Browsing by Subject "Administration, Oral"
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Item Open Access A new instrument for measuring anticoagulation-related quality of life: development and preliminary validation.(Health Qual Life Outcomes, 2004-05-06) Samsa, Greg; Matchar, David B; Dolor, Rowena J; Wiklund, Ingela; Hedner, Ewa; Wygant, Gail; Hauch, Ole; Marple, Cheryl Beadle; Edwards, RogerBACKGROUND: Anticoagulation can reduce quality of life, and different models of anticoagulation management might have different impacts on satisfaction with this component of medical care. Yet, to our knowledge, there are no scales measuring quality of life and satisfaction with anticoagulation that can be generalized across different models of anticoagulation management. We describe the development and preliminary validation of such an instrument - the Duke Anticoagulation Satisfaction Scale (DASS). METHODS: The DASS is a 25-item scale addressing the (a) negative impacts of anticoagulation (limitations, hassles and burdens); and (b) positive impacts of anticoagulation (confidence, reassurance, satisfaction). Each item has 7 possible responses. The DASS was administered to 262 patients currently receiving oral anticoagulation. Scales measuring generic quality of life, satisfaction with medical care, and tendency to provide socially desirable responses were also administered. Statistical analysis included assessment of item variability, internal consistency (Cronbach's alpha), scale structure (factor analysis), and correlations between the DASS and demographic variables, clinical characteristics, and scores on the above scales. A follow-up study of 105 additional patients assessed test-retest reliability. RESULTS: 220 subjects answered all items. Ceiling and floor effects were modest, and 25 of the 27 proposed items grouped into 2 factors (positive impacts, negative impacts, this latter factor being potentially subdivided into limitations versus hassles and burdens). Each factor had a high degree of internal consistency (Cronbach's alpha 0.78-0.91). The limitations and hassles factors consistently correlated with the SF-36 scales measuring generic quality of life, while the positive psychological impact scale correlated with age and time on anticoagulation. The intra-class correlation coefficient for test-retest reliability was 0.80. CONCLUSIONS: The DASS has demonstrated reasonable psychometric properties to date. Further validation is ongoing. To the degree that dissatisfaction with anticoagulation leads to decreased adherence, poorer INR control, and poor clinical outcomes, the DASS has the potential to help identify reasons for dissatisfaction (and positive satisfaction), and thus help to develop interventions to break this cycle. As an instrument designed to be applicable across multiple models of anticoagulation management, the DASS could be crucial in the scientific comparison between those models of care.Item Open Access A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis.(N Engl J Med, 2018-03-16) Le, Thuy; Kinh, Nguyen Van; Cuc, Ngo TK; Tung, Nguyen LN; Lam, Nguyen T; Thuy, Pham TT; Cuong, Do D; Phuc, Pham TH; Vinh, Vu H; Hanh, Doan TH; Tam, Vu Van; Thanh, Nguyen T; Thuy, Tran P; Hang, Nguyen T; Long, Hoang B; Nhan, Ho T; Wertheim, Heiman FL; Merson, Laura; Shikuma, Cecilia; Day, Jeremy N; Chau, Nguyen VV; Farrar, Jeremy; Thwaites, Guy; Wolbers, Marcel; IVAP InvestigatorsBACKGROUND: Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking. METHODS: In this open-label, noninferiority trial, we randomly assigned 440 HIV-infected adults who had talaromycosis, confirmed by either microscopy or culture, to receive either intravenous amphotericin B deoxycholate (amphotericin) (219 patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days, followed by 400 mg per day, for 11 days; thereafter, all the patients received maintenance therapy with itraconazole. The primary outcome was all-cause mortality at week 2. Secondary outcomes included all-cause mortality at week 24, the time to clinical resolution of talaromycosis, early fungicidal activity, relapse of talaromycosis, development of the immune reconstitution inflammatory syndrome (IRIS), and the side-effect profile. RESULTS: The risk of death at week 2 was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval [CI], -3.9 to 5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3% in the amphotericin group and 21.0% in the itraconazole group (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with amphotericin was associated with significantly faster clinical resolution and fungal clearance and significantly lower rates of relapse and IRIS than itraconazole. The patients who received amphotericin had significantly higher rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, and anemia than patients in the itraconazole group. CONCLUSIONS: Amphotericin was superior to itraconazole as initial treatment for talaromycosis with respect to 6-month mortality, clinical response, and fungicidal activity. (Funded by the Medical Research Council and others; IVAP Current Controlled Trials number, ISRCTN59144167 .).Item Open Access Addressing barriers to optimal oral anticoagulation use and persistence among patients with atrial fibrillation: Proceedings, Washington, DC, December 3-4, 2012.(American heart journal, 2014-09) Hess, Paul L; Mirro, Michael J; Diener, Hans-Christoph; Eikelboom, John W; Al-Khatib, Sana M; Hylek, Elaine M; Bosworth, Hayden B; Gersh, Bernard J; Singer, Daniel E; Flaker, Greg; Mega, Jessica L; Peterson, Eric D; Rumsfeld, John S; Steinberg, Benjamin A; Kakkar, Ajay K; Califf, Robert M; Granger, Christopher B; Atrial Fibrillation Think-Tank ParticipantsApproximately half of patients with atrial fibrillation and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3-4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to define reasons for oral anticoagulant underuse classified in ways that can guide intervention and improve use, to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational data sets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives.Item Open Access Association of Intracerebral Hemorrhage Among Patients Taking Non-Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality.(JAMA, 2018-02) Inohara, Taku; Xian, Ying; Liang, Li; Matsouaka, Roland A; Saver, Jeffrey L; Smith, Eric E; Schwamm, Lee H; Reeves, Mathew J; Hernandez, Adrian F; Bhatt, Deepak L; Peterson, Eric D; Fonarow, Gregg CAlthough non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH).To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulants [OACs]) and in-hospital mortality among patients with ICH.Retrospective cohort study of 141 311 patients with ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines-Stroke hospitals.Anticoagulation therapy before ICH, defined as any use of OACs within 7 days prior to hospital arrival.In-hospital mortality.Among 141 311 patients with ICH (mean [SD] age, 68.3 [15.3] years; 48.1% women), 15 036 (10.6%) were taking warfarin and 4918 (3.5%) were taking NOACs preceding ICH, and 39 585 (28.0%) and 5783 (4.1%) were taking concomitant single and dual antiplatelet agents, respectively. Patients with prior use of warfarin or NOACs were older and had higher prevalence of atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates were 32.6% for warfarin, 26.5% for NOACs, and 22.5% for no OACs. Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5% CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5% CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5% CI, 1.7% to 4.8%]; AOR, 1.21 [97.5% CI, 1.11-1.32]). Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD, -5.7% [97.5% CI, -7.3% to -4.2%]; AOR, 0.75 [97.5% CI, 0.69 to 0.81]). The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7% vs 47.1%; ARD, -15.0% [95.5% CI, -26.3% to -3.8%]; AOR, 0.50 [97.5% CI, 0.29 to 0.86]) than among those taking these agents without prior antiplatelet therapy (26.4% vs 31.7%; ARD, -5.0% [97.5% CI, -6.8% to -3.2%]; AOR, 0.77 [97.5% CI, 0.70 to 0.85]), although the interaction P value (.07) was not statistically significant.Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs. Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.Item Open Access Association of Preceding Antithrombotic Treatment With Acute Ischemic Stroke Severity and In-Hospital Outcomes Among Patients With Atrial Fibrillation.(JAMA, 2017-03) Xian, Ying; O'Brien, Emily C; Liang, Li; Xu, Haolin; Schwamm, Lee H; Fonarow, Gregg C; Bhatt, Deepak L; Smith, Eric E; Olson, DaiWai M; Maisch, Lesley; Hannah, Deidre; Lindholm, Brianna; Lytle, Barbara L; Pencina, Michael J; Hernandez, Adrian F; Peterson, Eric DImportance:Antithrombotic therapies are known to prevent stroke for patients with atrial fibrillation (AF) but are often underused in community practice. Objectives:To examine the prevalence of patients with acute ischemic stroke with known history of AF who were not receiving guideline-recommended antithrombotic treatment before stroke and to determine the association of preceding antithrombotic therapy with stroke severity and in-hospital outcomes. Design, Setting, and Participants:Retrospective observational study of 94 474 patients with acute ischemic stroke and known history of AF admitted from October 2012 through March 2015 to 1622 hospitals participating in the Get With the Guidelines-Stroke program. Exposures:Antithrombotic therapy before stroke. Main Outcomes and Measures:Stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS; range of 0-42, with a higher score indicating greater stroke severity and a score ≥16 indicating moderate or severe stroke), and in-hospital mortality. Results:Of 94 474 patients (mean [SD] age, 79.9 [11.0] years; 57.0% women), 7176 (7.6%) were receiving therapeutic warfarin (international normalized ratio [INR] ≥2) and 8290 (8.8%) were receiving non-vitamin K antagonist oral anticoagulants (NOACs) preceding the stroke. A total of 79 008 patients (83.6%) were not receiving therapeutic anticoagulation; 12 751 (13.5%) had subtherapeutic warfarin anticoagulation (INR <2) at the time of stroke, 37 674 (39.9%) were receiving antiplatelet therapy only, and 28 583 (30.3%) were not receiving any antithrombotic treatment. Among 91 155 high-risk patients (prestroke CHA2DS2-VASc score ≥2), 76 071 (83.5%) were not receiving therapeutic warfarin or NOACs before stroke. The unadjusted rates of moderate or severe stroke were lower among patients receiving therapeutic warfarin (15.8% [95% CI, 14.8%-16.7%]) and NOACs (17.5% [95% CI, 16.6%-18.4%]) than among those receiving no antithrombotic therapy (27.1% [95% CI, 26.6%-27.7%]), antiplatelet therapy only (24.8% [95% CI, 24.3%-25.3%]), or subtherapeutic warfarin (25.8% [95% CI, 25.0%-26.6%]); unadjusted rates of in-hospital mortality also were lower for those receiving therapeutic warfarin (6.4% [95% CI, 5.8%-7.0%]) and NOACs (6.3% [95% CI, 5.7%-6.8%]) compared with those receiving no antithrombotic therapy (9.3% [95% CI, 8.9%-9.6%]), antiplatelet therapy only (8.1% [95% CI, 7.8%-8.3%]), or subtherapeutic warfarin (8.8% [95% CI, 8.3%-9.3%]). After adjusting for potential confounders, compared with no antithrombotic treatment, preceding use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio [95% CI], 0.56 [0.51-0.60], 0.65 [0.61-0.71], and 0.88 [0.84-0.92], respectively) and in-hospital mortality (adjusted odds ratio [95% CI], 0.75 [0.67-0.85], 0.79 [0.72-0.88], and 0.83 [0.78-0.88], respectively). Conclusions and Relevance:Among patients with atrial fibrillation who had experienced an acute ischemic stroke, inadequate therapeutic anticoagulation preceding the stroke was prevalent. Therapeutic anticoagulation was associated with lower odds of moderate or severe stroke and lower odds of in-hospital mortality.Item Open Access Associations of Community and Individual Social Determinants of Health With Medication Adherence in Patients With Atrial Fibrillation: A Retrospective Cohort Study.(Journal of the American Heart Association, 2023-04) Boyd, Lisa M; Colavecchia, Anthony Carmine; Townsend, Kevin A; Kmitch, Laura; Broder, Leah; Hegeman-Dingle, Rozelle R; Ateya, Mohammad; Lattimer, Alan; Bosch, Ryan; Alvir, JoseBackground Despite guideline-recommended use of oral anticoagulation (OAC) for stroke prevention in atrial fibrillation (AF), OAC medication adherence among patients with AF in the United States ranges from 47% to 82%. To characterize potential causes of nonadherence, we analyzed associations between community and individual social risk factors and OAC adherence for stroke prevention in AF. Methods and Results A retrospective cohort analysis of patients with AF was conducted using the IQVIA PharMetrics Plus claims data from January 2016 to June 2020, and 3-digit ZIP code-level social risk scores were calculated using American Community Survey and commercial data. Logistic regression models evaluated associations between community social determinants of health, community social risk scores for 5 domains (economic climate, food landscape, housing environment, transportation network, and health literacy), patient characteristics and comorbidities, and 2 adherence outcomes: persistence on OAC for 180 days and proportion of days covered ≥0.80 at 360 days. Of 28 779 patients with AF included in the study, 70.8% of patients were male, 94.6% were commercially insured, and the average patient age was 59.2 years. Multivariable regression found that greater health literacy risk was negatively associated with 180-day persistence (odds ratio [OR]=0.80 [95% CI, 0.76-0.83]) and 360-day proportion of days covered (OR, 0.81 [95% CI, 0.76-0.87]). Patient age and higher AF stroke risk score and AF bleeding risk scores were positively associated with both 180-day persistence and 360-day proportion of days covered. Conclusions Social risk domains, such as health literacy, may affect OAC adherence among patients with AF. Future studies should explore associations between social risk factors and nonadherence with greater geographic granularity.Item Open Access Breast cancer oral anti-cancer medication adherence: a systematic review of psychosocial motivators and barriers.(Breast cancer research and treatment, 2017-09) Lin, Cheryl; Clark, Rachel; Tu, Pikuei; Bosworth, Hayden B; Zullig, Leah LPurpose
In the past decade, there has been an increase in the development and use of oral anti-cancer medications (OAMs), especially for breast cancer-the most prevalent cancer in women. However, adherence rates for OAMs are often suboptimal, leading to lower survival rate, increased risk of recurrence, and higher healthcare costs. Our goal was to identify potentially modifiable psychosocial facilitators and barriers that may be targeted to increase OAM adherence for breast cancer patients.Methods
We systematically searched PubMed for studies published in the U.S. by June 15, 2016 that addressed the following: (1) OAMs for breast cancer; (2) medication adherence; and (3) at least one psychosocial aspect of adherence.Results
Of the 1752 papers screened, 21 articles were included and analyzed. The most commonly reported motivators for adherence are patient-provider relationships (n = 11 studied, 82% reported significant association) and positive views and beliefs of medication (n = 9 studied, 89% reported significant association). We also identified consistent evidence of the impact of depression and emotions, perception of illness, concern of side effects, self-efficacy in medication management and decision making, knowledge of medication, and social support on OAM adherence.Conclusions
Compared to traditional demographic, system, and clinical-related factors that have been well documented in the literature but are not easily changed, these cognitive, psychological, and interpersonal factors are more amendable via intervention and therefore could generate greater benefit in improving patient compliance and health outcomes. As OAMs shift treatment administration responsibility onto patients, continuous provider communication and education on illness and regimen are the keys to supporting patients' medication behavior.Item Open Access Bupropion and Naltrexone in Methamphetamine Use Disorder.(The New England journal of medicine, 2021-01) Trivedi, Madhukar H; Walker, Robrina; Ling, Walter; Dela Cruz, Adriane; Sharma, Gaurav; Carmody, Thomas; Ghitza, Udi E; Wahle, Aimee; Kim, Mora; Shores-Wilson, Kathy; Sparenborg, Steven; Coffin, Phillip; Schmitz, Joy; Wiest, Katharina; Bart, Gavin; Sonne, Susan C; Wakhlu, Sidarth; Rush, A John; Nunes, Edward V; Shoptaw, StevenBackground
The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.Methods
We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses.Results
A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial.Conclusions
Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).Item Open Access Cognitive Function: Is There More to Anticoagulation in Atrial Fibrillation Than Stroke?(J Am Heart Assoc, 2015-08-03) Cao, Lin; Pokorney, Sean D; Hayden, Kathleen; Welsh-Bohmer, Kathleen; Newby, L KristinItem Open Access Colchicine effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): study protocol for a randomized controlled trial.(Trials, 2015-04-30) Leung, Ying-Ying; Thumboo, Julian; Wong, Bak Siew; Haaland, Ben; Chowbay, Balram; Chakraborty, Bibhas; Tan, Mann Hong; Kraus, Virginia BBACKGROUND: Despite the high prevalence and global impact of knee osteoarthritis (KOA), current treatments are palliative. No disease modifying anti-osteoarthritic drug (DMOAD) has been approved. We recently demonstrated significant involvement of uric acid and activation of the innate immune response in osteoarthritis (OA) pathology and progression, suggesting that traditional gout therapy may be beneficial for OA. We therefore assess colchicine, an existing commercially available agent for gout, for a new therapeutic application in KOA. METHODS/DESIGN: COLKOA is a double-blind, placebo-controlled, randomized trial comparing a 16-week treatment with standard daily dose oral colchicine to placebo for KOA. A total of 120 participants with symptomatic KOA will be recruited from a single center in Singapore. The primary end point is 30% improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at week 16. Secondary end points include improvement in pain, physical function, and quality of life and change in serum, urine and synovial fluid biomarkers of cartilage metabolism and inflammation. A magnetic resonance imaging (MRI) substudy will be conducted in 20 participants to evaluate change in synovitis. Logistic regression will be used to compare changes between groups in an intention-to-treat analysis. DISCUSSION: The COLKOA trial is designed to evaluate whether commercially available colchicine is effective for improving signs and symptoms of KOA, and reducing synovial fluid, serum and urine inflammatory and biochemical joint degradation biomarkers. These biomarkers should provide insights into the underlying mechanism of therapeutic response. This trial will potentially provide data to support a new treatment option for KOA. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov as NCT02176460 . Date of registration: 26 June 2014.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 Early adoption of dabigatran and its dosing in US patients with atrial fibrillation: results from the outcomes registry for better informed treatment of atrial fibrillation.(J Am Heart Assoc, 2013-11-25) Steinberg, Benjamin A; Holmes, Dajuanicia N; Piccini, Jonathan P; Ansell, Jack; Chang, Paul; Fonarow, Gregg C; Gersh, Bernard; Mahaffey, Kenneth W; Kowey, Peter R; Ezekowitz, Michael D; Singer, Daniel E; Thomas, Laine; Peterson, Eric D; Hylek, Elaine M; Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Investigators and PatientsBACKGROUND: Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown. METHODS AND RESULTS: We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P<0.0001), more likely to be white (92% versus 89%, P=0.005), more likely to have private insurance (33% versus 25%, P<0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P<0.0001). They had more new-onset atrial fibrillation (8.8% versus 4.1%, P<0.0001), lower CHADS2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P<0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P<0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow-up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P=0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P<0.0001). CONCLUSIONS: Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted. CLINICAL TRIAL REGISTRATION URL: Clinicaltrials.gov. Unique identifier: NCT01165710.Item Open Access Management of Atrial Fibrillation in Older Patients by Morbidity Burden: Insights From Get With The Guidelines-Atrial Fibrillation.(Journal of the American Heart Association, 2020-12) Dalgaard, Frederik; Xu, Haolin; Matsouaka, Roland A; Russo, Andrea M; Curtis, Anne B; Rasmussen, Peter Vibe; Ruwald, Martin H; Fonarow, Gregg C; Lowenstern, Angela; Hansen, Morten L; Pallisgaard, Jannik L; Alexander, Karen P; Alexander, John H; Lopes, Renato D; Granger, Christopher B; Lewis, William R; Piccini, Jonathan P; Al-Khatib, Sana MBackground Knowledge is scarce regarding how multimorbidity is associated with therapeutic decisions regarding oral anticoagulants (OACs) in patients with atrial fibrillation. Methods and Results We conducted a cross-sectional study of hospitalized patients with atrial fibrillation using the Get With The Guidelines-Atrial Fibrillation registry from 2013 to 2019. We identified patients ≥65 years and eligible for OAC therapy. Using 16 available comorbidity categories, patients were stratified by morbidity burden. A multivariable logistic regression model was used to determine the odds of receiving OAC prescription at discharge by morbidity burden. We included 34 174 patients with a median (interquartile range) age of 76 (71-83) years, 56.6% women, and 41.9% were not anticoagulated at admission. Of these patients, 38.6% had 0 to 2 comorbidities, 50.7% had 3 to 5 comorbidities, and 10.7% had ≥6 comorbidities. The overall discharge OAC prescription was high (85.6%). The prevalence of patients with multimorbidity increased from 59.7% in 2014 to 64.3% in 2019 (P trend=0.002). Using 0 to 2 comorbidities as the reference, the adjusted odds ratio (95% CI) of OAC prescription were 0.93 (0.82, 1.05) for patients with 3 to 5 comorbidities and 0.72 (0.60, 0.86) for patients with ≥6 comorbidities. In those with ≥6 comorbidities, the most common reason for nonprescription of OACs were frequent falls/frailty (31.0%). Conclusions In a contemporary quality-of-care database of hospitalized patients with atrial fibrillation eligible for OAC therapy, multimorbidity was common. A higher morbidity burden was associated with a lower odds of OAC prescription. This highlights the need for interventions to improve adherence to guideline-recommended anticoagulation in multimorbid patients with atrial fibrillation.Item Open Access Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study.(Br J Cancer, 2009-12-15) Reardon, DA; Desjardins, A; Vredenburgh, JJ; Gururangan, S; Sampson, JH; Sathornsumetee, S; McLendon, RE; Herndon, JE; Marcello, JE; Norfleet, J; Friedman, AH; Bigner, DD; Friedman, HSBACKGROUND: We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. METHODS: A total of 59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 mg kg(-1) bevacizumab biweekly and 50 mg m(-2) etoposide daily for 21 consecutive days each month. The primary end point was a 6-month progression-free survival, and secondary end points included safety and overall survival. Vascular endothelial growth factor (VEGF), VEGFR-2, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor-2alpha (HIF-2alpha) were assessed semiquantitatively in archival tumours using immunohistochemistry and were correlated with outcome. RESULTS: Among grade 3 and GBM patients, the 6-month progression-free survivals were 40.6% and 44.4%, the radiographic response rates were 22% and 37% and the median survivals were 63.1 and 44.4 weeks, respectively. Hypertension predicted better outcome among both grade 3 and GBM patients, whereas high CA9 and low VEGF were associated with poorer progression-free survival (PFS) among those with GBM. The most common grade > or = 3 adverse events included neutropaenia (24%), thrombosis (12%), infection (8%) and hypertension (3%). Two patients had asymptomatic, grade 1 intracranial haemorrhage and one on-study death occurred because of pulmonary embolism. CONCLUSION: Bevacizumab with metronomic etoposide has increased toxicity compared with previous reports of bevacizumab monotherapy. Its anti-tumour activity is similar to that of bevacizumab monotherapy or bevacizumab plus irinotecan. (ClinicalTrials.gov: NCT00612430).Item Open Access Microdosing and drug development: past, present and future.(Expert Opin Drug Metab Toxicol, 2013-07) Lappin, Graham; Noveck, Robert; Burt, TalINTRODUCTION: Microdosing is an approach to early drug development where exploratory pharmacokinetic data are acquired in humans using inherently safe sub-pharmacologic doses of drug. The first publication of microdose data was 10 years ago and this review comprehensively explores the microdose concept from conception, over the past decade, up until the current date. AREAS COVERED: The authors define and distinguish the concept of microdosing from similar approaches. The authors review the ability of microdosing to provide exploratory pharmacokinetics (concentration-time data) but exclude microdosing using positron emission tomography. The article provides a comprehensive review of data within the peer-reviewed literature as well as the latest applications and a look into the future, towards where microdosing may be headed. EXPERT OPINION: Evidence so far suggests that microdosing may be a better predictive tool of human pharmacokinetics than alternative methods and combination with physiologically based modelling may lead to much more reliable predictions in the future. The concept has also been applied to drug-drug interactions, polymorphism and assessing drug concentrations over time at its site of action. Microdosing may yet have more to offer in unanticipated directions and provide benefits that have not been fully realised to date.Item Open Access Oral sazetidine-A, a selective α4β2* nicotinic receptor desensitizing agent, reduces nicotine self-administration in rats.(Pharmacology, biochemistry, and behavior, 2019-04) Rezvani, Amir H; Wells, Corinne; Slade, Susan; Xiao, Yingxian; Kellar, Kenneth J; Levin, Edward DSazetidine-A selectively desensitizes α4β2 nicotinic receptors and also has partial agonist effects. We have shown that subcutaneous acute and repeated injections as well as chronic infusions of sazetidine-A significantly reduce intravenous (IV) nicotine self-administration in rats. To further investigate the promise of sazetidine-A as a smoking cessation aid, it is important to determine sazetidine-A effects with oral administration and the time-effect function for its action on nicotine self-administration. Young adult female Sprague-Dawley rats were trained to self-administer IV nicotine at the benchmark dose of 0.03 mg/kg/infusion dose in an operant FR1 schedule in 45-min sessions. After five sessions of training, they were tested for the effects of acute oral doses of sazetidine-A (0, 0.3, 1 and 3 mg/kg) given 30 min before testing. To determine the time-effect function, these rats were administered 0 or 3 mg/kg of sazetidine-A 1, 2, 4 or 23 h before the onset of testing. Our previous study showed that with subcutaneous injections, only 3 mg/kg of sazetidine-A significantly reduced nicotine self-administration, however, with oral administration of sazetidine-A lower dose of 1 mg/kg was also effective in reducing nicotine intake. A similar effect was seen in the time-effect study with 3 mg/kg of oral sazetidine-A causing a significant reduction in nicotine self-administration across all the time points of 1, 2, 4 or 23 h after oral administration. These results advance the development of sazetidine-A as a possible aid for smoking cessation by showing effectiveness with oral administration and persistence of the effect over the course of a day.Item Open Access Prioritizing Common Terminology and Measures to Advance Research on Oral Nicotine Product Use.(Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2024-04) Hrywna, Mary; Ozga, Jenny E; Stanton, Cassandra A; Chaffee, Benjamin W; Delnevo, Cristine D; Fucito, Lisa M; Jabba, Sairam V; Morean, Meghan E; Tackett, Alayna PItem 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.