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OBJECTIVE: This study was undertaken to evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox-Gastaut syndrome (LGS). METHODS: Eligible patients with LGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209). All patients were initially started on .2 mg/kg/day fenfluramine and after 1 month were titrated by effectiveness and tolerability, which were assessed at 3-month intervals. The protocol-specified treatment duration was 12 months, but COVID-19-related delays resulted in 142 patients completing their final visit after 12 months. RESULTS: As of October 19, 2020, 247 patients were enrolled in the OLE. Mean age was 14.3 ± 7.6 years (79 [32%] adults) and median fenfluramine treatment duration was 364 days; 88.3% of patients received 2-4 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was -28.6% over the entire OLE (n = 241) and -50.5% at Month 15 (n = 142, p < .0001); 75 of 241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in nondrop seizure frequency was -45.9% (n = 192, p = .0038). Generalized tonic-clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (p < .0001, n = 106) and 35.8% (p < .0001, n = 186), respectively. A total of 37.6% (95% confidence interval [CI] = 31.4%-44.1%, n = 237) of investigators and 35.2% of caregivers (95% CI = 29.1%-41.8%, n = 230) rated patients as Much Improved/Very Much Improved on the Clinical Global Impression of Improvement scale. The most frequent treatment-emergent adverse events were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed. SIGNIFICANCE: Patients with LGS experienced sustained reductions in drop seizure frequency on fenfluramine treatment, with a particularly robus

Bringing together individuals of diverse perspectives in a research team can be challenging, especially when one perspective has been largely unacknowledged. The phrase ‘Value co-creation’ is used in marketing to include the voice of the consumer in the development of offerings so as to create value for both the organisation and the consumer. This study examines how well value co-creation model captures a process of research collaboration that privileges marginalised voices in a culturally sensitive and safe way. We examine a project that brought together three different, but not necessarily mutually exclusive, groups of people: Aboriginal community members; health care practitioners, policymakers and marketing experts. It is revealed that the value co-creation model exemplifies many of the elements needed to weave together different methodological perspectives and manage the dynamics of a research team. However, some adaptations were required, particularly: the inclusion of a ‘cultural broker’; a means of ‘cultural governance’; and the addition of a sixth pillar to the model – ‘evaluation’.

IMPORTANCE: New treatment options are needed for patients with Lennox-Gastaut syndrome (LGS), a profoundly impairing, treatment-resistant, developmental and epileptic encephalopathy. OBJECTIVE: To evaluate the efficacy and safety of fenfluramine in patients with LGS. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted from November 27, 2017, to October 25, 2019, and had a 20-week trial duration. Patients were enrolled at 65 study sites in North America, Europe, and Australia. Included patients were aged 2 to 35 years with confirmed diagnosis of LGS and experienced 2 or more drop seizures per week during the 4-week baseline. Using a modified intent-to-treat method, data analysis was performed from November 27, 2017, to October 25, 2019. The database lock date was January 30, 2020, and the date of final report was September 11, 2021. INTERVENTIONS: Patients were randomized to receive either a 0.7-mg/kg/d or 0.2-mg/kg/d (maximum 26 mg/d) dose of fenfluramine or placebo. After titration (2-week period), patients were taking their randomized dose for 12 additional weeks. MAIN OUTCOMES AND MEASURES: Primary efficacy end point was percentage change from baseline in drop seizure frequency in patients who received 0.7 mg/kg/d of fenfluramine vs placebo. RESULTS: A total of 263 patients (median [range] age, 13 [2-35] years; 146 male patients [56%]) were randomized to the 0.7-mg/kg/d fenfluramine group (n = 87), 0.2-mg/kg/d fenfluramine group (n = 89), or placebo group (n = 87). The median percentage reduction in frequency of drop seizures was 26.5 percentage points in the 0.7-mg/kg/d fenfluramine group, 14.2 percentage points in the 0.2-mg/kg/d fenfluramine group, and 7.6 percentage points in the placebo group. The trial met its primary efficacy end point: patients in the 0.7-mg/kg/d fenfluramine group achieved a -19.9 percentage points (95% CI, -31.0 to -8.7 percentage points; P = .001)

INTRODUCTION: This study investigated differences between rural Australian First Nations and non-First Nations survey respondents' perceptions of COVID-19-related risks and analysed other variables that could predict an exacerbation of anxiety related to COVID-19 harms. METHODS: A cross-sectional online and paper survey of rural residents from the western regions of NSW, Australia, was conducted. Descriptive and multivariate statistical analyses were used to assess links between First Nations status and demographic measures including postcode, age, gender, education, rural or town/village location, proximity to medical services and living situation. The analysis included five items related to perceptions about COVID-19: perceived likelihood of contracting COVID-19 in the next 12 months, perceived harmfulness of the virus, how often people felt afraid, perception about respondents' ability to do something about the virus and perceived economic impacts of the pandemic. RESULTS: There were significant differences between First Nations (n=60) and non-First Nations (n= 639) respondents across all sociodemographic categories. The results reflect a significantly higher level of anxiety among the First Nations Australians in the sample: they felt afraid more often, felt it was highly likely they would catch the virus and if they did catch the virus perceived that it would be very harmful. Living with children under eighteen years of age and in small rural towns were key factors linked to feeling afraid of COVID-19 and First Nations status. CONCLUSION: Health risk communication in pandemic response should include an equitable focus on rural areas, recognising that First Nations Australians are a significant proportion of the rural population with different risk factors and concerns than those of non-First Nations Australians. This principle of First Nations-led design is critical to all health policy and planning. The Australian Government should include rural areas in plann

AbstractThe objective of this scoping review was to map the current practice and best evidence for embedding cultural safety in child protection responses for Aboriginal families in hospitals. Electronic databases were searched systematically and the reference lists examined. Efforts to reduce the risk of bias were made including using an inductive approach. Eight research papers were included following the exclusion of 25 papers for the final analysis. Three main themes in relation to what is necessary to embed cultural safety for Aboriginal families when child protection responses are raised in hospital were found. These were (a) relationships, (b) organisational processes and (c) culture. The analysis underscores the need for development of child protection strategies that focus on cultural safety rather than cultural competence alone. This provides some direction for policy and practice development in this field, and has also highlighted the deficiencies in evidence and urgent need for further research.

BACKGROUND: Healthy and sustainable food systems underpin the well-being of Indigenous peoples. Increasingly governments are taking action to improve diets via population-wide policies. The United Nations Declaration on the Rights of Indigenous People states that Indigenous peoples have the right to participate in all decisions that affect them. We analysed Australian national food and nutrition policy processes to determine: (i) the participation of Aboriginal organisations, (ii) the issues raised in Aboriginal organisations' policy submissions, and (iii) the extent to which Aboriginal organisations' recommendations were addressed in final policy documents. METHODS: Political economy and cultural safety lenses informed the study design. We analysed publicly-available documents for Australian population-wide food and nutrition policy consultations occurring 2008-2018. Data sources were policy documents, committee reports, terms of reference and consultation submissions. The submissions made by Aboriginal organisations were thematically analysed and key policy recommendations extracted. We examined the extent to which key recommendations made by Aboriginal organisations were included in the subsequent policy documents. RESULTS: Five food and nutrition policy processes received submissions from Aboriginal organisations. Key themes centred on self-determination, culturally-appropriate approaches to health, and the need to address food insecurity and social determinants of health. These messages were underrepresented in final policy documents, and Aboriginal people were not included in any committees overseeing policy development processes. CONCLUSION: This analysis suggests that very few Aboriginal organisations have participated in Australian population-wide food and nutrition policy processes and that these policy development processes are culturally unsafe. In order to operationalise First Nations peoples' right to self-determination, alternative mechanisms are requ

BACKGROUND: Aboriginal and Torres Strait Islander Australians experience persistent health and social inequities. Chronic conditions, many of which are diet-related, are leading contributors to the burden of disease and health inequity in Australia. First Nations Peoples have the right to be involved in all policy decisions affecting them. This review aimed to synthesise Aboriginal and Torres Strait Islander Peoples' concerns and priorities about food and nutrition in order to inform policies to improve health equity. METHODS: MEDLINE, CINAHL, Informit and Google Scholar were systematically searched to identify qualitative studies-published from January 2008-that included data from Aboriginal and/or Torres Strait Islander Peoples about their concerns and priorities related to food and nutrition. Data were extracted from included studies using a pre-determined template and study quality was assessed using the Aboriginal and Torres Strait Islander Quality Appraisal Tool. Qualitative findings were synthesised using inductive thematic analysis and categorised based on an ecological model of health. RESULTS: Twenty-one studies were included. Key factors influencing food and nutrition were identified across all levels of the ecological framework. These included interpersonal and institutional racism, junk food availability and marketing, food accessibility and affordability, housing conditions, food knowledge and cooking skills, and connection to family and culture. CONCLUSIONS: Documenting Aboriginal and Torres Strait Islander Peoples' lived experiences of the colonised food system is one step necessary for informing policy to tackle food and nutrition inequities. Based on existing qualitative research, food and nutrition policymakers should prioritise building a supportive food environment by focusing on self-determination; ensuring access to healthy, affordable food and safe housing; and by eliminating systemic racism.

OBJECTIVE: Fenfluramine has been shown to provide clinically meaningful and statistically significant reductions in convulsive seizure frequency in children and adolescents (aged 2-18 years) with Dravet syndrome in two randomized, placebo-controlled clinical trials. The objective of this analysis was to assess longer-term safety and efficacy of fenfluramine in patients who completed one of the double-blind studies and entered an open-label extension (OLE) study. METHODS: Patients enrolling in the OLE study initiated fenfluramine at 0.2 mg/kg/d regardless of their treatment assignment in the double-blind study. After 4 weeks, the fenfluramine dose could be titrated based on efficacy and tolerability to maximum of 0.7 mg/kg/d (absolute maximum 27 mg/d) or maximum of 0.4 mg/kg/d (absolute maximum 17 mg/d) in patients receiving concomitant stiripentol. The number and type of seizures were recorded daily in an electronic diary, and safety, including echocardiography, was assessed at Months 1, 2, and 3, and at 3-month intervals thereafter. RESULTS: A total of 232 patients were enrolled as of March 13, 2018. During this analysis period, patients were treated for a median 256 days (range = 46-634 days). Over the entire OLE analysis period, the median decrease in convulsive seizure frequency compared to baseline in the double-blind studies was -66.8% (range = -100% to 234.9%; P < .001). The median reduction in seizure frequency was similar in patients <6 (-75.7%) and ≥6 years old (-64.7%). The most commonly reported adverse events included pyrexia (21.6%), nasopharyngitis (19.4%), and decreased appetite (-15.9%). No valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) was observed. SIGNIFICANCE: Study results demonstrate that fenfluramine provides clinically meaningful (≥50%) seizure frequency reduction over an extended period in patients with Dravet syndrome. No patient developed VHD or PAH, and fenfluramine was generally well tolerated.

INTRODUCTION: Indigenous Peoples worldwide endure unacceptable health disparities with undernutrition and food insecurity often coexisting with obesity and chronic diseases. Policy-level actions are required to eliminate malnutrition in all its forms. However, there has been no systematic synthesis of the evidence of effectiveness of food and nutrition policies for Indigenous Peoples around the world. This review fills that gap. METHODS: Eight databases were searched for peer-reviewed literature, published between 2000 and 2019. Relevant websites were searched for grey literature. Articles were included if they were original studies, published in English and included data from Indigenous Peoples from Western colonised countries, evaluated a food or nutrition policy (or intervention), and provided quantitative impact/outcome data. Study screening, data extraction and quality assessment were undertaken independently by two authors, at least one of whom was Indigenous. A narrative synthesis was undertaken with studies grouped according to the NOURISHING food policy framework. RESULTS: We identified 78 studies from Canada, Australia, Aotearoa/New Zealand and the USA. Most studies evaluated targeted interventions, focused on rural or remote Indigenous communities. The most effective interventions combined educational strategies with policies targeting food price, composition and/or availability, particularly in retail and school environments. Interventions to reduce exposure to unhealthy food advertising was the only area of the NOURISHING framework not represented in the literature. Few studies examined the impact of universal food policies on Indigenous Peoples' diets, health or well-being. CONCLUSION: Both targeted and universal policy action can be effective for Indigenous Peoples. Actions that modify the structures and systems governing food supply through improved availability, access and affordability of healthy foods should be prioritised. More high-quality evide