Current Issue : January - March Volume : 2018 Issue Number : 1 Articles : 5 Articles
Background: This systematic review aimed to assess inhaled drug delivery in mechanically ventilated patients or in\nanimal models. Whole lung and regional deposition and the impact of the ventilator circuit, the artificial airways\nand the administration technique for aerosol delivery were analyzed.\nMethods: In vivo studies assessing lung deposition during invasive mechanical ventilation were selected based on\na systematic search among four databases. Two investigators independently assessed the eligibility and the risk of\nbias.\nResults: Twenty-six clinical and ten experimental studies were included. Between 30% and 43% of nominal drug\ndose was lost to the circuit in ventilated patients. Whole lung deposition of up to 16% and 38% of nominal dose\n(proportion of drug charged in the device) were reported with nebulizers and metered-dose inhalers, respectively.\nA penetration index inferior to 1 observed in scintigraphic studies indicated major proximal deposition. However,\nsubstantial concentrations of antibiotics were measured in the epithelial lining fluid (887 (406ââ?¬â??12,819) Ã?¼g/mL of\namikacin) of infected patients and in sub-pleural specimens (e.g., 197 Ã?¼g/g of amikacin) dissected from infected\npiglets, suggesting a significant distal deposition. The administration technique varied among studies and may explain\na degree of the variability of deposition that was observed.\nConclusions: Lung deposition was lower than 20% of nominal dose delivered with nebulizers and mostly occurred in\nproximal airways. Further studies are needed to link substantial concentrations of antibiotics in infected pulmonary\nfluids to pulmonary deposition. The administration technique with nebulizers should be improved in ventilated\npatients in order to ensure an efficient but safe, feasible and reproducible technique....
Background. To report on the activity of high-dose prolonged-infusion ifosfamide (HDIFX) chemotherapy in a retrospective series\nof patients affected bymyxoid liposarcoma treated at Fondazione IRCCS Istituto Nazionale dei Tumori inMilan, Italy. Patients and\nMethods. Patients with an advanced myxoid liposarcoma treated with HDIFX (14 g/sqm, i.v., prolonged infusion of 14 days every\n28 days) as a single agent between May 2002 and April 2017 were retrospectively reviewed. All pathologic diagnoses were centrally\nreviewed and molecularly confirmed. Response was evaluated by RECIST, and survival functions were computed by the Kaplan-\nMeier method. Results. Eleven patients with advanced myxoid liposarcoma were treated with HDIFX (male/female = 9/2, median\nage 33 years, range 31ââ?¬â??75). Among these, 1/11 received HDIFX in first line, 5/11 in second line, 3/11 in third line, and 2/11 in fourth\nline for a median course number of 3 (range 2ââ?¬â??7). No RECIST objective responses were observed. Overall median progression-free\nsurvival was 1,9 months.Median overall survival was 37 months. At a median follow-up of 115 months, 1 patient is alive. Conclusions.\nIn this series of patients affected by advanced myxoid liposarcoma, chemotherapy with HDIFX was essentially inactive....
Purpose. To compare the therapeutic results of two radiotherapy (RT) dose schedules in combined temozolomide- (TMZ-)\nRT treatment in newly diagnosed glioblastoma (GB), according to the O(6)-methylguanine-DNA methyltransferase (MGMT)\nmethylation status. Material and Method. Patients received either standard (60Gy) or moderately escalated dose (70Gy)\nradiotherapy (RT) with concomitant and adjuvant TMZ between June 2006 and October 2013. We retrospectively evaluated the\ntherapeutic effectiveness of RT schedules in terms ofOverall Survival (OS) and Progression-Disease Free Survival (PDFS) analyzing\nthe MGMT methylation status. Results. One hundred and seventeen patients were selected for the present analysis. Seventy-two\nout of the selected cases received the standard RT-TMZ course (SDRT-TMZ) whereas the remaining 45 underwent the escalated\nschedule (HDRT-TMZ). The analysis according to theMGMT promoter methylation status showed that, in unmethylated-MGMT\nGB patients, HDRT-TMZ and SDRT-TMZ groups had differentmedian OS (...
Administeringmore than one treatmentmay increase Praziquantel cure and egg reduction rates, thereby hastening achievement of\nschistosomiasis transmission control. A total of 431 S. mansoni-infected schoolchildren were randomized to receive either a single\nor repeated 40mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing\nscale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%)\n(...
Background\nA standard low-dosing schedule of rituximab (RTX; 2ââ?¬â?°Ã?â??ââ?¬â?°500 mg or 1ââ?¬â?°Ã?â??ââ?¬â?°1000 mg) is as effective for active rheumatoid arthritis (RA) as the registered dose (2ââ?¬â?°Ã?â??ââ?¬â?°1000 mg). Moreover, several small uncontrolled studies suggest that even lower-dosed treatment with RTX also leads to good treatment response in patients with RA. Retreatment with such an ââ?¬Ë?ultra-lowââ?¬â?¢ dose RTX in patients who responded well to RTX induction treatment is of special interest, as long-term use of lower RTX doses may lead to shorter infusion duration, lower risk of adverse events and lower costs. However, the effect of ultra-low dose of RTX has not been investigated using a controlled trial of proper design and dimensions.\n\nMethods/Design\nREDO is an investigator driven six-month pragmatic, double-blind, randomised controlled non-inferiority trial on the effects of ultra-low-dose RTX (1ââ?¬â?°Ã?â??ââ?¬â?°500 or 1ââ?¬â?°Ã?â??ââ?¬â?°200 mg) compared to standard low dose (1ââ?¬â?°Ã?â??ââ?¬â?°1000 mg) in RA patients who are being retreated with RTX. A total of 140 RA patients, having reached low disease activity (DAS28CRPââ?¬â?°<ââ?¬â?°2.9) after the previous RTX infusion and DAS28CRPââ?¬â?°<ââ?¬â?°3.5 at moment of retreatment, are randomised in a ratio of 1:2:2 to 1ââ?¬â?°Ã?â??ââ?¬â?°1000 mg, 1ââ?¬â?°Ã?â??ââ?¬â?°500 mg or 1ââ?¬â?°Ã?â??ââ?¬â?°200 mg. The primary objective is testing non-inferiority of the ultra-low-dose vs. standard low-dose RTX, by comparing mean change in DAS28CRP from baseline to six months to the non-inferiority margin of 0.6. Secondary outcomes over the same period are: function; quality of life; safety; costs; and pharmacokinetics and dynamics as process measures.\n\nDiscussion\nThis study protocol shares characteristics of both early dose finding trials as well as late pragmatic clinical studies. Several choices in the design of this trial are described and possible consequences for RA treatment and expected biosimilar introduction are discussed....
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