Investigational systemic drugs for moderate to severe plaque psoriasis: What’s new?

Introduction: The therapeutic armamentarium for the treatment of psoriasis, a chronic inflammatory skin disease, is now reasonably broad and structured, with several therapeutic agents that demonstrated a successful long-term control of this condition. However, there are still unfulfilled gaps resulting from the inherent limitations of existing therapies, which have paved the way for the identification of new therapeutic strategies or the improvement of the existing ones. Areas covered: The aim of this review is to thoroughly explore new therapeutic strategies and novel drugs that are currently in the pipeline for the treatment of psoriasis, focusing primarily on agents that are currently in phase I/II of clinical development. Some of which retrace already existing therapeutic approaches, such as the IL23/Th17 pathway inhibition, while others unveil new and yet unexplored ones. Expert opinion: Since the therapeutic landscape of psoriasis is wide, it is not yet clear whether novel agents will fill the remaining gaps in the context of a broader and more diversified set of oral and biologic therapies. Nevertheless, with the development of precision medicine approaches, the development of innovative targeted drugs will still have a therapeutic rationale in psoriasis

Hearing and justice: the link between hearing impairment in early childhood and youth offending in Aboriginal children living in remote communities of the Northern Territory, Australia

Background: High prevalence of chronic middle ear disease has persisted in Australian Aboriginal children, and the related hearing impairment (HI) has been implicated in a range of social outcomes. This study investigated the association between HI in early childhood and youth offending. Method: This was a retrospective cohort study of 1533 Aboriginal children (born between 1996 and 2001) living in remote Northern Territory communities. The study used linked individual-level information from health, education, child protection and youth justice services. The outcome variable was a youth being “found guilty of an offence”. The key explanatory variable, hearing impairment, was based on audiometric assessment. Other variables were: child maltreatment notifications, Year 7 school enrolment by mother, Year 7 school attendance and community ‘fixed- effects’. The Cox proportional hazards model was used to estimate the association between HI and youth offending; and the Royston R2 measure to estimate the separate contributions of risk factors to youth offending. Results: The proportion of hearing loss was high in children with records of offence (boys: 55.6%, girls: 36.7%) and those without (boys: 46.1%; girls: 49.0%). In univariate analysis, a higher risk of offending was found among boys with moderate or worse HI (HR: 1.77 [95% CI: 1.05–2.98]) and mild HI (HR: 1.54 [95% CI:1.06–2.23]). This association was attenuated in multivariable analysis (moderate HI, HR: 1.43 [95% CI:0.78–2.62]; mild HI, HR: 1.37 [95% CI: 0.83– 2.26]). No evidence for an association was found in girls. HI contributed 3.2% and 6.5% of variation in offending among boys and girls respectively. Factors contributing greater variance included: community ‘fixed-effects’ (boys: 14.6%, girls: 36.5%), child maltreatment notification (boys: 14.2%, girls: 23.9%) and year 7 school attendance (boys: 7.9%; girls 12.1%). Enrolment by mother explained substantial variation for girls (25.4%) but not boys (0.2%). Conclusion: There was evidence, in univariate analysis, for an association between HI and youth offending for boys however this association was not evident after controlling for other factors. Our findings highlight a range of risk factors that underpin the pathway to youth-offending, demonstrating the urgent need for interagency collaboration to meet the complex needs of vulnerable children in the Northern Territory.Vincent Yaofeng He, Jiunn-Yih Su, Steven Guthridge, Catia Malvaso, Damien Howard, Tamika Williams and Amanda Leac

Apremilast for the treatment of hidradenitis suppurativa associated with psoriatic arthritis in multimorbid patients: Case report and review of literature

INTRODUCTION: Hidradenitis suppurativa is a complex, chronic, difficult to treat condition belonging to the spectrum of cutaneous immune-mediated inflammatory diseases. Systemic treatment options for moderate-severe disease are limited to TNF-alpha antagonists and other biologic agents, with limited clinical evidence. PATIENT CONCERNS: We report two adult patients with severe hidradenitis suppurativa presenting concomitant psoriatic arthritis and multiple medical comorbidities. Both were ineligible or resistant to adalimumab, the only biologic drug approved for the treatment of hidradenitis. DIAGNOSIS: Both patients were diagnosed with severe Hurley III-stage disease and psoriatic arthritis, showing resistance to first-line systemic treatments and a complex comorbidity profile. INTERVENTIONS: Patients underwent treatment with apremilast, an oral phosphodiesterase-4 inhibitor, approved for the treatment of psoriatic arthritis. OUTCOMES: After 16 weeks of treatment, a clinically relevant improvement of inflammatory lesions, skin- and arthritis-related pain, and patient-reported outcomes was achieved in both patients. Apremilast was well tolerated and continued up to 48 weeks of treatment. CONCLUSION: We report the "real-life" use of apremilast in the treatment of multimorbid patients with hidradenitis suppurativa and review its potential role in the management of this severe condition

Adult developmental trajectories of pseudoneglect in the tactile, visual and auditory modalities

Joanna Brooks, Stephen Darling, Catia Malvaso, and Sergio Della Sal

The psychological effects of unemployment and unsatisfactory employment on young adults: findings from a 10-Year longitudinal study

Published online: 16 Aug 2017The purpose of the present study was to extend the external validity of an earlier longitudinal study of school leavers by including participants from a representative sample of secondary schools. Questionnaires were administered annually to a sample of South Australian school leavers over a 10-year period. At Time 1 participants were in the last compulsory year of high school aged around 15 years and at Time 10 they were aged around 25 years. Results confirmed those from an earlier longitudinal study showing that the transition from school to satisfactory employment was associated with significant improvements in psychological well-being, whereas transition from school to unemployment or unsatisfactory employment showed no change in psychological well-being. The current findings extended the external validity of the earlier study because whereas participants in the earlier study were sampled from co-educational metropolitan public high schools, the current study included participants from every kind of high school: single sex as well as co-educational, rural as well as metropolitan, and private as well as public.Anthony H. Winefield, Paul H. Delfabbro, Helen R. Winefield, David Duong, and Catia Malvas

Who is doing well: age 15 predictors of psychological and physical health in young adulthood

Objective: According to Diener (1984), wellbeing is a multi‐faceted concept reflecting satisfaction with life, good physical health, and fewer negative psychological symptoms. Using data from a 10‐year longitudinal study of school leavers (n = 390), we examine whether people aged 25 can be differentiated into clusters based on indicators of wellbeing, then whether membership in the healthy as opposed to the less healthy cluster can be predicted by age 15 variables. Method: Tested predictor variables at age 15 captured the major influences in Bronfenbrenner's Ecological Theory (1979) including individual, family, and social influences. Young adults (age 25) were differentiated into two clusters based on indicators of mental health and subjective wellbeing. Results: Poorer health, self‐image, family functioning, and peer relations at age 15 predicted poorer overall wellbeing at age 25. Conclusions: Results underscore the potential value of psychological support for adolescents within the school environment and the early identification of individuals at risk of problems which may persist into adulthood.Paul Delfabbro, Jeremy Stevenson, Catia Malvaso, David Duong, Helen Winefield, Anthony Winefield, Anne Hammarströ

PASH, PAPASH, PsAPASH, and PASS: The autoinflammatory syndromes of hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory disease usually involving the major skin folds characterized by a multifactorial pathogenesis and a wide spectrum of clinical manifestations. It can also rarely present in association with other diseases as complex clinical syndromes, causing additional diagnostic and therapeutic challenges. Different etiopathologic factors contribute to follicular inflammation and suppurative lesions of syndromic HS, including follicular hyperkeratinization and plugging, as well as activation of autoinflammatory pathways. Patients with syndromic HS frequently have a severe disease course, presenting with atypical skin involvement, signs of systemic inflammation, and resistance to conventional treatments. Systematic classification of syndromic HS is based on clinical, pathogenetic, and genetic factors, but it is constantly evolving due to increased disease awareness. Treatment of syndromic HS is difficult and should be personalized on a case-by-case basis. Investigating syndromic HS can lead to useful insights on genetics and pathogenesis, translating into new clinical approaches for sporadic hidradenitis. We review the classification, clinical presentation, disease associations, and therapeutic management of syndromic HS, focusing mainly on its autoinflammatory syndromes PASH, PAPASH, PsAPASH, and PASS

Prevalence of Neuropathic Pain and Related Characteristics in Hidradenitis Suppurativa : A Cross-Sectional Study

Background: Pain is a core symptom of hidradenitis suppurativa (HS) and is of complex, multifactorial origin. HS patients frequently report typical neuropathic pain qualities, but its prevalence has been poorly described. Methods: In this cross-sectional study, we examine the prevalence of neuropathic pain (NP) component and related pain-characteristics of a hospital-based cohort of patients with symptomatic HS. We administered the pain-DETECT tool (PDQ), a validated screening tool for NP, collecting clinical and patient-reported data on pain, pruritus and pain-management. We obtained 110 complete datasets from symptomatic HS patients (49.1% females; Hurley I (27.3%])-II (45.5%)-III (27.3%)). According to the PDQ tool, 30% of patients were classified with a high probability (>90%) of neuropathic pain (LNP). LNP status was significantly associated with increased pain severity, disease activity, pruritus intensity and use of pain medication. Regression analysis showed a significant impact of the PDQ score on patient-reported outcomes, including pain severity and the dimensions of activity and affective pain interference. HS patients may present a mixed chronic pain phenotype with a neuropathic component, thus requiring additional pain-assessments. A multi-modal approach to pain management, in combination with disease-specific treatment, should be implemented in future interventional studies

Baricitinib: therapeutic potential for moderate to severe atopic dermatitis

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease mediated by multiple signals including janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. Current therapeutic armamentarium consists of a limited number of drugs which may result in the insufficient management of AD. Preclinical evidence regarding inhibition of JAK/STAT led to the development of a promising class of therapeutics, namely, JAK inhibitors. Baricitinib, a novel JAK1/JAK2 inhibitor is currently under investigation in AD clinical trials. Areas covered: This review offers an overview of Baricitinib and examines clinical efficacy and safety data in patients with moderate-to-severe AD. Expert opinion: Baricitinib showed promising preliminary data in terms of efficacy in phase II and III trials, with a very rapid onset of response and great improvements of itch and sleep disturbances. These aforementioned aspects combined with the advantage of an oral formulation have reduced drug production costs compared to biologic agents and could lead to consideration of baricitinib as a first line systemic treatment. Also, in some countries, it could be a therapeutic option in the case of contraindication or failure of conventional systemic drugs prior to biologic therapies. Data related to long-term safety and efficacy will be important to refine the place-in-therapy of this drug

The psychological burden during COVID-19 pandemic in a cohort of patients affected by moderate-to-severe atopic dermatitis treated with dupilumab

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