| 1. |
- Aalbers, René, et al.
(författare)
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Randomized, Double-Blind, Dose-Finding Study for Tiotropium when Added to Olodaterol, Administered via the Respimat(®) Inhaler in Patients with Chronic Obstructive Pulmonary Disease.
- 2015
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Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 32:9, s. 809-822
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Tidskriftsartikel (refereegranskat)abstract
- Combining long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) is beneficial in chronic obstructive pulmonary disease (COPD), as the two classes of bronchodilator have complementary modes of action. The optimal dose for the fixed-dose combination of the LAMA tiotropium and the LABA olodaterol needed to be determined. In this phase II trial, the dose response of tiotropium on top of olodaterol was investigated in a free-dose combination, while other phase II studies have explored different doses of olodaterol on top of tiotropium, with both drugs delivered using the Respimat(®) inhaler.
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| 2. |
- Albayaty, Muna, et al.
(författare)
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Pharmacokinetic Evaluation of Once-Weekly and Once-Monthly Buprenorphine Subcutaneous Injection Depots (CAM2038) Versus Intravenous and Sublingual Buprenorphine in Healthy Volunteers Under Naltrexone Blockade : An Open-Label Phase 1 Study
- 2017
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Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 34:2, s. 560-575
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: CAM2038 q1w (once weekly) and q4w (once monthly) are investigational buprenorphine subcutaneous (SC) formulations based on FluidCrystal® injection depot technology. These two drug products are being developed for opioid dependence treatment, with a target for once-weekly and once-monthly SC dosing. The rationale for developing two products with different dosing frequencies is that treatment strategies/routines, and hence different treatment preferences, can vary between patients, different stages of opioid maintenance treatment, and countries. This study evaluated the pharmacokinetics and safety of buprenorphine and norbuprenorphine following administration of CAM2038 q1w or q4w versus active controls. Methods: Healthy volunteers were randomized to five treatment groups. All received a single intravenous dose of buprenorphine 600 µg, followed post-washout by a single dose of CAM2038 q4w 96 mg, a single dose of CAM2038 q4w 192 mg, or sublingual buprenorphine 8, 16, or 24 mg daily for 7 days, followed post-washout by a single dose of CAM2038 q4w 64 or 128 mg or four repeated weekly doses of CAM2038 q1w 16 mg. All subjects received daily naltrexone. Results: Eighty-seven subjects were randomized. Median buprenorphine tmax after CAM2038 q4w was 4–10 h (24 h for CAM2038 q1w); mean terminal half-life was 19–25 days (5 days for CAM2038 q1w). CAM2038 q4w showed dose-proportional buprenorphine release, with similar exposure to repeat-dose CAM2038 q1w at comparable monthly dose level. Both CAM2038 formulations showed complete absolute bioavailability of buprenorphine and 5.7- to 7.7-fold greater buprenorphine bioavailability versus sublingual buprenorphine. CAM2038 q1w and q4w were well tolerated; subjects’ acceptance was higher for CAM2038 than for sublingual buprenorphine 1 h post-dose. Conclusions: The pharmacokinetic profiles of CAM2038 q1w and q4w versus sublingual buprenorphine support expected treatment efficacy with once-weekly and once-monthly dosing, respectively. CAM2038 formulations were safe and showed good local tolerability. Trial registration: ISRCTN24987553. Funding: Camurus AB.
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| 3. |
- Alonso-Cotoner, Carmen, et al.
(författare)
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The Role of Purported Mucoprotectants in Dealing with Irritable Bowel Syndrome, Functional Diarrhea, and Other Chronic Diarrheal Disorders in Adults
- 2021
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Ingår i: Advances in Therapy. - : Springer. - 0741-238X .- 1865-8652. ; 38:5, s. 2054-2076
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Forskningsöversikt (refereegranskat)abstract
- Chronic diarrhea is a frequent presenting symptom, both in primary care medicine and in specialized gastroenterology units. It is estimated that more than 5% of the global population suffers from chronic diarrhea. and that about 40% of these subjects are older than 60 years. The clinician is frequently faced with the need to decide which is the best therapeutic approach for these patients. While the origin of chronic diarrhea is diverse, impairment of intestinal barrier function, dysbiosis. and mucosal micro-inflammation are being increasingly recognized as underlying phenomena characterizing a variety of chronic diarrheal diseases. In addition to current pharmacological therapies, there is growing interest in alternative products such as mucoprotectants, which form a mucoadhesive film over the epithelium to reduce and protect against the development of altered intestinal permeability, dysbiosis, and mucosal micro-inflammation. This manuscript focuses on chronic diarrhea in adults, and we will review recent evidence on the ability of these natural compounds to improve symptoms associated with chronic diarrhea and to exert protective effects for the intestinal barrier.
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| 4. |
- Andersen, Grit, et al.
(författare)
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Clinical Characteristics of a Non-Alcoholic Fatty Liver Disease Population Across the Fibrosis Spectrum Measured by Magnetic Resonance Elastography: Analysis of Screening Data
- 2020
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Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 37:12, s. 4866-4876
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is associated with liver-related complications and metabolic comorbidities. The phenotype is wide, ranging from simple steatosis to non-alcoholic steatohepatitis with advanced fibrosis. In this analysis of a phase 1 trial, clinical characteristics of screened subjects with NAFLD were studied according to the extent of fibrosis assessed using magnetic resonance elastography (MRE). Methods: One hundred ninety-four subjects with body mass index (BMI) of 25–40 kg/m2 and suspected NAFLD were assessed by MRE and grouped by MRE thresholds as a proxy for fibrosis staging (groups 0–4). Data were summarized by group levels, and correlation analyses between MRE values and clinical parameters (including magnetic resonance imaging-proton density fat fraction) were performed. Results: Most subjects had MRE values in the lower range (groups 0–1; N = 148). Type 2 diabetes (T2D) and BMI > 35 kg/m2 were more frequent in groups with higher than lower MRE values. Subjects in the highest MRE groups also tended to be older and have higher liver enzyme concentrations compared with lower MRE groups. No, or weak, correlations were found between MRE values and clinical parameters (all r values ≤ 0.45). Conclusions: There was considerable variation and overlap in clinical characteristics across the spectrum of liver stiffness. Although groups with high MRE values generally included more subjects with T2D and obesity, and had higher age and concentrations of liver enzymes, the clinical characteristics did not strongly correlate with MRE scores in this population. Trial Registration: Registered on Clinicaltrials.gov on November 29, 2017 (NCT03357380).
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| 5. |
- Antonini, Angelo, et al.
(författare)
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The Long-Term Impact of Levodopa/Carbidopa Intestinal Gel on ‘Off’-time in Patients with Advanced Parkinson’s Disease : A Systematic Review
- 2021
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Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 38:6, s. 2854-2890
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients with advanced Parkinson’s disease (PD) when other treatments have not given satisfactory results. Reduction in ‘off’-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on ‘off’-time. Methods: Studies were identified by searching PubMed, EMBASE and Ovid on 30 September 2019. Studies were included if they reported on patients with PD, had a sample size of ≥ 10, LCIG was an active intervention and ‘off’-time was reported for ≥ 12 months after initiation of LCIG treatment. Randomised clinical trials, retrospective and prospective observational studies, and other interventional studies were included for selection. Data were collected on: ‘off’-time (at pre-specified time periods and the end of follow-up), study characteristics, Unified Parkinson’s Disease Rating Scale (UPDRS) II, III and IV total scores, dyskinesia duration, quality of life scores, non-motor symptoms and safety outcomes. Results: Twenty-seven studies were included in this review. The improvement in ‘off’-time observed shortly after initiating LCIG was maintained and was statistically significant at the end of follow-up in 24 of 27 studies. ‘Off’-time was reduced from baseline to end of follow-up by 38–84% and was accompanied by a clinically meaningful improvement in quality of life. Stratified analysis of ‘off’-time demonstrated mean relative reductions of 47–82% at 3–6 months and up to 83% reduction at 3–5 years of follow-up. Most studies reported significant improvements in activities of daily living and motor complications. Most frequent adverse events were related to the procedure or the device. Conclusion: In one of the largest qualitative syntheses of published LCIG studies, LCIG treatment was observed to provide a durable effect in reducing ‘off’-time. Infographic: [Figure not available: see fulltext.] [MediaObject not available: see fulltext.]
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| 6. |
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| 7. |
- Bepari, A. K., et al.
(författare)
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Factors Driving Antimicrobial Resistance in Rural Bangladesh : A Cross-Sectional Study on Antibiotic Use-Related Knowledge, Attitude, and Practice Among Unqualified Village Medical Practitioners and Pharmacy Shopkeepers
- 2023
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Ingår i: Advances in Therapy. - : Springer. - 0741-238X .- 1865-8652. ; 40:8, s. 3478-3494
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Inappropriate antibiotic use in community settings significantly contributes to antimicrobial resistance (AMR) globally, compromising the quality of life and threatening public health. This study aimed to identify AMR contributing factors by analyzing the knowledge, attitude, and practice (KAP) of the unqualified village medical practitioners and pharmacy shopkeepers in rural Bangladesh. Methods: We performed a cross-sectional study where the participants were pharmacy shopkeepers and unqualified village medical practitioners aged ≥ 18 years and living in Sylhet and Jashore districts in Bangladesh. Primary outcome variables were knowledge, attitude, and practice of antibiotic use and AMR. Results: Among the 396 participants, all were male aged between 18 and 70 years, 247 were unqualified village medical practitioners, and 149 were pharmacy shopkeepers, and the response rate was 79%. Participants showed moderate to poor knowledge (unqualified village medical practitioners, 62.59%; pharmacy shopkeepers, 54.73%), positive to neutral attitude (unqualified village medical practitioners, 80.37%, pharmacy shopkeepers, 75.30%), and moderate practice (unqualified village medical practitioners, 71.44%; pharmacy shopkeepers, 68.65%) scores regarding antibiotic use and AMR. The KAP score range was 40.95–87.62%, and the mean score was statistically significantly higher for unqualified village medical practitioners than pharmacy shopkeepers. Multiple linear regression analysis suggested that having a bachelor’s degree, pharmacy training, and medical training were associated with higher KAP scores. Conclusion: Our survey results demonstrated that unqualified village medical practitioners and pharmacy shopkeepers in Bangladesh possess moderate to poor knowledge and practice scores on antibiotic use and AMR. Therefore, awareness campaigns and training programs targeting unqualified village medical practitioners and pharmacy shopkeepers should be prioritized, antibiotic sales by pharmacy shopkeepers without prescriptions should be strictly monitored, and relevant national policies should be updated and implemented.
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| 8. |
- Berg, Mats, et al.
(författare)
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A Novel Formulation of Mometasone Furoate in Psoriasis Patients: A Multicenter, Randomized, Double-Blind Clinical Study
- 2013
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Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 30:5, s. 503-516
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Tidskriftsartikel (refereegranskat)abstract
- Further formulations of mometasone furoate are needed for treatment of patients with plaque psoriasis to meet individual patient preferences. This has motivated the development of Ovixan(A (R)) (Galencia, Malmoe, Sweden), a formulation of mometasone furoate with different cosmetic properties than the commonly used formulation, Elocon(A (R)) (Merck [Schering Plough], Whitehouse Station, New Jersey, USA). This novel formulation of mometasone furoate was examined in a vasoconstrictor assay comparing its efficacy with that of Elocon. Subsequently, the new formulation was tested in a multicenter, randomized, double-blind clinical study in patients with plaque psoriasis. Healthy volunteers were included in the vasoconstrictor study. The treatments were randomly assigned to test fields on the forearms. The test fields were gently cleaned after treatment for 6 h. Skin color was measured during the following 24 h and area under the time curve was calculated. The clinical efficacy and tolerance of Ovixan was as compared to that of Elocon and their vehicles in a double-blind study in patients with plaque psoriasis. Patients with four symmetrically placed lesions on the arms or the legs were treated for 6 weeks. Primary endpoint was the change from baseline of the Total Severity Sign score for each treated lesion. The cosmetic characteristics of the two test preparations were assessed by an independent cosmetological institute. Ovixan was shown to have skin blanching potency almost identical to the vasoconstrictor potency of Elocon. Clinical equivalence of Ovixan to Elocon was demonstrated in the clinical study of the efficacy in patients with plaque psoriasis. A professional testing team clearly documented the cosmetic superiority of Ovixan as compared to Elocon. The results of the investigations show that Ovixan is equipotent to the commonly used formulation Elocon. However, the cosmetic properties are in favor of Ovixan. The effect of the cosmetic differences on patient preferences and patient adherence to prescribed treatment has to be investigated in further studies.
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| 9. |
- Bjermer, Leif H., et al.
(författare)
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Efficacy and Safety of Umeclidinium/Vilanterol in Current and Former Smokers with COPD : A Prespecified Analysis of The EMAX Trial
- 2021
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Ingår i: Advances in Therapy. - : Springer Science and Business Media LLC. - 0741-238X .- 1865-8652. ; 38:9, s. 4815-4835
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Smoking may reduce the efficacy of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD), but its impact on bronchodilator efficacy is unclear. This analysis of the EMAX trial explored efficacy and safety of dual- versus mono-bronchodilator therapy in current or former smokers with COPD. Methods: The 24-week EMAX trial evaluated lung function, symptoms, health status, exacerbations, clinically important deterioration, and safety with umeclidinium/vilanterol, umeclidinium, and salmeterol in symptomatic patients at low exacerbation risk who were not receiving ICS. Current and former smoker subgroups were defined by smoking status at screening. Results: The analysis included 1203 (50%) current smokers and 1221 (50%) former smokers. Both subgroups demonstrated greater improvements from baseline in trough FEV1 at week 24 (primary endpoint) with umeclidinium/vilanterol versus umeclidinium (least squares [LS] mean difference, mL [95% CI]; current: 84 [50, 117]; former: 49 [18, 80]) and salmeterol (current: 165 [132, 198]; former: 117 [86, 148]) and larger reductions in rescue medication inhalations/day over 24 weeks versus umeclidinium (LS mean difference [95% CI]; current: − 0.42 [− 0.63, − 0.20]; former: − 0.25 − 0.44, − 0.05]) and salmeterol (current: − 0.28 [− 0.49, − 0.06]; former: − 0.29 [− 0.49, − 0.09]). Umeclidinium/vilanterol increased the odds (odds ratio [95% CI]) of clinically significant improvement at week 24 in Transition Dyspnea Index versus umeclidinium (current: 1.54 [1.16, 2.06]; former: 1.32 [0.99, 1.75]) and salmeterol (current: 1.37 (1.03, 1.82]; former: 1.60 [1.20, 2.13]) and Evaluating Respiratory Symptoms–COPD versus umeclidinium (current: 1.54 [1.13, 2.09]; former: 1.50 [1.11, 2.04]) and salmeterol (current: 1.53 [1.13, 2.08]; former: 1.53 [1.12, 2.08]). All treatments were well tolerated in both subgroups. Conclusions: In current and former smokers, umeclidinium/vilanterol provided greater improvements in lung function and symptoms versus umeclidinium and salmeterol, supporting consideration of dual-bronchodilator therapy in symptomatic patients with COPD regardless of their smoking status.
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| 10. |
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