Burden of cytomegalovirus disease in allogeneic hematopoietic cell transplant recipients: a national, matched cohort study in an inpatient setting.

PURPOSE OF THE STUDY: No studies have compared the risk of mortality or graft-versus-host disease, in an inpatient setting in France, in allogeneic hematopoietic cell transplant recipients who develop cytomegalovirus disease with those who do not. This study assessed the impact of cytomegalovirus disease on clinical outcomes and healthcare resource utilization in allogeneic hematopoietic cell transplant recipients using the French Programme de Médicalisation des Systèmes d'Information database. PATIENTS AND METHODS: Recipients who had undergone allogeneic hematopoietic cell transplant in French hospitals between 2008 and 2011 were included in this retrospective, matched cohort study. Those with cytomegalovirus disease were each matched with two allogeneic hematopoietic cell transplant recipients without cytomegalovirus disease according to demographic and clinical characteristics. Probabilities of in-hospital mortality, graft rejection and/or graft-versus-host disease, and healthcare resource utilization were compared up to 12 months after cytomegalovirus disease diagnosis. RESULTS: Overall, 4884 transplant recipients were enrolled, of which 194 had cytomegalovirus disease. Of these, 165 recipients with cytomegalovirus disease were matched to 330 without cytomegalovirus disease (1:2 ratio). The development of cytomegalovirus disease was associated with a significantly higher risk of in-hospital mortality (relative risk = 1.7, p = 0.0005) and higher cumulative number of inpatient days (p < 0.0001), but was not associated with a significantly higher risk of graft rejection and/or graft-versus-host disease or healthcare costs. CONCLUSIONS: Due to the increased risk of in-hospital mortality and higher cumulative number of inpatient days in allogeneic hematopoietic cell transplant recipients with cytomegalovirus disease versus those without, new strategies to prevent and manage cytomegalovirus disease are warranted.

Patient and physician preferences for oral pharmacotherapy for overactive bladder: two discrete choice experiments.

OBJECTIVE: We examined patient and treating physician (general practitioners, urologists, and [uro]gynecologists) preferences for oral pharmacotherapy (antimuscarinics and beta-3 adrenoceptor agonists) for overactive bladder to gain a deeper understanding of which attributes drive their treatment decision-making and to quantify to what extent. RESEARCH DESIGN AND METHODS: Two separate discrete choice experiments were developed and validated using the input of patients and physicians. The patient experiment contained the following attributes: micturition frequency, incontinence, nocturia, urgency, dry mouth, constipation, increased heart rate, and increased blood pressure. The physician experiment contained two additional attributes: coping and atrial fibrillation. Both were fielded in five European countries. To allow for preference heterogeneity, utility functions were estimated using a mixed multinomial logit model. RESULTS: A total of 442 patient and 318 physician responses were analyzed. Patients ranked the attributes based on their largest potential impact on treatment value as follows: incontinence, nocturia, risk of an increased heart rate, urgency, frequency, risk of increased blood pressure, risk of constipation, and risk of dry mouth; and physicians as follows: incontinence, urgency, nocturia, frequency, risk of dry mouth, coping, risk of increased heart rate, risk of increased blood pressure, risk of atrial fibrillation, and risk of constipation. CONCLUSION AND LIMITATIONS: In their valuations, physicians put more emphasis on increasing benefits, whereas patients put more emphasis on limiting risks of side effects. Another contrast that emerged was that patients' valuations of side effects were found to be fairly insensitive to the presented risk levels (with the exception of risk of dry mouth), whereas physicians' evaluated all side effects in a risk-level dependent manner. The obtained utility functions can be used to predict whether, to what extent, and for which reasons patients and physicians would choose one oral pharmacotherapy over another, as well as to advance shared decision-making.

The effect of mirabegron on patient-related outcomes in patients with overactive bladder: the results of post hoc correlation and responder analyses using pooled data from three randomized Phase III trials.

PURPOSE: To understand how improvements in the symptoms of overactive bladder (OAB) seen with the ß3-adrenoceptor agonist mirabegron 50 mg, correlate with patient experience as measured by validated and standard patient-reported outcomes (PROs), and to identify whether there is overall directional consistency in the responsiveness of PROs to treatment effect. METHODS: In a post hoc analysis of pooled data from three randomized, double-blind, placebo-controlled, 12-week Phase III trials of mirabegron 50 mg once daily, responder rates for incontinence frequency (≥50 % reduction in incontinence episodes/24 h from baseline to final visit), micturition frequency (≤8 micturitions/24 h at final visit), and PROs [minimally important differences in patient perception of bladder condition (PPBC) and subsets of the overactive bladder questionnaire (OAB-q) measuring total health-related quality of life (HRQoL), and symptom bother] were evaluated individually and in combination. RESULTS: Mirabegron 50 mg demonstrated greater improvement from baseline to final visit than placebo for each of the responder analyses, whether for individual objective and subjective outcomes or combinations thereof. These improvements versus placebo were statistically significant for all double and triple responder analyses and for all single responder analyses except PPBC. PRO measurements showed directional consistency and significant correlations, and there were also significant correlations between objective and subjective measures of efficacy. CONCLUSIONS: The improvements in objective measures seen with mirabegron 50 mg translate into a meaningful clinical benefit as evident by the directional consistency seen in HRQoL measures of benefit.

Understanding the effects on HR-QoL of treatment for overactive bladder: a detailed analysis of EQ-5D clinical trial data for mirabegron.

BACKGROUND: Analysis of EQ-5D data often focuses on changes in utility, ignoring valuable information from other parts of the instrument. The objective was to explore how the utility index, EQ-5D profile, and EQ-VAS captured change in clinical trials of mirabegron, a new treatment for overactive bladder (OAB). DATA: Data were pooled from three phase III clinical trials that investigated the efficacy and safety of mirabegron vs placebo. Tolterodine ER 4 mg was included as an active control in one study: (1) placebo, mirabegron 50 mg and 100 mg, and tolterodine 4 mg ER; (2) placebo, mirabegron 50 mg and 100 mg; (3) placebo, and mirabegron 25 mg and 50 mg. Data were collected at baseline, week 4, 8, and 12. METHODS: Analyses were performed on full analysis and modified intention to treat (ITT) data sets using UK utilities. Analysis controlled for relevant patient characteristics. Analysis of Covariance identified changes from baseline at each time point in utilities and EQ-VAS. Areas Under the Curve were estimated to summarize inter-temporal differences in effect. EQ-5D profile data were analysed using the Paretian Classification of Health Change. RESULTS: In modified ITT analyses, mirabegron 50 mg was superior to tolterodine 4 mg in changes from baseline utilities after 12 weeks (p < 0.05); similarly, AUC results showed mirabegron 50 mg to be superior to tolterodine (p < 0.05) and placebo (p < 0.05) with the benefit already apparent at 4 weeks (p < 0.05). EQ-VAS more consistently indicated superior outcomes: all three mirabegron doses showed statistically significant greater effectiveness compared to tolterodine at 12 weeks. Individual EQ-5D dimensions and the overall profile showed no significant differences between study arms. CONCLUSION: Mirabegron showed quicker and superior improvement in HR-QoL compared to tolterodine 4 mg ER. A limitation of the study is that EQ-5D was a secondary outcome in the pivotal trials, which were not powered to measure differences on EQ-5D.

Rate, degree, and predictors of recovery from disability following ischemic stroke.

OBJECTIVE: To determine the rate, degree, and predictors of recovery from disabling ischemic stroke. METHODS: Patients with ischemic stroke enrolled in the Management of Atherothrombosis With Clopidogrel in High-Risk Patients (MATCH) study underwent long-term prospective assessment of their modified Rankin Scale (mRS) score. Disability (functionally dependent state) was defined as mRS > or = 3, and recovery (functionally independent state) was defined as mRS < 3. The timing and the independent predictors of recovery were determined using a Cox proportional hazards multiple regression analysis. RESULTS: Of 7,599 patients enrolled with ischemic stroke or TIA, 1,662 (21.8%) were disabled (mRS > or = 3) at baseline (median of 14 [0 to 96] days after stroke onset). Disability was moderate (mRS 3) in 931 (56%) patients, severe (mRS 4) in 691 (42%), and very severe (mRS 5) in 40 (2%). By 18 months, 877 (52.8%, 95% CI 50% to 55%) patients had recovered, 589 (63%, 60% to 66%) with moderate disability, 281 (41%, 37% to 44%) with severe disability, and 7 (17%, 7 to 33%) with very severe disability. Median time to recovery was 3 months for patients with moderate disability and 18 months for severe disability; 82.5% of severely disabled patients remained so at 18 months. Predictors of recovery were moderate disability (mRS 3) at baseline compared with severe (mRS 4: hazard ratio [HR] 2.13, 1.86 to 2.44) or very severe disabling stroke (HR 5.88, 2.86 to 12.5); younger women (aged <65 years, compared with > or =75 years; HR 1.85, 1.47 to 2.33); decreasing time (days) between the qualifying event and the baseline assessment (HR 1.01, 1.01 to 1.02); and the absence of previous ischemic stroke (HR 1.61, 1.35 to 1.92), concurrent peripheral artery disease (HR 1.61, 1.23 to 2.13), or diabetes (HR 1.30, 1.10 to 1.54). CONCLUSIONS: Half of patients with disabling ischemic stroke recovered within 18 months, and recovery was greatest within 6 months. Significant predictors of recovery included the severity of the index stroke and no history of ischemic stroke, peripheral artery disease, or diabetes.

Time frame and predictors of recovery from disability following recurrent ischemic stroke.

OBJECTIVE: To assess the rate, degree, and predictors of recovery from a disabled to nondisabled state in patients disabled after recurrent ischemic stroke. METHODS: Patients with ischemic stroke enrolled in the Management of Atherothrombosis with Clopidogrel in High Risk Patients (MATCH) Study underwent prospective assessment of their modified Rankin score (mRS) at 1, 3, 6, 12, and 18 months after enrollment and after recurrent stroke. Patients disabled (defined as mRS > or = 3) after recurrence were analyzed for recovery (defined as mRS < 3) during the 18 months, and predictors of recovery were sought using a Cox proportional-hazard multiple regression analysis. RESULTS: Three hundred forty-five (54%) of 637 patients were disabled after recurrent ischemic stroke; 115 (33%) patients had been disabled and 230 (66%) nondisabled before stroke recurrence. At recurrence, the degree of disability was moderate (mRS 3) in 135 (39%) patients, severe (mRS 4) in 139 (40%), and very severe (mRS 5) in 71 (21%). After 12 months' median follow-up, 117 (34%, 95% CI: 29 to 39%) had recovered: 68 (50%, 42 to 59%) of 135 moderately disabled, 45 (32%, 25 to 41%) of 139 severely disabled, and 4 (6%, 2 to 14%) of 71 very severely disabled; 70 (20.3%) patients died. From recurrence, median time to recovery was 6 months (mRS 3) and 18 months (mRS 4); 94% with very severe disability had not recovered at 18 months. Independent predictors of recovery were moderate disability at recurrence (mRS 3) compared with severe (mRS 4: hazard ratio [HR] 1.5; 95% CI 1.04 to 2.3) or very severe disability (mRS 5: HR 7.6; 2.7 to 20) and a nondisabled vs disabled state before recurrence (HR 4.0; 2.3 to 6.8). CONCLUSIONS: The rate of recovery from recurrent ischemic stroke was greatest in the first 6 months; one-third of patients recovered within 12 months. The significant predictors of recovery were a nondisabled state before recurrence and increasing severity of the recurrent stroke.