Diabetes and obesity burden and improvements in cardiometabolic parameters in patients with psoriasis or psoriatic arthritis receiving apremilast in a real-world setting.

Introduction: Patients with psoriasis and psoriatic arthritis have a higher prevalence of cardiometabolic comorbidities compared to the general population. Clinical data suggest apremilast may reduce weight and glycated hemoglobin (HbA1c).

Objective: To describe changes in cardiometabolic parameters among patients with psoriasis and psoriatic arthritis newly treated with apremilast by prediabetes/diabetes or obesity status.

Treatment Patterns and Negative Health Outcomes in Palmoplantar Pustulosis Patients in Germany and the US.

Introduction: Limited information exists on the epidemiology, treatment, and burden of palmoplantar pustulosis (PPP) and defining the optimal course of treatment remains challenging without approved targeted treatments in most countries. Here, we describe the clinical and demographic characteristics, treatments received, and negative health outcomes experienced among patients with PPP in the United States (US) and Germany.

Methods: Retrospective cohort study between 2016 and 2021 using data from the US Merative™ MarketScan® Research Database and IQVIA™ German Disease Analyzer.

Redefining Disease Severity with Special Area Involvement and Reflecting on Treatment Patterns in a Real-World Psoriasis Population.

Background: The International Psoriasis Council (IPC) recommends an approach that considers body surface area (BSA), involvement in special areas, and treatment history for classifying patients as candidates for topical or systemic treatment. This study aimed to quantify the burden of psoriasis by describing BSA distribution, special area involvement, and treatments in a real-world population.

Methods: This retrospective cohort study included patients with psoriasis from the Optum deidentified Electronic Health Records database with a BSA value (< 3%, 3-10%, and > 10%) recorded between 1 March 2014 and 1 September 2020.

Apremilast Adherence and Persistence in Patients with Psoriasis and Psoriatic Arthritis in the Telehealth Setting Versus the In-person Setting During the COVID-19 Pandemic.

Introduction: Limited access to healthcare during the COVID-19 pandemic prompted patients to seek care using telehealth. In this study, we assessed whether treatment patterns differed for patients with psoriasis (PsO) or psoriatic arthritis (PsA) initiating apremilast by either a telehealth or an in-person visit.

Methods: We estimated adherence and persistence among US patients in the Merative© MarketScan© Commercial and Supplemental Medicare Databases who newly initiated apremilast between April and June 2020, categorized by the type of visit (telehealth or in-person) when apremilast was first prescribed.

Characteristics and outcomes of patients with psoriasis treated with apremilast in the real-world in Austria - results the APPRECIATE study.

Background: Apremilast, an oral phosphodiesterase 4 inhibitor, is approved in the European Union for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients refractory or contraindicated to or intolerant of other systemic therapies.

Objectives: The APPRECIATE study assessed apremilast use in real-world practice and its clinical value to physicians and patients. APPRECIATE was a multinational, observational, retrospective, cross-sectional study.

Safety of Apremilast in Patients with Psoriasis and Psoriatic Arthritis: Findings from the UK Clinical Practice Research Datalink.

Introduction: This real-world safety analysis was requested by the European Medicines Agency following approval of apremilast, an oral treatment for psoriasis or psoriatic arthritis.

Objective: We aimed to compare incidence rates of adverse events of special interest identified a priori, in patients receiving apremilast with those receiving other systemic treatments for psoriasis or psoriatic arthritis.

Methods: This 5-year cohort study was conducted in Clinical Practice Research Datalink GOLD between January 2015 and June 2020.

Real-World Experience of Patient-Relevant Benefits and Treatment Satisfaction with Apremilast in Patients with Psoriasis: An Analysis of the APPRECIATE Study.

Introduction: In the real-world APPRECIATE study (NCT02740218), most patients with psoriasis demonstrated notable improvements on disease severity measures and reported clinically meaningful treatment benefits with apremilast.

Objective: We aim to further describe patient-relevant needs and benefits and patient satisfaction with apremilast, including subgroup analyses based on patient characteristics.

Methods: APPRECIATE, a multinational, retrospective, cross-sectional study, enrolled patients with chronic plaque psoriasis who started apremilast according to the European label.

Enhancing the reliability and throughput of neurosphere culture on hydrogel microwell arrays.

The neurosphere assay is the standard retrospective assay to test the self-renewal capability and multipotency of neural stem cells (NSCs) in vitro. However, it has recently become clear that not all neurospheres are derived from a NSC and that on conventional cell culture substrates, neurosphere motility may cause frequent neurosphere "merging" [Nat Methods 2006;3:801-806; Stem Cells 2007;25:871-874]. Combining biomimetic hydrogel matrix technology with microengineering, we developed a microwell array platform on which NSC fate and neurosphere formation can be unequivocally attributed to a single founding cell.

Conventional protein kinase C isoforms mediate neuroprotection induced by phorbol ester and estrogen.

Rapid signal transduction pathways play a prominent role in mediating neuroprotective actions of estrogen in the CNS. We have previously shown that estrogen-induced neuroprotection of primary cerebrocortical neurons from beta-amyloid peptide (Abeta) toxicity depends on activation of protein kinase C (PKC). PKC activation with phorbol-12-myristate-13-acetate (PMA) also provides neuroprotection in this paradigm.

Neuroprotective properties of selective estrogen receptor agonists in cultured neurons.

To investigate the role of the estrogen receptor (ER) in mediating neuroprotection, the neuroprotective profiles of selective ER agonists for ERalpha and ERbeta, propylpyrazole triol (PPT) and 2,3-bis(4-hydroxyphenyl) proprionitrile (DPN), respectively, were compared to that of 17beta-estradiol and 17alpha-estradiol in primary neuron cultures challenged by beta-amyloid toxicity. All compounds were found to be neuroprotective in an ER-dependent manner. However, protein kinase C (PKC) inhibition completely blocked the protective effects of 17beta-estradiol and 17alpha-estradiol and significantly attenuated PPT but not DPN neuroprotection.

The synthetic estrogen 4-estren-3 alpha,17 beta-diol (estren) induces estrogen-like neuroprotection.

Estrogen has demonstrated neuroprotective properties, which may underlie the observed preventive effect of estrogen-based hormone therapy (HT) against the development of neurodegenerative disorders such as Alzheimer's disease. Deleterious side effects of HT have increased efforts to develop safer compounds that selectively reproduce beneficial estrogen actions. Recently, 4-estren-3 alpha,17 beta-diol (estren) was identified as having estrogen agonist properties in bone, without significantly stimulating growth of reproductive tissues.

Estrogen activates protein kinase C in neurons: role in neuroprotection.

It has been previously demonstrated that estrogen can protect neurons from a variety of insults, including beta-amyloid (Abeta). Recent studies have shown that estrogen can rapidly modulate intracellular signaling pathways involved in cell survival. In particular, estrogen activates protein kinase C (PKC) in a variety of cell types.