Hope, despair and transformation: Climate change and the promotion of mental health and wellbeing

<p>Abstract</p> <p>Background</p> <p>This article aims to provide an introduction to emerging evidence and debate about the relationship between climate change and mental health.</p> <p>Discussion and Conclusion</p> <p>The authors argue that:</p> <p>i) the direct impacts of climate change such as extreme weather events will have significant mental health implications;</p> <p>ii) climate change is already impacting on the social, economic and environmental determinants of mental health with the most severe consequences being felt by disadvantaged communities and populations;</p> <p>iii) understanding the full extent of the long term social and environmental challenges posed by climate change has the potential to create emotional distress and anxiety; and</p> <p>iv) understanding the psycho-social implications of climate change is also an important starting point for informed action to prevent dangerous climate change at individual, community and societal levels.</p

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Community health and disaster recovery

Ronan, KR ORCiD: 0000-0002-2698-5886The purpose of this chapter is to give the reader a sense for current approaches to disaster recovery in relation to community health. In terms of learning outcomes, the aim is to help readers understand important terms and important historical information, including an almost exclusive focus in the past on reactive and expert-based models of disaster recovery. Related, a main learning outcome is to understand the rationale and research that has underpinned a move to more preventative and community-oriented approaches to disaster recovery. This chapter includes a discussion of these approaches including compatibility of current models with ICF criteria. Several discussion, case- and research-based examples and illustrations are also provided to amplify important points raised in the chapter

Natural disaster funding a submission by the Australian Psychological Society to the Productivity Commission /

Executive Summary and Recommendations: Prevention and preparedness are crucially important considerations in determining natural disaster funding priorities and are capable of having much greater magnitude of influence and cost effectiveness compared to emergency response and recovery. Natural disaster funding also needs to include psychosocial recovery, which is an essential component of restoring individuals’ and communities’ mental health and wellbeing. Natural disasters will almost always overwhelm existing psychosocial services, and Federal funding is needed to augment services to meet increased demand. The APS makes the following recommendations in relation to the Inquiry: Recommendation: Preventive and preparedness initiatives are crucial Preventive and preparedness initiatives are a crucial funding priority. These initiatives equip a community to protect itself from a future disaster, reduce the impact of an event on individuals and communities, hasten the recovery, and have a much greater magnitude of influence and effectiveness than initiatives that come after the disaster. From a psychological perspective, these initiatives would include a host of risk reduction initiatives, including behavioural risk reduction strategies, improved warning systems and public messaging, community disaster preparedness education programs, psychological and household preparedness, psychological first aid, as well as thorough evaluation of program effectiveness so that evidence-based best practices are prioritised. Recommendation: Psychosocial recovery models need to be 3-tiered, flexible, integrated and local Funding a 3-tiered model of psychosocial care is critical to cost-effective funding options as it directs the majority of an affected population to the least expensive, population-based assistance which is likely to meet their needs, and reduces the demands on primary and specialist mental health care resources. Funding mechanisms for identifying mental health risk and need in a timely way throughout the population impacted by disaster are essential. This enables rapid mental health triage so that people at high risk can be rapidly matched to brief, evidence-based care. The use of these triage systems for mental health enables rational allocation of limited resources. Psychosocial recovery funding needs to be provided to local leaders in disaster-affected regions so that they can develop an integrated system of psychosocial and mental health care for disaster recovery tailored to their particular area. This funding can also be used to provide additional training in levels 1, 2 and 3 psychosocial care to saturate the workforce and bolster the existing pathways of care. Funding of a centralised, non-governmental agency designed to promote excellence in psychosocial recovery would improve the quality, consistency, and coordination of psychosocial responses to disasters in Australia. Local leaders in a disaster-affected area could consult with this agency for support in planning, designing, administering and implementing large-scale psychosocial recovery programs, without having to reinvent the wheel each time a disaster affects a different area