Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Understanding the nature of family violence against women with insecure migration status in Australia

Feminist researchers have diversified understandings of family violence by examining how women's experiences are influenced by gender and its intersections with other social inequalities. This article seeks to contribute to intersectional and transnational feminist scholarship on violence that examines the influence of structural factors such as insecure migration status on the nature of women's lived experiences in Western industrialized countries. It reports on findings from a study with migrant women who experienced family violence in Victoria, Australia when their migration status was “insecure,” and examines similarities and differences in the forms and patterns of violence and abuse women described.</p

‘I felt I had no-one to depend on but myself’:examining how women with insecure migration status respond to domestic and family violence in Australia

Feminist research that takes an intersectional approach has highlighted how a woman's migration status can influence their ability to disclose domestic and family violence (DFV) and access formal support in the countries where they live, work and study. In recent years, research in Western multicultural societies such as Australia has shed light on the ways that restrictive state policies work against victim-survivors and can result in women delaying formal help-seeking, withstanding violence for longer periods and presenting at frontline services at a point of crisis. While important findings have been generated, very few Australian studies have documented responses to violence among women with insecure migration status, including the strategies they rely on to resist different forms of control and to keep themselves safe during a relationship with a violent partner. This article draws on data from a study with 18 victim-survivors who experienced DFV when they were living in Victoria, Australia, and their migration status was ‘insecure’, and 23 professional stakeholders. It explores how women drew on personal strategies to resist, cope with, put a stop to and survive DFV. The article uses ‘citizenship’ as a lens to interpret women's experiences and in doing so draws attention to the ways that women's options for responding to DFV were impacted by the conditional nature of their migration status. It also highlights women's expressions of agency and explores the actions victim-survivors took, which influenced their lived experiences in different ways in the weeks, months and years following their move to the country. The article seeks to contribute to scholarship that challenges assumptions of passivity in research on DFV with migrant women and draws attention to the ways that women worked to ensure their safety and survival despite the limited recognition of their experiences in state policies that address gendered violence.</p

Digital citizenship in a global society: a feminist approach

In an era of datafication, social networking, and globalization, “digital citizenship” has become an increasingly relevant and popular concept employed by diverse societal actors to promote digital capacity, literacy, and participation. To date, however, limited scholarly attention has been paid to the role of gender power relations in digital citizenship discourses, theories, or practices. In this paper, we conceptualize digital citizenship as a status (what it means to be a citizen), a practice (what it means to act as a citizen), and an intersubjective experience (what it means to occupy the outside, inside, or liminal space of citizenship). We argue that an intersectional, multi-layered, feminist approach to digital citizenship offers a valuable way to first analyze gender subordination and exclusionary practices in digital societies, and second to guide action that promotes a feminist democratic project of transformation and empowerment.</p

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre-eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially 'external' causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress-induced iron dysregulation, and (ii) its ability to awaken dormant, non-replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens. The extensive evidence discussed here implies, as was found with ulcers, that almost all chronic, infectious diseases do in fact harbour a microbial component. What differs is simply the microbes and the anatomical location from and at which they exert damage. This analysis offers novel avenues for diagnosis and treatment