Browsing by Subject "Drug Monitoring"
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Item Open Access A randomized, double-blind, placebo-controlled trial of pramipexole augmentation in treatment-resistant major depressive disorder.(The Journal of clinical psychiatry, 2013-07) Cusin, Cristina; Iovieno, Nadia; Iosifescu, Dan V; Nierenberg, Andrew A; Fava, Maurizio; Rush, A John; Perlis, Roy HBackground
Multiple treatments for patients with major depressive disorder (MDD) have demonstrated efficacy, but up to one-third of individuals with MDD do not achieve symptomatic remission despite various interventions. Existing augmentation or combination strategies can have substantial safety concerns that may limit their application.Method
This study investigated the antidepressant efficacy of a flexible dose of the dopamine agonist pramipexole as an adjunct to standard antidepressant treatment in an 8-week, randomized, double-blind, placebo-controlled trial conducted in a tertiary-level depression center. We randomized 60 outpatients (aged 18 to 75 years) with treatment-resistant nonpsychotic MDD (diagnosed according to DSM-IV) to either pramipexole (n = 30) or placebo (n = 30). Treatment resistance was defined as continued depression (Montgomery-Asberg Depression Rating Scale [MADRS] score ≥ 18) despite treatment with at least 1 prior antidepressant in the current depressive episode. Patients were recruited between September 2005 and April 2008. The primary outcome measure was the MADRS score.Results
The analyses that used a mixed-effects linear regression model indicated a modest but statistically significant benefit for pramipexole (P = .038). The last-observation-carried-forward analyses indicated that 40% and 33% of patients randomized to augmentation with pramipexole achieved response (χ(2) = 1.2, P = .27) and remission (χ(2) = 0.74, P = .61), respectively, compared to 27% and 23% with placebo; however, those differences were not statistically significant. Augmentation with pramipexole was well-tolerated, with no serious adverse effects identified.Conclusion
For patients who have failed to respond to standard antidepressant therapies, pramipexole is a safe and potentially efficacious augmentation strategy.Trial registration
ClinicalTrials.gov identifier: NCT00231959.Item Open Access An evaluation of patient self-testing competency of prothrombin time for managing anticoagulation: pre-randomization results of VA Cooperative Study #481--The Home INR Study (THINRS).(Journal of thrombosis and thrombolysis, 2010-10) Dolor, Rowena J; Ruybalid, R Lynne; Uyeda, Lauren; Edson, Robert G; Phibbs, Ciaran; Vertrees, Julia E; Shih, Mei-Chiung; Jacobson, Alan K; Matchar, David B; THINRS Site InvestigatorsPrior studies suggest patient self-testing (PST) of prothrombin time (PT) can improve the quality of anticoagulation (AC) and reduce complications (e.g., bleeding and thromboembolic events). "The Home INR Study" (THINRS) compared AC management with frequent PST using a home monitoring device to high-quality AC management (HQACM) with clinic-based monitoring on major health outcomes. A key clinical and policy question is whether and which patients can successfully use such devices. We report the results of Part 1 of THINRS in which patients and caregivers were evaluated for their ability to perform PST. Study-eligible patients (n = 3643) were trained to use the home monitoring device and evaluated after 2-4 weeks for PST competency. Information about demographics, medical history, warfarin use, medications, plus measures of numeracy, literacy, cognition, dexterity, and satisfaction with AC were collected. Approximately 80% (2931 of 3643) of patients trained on PST demonstrated competency; of these, 8% (238) required caregiver assistance. Testers who were not competent to perform PST had higher numbers of practice attempts, higher cuvette wastage, and were less able to perform a fingerstick or obtain blood for the cuvette in a timely fashion. Factors associated with failure to pass PST training included increased age, previous stroke history, poor cognition, and poor manual dexterity. A majority of patients were able to perform PST. Successful home monitoring of PT with a PST device required adequate levels of cognition and manual dexterity. Training a caregiver modestly increased the proportion of patients who can perform PST.Item Open Access At-Home Versus In-Clinic INR Monitoring: A Cost-Utility Analysis from The Home INR Study (THINRS).(Journal of general internal medicine, 2016-09) Phibbs, Ciaran S; Love, Sean R; Jacobson, Alan K; Edson, Robert; Su, Pon; Uyeda, Lauren; Matchar, David B; writing for the THINRS Executive Committee and Site InvestigatorsBackground
Effective management of patients using warfarin is resource-intensive, requiring frequent in-clinic testing of the international normalized ratio (INR). Patient self-testing (PST) using portable at-home INR monitoring devices has emerged as a convenient alternative. As revealed by The Home INR Study (THINRS), event rates for PST were not significantly different from those for in-clinic high-quality anticoagulation management (HQACM), and a cumulative gain in quality of life was observed for patients undergoing PST.Objective
To perform a cost-utility analysis of weekly PST versus monthly HQACM and to examine the sensitivity of these results to testing frequency.Patients/interventions
In this study, 2922 patients taking warfarin for atrial fibrillation or mechanical heart valve, and who demonstrated PST competence, were randomized to either weekly PST (n = 1465) or monthly in-clinic testing (n = 1457). In a sub-study, 234 additional patients were randomized to PST once every 4 weeks (n = 116) or PST twice weekly (n = 118). The endpoints were quality of life (measured by the Health Utilities Index), health care utilization, and costs over 2 years of follow-up.Results
PST and HQACM participants were similar with regard to gender, age, and CHADS2 score. The total cost per patient over 2 years of follow-up was $32,484 for HQACM and $33,460 for weekly PST, representing a difference of $976. The incremental cost per quality-adjusted life year gained with PST once weekly was $5566 (95 % CI, -$11,490 to $25,142). The incremental cost-effectiveness ratio (ICER) was sensitive to testing frequency: weekly PST dominated PST twice weekly and once every 4 weeks. Compared to HQACM, weekly PST was associated with statistically significant and clinically meaningful improvements in quality of life. The ICER for weekly PST versus HQACM was well within accepted standards for cost-effectiveness, and was preferred over more or less frequent PST. These results were robust to sensitivity analyses of key assumptions.Conclusion
Weekly PST is a cost-effective alternative to monthly HQACM and a preferred testing frequency compared to twice weekly or monthly PST.Item Open Access Does distance modify the effect of self-testing in oral anticoagulation?(The American journal of managed care, 2016-01) Rose, Adam J; Phibbs, Ciaran S; Uyeda, Lauren; Su, Pon; Edson, Robert; Shih, Mei-Chiung; Jacobson, Alan; Matchar, David BObjectives
Patient self-testing (PST) improves anticoagulation control and patient satisfaction. It is unknown whether these effects are more pronounced when the patient lives farther from the anticoagulation clinic (ACC). If the benefits of PST are limited to a subset of patients (those living farther from care), selectively providing PST to that subset could enhance cost-effectiveness.Study design
This is a secondary analysis of a randomized trial of PST versus usual ACC care, which involved 2922 patients of the Veterans Health Administration (VHA).Methods
Our 3 outcomes were the primary composite clinical end point (stroke, major hemorrhage, or death), anticoagulation control (percent time in therapeutic range), and satisfaction with anticoagulation care. We measured the driving distance between the patient's residence and the nearest VHA facility. We divided patients into quartiles by distance and looked for evidence of an interaction between distance and the effect of the intervention on the 3 outcomes.Results
The median driving distance was 12 miles (interquartile range = 6-21). Patients living in the farthest quartile had higher rates of the primary composite clinical end point in both groups compared with patients living in the nearest quartile. For PST, the hazard ratio (HR) was 1.77 (95% CI, 1.18-2.64), and for usual care, the HR was 1.81 (95% CI, 1.19-2.75). Interaction terms did not suggest that distance to care modified the effect of the intervention on any outcome.Conclusions
The benefits of PST were not enhanced among patients living farther from care. Restricting PST to patients living more than a certain distance from the ACC is not likely to improve its cost-effectiveness.Item Open Access Effect of home testing of international normalized ratio on clinical events.(The New England journal of medicine, 2010-10) Matchar, David B; Jacobson, Alan; Dolor, Rowena; Edson, Robert; Uyeda, Lauren; Phibbs, Ciaran S; Vertrees, Julia E; Shih, Mei-Chiung; Holodniy, Mark; Lavori, Philip; THINRS Executive Committee and Site InvestigatorsBackground
Warfarin anticoagulation reduces thromboembolic complications in patients with atrial fibrillation or mechanical heart valves, but effective management is complex, and the international normalized ratio (INR) is often outside the target range. As compared with venous plasma testing, point-of-care INR measuring devices allow greater testing frequency and patient involvement and may improve clinical outcomes.Methods
We randomly assigned 2922 patients who were taking warfarin because of mechanical heart valves or atrial fibrillation and who were competent in the use of point-of-care INR devices to either weekly self-testing at home or monthly high-quality testing in a clinic. The primary end point was the time to a first major event (stroke, major bleeding episode, or death).Results
The patients were followed for 2.0 to 4.75 years, for a total of 8730 patient-years of follow-up. The time to the first primary event was not significantly longer in the self-testing group than in the clinic-testing group (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; P=0.14). The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes. Over the entire follow-up period, the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range (absolute difference between groups, 3.8 percentage points; P<0.001). At 2 years of follow-up, the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy (P=0.002) and quality of life (P<0.001).Conclusions
As compared with monthly high-quality clinic testing, weekly self-testing did not delay the time to a first stroke, major bleeding episode, or death to the extent suggested by prior studies. These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT00032591.).Item Open Access Home monitoring of warfarin effects.(The New England journal of medicine, 2011-01) Lippi, Giuseppe; Franchini, MassimoItem Open Access Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation.(Blood, 2010-12) Wingard, John R; Carter, Shelly L; Walsh, Thomas J; Kurtzberg, Joanne; Small, Trudy N; Baden, Lindsey R; Gersten, Iris D; Mendizabal, Adam M; Leather, Helen L; Confer, Dennis L; Maziarz, Richard T; Stadtmauer, Edward A; Bolaños-Meade, Javier; Brown, Janice; Dipersio, John F; Boeckh, Michael; Marr, Kieren A; Blood and Marrow Transplant Clinical Trials NetworkInvasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P = .09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and overall survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803.Item Open Access Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data.(Lancet (London, England), 2012-01) Heneghan, Carl; Ward, Alison; Perera, Rafael; Self-Monitoring Trialist Collaboration; Bankhead, Clare; Fuller, Alice; Stevens, Richard; Bradford, Kairen; Tyndel, Sally; Alonso-Coello, Pablo; Ansell, Jack; Beyth, Rebecca; Bernardo, Artur; Christensen, Thomas Decker; Cromheecke, ME; Edson, Robert G; Fitzmaurice, David; Gadisseur, Alain PA; Garcia-Alamino, Josep M; Gardiner, Chris; Hasenkam, J Michael; Jacobson, Alan; Kaatz, Scott; Kamali, Farhad; Khan, Tayyaba Irfan; Knight, Eve; Körtke, Heinrich; Levi, Marcel; Matchar, David; Menéndez-Jándula, Bárbara; Rakovac, Ivo; Schaefer, Christian; Siebenhofer, Andrea; Souto, Juan Carlos; Sunderji, Rubina; Gin, Kenneth; Shalansky, Karen; Völler, Heinz; Wagner, Otto; Zittermann, ArminBackground
Uptake of self-testing and self-management of oral anticoagulation [corrected] has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism.Methods
We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat.Findings
Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12,800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0·51; 95% CI 0·31-0·85) but not for major haemorrhagic events (0·88, 0·74-1·06) or death (0·82, 0·62-1·09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0·33, 95% CI 0·17-0·66), as did participants with mechanical heart valve (0·52, 0·35-0·77). Analysis of major outcomes in the very elderly (age ≥85 years, n=99) showed no significant adverse effects of the intervention for all outcomes.Interpretation
Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up.Funding
UK National Institute for Health Research (NIHR) Technology Assessment Programme, UK NIHR National School for Primary Care Research.Item Open Access The impact of frequency of patient self-testing of prothrombin time on time in target range within VA Cooperative Study #481: The Home INR Study (THINRS), a randomized, controlled trial.(Journal of thrombosis and thrombolysis, 2015-07) Matchar, David B; Love, Sean R; Jacobson, Alan K; Edson, Robert; Uyeda, Lauren; Phibbs, Ciaran S; Dolor, Rowena JAnticoagulation (AC) is effective in reducing thromboembolic events for individuals with atrial fibrillation (AF) or mechanical heart valve (MHV), but maintaining patients in target range for international normalized ratio (INR) can be difficult. Evidence suggests increasing INR testing frequency can improve time in target range (TTR), but this can be impractical with in-clinic testing. The objective of this study was to test the hypothesis that more frequent patient-self testing (PST) via home monitoring increases TTR. This planned substudy was conducted as part of The Home INR Study, a randomized controlled trial of in-clinic INR testing every 4 weeks versus PST at three different intervals. The setting for this study was 6 VA centers across the United States. 1,029 candidates with AF or MHV were trained and tested for competency using ProTime INR meters; 787 patients were deemed competent and, after second consent, randomized across four arms: high quality AC management (HQACM) in a dedicated clinic, with venous INR testing once every 4 weeks; and telephone monitored PST once every 4 weeks; weekly; and twice weekly. The primary endpoint was TTR at 1-year follow-up. The secondary endpoints were: major bleed, stroke and death, and quality of life. Results showed that TTR increased as testing frequency increased (59.9 ± 16.7 %, 63.3 ± 14.3 %, and 66.8 ± 13.2 % [mean ± SD] for the groups that underwent PST every 4 weeks, weekly and twice weekly, respectively). The proportion of poorly managed patients (i.e., TTR <50 %) was significantly lower for groups that underwent PST versus HQACM, and the proportion decreased as testing frequency increased. Patients and their care providers were unblinded given the nature of PST and HQACM. In conclusion, more frequent PST improved TTR and reduced the proportion of poorly managed patients.Item Open Access Withdrawal severity and early response to treatment in the outpatient transition from opioid use to extended release naltrexone.(The American journal on addictions, 2018-09) Mannelli, Paolo; Swartz, Marvin; Wu, Li-TzyBACKGROUND AND OBJECTIVES:Long acting naltrexone has improved the therapy of opioid use disorder (OUD), and safe and effective withdrawal management during naltrexone induction may help advance treatment. Despite the uncertain role of opioid withdrawal in predicting successful outcomes, early symptom control may favor detoxification completion. METHODS:We explored withdrawal severity and early response to treatment, safety, and clinical measures in 35 adult patients with DSM-5 OUD during a 7-day office-based buprenorphine-naltrexone and ancillary medications transition to extended-release naltrexone (XR-NTX). RESULTS:Subjective and objective measures of withdrawal intensity improved consistently throughout treatment in the whole sample. Participants who went on to receive XR-NTX (n = 27, 77%) reported a greater attenuation of symptoms by treatment day 2 (r = .595, p = .001), and were less likely to be injection drug users (r = -.501, p = .004). Adverse events (AEs) were recorded in 20% of participants: the majority (n = 6, 85.7%) consisted of single episodes of increased withdrawal which were well controlled using ancillary medications. One serious AE was unrelated to treatment. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE:Early opioid withdrawal changes may be a useful indicator of treatment response, helping adjust the transition protocol to the individual patients' need and gather valuable information for a better understanding of the relationship between initiating and remaining in treatment. (Am J Addict 2018;27:471-476).