Understanding caregiver perspectives on challenges and solutions to pediatric asthma care for children with a previous hospital admission: a multi-site qualitative study.

OBJECTIVE: Pediatric hospital admissions for asthma provide an opportunity to trigger a review of the current management with an aim of preventing readmissions. However, caregiver voices on how best to improve care are missing. METHODS: As part of a larger, mixed methods cohort study, we identified caregivers of children aged 3-18 years who had an index hospital admission to a tertiary pediatric, mixed adult and pediatric, or regional hospital in Victoria, Australia, between 1st September 2017 and 31st August 2018 with a discharge diagnosis of "Asthma" or "Wheeze" based on International Classification of Disease-10 coding. We conducted qualitative semi-structured interviews with a purposive sample of 39 caregivers. We used content analysis to identify themes from the data. RESULTS: Caregivers identified both challenges associated with asthma care for children with a previous hospital admission as well as solutions to improve care and potentially reduce readmissions. Key challenges included: unclear pathways for follow up care, inconsistent advice, lack of personalized management, delays in getting a diagnosis, delays in the prescription of a preventer medication, and difficulty accessing primary care during exacerbations. Follow up with an "asthma specialist", early access to a trial of preventer medication, personalized Written Asthma Action Plans and increased access to and quality of community-based asthma support services were identified as key solutions. CONCLUSIONS: Caregivers have identified several potential solutions that could be implemented to improve care and possibly reduce pediatric asthma hospital readmissions. The challenge now is to co-design, embed and evaluate these in healthcare systems.Supplemental data for this article can be accessed at publisher's website.

Perspectives of Survivors of the Oklahoma City Bombing with and without PTSD 17 Months Postdisaster: A Qualitative Study.

This study compared perspectives of highly trauma-exposed Oklahoma City bombing survivors (N=141) with and without PTSD. Survivors' responses to questions about the effects of the bombing on their perspectives were hand-recorded and transcribed, six themes identified, and interrater reliability established. Both diagnostic groups (with and without PTSD) expressed greater appreciation for life, greater concern with human vulnerability and mortality, and positive changes in religion/spirituality as consequences of the bombing. Survivors with PTSD also expressed negative religious/spiritual changes and substantive gains in self-confidence. Results indicate that disaster survivors may experience profound changes in their perspectives with ramifications for their mental health.

Making Meaning of Disaster Experience in Highly Trauma-exposed Survivors of the Oklahoma City Bombing.

Survivors of disasters can be expected to form meaningful perspectives on their experiences that shape their trajectories of recovery; thus, these perspectives are important to study. If humans are naturally compelled to create meaning from traumatic experiences, the creation of meaning should be evident in survivors' discussion of the effects of the disaster in their lives. Therefore, the purpose of this study of highly trauma-exposed disaster survivors was to identify meaningful aspects or outcomes of their disaster experiences in their perspectives. This study examined a random sample (N=182) of survivors of the Oklahoma City bombing six months after the disaster using open-ended questions. Text responses (N=650) were compiled, themes identified by multiple coders, responses coded into the themes, interrater reliability established, and the themes were then interpreted. Six themes were identified and grouped into three general categories: personal aspirations (reprioritizing life and altruism and self-improvement), connection with others (a freestanding category/theme), and making meaning (appreciation for life, religion and spirituality, and contemplating life, death, and humanity), which contained the majority of the responses. The findings from this study affirm the human need to make meaning from the experience of a traumatic disaster and suggest the potential relevance to survivors' recovery of therapies based on the creation of meaning and the promotion of positive growth.

Mitochondrial chaperone TRAP1 activates the mitochondrial UPR and extends healthspan in Drosophila.

The molecular mechanisms influencing healthspan are unclear but mitochondrial function, resistance to oxidative stress and proteostasis are recurring themes. Tumor necrosis factor Receptor Associated Protein 1 (TRAP1), the mitochondrial analog of Hsp75, regulates levels of reactive oxygen species in vitro and is found expressed at higher levels in tumor cells where it is thought to play a pro-survival role. While TRAP1-directed compartmentalized protein folding is a promising target for cancer therapy, its role at the organismal level is unclear. Here we report that overexpression of TRAP1 in Drosophila extends healthspan by enhancing stress resistance, locomotor activity and fertility while depletion of TRAP1 has the opposite effect, with little effect on lifespan under both conditions. In addition, modulating TRAP1 expression promotes the nuclear translocation of homeobox protein Dve and increases expression of genes associated with the mitochondrial unfolded protein response (UPR(mt)), indicating an activation of this proteostasis pathway. Notably, independent genetic knockdown of components of the UPR(mt) pathway dampen the enhanced stress resistance observed in TRAP1 overexpression flies. Together these studies suggest that TRAP1 regulates healthspan, potentially through activation of the UPR(mt).

Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo.

Mutations in mitochondrial DNA polymerase (pol gamma) cause several progressive human diseases including Parkinson's disease, Alper's syndrome, and progressive external ophthalmoplegia. At the cellular level, disruption of pol gamma leads to depletion of mtDNA, disrupts the mitochondrial respiratory chain, and increases susceptibility to oxidative stress. Although recent studies have intensified focus on the role of mtDNA in neuronal diseases, the changes that take place in mitochondrial biogenesis and mitochondrial axonal transport when mtDNA replication is disrupted are unknown. Using high-speed confocal microscopy, electron microscopy and biochemical approaches, we report that mutations in pol gamma deplete mtDNA levels and lead to an increase in mitochondrial density in Drosophila proximal nerves and muscles, without a noticeable increase in mitochondrial fragmentation. Furthermore, there is a rise in flux of bidirectional mitochondrial axonal transport, albeit with slower kinesin-based anterograde transport. In contrast, flux of synaptic vesicle precursors was modestly decreased in pol gamma-alpha mutants. Our data indicate that disruption of mtDNA replication does not hinder mitochondrial biogenesis, increases mitochondrial axonal transport, and raises the question of whether high levels of circulating mtDNA-deficient mitochondria are beneficial or deleterious in mtDNA diseases.