scholarly journals Tiotropium in COPD: clinical outcomes and economic evidence

2010 ◽  
Vol 11 (1) ◽  
pp. 27-41
Author(s):  
Orietta Zaniolo ◽  
Viola Sacchi ◽  
Roberto W. Dal Negro
Keyword(s):  
Lung Function ◽  
Incremental Cost ◽  
Routine Care ◽  
Control Group ◽  
Clinical Effects ◽  
Duration Of Action ◽  
Cost Increase ◽  
Pharmaceutical Cost ◽  
Long Acting ◽  
Anticholinergic Bronchodilator

Tiotropium bromide is a once-daily anticholinergic bronchodilator with duration of action of at least 24 hours. In clinical trials, tiotropium has been compared with placebo, ipratropium or salmeterol, the most frequently used long-acting β2 agonist. When compared with ipratropium or placebo in COPD management, tiotropium resulted associated with FEV1, dyspnoea and health-related quality of life (QoL) improvement, along with reduced exacerbation and hospitalisation rates. In comparison to salmeterol, it proved to be superior in terms of lung function improvement and exacerbation risk reduction. Recently, the randomised, double-blind trial UPLIFT showed that 4 years of therapy with tiotropium were associated with improvements in lung function, QoL, and exacerbations, and with an effective reduction of mortality compared with control group in 5,993 patients with moderate to very-severe COPD. These encouraging clinical effects are to be traded against the pharmaceutical cost increase induced by the inclusion of tiotropium in routine care. However, published work indicates that this pharmaceutical cost increase may be totally or partially offset by the reduction in costs needed for exacerbations management and hospitalisations. Depending on the setting analysed, tiotropium is estimated to dominate ipratropium and salmeterol or to be associated with an incremental cost of less than € 2,500 per exacerbation avoided. An Italian model based on UPLIFT data shows that therapy including tiotropium induces an incremental cost of € 6,700 for year of life and of € 7,916 for Quality-adjusted Life Year gained, with respect to routine care alone. These values are much lower than commonly accepted thresholds and than cost/effectiveness results estimated for other long-acting bronchodilators. In conclusion, available evidence suggests that tiotropium may prove an appropriate therapeutic option with a largely affordable cost.

Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial

2021 ◽  
pp. 2102184
Author(s):  
Lata Jayaram ◽  
Alain C. Vandal ◽  
Catherina Chang ◽  
Chris Lewis ◽  
Cecilia Tong ◽  
...  
Keyword(s):  
Lung Function ◽  
Crossover Trial ◽  
Airflow Limitation ◽  
Smoking History ◽  
Double Blind ◽  
Intention To Treat ◽  
History Of ◽  
Long Acting ◽  
Anticholinergic Bronchodilator ◽  
Event Based

Tiotropium via HandiHaler® is an established long-acting, anticholinergic bronchodilator that prevents exacerbations and improves lung function in patients with COPD. We hypothesized that tiotropium would reduce pulmonary exacerbations and improve lung function in patients with stable bronchiectasis and airflow limitation, and assessed the effect of tiotropium on these outcomes. In a randomised, double-blind, 2-period crossover trial, we recruited adult patients from 3 hospitals in New Zealand. Patients were excluded if they had a smoking history of more than 20 pack years. Patients were assigned to either the tiotropium-placebo or placebo-tiotropium sequence in a 1:1 ratio, using randomly permuted blocks stratified by centre. Participants and investigators were masked to treatment allocation. Eligible patients received tiotropium 18mcg via the HandiHaler® device daily for 6 months followed by 6 months of placebo, or vice versa, with a washout period of 4 weeks. The primary endpoint was rate of event-based exacerbations during the 6-month period. Primary analyses were carried out in an intention-to-treat set. Ninety patients were randomly assigned and 85 completed both treatment cycles. The rate of exacerbations under the tiotropium treatment was 2.17 y−1 and 2.27 y−1 under placebo (rate ratio 0.96, 95% CI 0.72–1.27; p=0.77). Tiotropium, as compared with placebo, improved FEV1 by 58 mL (95% CI 23–92; p=0.002). Adverse events were similar under both treatments. Tiotropium via HandiHaler® over 6 months significantly improved lung function but not frequency of exacerbations. Further research is required to understand the clinical context and significance of these findings.

scholarly journals Metal additive manufacturing and possible clinical markers for the monitoring of exposure-related health effects

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248601
Author(s):  
Stefan A. Ljunggren ◽  
Liam J. Ward ◽  
Pål Graff ◽  
Anders Persson ◽  
Malin Leijon Lind ◽  
...  
Keyword(s):  
Additive Manufacturing ◽  
Lung Function ◽  
Health Effects ◽  
Function Analysis ◽  
Biological Fluids ◽  
Inflammatory Marker ◽  
Metal Exposure ◽  
Control Group ◽  
Clinical Effects ◽  
Clinical Markers

Additive manufacturing (AM) includes a series of techniques used to create products, in several different materials, such as metal, polymer or ceramics, with digital models. The main advantage of AM is that it allows the creation of complex structures, but AM promises several additional advantages including the possibility to manufacture on demand or replacing smaller worn parts by directly building on an existing piece. Therefore, the interest for and establishment of AM is rapidly expanding, which is positive, however it is important to be aware that new techniques may also result in new challenges regarding health and safety issues. Metals in blood and possible clinical effects due to metal exposure were investigated in AM operators at one of the first serial producing AM facilities in the world during two consecutive years with implementation of preventive measures in-between. As comparison, welders and office workers as control group were investigated. Health investigations comprised of surveys, lung function tests, antioxidant activity and vascular inflammation as well as renal- and hepatic function analysis. AM operators had significantly reduced nickel levels in blood (10.8 vs 6.2 nmol/L) as well as improved lung function (80 vs 92% of predicted) from year 1 to year 2. This is in line with previously published results displaying reduced exposure. Blood cobalt and nickel levels correlated with previously reported urinary levels, while blood chromium did not. Multivariate modelling showed that blood cobalt, antioxidant/inflammatory marker serum amyloid A1/serum paraoxonase/arylesterase 1 activity and the hepatic markers aspartate transaminase, alanine transaminase, and alkaline phosphatase were higher in AM operators compared to controls. The study show that the selected clinical analyses could function as a complement to metal analyses in biological fluids when investigating exposure-related health effects in AM operators. However, validation in larger cohorts is necessary before more definite conclusions could be drawn.

MODULATION OF TRIGLYCERIDES IN FEMALE RATTUS RATTUS WITH STEROID CONTRACEPTIVE ALGESTONE ACETOPHENIDE (DHPA)

2019 ◽  
Vol 25 (1) ◽  
Author(s):  
ASHOK KUMAR ◽  
ALPANA PARMAR ◽  
ANAND KUMAR BAJPEYEE
Keyword(s):  
Mixed Type ◽  
Rattus Rattus ◽  
Young Female ◽  
Female Rats ◽  
Control Group ◽  
Black Rat ◽  
Long Acting ◽  
Steroid Contraceptive

Young female Black rat (Rattus rattus), were administered monthly long acting steroid contraceptive to induce hypertriglyceridemia. It was observed that by 3 weeks of the second injection of estrogen containing mixed type of contraceptive, female rats developed consistent and frank hyperglyceridemia . TG in the treated rats was 195.8 ± 7.44 mg /100 ml as compared to 91.5 ± 6.27 mg/100ml in plasma of the control group.

scholarly journals Prognostic and functional impact of perioperative LAMA/LABA inhaled therapy in patients with lung cancer and chronic obstructive pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yoko Azuma ◽  
Atsushi Sano ◽  
Takashi Sakai ◽  
Satoshi Koezuka ◽  
Hajime Otsuka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Postoperative Complications ◽  
Lung Function ◽  
Retrospective Review ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Inhaled Therapy ◽  
Long Acting

Abstract Background Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting β2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients. Methods Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical record to evaluate that LAMA/LABA might be an optimal regimen for patients with COPD undergoing surgery for lung cancer. All patients were received perioperative rehabilitation and divided into 3 groups according to the type of perioperative inhaled therapy and management: LAMA/LABA (n = 64), LAMA (n = 23) and rehabilitation only (no bronchodilator) (n = 43). We conducted a retrospective review of their medical records. Results Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p < 0.001 for both forced expiratory volume in 1 s (FEV1) and percentage of predicted forced expiratory volume in 1 s (FEV1%pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, LAMA/LABA 223.1 mL vs. LAMA 130.0 mL, ΔFEV1%pred, LAMA/LABA 10.8% vs. LAMA 6.8%; both p < 0.05). Postoperative complications were lower frequent in the LAMA/LABA group than in the LAMA group (p = 0.007). In patients with moderate to severe air flow limitation (n = 61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with the LAMA (p = 0.049, p = 0.026) and rehabilitation-only groups (p = 0.001, p < 0.001). Perioperative LAMA/LABA therapy was also associated with lower recurrence rates (vs. LAMA p = 0.006, vs. rehabilitation-only p = 0.008). Conclusions We believe this treatment combination is optimal for patients with lung cancer and COPD.

scholarly journals Effects of long-acting, broad spectra anthelmintic treatments on the rumen microbial community compositions of grazing sheep

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina D. Moon ◽  
Luis Carvalho ◽  
Michelle R. Kirk ◽  
Alan F. McCulloch ◽  
Sandra Kittelmann ◽  
...  
Keyword(s):  
Archaeal Community ◽  
Fungal Communities ◽  
Control Group ◽  
Microbiota Composition ◽  
Rumen Microbiota ◽  
Treatment Groups ◽  
Methanobrevibacter Ruminantium ◽  
Group 12 ◽  
Relative Abundances ◽  
Long Acting

AbstractAnthelmintic treatment of adult ewes is widely practiced to remove parasite burdens in the expectation of increased ruminant productivity. However, the broad activity spectra of many anthelmintic compounds raises the possibility of impacts on the rumen microbiota. To investigate this, 300 grazing ewes were allocated to treatment groups that included a 100-day controlled release capsule (CRC) containing albendazole and abamectin, a long-acting moxidectin injection (LAI), and a non-treated control group (CON). Rumen bacterial, archaeal and protozoal communities at day 0 were analysed to identify 36 sheep per treatment with similar starting compositions. Microbiota profiles, including those for the rumen fungi, were then generated for the selected sheep at days 0, 35 and 77. The CRC treatment significantly impacted the archaeal community, and was associated with increased relative abundances of Methanobrevibacter ruminantium, Methanosphaera sp. ISO3-F5, and Methanomassiliicoccaceae Group 12 sp. ISO4-H5 compared to the control group. In contrast, the LAI treatment increased the relative abundances of members of the Veillonellaceae and resulted in minor changes to the bacterial and fungal communities by day 77. Overall, the anthelmintic treatments resulted in few, but highly significant, changes to the rumen microbiota composition.

scholarly journals Dynamic evolution of emphysema and airway remodeling in two mouse models of COPD

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yue Yang ◽  
Tingting Di ◽  
Zixiao Zhang ◽  
Jiaxin Liu ◽  
Congli Fu ◽  
...  
Keyword(s):  
Lung Function ◽  
Mouse Models ◽  
Lung Tissue ◽  
Airway Remodeling ◽  
Exposed Group ◽  
The Body ◽  
Mouse Lung ◽  
Control Group ◽  
Suitable Model ◽  
Exposure Method

Abstract Background Establishment of a mouse model is important for investigating the mechanism of chronic obstructive pulmonary disease (COPD). In this study, we observed and compared the evolution of the pathology in two mouse models of COPD induced by cigarette smoke (CS) exposure alone or in combination with lipopolysaccharide (LPS). Methods One hundred eight wild-type C57BL/6 mice were equally divided into three groups: the (1) control group, (2) CS-exposed group (CS group), and (3) CS + LPS-exposed group (CS + LPS group). The body weight of the mice was recorded, and noninvasive lung function tests were performed monthly. Inflammation was evaluated by counting the number of inflammatory cells in bronchoalveolar lavage fluid and measuring the expression of the IL-6 mRNA in mouse lung tissue. Changes in pathology were assessed by performing hematoxylin and eosin and Masson staining of lung tissue sections. Results The two treatments induced emphysema and airway remodeling and decreased lung function. Emphysema was induced after 1 month of exposure to CS or CS + LPS, while airway remodeling was induced after 2 months of exposure to CS + LPS and 3 months of exposure to CS. Moreover, the mice in the CS + LPS group exhibited more severe inflammation and airway remodeling than the mice in the CS group, but the two treatments induced similar levels of emphysema. Conclusion Compared with the single CS exposure method, the CS + LPS exposure method is a more suitable model of COPD in airway remodeling research. Conversely, the CS exposure method is a more suitable model of COPD for emphysema research due to its simple operation.

565 A novel long-acting interleukin-7 agonist, NT-I7, increases cytotoxic CD8+ T cells and enhances survival in mouse glioma models

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A599-A599
Author(s):  
Subhajit Ghosh ◽  
Ran Yan ◽  
Sukrutha Thotala ◽  
Arijita Jash ◽  
Anita Mahadevan ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Standard Of Care ◽  
Control Group ◽  
Cervical Lymph Nodes ◽  
Cd8 Cells ◽  
Interleukin 7 ◽  
Long Acting

BackgroundRadiation (RT) and temozolomide (TMZ), which are standard of care for patients with glioblastoma (GBM), can cause prolonged severe lymphopenia. Lymphopenia, in turn, is an independent risk factor for shorter survival. Interleukin-7 (IL-7) is a cytokine that is required for T cell homeostasis and proliferation. IL-7 levels are inappropriately low in GBM patients with lymphopenia. NT-I7 (efineptakin alfa) is a long-acting recombinant human IL-7 that supports the proliferation and survival CD4+ and CD8+ cells in both human and mice. We tested whether NT-I7 rescues treatment-induced lymphopenia and improves survival.MethodsImmunocompetent C57BL/6 mice bearing two intracranial glioma models (GL261 and CT2A) were treated with RT (1.8 Gy/day x 5 days), TMZ (33 mg/kg/day x 5 days) and/or NT-I7 (10 mg/kg on the final day of RT completion). We profiled the CD3, CD8, CD4, FOXP3 cells in peripheral blood over time. We also immunoprofiled cervical lymph nodes, bone marrow, thymus, spleen, and the tumor 6 days after NT-I7 treatment. Survival was monitored daily.ResultsMedian survival in mice treated with NT-I7 combined with RT was significantly longer than RT alone (GL261: 40d vs 34d, p<0.0021; CT2A: 90d vs 40d, p<0.0499) or NT-I7 alone (GL261: 40d vs 24d, p<0.008; CT2A: 90d vs 32d, p<0.0154). NT-I7 with RT was just as effective as NT-I7 combined with RT and TMZ in both GL261(40d vs 47d) and CT2A (90d vs 90d). Cytotoxic CD8+ T cells were increased in both peripheral blood (0.66 x 105 to 3.34 x 105; P≤0.0001) and tumor (0.53 x 103 to 1.83 x 103; P≤0.0001) in mice treated with NT-I7 when compared to control. Similarly, NT-I7 in combination with RT increased the CD8+ T cells in peripheral blood (0.658 x 105 to 1.839 x 105 P≤0.0001) when compared to RT alone. There were decreases in tumor infiltrating FOXP3+ T-reg cells in mice treated with NT-I7 (1.9 x 104 to 0.75 x 104 P≤0.0001) and NT-I7 + RT (1.9 x 104 to 0.59 x 104 P≤0.0001) when compared to the control group without NT-I7. In addition, NT- I7 treatment increased CD8+ T cells in thymus, spleen, and lymph nodes.ConclusionsNT-I7 enhances cytotoxic CD8+ T lymphocytes systemically and in the tumor microenvironment, and improves survival. A phase I/II trial to evaluate NT-I7 in patients with high-grade gliomas is ongoing (NCT03687957).

scholarly journals Adding low concentrations of clonidine to ropivacaine for transversus abdominis plane blocks does not reduce plasma ropivacaine levels, suggesting a lack of vasoconstrictor effect

2019 ◽  
Vol 47 (2) ◽  
pp. 134-140
Author(s):  
Jennifer M Crawford ◽  
John A Loadsman ◽  
Kenny XF Yang ◽  
Peter CA Kam
Keyword(s):  
Local Anaesthetics ◽  
Transversus Abdominis ◽  
Control Group ◽  
Transversus Abdominis Plane ◽  
Nerve Blocks ◽  
Duration Of Action ◽  
Low Concentrations ◽  
Vasoconstrictor Effect ◽  
Surrogate Measure ◽  
To Receive

Clonidine has been used successfully to prolong the duration of action of local anaesthetics in peripheral nerve blocks, but its mechanism of action in this setting remains unclear. Some studies suggest that clonidine exerts a vasoconstrictor effect, limiting the washout of local anaesthetic from its site of deposition. We investigated this potential vasoconstrictor effect, using plasma ropivacaine concentrations as a surrogate measure of vasoconstriction, in patients who received transversus abdominis plane (TAP) blocks with and without clonidine. Eighty women undergoing laparoscopic gynaecological surgery were randomly assigned to receive one of four TAP block solutions: 0.2% ropivacaine (control), ropivacaine with clonidine 2 μg/kg (clonidine), ropivacaine with 1:400,000 adrenaline (adrenaline) or ropivacaine and a subcutaneous injection of clonidine 2 μg/kg (SC clonidine). The primary outcome was total venous plasma ropivacaine concentrations up to 6 h after the block. There were no significant differences in plasma ropivacaine concentrations between the control group and the clonidine group at any timepoint in the study, nor were there differences in either the mean maximum ropivacaine concentration ( Cmax) (1.99 μg/mL versus 2.05 μg/mL, P = 0.712) or the time to maximum concentration ( Tmax) (51.0 min versus 56.0 min, P = 0.537). The SC clonidine group also did not differ significantly from the controls ( Cmax 2.13 μg/mL versus 1.99 μg/mL, P = 0.424; Tmax 43.5 min versus 51.0 min, P = 0.201). Plasma ropivacaine concentrations in the adrenaline group were significantly lower than the controls from 10 to 90 min ( P < 0.003 for each comparison), and the Cmax was less than that of the control group (1.36 μg/mL versus 1.99 μg/mL, P < 0.001) with a longer Tmax (103.5 min versus 51.0 min, P = 0.001). These findings indicate that clonidine at a concentration of 1.35 μg/mL added to ropivacaine for TAP blocks did not produce a reduction in plasma ropivacaine concentrations. This suggests a lack of vasoconstrictor effect during TAP blocks. Further studies should evaluate whether vasoconstriction occurs when clonidine is used at higher concentrations or for other blocks.

Efficacy of Intravitreal Triamcinolone after or Concomitant with Laser Photocoagulation in Nonproliferative Diabetic Retinopathy with Macular Edema

2009 ◽  
Vol 19 (4) ◽  
pp. 630-637 ◽  
Author(s):  
Erdinc Aydin ◽  
Helin Deniz Demir ◽  
Huseyin Yardim ◽  
Unal Erkorkmaz
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Edema ◽  
Laser Photocoagulation ◽  
Control Group ◽  
Clinical Effects ◽  
Intravitreal Triamcinolone ◽  
Nonproliferative Diabetic Retinopathy ◽  
Significant Difference ◽  
Group 3 ◽  
The Mean

Purpose To investigate the clinical effects and outcomes of intravitreal injection of 4 mg of triamcinolone acetonide (IVTA) after or concomitant with macular laser photocoagulation (MP) for clinically significant macular edema (CSME). Methods Forty-nine eyes of 49 patients with nonproliferative diabetic retinopathy and CSME were randomized into three groups. The eyes in the laser group (n=17), group 1, were subjected to MP 3 weeks after IVTA; the eyes in the IVTA group (n=13), group 2, were subjected to MP, concomitant with IVTA; the eyes in the control group (n=19), group 3, underwent only IVTA application. Visual acuity (VA), fundus fluorescein angiography, and photography were performed in each group. Results In the first group, the mean VA improved from 0.17±0.09 at baseline to 0.28±0.15 (p=0.114) and in the second group, deteriorated from 0.19±0.08 at baseline to 0.14±0.08 at the sixth month (p=0.141), respectively. In Group 3, the mean VA improved from 0.16±0.08 at baseline to 0.28±0.18 (p=0.118) at the end of the follow-up. When VA was compared between the control and study groups, significant difference was detected at the sixth month (p=0.038). Conclusions MP after IVTA improved VA, rather than MP concomitant with IVTA, and only IVTA application for CSME. MP after IVTA may reduce the recurrence of CSME and needs further investigations in a longer period.

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