Dose Of FP Research Articles

Influence of three microbial feed additives of Megasphaera elsdenii, Saccharomyces cerevisiae and Lactobacillus sp. on ruminal methane and carbon dioxide production, and biofermentation kinetics.

This study was performed to investigate the effects of Megasphaera elsdenii (Me), Saccharomyces cerevisiae (SC) and lactic acid bacteria (FP-Lactobacillus fermentum plus Lactobacillus plantarum) alone or in combination on biogas production and ruminal biofermentation parameter in a heterofermenter system. Eight treatments were evaluated; (i) control (without additive; CON); (ii) Me; (iii) SC; (iv) FP; (v) Me plus SC (MSC); (vi) Me plus FP (MFP); (vii) SC plus FP (SCFP) and (viii) Me plus SC plus FP (MSCFP). Doses of FP, Me and SC were 1·5×108 (CFU per ml), 1·5×108 (CFU per ml) and 1·4×107 (CFU 0·002-1 g), respectively. Biogas production in all time increased (P<0·05) by MSCFP than CON additive. The proportional methane (CH4 ) decreased (P<0·05) in MSCFP and FP, while carbon dioxide (CO2 ) was decreased (P<0·05) by SC compared MSCFP and MSC. The proportional CO2 decreased (P<0·05) by MSCFP and FP additive. The mean concentration of NH3 -N was not affected by treatments. Concentration of total volatile fatty acids and the percent of acetate and propionate was not affected by treatments. The highest (P<0·05) percent of butyrate and valerate were observed in MSCFP additive. The experiment showed that microbial additives of FP, SCFP and MSCFP reduced proportional CH4 and CO2 . Microbial additives of MFP and MSCFP had a sustainable positive efficiency on pH and volatile fatty acids and mitigate CH4 and CO2 . The use of microbial additives control on the ruminal pH (MFP) and improve VFA such as butyrate (MSC, MSCFP) and valerate (MSCFP) and reduce the greenhouse gases production showed a reduced risk of ruminal acidosis.

Parametric and kinetic investigations on segregated and mixed textile effluent streams using Moringa oleifera seed powders of different sizes

This study aimed at evaluating the Moringa oleifera (M. oleifera) seed powder for treatment of segregated (dye rich, DR; and starch rich, SR) and mixed wastewater (AM) streams of a textile industry. Two different sizes (<600 μm and <300 μm) of seed powders (coarse powder, CP; fine powder, FP) were prepared and characterized in terms of point of zero charge, swelling ratio, Fourier Transform Infrared Spectroscopy, X-ray diffraction analysis, and zeta potential measurements. The swelling ratio for CP and FP were observed as 38 and 42.6%, respectively. The pHzpc values were found to be varying between 5.5–6 for both powders. The effect of different operational parameters such as dose of coagulant, 1–8 g/L; sedimentation time, 30–360 min; coagulation-flocculation pH, 6–9 was investigated in this study, with respect to turbidity as performance indicator. The chemical oxygen demand (COD) and color measurements were done after the optimization of operational parameters. At optimized pH (DR, 6.5; SR, 7.5; AM, 8.0), the optimum dose of CP and FP were determined as 3, 3, 2 and 3, 2, 1 mg/L for DR, SR, and AM wastewater samples, respectively. With respect to residual turbidity, optimum sedimentation time was observed as 300, 240, 60, 60, 120, and 120 min for DR_CP, DR_FP, SR_CP, SR_FP, AM_CP, AM_FP, respectively. The sedimentation kinetic investigations revealed that turbidity removal follows second-order kinetics for both the studied coagulants. Statistical analysis revealed that CP has the potential of better color and COD removal, as compared to FP.

Treatment adherence and level of control in moderate persistent asthma in children and adolescents treated with fluticasone and salmeterol

ObjectiveThere is a scarcity of studies that assessed the association between adherence to combination therapy and asthma control in pediatric patients. The authors investigated the association between adherence to fluticasone propionate/salmeterol xinafoate combination‐metered aerosol and the level of asthma control in children. MethodsThis was a prospective observational study of 84 patients aged 5–16 years with moderate persistent asthma, who remained uncontrolled despite the use of 1000μg/day of inhaled nonextrafine‐hydrofluoric alkane‐beclomethasone dipropionate in the three months prior to study enrollment. Participants were prescribed two daily doses of FP (125μg)/salmeterol xinafoate (25μg) combination by metered aerosol/spacer for six months. Adherence rates were assessed using the device's dose counter after the 2nd, 4th, and 6th months of follow up. Asthma control was assessed using a simplified Global Initiative for Asthma 2014 Report classification. ResultsMean adherence rates after the second, fourth, and sixth months were 87.8%, 74.9%, and 62.1% respectively, for controlled asthma, and 71.7%, 56.0%, and 47.6% respectively, for uncontrolled asthma (all p‐values≤0.03). The proportion of children achieving asthma control increased to 42.9%, 67.9% and 89.3% after the 2nd, 4th and 6th months of follow‐up, respectively (p≤0.001). ConclusionAdherence rates between 87.8% in the 2nd month and 62.1% in the 6th month were strong determinants of asthma control.

Treatment adherence and level of control in moderate persistent asthma in children and adolescents treated with fluticasone and salmeterol

ObjectiveThere is a scarcity of studies that assessed the association between adherence to combination therapy and asthma control in pediatric patients. The authors investigated the association between adherence to fluticasone propionate/salmeterol xinafoate combination-metered aerosol and the level of asthma control in children. MethodsThis was a prospective observational study of 84 patients aged 5–16 years with moderate persistent asthma, who remained uncontrolled despite the use of 1000μg/day of inhaled nonextrafine-hydrofluoric alkane-beclomethasone dipropionate in the three months prior to study enrollment. Participants were prescribed two daily doses of FP (125μg)/salmeterol xinafoate (25μg) combination by metered aerosol/spacer for six months. Adherence rates were assessed using the device's dose counter after the 2nd, 4th, and 6th months of follow up. Asthma control was assessed using a simplified Global Initiative for Asthma 2014 Report classification. ResultsMean adherence rates after the second, fourth, and sixth months were 87.8%, 74.9%, and 62.1% respectively, for controlled asthma, and 71.7%, 56.0%, and 47.6% respectively, for uncontrolled asthma (all p-values≤0.03). The proportion of children achieving asthma control increased to 42.9%, 67.9% and 89.3% after the 2nd, 4th and 6th months of follow-up, respectively (p≤0.001). ConclusionAdherence rates between 87.8% in the 2nd month and 62.1% in the 6th month were strong determinants of asthma control.

Short and long‐term safety of MP29‐02*: a new therapy for the treatment of allergic rhinitis

Method 4022 patients (>=12 years old) were randomized into 4, 14-day double-blind, placebo-controlled SAR trials to receive MP29-02*, AZE, FP or placebo nasal sprays (all given as 1 spray/nostril bid). 612 patients (>=12 years old) were randomized into a 1-year, open-label, active-controlled, parallel-group chronic rhinitis trial to receive MP29-02* (1 spray/nostril bid) or FP nasal spray (2 sprays/nostril qd). For all studies the total daily dose of AZE and FP was 548 g and 200 μg respectively. Safety was assessed by incidence, type, and severity of adverse events, vital signs and nasal examination.

119

Introduction: Fondaparinux (FP, Arixtra®) is a preferred drug for venous thromboembolism (VTE) prophylaxis in critically ill patients. However, it is contraindicated in renal failure due to concerns of drug accumulation and increased bleeding risk. We sought to prospectively study FP for VTE prophylaxis in critically ill patients with renal failure at an extended dosing interval of 2.5 mg every 48 hours (q48h), instead of the usual q24h. Hypothesis: FP, dosed at an extended interval regimen of 2.5 mg q48h in critically ill patients with renal failure, results in satisfactory peak (Pk) and trough (Tr) plasma FP levels. Methods: ICU patients with renal failure (acute or chronic, creatinine clearance < 30 ml/min, +/- dialytic therapy) were prospectively studied while receiving FP, dosed at 2.5 mg q48h. FP Pk and Tr plasma levels were obtained around doses 1-5. FP levels (µg/ml) are expressed as mean±SD for each dose and as % within 2 SD of reported levels in patients with normal renal function (Pk=0.47 ± 0.2 and Tr=0.18 ± 0.1). Clinical efficacy was assessed with lower extremity venous duplex scans at study entry and completion. Major and minor bleeding events were recorded. Results: Twenty one patients were studied to date, 13 on dialytic therapy. Patients received an average of 5 doses of FP. Mean of FP Pk and Tr levels for doses 1-5 were 0.34 ± 0.1 (n=60) and 0.15 ± 0.1 (n=47), respectively. For doses 1, 3, and 5, Pk levels were 0.23 ± 0.1 (n=20), 0.37 ± 0.1 (n=9), and 0.42 ± 0.1 (n=6), and Tr levels were 0.11 ± 0.1 (n=18), 0.20 ± 0.1 (n=10), and 0.18 ± 0.1 (n=4). There was a significant increase in Pk levels from dose 1 to dose 3 and 5, (p<0.005 by ANOVA and post-hoc). No significant difference was present after dose 3 for Pk or Tr levels. Overall, 98% of Pk and 95% of Tr levels were within the acceptable prophylaxis range. No VTE events were noted. There were no major and 3 minor bleeding events through dose 5. Conclusions: FP dosed at an extended interval regimen of 2.5 mg q48h for VTE prophylaxis in ICU patients with renal failure results in satisfactory Pk and Tr levels. This dosing regimen appears pharmacologically sound, effective and safe in this patient population.

EL26 - Esophageal Cancer: Esophageal Cancer Drug Therapy

ABSTRACT For resectable esophageal cancer (stage II/II, non-T4), two courses of pre-operative chemotherapy with 5-fluorouracil (5-FU) plus cisplatin (CDDP) (FP) showed a significant survival benefit compared with post-operative chemotherapy with the same regimen in JCOG9907 trial (5-year survival rate; 60% versus 38%). On the other hand, the definitive chemoradiation therapy with FP (total 60Gy) resulted in a 5-year survival rate of 37% (JCOG9906 trial). At present, the standard treatment of resectable esophageal cancer is neoadjuvant chemotherapy with FP followed by surgery. Now neoadjuvant chemotherapy with triplet chemotherapy (docetaxel plus FP) and pre-operative chemoradiation therapy has been investigated in comparison with neoadjuvant FP. For locally advanced esophageal cancer (T4 and/or M1 lymph), JCOG0303 trial comparing standard dose of FP (5-FU 700 mg/m2/day, days 1–4, 29–32, CDDP 70 mg/m2 days 1, 29) with low dose FP (5-FU 200 mg/m2/day, 5 days per week, CDDP 4 mg/m2/day, 5 days per week, 6 weeks) concomitant with radiation therapy (total 60 Gy) showed equivalent survival curves (3-year survival rate; 28% versus 27%), no benefit of low dose FP. Thus, chemoradiation therapy with standard dose FP is recommended for locally advanced esophageal cancer. However, late toxic effects, especially in lung and heart, are a substantial problem. While radiation dose of 50.4 Gy is a global standard, it is expected that progression in radiation methods will reduce late toxic effects. For metastatic disease, FP is a standard chemotherapy, resulting in a response rate about 30% and median survival time of 7–8 months. Docetaxel and paclitaxel showed response rates of 30–40% in the second-line setting. Triplet therapy with taxane added to FP and molecular target agents such as anti-EGFR monoclonal antibody are expected to improve the efficacy.

MP29-02 (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate) in the treatment of seasonal allergic rhinitis: A randomized, double-blind, placebo-controlled trial of efficacy and safety

Many patients with allergic rhinitis (AR) have uncontrolled symptoms despite available treatment options. This study was designed to evaluate the efficacy and safety of MP29-02 (a novel intranasal formulation of fluticasone propionate [FP] and azelastine [AZ] hydrochloride), compared with monotherapy with FP, AZ, and placebo sprays for the treatment of seasonal allergic rhinitis (SAR). This 2-week randomized, double-blind, placebo-controlled trial was conducted in 779 patients with moderate-to-severe SAR. Treatments were administered 1 spray/nostril twice daily in the same vehicle and delivery device. Daily doses of AZ and FP were 548 and 200 micrograms, respectively. The primary efficacy variable was the 12-hour reflective total nasal symptom score (rTNSS), consisting of nasal congestion, sneezing, itchy nose, and runny nose. Secondary efficacy variables were (1) 12-hour reflective individual nasal symptom scores; (2) onset of action; (3) 12-hour reflective total ocular symptom score (rTOSS), including itchy eyes, watery eyes, and red eyes; and (4) the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score. MP29-02 significantly reduced the mean rTNSS from baseline by -5.54 points compared with FP (-4.55; p = 0.038), AZ (-4.54; p = 0.032), and placebo (-3.03; p < 0.001), improving the rTNSS by 39% beyond the contribution of FP. All individual nasal symptoms contributed to the efficacy of MP29-02. Onset of action was within 30 minutes. MP29-02 significantly improved rTOSS compared with placebo, provided a clinically important improvement in the overall RQLQ score, and was well tolerated. In this study, MP29-02 provided more complete symptom relief than two widely used first-line AR treatments and was well tolerated.

P172 Fluticasone/salmeterol combination confers significant benefits in smoking asthmatics

RationaleSmoking is known to increase airway inflammation and induce relative resistance to of inhaled steroids.ObjectivesThis study aimed to evaluate the effects of adding salmeterol to fluticasone (FPSM) versus doubling the...

Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over

Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over

Ciclesonide versus other inhaled steroids for chronic asthma in children and adults.

Inhaled corticosteroids (ICS) are an integral part of asthma management, and act as an anti-inflammatory agent in the airways of the lung. These agents confer both significant benefit in terms of symptom management and improvement in lung function, but may also cause harm in terms of local and systemic side-effects. Ciclesonide is a novel steroid that is metabolised to its active component in the lung, making it a potentially useful for reducing local side effects. To assess the efficacy and adverse effects of ciclesonide relative to those of other inhaled corticosteroids in the management of chronic asthma. We searched the Cochrane Airways Group register of trials with pre-defined terms. Additional searches of PubMed and Clinicalstudyresults.org were undertaken. The literature searches for this review are current up to June 2007. Randomised parallel or crossover studies were eligible for the review. We included studies comparing ciclesonide with other steroids both at nominally equivalent dose or lower doses of ciclesonide. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. Twenty one trials involving 7243 participants were included. Equal daily doses of ciclesonide and beclomethasone (BDP) or budesonide (BUD) gave similar results for peak expiratory flow rates (PEF), although forced vital capacity (FVC) was higher with ciclesonide. Data on forced expired volume in one second (FEV1) were inconsistent. Withdrawal data and symptoms were similar between treatments. Compared with the same dose of fluticasone (FP), data on lung function parameters (FEV1, FVC and PEF) did not differ significantly. Paediatric quality of life score favoured ciclesonide. Candidiasis was less frequent with ciclesonide, although other side-effect outcomes did not give significant differences in favour of either treatment. When lower doses of ciclesonide were compared to BDP or BUD, the difference in FEV1 did not reach significance but we cannot exclude a significant effect in favour of BDP/BUD. Other lung function outcomes did not give significant differences between treatments. Paediatric quality of life scores did not differ between treatments. Adverse events occurred with similar frequency between ciclesonide and BDP/BUD. Comparison with FP at half the nominal dose was undertaken in three studies, which indicated that FEV1 was not significantly different, but was not equivalent between the treatments (per protocol: -0.05 L 95% confidence intervals -0.11 to 0.01). The results of this review give some support to ciclesonide as an equivalent therapy to other ICS at similar nominal doses. The studies assessed low doses of steroids, in patients whose asthma required treatment with low doses of steroids. At half the dose of FP and BDP/BUD, the effects of ciclesonide were more inconsistent The effect on candidiasis may be of importance to people who find this to be problematic. The role of ciclesonide in the management of asthma requires further study, especially in paediatric patients. Further assessment against FP at a dose ratio of 1:2 is a priority.

Excellent Cecal Cleansing with Split Dose of Phosphosoda and 30 mg of Bisacodyl – A Retrospective Study Using Cecal Photograph as a Reflector of the Quality of Colon Cleansing

Purpose: Poor colon preparation was noted be 18% during an audit of the quality of colonoscopy preparation using polyethylene glycol based (PEG) solution in 2002. Since then, a series of changes have been made to our colon preparation protocol, which reduced the poor preparation rate to 8% & currently to 1%. Cecum appears to be the last to get cleaned out and is often obscured by stools despite excellent cleansing of the rest of the colon. Hence, 300 cecal photographs were graded to assess colon cleansing with different regimens by a single observer to avoid interobserver reporting bias. We also analysed the relationship between the quality of cecal image & colon polyp detection rate. Methods: 100 consecutive colonoscopies in each group were compared. Group A: 1 gallon of polyethylene glycol (PEG) the evening before procedure. Group B: 1.5 ounces phosphosoda (P) the evening before & 1.5 ounces on the day of procedure. Group C: Group B regimen + 10 mg of bisacodyl at noon and the evening before and on the day of procedure (P + BIS). Assessment: The cecal photograph was graded on a scale of 1–3: 1 = stool obscured the mucosa; 2 = 50–100% of mucosa visualized; specs of stool; 3 = Entire (100%) of the mucosa visualized (excellent prep); no stool. Endpoints: Mean colon cleansing (MCC) score & polyp detection for each preparation. Results:Excellent visualization of cecum (Grade 3) – Clean with 100% mucosal visualization: 57% in the split dose of P + 30 mg BIS, 20% in the PEG, & 24% in the split dose of FP (P < 0.001). MCC Score: 2.47 ± 0.69 in the split dose of P + 30 mg of BIS, 1.98 ± 0.71 in the split dose of P, & 1.92 ± 0.6 9 in the PEG respectively, P < .0001. The MCC score was higher in the P+BIS group in men (P < .0001); females (P= 0.04); age < 65 yrs (P < 0.0001) & ≥65 yrs (P < 0.0001). Polyp detection: In the P+BIS group, there was a correlation between the quality of cecal image and polyp detection (P= 0.04). Conclusion: Using the cecal photograph as a reflector of the quality of colon cleansing, the split dose of phosphosoda & 30 mg bisacodyl proved to be superior to other regimens.[figure1]Figure

Graded G-protein uncoupling by pertussis toxin treatment of human polymorphonuclear leukocytes.

Pertussis toxin (PT) inhibits polymorphonuclear leukocyte (PMN) function by ADP-ribosylating and inactivating guanine nucleotide binding proteins (G-proteins) that transduce activation by chemoattractants such as N-formyl peptides (FP). Studies of PMN activation during the time course of PT treatment yielded these results. 1) Responses were differentiated based on their sensitivity to PT treatment. Suboptimal PT treatment that resulted in 50% inhibition of the FP-induced actin-associated right angle light scatter response resulted in greater than 90% inhibition of oxidant production. Exhaustive PT treatment was required to completely inhibit the right angle light scatter response. This is consistent with previous observations that, relative to oxidant production, actin polymerization requires 100-fold fewer active N-formylpeptide receptors to elicit the response. This differential sensitivity to PT treatment has important implications for studies that use pertussis toxin to determine if the neutrophil G-protein is involved in the signaling of responses. If inhibition of oxidant production is used as the only indicator of the effectiveness of PT treatment, significant cytoskeletal changes may still be activated in these cells. Inhibition of actin polymerization is a much more rigorous indicator of complete G-protein inhibition by PT. 2) Analysis of FP-induced actin polymerization and cytosolic calcium elevation using flow cytometry, which measures individual cell responses, revealed that PT treatment resulted in the conversion of PMN from a responding to a non-responding population. In contrast, in control PMN, submaximal doses of FP caused submaximal stimulation of all the cells. The all-or-none effect of PT may result from heterogeneous insertion of the A-promoter of PT into the cell or it may result from a sharp threshold of coupled G-proteins required to transduce the responses.