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ABSTRACT: Psoriasis is a common inflammatory skin disease and is associated with systemic comorbidities such as
metabolic syndrome, diabetes mellitus, and cardiovascular (CV) disease. Recent evidence suggests that
psoriasis, especially if severe, is an independent risk factor for major adverse cardiac events (MACE)
such as myocardial infarction, stroke and CV related death. However, traditional risk stratification tools
such as the Framingham Risk Score (FRS) may underestimate long term MACE risk in this population.
Thus, the ideal approach for risk stratification and lipid treatment in psoriasis is unknown. In a recent
EULAR consensus statement, it was recommended that traditional risk estimates for patients with
rheumatoid and psoriatic arthritis be multiplied by 1.5 given the risk of CV disease. We sought to
quantify the effect of psoriasis on ten-year FRS and demonstrate how this impacts CV risk
reclassification in a clinical practice. We enrolled consecutive patients in a Preventive Cardiology
practice dedicated to psoriasis. We calculated the attributable risk (AR) of psoriasis on MACE to be
6.5% from the General Practice Research Database, a validated, population-based study. CV risk was
estimated using ten-year FRS based on total cholesterol before and after considering psoriasis AR, and
risk categories were based on lipid guidelines. A total of 103 patients (45±17 years, 60% male, 48%
hypertension, 36% tobacco use, 10% diabetes) were enrolled. Despite having a higher than expected
prevalence of established risk factors, our patients were at low risk (o10%) for 10-year CV events (male
mean FRS 8.3±9.25, female 5.8±5.81) given their young age. After adding the 6.5% from psoriasis
AR (male FRS 14.77 ± 9.25, female 12.26 ± 5.81), 50.5% of the entire sample was reclassified to a
higher-risk category. A total of 48% of males (n¼31) and 49% of females (n¼19) moved from low to
intermediate risk, and 3% (n¼2) of males moved from intermediate to high risk. Overall, this would
have resulted in a change of treatments and goals in half of the clinic patients per CV guidelines. FRS
may underestimate CV risk in this young sample of psoriasis patients. When considering the AR of
psoriasis on MACE, a significant portion of patients were reclassified into a higher risk category thereby
changing treatment goals. Larger population-based studies are needed to confirm these findings.
Journal of Investigative Dermatology 06/2011; 131(6-131):1389-1390. · 6.31 Impact Factor
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ABSTRACT: Psoriasis is a common disease frequently studied in large databases. To date the validity of psoriasis information has not been established in The Health Improvement Network (THIN).
To investigate the validity of THIN for identifying patients with psoriasis and to determine if the database can be used to determine the natural history of the disease.
First, we conducted a cross-sectional study to determine if psoriasis prevalence in THIN is similar to expected. Second, we created a cohort of 4900 patients, aged 45-64 years, with a psoriasis diagnostic Read Code and surveyed their general practitioners (GPs) to confirm the diagnosis clinically. Third, we created models to determine if psoriasis descriptors (extent, severity, duration and dermatologist confirmation) could be accurately captured from database records.
Psoriasis prevalence was 1·9%, and showed the characteristic age distribution expected. GP questionnaires were received for 4634 of 4900 cohort patients (95% response rate), and psoriasis diagnoses were confirmed in 90% of patients. Duration of disease in the database showed substantial agreement with physician query (κ = 0·69). GPs confirmed that the psoriasis diagnosis was corroborated by a dermatologist in 91% of patients whose database records contained a dermatology referral code associated with a psoriasis code. We achieved good discrimination between patients with and without extensive disease based on the number of psoriasis codes received per year (area under curve = 0·8).
THIN is a valid data resource for studying psoriasis and can be used to identify characteristics of the disease such as duration and confirmation by a dermatologist.
British Journal of Dermatology 11/2010; 164(3):602-9. · 3.67 Impact Factor
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ABSTRACT: Severe psoriasis is associated with excess mortality and increased risk of cardiovascular death. Population-based data evaluating cause-specific mortality in patients with psoriasis are limited.
To describe cause-specific mortality in patients with severe psoriasis.
We performed a cohort study from 1987 to 2002 of patients ≥18 years using the General Practice Research Database. We compared patients with a psoriasis code and a history of systemic therapy consistent with severe psoriasis (n=3603) with patients with no history of psoriasis (n=14,330). Age- and sex-adjusted Cox models were created for each of the leading causes of death defined by the Centers for Disease Control.
Patients with severe psoriasis were at increased risk of death from cardiovascular disease [hazard ratio (HR) 1·57, 95% confidence interval (CI) 1·26-1·96], malignancies (HR 1·41, 95% CI 1·07-1·86), chronic lower respiratory disease (HR 2·08, 95% CI 1·24-3·48), diabetes (HR 2·86, 95% CI 1·08-7·59), dementia (HR 3·64, 95% CI 1·36-9·72), infection (HR 1·65, 95% CI 1·26-2·18), kidney disease (HR 4·37, 95% CI 2·24-8·53) and unknown/missing causes (HR 1·43, 95% CI 1·09-1·89). The absolute and excess risk of death was highest for cardiovascular disease (61·9 and 3·5 deaths per 1000 patient-years, respectively).
Severe psoriasis is associated with an increased risk of death from a variety of causes, with cardiovascular death being the most common aetiology. These patients were also at increased risk of death from causes not previously reported, such as infection, kidney disease and dementia. Additional studies are necessary to determine the degree to which excess causes of death are due to psoriasis, its treatments, associated behaviours, or other factors.
British Journal of Dermatology 09/2010; 163(3):586-92. · 3.67 Impact Factor
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ABSTRACT: Background The development of a simple, reliable, valid and responsive method for measuring the extent of skin involvement in psoriasis is important for use in epidemiological studies.Objectives We sought to investigate the psychometric characteristics of the Patient Report of Extent of Psoriasis Involvement (PREPI), a single-question method for measuring body surface area affected by psoriasis.Methods This was a cross-sectional study of 140 patients with psoriasis, with an exploratory prospective longitudinal cohort component. Reliability was measured via a test-retest approach and criterion validity was investigated by comparing the PREPI with an assessment of body surface area of involvement by a dermatologist. We additionally compared Skindex-29 scores with the PREPI. To demonstrate responsiveness and establish a minimally important difference in the PREPI, we created receiver operating characteristic curves for the PREPI instrument.Results The test-retest reliability of the PREPI was nearly perfect [intraclass correlation coefficient (ICC) = 0·99, 95% confidence interval (CI) 0·97–0·99], and there was substantial agreement between patient and physician assessments (ICC = 0·82, 95% CI 0·75–0·87). The PREPI showed significant correlations with all Skindex-29 domains. We found the PREPI to be responsive to change and identified changes in the PREPI score that have good discrimination between patients with and without a minimally important clinical difference.Conclusions Our study suggests that the PREPI is a reliable, valid and responsive measure of body surface area affected by psoriasis that may be useful for future epidemiological research.
British Journal of Dermatology 03/2010; 162(4):835 - 842. · 3.67 Impact Factor
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ABSTRACT: Lymphedema is one of many arm problems reported by breast cancer survivors. Understanding the impact of lymphedema on quality of life requires consideration that arm symptoms may occur with or without lymphedema. It was hypothesized that specific arm symptoms and pain, related or unrelated to lymphedema, would be more associated with quality of life outcomes than arm swelling. The relation of arm swelling and of arm symptoms and associated severity with a range of quality of life outcomes following breast cancer treatment was assessed in a diverse sample of 295 women, 141 of whom had a clinical diagnosis of lymphedema. Arm swelling (as defined by interlimb volume or circumference differences) and lymphedema severity (defined by Common Toxicity Criteria) were less correlated with quality of life than total number of arm symptoms and specific individual symptoms. Pain in the affected arm correlated with poor quality of life outcomes, regardless of arm swelling. When evaluating the impact of lymphedema on quality of life, arm swelling may not be as important as the total number and specific types of arm symptoms present, as these may be more informative about quality of life outcomes in survivors of breast cancer with and without lymphedema.
Lymphology 03/2010; 43(1):1-13. · 1.02 Impact Factor
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ABSTRACT: Limited empirical data are available on the effects of genetic counseling and testing among African American women.
To evaluate the effects of genetic counseling and testing in African American women based on different levels of exposure: (a) women who were randomized to culturally tailored (CTGC) and standard genetic counseling (SGC) to women who declined randomization (non-randomized group), (b) participants and non-participants in genetic counseling, and (c) BRCA1 and BRCA2 (BRCA1/2) test result acceptors and decliners.
Randomized trial of genetic counseling conducted from February 2003 to November 2006.
We evaluated changes in perceived risk of developing breast cancer and cancer worry.
Women randomized to CTGC and SGC did not differ in terms of changes in risk perception and cancer worry compared to decliners. However, counseling participants had a significantly greater likelihood of reporting reductions in perceived risk compared to non-participants (p = 0.03). Test result acceptors also had a significantly greater likelihood of reporting decreases in cancer worry (p = 0.03). However, having a cancer history (p = 0.03) and a BRCA1/2 prior probability (p = 0.04) were associated with increases in cancer worry.
Although CTGC did not lead to significant improvements in perceived risk or psychological functioning, African American women may benefit from genetic counseling and testing. Continued efforts should be made to increase access to genetic counseling and testing among African American women at increased risk for hereditary disease. But, follow-up support may be needed for women who have a personal history of cancer and those with a greater prior probability of having a BRCA1/2 mutation.
Public Health Genomics 03/2010; 13(7-8):440-8. · 2.33 Impact Factor
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ABSTRACT: The development of a simple, reliable, valid and responsive method for measuring the extent of skin involvement in psoriasis is important for use in epidemiological studies.
We sought to investigate the psychometric characteristics of the Patient Report of Extent of Psoriasis Involvement (PREPI), a single-question method for measuring body surface area affected by psoriasis.
This was a cross-sectional study of 140 patients with psoriasis, with an exploratory prospective longitudinal cohort component. Reliability was measured via a test-retest approach and criterion validity was investigated by comparing the PREPI with an assessment of body surface area of involvement by a dermatologist. We additionally compared Skindex-29 scores with the PREPI. To demonstrate responsiveness and establish a minimally important difference in the PREPI, we created receiver operating characteristic curves for the PREPI instrument.
The test-retest reliability of the PREPI was nearly perfect [intraclass correlation coefficient (ICC) = 0.99, 95% confidence interval (CI) 0.97-0.99], and there was substantial agreement between patient and physician assessments (ICC = 0.82, 95% CI 0.75-0.87). The PREPI showed significant correlations with all Skindex-29 domains. We found the PREPI to be responsive to change and identified changes in the PREPI score that have good discrimination between patients with and without a minimally important clinical difference.
Our study suggests that the PREPI is a reliable, valid and responsive measure of body surface area affected by psoriasis that may be useful for future epidemiological research.
British Journal of Dermatology 11/2009; 162(4):835-42. · 3.67 Impact Factor
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ABSTRACT: Validated outcome measures in dermatology help standardize and improve patient care. A scoring system of skin disease severity in dermatomyositis known as the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) has been developed.
To simplify and improve the tool for clinical research and care, we modified the CDASI and validated the new version, v2.
The original CDASI has four activity and two damage measures. The modified CDASI has three activity and two damage measures. The skin disease of 20 patients with dermatomyositis was evaluated by the same dermatologist using both the original and the modified CDASI. Global validation measures were implemented to assess overall skin disease state, skin disease activity and skin damage. Spearman's rho (r(sp)), adjusted for multiple observations on subjects, was used to determine the relationship between the two versions of the CDASI and their correlation with the physician global measures (PGMs).
The total score and activity and damage subscores of the original and the modified CDASI correlated perfectly with each other (r(sp) = 0.99, 1.00, 1.00). The PGM-overall skin scale correlated with the total scores (r(sp) = 0.72, r(sp) = 0.76) and activity subscores (r(sp) = 0.68, r(sp) = 0.63) but not with the damage subscores (r(sp) = 0.14, r(sp) = 0.15) of the original and the modified CDASI, respectively. However, the PGM-activity and PGM-damage scales correlated with the activity (r(sp) = 0.76, r(sp) = 0.75) and damage subscores (r(sp) = 0.90, r(sp) = 0.90), respectively, of the original and the modified CDASI.
The modified CDASI is perfectly correlated with the original CDASI. It has equally good concurrent validity with the PGM-overall skin and PGM-activity scales. The CDASI subscores have equally good concurrent validity with the PGM-activity and PGM-damage scales. We suggest that PGMs of skin disease activity and damage should be assessed separately for greater specificity. The modified CDASI is a refined and equally as useful outcome measure.
British Journal of Dermatology 10/2009; 162(3):669-73. · 3.67 Impact Factor
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R.Q. Klein,
C.A. Bangert,
M. Costner,
M.K. Connolly,
A. Tanikawa,
J. Okawa,
M. Rose,
S.S. Fakharzadeh,
D. Fiorentino,
L.A. Lee,
R.D. Sontheimer,
L. Taylor, A.B. Troxel,
V.P. Werth
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ABSTRACT: Background Reliable and validated measures of skin disease severity are needed for cutaneous dermatomyositis (DM). Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), Dermatomyositis Skin Severity Index (DSSI) and Cutaneous Assessment Tool (CAT) skin indices have been developed as outcome instruments.Objectives We sought to demonstrate reliability and validity of the CDASI, and to compare the CDASI with other potential tools for use in measuring disease severity in cutaneous dermatomyositis.Patients and methods CDASI has four activity and two damage measures, with scores from 0 to 148. DSSI assesses activity based on body surface area and severity on a scale of 0–72. CAT uses 21 activity and damage items, for a range of 0–175 for activity and 0–33 for damage. Ten dermatologists used the instruments to score the same 12–16 patients in one session. Global validation measures were administered to physicians and patients.Results Global validation measures correlated with the three outcome instruments (P < 0·0001). CAT displayed lower inter- and intrarater reliability relative to the CDASI. All scales correlate better with physician than patient global skin measures.Conclusions It appears that the CDASI may be a useful outcome measure for studies of cutaneous DM. Further testing to compare responsiveness of all three measures is necessary.
British Journal of Dermatology 07/2008; 159(4):887 - 894. · 3.67 Impact Factor
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R Q Klein,
C A Bangert,
M Costner,
M K Connolly,
A Tanikawa,
J Okawa,
M Rose,
S S Fakharzadeh,
D Fiorentino,
L A Lee,
R D Sontheimer,
L Taylor, A B Troxel,
V P Werth
[show abstract]
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ABSTRACT: Reliable and validated measures of skin disease severity are needed for cutaneous dermatomyositis (DM). Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), Dermatomyositis Skin Severity Index (DSSI) and Cutaneous Assessment Tool (CAT) skin indices have been developed as outcome instruments.
We sought to demonstrate reliability and validity of the CDASI, and to compare the CDASI with other potential tools for use in measuring disease severity in cutaneous dermatomyositis.
CDASI has four activity and two damage measures, with scores from 0 to 148. DSSI assesses activity based on body surface area and severity on a scale of 0-72. CAT uses 21 activity and damage items, for a range of 0-175 for activity and 0-33 for damage. Ten dermatologists used the instruments to score the same 12-16 patients in one session. Global validation measures were administered to physicians and patients.
Global validation measures correlated with the three outcome instruments (P < 0.0001). CAT displayed lower inter- and intrarater reliability relative to the CDASI. All scales correlate better with physician than patient global skin measures.
It appears that the CDASI may be a useful outcome measure for studies of cutaneous DM. Further testing to compare responsiveness of all three measures is necessary.
British Journal of Dermatology 06/2008; 159(4):887-94. · 3.67 Impact Factor
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M. S. Krathen,
J. Dunham,
E. Gaines,
J. Junkins-Hopkins,
E. Kim,
S. L. Kolasinski,
C. Kovarik,
J. Kwan-Morley,
J. Okawa,
K. Propert,
N. Rogers,
M. Rose,
P. Thomas, A. B. Troxel,
A. Van Voorhees,
J. Von Feldt,
A. L. Weber,
V. P. Werth
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ABSTRACT: Objective
To evaluate the validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) for use by rheumatologists via reliability testing, and to extend the validation for dermatologists.Methods
Fourteen subjects with cutaneous lupus erythematosus (CLE; n = 10), a mimicker skin disease only (a cutaneous lesion that may appear clinically similar to CLE; n = 1), or both (n = 3) were rated with the CLASI by academic-based dermatologists (n = 5) and rheumatologists (n = 5).ResultsThe dermatology intraclass correlation coefficient (ICC) was 0.92 for activity and 0.82 for damage; for rheumatology the ICC was 0.83 for activity and 0.86 for damage. For intrarater reliability, the dermatology Spearman's rho was 0.94 for activity and 0.97 for damage; for rheumatology the Spearman's rho was 0.91 for activity and 0.99 for damage.Conclusion
Our data confirm the reliability of the CLASI when used by dermatologists and support the CLASI as a reliable instrument for use by rheumatologists.
Arthritis & Rheumatism 02/2008; 59(3):338 - 344. · 7.87 Impact Factor
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ABSTRACT: Combined hormone replacement therapy (CHRT) containing estrogens and progestins is associated with breast cancer risk. The authors evaluated interactions between CHRT use and progestin metabolism genotypes at CYP3A4 and the progesterone receptor (PGR) and their effects on breast cancer risk using the population-based Women's Insights and Shared Experiences (WISE) Study (1999-2002) of postmenopausal Caucasian women (522 breast cancer cases, 708 controls). The authors observed an elevated risk of ductal tumors in women with 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.35, 95% confidence interval (CI): 1.13, 9.99; two-sided p(interaction) = 0.035). They also observed an elevated risk of progesterone receptor-positive tumors in women who had had 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.82, 95% CI: 1.26, 11.55; p = 0.028). Finally, they observed an increased risk of estrogen receptor-negative tumors in women without CHRT exposure and CYP3A4*1B alleles compared with those who had neither factor (odds ratio = 6.46, 95% CI: 2.02, 20.66; p = 0.024), although the biologic interpretation of this result requires further study. When stratified by recency of use, PGR effects were observed only in current CHRT users, while CYP3A4 effects were observed only in former CHRT users. Breast cancer risk in women who have used CHRT may be influenced by genetic factors involved in progestin metabolism.
American journal of epidemiology 01/2008; 166(12):1392-9. · 5.59 Impact Factor
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ABSTRACT: Optimization of oxygen tolerance extension by intermittent exposure was studied in groups of 20 rats exposed to systematically varied patterns of alternating oxygen and normoxic breathing periods at 4.0, 2.0, and 1.5 ATA. Oxygen periods of 20, 60, and 120 min were alternated with normoxic intervals that provided oxygen-to-normoxia ratios of 4:1, 2:1, 1:1, and 1:3. In general, median survival times had nearly linear relationships to increasing normoxic intervals with oxygen period held constant. Exceptions occurred at 4.0 and 2.0 ATA where a 5-min normoxic interval was too short for adequate recovery even with a 20-min oxygen period, and an oxygen period of 120 min was too long even with a normoxic interval of 30 min. These exceptions did not occur at 1.5 ATA. Survival time for many intermittent exposure patterns was equivalent to that for continuous exposure to an oxygen pressure definable as a time-weighted average of the alternating oxygen and normoxia periods. However, this predictive method underestimated the degree of protection achieved by several of the intermittent exposure patterns, especially those performed at 4.0 ATA. Results provided guidance for selection of intermittent exposure patterns for direct evaluation in humans breathing oxygen at 2.0 ATA. Definition of intermittent exposure patterns and conditions that produced prominent gains in oxygen tolerance can also facilitate the performance of future experiments designed to study potential mechanisms for oxygen tolerance extension by intermittent exposure. Heat shock and oxidation-specific stress proteins that are induced by exposure to oxidant injury are suggested for emphasis in such investigations.
Journal of Applied Physiology 04/2006; 100(3):869-79. · 3.75 Impact Factor
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ABSTRACT: OBJECTIVE: To determine the incidence of depression, anxiety, and suicidality in patients with psoriasis compared with the general population. DESIGN: A population-based cohort study using data collected as part of patient's electronic medical record from 1987 to 2002. SETTING: General Practice Research Database. PATIENTS: Analyses included 146 042 patients with mild psoriasis, 3956 patients with severe psoriasis, and 766 950 patients without psoriasis. Five controls without psoriasis were selected from the same practices and similar cohort entry dates as patients with psoriasis. MAIN OUTCOME MEASURE: Clinical diagnoses of depression, anxiety, and suicidality among patients. RESULTS: The adjusted hazard ratios (HRs) for receiving a diagnosis of depression, anxiety, and suicidality in patients with psoriasis compared with controls were 1.39 (95% confidence interval [CI], 1.37-1.41), 1.31 (95% CI, 1.29-1.34), and 1.44 (95% CI, 1.32-1.57), respectively. The adjusted HR of depression was higher in severe (HR, 1.72; 95% CI, 1.57-1.88) compared with mild psoriasis (HR, 1.38; 95% CI, 1.35-1.40). Younger patients with psoriasis had elevated HRs of outcomes compared with older patients with psoriasis. CONCLUSIONS: Patients with psoriasis have an increased risk of depression, anxiety, and suicidality. We estimate that in the United Kingdom, in excess of 10 400 diagnoses of depression, 7100 diagnoses of anxiety, and 350 diagnoses of suicidality are attributable to psoriasis annually. It is important for clinicians to evaluate patients with psoriasis for these conditions to improve outcomes. Future investigation should determine the mechanisms by which psoriasis is associated with psychiatric outcomes as well as approaches for prevention.
Arch Dermatol. 146(8):891-5.
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ABSTRACT: Objective: To determine the incidence of depression, anxiety, and suicidality in patients with psoriasis compared with the general population.
Design: A population-based cohort study using data collected as part of patient's electronic medical record from 1987 to 2002.
Setting: General Practice Research Database.
Patients: Analyses included 146 042 patients with mild psoriasis, 3956 patients with severe psoriasis, and 766 950 patients without psoriasis. Five controls without psoriasis were selected from the same practices and similar cohort entry dates as patients with psoriasis.
Main Outcome Measure: Clinical diagnoses of depression, anxiety, and suicidality among patients.
Results: The adjusted hazard ratios (HRs) for receiving a diagnosis of depression, anxiety, and suicidality in patients with psoriasis compared with controls were 1.39 (95% confidence interval [CI], 1.37-1.41), 1.31 (95% CI, 1.29-1.34), and 1.44 (95% CI, 1.32-1.57), respectively. The adjusted HR of depression was higher in severe (HR, 1.72; 95% CI, 1.57-1.88) compared with mild psoriasis (HR, 1.38; 95% CI, 1.35-1.40). Younger patients with psoriasis had elevated HRs of outcomes compared with older patients with psoriasis.
Conclusions: Patients with psoriasis have an increased risk of depression, anxiety, and suicidality. We estimate that in the United Kingdom, in excess of 10 400 diagnoses of depression, 7100 diagnoses of anxiety, and 350 diagnoses of suicidality are attributable to psoriasis annually. It is important for clinicians to evaluate patients with psoriasis for these conditions to improve outcomes. Future investigation should determine the mechanisms by which psoriasis is associated with psychiatric outcomes as well as approaches for prevention.
Arch Dermatol. 146(8):891-895.
