronic mental illnesses in the USA and China. Trials were published in the 1990s and were of short duration (six to 10 weeks). Overall, the risk of bias was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, and attrition and outcome data were not fully reported. Findings were sparse, no study reported on the primary outcome 'no clinically important improvement in tardive dyskinesia symptoms,' but two small studies (37 participants) found no difference on the tardive dyskinesia symptoms scale Abnormal Involuntary Movement Scale (AIMS) scores between diltiazem or flunarizine and placebo after three to four weeks' treatment (MD ‐0.71, 95% CI ‐2.68 to 1.26, very low quality evidence). Only one study randomising 20 participants reported on adverse events, and reported that there were no adverse events with flunarizine or with placebo (very low quality evidence). One study with 18 participants reported no events of deterioration in mental state with diltiazem or with placebo (very low quality evidence). No studies reported on acceptability of treatment or on social confidence, social inclusion, social networks or personalised quality of life outcomes designated important to patients. Authors' conclusionsAvailable evidence from randomised controlled trials is extremely limited and very low quality, conclusions cannot be drawn. The effects of calcium channel blockers for antipsychotic‐induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well‐designed randomised trials

Physics Analysis Expert PAX: First Applications

PAX (Physics Analysis Expert) is a novel, C++ based toolkit designed to assist teams in particle physics data analysis issues. The core of PAX are event interpretation containers, holding relevant information about and possible interpretations of a physics event. Providing this new level of abstraction beyond the results of the detector reconstruction programs, PAX facilitates the buildup and use of modern analysis factories. Class structure and user command syntax of PAX are set up to support expert teams as well as newcomers in preparing for the challenges expected to arise in the data analysis at future hadron colliders.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 7 pages, LaTeX, 10 eps figures. PSN THLT00

European network for promoting the physical health of residents in psychiatric and social care facilities (HELPS): background, aims and methods

Background People with mental disorders have a higher prevalence of physical illnesses and reduced life expectancy as compared with the general population. However, there is a lack of knowledge across Europe concerning interventions that aim at reducing somatic morbidity and excess mortality by promoting behaviour-based and/or environment-based interventions. Methods and design HELPS is an interdisciplinary European network that aims at (i) gathering relevant knowledge on physical illness in people with mental illness, (ii) identifying health promotion initiatives in European countries that meet country-specific needs, and (iii) at identifying best practice across Europe. Criteria for best practice will include evidence on the efficacy of physical health interventions and of their effectiveness in routine care, cost implications and feasibility for adaptation and implementation of interventions across different settings in Europe. HELPS will develop and implement a "physical health promotion toolkit". The toolkit will provide information to empower residents and staff to identify the most relevant risk factors in their specific context and to select the most appropriate action out of a range of defined health promoting interventions. The key methods are (a) stakeholder analysis, (b) international literature reviews, (c) Delphi rounds with experts from participating centres, and (d) focus groups with staff and residents of mental health care facilities. Meanwhile a multi-disciplinary network consisting of 15 European countries has been established and took up the work. As one main result of the project they expect that a widespread use of the HELPS toolkit could have a significant positive effect on the physical health status of residents of mental health and social care facilities, as well as to hold resonance for community dwelling people with mental health problems. Discussion A general strategy on health promotion for people with mental disorders must take into account behavioural, environmental and iatrogenic health risks. A European health promotion toolkit needs to consider heterogeneity of mental disorders, the multitude of physical health problems, health-relevant behaviour, health-related attitudes, health-relevant living conditions, and resource levels in mental health and social care facilities

Completing the adaptive turn: An integrative view of strategy implementation

Based on our review of the past forty years of strategy implementation research, we find that the focus of the research area has moved from the pioneering structural control view to a more adaptive conception of strategy implementation. While early research focused mainly on how to conceptualize strategy implementation plans and how to establish optimal structures, systems, incentives, and controls for strategy implementation, the adaptive turn has shifted the research emphasis on to how organizations make sense of and enact strategies in practice. Although this adaptive turn has contributed significantly to understanding how strategies are implemented and adapted, it has also led to a further fragmentation of the field. We put forward an integrative view that aims at combining the distinctive strengths of the two complementary views. Instead of focusing either on conceptualizing or on enacting, we call for researchers to examine the continuous interplay of conceptualizing and enacting strategies at multiple hierarchical levels and in multiple organizational units simultaneously. We hope that our review will inspire future strategy implementation research to complete the adaptive turn through an enhanced, integrative view of strategy implementation

A Goal-based Framework for Contextual Requirements Modeling and Analysis

Requirements Engineering (RE) research often ignores, or presumes a uniform nature of the context in which the system operates. This assumption is no longer valid in emerging computing paradigms, such as ambient, pervasive and ubiquitous computing, where it is essential to monitor and adapt to an inherently varying context. Besides influencing the software, context may influence stakeholders' goals and their choices to meet them. In this paper, we propose a goal-oriented RE modeling and reasoning framework for systems operating in varying contexts. We introduce contextual goal models to relate goals and contexts; context analysis to refine contexts and identify ways to verify them; reasoning techniques to derive requirements reflecting the context and users priorities at runtime; and finally, design time reasoning techniques to derive requirements for a system to be developed at minimum cost and valid in all considered contexts. We illustrate and evaluate our approach through a case study about a museum-guide mobile information system

The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility.

BackgroundThe p6 region of the HIV-1 structural precursor polyprotein, Gag, contains two motifs, P7TAP11 and L35YPLXSL41, designated as late (L) domain-1 and -2, respectively. These motifs bind the ESCRT-I factor Tsg101 and the ESCRT adaptor Alix, respectively, and are critical for efficient budding of virus particles from the plasma membrane. L domain-2 is thought to be functionally redundant to PTAP. To identify possible other functions of L domain-2, we examined this motif in dominant viruses that emerged in a group of 14 women who had detectable levels of HIV-1 in both plasma and genital tract despite a history of current or previous antiretroviral therapy.ResultsRemarkably, variants possessing mutations or rare polymorphisms in the highly conserved L domain-2 were identified in seven of these women. A mutation in a conserved residue (S40A) that does not reduce Gag interaction with Alix and therefore did not reduce budding efficiency was further investigated. This mutation causes a simultaneous change in the Pol reading frame but exhibits little deficiency in Gag processing and virion maturation. Whether introduced into the HIV-1 NL4-3 strain genome or a model protease (PR) precursor, S40A reduced production of mature PR. This same mutation also led to high level detection of two extended forms of PR that were fairly stable compared to the WT in the presence of IDV at various concentrations; one of the extended forms was effective in trans processing even at micromolar IDV.ConclusionsOur results indicate that L domain-2, considered redundant in vitro, can undergo mutations in vivo that significantly alter PR function. These may contribute fitness benefits in both the absence and presence of PR inhibitor

‘Is every YouTuber going to make a coming out video eventually?’: YouTube celebrity video bloggers and lesbian and gay identity

A significant number of YouTube celebrity video bloggers (vloggers) have used the platform to come out publicly as lesbian or gay. This article interrogates the cultural work of YouTube celebrity coming outs, through the case studies of two of the most prominent gay vloggers: Ingrid Nilsen and Connor Franta. This article explores how the coming out moments of these vloggers, as articulated in their coming out vlogs and the wider media discourses surrounding these, make legible a normative gay youth subject position which is shaped by the specific tropes, conventions and commercial rationale of YouTube fame itself. I define this subject position as 'proto-homonormative.' It positions a "successful" gay adulthood, defined through the neoliberal ideals of authenticity, self-branding and individual enterprise bound to the phenomenon of YouTube celebrity, as contingent upon a particular personal relationship with one's non-normative sexuality. I interrogate how the emotional contours of Nilsen and Franta’s coming out narratives, their represented abilities to channel their non-normative sexualities into lucrative celebrity brands, and their construction as gay and lesbian ‘role models’ by the mainstream media, delineates a journey into "acceptance" and "pride" in one's gay sexuality as the expected narrative of contemporary gay life. This narrative, I argue, cements the default normativity of heterosexuality in mainstream culture, and produces a narrow framework of “acceptable” gay youth subjectivity which is aligned with the ideals of neoliberalism embodied in the figure of the YouTube celebrity vlogger

Physicality and Cooperative Design

CSCW researchers have increasingly come to realize that material work setting and its population of artefacts play a crucial part in coordination of distributed or co-located work. This paper uses the notion of physicality as a basis to understand cooperative work. Using examples from an ongoing fieldwork on cooperative design practices, it provides a conceptual understanding of physicality and shows that material settings and co-worker’s working practices play an important role in understanding physicality of cooperative design