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  • 1
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    Leflunomide for Inflammatory Arthritis in End-Stage Renal Disease on Peritoneal Dialysis: A Pharmacokinetic and Pharmacogenetic Study
    SAGE Publications ; 2013
    In:  Annals of Pharmacotherapy Vol. 47, No. 3 ( 2013-03), p. e15-e15
    Details
    In: Annals of Pharmacotherapy, SAGE Publications, Vol. 47, No. 3 ( 2013-03), p. e15-e15
    Abstract: To study the pharmacokinetics and pharmacogenetics of leflunomide and document its efficacy and safety in the treatment of inflammatory arthritis in a patient with end-stage renal disease (ESRD) who was on peritoneal dialysis. CASE SUMMARY Therapy for a 78-year-old man with ESRD who required peritoneal dialysis was started with leflunomide 10 mg/day for psoriatic arthritis. The dosage was increased to 20 mg/day after 3 months. Monitoring was continued until the patient's unexpected death from myocardial infarction at 8 months. Total and unbound teriflunomide (the active metabolite of leflunomide) concentrations were measured by liquid-chromatography-tandem mass spectrometry. Genotyping for CYP2C19 and ABCG2 polymorphisms, both known to influence teriflunomide pharmacokinetics, was also performed. DISCUSSION Total concentrations of teriflunomide varied between 5.2 and 23.2 mg/L, while unbound concentrations varied between 0.0306 and 0.1468 mg/L. The unbound fraction varied between 0.367% and 0.71%. Teriflunomide was found in the dialysate at a concentration of 0.0981 mg/L. A single CYP2C19 loss of function allele was present, as was wild-type ABCG2. Leflunomide appeared to be therapeutically effective, as evidenced by a reduction in daily prednisolone dosage from 20 mg to 6mg; the Disease Activity Score in 28 joints (DAS28) was 5.46 at enrollment and 4.03 after 7 months. Health Assessment Questionnaire—Disability Index improved from 0.5 to 0.125 at 7 months. Numerous significant adverse events that were considered unrelated to leflunomide occurred. CONCLUSIONS Dose adjustment for leflunomide does not appear to be required in the context of ESRD requiring peritoneal dialysis. We present novel evidence that a small amount of teriflunomide is removed by peritoneal dialysis. This case suggests that leflunomide is safe to use as therapy for inflammatory arthritis despite the presence of ESRD requiring peritoneal dialysis.
    Type of Medium: Online Resource
    ISSN: 1060-0280 , 1542-6270
    URL: Article
    DOI: 10.1345/aph.1R542
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
    detail.hit.zdb_id: 2053518-1
    SSG: 15,3
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  • 2
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    The association of depression and anxiety with treatment outcomes in patients with rheumatoid arthritis – a pooled analysis of five randomised controlled trials
    SAGE Publications ; 2022
    In:  Therapeutic Advances in Musculoskeletal Disease Vol. 14 ( 2022-01), p. 1759720X2211116-
    Details
    In: Therapeutic Advances in Musculoskeletal Disease, SAGE Publications, Vol. 14 ( 2022-01), p. 1759720X2211116-
    Abstract: Rheumatoid arthritis (RA) is an inflammatory autoimmune condition associated with an increased risk of developing depression and anxiety. Depression and anxiety are associated with worse outcomes in RA, but the magnitude of the effect of each condition on RA outcomes is unclear. It is also unknown how pharmacological treatment of depression affects RA outcomes. Objective: The primary aim of this study was to investigate the association of comorbid depression and anxiety with remission in patients with RA. Secondary aims were to determine the association between comorbid depression and anxiety on patient-reported outcomes and the relationship between concomitant use of antidepressants and remission in patients with depression. Design: Data from patients with moderate to severe RA were pooled from five randomised controlled trials investigating tocilizumab and conventional synthetic disease-modifying agents. Methods: Remission was defined as a clinical disease activity index (CDAI) of ⩽2.8 and simple disease activity index (SDAI) of ⩽3.3. The association between the time to reach remission and depression and anxiety was analysed using Cox proportional hazard analysis. Results: Individual patient data were available from 5502 subjects, of whom 511 had depression, 236 had anxiety and 387 were using antidepressants. Depression was significantly associated with reduced remission [adjusted HR (95% CI): 0.62 (0.48–0.80), p  〈  0.001 and adjusted HR (95% CI): 0.59 (0.44–0.79), p  〈  0.001] using CDAI and SDAI, respectively. Depression was associated with a lower likelihood of achieving more subjective outcomes (⩽1 physician global assessment, ⩽1 patient global assessment) and ⩽1 28-swollen joint count, but not ⩽1 28-tender joint count or C-reactive protein measurement. Treatment with antidepressants did not improve outcomes for patients with depression. Anxiety was not significantly associated with RA remission. Conclusion: Comorbid depression, but not anxiety, was associated with less frequent remission. Concomitant antidepressant use was not associated with improvements in RA outcomes in patients with depression.
    Type of Medium: Online Resource
    ISSN: 1759-720X , 1759-7218
    URL: Article
    DOI: 10.1177/1759720X221111613
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2022
    detail.hit.zdb_id: 2516075-8
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  • 3
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    Feasibility of a Patient-Centered Deprescribing Process to Reduce Inappropriate Use of Proton Pump Inhibitors
    SAGE Publications ; 2015
    In:  Annals of Pharmacotherapy Vol. 49, No. 1 ( 2015-01), p. 29-38
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    In: Annals of Pharmacotherapy, SAGE Publications, Vol. 49, No. 1 ( 2015-01), p. 29-38
    Abstract: Background: Proton pump inhibitors (PPIs) are inappropriately prescribed in up to 50% of users. Systematic medication review and cessation of inappropriate medications or deprescribing may improve patient outcomes and reduce costs. Objective: The aim of this study was to assess the feasibility of a patient-centered deprescribing process in a population of adults with complex polypharmacy. Methods: This was a prospective feasibility study. Participants were recruited from hospital outpatient clinics. The patient-centered deprescribing process consisted of 5 steps: comprehensive medication history, identification of potentially inappropriate medications, determining if the medication can be ceased, planning the withdrawal regimen (eg, tapering where necessary), and provision of monitoring, support, and documentation. Feasibility was determined by assessing time taken to complete the different steps of the deprescribing process and participant feedback. Results: In all, 57 PPI users were recruited; participants were 70 ± 14 years old and took 14 ± 6 medications. The indication for PPI use was verified in 43 participants and judged as potentially inappropriate in 19 (44%); 8 were suitable for trial withdrawal, and 6 consented. All 6 successfully ceased (n = 3) or reduced (n = 3) their PPI use, and this was sustained at 6 months postintervention in 4 participants. Conclusions: The patient-centered deprescribing process can safely reduce inappropriate PPI prescribing in a small proportion of people. Although the process was acceptable to participants, difficulties in accessing complete medical histories, time limitations, and minimal evidence to support effectiveness in certain indications were barriers to implementation of the process in clinical practice.
    Type of Medium: Online Resource
    ISSN: 1060-0280 , 1542-6270
    URL: Article
    DOI: 10.1177/1060028014558290
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2053518-1
    SSG: 15,3
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  • 4
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    Methotrexate, blood pressure and markers of arterial function in patients with rheumatoid arthritis: a repeated cross-sectional study
    SAGE Publications ; 2017
    In:  Therapeutic Advances in Musculoskeletal Disease Vol. 9, No. 9 ( 2017-09), p. 213-229
    Details
    In: Therapeutic Advances in Musculoskeletal Disease, SAGE Publications, Vol. 9, No. 9 ( 2017-09), p. 213-229
    Abstract: Methotrexate (MTX) treatment in rheumatoid arthritis (RA) has been associated with lower cardiovascular risk compared to other disease-modifying antirheumatic drugs (DMARDs). We sought to identify whether the MTX-associated cardioprotection involves changes in blood pressure (BP) and/or arterial function. Methods: Clinic and 24-hour peripheral and central systolic and diastolic BP (SBP and DBP), augmentation index (AIx), pulse wave velocity (PWV) and plasma asymmetric dimethylarginine (ADMA) were assessed in RA patients on stable treatment with either MTX ± other DMARDs (MTX group, n = 56, age 61 ± 13 years, 70% females) or other DMARDs (non-MTX group, n = 30, age 63 ± 12 years, 76% females). Measurements were performed at baseline and after 8 months. Results: After adjusting for visit, age, gender, body mass index, folic acid use and 28-joint disease activity score, the MTX group had significantly lower clinic peripheral SBP (−7.7 mmHg, 95% CI −13.2 to −2.3, p = 0.006) and DBP (−6.1 mmHg, 95% CI −9.8 to −2.4, p = 0.001) and clinic central SBP (−7.8 mmHg, 95% CI −13.1 to −2.6, p = 0.003) and DBP (−5.4 mmHg, 95% CI −9.1 to −1.6, p = 0.005) versus the non-MTX group. Furthermore, the MTX group had significantly lower 24-hour peripheral and central SBP and DBP and PWV versus the non-MTX group ( p 〈 0.01 for all comparisons). By contrast, there were no significant between-group differences in AIx and ADMA. Conclusions: RA patients on MTX treatment had significantly lower clinic and 24-hour peripheral and central BP compared to those who did not take MTX. The lower BP with MTX may be related to differences in PWV, but not in AIx or ADMA concentrations. Further longitudinal studies including randomized controlled trials are warranted to confirm these findings, to identify other possible mechanisms responsible for the effects of MTX on BP and PWV, and to establish whether these effects might account for the reduced cardiovascular risk with MTX.
    Type of Medium: Online Resource
    ISSN: 1759-720X , 1759-7218
    URL: Article
    DOI: 10.1177/1759720X17719850
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
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  • 5
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    Pharmacogenomic substudies of randomized controlled trials: consideration of safety outcomes
    SAGE Publications ; 2014
    In:  Therapeutic Advances in Drug Safety Vol. 5, No. 2 ( 2014-04), p. 62-66
    Details
    In: Therapeutic Advances in Drug Safety, SAGE Publications, Vol. 5, No. 2 ( 2014-04), p. 62-66
    Type of Medium: Online Resource
    ISSN: 2042-0986 , 2042-0994
    URL: Article
    DOI: 10.1177/2042098613520030
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
    detail.hit.zdb_id: 2583589-0
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  • 6
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    Pharmacists in Australian general practice: an opportunity for expertise in precision medicine
    SAGE Publications ; 2015
    In:  Therapeutic Advances in Drug Safety Vol. 6, No. 5 ( 2015-10), p. 186-188
    Details
    In: Therapeutic Advances in Drug Safety, SAGE Publications, Vol. 6, No. 5 ( 2015-10), p. 186-188
    Type of Medium: Online Resource
    ISSN: 2042-0986 , 2042-0994
    URL: Article
    DOI: 10.1177/2042098615599947
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
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  • 7
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    Concomitant beta-blocker use is associated with a reduced rate of remission in patients with rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs: a post hoc multicohort analysis
    SAGE Publications ; 2021
    In:  Therapeutic Advances in Musculoskeletal Disease Vol. 13 ( 2021-01), p. 1759720X2110090-
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    In: Therapeutic Advances in Musculoskeletal Disease, SAGE Publications, Vol. 13 ( 2021-01), p. 1759720X2110090-
    Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with increased risk of cardiovascular disease (CVD). Treatment for CVD may involve pharmacological agents that antagonise beta adrenergic receptors. These receptors may play an important role in immunology, and the effects of beta-blockers (BB) in RA is unknown. The aim of this study was to investigate the association between BB use and remission in patients with RA initiating tocilizumab +/− conventional synthetic (cs-) DMARD therapy. Methods: Data was pooled from five randomised trials investigating tocilizumab and/or csDMARD treatment in RA (primarily methotrexate). The association between BB use and remission according to the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) was assessed by Cox proportional hazard analysis. Sensitivity analysis in patients with pre-existing CVD and an exploratory analysis of the impact of other CVD drugs were conducted. Results: Data were available from 5502 participants, 594 (10.8%) of whom were using systemic BB. BB use was associated with less frequent SDAI remission in the total [adjusted hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.57–0.87, p = 0.001] and CVD cohort [adjusted HR 0.72 (0.57–0.90, p = 0.005)] . The association was consistent between trials (interaction p = 0.44) and treatment arms (interaction p = 0.06). No significant association between remission and β1-receptor selectivity was identified ( p = 0.16), and the association was independent from other cardiovascular drug use. Similar associations between BB use and CDAI remission were observed. Conclusion: In a large, pooled cohort of RA patients initiating csDMARDs and/or tocilizumab, BB use was independently associated with less frequent remission.
    Type of Medium: Online Resource
    ISSN: 1759-720X , 1759-7218
    URL: Article
    DOI: 10.1177/1759720X211009020
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
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  • 8
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    Medication Regimen Complexity and Unplanned Hospital Readmissions in Older People
    SAGE Publications ; 2014
    In:  Annals of Pharmacotherapy Vol. 48, No. 9 ( 2014-09), p. 1120-1128
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    In: Annals of Pharmacotherapy, SAGE Publications, Vol. 48, No. 9 ( 2014-09), p. 1120-1128
    Abstract: Background: Medication-related problems and adverse drug events are leading causes of preventable hospitalizations. Few previous studies have investigated the possible association between medication regimen complexity and unplanned rehospitalization. Objective: To investigate the association between discharge medication regimen complexity and unplanned rehospitalization over a 12-month period. Method: The prospective study comprised patients aged ≥70 years old consecutively admitted to a Geriatrics Evaluation and Management (GEM) unit between October 2010 and December 2011. Medication regimen complexity at discharge was calculated using the 65-item validated Medication Regimen Complexity Index (MRCI). Cox proportional-hazards regression was used to compute unadjusted and adjusted hazard ratios (HRs) with 95% CIs for factors associated with rehospitalization over a 12-month follow-up period. Result: Of 163 eligible patients, 99 patients had one or more unplanned hospital readmissions. When adjusting for age, sex, activities of daily living, depression, comorbidity, cognitive status, and discharge destination, MRCI (HR = 1.01; 95% CI = 0.81-1.26), number of discharge medications (HR = 1.01; 95% CI = 0.94-1.08), and polypharmacy (≥9 medications; HR = 1.12; 95% CI = 0.69-1.80) were not associated with rehospitalization. In patients discharged to nonhome settings, there was an association between rehospitalization and the number of discharge medications (HR = 1.12; 95% CI = 1.01-1.25) and polypharmacy (HR = 2.24; 95% CI = 1.02-4.94) but not between rehospitalization and MRCI (HR = 1.32; 95% CI = 0.98-1.78). Conclusion: Medication regimen complexity was not associated with unplanned hospital readmission in older people. However, in patients discharged to nonhome settings, the number of discharge medications and polypharmacy predicted rehospitalization. A patient’s discharge destination is an important factor in unplanned medication-related readmissions.
    Type of Medium: Online Resource
    ISSN: 1060-0280 , 1542-6270
    URL: Article
    DOI: 10.1177/1060028014537469
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
    detail.hit.zdb_id: 2053518-1
    SSG: 15,3
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  • 9
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    The Resource for Applied Cognitive and Systems Engineering (TRACE-SE): An Approach to Understanding the GAP
    SAGE Publications ; 2006
    In:  Proceedings of the Human Factors and Ergonomics Society Annual Meeting Vol. 50, No. 17 ( 2006-10), p. 1872-1876
    Details
    In: Proceedings of the Human Factors and Ergonomics Society Annual Meeting, SAGE Publications, Vol. 50, No. 17 ( 2006-10), p. 1872-1876
    Abstract: Today's workplaces are complex organizations in which people connect to information, people, and the world through advanced technology. Accordingly, the nature of work evolves as the workplace adds technologies that challenge traditional skills and increase demands for highly specialized cognitive skills. Systems must therefore be designed to account for the cognitive strengths and limitations of users and support decision-based operations. Traditional systems engineering practices, however, frequently fail to expressly consider cognitive factors in design or consider them belatedly in the design cycle. As a result, systems are often designed that do not fully leverage the cognitive strengths of the human user or compensate for their limitations. Yet, embedding cognitive engineering methods into established systems engineering processes can be complex and expensive without tools to structure and support it. The Resource for Applied Cognitive Engineering and Systems Engineering (TRACE-SE) is a prototype web-based tool that can be used to begin bridging the gap that exists between cognitive and systems engineering. TRACE-SE provides the information needed to simultaneously support both cognitive and systems engineers in the design of user-centered systems that can produce superior decision making, improved safety, and greater operator productivity.
    Type of Medium: Online Resource
    ISSN: 2169-5067 , 1071-1813
    URL: Article
    DOI: 10.1177/154193120605001733
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2006
    detail.hit.zdb_id: 2415770-3
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  • 10
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    Medication Regimen Complexity and Polypharmacy as Factors Associated With All-Cause Mortality in Older People : A Population-Based Cohort Study
    SAGE Publications ; 2016
    In:  Annals of Pharmacotherapy Vol. 50, No. 2 ( 2016-02), p. 89-95
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    In: Annals of Pharmacotherapy, SAGE Publications, Vol. 50, No. 2 ( 2016-02), p. 89-95
    Abstract: Objectives: To investigate whether medication regimen complexity and/or polypharmacy are associated with all-cause mortality in older people. Methods: This was a population-based cohort study among community-dwelling and institutionalized people ≥60 years old (n = 3348). Medication regimen complexity was assessed using the 65-item Medication Regimen Complexity Index (MRCI) in 10-unit steps. Polypharmacy was assessed as a continuous variable (number of medications). Mortality data were obtained from the Swedish National Cause of Death Register. Cox proportional hazard models were used to compute unadjusted and adjusted hazard ratios (HRs) and 95% CIs for the association between regimen complexity and polypharmacy with all-cause mortality over a 3-year period. Subanalyses were performed stratifying by age (≤80 and 〉 80 years), sex, and cognition (Mini-Mental State Examination [MMSE] 〈 26 and ≥26). Results: During follow-up, 14% of the participants (n = 470) died. After adjusting for age, sex, comorbidity, educational level, activities of daily living, MMSE, and residential setting, a higher MRCI was associated with mortality (adjusted HR = 1.12; 95% CI = 1.01-1.25). Polypharmacy was not associated with mortality (adjusted HR = 1.03; 95% CI = 0.99-1.06). When stratifying by sex, both MRCI and polypharmacy were associated with mortality in men but not in women. MRCI was associated with mortality in participants ≤80 years old and in participants with MMSE ≥26 but not in participants 〉 80 years old or with MMSE 〈 26. Conclusion: Regimen complexity was a better overall predictor of mortality than polypharmacy. However, regimen complexity was not predictive of mortality in women, in participants 〉 80 years old, or in those with MMSE 〈 26. These different associations with mortality deserve further investigation.
    Type of Medium: Online Resource
    ISSN: 1060-0280 , 1542-6270
    URL: Article
    DOI: 10.1177/1060028015621071
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
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