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Psoriasis is a chronic inflammatory skin disorder involving marked immunological changes. IL-17-targeting biologics have been successful in reducing the disease burden of psoriasis patients with moderate-to-severe disease. Unfortunately, the stratum corneum prevents penetration of large molecule weight proteins, including monoclonal antibodies. Thus, for the majority of psoriasis patients ineligible for systemic treatments, a small molecule targeting RORγt, the master regulator of IL-17 family cytokines, may represent an alternative topical medicine with biologic-like efficacy.The preclinical studies described in this manuscript bridge the gap from bench to bedside to provide the scientific foundation for a compound entering clinical trials for patients with mild to moderate psoriasis. In addition to several ex vivo reporter assays, primary T cell cultures, and the imiquimod mouse model, we demonstrate efficacy in a newly developed human ex vivo skin assay, where Th17-skewed cytokine expression is induced from skin-resident immune cells. Importantly, the skin barrier remains intact allowing for the demonstration of topical drug delivery. With the development of this novel assay, we demonstrate potent compound activity in the target tissue: human skin. Finally, target engagement by this small molecule was confirmed in ex vivo lesional psoriatic skin.Our work describes a progressive series of assays to demonstrate the potential clinical value of a novel RORγ inverse agonist small molecule with high potency and selectivity, which will enter clinical trials in late 2015 for psoriasis patients.

ObjectiveThe prevalence of type 2 diabetes mellitus (T2DM) in Vietnam has doubled from 3% to 6% over the last decades, with potential consequences for persons with diabetes and their caregivers. This study aimed to assess caregiver burdens and factors associated with caregiver burden.MethodA cross-sectional study was conducted in 2019, using data from 1,241 informal caregivers (ICGs). Caregiver burden was scored from 0-32 using 8 questions from the Zarit Burden Interview (ZBI). Quantile regression analysis was used to identify factors associated with caregiver burden.ResultsThe median score of the ZBI was 7.0 (Q1-Q3: 2.0-10.0), indicating that the burden among caregiver of persons with T2DM is not high. Quantile regression showed that the higher the monthly income, the lower the burden among caregivers (50% quantile and 75% quantile of burden: -0.004). Lower educational level (25%Q: 4.0, 50%Q; 3.0, 75%Q: 2.16), being a farmer (25%Q: 2.0) and providing care to other people besides the person with T2DM (25%Q: 2.0, 50%Q; 2.54, 75%Q: 1.66) were associated with higher burden on caregivers.ConclusionThe study found that caregivers facing additional life stressors, such as low income or other caregiving responsibilities, reported higher levels of burden. These findings could inform the development of interventions targeted at supporting informal caregivers in rural areas in low- and middle-income countries.

ObjectivesPeople with diabetes are at high risk of polypharmacy owing to complex treatment of diabetes and comorbidities. Polypharmacy is associated with increased risk of adverse reactions and decreased compliance. Therefore, the objectives of this study were to assess polypharmacy in people with type 2 diabetes (T2D) and associated diabetes-related factors in rural areas in Vietnam.MethodPeople with T2D (n = 806) who had received treatment for diabetes at a district hospital were invited to participate in a questionnaire-based cross-sectional survey. Polypharmacy was defined as ≥5 types of medicine and assessed as a) prescription medicine and non-prescription/over the counter (OTC) medicine and b) prescription medicine and non-prescription/OTC, herbal and traditional medicine, and dietary supplement. Multiple logistic regression was used to investigate the association between polypharmacy and diabetes specific factors: duration, comorbidities and diabetes-related distress.ResultsOf the people with T2D, 7.8% had a medicine use corresponding to polypharmacy (prescription medicine and non-prescription/OTC), and 40.8% when herbal and traditional medicine, and dietary supplement were included. Mean number of medicine intake (all types of medicines and supplements) were 3.8±1.5. The odd ratios (ORs) of polypharmacy (medicine and supplements) increased with diabetes duration (5 years OR = 1.74; 95%CI: 1.14-2.64 as compared to ≤1-year duration of diabetes), number of comorbidities (1-2 comorbidities: OR = 2.0; 95%CI: 1.18-3.42; ≥3 comorbidities: OR = 2.63;95%CI: 1.50-4.61 as compared to no comorbidities), and suffering from diabetes-related distress (OR = 1.49; 95%CI: 1.11-2.01) as compared to those without distress.ConclusionsIn rural northern Vietnam, persons with longer duration of T2D, higher number of comorbidities and diabetes-related stress have higher odds of having a medicine use corresponding to polypharmacy. A high proportion of people with T2D supplement their prescription, non-prescription/OTC medicine with herbal and traditional medicine and dietary supplements.

BackgroundClonorchiasis, caused by the fish-borne trematode Clonorchis sinensis, is a neglected tropical disease and a public health issue in endemic countries. In Vietnam, an in-depth analysis of risk factors for the condition is missing up to now. This study aimed to determine the prevalence of C. sinensis infection and associated risk factors in rural communities in northern Vietnam.Methodology/principal findingsA cross-sectional survey was conducted in 4 communes in Yen Bai and Thanh Hoa provinces where clonorchiasis is known to be present and raw fish consumption is a common. Using a simple random sampling approach, stool was collected from 841 participants over 6 years old for coprological examination, and a questionnaire measured knowledge, attitudes, and practices with regard to clonorchiasis in 757 participants over 15 years old. Univariable and multivariable logistic regression models were run to identify risk factors for infection with C. sinensis. The overall prevalence of C. sinensis infection was 40.4%, with commune prevalences ranging between 26.5% and 53.3%. In the final model, males were significantly more likely to be infected with C. sinensis (OR 2.00; 95% CI 1.31-3.05). Recent (i.e. last year) consumption of raw fish (OR 8.00, 95% CI 4.78-13.36), low education level (OR 5.57; 95% CI 2.37-13.07), lack of treatment (OR 1.82, 95% CI 1.15-2.89), being between 19 to 39 years old (OR 6.46; 95% CI 1.25-33.37), and the presence of an unhygienic toilet (OR 2.74, 95% CI 1.53-4.92) were significantly associated with C. sinensis infection.Conclusion/significanceThis study demonstrated a high prevalence of C. sinensis infection in rural communities in northern Vietnam. Thus, control measures including, mass drug administration for those communes should be applied to reduce the prevalence. Moreover, specific health education activities should be developed for risk groups in C. sinensis endemic areas.