A systematic review of the psychosocial factors associated with pain in children with juvenile idiopathic arthritis.

BACKGROUND: Pain is one of the most frequently reported experiences amongst children with Juvenile Idiopathic Arthritis (JIA); however, the management of JIA pain remains challenging. As pain is a multidimensional experience that is influenced by biological, psychological, and social factors, the key to effective pain management lies in understanding these complex relationships. The objective of this study is to systematically review the literature on psychosocial factors of children with JIA and their caregivers 1) associated with and 2) predictive of later JIA pain intensity, frequency, and sensitivity in children 0-17 years of age. METHODS: The Joanna Briggs Institute methodology for etiology and risk and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement guided the conduct and reporting of this review. Terms related to pain and JIA were searched in English without date restrictions across various databases (PubMed, CINAHL, PsycINFO, Embase, Scopus, and the Cochrane Central Register of Controlled Trials) in September 2021. Two independent reviewers identified, extracted data from, and critically appraised the included studies. Conflicts were resolved via consensus. RESULTS: Of the 9,929 unique studies identified, 61 were included in this review and reported on 516 associations. Results were heterogeneous, likely due to methodological differences and moderate study quality. Results identified predominantly significant associations between pain and primary and secondary appraisals (e.g., more child pain beliefs, lower parent/child self-efficacy, lower child social functioning), parent/child internalizing symptoms, and lower child well-being and health-related quality of life. Prognostically, studies had 1-to-60-month follow-up periods. Fewer beliefs of harm, disability, and no control were associated with lower pain at follow-up, whereas internalizing symptoms and lower well-being were predictive of higher pain at follow-up (bidirectional relationships were also identified). CONCLUSIONS: Despite the heterogeneous results, this review highlights important associations between psychosocial factors and JIA pain. Clinically, this information supports an interdisciplinary approach to pain management, informs the role of psychosocial supports, and provides information to better optimize JIA pain assessments and interventions. It also identifies a need for high quality studies with larger samples and more complex and longitudinal analyses to understand factors that impact the pain experience in children with JIA. TRIAL REGISTRATION: PROSPERO CRD42021266716.

Healthcare worker perspectives on mother's insufficient milk supply in Malawi.

BACKGROUND: Human milk insufficiency is a significant barrier to implementing breastfeeding, and it is identified as a prevalent concern in 60-90% of mothers in low-and-middle-income countries. Breastmilk insufficiency can lead to hypoglycemia, hypernatremia, nutritional deficiencies, and failure to thrive in newborns and infants. Studies investigating the impact of breastfeeding interventions to improve milk production highlight inconsistencies between healthcare workers and mothers perceived support, as well as gaps in practical knowledge and training. The aim of this study was to determine perceptions surrounding human milk insufficiency from Malawian healthcare workers. METHODS: This study is a secondary analysis of 39 interviews with healthcare workers from one tertiary and three district hospitals in Malawi employing content analysis. Interviewed healthcare workers included nurses, clinical officers, midwives, and medical doctors. An inclusive coding framework was developed to identify themes related to human milk insufficiency, which were analyzed using an iterative process with NVivo12 software. Researchers focused on themes emerging from perceptions and reasons given by healthcare workers for human milk insufficiency. RESULTS: Inability to produce adequate breastmilk was identified as a prevalent obstacle mothers face in the early postpartum period in both district and tertiary facilities in Malawi. The main reasons given by participants for human milk insufficiency were mothers' perceived normalcy of milk insufficiency, maternal stress, maternal malnutrition, and traditional beliefs around food and eating. Three focused solutions were offered by participants to improve mother's milk production - improving education for mothers and training for healthcare providers on interventions to improve mother's milk production, increasing breastfeeding frequency, and ensuring adequate maternal nutrition pre- and post-partum. CONCLUSION: Health care workers perspectives shed light on the complexity of causes and solutions for human milk insufficiency in Malawi. This research highlights that a respectful professional relationship between health care workers and mothers is an essential bridge to improving communication, detecting human milk insufficiency early, and implementing appropriate interventions. The results of this study may help to inform research, clinical practice, and education in Malawi to improve human milk production.

Radiation dose enhancement using gold nanoparticles with a diamond linear accelerator target: a multiple cell type analysis.

Radiotherapy (RT) is an effective cancer treatment modality, but standard RT often causes collateral damage to nearby healthy tissues. To increase therapeutic ratio, radiosensitization via gold nanoparticles (GNPs) has been shown to be effective. One challenge is that megavoltage beams generated by clinical linear accelerators are poor initiators of the photoelectric effect. Previous computer models predicted that a diamond target beam (DTB) will yield 400% more low-energy photons, increasing the probability of interacting with GNPs to enhance the radiation dose by 7.7-fold in the GNP vicinity. After testing DTB radiation coupled with GNPs in multiple cell types, we demonstrate decreased head-and-neck cancer (HNC) cell viability in vitro and enhanced cell-killing in zebrafish xenografts compared to standard RT. HNC cell lines also displayed increased double-stranded DNA breaks with DTB irradiation in the presence of GNPs. This study presents preclinical responses to GNP-enhanced radiotherapy with the novel DTB, providing the first functional data to support the theoretical evidence for radiosensitization via GNPs in this context, and highlighting the potential of this approach to optimize the efficacy of RT in anatomically difficult-to-treat tumors.

The identification of dual protective agents against cisplatin-induced oto- and nephrotoxicity using the zebrafish model.

Dose-limiting toxicities for cisplatin administration, including ototoxicity and nephrotoxicity, impact the clinical utility of this effective chemotherapy agent and lead to lifelong complications, particularly in pediatric cancer survivors. Using a two-pronged drug screen employing the zebrafish lateral line as an in vivo readout for ototoxicity and kidney cell-based nephrotoxicity assay, we screened 1280 compounds and identified 22 that were both oto- and nephroprotective. Of these, dopamine and L-mimosine, a plant-based amino acid active in the dopamine pathway, were further investigated. Dopamine and L-mimosine protected the hair cells in the zebrafish otic vesicle from cisplatin-induced damage and preserved zebrafish larval glomerular filtration. Importantly, these compounds did not abrogate the cytotoxic effects of cisplatin on human cancer cells. This study provides insights into the mechanisms underlying cisplatin-induced oto- and nephrotoxicity and compelling preclinical evidence for the potential utility of dopamine and L-mimosine in the safer administration of cisplatin.