Secukinumab in the treatment of psoriasis: patient selection and perspectives.

Secukinumab is a human monoclonal antibody targeting IL-17A that has been approved for three indications: moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In Phase III clinical trials for each of these three indications, secukinumab has proven to be both highly efficacious and well-tolerated. However, several biologic medications are currently approved for the treatment of moderate-to-severe plaque psoriasis, and many demonstrate excellent efficacy and safety. Due to this wide selection, it is often unclear how to choose biologics for specific patients. Important considerations in biologic selection include clinical efficacy, safety, cost, convenience, onset of action, and management of comorbid disease. This article aims to outline the key considerations in patient selection for the treatment of plaque psoriasis with secukinumab

Profile of tildrakizumab-asmn in the treatment of moderate-to-severe plaque psoriasis: evidence to date.

Plaque psoriasis is an immune-mediated skin disease that affects roughly 3% of adults in the United States. Advances over the past 20 years in understanding the immune-mediated pathophysiology of psoriasis have led to the development of targeted biologic therapies for this condition. Currently, biologic medications approved for the treatment of plaque psoriasis include tumor necrosis factor α inhibitors, interleukin (IL)-17 or IL-17 receptor inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors. Tildrakizumab-asmn is a monoclonal antibody that targets the p19 subunit of IL-23 and is approved for use in adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This article reviews the current pharmacologic, efficacy, and safety data on tildrakizumab-asmn

Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives.

Tofacitinib is an oral Janus kinase inhibitor approved for the treatment of psoriatic arthritis (PsA). It provides an alternative option for patients who have had an inadequate response and tolerance to other disease modifying antirheumatic drugs (DMARDs). It has demonstrated comparable efficacy to biologics, is effective in the management of treatment resistant disease, and is reported to improve enthesitis, dactylitis, and radiographic progression. Tofacitinib is also associated with an increased risk of serious infections, malignancy, and laboratory abnormalities. There is currently a large armamentarium of therapies for psoriatic arthritis, and choosing among treatments can be challenging. Due to this wide selection, a thorough assessment of psoriatic disease phenotype, patient preference, disease presentation, and comorbidities is critical. This review addresses key considerations in patient selection for the treatment of PsA with tofacitinib

Acrodermatitis continua of Hallopeau: clinical perspectives.

Acrodermatitis continua of Hallopeau (ACH) is a rare, sterile pustular eruption of one or more digits. The condition presents with tender pustules and underlying erythema on the tip of a digit, more frequently arising on a finger than a toe. As far as classification, ACH is considered a localized form of pustular psoriasis. The eruption typically occurs after local trauma or infection, but such a history is not always present and various other etiologies have been described including infectious, neural, inflammatory, and genetic causes. The natural progression of ACH is chronic and progressive, often resulting in irreversible complications such as onychodystrophy that can result in anonychia, as well as osteitis that can result in osteolysis of the distal phalanges. Because of the rarity of ACH, there have been no randomized controlled studies to evaluate therapies, resulting in an absence of standardized treatment guidelines. In clinical practice, a wide variety of treatments have been attempted, with outcomes ranging from recalcitrance to complete resolution. In recent years, the introduction of biologics has provided a new class of therapy that has revolutionized the treatment of ACH. Specifically, rapid and sustained responses have been reported with the use of anti-tumor necrosis factor agents like infliximab, adalimumab, and etanercept; IL-17 inhibitors like secukinumab; IL-12/23 inhibitors like ustekinumab; and IL-1 inhibitors like anakinra. Nevertheless, there remains a considerable need for more research into treatment for the benefit of individual patients with ACH as well as for the clinical knowledge gained by such efforts. The purpose of this review is to provide a comprehensive overview of the key features of ACH as well as a discussion of clinical management strategies for this unique and debilitating condition

Aquatic ecosystem response to climate, fire, and the demise of montane rainforest, Tasmania, Australia

The 2019/2020 southeast Australian fires ravaged the environment and threatened endemic vegetation groups, including the Tasmanian montane rainforest. This endemic biome, dominated by Athrotaxis species and Nothofagus gunnii, is declining due to increased aridity and fire frequency (years between fire events). Little is known about the impacts of fire and the montane rainforest decline on aquatic ecosystems in the region, yet aquatic ecosystems are strongly reliant on the terrestrial environment for nutrients and humic acids to support their ecosystem health. Here we evaluate the impacts of repeat fires and decline in montane rainforest species on the aquatic ecosystem of Lake Osborne, Tasmania, Australia, during the past 6500 years using a palaeoecological approach. Newly obtained data including organic carbon (δ13C) and nitrogen (δ15N) isotope composition, visible reflectance spectroscopy (R650–700 as a measure of chlorophyll a and derivatives), and diatom remains are compared with previously published charcoal, pollen, micro-X-Ray fluorescence, magnetic susceptibility, and organic carbon and nitrogen elemental data. Results suggest repeat fire occurrence from 6300 to 4200 years ago caused a decline in montane rainforest, increased erosion, and high aquatic productivity, pH, and conductivity (as indicated by diatoms Epithemia species, Fragilaria type species, Karayevia clevei, and Tabellaria flocculosa). Recovery of montane rainforest due to low fire activity from 4200 to 3000 years ago caused an anomalous assemblage of diatoms dominated by Aulacoseira species along with a less productive aquatic environment (inferred from low δ13C and δ15N, R650–700, and percent macrophytes and algal remains), higher lake level and clearer waters at Lake Osborne. A fire event 2500 years ago caused the removal of montane rainforest and a shift to Eucalyptus dominance within the catchment, leading to an increase in aquatic productivity, and a shift toward benthic diatom taxa dominant in clearer waters-characteristic of eastern Tasmanian sites. The aquatic environment at Lake Osborne for the past 6500 years has responded to increased fire frequency, declines in the montane rainforest and climate change. Fire disturbance removes montane rainforest, burns the underlying soils resulting in erosion of terrigenous material and increases aquatic productivity with communities that favour higher conductivity and low light conditions. With projected increases in fire frequency and loss of rainforest, freshwater ecosystems are vulnerable to changes in physical characteristics, productivity, species assemblages, and ecological resilience

Factors Influencing Sleep Difficulty and Sleep Quantity in the Citizen Pscientist Psoriatic Cohort.

IntroductionSleep is essential for overall health and well-being, yet more than one-third of adults report inadequate sleep. The prevalence is higher among people with psoriasis, with up to 85.4% of the psoriatic population reporting sleep disruption. Poor sleep among psoriasis patients is particularly concerning because psoriasis is independently associated with many of the same comorbidities as sleep dysfunction, including cardiovascular disease, obesity, and depression. Given the high prevalence and serious consequences of disordered sleep in psoriasis, it is vital to understand the nature of sleep disturbance in this population. This study was designed to help meet this need by using survey data from Citizen Pscientist, an online patient portal developed by the National Psoriasis Foundation.MethodsOur analysis included 3118 participants who identified as having a diagnosis by a physician of psoriasis alone or psoriasis with psoriatic arthritis. Demographic information, psoriasis severity and duration, sleep apnea status, smoking and alcohol consumption, itch timing, and sleep characteristics were included. Two separate multivariate logistic regression models in STATA were used to determine whether the presence of psoriatic arthritis, age, gender, body mass index, comorbid sleep apnea, psoriasis severity, timing of worst itch, smoking status, or high-risk alcohol consumption were associated with sleep difficulty or low sleep quantity, defined by the American Academy of Sleep Medicine as less than 7 h of sleep per night on average.ResultsResults from the multivariate logistic regressions found that sleep difficulty was associated with psoriatic arthritis (OR 2.15, 95% CI [1.79-2.58]), female gender (2.03 [1.67-2.46]), obese body mass index (BMI ≥ 30) (1.25 [1.00-1.56]), sleep apnea (1.41 [1.07-1.86]), psoriasis severity of moderate (1.59 [1.30-1.94]) or severe (2.40 [1.87-3.08]), and smoking (1.60 [1.26-2.02]). Low sleep quantity was associated with obese BMI (1.62 [1.29-2.03]), sleep apnea (1.30 [1.01-1.68]), psoriasis severity of moderate (1.41 [1.16-1.72]) or severe (1.40 [1.11-1.76]), and smoking (1.62 [1.31-2.00]). Sleep difficulty and low sleep quantity were not associated with age, alcohol consumption, or timing of worst itch.ConclusionThese results are potentially meaningful in several aspects. We identify an important distinction between sleep difficulty and sleep quantity in psoriatic disease, whereby having psoriatic arthritis and being female are each associated with sleep difficulty despite no association with low sleep quantity. Furthermore, there is conflicting evidence from prior studies as to whether psoriasis severity is associated with sleep difficulty, but this well-powered, large study revealed a strong, graded relationship between psoriasis severity and both sleep difficulty and low sleep quantity. Overall, our results show that both sleep difficulty and low sleep quantity were associated with multiple factors in this analysis of a large psoriatic cohort. These findings suggest that dermatologists may gather clinically useful information by screening psoriatic patients for trouble sleeping and low sleep quantity to identify potential comorbidities and to more effectively guide disease management

Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial

Importance Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results. Objective To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes. Design, Setting, and Participants Multicenter (26 pediatric endocrinology clinics), double-blind, placebo-controlled randomized clinical trial involving 140 adolescents aged 12.1 to 19.6 years (mean [SD] 15.3 [1.7] years) with mean type 1 diabetes duration 7.0 (3.3) years, mean body mass index (BMI) 94th (4) percentile, mean total daily insulin 1.1 (0.2) U/kg, and mean HbA1c 8.8% (0.7%). Interventions Randomization to receive metformin (n = 71) (≤2000 mg/d) or placebo (n = 69). Main Outcomes and Measures Primary outcome was change in HbA1c from baseline to 26 weeks adjusted for baseline HbA1c. Secondary outcomes included change in blinded continuous glucose monitor indices, total daily insulin, BMI, waist circumference, body composition, blood pressure, and lipids. Results Between October 2013 and February 2014, 140 participants were enrolled. Baseline HbA1c was 8.8% in each group. At 13-week follow-up, reduction in HbA1c was greater with metformin (−0.2%) than placebo (0.1%; mean difference, −0.3% [95% CI, −0.6% to 0.0%]; P = .02). However, this differential effect was not sustained at 26-week follow up when mean change in HbA1c from baseline was 0.2% in each group (mean difference, 0% [95% CI, −0.3% to 0.3%]; P = .92). At 26-week follow-up, total daily insulin per kg of body weight was reduced by at least 25% from baseline among 23% (16) of participants in the metformin group vs 1% (1) of participants in the placebo group (mean difference, 21% [95% CI, 11% to 32%]; P = .003), and 24% (17) of participants in the metformin group and 7% (5) of participants in the placebo group had a reduction in BMI z score of 10% or greater from baseline to 26 weeks (mean difference, 17% [95% CI, 5% to 29%]; P = .01). Gastrointestinal adverse events were reported by more participants in the metformin group than in the placebo group (mean difference, 36% [95% CI, 19% to 51%]; P < .001). Conclusions and Relevance Among overweight adolescents with type 1 diabetes, the addition of metformin to insulin did not improve glycemic control after 6 months. Of multiple secondary end points, findings favored metformin only for insulin dose and measures of adiposity; conversely, use of metformin resulted in an increased risk for gastrointestinal adverse events. These results do not support prescribing metformin to overweight adolescents with type 1 diabetes to improve glycemic control