Advancing donor management research: design and implementation of a large, randomized, placebo-controlled trial

BACKGROUND:Given the persistent shortage of organs for transplantation, new donor management strategies to improve both organ utilization and quality of procured organs are needed. Current management protocols for the care of the deceased donor before organ procurement are based on physiological rationale, experiential reasoning, and retrospective studies without rigorous testing. Although many factors contribute to the lack of controlled clinical trials in donor management, a major factor is the unique challenges posed by research in the brain-dead organ donor.METHODS AND RESULTS:This article describes the study design and the challenges faced during implementation of the Beta-agonists for Oxygenation in Lung Donors (BOLD) study, a randomized, placebo-controlled clinical trial of nebulized albuterol vs. placebo in 500 organ donors. The study design and implementation are described with emphasis on aspects of the study that are unique to research in brain-dead organ donors.CONCLUSIONS:Experience gained during the design and implementation of the BOLD study should be useful for investigators planning future clinical trials in the brain-dead donor population and for intensivists who are involved in the care of the brain-dead organ donor.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

The use of the SF-36 questionnaire in adult survivors of childhood cancer: evaluation of data quality, score reliability, and scaling assumptions

BACKGROUND: The SF-36 has been used in a number of previous studies that have investigated the health status of childhood cancer survivors, but it never has been evaluated regarding data quality, scaling assumptions, and reliability in this population. As health status among childhood cancer survivors is being increasingly investigated, it is important that the measurement instruments are reliable, validated and appropriate for use in this population. The aim of this paper was to determine whether the SF-36 questionnaire is a valid and reliable instrument in assessing self-perceived health status of adult survivors of childhood cancer. METHODS: We examined the SF-36 to see how it performed with respect to (1) data completeness, (2) distribution of the scale scores, (3) item-internal consistency, (4) item-discriminant validity, (5) internal consistency, and (6) scaling assumptions. For this investigation we used SF-36 data from a population-based study of 10,189 adult survivors of childhood cancer. RESULTS: Overall, missing values ranged per item from 0.5 to 2.9 percent. Ceiling effects were found to be highest in the role limitation-physical (76.7%) and role limitation-emotional (76.5%) scales. All correlations between items and their hypothesised scales exceeded the suggested standard of 0.40 for satisfactory item-consistency. Across all scales, the Cronbach's alpha coefficient of reliability was found to be higher than the suggested value of 0.70. Consistent across all cancer groups, the physical health related scale scores correlated strongly with the Physical Component Summary (PCS) scale scores and weakly with the Mental Component Summary (MCS) scale scores. Also, the mental health and role limitation-emotional scales correlated strongly with the MCS scale score and weakly with the PCS scale score. Moderate to strong correlations with both summary scores were found for the general health perception, energy/vitality, and social functioning scales. CONCLUSION: The findings presented in this paper provide support for the validity and reliability of the SF-36 when used in long-term survivors of childhood cancer. These findings should encourage other researchers and health care practitioners to use the SF-36 when assessing health status in this population, although it should be recognised that ceiling effects can occur

Development of physical and mental health summary scores from the patient-reported outcomes measurement information system (PROMIS) global items

The use of global health items permits an efficient way of gathering general perceptions of health. These items provide useful summary information about health and are predictive of health care utilization and subsequent mortality. Analyses of 10 self-reported global health items obtained from an internet survey as part of the Patient-Reported Outcome Measurement Information System (PROMIS) project. We derived summary scores from the global health items. We estimated the associations of the summary scores with the EQ-5D index score and the PROMIS physical function, pain, fatigue, emotional distress, and social health domain scores. Exploratory and confirmatory factor analyses supported a two-factor model. Global physical health (GPH; 4 items on overall physical health, physical function, pain, and fatigue) and global mental health (GMH; 4 items on quality of life, mental health, satisfaction with social activities, and emotional problems) scales were created. The scales had internal consistency reliability coefficients of 0.81 and 0.86, respectively. GPH correlated more strongly with the EQ-5D than did GMH (r = 0.76 vs. 0.59). GPH correlated most strongly with pain impact (r = −0.75) whereas GMH correlated most strongly with depressive symptoms (r = −0.71). Two dimensions representing physical and mental health underlie the global health items in PROMIS. These global health scales can be used to efficiently summarize physical and mental health in patient-reported outcome studies

Measuring the effect of intimate partner violence on health-related quality of life: a qualitative focus group study

Abstract Background Health related quality of life (HRQOL) can be measured by a wide range of instruments, many of which have been designed for specific conditions or uses. Preference-based measures assess the value individuals place on health, and are included in economic evaluations of treatments and interventions (such as cost effectiveness analysis). As economic evaluation becomes more common, it is important to assess the applicability of preference-based health related quality of life (HRQOL) measures to public health issues. This study investigated the usefulness of such instruments in the context of intimate partner violence (IPV), a public health concern that that can seriously affect quality of life. Methods The study consisted of focus groups with abused women to determine the aspects of life affected by IPV, and an analysis of existing HRQOL measures. Eight focus groups (n = 40) were conducted in which participants discussed the domains of health affected by IPV. Results were content analyzed and compared with the domains of health included in four commonly-used, preference-based HRQOL measures. Results The average focus group participant was 43 years old, unemployed, African American, with 3 children. Domains of health reported to be affected by IPV included physical functioning, emotional and psychological functioning, social functioning and children\u27s functioning. Psychological health was the most severely affected domain. The Short Form 36, the Health Utilities Index, the EuroQol 5D, and the Quality of Well-being Scale were found to vary in the degree to which they include domains of health important in IPV. Psychological health is included to a limited extent, and the spill-over effect of a condition on other family members, including children, is not included at all. Conclusion Emotional and psychological health plays an important role in the overall HRQOL of abused women but is relatively underemphasized in preference-based HRQOL measures. This may lead to an underestimation of the impact of partner violence on HRQOL when using these measures and in economic evaluations that rely thereon. Holistic measurement approaches or expanded measures that capture the far-reaching effects of IPV on HRQOL may be needed to accurately measure the effect of this condition on women\u27s health

Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome

Post-mastectomy pain syndrome (PMPS) is a recognised complication of breast surgery although little is known about the long-term outcome of this chronic pain condition. In 1996, Smith et al identified a prevalence rate of PMPS of 43% among 408 women in the Grampian Region, Northeast Scotland. The aim of this study was to assess long-term outcome at 7–12 years postoperatively in this cohort of women, to describe the natural history of PMPS and impact of pain upon quality of life. Chronic pain and quality of life were assessed using the McGill Pain Questionnaire (MPQ) and Short Form-36 (SF-36). Of 175 women reporting PMPS in 1996, 138 were eligible for questionnaire follow-up in 2002. Mean time since surgery was 9 years (s.d. 1.8 years). A response rate of 82% (113 out of 138) was achieved; 59 out of 113 (52%) women reported continued PMPS and 54 out of 113 (48%) women reported their PMPS had resolved since the previous survey in 1996. Quality of life scores were significantly lower in women with persistent PMPS compared to those women whose pain had resolved. However, for women with persistent PMPS, SF-36 scores had improved over time. Risk factors for persistent PMPS included younger age and heavier weight. This study found that, of women reporting PMPS in 1996, half of those surveyed in 2002 continued to experience PMPS at a mean of 9 years after surgery

Estimates of success in patients with sciatica due to lumbar disc herniation depend upon outcome measure

The objectives were to estimate the cut-off points for success on different sciatica outcome measures and to determine the success rate after an episode of sciatica by using these cut-offs. A 12-month multicenter observational study was conducted on 466 patients with sciatica and lumbar disc herniation. The cut-off values were estimated by ROC curve analyses using Completely recovered or Much better on a 7-point global change scale as external criterion for success. The cut-off values (references in brackets) at 12 months were leg pain VAS 17.5 (0–100), back pain VAS 22.5 (0–100), Sciatica Bothersomeness Index 6.5 (0–24), Maine-Seattle Back Questionnaire 4.5 (0–12), and the SF-36 subscales bodily pain 51.5, and physical functioning 81.7 (0–100, higher values indicate better health). In conclusion, the success rates at 12 months varied from 49 to 58% depending on the measure used. The proposed cut-offs may facilitate the comparison of success rates across studies

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Background: Randomised controlled trials (RCTs) are perceived as the gold-standard method for evaluating healthcare interventions, and increasingly include quality of life (QoL) measures. The observed results are susceptible to bias if a substantial proportion of outcome data are missing. The review aimed to determine whether imputation was used to deal with missing QoL outcomes. Methods: A random selection of 285 RCTs published during 2005/6 in the British Medical Journal, Lancet, New England Journal of Medicine and Journal of American Medical Association were identified. Results: QoL outcomes were reported in 61 (21%) trials. Six (10%) reported having no missing data, 20 (33%) reported ≤ 10% missing, eleven (18%) 11%–20% missing, and eleven (18%) reported >20% missing. Missingness was unclear in 13 (21%). Missing data were imputed in 19 (31%) of the 61 trials. Imputation was part of the primary analysis in 13 trials, but a sensitivity analysis in six. Last value carried forward was used in 12 trials and multiple imputation in two. Following imputation, the most common analysis method was analysis of covariance (10 trials). Conclusion: The majority of studies did not impute missing data and carried out a complete-case analysis. For those studies that did impute missing data, researchers tended to prefer simpler methods of imputation, despite more sophisticated methods being available.The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. Shona Fielding is also currently funded by the Chief Scientist Office on a Research Training Fellowship (CZF/1/31)

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Peer reviewedPublisher PD

Effectiveness of percutaneous laser disc decompression versus conventional open discectomy in the treatment of lumbar disc herniation; design of a prospective randomized controlled trial

Background. The usual surgical treatment of refractory sciatica caused by lumbar disc herniation, is open discectomy. Minimally invasive procedures, including percutaneous therapies under local anesthesia, are increasingly gaining attention. One of these treatments is Percutaneous Laser Disc Decompression (PLDD). This treatment can be carried out in an outpatient setting and swift recovery and return to daily routine are suggested. Thus far, no randomized trial into cost-effectiveness of PLDD versus standard surgical procedure has been performed. We present the design of a randomized controlled trial, studying the cost-effectiveness of PLDD versus conventional open discectomy in patients with sciatica from lumbar disc herniation. Methods/design. The study is a randomized prospective multi-center trial, in which two treatment strategies are compared in a parallel group design. Patients (age 18-70 years) visiting the neurosurgery department of the participating hospitals, are considered for inclusion in the trial when sciatica due to lumbar disc herniation has lasted more than 8 weeks. Patients with disc herniation smaller than 1/3 of the spinal canal diameter, without concomitant lateral recess stenosis or sequestration, are eligible for participation, and are randomized into one of two treatment arms; either Percutaneous Laser Disc Decompression or conventional discectomy. The functional outcome of the patient, as assessed by the Roland Disability Questionnaire for Sciatica at 8 weeks and 1 year after treatment, is the primary outcome measure. The secondary outcome parameters are recovery as perceived by the patient, leg and back pain, incidence of re-intervention, complications, quality of life, medical consumption, absence of work and secondary costs. Discussion. Open discectomy is still considered to be the golden standard in the surgical treatment of lumbar disc herniation. Whether Percutaneous Laser Disc Decompression has at least as much efficacy as the standard surgical procedure, and is more cost-effective, will be determined by this trial. Trial registration. Current Controlled Trials ISRCTN25884790