Secukinumab in Pediatric Patients with Plaque Psoriasis: Pooled Safety Analysis from Two Phase 3 Randomized Clinical Trials

peer reviewe

Prognostic value of circulating tumor cells and disseminated tumor cells in patients with ovarian cancer: a systematic review and meta-analysis

Recent studies have shown diagnostic and prognostic values of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in various cancers, including ovarian cancer. We aimed to evaluate the association of CTCs and/or DTCs with the clinical outcomes of ovarian cancer. Clinical studies of CTCs/DTCs of ovarian cancer were included for systematic review and meta-analysis. A total of 236 studies were screened but only 16 qualified studies with 1623 subjects were included. Odds ratio (OR) showed CTCs/DTCs were not significantly associated with serous carcinoma (OR = 0.71 [0.49, 1.05]), lymph node metastasis (OR 1.14 [0.67, 1.93]), and residual disease (OR 1.45 [0.90, 2.34]); but significantly associated with advanced tumor staging (OR = 1.90 [1.02, 3.56]). The overall pooled hazard ratio (HR) of CTCs/DTCs on OS and PFS/DFS was 1.94 [1.56– 2.40] and 1.99 [1.59–2.50], respectively. Subgroup analyses revealed that CTCs were significantly associated OS (HR 1.97 [1.50-2.58]) and PFS/DFS (HR 2.52 [1.83-3.48]), while DTCs was significantly associated OS (HR 1.89 [1.33, 2.68]) and PFS/DFS (HR 1.60 [1.17, 2.19]). Meta-analysis showed strong relationship of CTCs/DTCs with advanced staging, treatment response and poor prognosis in patients with ovarian cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-015-0168-9) contains supplementary material, which is available to authorized users

Artificial intelligence (AI): multidisciplinary perspectives on emerging challenges, opportunities, and agenda for research and practice

As far back as the industrial revolution, great leaps in technical innovation succeeded in transforming numerous manual tasks and processes that had been in existence for decades where humans had reached the limits of physical capacity. Artificial Intelligence (AI) offers this same transformative potential for the augmentation and potential replacement of human tasks and activities within a wide range of industrial, intellectual and social applications. The pace of change for this new AI technological age is staggering, with new breakthroughs in algorithmic machine learning and autonomous decision making engendering new opportunities for continued innovation. The impact of AI is significant, with industries ranging from: finance, retail, healthcare, manufacturing, supply chain and logistics all set to be disrupted by the onset of AI technologies. The study brings together the collective insight from a number of leading expert contributors to highlight the significant opportunities, challenges and potential research agenda posed by the rapid emergence of AI within a number of domains: technological, business and management, science and technology, government and public sector. The research offers significant and timely insight to AI technology and its impact on the future of industry and society in general

Characterization of T cell clones derived from a mixed lymphocyte reaction

Monoclonal T cells with distinct function and specificity were isolated and characterized. The method used to obtain monoclonal T cells involved four steps: First, C57BL/6 spleen cells were cultured with irradiated D-BA/2 spleen cells in vitro. Second, the activated C57BL/6 cells were maintained for several months in a medium containing T Cell Growth Factor(TCGF) , irradia'ted DBA/2 and C57BL/6 spleen cells. Third, the activated cells were cloned in microtiter wells by limiting dilution. Fourth, wells detected to contain growth were expanded and tested for their functional activities. Using this method, three classes of clones were derived. The first class of clones were cytotoxic clones, presumably of H-2[sup b] phenotype, which have different specificities against foreign histocompatibility antigens. The second class of clones was an H-2[sup b], Thy 1⁺, Lyt 2⁺ and Lyt 1 low cytotoxic clone whose specificity was against cells carrying H-2D[sup b], antigens. The supernatant derived from this clone nonspecifically supressed CTL generation and mitogen activation, but was weakly toxic in the ⁵¹Cr release assay. The third class of clones was an H-2[sup d], Thy 1⁺ Lyt 1⁻ and Lyt 2⁻ clone which helped augment the CTL responses of cells carrying the H-2D[sup b] antigens. This clone required accessory cells for its helper function and was effective only when added during the early phase of the CTL response. The supernatant derived from this clone exhibited the same properties as the clone and acted in synergy with TCGF in the augmentation of CTL responses.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat

Characterization of an antigen-specific T helper cell clone and its products

A T helper cell clone, referred to as clone 9, was derived from an allogeneic mixed lymphocyte culture. Clone 9, as well as supernatant factor(s) derived from it, could help the cytotoxic T lymphocyte (CTL) responses of H-2 Db (Db) responder cells to alloantigens, or they could help the CTL responses of non- Db responder cells to Db alloantigens. Clone 9 cells or their factor(s) were active only when added during the first 24 hours of a five-day culture period. Clone 9 or its factor(s) could also synergize with interleukin-2 (IL-2)-containing medium in mounting cytotoxic responses to alloantigens. The helper activity in clone 9 supernatant was not due to IL-2 and it was specifically absorbed out by Db -spleen cells. The characterization of the Db -specific helper factor(ASHF) was facilitated by the isolation of a T hybridoma clone (clone 25), obtained from fusion of clone 9 cells with the T cell lymphoma, BW5147, and a B cell hybridoma that produced an IgM monoclonal antibody (clone 30 IgM) which bound ASHF. An additional monoclonal antibody (F23.1), which recognizes a determinant of the Vβ8 family of the T cell receptor, was also particularly useful for the characterization of ASHF. Analysis with these reagents showed that both clone 30 IgM and F23.1 immunoadsorbents could retain ASHF activity. Preabsorption of the ASHF with Db spleen cells prior to affinity purification over a clone 30 IgM column resulted in the absorption of Db-specific helper activity as well as the loss of a 50,000 molecular weight (MW) band on SDS-PAGE under reducing conditions. Furthermore, affinity purification of ASHF over the F23.1 immunoadsorbent, but not an irrelevant monoclonal antibody (mAb) column, also yielded a 50,000 MW molecule. Taken together, these findings suggest that the 50,000 MW molecule is a component of the ASHF and it is intimately related to the B chain of the T-cell receptor. The mode of action of clone 9 and its products in the induction bfCTL responses was also investigated. It was found that clone 9 and ASHF could help CTL responses by inducing IL-2 production in B6-stimulated cultures. In addition to ASHF, clone 9 cells also produced an additional factor(s) which participated in the induction of CTL responses. This additional factor(s) was referred to as IL-X. IL-X synergized with excess human recombinant IL-2 in the activation of CTL precursors (CTL-P) in the absence of antigenic stimulation. A model which involves the participation of ASHF, T helper cells, IL-2 and IL-X in the induction of CTL responses is proposed.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat

Safety and Efficacy of VP-102 (Cantharidin, 0.7% w/v) in Molluscum Contagiosum by Body Region: Post hoc Pooled Analyses from Two Phase III Randomized Trials.

Trial registration>ClinicalTrials.gov identifier nos. NCT03377790 (for CAMP-1) and NCT03377803 (for CAMP-2).BackgroundVP-102 is drug-device combination product containing cantharidin (0.7% w/v) and has undergone Phase III clinical trials for the treatment of molluscum contagiosum (molluscum). Efficacy and safety may differ by body region due to variable skin anatomy.ObjectiveWe investigated the pooled safety and efficacy of VP-102 by affected body region.MethodsIndividuals at least two years of age with molluscum were randomized to topical VP-102 or vehicle once every 21 days until clear (maximum of four applications). Participants were assigned to body region groups where lesions were present at baseline. Body region lesion counts were recorded at each visit. Efficacy was measured by the percentage of participants with complete clearance of lesions by region. Pre-specified adverse events (AEs) were analyzed for those treated in the region on that visit.ResultsParticipants had a mean of two regions affected at baseline. Complete clearance was significantly higher in the VP-102-treated group than with vehicle application in all regions at the last visit (P<0.01 for each region). The incidence of pre-specified AEs was consistent across regions. However, these analyses were post hoc, and individual lesions were not tracked for efficacy.ConclusionVP-102 treatment shows consistent safety and efficacy across molluscum body regions

A2310 and A2311 Padiatrics Post-Hoc Safety Analysis Abstract

Plaque psoriasis affects adults and children. Secukinumab, a fully human monoclonal anti-interleukin-17A antibody, has proven efficacious in adults in the long-term treatment of multiple manifestations of psoriatic disease, with a favorable safety profile. Long-term pooled safety data for secukinumab in adult patients with moderate to severe plaque psoriasis have been reported earlier. Here, we report a pooled safety analysis from two phase 3 studies up to 52 weeks in pediatric patients with moderate to severe plaque psoriasis

Impact of Topical Vehicles and Cutaneous Delivery Technologies on Patient Adherence and Treatment Outcomes in Acne and Rosacea

OBJECTIVE: Topical therapies remain the mainstay in treating patients with acne and rosacea. However, emerging real-world evidence demonstrates that desired treatment outcomes might not be achieved if patient satisfaction and adherence are low. Poor tolerability of active drug(s) and vehicle components and/or the drug delivery system could negatively influence adherence. Additionally, adherence might be lower with complex treatment regimens involving the application of multiple topical formulations. Optimizing vehicle tolerability and simplifying regimens that use fixed-dose combinations may improve treatment outcomes, better patient satisfaction, and reduce overall treatment costs. This qualitative review discusses several innovative drug delivery technologies and formulations aimed at improving patient satisfaction and adherence. METHODS: The authors conducted a search of current and emerging topical drug delivery technologies used in clinical studies, reviewed primary literature on the chemical characteristics of topical dosage forms, and compared the impacts on treatment outcomes for acne and rosacea. RESULTS: This article provides insight into innovative vehicles and drug delivery systems that have emerged allowing for fixed-dose combinations of incompatible active drugs and improving the tolerability of historically irritative active ingredients. LIMITATIONS: Further research is needed to fully highlight the impact of patient satisfaction and modern topical formulations on adherence and treatment outcomes. CONCLUSION: Drug microencapsulation is a delivery technology that has enabled development of a topical fixed-dose combination of benzoyl peroxide and tretinoin preventing the oxidation of tretinoin by benzoyl peroxide and improving the tolerability of the active ingredients

Consensus on Neonatal Through Preadolescent Acne

Acne vulgaris is the most common dermatological disorder. Pediatric acne may be a manifestation of the underlying pathology and can occur in the first weeks, months, or years of life. Acne in childhood can be categorized by age and pubertal status. An expert panel of pediatric dermatologists and dermatologists developed a consensus paper on neonatal through preadolescent acne, providing information on differential diagnosis, prevention, treatment, and maintenance of the condition. A systematic literature review explored present clinical guidelines, treatment options, and therapeutic approaches addressing neonatal through preadolescent acne. The information from the literature searches was used together with the panel's expert opinion and experience to adopt consensus statements following established standards. The panel members reached unanimous consensus on seven statements addressing the various age categories of pediatric acne: neonatal acne: birth to ≤ 8 weeks; infantile acne: 8 weeks to ≤1 year; mid-childhood acne: 1 year to <7 years; preadolescent acne: ≥7 to 12 years; adolescent acne: ≥12 to 19 years or after menarche for girls. Health care providers treating children need to pay more attention to pediatric acne and should monitor the risk of endocrine-associated abnormalities, especially in mild-childhood acne. When prescribing acne treatment, newer medications approved for use in children older than nine years of age may offer a suitable option. The differential diagnosis of pediatric acne, as well as its treatment and maintenance, requires much more attention and consideration from health care providers treating children. J Drugs Dermatol. 2020;19(6):592-600. doi:10.36849/JDD.2020.5065

Machine Learning for Direct Marketing Response Models: Bayesian Networks with Evolutionary Programming

Machine learning methods are powerful tools for data mining with large noisy databases and give researchers the opportunity to gain new insights into consumer behavior and to improve the performance of marketing operations. To model consumer responses to direct marketing, this study proposes Bayesian networks learned by evolutionary programming. Using a large direct marketing data set, we tested the endogeneity bias in the recency, frequency, monetary value (RFM) variables using the control function approach; compared the results of Bayesian networks with those of neural networks, classification and regression tree (CART), and latent class regression; and applied a tenfold cross-validation. The results suggest that Bayesian networks have distinct advantages over the other methods in accuracy of prediction, transparency of procedures, interpretability of results, and explanatory insight. Our findings lend strong support to Bayesian networks as a robust tool for modeling consumer response and other marketing problems and for assisting management decision making.direct marketing, Bayesian networks, evolutionary programming, machine learning, data mining