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Scabies and related bacterial skin and soft tissue infections (SSTIs) are highly prevalent in many tropical, low- and middle-income settings. These skin conditions contribute to higher healthcare costs and burdens on healthcare systems. The Big Skin Health Intervention Fiji Trial ("Big SHIFT") carried out surveillance for scabies and SSTIs from July 2018 to June 2019 in the Northern Division of Fiji, an area with high prevalence of scabies, prior to a division-wide ivermectin-based mass drug administration (MDA) campaign. Using data from Big SHIFT, we sought to estimate the annual direct healthcare costs of scabies and related SSTIs for the Northern Division and extrapolate these costs to the national level. We categorized SSTIs as being potentially scabies-related or unlikely scabies-related, based on a previous study. The analysis used a health system perspective, with the main resource use categories of outpatient visits, bed days during admissions, medicines, and diagnostic tests. We extrapolated the total annual number of cases and direct healthcare costs for all divisions in Fiji based upon previous scabies and impetigo prevalence data across all divisions. The average cost per PHC presentation for scabies was US$17.7, and for potentially scabies-related SSTI was $18.3. The average cost per hospital admission for a potentially scabies-related SSTI case was $439. The estimated annual healthcare costs of scabies and related SSTIs in Fiji was US$3.0 million, with cost per capita of $3.3. Scabies and related SSTIs lead to a heavy economic burden in Fiji and prevention would reduce these healthcare costs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Akpan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: There is still no effective treatment for the gastrointestinal side effects of radiation therapy. Multilineage-differentiating stress-enduring (Muse) cells are tissue stem cells that have the ability to spontaneously home in on injured tissues and repair them. Several clinical trials have shown that stem cell therapy using human bone marrow-derived Muse (hBM-Muse) cells is effective in treating various diseases, but it is not known whether they are effective in treating radiation-induced intestinal injury. In this study, we investigated whether hBM-Muse cells are homing to the radiation-damaged intestine and promote its repair., Methods and Materials: hBM-Muse cells were injected into the tail vein of mice 2 hours after high-dose total body irradiation. Then, homing analysis, crypt assay, bromodeoxyuridine assay, Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay, immunostaining, and survival time measurements were performed. In addition, we analyzed the expression of sphingosine monophosphate (S1P), a Muse cell-inducing factor, in the mouse small intestine after irradiation. Finally, we investigated whether the administration of JTE-013, an S1P receptor 2-specific antagonist, inhibits hBM-Muse cells homing to the injured intestine., Results: S1P expression increased in mouse intestine after irradiation, with hBM-Muse cells homing in on the injured intestine. Injection of hBM-Muse cells after radiation exposure significantly increased the number of crypts, proliferating cells in the crypts, and small intestinal component cells such as intestinal stem cells inhibited radiation-induced apoptosis and prolonged mouse survival. Treatment with JTE-013 significantly inhibited intestinal homing and therapeutic effects of hBM-Muse cells. These findings indicate that hBM-Muse cells homed in on the injured intestine through the S1P-S1P receptor 2 interaction to exert therapeutic effects on the radiation-induced intestinal injury., Conclusions: This study indicates that hBM-Muse cells are effective in treating radiation-induced intestinal injury, suggesting that hBM-Muse cell-based stem cell therapy has the potential to overcome gastrointestinal side effects that limit the indications for radiation therapy., Competing Interests: None., (© 2024 The Author(s).)

Background: Clinical practice guidelines (CPGs) improve patient care by standardising medical practice. However, little is known about their applicability in low-resource settings. Since 2010, Fiji has introduced guidelines to increase the application of evidence-based practice., Aims: We describe the dissemination, utility and monitoring of guideline implementation in Fiji, a low-resource setting in the Pacific., Methods: A mixed-methods design included a survey and focus groups. All 178 doctors in five departments at Fiji's largest tertiary hospital were invited to participate. Subsequently, two focus group interviews explored clinicians' perspectives in more detail. Analysis included data description, multi-variable logistic, multinomial regression and manifest content analyses., Results: The response rate was 74%. Most doctors agreed that CPGs were good for patient management (100%), doctors continuing medical education (CME) (96%), patient education (73%), supported by systematic reviews (91%) and consistent with existing norms/values (83%). Ninety-five per cent stated that CPGs increased the quality of care, and 80% stated that CPGs increased physician satisfaction. Approximately two-thirds stated that CPGs decreased medical-legal problems (63%) and malpractice suits (68%). Sixty to 90% of doctors disagreed that CPGs were oversimplified/cookbook medicine (60%), too rigid to apply individually (65%), challenged physician autonomy (60%) or were ambiguous/unclear (86%) or not practical (89%). The preferred method of dissemination was CME, and quick reference guides were best for implementation. No formal CPG monitoring existed in any department., Conclusion: Most physicians found CPGs to be valuable for improving the consistency of care. In low-resource settings, dissemination of guidelines should be paired with CME to improve their uptake. Increased monitoring of guideline use appears necessary., (© 2024 Royal Australasian College of Physicians.)

Angiosarcoma is a rare refractory soft-tissue tumor with a poor prognosis and is treated by radiotherapy. The fibroblast growth factor 1 (FGF1) mutant, with enhanced thermostability due to several substituted amino acids, inhibits angiosarcoma cell metastasis, yet the mechanism of action is unclear. This study aims to clarify the FGF1 mutant mechanism of action using ISOS-1 mouse angiosarcoma cells. The wild-type FGF1 or FGF1 mutant was added to ISOS-1 cells and cultured, evaluating cell numbers over time. The invasive and migratory capacity of ISOS-1 cells was assessed by transwell analysis. ISOS-1 cell radiosensitivity was assessed by colony formation assay after X-ray irradiation. To examine whether mitogen-activated protein kinase (MEK) inhibitor counteracts the FGF1 mutant effects, a combination of MEK inhibitor and FGF1 mutant was added to ISOS-1 cells and cultured. The FGF1 mutant was observed to inhibit ISOS-1 cell proliferation, invasion and migration by sustained FGF1 signaling activation. A MEK inhibitor suppressed the FGF1 mutant-induced inhibition of proliferation, invasion and migration of ISOS-1 cells. Furthermore, the FGF1 mutant enhanced radiosensitivity of ISOS-1 cells, but MEK inhibition suppressed the increased radiosensitivity. In addition, we found that the FGF1 mutant strongly inhibits actin polymerization, suggesting that actin cytoskeletal dynamics are closely related to ISOS-1 cell radiosensitivity. Overall, this study demonstrated that in ISOS-1 cells, the FGF1 mutant inhibits proliferation, invasion and migration while enhancing radiosensitivity through sustained activation of the MEK-mediated signaling pathway., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Rheumatic heart disease (RHD) is an important and preventable cause of morbidity and mortality among children and young adults in low-income and middle-income countries, as well as among certain at-risk populations living in high-income countries. The 2012 World Heart Federation echocardiographic criteria provided a standardized approach for the identification of RHD and facilitated an improvement in early case detection. The 2012 criteria were used to define disease burden in numerous epidemiological studies, but researchers and clinicians have since highlighted limitations that have prompted a revision. In this updated version of the guidelines, we incorporate evidence from a scoping review, an expert panel and end-user feedback and present an approach for active case finding for RHD, including the use of screening and confirmatory criteria. These guidelines also introduce a new stage-based classification for RHD to identify the risk of disease progression. They describe the latest evidence and recommendations on population-based echocardiographic active case finding and risk stratification. Secondary antibiotic prophylaxis, echocardiography equipment and task sharing for RHD active case finding are also discussed. These World Heart Federation 2023 guidelines provide a concise and updated resource for clinical and research applications in RHD-endemic regions., (© 2023. Springer Nature Limited.)

Syphilis is an important global health threat and little has changed in its treatment since the mid-20th century. For late-latent or syphilis infection of unknown duration, the standard treatment of multiple intramuscular injections of benzathine penicillin G (BPG) are associated with significant pain and distress to clients and caregivers, negatively impacting on treatment completion. Based on pharmacokinetic modelling from a Phase I study of subcutaneous infusion of high dose BPG (SCIP), we present its feasibility, safety and tolerability for treatment of syphilis in a single infusion. SCIP leads to more sustained penicillin concentrations above the desired target with less reported pain and reduced clinic visits.