| 1. |
- Abd-Elaziz, Khalid, et al.
(författare)
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First-in-Man Safety, Tolerability, and Pharmacokinetics of a Novel and Highly Selective Inhibitor of Matrix Metalloproteinase-12, FP-025 : Results from Two Randomized Studies in Healthy Subjects
- 2021
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Ingår i: Clinical Drug Investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 41:1, s. 65-76
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Matrix metalloproteinases (MMPs) are proteases with different biological and pathological activities, and many have been linked to several diseases. Targeting individual MMPs may offer a safer therapeutic potential for several diseases. We assessed the safety, tolerability, and pharmacokinetics of FP-025, a novel, highly selective oral matrix metalloproteinase-12 inhibitor, in healthy subjects. Methods: Two randomized, double-blind, placebo-controlled studies were conducted. Study I was a first-in-man study, evaluating eight single ascending doses (SADs) (50–800 mg) in two formulations: i.e., neat FP-025 in capsule (API-in-Capsule) and in an amorphous solid dispersion (ASD-in-Capsule) formulation. In Study II, three multiple ascending doses (MADs) (100, 200, and 400 mg, twice daily) of FP-025 (ASD-in-Capsule) were administered for 8 days, including a food-effect evaluation. Results: Ninety-six subjects were dosed. Both formulations were well tolerated with one adverse event (AE) reported in the 800 mg API-in-Capsule SAD group and seven AEs throughout the MAD groups. The exposure to FP-025 was low with the API-in-Capsule formulation; it increased dose-dependently with the ASD-in-Capsule formulation, with which exposure to FP-025 increased in a greater-than-dose-proportional manner at lower doses (≤ 100 mg) but less proportionally at higher doses. The elimination half-life (t1/2) was between 6 (Study I) and 8 h (Study II). Accumulation of FP-025 was approximately 1.7-fold in the MAD study. Food intake delayed the rate of absorption, but without effect in the extent of absorption or bioavailability. Conclusion: FP-025 was well tolerated and showed a favorable pharmacokinetic profile following ASD-in-Capsule dosing. Efficacy studies in target patient populations, including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis, are warranted. Trial registration number: www.clinicaltrials.gov: NCT02238834 (Study I); NCT03304964 (Study II). Trial registration date: Study I was registered on 12 September 2014 while study II was registered on 9 October 2017.
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| 2. |
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| 3. |
- Biffi, Annalisa, et al.
(författare)
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Adherence to Antidepressants and Mortality in Elderly Patients with Cardiovascular Disease
- 2018
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Ingår i: Clinical drug investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 38:7, s. 593-602
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Tidskriftsartikel (refereegranskat)abstract
- Background and ObjectiveConflicting findings from studies evaluating the association between use of antidepressant drugs and mortality have been reported. We tested the hypothesis that better adherence to antidepressant therapy may reduce mortality.MethodsThe cohort included 29,845 individuals aged >= 65 years from several Italian health units who were newly treated with antidepressant drugs after hospital discharge with a diagnosis for cardiovascular disease during 2008-2010. These individuals were observed from the first prescription until the end of data availability (i.e. 2012-2014, depending on the local database). During this period, information on (1) prescription of antidepressants and other medications and (2) death from any cause (outcome) was recorded. Proportional hazards models were fitted to estimate the association between better adherence to antidepressants (defined as proportion of days covered > 75%) and outcome, by adjusting and stratifying for several covariates.ResultsPatients with better adherence to antidepressants had a reduced mortality of 9% (95% CI 3-14). Patients who did not use other medicaments during follow-up had reduced mortality associated with better adherence to antidepressants of 21% (- 1-38), 14% (7-20), 20% (13-26) and 13% (7-19) for no users of antihypertensive agents, lipid-lowering agents, other cardiovascular drugs and antidiabetics, respectively.ConclusionsBetter adherence to antidepressants is associated with reduced all-cause mortality, mainly in patients who did not use other pharmacological treatments. Behavioural changes to enhance adherence among the elderly with cardiovascular disease might offer important benefits in reducing their mortality.
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| 4. |
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| 5. |
- Cazzola, M., et al.
(författare)
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Onset of action of formoterol versus salmeterol via dry powder inhalers in moderate chronic obstructive pulmonary disease: A randomized, placebo-controlled, double-blind, crossover study
- 2012
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Ingår i: Clinical Drug Investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 32:3, s. 147-155
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bronchodilator therapy is central to the symptomatic management of chronic obstructive pulmonary disease (COPD), and treatment with short-acting bronchodilators is recommended in patients with mild COPD. Objective: This study aimed to evaluate the onset of effect of single-dose formoterol 9 μg versus single-dose salmeterol 50 μg in patients with moderate COPD. Methods: In this multicentre, double-blind, double-dummy, placebo-controlled, three-way single-dose crossover study, patients ≥40 years of age with moderate COPD were randomized to single-dose formoterol 9 μg via Turbuhaler® plus placebo via Diskus®, single-dose salmeterol 50 μg via Diskus® plus placebo via Turbuhaler® or placebo via Turbuhaler® and Diskus® (washout period 2-7 days). Terbutaline 0.5mg/actuation via Turbuhaler® was used as reliever medication throughout. The primary endpoint was forced expiratory volume in 1 second (FEV 1) at 5 minutes post-dose. Secondary endpoints included proportion of patients achieving ≥12%increase in FEV1 at 5 minutes post-dose. Results: 109 patients were randomized, and 108 completed the study. The increase in FEV1 5 minutes post-dose versus pre-dose was 7.2% for formoterol, 4.1% for salmeterol and 0.7% for placebo, and significantly greater for formoterol versus salmeterol (ratio of treatment effects: 1.030; 95% CI 1.008, 1.052; p = 0.009), for formoterol versus placebo (1.064, 95% CI 1.041, 1.087; p < 0.001) and for salmeterol versus placebo (1.033, 95% CI 1.011, 1.056; p = 0.003). The proportions of patients with ≥12% increase in FEV 1 5 minutes post-dose were 23.1%, 9.2%and 6.4%for formoterol, salmeterol and placebo, respectively; this was statistically significantly larger after formoterol than salmeterol (p = 0.008) or placebo (p < 0.001). All treatments were well tolerated. Conclusion: In COPD patients, formoterol 9 μg has an onset of bronchodilatory effect that is more rapid than salmeterol 50 μg based on FEV 1 at 5minutes post-dose. © 2012 Adis Data Information BV. All rights reserved.
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| 6. |
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| 7. |
- Chauca Strand, Gabriella, 1995, et al.
(författare)
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Cancer Drugs Reimbursed with Limited Evidence on Overall Survival and Quality of Life : Do Follow-Up Studies Confirm Patient Benefits?
- 2023
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Ingår i: Clinical drug investigation. - : Springer. - 1173-2563 .- 1179-1918. ; 43:8, s. 621-633
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Tidskriftsartikel (refereegranskat)abstract
- Background and ObjectiveCancer drug costs have increased considerably within healthcare systems, but many drugs lack quality-of-life (QoL) and overall survival (OS) data at the time of reimbursement approval. This study aimed to review the extent of subsequent literature documenting improvements in OS and QoL for cancer drug indications where no such evidence existed at the time of reimbursement approval.MethodsDrug indications with claims of added therapeutical value but a lack of evidence on OS and QoL that were reimbursed between 2010 and 2020 in Sweden were included for review. Searches were conducted in PubMed and ClinicalTrial.gov for randomized controlled trials examining OS and QoL.ResultsOf the 22 included drug indications, seven were found to have at least one trial with conclusive evidence of improvements in OS or QoL after a mean follow-up of 6.6 years. The remaining 15 drug indications either lacked subsequent randomized controlled trial data on OS or QoL (n = 6) or showed no statistically significant improvements (n = 9). Only one drug demonstrated evidence of improvement in both OS and QoL for its indication.ConclusionsA considerable share of reimbursed cancer drug indications continue to lack evidence of improvement in both OS and QoL. With limited healthcare resources and an increasing cancer burden, third-party payers have strong incentives to require additional post-reimbursement data to confirm any improvements in OS and QoL.
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| 8. |
- Claesson, Cecilia B., et al.
(författare)
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Drug use in Swedish nursing homes
- 1998
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Ingår i: Clinical drug investigation. - 1173-2563 .- 1179-1918. ; 16:6, s. 441-52
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Cornelius, C, et al.
(författare)
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Self-reported symptoms in the elderly and association with drug use
- 1997
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Ingår i: Clinical drug investigation. - 1173-2563 .- 1179-1918. ; 13:2, s. 105-117
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Tidskriftsartikel (refereegranskat)abstract
- Summary: In a cross-sectional study, we have investigated the prevalence of self-reported symptoms and their association with medicinal drug use in elderly people. Data from the Kungsholmen Project were used, a population-based study of elderly people aged 75 years and over in Stockholm, Sweden. The study sample comprised 1800 persons. Information on the occurrence of 22 different symptoms and the actual drug use was obtained at interviews with the participants. The relation of symptoms to age, gender and housing, and their association with drug use was analysed using logistic regression. The most commonly reported symptoms were pain and tiredness. In general, symptoms were more common in women and at higher ages. Many of the associations between symptoms and drug use reflected established treatments. However, some were suggestive of inappropriate treatment or dosage; for example, the association between tiredness and the use of anxiolytics and hypnotics-sedatives.
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| 10. |
- EHINGER, JOHANNES, et al.
(författare)
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Bioequivalence and Tolerability Assessment of a Novel Intravenous Ciclosporin Lipid Emulsion Compared to Branded Ciclosporin in Cremophor(®) EL.
- 2013
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Ingår i: Clinical Drug Investigation. - : Springer Science and Business Media LLC. - 1179-1918 .- 1173-2563. ; 33:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ciclosporin is used as an immunosuppressant in current clinical practice but recent research implies novel indications for the drug, such as neuro- and cardioprotection. The intravenous formulation currently on the market, Sandimmune(®) Injection (Sandimmune(®)), uses Cremophor(®) EL as emulsifying excipient. Cremophor(®) EL is known to cause hypersensitivity reactions in some patients, ranging from skin reactions to potentially fatal anaphylactic shock. OBJECTIVES: The primary objective was to assess if CicloMulsion(®), a Cremophor(®) EL-free lipid emulsion of ciclosporin for intravenous administration, is bioequivalent to Sandimmune(®), and the secondary objective was to compare the tolerability profiles of the two preparations. METHODS: This was a single-centre, open-label, subject-blind, laboratory-blind, single-dose, randomized, two-treatment, two-period, two-sequence crossover study of the pharmacokinetics of two formulations of intravenous ciclosporin. Fifty-two healthy volunteer subjects were administered 5 mg/kg of each of the two formulations of ciclosporin as a 4-h intravenous infusion. The last blood sample was acquired 48 h after the end of the infusion. Bioequivalence assessments according to current guidelines were performed. RESULTS: The geometric mean ratios for CicloMulsion(®)/Sandimmune(®) (90 % confidence interval [CI]) were 0.90 (0.88, 0.92) for AUC(0-last) (area under the blood concentration-time curve from time zero to time of last measurable concentration) and 0.95 (0.92, 0.97) for C(max) (maximum blood concentration). For all additional variables analysed, the 90 % CIs were also within the accepted bioequivalence range of 0.80-1.25. One anaphylactoid and one anaphylactic reaction, both classified as serious adverse events, were reported after treatment with Sandimmune(®). No serious adverse events were recorded after treatment with CicloMulsion(®). CONCLUSION: We have assessed the pharmacokinetics and tolerability of a new Cremophor(®) EL-free lipid emulsion of ciclosporin, CicloMulsion(®), compared to Sandimmune(®). The proportion of adverse events was significantly higher for the Cremophor(®) EL-based product Sandimmune(®). We conclude that CicloMulsion(®) is bioequivalent to Sandimmune(®) and exhibits fewer adverse reactions.
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| 11. |
- Foster, Josh, et al.
(författare)
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Acetaminophen (Paracetamol) Induces Hypothermia During Acute Cold Stress
- 2017
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Ingår i: Clinical drug investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 37:11, s. 1055-1065
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acetaminophen is an over-the-counter drug used to treat pain and fever, but it has also been shown to reduce core temperature (Tc) in the absence of fever. However, this side effect is not well examined in humans, and it is unknown if the hypothermic response to acetaminophen is exacerbated with cold exposure. Objective: To address this question, we mapped the thermoregulatory responses to acetaminophen and placebo administration during exposure to acute cold (10 °C) and thermal neutrality (25 °C). Methods: Nine healthy Caucasian males (aged 20–24 years) participated in the experiment. In a double-blind, randomised, repeated measures design, participants were passively exposed to a thermo-neutral or cold environment for 120 min, with administration of 20 mg/kg lean body mass acetaminophen or a placebo 5 min prior to exposure. Tc, skin temperature (Tsk), heart rate, and thermal sensation were measured every 10 min, and mean arterial pressure was recorded every 30 min. Data were analysed using linear mixed effects models. Differences in thermal sensation were analysed using a cumulative link mixed model. Results: Acetaminophen had no effect on Tc in a thermo-neutral environment, but significantly reduced Tc during cold exposure, compared with a placebo. Tc was lower in the acetaminophen compared with the placebo condition at each 10-min interval from 80 to 120 min into the trial (all p < 0.05). On average, Tc decreased by 0.42 ± 0.13 °C from baseline after 120 min of cold exposure (range 0.16–0.57 °C), whereas there was no change in the placebo group (0.01 ± 0.1 °C). Tsk, heart rate, thermal sensation, and mean arterial pressure were not different between conditions (p > 0.05). Conclusion: This preliminary trial suggests that acetaminophen-induced hypothermia is exacerbated during cold stress. Larger scale trials seem warranted to determine if acetaminophen administration is associated with an increased risk of accidental hypothermia, particularly in vulnerable populations such as frail elderly individuals.
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| 12. |
- Giron, MST, et al.
(författare)
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Drug use patterns in a very elderly population : a seven-year review
- 1999
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Ingår i: Clinical drug investigation. - 1173-2563 .- 1179-1918. ; 17:15, s. 389-98
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the extent and rate of drug use and to evaluate the patterns of drug use over time in a very elderly population, we analysed drug use data from phases I (1987-1989) and IV (1994-1996) of the Kungsholmen project, an ongoing longitudinal study on aging in Stockholm, Sweden.Study Participants: Complete drug information was obtained from 1001 subjects in the 1987-1989 study period, and 681 subjects in 1994-1996. The participants were predominantly women and the average age was 85.8 years in 1987-1989 and 86.9 years in 1994-1996.Results: The proportion of users increased from 87.6 to 94.1% and the overall average number of drugs used per subject increased significantly (p < 0.001) from 3.4 to 4.6. Significant differences (p < 0.05) were noted in all age groups and in all types of housing. The frequency of use increased for all classes of drugs. The most frequently used in both study periods were drugs for the nervous system, cardiovascular system, and alimentary tract and metabolism. With regard to therapeutic categories of drugs, the use of vitamins, antithrombotic agents, antianaemic preparations, ACE inhibitors, antibacterials, analgesics, psychoanaleptics, and antiglaucoma preparations increased significantly (p < 0.05). The increased use of these drugs indicated heightened awareness of the most common and preventable medical conditions affecting the elderly and the use of newer classes of drugs. This also study confirmed a high prevalence of drug use and polypharmacy even in the very elderly, and the importance of evaluating the effects and appropriateness of drug use in this population.
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| 13. |
- Hasvold, Pal, et al.
(författare)
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Association Between Paradoxical HDL Cholesterol Decrease and Risk of Major Adverse Cardiovascular Events in Patients Initiated on Statin Treatment in a Primary Care Setting
- 2016
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Ingår i: Clinical drug investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 36:3, s. 225-233
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are unrelated. Many patients initiated on statins experience a paradoxical decrease in HDL-C. The aim of this study was to evaluate the association between a decrease in HDL-C and risk of major adverse cardiovascular events (MACE). Methods Data from 15,357 primary care patients initiated on statins during 2004-2009 were linked with data from mandatory national hospital, drug-dispensing, and cause-of-death registers, and were grouped according to HDL-C change: decreased >= 0.1 mmol/L, unchanged +/- 0.1 or >= 0.1 mmol/L increased. To evaluate the association between decrease in HDL-C and risk of MACE, a sample of propensity score-matched patients from the decreased and unchanged groups was created, using the latter group as reference. MACE was defined as myocardial infarction, unstable angina pectoris, ischaemic stroke, or cardiovascular mortality. Cox proportional hazards models were used to estimate relative risks. Results HDL-C decreased in 20 %, was unchanged in 58%, and increased in 22 % of patients initiated on statin treatment (96 % treated with simvastatin). The propensity score-matched sample comprised 5950 patients with mean baseline HDL-C and LDL-C of 1.69 and 4.53 mmol/L, respectively. HDL-C decrease was associated with 56 % higher MACE risk (hazard ratio 1.56; 95 % confidence interval 1.12-2.16; p < 0.01) compared with the unchanged HDL-C group. Conclusions Paradoxical statin-induced reduction in HDL-C was relatively common and was associated with increased risk of MACE.
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| 14. |
- Holl, Katsiaryna, et al.
(författare)
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The Impact of Childhood Acute Otitis Media on Parental Quality of Life in a Prospective Observational Cohort Study
- 2015
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Ingår i: Clinical drug investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 35:10, s. 613-624
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Tidskriftsartikel (refereegranskat)abstract
- Acute otitis media (AOM) not only affects childhood quality of life (QoL), but can also affect parental QoL. We adapted a previously published questionnaire on the effect of childhood recurrent ear, nose and throat infections on parental QoL for use with AOM and used it in an observational, multicentre, prospective study of children with AOM. The AOM-specific parental QoL questionnaire grouped 15 items into emotional, daily disturbance, total and overall parental QoL impact scores. The questionnaire was assessed using item-convergent and item-discriminant validity criteria and internal consistency reliability; and then used with parents of children aged < 6 years diagnosed with AOM at 73 practices in Germany, Italy, Spain, Sweden and the UK. Bivariate analyses explored the differences in mean parental QoL impact scores by various characteristics. The questionnaire demonstrated good to excellent internal consistency reliability for the various components (Cronbach's alpha 0.82-0.97). There were 1419 AOM episodes among 5882 healthy children over 1 year, of which 1063 episodes (74.9 %) among 852 children had a questionnaire. Parents reported interrupted sleep (68.4 %), worry (51.0 %), altered daily schedule (44.6 %) and less leisure time (41.5 %) with a score a parts per thousand yen3 (1 = least to 5 = most impact). Factors that adversely affected parental QoL included: increased parental perception of AOM severity, younger child age and multiple AOM episodes. The AOM-specific parental QoL questionnaire demonstrated good performance across five European countries. Parental QoL was affected by childhood AOM proportionally to severity, number of episodes and younger child age.
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| 15. |
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| 16. |
- Kiladjian, Jean-Jacques, et al.
(författare)
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Efficacy and Safety of Cytoreductive Therapies in Patients with Essential Thrombocythaemia Aged > 80 Years : An Interim Analysis of the EXELS Study
- 2013
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Ingår i: Clinical drug investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 33:1, s. 55-63
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Tidskriftsartikel (refereegranskat)abstract
- Background The median age of patients diagnosed with essential thrombocythaemia (ET) is 65-70 years but the management of very elderly patients (aged >80 years) with ET has not been well characterized. Objective This study aimed to document the treatment patterns of very elderly patients with ET in a multinational, real-world setting. Study Design EXELS (Evaluation of Xagrid Efficacy and Long-term Safety) is a phase IV observational study, designed to monitor the efficacy and safety of cytoreductive therapies in clinical practice. In total, 3,598 high-risk patients with ET were recruited from May 2005 to April 2009, in 13 European countries. Data were collected at registration and every 6 months thereafter for 5 years. This analysis was performed on a data-cut taken approximately 2 years after the last patient was registered. Patients In total, 395 patients aged >80 years at registration into EXELS were included in the analysis; of these, 42.2 % had experienced a previous thrombohaemorrhagic event. Results At registration, the most frequently prescribed cytoreductive therapy for patients aged >80 years was hydroxycarbamide (HC), which accounted for 82.8 % of patients whereas anagrelide use was less frequent (8.6 %). Very elderly patients were more likely to be switched from anagrelide than from HC (47.1 vs. 17.4 %; 95 % confidence interval for difference in proportion 12.4-46.9; Chi-squared test p < 0.001). Median platelet count during treatment was similar to 430 x 10(9)/L. In patients aged >80 years, the main reason for switch was intolerance/side effects (34.1 %); 0/16 patients reported treatment with anagrelide was non-efficacious compared with 8/57 (14 %) patients receiving HC, and 7/16 (43.8 %) anagrelide patients switched because of intolerance versus 18/57 (31.6 %) patients receiving HC. At least one predefined clinical event (PDE) was experienced by 27.3 % of patients aged >80 years. The most common PDEs reported in the very elderly age group were death (non-PDE related; 11.1 %), other cardiovascular symptoms (5.8 %), haematological transformation (3.8 %), congestive heart failure (3.3 %), myocardial infarction and angina (2.8 %), and thromboembolic events (6.3 %). Conclusion Well-tolerated and effective cytoreductive therapy has been achieved in patients aged >80 years by following individual treatment modalities that appear in agreement with the recent European LeukemiaNet (ELN) guidelines. Clinical Trial Registration Registered as ClinicalTrials.gov identifier NCT00567502; Protocol No: SPD422-401.
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| 17. |
- Li, X., et al.
(författare)
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Direct and Indirect Costs of Influenza-Like Illness Treated with and Without Oseltamivir in 15 European Countries: A Descriptive Analysis Alongside the Randomised Controlled ALIC(4)E Trial
- 2021
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Ingår i: Clinical Drug Investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 41:8, s. 685-699
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective Influenza-like illness (ILI) leads to a substantial disease burden every winter in Europe; however, oseltamivir is not frequently prescribed to ILI patients in the primary-care setting. An open-label, multi-country, multi-season, randomised controlled trial investigated the effectiveness of oseltamivir for treating ILI in 15 European countries. We aimed to evaluate whether patients presenting with ILI in primary care and being managed with the addition of oseltamivir to usual care had lower average direct and indirect costs compared to patients with usual care alone. Methods Resource use data were extracted from participants' daily diaries. Itemised country-specific unit costs were collected through official tariffs, pharmacies or literature. Costs were converted to 2018 values. The null hypothesis was tested based on one-sided credible intervals (CrIs) obtained by bootstrapping. Base-case analysis estimated direct cost and productivity losses using itemised costed resource use and the human capital approach. Scenario analyses with self-reported spending rather than itemised costing were also performed. Results Patients receiving oseltamivir (N = 1306) reported fewer healthcare visits, medication uses, hospital attendances and paid-work hours lost than the other patients (N = 1298). Excluding the oseltamivir cost, the average direct costs were lower in patients treated with oseltamivir from all perspectives, but these differences were not statistically significant (perspective of patient: euro17 [0-95% Crl: 16-19] vs. euro24 [5-100% Crl: 18-29]; healthcare provider: euro37 [28-67] vs. euro44 [25-55]; healthcare payers: euro54 [45-85] vs. euro68 [45-81]; and society: euro423 [399-478] vs. euro451 [390-478]). Scenario and age-group analyses confirmed these findings, but with some between-country differences. Conclusion The average direct and indirect costs were consistently lower in patients treated with oseltamivir than in patients without from four perspectives (excluding the oseltamivir cost). However, these differences were not statistically significant.
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| 18. |
- Lundberg, Johan, et al.
(författare)
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Economic Evaluation of Posaconazole Versus Fluconazole or Itraconazole in the Prevention of Invasive Fungal Infection in High-Risk Neutropenic Patients in Sweden
- 2014
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Ingår i: Clinical drug investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 34:7, s. 483-489
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Tidskriftsartikel (refereegranskat)abstract
- Background In patients undergoing induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), posaconazole has been proven more effective in the prevention of invasive fungal infection (IFI) than fluconazole or itraconazole (standard azoles) The current analysis seeks to estimate the cost effectiveness of prophylactic posaconazole compared with standard azoles in AML or MDS patients with severe chemotherapyinduced neutropenia in Sweden. Methods A decision-analytic model was used to estimate life expectancy, costs, and quality-adjusted life-years (QALYs). Efficacy data were derived from a phase III clinical trial. Life expectancy and quality of life data were collected from the literature. A modified Delphi method was used to gather expert opinion on resource use for an IFI. Unit costs were captured from hospital and pharmacy pricelists. A probabilistic sensitivity analysis (PSA) was used to investigate the impact of uncertainty in the model parameters on the cost-effectiveness results. Results The estimated mean direct cost per patient with posaconazole prophylaxis was 46,8(3 Swedish kronor (SEK) (epsilon 5,387) and SEK50,017 (epsilon 5,746) with standard azoles. Prophylaxis with posaconazole resulted in 0.075 QALYs gained compared with standard azoles. At a cost-effectiveness threshold of SEK500,000/QALY the PSA demonstrated a more than (5 % probability that posaconazole is cost effective versus standard azoles for the prevention of IFI in high-risk neutropenic patients in Sweden. Conclusion Given the assumptions, methods, and data used, posaconazole is expected to be cost effective compared with standard azoles when used as antifungal prophylaxis in AML or MDS patients with chemotherapyinduced prolonged neutropenia in Sweden.
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| 19. |
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| 20. |
- Olsson, Jonny, et al.
(författare)
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Quality of Drug Prescribing in Elderly People in Nursing Homes and Special Care Units for Dementia : A Cross-Sectional Computerized Pharmacy Register Analysis
- 2010
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Ingår i: Clinical drug investigation. - Auckland : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 30:5, s. 289-300
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Tidskriftsartikel (refereegranskat)abstract
- Background: Drug prescribing to the elderly is extensive and often inappropriate. Furthermore, the number of drugs used is the most important risk factor for adverse drug reactions. Despite this, drug prescribing in the elderly in Sweden is high and increasing. In 2003 the Swedish National Board of Health and Welfare launched a set of indicators to evaluate the quality of drug therapy in the elderly. Use of this tool in combination with the Swedish computerized national register covering all persons receiving multi-dose drug dispensing (drugs dispensed in one dose unit bag for each dose occasion) would enable detection of inappropriate drug prescribing and could help reduce the risk of drug-related problems among the elderly. Objectives: To assess the extent and quality of drug prescribing in younger and older elderly residents receiving multi-dose drug dispensing in ordinary nursing homes (NHs) and special care units for dementia (NHDs), and to evaluate the relationship between the quality of prescribing and the number of prescribers per resident, in a Swedish county. Methods: The computerized national pharmacy drug register provided the database and a cross-sectional design was used. Selected drug-specific quality indicators proposed by the Swedish National Board of Health and Welfare in 2003 were used to assess the quality of drug prescribing. Results: This study included 3705 residents. Their mean age was 85 years and 72% were women. The mean number of prescribed drugs was 10.3 per resident. The proportion of residents with prescriptions for psychotropic drugs was 80% in NHs and 85% in NHDs. The prevalence of each drug-specific quality indicator was as follows: long-acting benzodiazepines 16.4% (NHs) versus 11.7% (NHDs), anticholinergic drugs 20.7% versus 18.5%, drug duplication 14.6% versus 13.6%, three or more psychotropic drugs 25.6% versus 35.3%, class C interactions (drug combinations that may require dose adjustment) 41.9% versus 38.7% and class D interactions (drug combinations that should be avoided) 8.1% versus 5.6%. Younger elderly residents (age 65-79 years) had a lower quality of drug prescribing. An increasing number of prescribers per resident was associated with a lower quality of drug therapy. Conclusions: We found a lower quality of drug prescribing, e.g. anticholinergic drugs prescribed to approximately 20% of residents of NHs and NHDs, and a higher rate of psychotropic drug use (>=80%) compared with previous studies in NHs. Our results also demonstrated a negative correlation between quality of prescribing and number of prescribers per resident.
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| 21. |
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| 22. |
- Walfridsson, Håkan, et al.
(författare)
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Effects of AZD0837, a novel direct thrombin inhibitor, on the electrophysiological properties of the human heart: a randomized, double-blind, parallel-group, placebo-controlled study.
- 2010
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Ingår i: Clinical drug investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 30:7, s. 461-71
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: AZD0837 is an investigational oral anticoagulant that is bioconverted to its active form, AR-H067637, a selective direct thrombin inhibitor. OBJECTIVES: The objectives of the present study were to investigate if there are any clinically relevant adverse effects of intravenous AZD0837 on cardiac conduction, refractoriness and repolarization, and to study its safety and tolerability. METHODS: In this randomized, double-blind, parallel-group, placebo-controlled study (study code D1250C00026), invasive electrophysiological measurements were performed twice in 30 subjects with a history of, or ongoing, atrial flutter, starting 30 minutes after successful ablation of atrial flutter and then 60 minutes after start of an intravenous infusion of AZD0837. Pre-study warfarin therapy was not an exclusion criterion. The stimulation protocol was performed mainly at 500 and 400 ms drive cycle length. A 12-lead ECG was also recorded before and during AZD0837 infusion. Plasma concentrations of AZD0837 and its metabolites were obtained at predefined timepoints. RESULTS: Measurements were made at baseline and during stable plasma concentrations of the prodrug AZD0837 (mean +/- standard deviation 7.96 +/- 2.38 micromol/L, approximate target of 10 micromol/L), the intermediate metabolite AR-H69927 (1.26 +/- 0.39 micromol/L, target 1-2 micromol/L) and the active direct thrombin inhibitor AR-H067637 (0.35 +/- 0.14 micromol/L, target 0.5-1.0 micromol/L). There were no clinically relevant effects on cardiac conduction (QRS duration, PR interval, His bundle electrogram, Wenckebach point), refractoriness (atrial, atrioventricular and ventricular effective refractory periods) or repolarization (QT, QT interval corrected for heart rate using Fridericia's formula, QRS onset to the top of the T wave [QT(top)], QRS onset to the end of the T wave [QT(end)] or QT(top) - QT(end)). CONCLUSIONS: AZD0837 was well tolerated, and had no clinically relevant effects on cardiac electrophysiology of the target population, either in subjects previously treated with warfarin or in those without previous treatment.
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| 24. |
- Wintzell, Viktor, et al.
(författare)
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Data Mining for Adverse Events of Tumor Necrosis Factor-Alpha Inhibitors in Pediatric Patients : Tree-Based Scan Statistic Analyses of Danish Nationwide Health Data
- 2020
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Ingår i: Clinical drug investigation. - : Springer. - 1173-2563 .- 1179-1918. ; 40:12, s. 1147-1154
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Tumor necrosis factor-alpha (TNF-α) inhibitors are efficacious and considered generally safe in adults. However, pediatric-specific safety evidence is scarce. The aim of this study was to screen for signals of previously unknown adverse events of TNF-α inhibitors in pediatric patients.METHODS: We conducted a data-mining study based on routinely collected, nationwide Danish healthcare data for 2004-2016. Using tree-based scan statistics to identify events with unexpectedly high incidence during TNF-α inhibitor use among patients with inflammatory bowel disease or juvenile idiopathic arthritis, two analyses were performed: comparison with episodes of no use and with other time periods from the same patient. Based on incident physician-assigned diagnosis codes from outpatient and inpatient visits in specialist care, we screened thousands of potential adverse events while adjusting for multiple testing.RESULTS: We identified 1310 episodes of new TNF-α inhibitor use that met the eligibility criteria. Two signals of adverse events of TNF-α inhibitors, as compared with no use, were detected. First, there were excess events of dermatologic complications (ICD-10: L00-L99, 87 vs. 44 events, risk difference [RD] 3.3%), which have been described previously in adults and children. Second, there were excess events of psychiatric diagnosis adjustment disorders (ICD-10: F432, 33 vs. 7 events, RD 2.0%), which was likely associated with the underlying disease and its severity, rather than with the treatment. The self-controlled analysis generated no signal.CONCLUSIONS: No signals of previously unknown adverse events of TNF-α inhibitors in pediatric patients were detected. The study showed that real-world data and newly developed methods for adverse events data mining can play a particularly important role in pediatrics where pre-approval drug safety data are scarce.
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| 25. |
- Witthaut, Jörg, et al.
(författare)
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Determining Clinically Important Changes in Range of Motion in Patients with Dupuytren's Contracture : Secondary Analysis of the Randomized, Double-Blind, Placebo-Controlled CORD I Study
- 2011
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Ingår i: Clinical drug investigation. - 1173-2563 .- 1179-1918. ; 31:11, s. 791-798
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Injectable collagenase Clostridium histolyticum is efficacious in correcting Dupuytren's contracture as assessed by changes in the angle of contracture and range of motion (ROM). However, clinically important changes in ROM have not been evaluated in depth. The objective of this secondary analysis of the CORD I trial was to identify severity levels using baseline ROM, estimate a clinically important difference (CID) for ROM, and link the results to collagenase treatment and patient satisfaction. METHODS: In the CORD I trial, patients with Dupuytren's disease and joint contractures ≥20° were randomized to receive a maximum of three collagenase 0.58 mg or placebo injections into the cord of the affected hand at 30-day intervals. The primary endpoint was reduction in contracture to ≤5° 30 days after the last injection (day 30). The secondary endpoints, which are reported in this analysis, were ROM, physician- and patient-rated severity ('normal', 'mild', 'moderate', 'severe') and improvement, and treatment satisfaction. Linear regression was used to model data for severity classification and CID estimation for ROM based on physician and patient ratings. RESULTS: At baseline, mean ROM was 43.9° in the collagenase-treated joints (n = 197) and 45.3° in the placebo-treated joints (n = 102). On day 30, mean ROM was 80.7° in the collagenase-treated joints and 49.5° in the placebo-treated joints. The mean increase in ROM was 36.7° in the collagenase-treated joints (p < 0.001) and 4.0° in the placebo-treated joints (not significant). The estimated CID for ROM was 13.5° (95% CI 11.9, 15.1), reflecting a one-category change in severity. The mean increase in ROM exceeded the CID in the collagenase-treated joints but not in the placebo-treated joints; the difference between collagenase treatment and placebo in the mean increase in ROM also exceeded the CID, implying that the improvement with collagenase was clinically relevant. The severity classification for ROM was: ≥67.0° ('normal'), ≥54.3 and <67.0° ('mild'), ≥41.6 and <54.3° ('moderate'), and <41.6° ('severe'). More collagenase- than placebo-treated patients achieved 'normal' (81% vs 25%; p < 0.0001) status, and more collagenase- than placebo-treated patients reported being 'very/quite satisfied' (87% vs 32%; p < 0.001). CONCLUSION: Injectable collagenase significantly improves ROM and treatment satisfaction versus placebo. ROM improvements are clinically relevant as well as statistically significant. These data support the potential need to include ROM and physician- and patient-rated severity and satisfaction as standard assessments for Dupuytren's contracture treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00528606; other study identification number: AUX-CC-857 (Auxilium Pharmaceuticals, Inc.).
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