Triple antiplatelet therapy for preventing vascular events: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Dual antiplatelet therapy is usually superior to mono therapy in preventing recurrent vascular events (VEs). This systematic review assesses the safety and efficacy of triple antiplatelet therapy in comparison with dual therapy in reducing recurrent vascular events.</p> <p>Methods</p> <p>Completed randomized controlled trials investigating the effect of triple versus dual antiplatelet therapy in patients with ischaemic heart disease (IHD), cerebrovascular disease or peripheral vascular disease were identified using electronic bibliographic searches. Data were extracted on composite VEs, myocardial infarction (MI), stroke, death and bleeding and analysed with Cochrane Review Manager software. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using random effects models.</p> <p>Results</p> <p>Twenty-five completed randomized trials (17,383 patients with IHD) were included which involving the use of intravenous (iv) GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban), aspirin, clopidogrel and/or cilostazol. In comparison with aspirin-based therapy, triple therapy using an intravenous GP IIb/IIIa inhibitor significantly reduced composite VEs and MI in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) (VE: OR 0.69, 95% CI 0.55-0.86; MI: OR 0.70, 95% CI 0.56-0.88) and ST elevation myocardial infarction (STEMI) (VE: OR 0.39, 95% CI 0.30-0.51; MI: OR 0.26, 95% CI 0.17-0.38). A significant reduction in death was also noted in STEMI patients treated with GP IIb/IIIa based triple therapy (OR 0.69, 95% CI 0.49-0.99). Increased minor bleeding was noted in STEMI and elective percutaneous coronary intervention (PCI) patients treated with GP IIb/IIIa based triple therapy. Stroke events were too infrequent for us to be able to identify meaningful trends and no data were available for patients recruited into trials on the basis of stroke or peripheral vascular disease.</p> <p>Conclusions</p> <p>Triple antiplatelet therapy based on iv GPIIb/IIIa inhibitors was more effective than aspirin-based dual therapy in reducing VEs in patients with acute coronary syndromes (STEMI and NSTEMI). Minor bleeding was increased among STEMI and elective PCI patients treated with a GP IIb/IIIa based triple therapy. In patients undergoing elective PCI, triple therapy had no beneficial effect and was associated with an 80% increase in transfusions and an eightfold increase in thrombocytopenia. Insufficient data exist for patients with prior ischaemic stroke and peripheral vascular disease and further research is needed in these groups of patients.</p

Myosin light chain-actin interaction regulates cardiac contractility

The amino-terminal domain of the essential myosin light chain (MLC-1) binds to the carboxy terminus of the actin molecule. We studied the functional role of this interaction by two approaches: first, incubation of intact and chemically skinned human heart fibers with synthetic peptide corresponding to the sequences 5 through 14 (P5-14), 5 through 8 (P5-8), and 5 through 10 (P5-10) of the human ventricular MLC-1 (VLC-1) to saturate actin-binding sites, and second, incubation of skinned human heart fibers with a monoclonal antibody (MabVLC-1) raised against the actin-interacting N-terminal domain of human VLC-1 using P5-14 as antigen to deteriorate VLC-1 binding to actin. P5-14 increased isometric tension generation of skinned human heart fibers at both submaximal and maximal Ca2+ activation, the maximal effective peptide dosage being in the nanomolar range. A scrambled peptide of P5-14 with random sequence had no effects up to 10(-8) mol/L, ie, where P5-14 was maximally effective. P5-8 and P5-10 increased isometric force to the same extent as P5-14, but micromolar concentrations were required. Amplitude of isometric twitch contraction, rate of tension development, rate of relaxation, and shortening velocity at near-zero load of electrically driven intact human atrial fibers increased significantly on incubation with P5-14. These alterations were not associated with modulation of intracellular Ca2+ transients as monitored by fura 2 fluorescence measurements. Incubation of skinned human heart fibers with MabVLC-1 increased isometric tension at both submaximal and maximal Ca2+ activation levels, having a maximal effective concentration in the femtomolar range

An integrated intervention to reduce intimate partner violence and psychological distress with refugees in low-resource settings: study protocol for the Nguvu cluster randomized trial

Abstract Background Intimate partner violence (IPV) is a critical public health and human rights concern globally, including for refugee women in low-resource settings. Little is known about effective interventions for this population. IPV and psychological distress have a bi-directional relationship, indicating the potential benefit of a structured psychological component as part of efforts to reduce IPV for women currently in violent relationships. Methods This protocol describes a cluster randomized controlled trial aimed at evaluating an 8-session integrated psychological and advocacy intervention (Nguvu) with female adult survivors of past-year IPV displaying moderate to severe psychological distress. Outcomes are reductions in: recurrence of IPV; symptoms of anxiety, depression and post-traumatic stress (primary); and functional impairment (secondary). Hypothesized mediators of the intervention are improvements in social support, coping skills and support seeking. We will recruit 400 participants from existing women’s support groups operating within villages in Nyarugusu refugee camp, Tanzania. Women’s groups will be randomized to receive the intervention (Nguvu and usual care) or usual care alone. All eligible women will complete a baseline assessment (week 0) followed by a post-treatment (week 9) and a 3-month post-treatment assessment (week 20). The efficacy of the intervention will be determined by between-group differences in the longitudinal trajectories of primary outcomes evaluated using mixed-effects models. Study procedures have been approved by Institutional Review Boards in the United States and Tanzania. Discussion This trial will provide evidence on the efficacy of a novel integrated group intervention aimed at secondary prevention of IPV that includes a structured psychological component to address psychological distress. The psychological and advocacy components of the proposed intervention have been shown to be efficacious for their respective outcomes when delivered in isolation; however, administering these approaches through a single, integrated intervention may result in synergistic effects given the interrelated, bidirectional relationship between IPV and mental health. Furthermore, this trial will provide information regarding the feasibility of implementing a structured intervention for IPV and mental health in a protracted humanitarian setting. Trial registration ISRCTN65771265 , June 27, 2016

Developing an integrated intervention to address intimate partner violence and psychological distress in Congolese refugee women in Tanzania

© 2019 The Author(s). Background: Multi-sectoral, integrated interventions have long been recommended for addressing mental health and its social determinants (e.g., gender-based violence) in settings of ongoing adversity. We developed an integrated health and protection intervention to reduce psychological distress and intimate partner violence (IPV), and tested its delivery by lay facilitators in a low-resource refugee setting. Methods: Formative research to develop the intervention consisted of a structured desk review, consultation with experts and local stakeholders (refugee incentive workers, representatives of humanitarian agencies, and clinical experts), and qualitative interviews (40 free list interviews with refugees, 15 key informant interviews). Given existing efforts by humanitarian agencies to prevent gender-based violence in this particular refugee camp, including with (potential) perpetrators, we focused on a complementary effort to develop an integrated intervention with potential to reduce IPV and associated mental health impacts with female IPV survivors. We enrolled Congolese refugee women with elevated psychological distress and past-year histories of IPV (n = 60) who received the intervention delivered by trained and supervised lay refugee facilitators. Relevance, feasibility and acceptability of the intervention were evaluated through quantitative and qualitative interviews with participants. We assessed instrument test-retest reliability (n = 24), inter-rater reliability (n = 5 interviews), internal consistency, and construct validity (n = 60). Results: We designed an 8-session intervention, termed Nguvu ('strength'), incorporating brief Cognitive Processing Therapy (focused on helping clients obtaining skills to overcome negative thoughts and self-perceptions and gain control over the impact these have on their lives) and Advocacy Counseling (focused on increasing autonomy, empowerment and strengthening linkages to community supports). On average, participants attended two-thirds of the sessions. In qualitative interviews, participants recommended adaptations to specific intervention components and provided recommendations regarding coordination, retention, safety concerns and intervention participation incentives. Analysis of the performance of outcome instruments overall revealed acceptable reliability and validity. Conclusions: We found it feasible to develop and implement an integrated, multi-sectoral mental health and IPV intervention in a refugee camp setting. Implementation challenges were identified and may be informative for future implementation and evaluation of multi-sectoral strategies for populations facing ongoing adversity. Trial registration: ISRCTN65771265, June 27, 2016

Examining implementation of an intervention to reduce psychological distress and intimate partner violence in a refugee camp setting

An integrated approach to reduce intimate partner violence and improve mental health in humanitarian settings requires coordination across health and protection services. We developed and tested the Nguvu intervention, which combined evidence-based interventions for psychological distress and intimate partner violence among Congolese refugee women in Nyarugusu refugee camp (Tanzania). We conducted 29 semi-structured interviews with Nguvu participants and stakeholders to explore the relevance, acceptability, feasibility, and impact of this intervention. Participants reported that the intervention aligned with needs and filled a gap in programming, yet further adaptations may improve the fit of the intervention. The Nguvu intervention was acceptable to participants, including group discussion of sensitive topics. Confidentiality was highly regarded among staff and participants, which improved safety and acceptability. It was feasible to train non-specialist refugee workers to deliver the intervention with adequate supervision. Facilitators noted contextual challenges that made it difficult to implement the intervention: limited infrastructure, competing priorities, and population mobility. The intervention was perceived to improve awareness of the association between violence and mental health, reduce self-blame, and build skills to improve wellbeing. Recommended adaptations reveal promising, yet challenging future directions for addressing social determinants of mental health and implementing multi-sectoral programmes in complex humanitarian settings

Multilevel determinants of integrated service delivery for intimate partner violence and mental health in humanitarian settings

Inter-agency guidelines recommend that survivors of intimate partner violence in humanitarian settings receive multisectoral services consistent with a survivor-centered approach. Providing integrated services across sectors is challenging, and aspirations often fall short in practice. In this study, we explore factors that influence the implementation of a multisectoral, integrated intervention intended to reduce psychological distress and intimate partner violence in Nyarugusu Refugee Camp, Tanzania. We analyzed data from a desk review of donor, legal, and policy documents; a gender-based violence services mapping conducted through 15 interviews and 6 focus group discussions; and a qualitative process evaluation with 29 stakeholders involved in the implementation of the integrated psychosocial program. We identified the challenges of implementing a multisectoral, integrated intervention for refugee survivors of intimate partner violence at the structural, inter-institutional, intra-institutional, and in social and interpersonal levels. Key determinants of successful implementation included the legal context, financing, inter-agency coordination, engagement and ownership, and the ability to manage competing priorities. Implementing a multisectoral, integrated response for survivors of intimate partner violence is complex and influenced by interrelated factors from policy and financing to institutional and stakeholder engagement. Further investment in identifying strategies to overcome the existing challenges of implementing multisectoral approaches that align with global guidelines is needed to effectively address the burden of intimate partner violence in humanitarian settings

Evaluation of an integrated intervention to reduce psychological distress and intimate partner violence in refugees:Results from the Nguvu cluster randomized feasibility trial

IntroductionThe complex relationship between intimate partner violence and psychological distress warrants an integrated intervention approach. In this study we examined the relevance, acceptability, and feasibility of evaluating a multi-sectoral integrated violence- and mental health-focused intervention (Nguvu).MethodsWe enrolled 311 Congolese refugee women from Nyarugusu refugee camp in Tanzania with past-year intimate partner violence and elevated psychological distress in a feasibility cluster randomized trial. Women were recruited from local women's groups that were randomized to the Nguvu intervention or usual care. Participants from women's groups randomized to Nguvu received 8 weekly sessions delivered by lay refugee incentive workers. Psychological distress, intimate partner violence, other wellbeing, and process indicators were assessed at baseline and 9-weeks post-enrollment to evaluate relevance, acceptability, and feasibility of implementing and evaluating Nguvu in refugee contexts.ResultsWe found that Nguvu was relevant to the needs of refugee women affected by intimate partner violence. We found reductions in some indicators of psychological distress, but did not identify sizeable changes in partner violence over time. Overall, we found that Nguvu was acceptable and feasible. However, challenges to the research protocol included baseline imbalances between study conditions, differential intervention completion related to intimate partner violence histories, differences between Nguvu groups and facilitators, and some indication that Nguvu may be less beneficial for participants with more severe intimate partner violence profiles.ConclusionsWe found evidence supporting the relevance of Nguvu to refugee women affected by partner violence and psychological distress and moderate evidence supporting the acceptability and feasibility of evaluating and implementing this intervention in a complex refugee setting. A definitive cluster randomized trial requires further adaptations for recruitment and eligibility screening, randomization, and retention.Trial registrationISRCTN65771265, June 27, 2016

Distribution and function of sodium channel subtypes in human atrial myocardium

<p>Voltage-gated sodium channels composed of a pore-forming alpha subunit and auxiliary beta subunits are responsible for the upstroke of the action potential in cardiac muscle. However, their localization and expression patterns in human myocardium have not yet been clearly defined. We used immunohistochemical methods to define the level of expression and the subcellular localization of sodium channel alpha and beta subunits in human atrial myocytes. Na(v)1.2 channels are located in highest density at intercalated disks where beta 1 and beta 3 subunits are also expressed. Na(v)1.4 and the predominant Na(v)1.5 channels are located in a striated pattern on the cell surface at the z-lines together with beta 2 subunits. Na(v)1.1, Na(v)1.3, and Na(v)1.6 channels are located in scattered puncta on the cell surface in a pattern similar to beta 3 and beta 4 subunits. Na(v)1.5 comprised approximately 88% of the total sodium channel staining, as assessed by quantitative immunohistochemistry. Functional studies using whole cell patch-clamp recording and measurements of contractility in human atrial cells and tissue showed that TTX-sensitive (non-Na(v)1.5) alpha subunit isoforms account for up to 27% of total sodium current in human atrium and are required for maximal contractility. Overall, our results show that multiple sodium channel alpha and beta subunits are differentially localized in subcellular compartments in human atrial myocytes, suggesting that they play distinct roles in initiation and conduction of the action potential and in excitation-contraction coupling. TTX-sensitive sodium channel isoforms, even though expressed at low levels relative to TTX-sensitive Na(v)1.5, contribute substantially to total cardiac sodium current and are required for normal contractility. This article is part of a Special Issue entitled "Na+ Regulation in Cardiac Myocytes". (C) 2013 Elsevier Ltd. All rights reserved.</p>