Psychometric evaluation of a visual analog scale for the assessment of anxiety

<p>Abstract</p> <p>Background</p> <p>Fast-acting medications for the management of anxiety are important to patients and society. Measuring early onset, however, requires a sensitive and clinically responsive tool. This study evaluates the psychometric properties of a patient-reported Global Anxiety - Visual Analog Scale (GA-VAS).</p> <p>Methods</p> <p>Data from a double-blind, randomized, placebo-controlled study of lorazepam and paroxetine in patients with Generalized Anxiety Disorder were analyzed to assess the reliability, validity, responsiveness, and utility of the GA-VAS. The GA-VAS was completed at clinic visits and at home during the first week of treatment. Targeted psychometric analyses—test-retest reliabilities, validity correlations, responsiveness statistics, and minimum important differences—were conducted.</p> <p>Results</p> <p>The GA-VAS correlates well with other anxiety measures, at Week 4, <it>r </it>= 0.60 (<it>p </it>< 0.0001) with the Hamilton Rating Scale for Anxiety and <it>r </it>= 0.74 (<it>p </it>< 0.0001) with the Hospital Anxiety and Depression Scale - Anxiety subscale. In terms of convergent and divergent validity, the GA-VAS correlated -0.54 (<it>p </it>< 0.0001), -0.48 (<it>p </it>< 0.0001), and -0.68 (<it>p </it>< 0.0001) with the SF-36 Emotional Role, Social Function, and Mental Health subscales, respectively, but correlated much lower with the SF-36 physical functioning subscales. Preliminary minimum important difference estimates cluster between 10 and 15 mm.</p> <p>Conclusions</p> <p>The GA-VAS is capable of validly and effectively capturing a reduction in anxiety as quickly as 24 hours post-dose.</p

Pharmacodynamic differentiation of lorazepam sleepiness and dizziness using an ordered categorical measure

Categorical measures of lorazepam sleepiness and dizziness were modeled to identify differences in pharmacodynamic (PD) parameters between these adverse events (AEs). Differences in data-derived PD parameters were compared with relative incidence rates in the drug label (15.7% and 6.9%, respectively). Healthy volunteers ( n  = 20) received single oral doses of 2 mg lorazepam or placebo in a randomized, double-blind, cross-over fashion. A seven-point categorical scale measuring the intensity of AEs was serially administered over 24 h. The maximum score (MaxS), and area under the effect curve (AUEC) were determined by noncompartmental methods and compared using a paired t -test. Individual scores were modeled using a logistic function implemented in NONMEM. AUEC and MaxS for sleepiness were significantly higher than dizziness (20.35 vs. 9.76, p  < 0.01) and (2.35 vs. 1.45, p  < 0.01). Model slope estimates were similar for sleepiness and dizziness (0.21 logits × mL/ng vs. 0.19 logits × mL/ng), but baseline logits were significantly higher for sleepiness (−2.81 vs. −4.34 logits). Data-derived PD parameters were in concordance with label incidence rates. The higher intensity of sleepiness may be directly related to baseline (no drug present) while the increase in intensity as a result of drug was relatively similar for both AEs. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3628–3641, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77428/1/22093_ftp.pd

Comparing the cost-effectiveness and clinical effectiveness of a new community in-reach rehabilitation service with the cost-effectiveness and clinical effectiveness of an established hospital-based rehabilitation service for older people: a pragmatic randomised controlled trial with microcost and qualitative analysis – the Community In-reach Rehabilitation And Care Transition (CIRACT) study

Background: Older people represent a significant proportion of patients admitted to hospital as a medical emergency. Compared with the care of younger patients, their care is more challenging, their stay in hospital is much longer, their risk of hospital-acquired problems is much higher and their 28-day readmission rate is much greater. Objective: To compare the clinical effectiveness, microcosts and cost-effectiveness of a Community In-reach Rehabilitation And Care Transition (CIRACT) service with the traditional hospital-based rehabilitation (THB-Rehab) service in patients aged ≥ 70 years. Methods: A pragmatic randomised controlled trial with an integral health economic study and parallel qualitative appraisal was undertaken in a large UK teaching hospital, with community follow-up. Participants were individually randomised to the intervention (CIRACT service) or standard care (THB-Rehab service). The primary outcome was hospital length of stay; secondary outcomes were readmission within 28 and 91 days post discharge and super spell bed-days (total time in NHS care), functional ability, comorbidity and health-related quality of life, all measured at day 91, together with the microcosts and cost-effectiveness of the two services. A qualitative appraisal provided an explanatory understanding of the organisation, delivery and experience of the CIRACT service from the perspective of key stakeholders and patients. Results: In total, 250 participants were randomised (n = 125 CIRACT service, n = 125 THB-Rehab service). There was no significant difference in length of stay between the CIRACT service and the THB-Rehab service (median 8 vs. 9 days). There were no significant differences between the groups in any of the secondary outcomes. The cost of delivering the CIRACT service and the THB-Rehab service, as determined from the microcost analysis, was £302 and £303 per patient respectively. The overall mean costs (including NHS and personal social service costs) of the CIRACT and THB-Rehab services calculated from the Client Service Receipt Inventory were £3744 and £3603 respectively [mean cost difference £144, 95% confidence interval –£1645 to £1934] and the mean quality-adjusted life-years for the CIRACT service were 0.846 and for the THB-Rehab service were 0.806. The incremental cost-effectiveness ratio (ICER) from a NHS and Personal Social Services perspective was £2022 per quality-adjusted life-year. Although the CIRACT service was highly regarded by those who were most involved with it, the emergent configuration of the service working across organisational and occupational boundaries was not easily incorporated by the current established community services. Conclusions: The CIRACT service did not reduce hospital length of stay or short-term readmission rates compared with the standard THB-Rehab service, although it was highly regarded by those who were most involved with it. The estimated ICER appears cost-effective although it is subject to much uncertainty, as shown by points spanning all four quadrants of the cost-effectiveness plane. Microcosting work-sampling methodology provides a useful method to estimate the cost of service provision. Limitations in sample size, which may have excluded a smaller reduction in length of stay, and lack of blinding, which may have introduced some cross-contamination between the two groups, must be recognised. Reducing hospital length of stay and hospital readmissions remains a priority for the NHS. Further studies are necessary, which should be powered with larger sample sizes and use cluster randomisation (to reduce bias) but, more importantly, should include a more integrated community health-care model as part of the CIRACT team

A statistical approach for classifying change in cognitive function in individuals following pharmacologic challenge: an example with alprazolam

The effects of any drug treatment on cognitive function are typically studied in groups of subjects. Observations made about the behavior of the drug, in the study sample, are then generalized to the population from which the sample was drawn. However, the magnitude and pharmacodynamic qualities of the response to many central nervous system-active drugs are known to vary in the population. Therefore, it is useful to consider statistical models for the detection of cognitive change in response to a drug treatment in individual subjects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46374/1/213_2006_Article_331.pd

Pregabalin reduces sleep disturbance in patients with generalized anxiety disorder via both direct and indirect mechanisms

Background and Objectives: To characterize the impact of pregabalin on sleep in patients with generalized anxiety disorder (GAD) and to determine whether the impact is a direct or an indirect effect, mediated through the reduction of anxiety symptoms. Methods: A post-hoc analysis of data from a randomized, double-blind, placebo- and active-controlled study in patients with GAD was conducted. Patients received pregabalin 300 mg/day, venlafaxine XR 75 mg/day or placebo for a week, followed by pregabalin 300-600 mg/day, venlafaxine XR 75-225 mg/day, or placebo for 7 weeks. Treatment effect on sleep was evaluated using the Medical Outcomes Study Sleep Scale. Anxiety symptoms were assessed with the Hamilton Anxiety Rating Scale. A mediation model was used to estimate separately for both treatment arms the direct and indirect treatment effects on sleep disturbance. Results: Compared with placebo (n = 128), treatment with pregabalin (n = 121) significantly reduced scores on the sleep disturbance subscale and Sleep Problems Index II at both week 4 and week 8, and the sleep adequacy subscale at week 8. Venlafaxine XR (n = 125) had no significant effect on these measures. The mediation model indicated that 53% of the total pregabalin effect on sleep disturbance was direct (p < 0.01) and 47% indirect, mediated through anxiety symptoms (p < 0.05). Conclusions: Pregabalin decreased sleep disturbance in patients with GAD both directly, and indirectly by reducing anxiety symptoms. Given the drug specificity of the results, this study provides evidence of an additional important pathway of action for pregabalin and its efficacy in GAD

Cost-effectiveness analysis of using onasemnogene abeparvocec (AVXS-101) in spinal muscular atrophy type 1 patients

Background: Spinal muscular atrophy type 1 (SMA1) is a devastating genetic disease for which gene-replacement therapy may bring substantial survival and quality of life benefits. Objective: This study investigated the cost-effectiveness of onasemnogene abeparvovec (AVXS-101) gene-replacement therapy for SMA1. Study design: A Markov model was used to estimate the incremental cost-effectiveness ratio (ICER), expressed as cost/quality-adjusted life year ($/QALY), of AVXS-101 versus nusinersen over a lifetime. Survival, healthcare costs and QALYs were estimated using natural history data for SMA patients who achieved motor milestones (sitting/walking). Health utility weights were obtained from the CHERISH trial. Setting: USA; commercial payer perspective Participants: SMA1 infants Interventions: AVXS-101 was compared to nusinersen. Main outcome measure: The primary outcome was the ICER. Results: Expected survival (undiscounted) over a lifetime predicted by the model was 37.20 life years for AVXS-101 and 9.68 for nusinersen (discounted QALYs, 15.65 and 5.29, respectively). Using a potential AVXS-101 price range ($2.5-5.0M/treatment), the average lifetime cost/patient was $4.2–6.6M for AVXS-101 and$6.3M for nusinersen. The ICER range was (-$203,072) to$31,379 per QALY gained for AVXS-101 versus nusinersen, indicating that AVXS-101 was cost-effective with prices of ≤$5M. Conclusion: Single-dose AVXS-101 was cost-effective compared to chronic nusinersen for SMA1 patients