Developing contents for a digital adherence tool: A formative mixed-methods study among children and adolescents living with HIV in Tanzania.

Optimal adherence (>95%) to antiretroviral treatment (ART) remains a challenge among children and adolescents living with HIV (CALHIV). Digital adherence tools (DAT) with reminder cues have proven feasible among adult people living with HIV (PLHIV), with some concerns about the risk of HIV status disclosure. We aimed to assess the needs, contents and acceptability of an SMS-based DAT among CALHIV. We first conducted a survey to understand potential barriers to using DAT among CALHIV, then tested the DAT intervention among purposively selected participants. The DAT intervention included using the Wisepill device, receiving daily reminder SMS and receiving adherence reports on how they had taken medication in the past month. The content of the reminder SMS differed over time from asking if the medication was taken to a more neutral SMS like "take care". Afterwards, we conducted exit interviews, in-depth interviews, and focus-group discussions. We analysed quantitative findings descriptively and used thematic content analysis for qualitative data. We included 142 children and 142 adolescents in the survey, and 20 of each used the intervention. Eighty-five percent (121/142) of surveyed participants indicated they would like to receive reminder SMS. Most of them (97/121-80%) of children and 94/121(78%) of adolescents would prefer to receive daily reminders. Participants who used the DAT mentioned to be happy to use the device. Ninety percent of them had good experience with receiving reminders and agreed that the SMS made them take medication. However, 25% experienced network problems. Participants preferred neutral reminder SMSs that did not mention the word 'medication', but preserved confidentiality. The provided adherence reports inspired participants to improve their adherence. None of the participants experienced unwanted disclosure or stigmatisation due to DAT. However, 5% of adolescents were concerned about being monitored daily. This study showed that DAT is acceptable and provided insight of the needed SMS content for a customized DAT for CALHIV.

Current knowledge on autoantigens and autoantibodies in psoriasis.

In the past decades, clinical and experimental evidence has demonstrated that psoriasis is an immune-mediated inflammatory disease of the skin that occurs in genetically susceptible individuals. Psoriasis also shows clear autoimmune pathomechanisms, but specific cellular targets for the onset and maintenance of psoriatic lesions were not established until 2014. Since then, four psoriasis autoantigens were discovered, namely cathelicidin LL-37, melanocytic ADAMTSL5, lipid antigen PLA2G4D and keratin 17. Autoreactive T cells against these autoantigens were found in a number of patients with moderate-to-severe plaque psoriasis. Moreover, the discovery of autoantibodies against LL-37 and ADAMTSL5 and their strong association with psoriatic arthritis (PsA) suggest a potential role of these autoantibodies in the pathogenesis of PsA. This review discusses the current studies on psoriatic autoantigens and the associated circulating autoantibodies and their mechanisms involved in the development and maintenance of psoriatic plaques. Recent autoimmune evidence fuelled the discussion on psoriasis as an autoimmune skin disorder and has the potential to develop new treatment strategies with protective and therapeutic antigen-targeted methods.

The TNF/IL-23/IL-17 axis-Head-to-head trials comparing different biologics in psoriasis treatment.

Psoriasis is a T cell-mediated disease with autoimmune characteristics modulated by genetic susceptibility along with environmental triggers. Inflammatory pathways marked with excessive production of cytokines IL-12 and IL-23, drive differentiation of pathogenic T cell responses resulting in TNF and IL-17 production. These cytokines are an integral part of the TNF/IL-23/IL-17 axis, which is responsible for maintaining inflammation in psoriatic skin. Our improved understanding of the immunopathogenesis led to the development of biological drugs in the treatment of moderate-to-severe disease. Biologics have revolutionized the management of psoriasis, highlighting the central role of TNF/IL-23/IL-17 axis in the physiopathology of the disease. Still, psoriasis usually requires long-term treatment, aiming to fully remove psoriatic lesions without experiencing adverse events. In this review, we discuss the recent findings of all 27 available head-to-head trials investigating the efficacy and safety of systemic and biologic therapies in moderate-to-severe psoriasis vulgaris, as it is thought to provide more useful knowledge than placebo intervention alone. According to our evaluation, inhibitors that specifically target IL-23 or IL-17 are clinically more beneficial than inhibitors of IL-12/IL-23 and TNF. More informative results might be obtained by comparing these more efficient biological agents to each other. In addition, newer therapies for psoriasis using small-molecule drugs may represent important advances compared to well-established biologics as these are less expensive and orally administered.