| 1. |
- Olsson, Anders, 1940-, et al.
(författare)
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A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: The treat-to-target (3T) study
- 2003
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Ingår i: Clinical Therapeutics. - 0149-2918 .- 1879-114X. ; 25:1, s. 119-138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Guidelines for the prevention of coronary heart disease call for low-density lipoprotein cholesterol (LDL-C) reduction as the primary target of treatment and reduction of triglycerides (TG) as an additional target. Objective: The purpose of this study was to investigate the ability of atorvastatin and simvastatin to reduce LDL-C and TG concentrations and to meet 3 target lipid levels: LDL-C less than or equal to2.6 mmol/L; TG less than or equal to1.5 mmol/L; and both LDL-C less than or equal to2.6 mmol/L and TG less than or equal to1.5 mmol/L. Methods: The Treat-to-Target (3T) Study was a 52-week, multicenter, randomized, parallel-group study. Using the double-blind, double-dummy technique, adult patients aged 35 to 75 years with cardiovascular disease and dyslipidemia, defined as LDL-C concentration less than or equal to4.0 mmol/L (greater than or equal to155 mg/dL), were randomised in a 1:1 ratio to receive once-daily oral treatment with 20 mg atorvastatin or 20 mg simvastatin. Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National Cholesterol Education Program level of LDL-C (less than or equal to2.6 mmol/L [100 mg/dL]) was not reached at 8 weeks. Results: The intent-to-treat analysis included 552 patients (418 men, 134 women) randomized to receive atorvastatin and 535 (404 men, 131 women) randomized to receive simvastatin. The number of patients enrolled in the study allowed the evaluation of the drugs' effects on TG. Patient demographic characteristics were similar for the 2 treatment groups, and there were no differences in baseline lipid values. Compared with simvastatin, atorvastatin produced significantly greater reductions in LDL-C (8 weeks: -46% vs -40%, P < 0.001; 52 weeks: -49% vs -44%, P < 0.001) and in TG (8 weeks: -23% vs -14%, P < 0.001; 52 weeks: -24% vs -16%, P < 0.001). Compared with simvastatin-treated patients, a significantly greater number of atorvastatin-treated patients reached the LDL-C target after 8 weeks (45% vs 24%; P < 0.001). Fewer atorvastatin patients needed to have their dose doubled; nevertheless more atorvastatin patients reached the LDL-C target after 52 weeks (61% vs 41%; P < 0.001). Both statins were well tolerated. Muscular symptoms occurred in 12 patients (2.2%) in the atorvastatin group and in 13 patients (2.4%) in the simvastatin group. Conclusions: Atorvastatin 20 or 40 mg/d for up to 1 year of treatment was significantly more effective than simvastatin 20 or 40 mg/d in reducing LDL-C and TG levels and at achieving recommended lipid targets in this selected patient population with cardiovascular disease and dyslipidemia. Both statins were well tolerated.
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| 2. |
- Blumenschein, Karen, et al.
(författare)
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Use of contingent valuation to place a monetary value on pharmacy services: An overview and review of the literature
- 1999
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Ingår i: Clinical therapeutics. - : EM Inc USA. - 1879-114X .- 0149-2918. ; 21:8, s. 1402-1417
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Tidskriftsartikel (refereegranskat)abstract
- An important goal for the pharmacy profession is to quantify the economic value of pharmacy services. The contingent valuation (CV), or willingness-to-pay method, offers one approach to valuing the benefits of pharmacy services. The potential advantage CV offers is that it reflects, in a single monetary amount, the entire range of attributes (both benefits and “nonbenefits”) offered by the good or service being valued. This paper provides a brief overview of the CV method and reviews 10 published studies that used a willingness-to-pay question to place a monetary value on pharmacy services. Suggestions for other researchers wishing to use this method are provided.
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| 3. |
- Jacobsson, F., et al.
(författare)
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Safety profile and tolerability of intravenous AR-C69931MX, a new antiplatelet drug, in unstable angina pectoris and non-Q-wave myocardial infarction
- 2002
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Ingår i: Clinical Therapeutics. - 0149-2918 .- 1879-114X. ; 24:5, s. 752-765
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Tidskriftsartikel (refereegranskat)abstract
- Background: Thrombin generation and platelet aggregation in the disrupted atherosclerotic plaque are the major reasons for thrombus formation associated with acute coronary events. AR-C69931MX is a new agent that inhibits adenosine diphosphate-induced platelet aggregation by antagonism of the P2T purinoceptor. Objective: This study assessed the safety profile, tolerability, and plasma concentrations at steady state of intravenous AR-C69931MX in patients with unstable angina pectoris or non-Q-wave myocardial infarction (MI). Methods: This was a Phase II, multicenter, double-blind, randomized, placebo-controlled trial. Patients with unstable angina or non-Q-wave MI were randomized to a 72-hour infusion of AR-C69931MX or placebo as adjunctive therapy to aspirin and low-molecular-weight heparin. Other treatment was at the discretion of the local investigator. Outcomes were assessed at 30 days. Results: Ninety-four patients were randomized and 91 received treatment (45 AR-C69931MX, 46 placebo). Plasma concentrations of AR-C69931MX were within the expected range, there were no signs of accumulation, and interindividual variability in clearance was low. Four patients receiving AR-C69931MX discontinued treatment due to minor bleeding events, and 5 patients receiving placebo discontinued treatment due to other adverse events or deterioration in their condition. No serious bleeding events were seen during treatment. The incidence of =1 episode of minor bleeding was slightly higher in patients receiving AR-C69931MX compared with those receiving placebo (38% vs 26%, respectively). The drug was well tolerated hemodynamically, and there were no significant changes in other laboratory values between groups. Conclusions: As adjunctive therapy to aspirin and low-molecular-weight heparin in patients with unstable angina or non-Q-wave MI, intravenous AR-C69931MX was well tolerated, with no difference in the incidence of serious adverse events compared with placebo.
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| 4. |
- Olsson, Anders, 1940-, et al.
(författare)
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Comparison of the efficacy and tolerability of fluvastatin extended-release and immediate-release formulations in the treatment of primary hypercholesterolemia : A randomized trial
- 2001
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Ingår i: Clinical Therapeutics. - 0149-2918 .- 1879-114X. ; 23:1, s. 45-61
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Tidskriftsartikel (refereegranskat)abstract
- Background: A new extended-release (ER) formulation of fluvastatin 80 mg has been developed for once-daily treatment of primary hypercholesterolemia. Objective: The purpose of this study was to compare the lipid-lowering efficacy and tolerability of fluvastatin ER (80 mg once daily) versus fluvastatin immediate-release (IR) (40 mg once or twice daily). Methods: Following a 4-week placebo/dietary run-in period, patients with primary hypercholesterolemia type IIa or IIb (low-density lipoprotein cholesterol [LDL-C] =160 mg/dL and triglycerides [TG] =400 mg/dL) were randomized (2:1:1) to receive fluvastatin ER 80 mg once daily at bedtime (QPM), fluvastatin IR 40 mg QPM, or fluvastatin IR 40 mg BID for 24 weeks. Patients who had homozygous familial hypercholesterolemia, type I, III, IV, V, or secondary hyperlipoproteinemia, diabetes, or evidence of liver or renal impairment were excluded. At weeks 0, 2, 4, 8, 12, 16, 20, and 24 of the active-treatment period, levels of LDL-C, high-density lipoprotein cholesterol (HDL-C), TG, and total cholesterol (TC) were measured. Results: Of the 1183 patients enrolled, 695 were randomly assigned to treatment, 346 to fluvastatin ER 80 mg QPM, 174 to fluvastatin IR 40 mg QPM, and 175 to fluvastatin IR 40 mg BID. Patients were well matched between groups, with a mean age of-56 years and body mass index of 27 kg/m2, 56.0% of patients (389/695) were female and 97.7% (679/695) were white. Fluvastatin ER 80 mg QPM lowered LDL-C levels significantly more than did fluvastatin IR 40 mg QPM (33.7% vs 24.4%, P < 0.001) and as effectively as fluvastatin IR 40 mg BID (33.9%). More than half of the patients administered fluvastatin ER 80 mg QPM and IR 40 mg BID achieved reductions in LDL-C levels of =35%, more than half of those administered fluvastatin IR 40 mg QPM experienced reductions in LDL-C levels of =25%. The mean reductions in LDL:HDL ratio, TC, and apolipoprotein B levels in the fluvastatin ER 80 mg QPM group were significantly greater than the reductions in the IR 40 mg QPM group (P < 0.001). In patients with mixed dyslipidemia, fluvastatin ER 80 mg reduced triglycerides by 21.8% (median 28%) and increased HDL-C by 14.5%. Fluvastatin ER 80 mg QPM was well tolerated, with incidences of clinically notable elevations in alanine aminotransferase, aspartate aminotransferase, and creatine kinase levels and musculoskeletal adverse events comparable to those in the IR 40 mg QPM group. Conclusion: The ER 80-mg formulation of fluvastatin is effective and well tolerated as a once-daily starting and maintenance treatment for primary hypercholesterolemia.
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| 5. |
- Stenqvist, Monika, et al.
(författare)
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Penetration of Loracarbef into the maxillary sinus : a pharmacokinetic assessment
- 1996
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Ingår i: Clinical Therapeutics. - 0149-2918 .- 1879-114X. ; 18:2, s. 273-84
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Tidskriftsartikel (refereegranskat)abstract
- Loracarbef, a beta-lactam antibiotic of the carbacephem class, is active in vitro against pathogens associated with acute maxillary sinusitis. To study the extent and duration of maxillary sinus fluid penetration after administration of loracarbef, 20 patients (10 men, 10 women; average age, 41 +/- 13 years) with acute sinusitis were treated with loracarbef 400 mg every 12 hours for 10 days. A lavage catheter was inserted into the maxillary sinus, and 150-microL sinus fluid samples were obtained at 0 (baseline), 0.5, 1, 1.5, 2, and 2.5 hours after the first dose and at 24 and 48 hours (12 hours after the second and fourth doses, respectively). Venous blood samples were obtained at the same times. Maxillary fluid and serum samples were frozen immediately at -20 degrees C to -70 degrees C until later bioassay using a direct agar diffusion method. Excluding missing data or inappropriately timed samples, the mean (+/- SD) sinus fluid concentrations were 0.16 +/- 0.12 microgram/mL at baseline, 0.23 +/- 0.17 microgram/mL at 0.5 hour, 1.11 +/- 1.44 micrograms/mL at 1 hour, 1.63 +/- 2.07 micrograms/mL at 1.5 hours, 1.75 +/- 2.01 micrograms/mL at 2 hours, and 1.60 +/- 1.96 micrograms/mL at 2.5 hours after dose. The mean sinus fluid concentration before the third dose (approximately 12 hours after the second dose) was 1.01 +/- 0.89 microgram/mL and before the fifth dose (approximately 12 hours after the fourth dose) was 0.88 +/- 0.90 microgram/mL. Taking the highest sinus fluid concentration measured in each patient, the mean peak sinus fluid concentration was 2.12 +/- 1.98 micrograms/mL (range, 0 to 6.7 micrograms/mL). The pretherapy peripheral leukocyte count appeared to have a statistically significant association (P < 0.01) with loracarbef sinus fluid penetration as estimated by the sinus fluid area under the concentration-time curve at 0 to 2.5 hours. Loracarbef 400 mg twice daily achieved sinus fluid concentrations that appeared to exceed the minimum concentration required to inhibit 90% of relevant acute sinusitis pathogens throughout the 12-hour interdose interval in most patients with acute maxillary sinusitis.
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| 6. |
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| 7. |
- Amundstuen Reppe, Linda, et al.
(författare)
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Relationship Between Time Consumption and Quality of Responses to Drug-related Queries: A Study From Seven Drug Information Centers in Scandinavia
- 2016
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Ingår i: Clinical Therapeutics. - : ELSEVIER. - 0149-2918 .- 1879-114X. ; 38:7, s. 1738-1749
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aims of this study were to assess the quality of responses produced by drug information centers (DICs) in Scandinavia, and to study the association between time consumption processing queries and the quality of the responses. Methods: We posed six identical drug-related queries to seven DICs in Scandinavia, and the time consumption required for processing them was estimated. Clinical pharmacologists (internal experts) and general practitioners (external experts) reviewed responses individually. We used mixed model linear regression analyses to study the associations between time consumption on one hand and the summarized quality scores and the overall impression of the responses on the other hand. Findings: Both expert groups generally assessed the quality of the responses as "satisfactory" to "good." A few responses were criticized for being poorly synthesized and less relevant, of which none were quality-assured using co-signatures. For external experts, an increase in time consumption was statistically significantly associated with a decrease in common quality score (change in score, -0.20 per hour of work; 95% CI, -0.33 to -0.06; P = 0.004), and overall impression (change in score, -0.05 per hour of work; 95% CI, -0.08 to -0.01; P = 0.005). No such associations were found for the internal experts assessment. Implications: To our knowledge, this is the first study of the association between time consumption and quality of responses to drug-related queries in DICs. The quality of responses were in general good, but time consumption and quality were only weakly associated in this setting. (C) 2016 The Authors. Published by Elsevier HS Journals, Inc.
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| 8. |
- Anthony, Lowell, et al.
(författare)
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Understanding the Patient Experience with Carcinoid Syndrome : Exit Interviews from a Randomized, Placebo-controlled Study of Telotristat Ethyl
- 2017
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Ingår i: Clinical Therapeutics. - : Elsevier. - 0149-2918 .- 1879-114X. ; 39:11, s. 2158-2168
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in FELESTAR, a Phase HI study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview sub study was conducted to provide insight into the patient experience in ILLESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful. Methods: Participating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at the end of the double-blind treatment period. Patients and interviewers were blinded to treatment. Findings: All 35 interviewed participants reported diarrhea and/or excessive BMs at baseline. Patients reported that these symptoms negatively affected emotional, social, physical, and occupational well-being. Prespecified criteria for treatment response (achieving >= 30% reduction in BM frequency for at least 50% of the days) were met by 8 of 26 patients taking telotristat ethyl and 1 of 9 patients taking placebo. All 8 patients taking telotristat ethyl described clinically meaningful reductions in BM frequency and were very satisfied with the ability of the study drug to control their carcinoidsyndrome symptoms. Overall, reports of being very satisfied were observed in 12 patients taking telotristat ethyl and 0 taking placebo. Implications: Patient interviews revealed that I ELESTAR patients, at baseline, were significantly affected by their high BM frequency. Patient reports of their clinical trial experience supported the significance of the primary end point and clinical responder analysis in TELESTAR, helping identify and understand clinically meaningful change produced by telotristat ethyl. (C) 2017 The Authors. Published by Elsevier HS Journals, Inc.
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| 9. |
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| 10. |
- By, Asa, et al.
(författare)
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Comparing Health Outcomes and Costs of General Vaccination with Pneumococcal Conjugate Vaccines in Sweden: A Markov Model
- 2012
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Ingår i: Clinical Therapeutics. - : Elsevier BV. - 0149-2918 .- 1879-114X. ; 34:1, s. 177-189
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Tidskriftsartikel (refereegranskat)abstract
- Background: Two new pneumococcal conjugate vaccines were licensed to immunize infants and young children against pneumococcal disease. Objectives: The objective of this study was to estimate the expected health benefits, costs, and incremental cost-effectiveness of routine vaccination with the 10-valent pneumococcal nontypeable hemophilus influenza protein-D conjugate vaccine (PHiD-CV) compared with the 13-valent pneumococcal conjugate vaccine (PCV13) in Sweden. Methods: A Markov cohort model was used to estimate the effect of vaccination at vaccine steady state, taking a societal perspective and using a 2+1 vaccination schedule. Price parity was assumed between the vaccines. Outcomes were measured by reduction in disease burden, costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. Results: The results predicted that PCV13 would prevent 3 additional cases of invasive pneumococcal disease and 34 additional cases of pneumonia, whereas PHiD-CV would avoid 3 additional cases of mastoiditis, 1010 tube insertions, and 10,420 cases of ambulatory acute otitis media compared with PCV13. By combining morbidity and mortality benefits of all clinical outcomes, PHiD-CV would generate 45.3 additional QALYs compared with PCV13 and generate savings of an estimated 62 million Swedish kronors. Conclusion: The present study predicted lower costs and better health outcome (QALYs) gained by introducing PHiD-CV compared with PCV13 in routine vaccination. Our results indicated that PHiD-CV is cost-effective compared with PCV13 in Sweden. (Clin Ther. 2012;34:177-189) (C) 2012 Elsevier HS Journals, Inc. All rights reserved.
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| 11. |
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| 12. |
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| 13. |
- Chen, Yundai, et al.
(författare)
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Treatment Trends, Effectiveness, and Safety of Statins on Lipid Goal Attainment in Chinese Percutaneous Coronary Intervention Patients : a Multicenter, Retrospective Cohort Study
- 2017
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Ingår i: Clinical Therapeutics. - : ELSEVIER. - 0149-2918 .- 1879-114X. ; 39:9, s. 1827-1839
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Limited data exist on the use of statins in Chinese patients with coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI). We therefore conducted this study to observe the usage trend and the effectiveness of statins on LDL-C goal attainment and other lipid parameters among PCI-treated patients.Methods: This multicenter, retrospective, observational, longitudinal cohort study was conducted in PCI-treated patients with CAD between July 1, 2011, and February 28, 2015. Primary study outcomes included statin treatment pattern after PCI and proportion of patients achieving target (LDL-C) levels 1 month after PCI and initiating statin therapy.Findings: Data were analyzed for 2708 patients (mean age, 59 [10] years; median body mass index, 25.6 [4.0] kg/m(2)). From baseline to the end of 1 month, atorvastatin and rosuvastatin were the most prescribed statins; 20 mg and 10 mg were the most prescribed doses and therefore chosen for efficacy comparisons. In patients without dose changes, LDL-C reduction with rosuvastatin 10 mg was significantly greater compared with atorvastatin 20 mg (-0.67 mmol/L [from 2.44 mmol/L to 1.77 mmol/L] vs 0.54 mmol/L [from 2.40 mmol/L to 1.86 mmol/L]; P = 0.008). However, there was no difference in HDL-C, triglyceride, or total cholesterol values between groups. Age and LDL-C levels at baseline were significantly associated with target LDL-C achievement.
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| 14. |
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| 18. |
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| 20. |
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| 21. |
- Lindgren, Peter, et al.
(författare)
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The long-term cost-effectiveness of clopidogrel plus aspirin in patients undergoing percutaneous coronary intervention in Sweden
- 2005
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Ingår i: Clinical Therapeutics. - : Elsevier BV. - 0149-2918 .- 1879-114X. ; 27:1, s. 100-110
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Percutaneous CoronaryIntervention-Clopidogrel in Unstable Angina to Prevent Recurrent Events (PCI-CURE) study, which examined the effect of adding clopidogrel to aspirin versus aspirin alone in patients with unstable coronary artery disease (CAD) undergoing PCI, found a relative risk reduction in cardiovascular deaths and myocardial infarction among those treated with clopidogrel. In addition, a within-trial cost-effectiveness analysis showed favorable costs per event avoided. However, to estimate the long-term effects, a modeling approach is necessary. Objectives: The purpose of this study was to estimatethe long-term cost-effectiveness of treating patients undergoing PCI with clopidogrel plus aspirin in Sweden. Methods: A Markov model was developed. Transitionprobabilities were estimated based on a register of patients treated in the coronary care units at 74 (out of 78) hospitals throughout Sweden. Patients were assumed to be treated for 1 year with an effect based on data from the PCI-CURE study. Costs were collected from published sources and recalculated to year-2004 euros (1.00 = US $1.24). Life-years gained were used as the measure of effectiveness. The perspective was that of the Swedish society, with a separate analysis using a health care cost perspective. Results: After inclusion and exclusion criteria were applied, 3474 patients were included in the model analysis. The model predicted a net gain in survival of 0.04 year per patient when adding clopidogrel. This yielded a net increase of 449 if only direct costs were included, with indirect costs, the net increase was 332. The resulting cost-effectiveness ratios were €10,993 and 8127 per life-year gained. Conclusions: The predicted cost-effectiveness ratios were well below the threshold values generally considered cost-effective. Adding clopidogrel to aspirin appeared to be cost-effective in this model analysis of patients with unstable CAD undergoing PCI in Sweden. Copyright © 2005 Excerpta Medica, Inc.
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| 22. |
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| 23. |
- Olsson, Anders G.
(författare)
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Expanding options with a wider range of rosuvastatin doses
- 2006
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Ingår i: Clinical Therapeutics. - : Elsevier BV. - 0149-2918 .- 1879-114X. ; 28:11, s. 1747-1763
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Tidskriftsartikel (refereegranskat)abstract
- Background: The dose range for rosuvastatin in Europe has recently been expanded to 5 to 40 mg and is now in line with the dose range currently available in the United States. Objective: The goal of this article was to review the efficacy and safety data available for the rosuvastatin 5-mg dose and discuss these data in the context of the full 5- to 40-mg dose range. Methods: Articles referring to clinical efficacy or safety data for the 5-mg dose of rosuvastatin were identified and reviewed after a search of the MEDLINE database (2000-August 2006, English language only) using the search term rosuvastatin. Proceedings from major cardiology congresses (2000-2006) were also searched for additional information. Results: Rosuvastatin 5 mg is significantly (P < 0.001) more effective at reducing low-density lipoprotein cholesterol (LDL-C) and total cholesterol (42% and 30%) levels compared with atorvastatin 10 mg (36% and 27%), simvastatin 20 mg (36% and 25%), and pravastatin 20 mg (27% and 19%). Rosuvastatin 5 mg allows significantly more patients to reach their LDL-C goals as recommended by the 2003 European guidelines and the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (49%-52% and 67%-71%) than atorvastatin 10 mg (36%, P < 0.001, 53%, P < 0.01), simvastatin 20 mg (37%, P < 0.001, 64%, P < 0.05), and pravastatin 20 mg (12%, P < 0.001, 49%, P < 0.001). Rosuvastatin is well tolerated across the 5- to 40-mg dose range, with a type and incidence of adverse events similar to the other commonly available, but less effective, statins. The introduction of a 5-mg dose offers greater flexibility to prescribing physicians in that it provides an additional dosing option for those patients who are at a lower cardiovascular risk or who have an increased potential for developing myopathy with statin therapy. Conclusions: Rosuvastatin 5 mg is well tolerated and has beneficial effects across the atherogenic lipid profile by reducing LDL-C and total cholesterol, raising high-density lipoprotein cholesterol, and helping a greater proportion of patients reach their LDL-C goals. © 2006 Excerpta Medica, Inc.
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| 29. |
- Weickert, Martin O., et al.
(författare)
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Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome
- 2018
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Ingår i: Clinical Therapeutics. - : ELSEVIER. - 0149-2918 .- 1879-114X. ; 40:6, s. 952-962
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In the placebo-controlled Phase III TELE-STAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and >= 4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m(2)) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.Methods: Assessment of the occurrence of weight change >= 3% at week 12 was prespecified in the statistical analysis plan.Findings: In 120 patients with weight data available, weight gain >= 3% was observed in 2 of 39 patients (5.1%) taking placebo [1.1), 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss >= 3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.
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| 30. |
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| 31. |
- Björkander, Janne, et al.
(författare)
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Intravenous immunoglobulin and hepatitis C virus: the Scandinavian experience
- 1996
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Ingår i: Clinical Therapeutics. - 0149-2918. ; 18:Suppl 2, s. 73-82
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Tidskriftsartikel (refereegranskat)abstract
- In Sweden, 44 patients were reported to have contracted hepatitis C virus (HCV) infections from treatment with intravenous immunoglobulin. Gammagard was the product implicated in HCV transmission in 12 patients; 8 of these 12 patients were HCV ribonucleic acid (RNA)-negative during the 2 years before Gammagard was administered and 10 showed clustering by sequencing of the HCV core gene. Further studies are being conducted to correlate the sequenced HCV RNA with specific batches of Gammagard. Nine patients who received Gammonativ in 1983 and 1984 had a strong time-related possibility of HCV infection. Sequencing analyses are being performed in these patients as is being done for the patients who received Gammagard. Another 21 patients who received Gammonativ from 1982 to 1985 are probably infected with HCV, but confirmation of implicated batches is lacking. The association between Sandoglobulin and HCV is questionable in two patients, although plausible because of a time relationship. In Norway, relationships between Gammonativ and the incidence of HCV infection are similar to those in the 21 sporadic cases in Sweden. Also in Denmark and Finland, HCV infection appears to be related to the lack of additional viral inactivation steps used in the preparation of intravenous immunoglobulin. Clearly, there is a need for increased antiviral inactivation and antiviral screening in the production of intravenous immunoglobulin products.
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| 37. |
- Ben-Menachem, Elinor, 1945, et al.
(författare)
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Topiramate monotherapy in the treatment of newly or recently diagnosed epilepsy.
- 2008
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Ingår i: Clinical therapeutics. - 0149-2918. ; 30:7, s. 1180-95
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The efficacy of topiramate (TPM) as an adjunctive treatment for epilepsy has been established in placebo-controlled clinical trials. Clinical trials of antiepileptic monotherapy usually evaluate low and high doses of study drug or compare study drug with another active agent. OBJECTIVE: This article reviews available evidence for the use of TPM as monotherapy in patients with newly or recently diagnosed epilepsy. METHODS: A search of MEDLINE, EMBASE, BIOSIS, SCISEARCH, and the Cochrane Database of Systematic Reviews (all years) for reports of controlled trials of TPM monotherapy in patients with recently diagnosed (within the previous 3 years) epilepsy was conducted in January 2008 using the terms topiramate, epilepsy, newly diagnosed, recently diagnosed, and monotherapy. Identified trials were included in the review if they were published in peer-reviewed journals and enrolled > or = 20 patients. RESULTS: Three randomized, double-blind, controlled trials met the criteria for inclusion in the review. In a comparison of TPM 50 and 500 mg/d, the higher dose was associated with significantly greater freedom from seizures at 6 months compared with the lower dose (54% vs 39%, respectively; P = 0.02). The time to first seizure was significantly associated with mean plasma TPM concentrations (P = 0.015). In a comparison of TPM 50 and 400 mg/d, the time to first seizure was significantly longer with the higher dose compared with the lower dose (P<0.001, Kaplan-Meier analysis), and the probability of 12-month seizure freedom was significantly higher (76% vs 59%, respectively; P = 0.001). Again, the time to first seizure was significantly associated with mean plasma TPM concentrations (P = 0.029). In a comparative study of TPM 100 and 200 mg/d, carbamazepine 600 mg/d, and valproate 1250 mg/d, there was no significant difference in rates of 6-month seizure freedom with TPM 100 and 200 mg/d (49% and 44%, respectively), carbamazepine (44%), and valproate (44%). Adverse events in the 3 studies were similar between TPM dose groups, although the incidence generally increased with increasing doses, occurred early in treatment, and decreased with prolonged therapy. In a pooled analysis of the 3 trials, the most commonly occurring adverse events during dose titration were paresthesia (25%), fatigue (16%), dizziness (13%), somnolence (13%), and nausea (10%); the most frequent adverse events during maintenance therapy were headache (20%), decreased appetite (11%), and weight loss (11%). CONCLUSION: In the 3 studies reviewed, TPM monotherapy was effective and generally well tolerated in patients with newly diagnosed epilepsy.
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| 40. |
- Ghatnekar, Ola, et al.
(författare)
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Direct hospital resource utilization and costs of treating patients with multiple myeloma in Southwest Sweden: a 5-year retrospective analysis.
- 2008
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Ingår i: Clinical Therapeutics. - : Elsevier BV. - 0149-2918. ; 30:9, s. 1704-1713
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Approximately 570 patients are diagnosed with multiple myeloma (MM) in Sweden each year. Few studies have estimated the cost of treatment for these patients. OBJECTIVE: The purpose of this study was to retrospectively investigate the direct hospital resource utilization and costs associated with the treatment of patients with MM in southwest Sweden. METHODS: Patients aged > or =18 years who initiated first-line chemotherapy in the year 2001 at hospitals in southwestern Sweden were included in this retrospective chart review. Direct hospital-based resources and their corresponding costs (year-2006 euros) for each patient were calculated until the patient's death, or until December 31, 2005. Costs for outpatient and terminal stage care related to MM were not included. RESULTS: Ninety-four patients were included; 20 were still alive at study completion. Mean age at diagnosis was 76 years and patients were followed for a mean of 32.7 months; 55% were males and 74% had at least 1 comorbidity. First-, second-, and third-line treatment lasted a mean of 24.3, 5.8, and 2.6 months, and included 2.8, 2.6, and 3.1 chemotherapy drugs per patient, respectively. Of the 80 patients who received first-line chemotherapy, 72 were prescribed melphalan and 55 patients received a combination of melphalan and prednisone, as recommended by Swedish treatment guidelines. The mean total cost per patient was euro88,199, or euro2770 per patient-month. Therapy-induced and comorbidity-related events constituted 42% of total costs, as much as autologous stem-cell transplantation and inpatient care together. Chemotherapy, bisphosphonate, and blood cell-enhancement drugs each amounted to only 2% of total costs, but chemotherapy drugs increased from euro29/month in first-line therapy to euro453/month in third-line therapy. CONCLUSIONS: The cost of treating Swedish patients with MM varied greatly between individuals but, overall, chemotherapy drugs constituted only a minor part of the total monthly cost (2%), whereas costs for inpatient stays and therapy-induced adverse events or comorbidity-related events accounted for 35% and42%, respectively. There was no significant differencein monthly cost between treatment lines.
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- Ma, Changsheng, et al.
(författare)
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Effect of Dronedarone in the Treatment of Atrial Fibrillation in the Asian Population : Post Hoc Analysis of the ATHENA Trial
- 2022
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Ingår i: Clinical Therapeutics. - : Elsevier BV. - 0149-2918. ; 44:9, s. 1203-1213
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Limited data are available on the impact of dronedarone treatment in Asian patients with atrial fibrillation (AF) or atrial flutter (AFL). This post hoc analysis evaluated the efficacy and safety of dronedarone compared with placebo in populations from Asian and non-Asian regions randomized in the ATHENA trial (A Placebo-Controlled, Double-blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg BID for the Prevention of CV Hospitalization or Death From Any Cause in Patients With AF/AFL). Methods: Time to first hospitalization for cardiovascular events or death from any cause (primary outcome) and time to first AF/AFL event recurrence (secondary outcome) were analyzed by Kaplan-Meier curves and Cox proportional hazards regression. Findings: The risk of experiencing the primary composite outcome was significantly lower in the dronedarone-treated patients in both the Asian (hazard ratio = 0.541; 95% CI, 0.320–0.914]) and non-Asian (hazard ratio = 0.768; 95% CI, 0.696–0.848) populations than in the placebo-treated patients. The median time to the first AF/AFL event recurrence was longer in the dronedarone-treated population than in the placebo-treated populations: 183 vs 92 days (P = 0.165) in the Asian population and 534 vs 196 days (P < 0.001) in the non-Asian population. Treatment-emergent adverse events in Asian (81.2% vs 78.4%) and non-Asian (71.4% vs 68.7%) populations and serious treatment-emergent adverse events in Asian (14.3% vs 15.7%) and non-Asian (20.3% vs 21.5%) patients were comparable in patients taking dronedarone compared with those taking placebo. Implication: Efficacy and tolerability of dronedarone were consistent in the Asian population compared with the non-Asian population in the ATHENA trial. These finding may aid Asian health care professionals to select the appropriate first-line treatment for Asian patients with AF/AFL.
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- Mellström, Dan, 1945, et al.
(författare)
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Proportion and Characteristics of Patients in Sweden Remaining at High Risk of Fracture Despite Prior Treatment
- 2016
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Ingår i: Clinical Therapeutics. - : Elsevier BV. - 0149-2918. ; 38:7, s. 1686-1695
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Fragility fractures axe a clinical consequence of osteoporosis (OP). Evidence suggests however, current OP treatments may be inadequate in reducing fracture risk. The purpose of this study was to estimate the proportion and characteristics of Swedish patients who remain at high risk of fracture after 2 years of treatment, as evidenced by osteoporotic bone mineral density (BMD), a decrease in BMD, or the occurrence of new fractures. Methods: This was a retrospective, descriptive analysis of a subset of participants obtained from a Swedish osteoporosis patient registry from 1991 to 2009. Patients were required to be osteoporotic, to be treatment naive at baseline, to have returned for at least 1 follow-up visit, and to have reported osteoporosis treatment use for >= 2 years after the baseline visit with a BMD T score. Two overlapping cohorts remaining at high risk of fracture were defined using the BMD T score measured after 2 years of treatment from baseline. The osteoporosis cohort comprised patients who remained osteoporotic, whereas the BMD decrease cohort included patients whose total hip or lumbar spine T score decreased by >= 3%. Findings: A total of 3292 osteoporotic patients were identified in the registry, of whom 392 met the study inclusion criteria. The mean (SD) patient age was 68.3 (8.5) years, with most patients being female (92.3%). Among all patients, 297 (75.8%) remained osteoporotic after at least 2 years of treatment, 90 (23.0%) experienced a BMD decrease of >= 3%, and 23 (5.9%) reported an incident fracture between the baseline and first follow-up visit. More than three-quarters (76.8%) of all patients reported taking bisphosphonates, whereas only 72.4% and 47.8% reported this in the osteoporosis and BMD decrease cohorts, respectively. Raloxifene was the only nonbisphosphonate used, with 24.2% of all patients reportedly taking it. Implications: This study highlighted that despite 2 years of osteoporosis treatment, a high percentage of patients remain at high risk of fracture. There is a need for improved treatment strategies that reduce fracture risk and improve patient outcomes in the real-world setting.
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- Rydholm, H., et al.
(författare)
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Reducing Adverse Effects During Drug Development: The Example of Lesogaberan and Paresthesia
- 2016
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Ingår i: Clinical Therapeutics. - : Elsevier BV. - 0149-2918. ; 38:4, s. 946-960
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Lesogaberan, a gamma-aminobutyric acid (GABA)(B) receptor agonist, was developed for the treatment of gastroesophageal reflux disease in patients with a partial response to proton pump inhibitor therapy. A high prevalence of paresthesia was observed in healthy individuals after dosing with lesogaberan in early-phase clinical trials. The aim of this review was to gain further insight into paresthesia caused by lesogaberan by summarizing the relevant preclinical and clinical data. Methods: This study was a narrative review of the literature and unpublished data. Findings: The occurrence of paresthesia may depend on the route or rate of drug administration; several studies were conducted to test this hypothesis, and formulations were developed to minimize the occurrence of paresthesia. Phase I clinical studies showed that, in healthy individuals, paresthesia occurred soon after administration of lesogaberan in a dose-dependent manner regardless of the route of administration. The occurrence of paresthesia could be decreased by fractionating the dose or reducing the rate of administration. These findings suggest that the initial rate of absorption plays an important part in the development of paresthesia. Modified-release formulations minimize the occurrence of paresthesia while retaining the anti-reflux activity of the drug, as measured by esophageal pH and the number of transient lower esophageal sphincter relaxations. Implications: The development of lesogaberan was halted because the effect on gastroesophageal reflux disease symptoms observed in Phase II studies was not considered clinically meaningful in the target patient population. Nevertheless, it is an example of successful formulation development designed to minimize the occurrence of a compound's adverse effect while retaining its pharmacodynamic action. (C) 2016 Elsevier HS Journals, Inc. All rights reserved.
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