Browsing by Subject "COMBINATION THERAPY"

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  • Turner, Dan; Bishai, Jason; Reshef, Leah; Abitbol, Guila; Focht, Gili; Marcus, Dana; Ledder, Oren; Lev-Tzion, Raffi; Orlanski-Meyer, Esther; Yerushalmi, Baruch; Aloi, Marina; Griffiths, Anne M.; Albenberg, Lindsey; Kolho, Kaija-Leena; Assa, Amit; Cohen, Shlomi; Gophna, Uri; Vlamakis, Hera; Lurz, Eberhard; Levine, Arie (2020)
    Background: Alterations in the microbiome have been postulated to drive inflammation in IBD. In this pilot randomized controlled trial, we evaluated the effectiveness of quadruple antibiotic cocktail in addition to intravenous-corticosteroids (IVCSs) in acute severe colitis (ASC). Methods: Hospitalized children with ASC (pediatric ulcerative colitis activity index [PUCAI] >= 65) were randomized into 2 arms: the first received antibiotics in addition to IVCS (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin [IVCS+AB]), whereas the other received only IVCS for 14 days. The primary outcome was disease activity (PUCAI) at day 5. Microbiome was analyzed using 16S rRNA gene and metagenome. Results: Twenty-eight children were included: 16 in the AB + IVCS arm and 12 in the IVCS arm (mean age 13.9 +/- 4.1 years and 23 [82%] with extensive colitis). The mean day-5 PUCAI was 25 +/- 16.7 vs 40.4 +/- 20.4, respectively (P = 0.037). Only 3 and 2 children, respectively, required colectomy during 1-year follow-up (P = 0.89). Microbiome data at time of admission were analyzed for 25 children, of whom 17 (68%) had a predominant bacterial species (>33% abundance); response was not associated with the specific species, whereas decreased microbiome diversity at admission was associated with day-5 response in the IVCS arm. Conclusion: Patients with ASC have alterations in the microbiome characterized by loss of diversity and presence of predominant bacterial species. Quadruple therapy in addition to IVCS improved disease activity on day 5, but larger studies are needed to determine whether this is associated with improved long-term outcomes.
  • Khan, Daulat Haleem; Bashir, Sajid; Khan, Muhammad Imran; Figueiredo, Patricia; Santos, Hélder A.; Peltonen, Leena (2020)
    The aim of the present study was to prepare niosomal formulations for dual drug therapy of ceftriaxone sodium and poorly water-soluble rifampicin by the ecological probe sonication method. Pluronic L121 and Span 60 were used as surface active agents and the optimization of the composition was made with the aid of Design of Experiment (DoE) concept. Concentration levels of charge inducing agent, dicetylphosphate (DCP), and Pluronic L121 were studied as variables. Prepared niosomes with varying concentrations of DCP and Pluronic L121 resulted in small sized niosomes with sizes ranging from 165 nm to 893 nm. During the four weeks stability testing, the particle sizes of the empty niosomes were reduced, while the particle sizes of the drug loaded niosomes were increased very slightly. The optimized formulations resulted in stable niosomes with high drug entrapment efficiencies: entrapment efficiency was 99% for rifampicin and 96% for ceftriaxone. All the niosomal formulations showed faster in vitro drug release rates as compared to bulk drug formulations. In conclusion, ceftriaxone and rifampicin loaded niosomes prepared with Pluronic L121 and Span 60 resulted in stable, small sized niosomes with high drug entrapment efficiencies and improved drug release profiles.
  • Vaananen, Tuija; Vuolteenaho, Katriina; Kautiainen, Hannu; Nieminen, Riina; Mottonen, Timo; Hannonen, Pekka; Korpela, Markku; Kauppi, Markku J.; Laiho, Kari; Kaipiainen-Seppanen, Oili; Luosujarvi, Riitta; Uusitalo, Tea; Uutela, Toini; Leirisalo-Repo, Marjatta; Moilanen, Eeva; NEO-RACo Study Grp (2017)
    Objective YKL-40, a chitinase-like glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate auto-antigen in rheumatoid arthritis (RA). In the present study, we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aiming for early remission. Methods Ninety-nine patients with early DMARD-naive RA participated in the NEO-RACo study. For the first four weeks, the patients were treated with the combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone (FIN-RACo DMARD combination), and subsequently randomized to receive placebo or infliximab added on the treatment for further 22 weeks. Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay. Results At the baseline, plasma YKL-40 concentration was 57 +/- 37 ( mean +/- SD) ng/ml. YKL-40 was significantly associated with the disease activity score, interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks' treatment. The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment, and there was no further reduction when the tumour necrosis factor-alpha antagonist infliximab was added on the combination treatment. Conclusions High YKL-40 levels were found to be associated with disease activity in early DMARD-naive RA and during intensive treat-to-target therapy. The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission.
  • Glinatsi, Daniel; Heiberg, Marte S.; Rudin, Anna; Nordstrom, Dan; Haavardsholm, Espen A.; Gudbjornsson, Bjorn; Ostergaard, Mikkel; Uhlig, Till; Grondal, Gerdur; Horslev-Petersen, Kim; van Vollenhoven, Ronald; Hetland, Merete L. (2017)
    Background: New targeted therapies and improved treatment strategies have dramatically improved the outcomes of patients with rheumatoid arthritis (RA). However, it is unknown whether different early aggressive interventions can induce stable remission or a low-active disease state that can be maintained with conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy, and whether they differ in efficacy and safety. The Nordic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) study will assess and compare (1) the proportion of patients who achieve remission in a head-to-head comparison between csDMARD plus glucocorticoid therapy and three different biological DMARD (bDMARD) therapies with different modes of action and (2) two de-escalation strategies in patients who respond to first-line therapy. Methods/design: In a pragmatic, 80-160-week, multicenter, randomized, open-label, assessor-blinded, phase 4 study, 800 patients with early RA (symptom duration less than 24 months) are randomized 1: 1: 1: 1 to one of four different treatment arms: (1) aggressive csDMARD therapy with methotrexate + sulphasalazine + hydroxychloroquine + i. a. glucocorticoids (arm 1A) or methotrexate + prednisolone p.o. (arm 1B), (2) methotrexate + certolizumab-pegol, (3) methotrexate + abatacept, or (4) methotrexate + tocilizumab. The primary clinical endpoint is the proportion of patients reaching Clinical Disease Activity Index (CDAI) remission at week 24. Patients in stable remission over 24 consecutive weeks enter part 2 of the study earliest after 48 weeks. Patients not achieving sustained CDAI remission over 24 consecutive weeks, exit the study after 80 weeks. In part 2, patients are re-randomized to two different de-escalation strategies, either immediate or delayed (after 24 weeks) tapering, followed by cessation of study medication. All patients remain on stable doses of methotrexate. The primary clinical endpoint in part 2 is the proportion of patients in remission (CDAI Discussion: NORD-STAR is the first investigator-initiated, randomized, early RA trial to compare (1) csDMARD and three different bDMARD therapies head to head and (2) two different de-escalation strategies. The trial has the potential to identify which treatment strategy to apply in early RA to achieve the best possible outcomes for both patients and society.
  • SUCCESS Study Investigators; Färkkilä, Martti (2010)
    The benefit of extending treatment duration with peginterferon (PEG-IFN) and ribavirin (RI3V) from 48 weeks to 72 weeks for patients with chronic hepatitis C genotype 1 infection has not been well established. In this prospective, international, open-label, randomized, multicenter study, 1,428 treatment-nave patients from 133 centers were treated with PEG-IFN alfa-26 (1.5 mu g/kg/week) plus RBV (800-1,400 mg/day). Patients with detectable hepatii is C virus (HCV) RNA and a >= 2-logio drop in IICV RNA levels at week 12 (slow responders) were randomized 1:1 to receive 48 weeks (n = 86) or 72 weeks (n = 73) of treatment. Sustained virologic response (SVR) rates were 43% in slow responders treated for 48 weeks and 48% in slow responders treated for 72 weeks (P = 0.644). Relapse rates were similar in slow responders treated for 48 or 72 weeks (47% versus 33%, P = 0.169). The safety profile was similar in both treatment arms; serious adverse events leading to discontinuation of treatment were observed in 3.5% of slow responders treated for 48 weeks and 8.2% of those treated for 72 weeks. Among slow responders with a
  • Li, Wei; Liu, Zehua; Fontana, Flavia; Ding, Yaping; Liu, Dongfei; Hirvonen, Jouni Tapio; Almeida Santos, Helder (2018)
    In the past two decades, porous silicon (PSi) has attracted increasing attention for its potential biomedical applications. With its controllable geometry, tunable nanoporous structure, large pore volume/high specific surface area, and versatile surface chemistry, PSi shows significant advantages over conventional drug carriers. Here, an overview of recent progress in the use of PSi in drug delivery and cancer immunotherapy is presented. First, an overview of the fabrication of PSi with various geometric structures is provided, with particular focus on how the unique geometry of PSi facilitates its biomedical applications, especially for drug delivery. Second, surface chemistry and modification of PSi are discussed in relation to the strengthening of its performance in drug delivery and bioimaging. Emerging technologies for engineering PSi-based composites are then summarized. Emerging PSi advances in the context of cancer immunotherapy are also highlighted. Overall, very promising research results encourage further exploration of PSi for biomedical applications, particularly in drug delivery and cancer immunotherapy, and future translation of PSi into clinical applications.