Stephen R. Rapp

Psoriasis causes as much disability as other major medical diseases

BACKGROUND Little is known about how the health-related quality of life (HRQL) associated with psoriasis compares with that of other patient populations. OBJECTIVE We describe HRQL associated with psoriasis and compare it with HRQL of patients with other major chronic health conditions. A second aim is to identify which specific aspects of psoriasis contribute most to HRQL. METHODS A total of 317 patients completed a non-disease-specific measure of HRQL. Responses were compared with those of patients with 10 other chronic health conditions. HRQL was regressed on ratings of 18 aspects of psoriasis. RESULTS Patients with psoriasis reported reduction in physical functioning and mental functioning comparable to that seen in cancer, arthritis, hypertension, heart disease, diabetes, and depression. Six aspects of psoriasis predicted physical functioning, and 5 different disease aspects predicted mental functioning. CONCLUSION The impact of psoriasis on HRQL is similar to that of other major medical diseases. Different aspects of psoriasis are related to the different dimensions of HRQL supporting the need for multidimensional treatment models.

Effects of Conjugated Equine Estrogen on Stroke in the Women’s Health Initiative

Background— The Women’s Health Initiative (WHI) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women. The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke. This report provides a thorough analysis of the stroke finding using the final results from the completed trial database. Methods and Results— The WHI Estrogen Alone hormone trial is a multicenter, double-blind, placebo-controlled, randomized clinical trial in 10 739 women aged 50 to 79 years who were given daily conjugated equine estrogen (CEE; 0.625 mg; n=5310) or placebo (n=5429). During an average follow-up of 7.1 years, there were 168 strokes in the CEE group and 127 in the placebo group; 80.3% of strokes were ischemic. For all stroke the intention-to-treat hazard ratio [HR] (95% CI) for CEE versus placebo was 1.37 (1.09 to 1.73). The HR (95% CI) was 1.55 (1.19 to 2.01) for ischemic stroke and 0.64 (0.35, 1.18) for hemorrhagic stroke. The HRs indicate excess risk of ischemic stroke was apparent in all categories of baseline stroke risk, including younger and more recently menopausal women and in women with prior or current use of statins or aspirin. Conclusions— CEE increases the risk of ischemic stroke in generally healthy postmenopausal women. The excess risk appeared to be present in all subgroups of women examined, including younger and more recently menopausal women. There was no convincing evidence to suggest that CEE had an effect on the risk of hemorrhagic stroke.

Phase II Study of Donepezil in Irradiated Brain Tumor Patients: Effect on Cognitive Function, Mood, and Quality of Life

PURPOSE A prospective, open-label phase II study was conducted to determine whether donepezil, a US Food and Drug Administration-approved reversible acetylcholinesterase inhibitor used to treat mild to moderate Alzheimers type dementia, improved cognitive functioning, mood, and quality of life (QOL) in irradiated brain tumor patients. PATIENTS AND METHODS Thirty-four patients received donepezil 5 mg/d for 6 weeks, then 10 mg/d for 18 weeks, followed by a washout period of 6 weeks off drug. Outcomes were assessed at baseline, 12, 24 (end of treatment), and 30 weeks (end of wash-out). All tests were administered by a trained research nurse. RESULTS Of 35 patients who initiated the study, 24 patients (mean age, 45 years) remained on study for 24 weeks and completed all outcome assessments. All 24 patients had a primary brain tumor, mostly low-grade glioma. Scores significantly improved between baseline (pretreatment) and week 24 on measures of attention/concentration, verbal memory, and figural memory and a trend for verbal fluency (all P < .05). Confused mood also improved from baseline to 24 weeks (P = .004), with a trend for fatigue and anger (all P < .05). Health-related QOL improved significantly from baseline to 24 weeks, particularly, for brain specific concerns with a trend for improvement in emotional and social functioning (all P < .05). CONCLUSION Cognitive functioning, mood, and health-related QOL were significantly improved following a 24-week course of the acetylcholinesterase inhibitor donepezil. Toxicities were minimal. We are planning a double blinded, placebo-controlled, phase III trial of donepezil to confirm these favorable results.

The Women’s Health Initiative Memory Study (WHIMS): A Trial of the Effect of Estrogen Therapy in Preventing and Slowing the Progression of Dementia

Evidence from animal, human cross-sectional, case-control, and prospective studies indicate that hormone replacement therapy (HRT) is a promising treatment to delay the onset of symptoms of dementia. The Womens Health Initiative Memory Study (WHIMS) is the first double-masked, randomized, placebo-controlled, long-term clinical trial designed to test the hypothesis that HRT reduces the incidence of all-cause dementia in women aged 65 and older. WHIMS, an ancillary study to the Womens Health Initiative (WHI) funded by the National Institutes of Health, will recruit a subgroup of women aged 65 and older from among those enrolling in the HRT trial of the WHI. The WHI clinical centers and 10 affiliated satellites plan to enroll approximately 8300 women into WHIMS over a 2-year period. Participants will be followed annually for 6 years, receiving cognitive assessments via the Modified Mini-Mental State (3MS) Examination. Women who screen positively for cognitive impairment on the basis of an educational and age-adjusted 3MS cutpoint proceed to more extensive neuropsychological testing and neurologic evaluation. Each woman suspected to have dementia then undergoes a series of laboratory tests that confirm the clinical diagnosis and classify the type of dementia. WHIMS is designed to provide more than 80% statistical power to detect a 40% reduction in the rate of all-cause dementia, an effect that could have profound public health implications for older womens health and functioning.

Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial.

CONTEXT The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning. OBJECTIVE To determine whether G. biloba slows the rates of global or domain-specific cognitive decline in older adults. DESIGN, SETTING, AND PARTICIPANTS The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years. INTERVENTION Twice-daily dose of 120-mg extract of G. biloba (n = 1545) or identical-appearing placebo (n = 1524). MAIN OUTCOME MEASURES Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests. RESULTS Annual rates of decline in z scores did not differ between G. biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P = .71; for ADAS-Cog, P = .97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P > .05). CONCLUSION Compared with placebo, the use of G. biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00010803.

Measuring Adherence to Behavioral and Medical Interventions

Measuring adherence to medical and behavioral interventions is important to clinicians and researchers since inadequate adherence can reduce the effectiveness of an intervention. Unfortunately, there is no gold standard for measuring adherence across health behaviors. Adherence needs to be defined situationally with parameters of acceptable adherence carefully delineated and appropriate to the health behavior being studied. Additionally, measurement methods must be valid, reliable, and sensitive to change; this paper reviews these criteria. Methods used to measure adherence to dietary interventions include 24-hour recalls, food diaries, and food frequency questionnaires. Direct and indirect calorimetry, doubly labeled water, and a variety of self-report methods can be used to measure adherence in physical activity interventions. Adherence to pharmacological interventions is assessed using self-report methods, biochemical measures, medication counts, and the automated pharmacy database review strategy. The strengths and weaknesses of these methods for measuring adherence to dietary, physical activity, and pharmacological interventions are reviewed. Control Clin Trials 2000;21:188S-194S

The economic impact of psoriasis increases with psoriasis severity

BACKGROUND Psoriasis treatments are known to be costly, but little is known about the financial impact of psoriasis and the way in which it relates to the severity of the disease. OBJECTIVE This study was performed to obtain an estimate of the treatment costs faced by patients with psoriasis. METHODS A total of 578 anonymous mail surveys were distributed to patients with psoriasis; 318 surveys were returned (55%). Psoriasis severity was assessed with the previously validated Self-Administered Psoriasis Area Severity Index (SAPASI). RESULTS The total and out-of-pocket expenses to care for psoriasis were correlated with psoriasis severity (r = 0.26, p = 0.0001). There were no sex (p = 0.9) or racial (p = 0.4) differences in total expenditures. Severity was correlated with how bothersome to the patient was the cost of treatment (r = 0.30, p = 0.0001), the time required for treatment (r = 0.38, p = 0.0001), and the time lost from work (r = 0.23, p = 0.0001). Lower quality of life at work and in money matters also correlated with severity of psoriasis. Higher family income was associated with less time spent caring for psoriasis and less interference with work around the home. CONCLUSION As expected, the expenses caring for psoriasis are greater for patients with more severe disease. These costs and other financial implications are associated with lower quality of life for patients with more severe psoriasis.

The Physical, Psychological and Social Impact of Psoriasis

Psoriasis is a chronic, disabling skin disease affecting up to 2 percent of the population. Little is known about how physical, psychological and social features of the illness interact to create a negative impact. In this article, a biopsychosocial model of the impact of psoriasis is described, and results from a survey of 317 psoriasis patients are presented. The types of functional disability, psychological distress and disease-related stressors are described for highly strained patients (i.e. those with disease-related suicidal ideation) and compared with less strained patients (i.e. those without suicidal ideation). As predicted by the model, significantly more disability, psychological distress and disease-related stressors are found among highly strained patients. Logistical regression analysis revealed that strain is more strongly associated with disability, distress and disease-related stress level than with disease severity. Implications for research and clinical interventions are discussed.

Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults: The LIFE Randomized Trial

IMPORTANCE Epidemiological evidence suggests that physical activity benefits cognition, but results from randomized trials are limited and mixed. OBJECTIVE To determine whether a 24-month physical activity program results in better cognitive function, lower risk of mild cognitive impairment (MCI) or dementia, or both, compared with a health education program. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial, the Lifestyle Interventions and Independence for Elders (LIFE) study, enrolled 1635 community-living participants at 8 US centers from February 2010 until December 2011. Participants were sedentary adults aged 70 to 89 years who were at risk for mobility disability but able to walk 400 m. INTERVENTIONS A structured, moderate-intensity physical activity program (n = 818) that included walking, resistance training, and flexibility exercises or a health education program (n = 817) of educational workshops and upper-extremity stretching. MAIN OUTCOMES AND MEASURES Prespecified secondary outcomes of the LIFE study included cognitive function measured by the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale (score range: 0-133; higher scores indicate better function) and the revised Hopkins Verbal Learning Test (HVLT-R; 12-item word list recall task) assessed in 1476 participants (90.3%). Tertiary outcomes included global and executive cognitive function and incident MCI or dementia at 24 months. RESULTS At 24 months, DSC task and HVLT-R scores (adjusted for clinic site, sex, and baseline values) were not different between groups. The mean DSC task scores were 46.26 points for the physical activity group vs 46.28 for the health education group (mean difference, -0.01 points [95% CI, -0.80 to 0.77 points], P = .97). The mean HVLT-R delayed recall scores were 7.22 for the physical activity group vs 7.25 for the health education group (mean difference, -0.03 words [95% CI, -0.29 to 0.24 words], P = .84). No differences for any other cognitive or composite measures were observed. Participants in the physical activity group who were 80 years or older (n = 307) and those with poorer baseline physical performance (n = 328) had better changes in executive function composite scores compared with the health education group (P = .01 for interaction for both comparisons). Incident MCI or dementia occurred in 98 participants (13.2%) in the physical activity group and 91 participants (12.1%) in the health education group (odds ratio, 1.08 [95% CI, 0.80 to 1.46]). CONCLUSIONS AND RELEVANCE Among sedentary older adults, a 24-month moderate-intensity physical activity program compared with a health education program did not result in improvements in global or domain-specific cognitive function. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01072500.

Do optimism and pessimism predict physical functioning

Dispositional optimism has been shown to be related to self-report measures of health and well-being, yet little research has examined the relationship between optimism and more objective measures of functioning. The purpose of this study was to examine the relationship between optimism and pessimism and objective physical functioning. Four hundred eighty community-dwelling older adults with knee pain completed a measure of optimism and pessimism and were observed performing four daily activities (walking, lifting an object, climbing stairs, and getting into and out of a car). Results indicated that pessimism was significantly related to performance on all four tasks (p < .001), while optimism was related to performance only on the walking task (p < .05), after controlling for demographic and health variables.