Among non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97-99% with 12week, multi-targeted OBV/PTV/r+DSV±RBV regimens and 66-82% with 24-48 total weeks of TPV+PegIFN/RBV. OBV/PTV/r+DSV±RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events.

In this study, ombitasvir and ABT-450/r ± RBV regimens were generally well-tolerated. Sustained virologic response was achieved in most patients with HCV genotype 1 or 2 infection, but low SVR rates were observed in HCV genotype 3-infected patients.

Oral folate fortification has been successful in many developed nations, however, developing countries still face low compliance and high incidence of folate deficiency associated with low birth weight infants and preterm deliveries. We report safe and efficient approach for transdermal systemic folate delivery using fluidising liposomes (120 ± 4 nm) stabilised within 3D matrix of naturally occurring cosmetic bases: Fuller’s earth and henna with room temperature stability. The proof of stratum corneum fluidisation was established ex-vivo by Langmuir-Blodgett film, FTIR and confocal imaging in rat skin. In-vivo topical application in rats showed 11-fold increase in plasma folate within 2 hr, confirming systemic delivery through skin. Efficacy study in folate deficient rats over 4 weeks showed significantly higher plasma levels compared to oral delivery with significant skin depot. Sub-acute toxicity studies in rats at 750-fold higher doses showed safety after 4 weeks daily application. Primary irritation patch test on 25 healthy human volunteers proved non-irritant nature of the nutricosmetics. The technology is first demonstration of transdermal folate fortification with nanosized liposome incorporated in cosmetics, without synthetic surfactants/ethanol or need of external energy. The platform technology opens the possibility of delivering multiple nutrients systemically through skin and can be scaled for affordable community fortification.

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Skin is the outermost and largest protective covering of the body. The uppermost layer of the skin, stratum corneum also called the horny layer is composed of keratin-filled cells covered by a lipid matrix which shields the skin from physical and chemical entrants. The lipid lamellar structure comprises of ceramides, cholesterol, fatty acids and proteins. Chemical enhancers that mimic the lamellar chemistry, reversibly fluidize the latter can be utilized for enhancing transport of cargo across the epidermis into the dermis. This review deals with the stratum corneum chemistry, mechanisms to modulate its packing with the aid of chemical enhancers, biophysical techniques for characterization and applications in the design of nature-inspired biocompatible lipid nanostructures for transdermal delivery of drugs and bioactive agents.

Background:Methotrexate (MTX) is often used as first-line therapy for patients (pts) with psoriatic arthritis (PsA) despite limited efficacy and data on appropriate dosage. Minimal Disease Activity (MDA) is suggested as an optimal treat-to-target outcome. Biologic disease-modifying antirheumatic drugs (bDMARDs) have demonstrated improved outcomes (including MDA rates) over MTX. However, more data are needed to define the optimal timing of bDMARD initiation and characterize efficacy of MTX dose escalation, to achieve optimal outcomes.Objectives:To compare achievement of MDA between adding adalimumab (ADA) vs escalating MTX dose in PsA pts with inadequate disease control after initial MTX therapy.Methods:The open-label, 2-part CONTROL study enrolled bDMARD-naive adult pts with active PsA (not in MDA at screening and ≥3 tender and ≥3 swollen joints) despite MTX 15 mg every wk (ew) for ≥4 wks. Pts were randomized to ADA 40 mg every other wk + MTX 15 mg (ADA+MTX) or escalated MTX to 20–25 mg ew or highest tolerable dose during 16-wk part 1 (Fig 1). The primary endpoint was achievement of MDA, defined as fulfilling ≥5 of the 7 criteria: tender joint count 68 (TJC68) ≤1, swollen joint count 66 (SJC66) ≤1, Psoriasis Area Severity Index (PASI) ≤1 or body surface area (BSA) ≤3%, pt’s pain (visual analogue scale [VAS] 0–100) ≤15, Pt’s Global Assessment of disease activity (PtGA) VAS ≤20, Health Assessment Questionnaire Disability Index (HAQ-DI) ≤0.5 and tender entheseal points (0–8) ≤1. Key secondary efficacy endpoints were achievement of ACR20 and PASI75 and change from baseline in HAQ-DI and Leeds Enthesitis Index (LEI) at wk 16.Results:Overall, 246 pts were randomized; 245 received treatment (ADA+MTX, n=123; escalated MTX, n=122); 117 (95%) pts and 110 (90%) pts, respectively, completed part 1. Baseline characteristics were similar between groups (Table). During part 1, the average dose of MTX was 21.8 mg/wk (55% on oral MTX) in the escalated MTX group. Significantly higher proportion of pts in ADA+MTX (42%) vs escalated MTX (13%) group achieved MDA at wk 16 (non-responder imputation [NRI]; difference [95% CI] 28% [18%–39%];P<0.001;Fig 2). Observed case analysis confirmed the NRI analysis. Lower MDA rates at wk 16 were observed in the escalated MTX arm regardless of prior MTX duration (Fig 2). Significant improvements in key secondary endpoints were also observed with ADA+MTX vs escalated MTX (allP<0.05;Fig 2). In part 1, the proportion of patients with adverse events was similar between groups (ADA+MTX, 62% vs escalated MTX, 57%); no opportunistic infections, tuberculosis, malignancies, or deaths were reported during part 1.Conclusion:A significantly higher proportion of pts achieved MDA at wk 16 after introducing ADA compared with escalating MTX dose; higher rates were observed regardless of prior MTX duration. Significantly higher responses in musculoskeletal, skin, and quality of life measures were observed with ADA+MTX vs escalated MTX. No new safety signals with ADA were identified in this pt population.Table 1.Baseline DemographicsCharacteristics, mean (SD)ADA+MTXn=123Escalated MTXn=122Female, n (%)64 (52.0)59 (48.4)Age, y51.4 (12.2)48.8 (12.7)BSA >3%, n (%)74 (60.2)78 (63.9)Pt pain63.7 (19.5)62.3 (20.9)PtGA65.0 (19.9)62.9 (20.9)HAQ-DI1.2 (0.6)1.2 (0.7)LEI + plantar count3.5 (2.1)3.5 (2.1)Disclosure of Interests:Laura C Coates: None declared, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai, Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Erin McDearmon-Blondell Shareholder of: AbbVie, Employee of: AbbVie, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Liang Chen Shareholder of: AbbVie, Employee of: AbbVie, Mudra Kapoor Shareholder of: AbbVie, Employee of: AbbVie, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

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Indian communities have the ancient cultural practice of gentle oil massage for infants which has been shown to play a beneficial role in neuro-motor development. The concept of incorporating nanosized liposomes of micronutrients (i.e., iron, folate, vitamin B12, and vitamin D) in the body oil leverages this practice for transdermal supplementation of essential micro-nutrients. This paper describes the experience of developing an intervention in the form of body oil containing nanosized liposomes of iron and micro-nutrients built on the social context of infant oil massage using a theory of change approach. The process of development of the intervention has been covered into stages such as design, decide and implement. The design phase describes how the idea of nanosized liposomal encapsulated micronutrient fortified (LMF) body oil was conceptualized and how its feasibility was assessed through initial formative work in the community. The decide phase describes steps involved while scaling up technology from laboratory to community level. The implementation phase describes processes while implementing the intervention of LMF oil in a community-based randomized controlled study. Overall, the theory of change approach helps to outline the various intermediate steps and challenges while translating novel technologies for transdermal nutrient fortification to community level. In our experience, adaptation in the technology for large scale up, formative work and pilot testing of innovation at community level were important processes that helped in shaping the innovation. Meticulous mapping of these processes and experiences can be a useful guide for translating similar innovations.