The National Psoriasis Foundation psoriasis treatment targets in real-world patients: prevalence and association with patient-reported outcomes in the Corrona Psoriasis Registry.

INTRODUCTION: The National Psoriasis Foundation (NPF) published treat-to-target guidelines for psoriasis, yet their applicability in clinical practice remains unknown. OBJECTIVES: To estimate the proportion of psoriasis patients meeting the NPF's body surface area (BSA) 'target' (≤1%) and 'acceptable' (≤3%) response criteria and the cross-sectional associations of these criteria with patient-reported outcomes (PROs) in the Corrona Psoriasis Registry. METHODS: Separately for three independent cross-sectional cohorts of patients at the (i) enrolment, (ii) 6-month and (iii) 12-month visits, we calculated the proportion of patients with BSA ≤1% and ≤3%. Furthermore, we calculated odds ratios estimating the risk of PROs associated with not meeting criteria in the 6-month cohort. RESULTS: The enrolment, 6- and 12-month cohorts included 2794, 1310 and 629 patients, respectively. At enrolment, 24% of patients had a BSA ≤ 1% and 41% a BSA ≤ 3%. In the 6-month cohort, 43%/64% had a BSA ≤ 1%/BSA ≤ 3%. In the 12-month cohort, 46%/69% of patients had a BSA ≤ 1%/BSA ≤ 3%. Patients not at target/acceptable criteria had higher odds for worse quality of life compared with those who were. CONCLUSION: While most patients at 6- and 12-month visits were at the 'acceptable' response, less than half were at the 'target' response despite systemic therapy. There remain unmet needs to optimize psoriasis therapy and further validate current treat-to-target guidelines.

Effects of collagen microstructure and material properties on the deformation of the neural tissues of the lamina cribrosa.

It is widely considered that intraocular pressure (IOP)-induced deformation within the neural tissue pores of the lamina cribrosa (LC) contributes to neurodegeneration and glaucoma. Our goal was to study how the LC microstructure and mechanical properties determine the mechanical insult to the neural tissues within the pores of the LC. Polarized light microscopy was used to measure the collagen density and orientation in histology sections of three sheep optic nerve heads (ONH) at both mesoscale (4.4µm) and microscale (0.73µm) resolutions. Mesoscale fiber-aware FE models were first used to calculate ONH deformations at an IOP of 30mmHg. The results were then used as boundary conditions for microscale models of LC regions. Models predicted large insult to the LC neural tissues, with 95th percentile 1st principal strains ranging from 7 to 12%. Pores near the scleral boundary suffered significantly higher stretch compared to pores in more central regions (10.0±1.4% vs. 7.2±0.4%; p=0.014; mean±SD). Variations in material properties altered the minimum, median, and maximum levels of neural tissue insult but largely did not alter the patterns of pore-to-pore variation, suggesting these patterns are determined by the underlying structure and geometry of the LC beams and pores. To the best of our knowledge, this is the first computational model that reproduces the highly heterogeneous neural tissue strain fields observed experimentally. STATEMENT OF SIGNIFICANCE: The loss of visual function associated with glaucoma has been attributed to sustained mechanical insult to the neural tissues of the lamina cribrosa due to elevated intraocular pressure. Our study is the first computational model built from specimen-specific tissue microstructure to consider the mechanics of the neural tissues of the lamina separately from the connective tissue. We found that the deformation of the neural tissue was much larger than that predicted by any recent microstructure-aware models of the lamina. These results are consistent with recent experimental data and the highest deformations were found in the region of the lamina where glaucomatous damage first occurs. This study provides new insight into the complex biomechanical environment within the lamina.

What is a typical optic nerve head?

Whereas it is known that elevated intraocular pressure (IOP) increases the risk of glaucoma, it is not known why optic nerve heads (ONHs) vary so much in sensitivity to IOP and how this sensitivity depends on the characteristics of the ONH such as tissue mechanical properties and geometry. It is often assumed that ONHs with uncommon or atypical sensitivity to IOP, high sensitivity in normal tension glaucoma or high robustness in ocular hypertension, also have atypical ONH characteristics. Here we address two specific questions quantitatively: Do atypical ONH characteristics necessarily lead to atypical biomechanical responses to elevated IOP? And, do typical biomechanical responses necessarily come from ONHs with typical characteristics. We generated 100,000 ONH numerical models with randomly selected values for the characteristics, all falling within literature ranges of normal ONHs. The models were solved to predict their biomechanical response to an increase in IOP. We classified ONH characteristics and biomechanical responses into typical or atypical using a percentile-based threshold, and calculated the fraction of ONHs for which the answers to the two questions were true and/or false. We then studied the effects of varying the percentile threshold. We found that when we classified the extreme 5% of individual ONH characteristics or responses as atypical, only 28% of ONHs with an atypical characteristic had an atypical response. Further, almost 29% of typical responses came from ONHs with at least one atypical characteristic. Thus, the answer to both questions is no. This answer held irrespective of the threshold for classifying typical or atypical. Our results challenge the assumption that ONHs with atypical sensitivity to IOP must have atypical characteristics. This finding suggests that the traditional approach of identifying risk factors by comparing characteristics between patient groups (e.g. ocular hypertensive vs. primary open angle glaucoma) may not be a sound strategy.

Public health benefits of reducing air pollution in Shanghai: a proof-of-concept methodology with application to BenMAP.

In recent years, levels of particulate matter (PM) air pollution in China have been relatively high, exceeding China's Class II standards in many cities and impacting public health. This analysis takes Chinese health impact functions and underlying health incidence, applies 2010-2012 modeled and monitored PM air quality data, and estimates avoided cases of mortality and morbidity in Shanghai, assuming achievement of China's Class II air quality standards. In Shanghai, the estimated avoided all cause mortality due to PM10 ranged from 13 to 55 cases per day and from 300 to 800 cases per year. The estimated avoided impact on hospital admissions due to PM10 ranged from 230 cases to 580 cases per day and from 5400 to 7900 per year. The estimated avoided impact on all cause mortality due to PM2.5 ranged from 6 to 26 cases per day and from 39 to 1400 per year. The estimated impact on all cause mortality of a year exposure to an annual or monthly mean PM2.5 concentration ranged from 180 to 3500 per year. In Shanghai, the avoided cases of all cause mortality had an estimated monetary value ranging from 170 million yuan (1 US dollar=4.2 yuan Purchasing Power Parity) to 1200 million yuan. Avoided hospital admissions had an estimated value from 20 to 43 million yuan. Avoided emergency department visits had an estimated value from 5.6 million to 15 million yuan. Avoided outpatient visits had an estimated value from 21 million to 31 million yuan. In this analysis, available data were adequate to estimate avoided health impacts and assign monetary value. Sufficient supporting documentation was available to construct and format data sets for use in the United States Environmental Protection Agency's health and environmental assessment model, known as the Environmental Benefits Mapping and Analysis Program - Community Edition ("BenMAP-CE").

Patient satisfaction with treatments for moderate-to-severe plaque psoriasis in clinical practice.

BACKGROUND: Treatment satisfaction among patients with moderate-to-severe psoriasis has not been studied and compared across treatments using a validated instrument. OBJECTIVES: To assess patient-reported satisfaction with systemic and phototherapy treatments for moderate-to-severe psoriasis in clinical practice and to correlate satisfaction with disease severity and quality-of-life measures. METHODS: This was a cross-sectional study of 1182 patients with moderate-to-severe psoriasis in the Dermatology Clinical Effectiveness Research Network in the U.S.A. Patients receiving either topical therapies only; monotherapy with oral systemic therapies, biologics or narrowband ultraviolet B phototherapy; or combination therapy with biologics and methotrexate completed the Treatment Satisfaction Questionnaire for Medication version II. RESULTS: Median unadjusted overall satisfaction scores were highest for patients receiving biologic monotherapies, biologic-methotrexate combinations, or phototherapy (83.3); scores were lowest for those receiving topical therapies only or acitretin (66.7). In fully adjusted models, compared with patients receiving methotrexate monotherapy, those receiving adalimumab, etanercept, ustekinumab, phototherapy or adalimumab with methotrexate had significantly higher median overall satisfaction scores by 7.2-8.3 points, while those receiving topical therapies only had significantly lower overall satisfaction by 8.9 points. Adjusted convenience scores were lowest for patients receiving topical therapies only or infliximab. Modest but significant correlations were found between the overall satisfaction subscale and both the Psoriasis Area and Severity Index (ρ = -0.36, P < 0.001) and the Dermatology Life Quality Index (ρ = -0.47, P < 0.001). CONCLUSIONS: Discernible differences were found in treatment satisfaction among therapies, particularly regarding treatment effectiveness and convenience. Further application of treatment satisfaction measures may inform treatment decisions and guideline development.

Psoriasis is associated with decreased plasma adiponectin levels independently of cardiometabolic risk factors.

BACKGROUND: Psoriasis is an inflammatory skin disease that may be associated with an adverse cardiometabolic profile including modulated plasma adiponectin and leptin levels. Whether these levels are independent of cardiometabolic risk factors, which are also prevalent in psoriasis, is not known. METHODS: A consecutive sample of 122 participants with varying degrees of psoriasis severity, and a random sample of 134 participants without psoriasis, were recruited for this case-control study. Cardiometabolic risk factors including traditional cardiovascular risk factors, waist circumference, insulin resistance, and total plasma adiponectin and leptin were measured. Total plasma adiponectin and leptin levels were compared in unadjusted and adjusted analyses by psoriasis status. RESULTS: Participants with psoriasis had mostly mild disease and were mainly on topical therapies, but still had a more adverse cardiometabolic profile compared with those without psoriasis. Furthermore, plasma adiponectin levels were significantly lower in participants with psoriasis than those without {7.13 µg/mL [interquartile range (IQR) 4.9-11.3) vs. 14.5 µg/mL (IQR 8.4-24.1); P < 0.001]}. Plasma leptin (ng/mL) levels were higher in the psoriasis group but this did not reach statistical significance [11.3 (IQR 6.4-21.8) vs. 9.8 (IQR 4.9-20.5); P = 0.07]. In multivariable modelling, plasma adiponectin levels were still negatively associated with psoriasis status after adjusting for waist size (% difference = -41.2%, P < 0.001), insulin resistance (% difference = -39.5%, P < 0.001), and both waist size and insulin resistance (% difference = -38.5%, P < 0.001). CONCLUSIONS: Plasma levels of adiponectin were lower in psoriasis, and this relationship persisted after adjusting for cardiometabolic risk factors known to decrease adiponectin levels. These findings suggest that inflammation present in psoriasis may be associated with adipose tissue dysfunction; however, direct studies of adipose tissue are needed to confirm this.

Climate change-related temperature impacts on warm season heat mortality: a proof-of-concept methodology using BenMAP.

Climate change is anticipated to raise overall temperatures and is likely to increase heat-related human health morbidity and mortality risks. The objective of this work was to develop a proof-of-concept approach for estimating excess heat-related premature deaths in the continental United States resulting from potential changes in future temperature using the BenMAP model. In this approach we adapt the methods and tools that the US Environmental Protection Agency uses to assess air pollution health impacts by incorporating temperature modeling and heat mortality health impact functions. This new method demonstrates the ability to apply the existing temperature-health literature to quantify prospective changes in climate-sensitive heat-related mortality. We compared estimates of future temperature with and without climate change and applied heat-mortality health functions to estimate relative changes in heat-related premature mortality. Using the A1B emissions scenario, we applied the GISS-II global circulation model downscaled to 36-km using MM5 and formatted using the Meteorology-Chemistry Interface Processor. For averaged temperatures derived from the 5 years 2048-2052 relative to 1999-2003 we estimated for the warm season May-September a national U.S. estimate of annual incidence of heat-related mortality to be 3700-3800 from all causes, 3500 from cardiovascular disease, and 21 000-27 000 from nonaccidental death, applying various health impact functions. Our estimates of mortality, produced to validate the application of a new methodology, suggest the importance of quantifying heat impacts in economic assessments of climate change.

Potentially modifiable risk factors for adverse pregnancy outcomes in women with psoriasis.

BACKGROUND: Data on pregnancy outcomes among women with psoriasis are lacking. However, there are several known comorbidities of psoriasis, including obesity, smoking and depression, each of which increases the risk for negative birth outcomes. OBJECTIVES: To determine if pregnant women with psoriasis have an excess of potentially modifiable risk factors for adverse pregnancy outcomes. METHODS: Prospectively collected data from the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project were analysed to compare the prevalence of selected risk factors between 170 pregnant women with psoriasis and 158 nondiseased controls. RESULTS: Women with psoriasis were more likely to be overweight/obese prior to pregnancy (P < 0.0001), to smoke (P < 0.0001), or to have a diagnosis of depression (P = 0.03), and were less likely to have been taking preconceptional vitamin supplements (P = 0.004). After controlling for race/ethnicity and socioeconomic status, women with psoriasis were 2.37 (95% confidence interval 1.45-3.87) times more likely to be overweight/obese as women without psoriasis. Duration of disease, age at onset, measures of disease impact during pregnancy, or use of biologics in pregnancy were not significant predictors of overweight/obesity in the subset of psoriatic women. CONCLUSIONS: Pregnant women with psoriasis may be at increased risk for adverse pregnancy outcomes due to comorbidities or other health behaviours associated with the disease. These should be taken into consideration during clinical treatment of women with psoriasis who are in their childbearing years.

The role of time-resolved 3D contrast-enhanced MR angiography in the assessment and grading of cerebral arteriovenous malformations.

PURPOSE: To assess the role of three-dimensional (3D) contrast-enhanced, time-resolved MR angiography (CE TR MRA) in patients with intracranial arteriovenous malformations (AVMs). METHODS: We studied 12 patient with intracranial AVMs on a 3.0T MR imaging system (Magentom TIM Trio, Siemens Medical Solutions, Erlangen, Germany) using 3D CE TR MRA with autocalibrating partially parallel acquisitions and echo sharing schemes, which provided temporal resolution of 0.58 or 1.7s and near isotropic voxels. We qualitatively assessed image quality of the 3D CE TR MRA and compared the grading of the AVMs based on modified Spetzler-Martin system for 3D CE TR MRA and catheter digital subtraction angiography (DSA). RESULTS: CE TR MRA provided good quality images in the 3 standard orthogonal planes, and good arterial-venous separation in all cases. All AVMs were correctly graded by CE TR MRA when compared with DSA. 3D CE TR MRA provides a non-invasive alternative to DSA for the evaluation of cerebral AVMs.

Suicide mortality of young, middle-aged and elderly males and females in Japan for the years 1953-96: time series analysis for the effects of unemployment, female labour force, young and aged population, primary industry and population density.

Effects of nine social life indicators on age-adjusted and age-specific annual suicide mortality of male and female Japanese population in the years 1953-96 were investigated by multiple regression analysis on time series data. Unemployment rate was significantly related to the age-adjusted mortality in both males and females. Also, female labour force participation was positively related to the male mortality; persons and 65 and above was inversely related to the male mortality. Results on the age-specific mortality indicated that: during the 44 yr, (1) unemployment significantly related with the mortality of young, middle-aged and elderly males and young females; (2) female labour force participation significantly related with the mortality of young and elderly males and young females; aged population significantly related with the mortality of middle-aged and elderly males; (4) young population significantly related with the mortality of young and middle-aged males and females; (5) divorce significantly related with the mortality of middle-aged and elderly males and young males and females; (6) persons employed in primary industries significantly related with the mortality in middle-aged males and young males and females; and (7) population density significantly related with the mortality of middle-aged males and young females.

The Cutaneous Lupus Erythematosus Disease Activity and Severity Index: expansion for rheumatology and dermatology.

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). RESULTS: The 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.

Effects of urbanization, economic development, and migration of workers on suicide mortality in Japan.

The relationships between male or female age-adjusted suicide mortality and social life factors for all 47 Japanese prefectures in 1980, 1985 and 1990 were investigated by stepwise multiple regression analysis after classification of 20 social life indicators by factor analysis. During this period, Japan experienced the second economic crisis (the so-called secondary oil crisis) in 1980-1983 and economic prosperity (bubble economy) in 1986-1990. In all the three years, male suicide mortality was significantly related inversely to the urbanization and economic development factor, the result of which was consistent with the data in our previous study for the years 1970 and 1975. Similarly, the male mortality was positively related to the factor of migration of workers in the three years. No factor significantly related to female mortality for all the three years was found. It is suggested that (1) urbanization was a major determinant which prevented male suicide mortality during the past 20 years (1970-1990) in Japan; (2) migration of workers became an important factor for male suicide mortality during these 10 years; and (3) female suicide mortality was less vulnerable to social life factors for these 20 years than the male mortality.

Particulate matter and particle-attached polycyclic aromatic hydrocarbons in the indoor and outdoor air of Tokyo measured with personal monitors.

Using two types of personal monitors for suspended particulate matter of diameter under 10 microm (PM-10) and for particles of diameter under 1 microm with attached polycyclic aromatic hydrocarbons (PPAH), we measured the PM-10 and PPAH concentrations in the indoor and outdoor air in various locations in the Tokyo area. The major findings were as follows. (1) The PPAH concentrations in a clean living room increased rapidly within several minutes after one cigarette was smoked. (2) Using the average indoor concentrations of PM-10 and PPAH in a department store as control concentrations, respectively, where the average indoor PM-10 concentration was closest to an annual average outdoor concentration in Japan, the mean value for indoor air concentrations of PM-10 by location ranged from 2.2 to 6.2 times the control concentration, and the mean value for indoor air concentrations of PPAH by location ranged from 1.0 to 32.2 times the control concentration. (3) Using the same control concentrations, the mean value of outdoor concentrations of PM-10 by location ranged from 1.6 to 8.5 times the control concentration, while the mean value of outdoor concentrations of PPAH by location were up to 353.7 times the control concentration. The major polluted places were main traffic roads, highways, and street tunnels. (4) The correlation coefficient between the PM and the PPAH concentrations in the total monitoring time was 0.014, which was not significant (P>0.05).

Papulosquamous disorders of the elderly.

Several papulosquamous skin conditions occur in the elderly, including inherited and acquired ichthyoses, psoriasis, cutaneous lymphoma, and cutaneous connective tissue diseases. The clinical presentations can be quite helpful in diagnosing these conditions, and confirmatory histology and immunologic testing can often better define the specific entities. Treatment often involves identifying underlying systemic causes, as well as specific approaches based on the diagnosis and severity of clinical presentation.

An ex post cost-benefit analysis of the nitrogen dioxide air pollution control program in Tokyo.

The benefits and costs of past nitrogen dioxide (NO2) control policies were calculated for Tokyo, Japan, using environmental, economic, political, demographic, and medical data from 1973 to 1994. The benefits of NO2 control were estimated as medical expenses and lost work time due to hypothetical no-control air concentrations of NO2. Direct costs were calculated as annualized capital expenditures and 1 year's operating costs for regulated industries plus governmental agency expenses. The major findings were as follows: (1) Using Tokyo's average medical cost of pollution-related illness, the best net estimate of the avoided medical costs due to incidence of phlegm and sputum in adults was 730 billion yen ($6.08 billion; 1 U.S. dollar = 120 yen). (2) The best net estimate of the avoided medical costs due to incidence of lower respiratory illness in children was 93 billion yen ($775 million). (3) Using Tokyo's average duration of pollution-related illness and average wages, the best net estimate of the avoided costs of lost wages in workers was 760 billion yen ($6.33 billion). (4) The best net estimate of the avoided costs of lost wages in mothers caring for their sick children was 100 billion yen ($833 million). (5) Using Tokyo-specific data, the best net costs were estimated as 280 billion yen ($2.33 billion). (6) Using human health and productivity benefits, and annualized capital cost and operating cost estimates, the best net benefits-to-costs ratio was 6:1 (upper limit 44:1; lower limit 0.3:1). Benefit calculations were sensitive to assumptions of mobile source emissions and certain health impacts that were not included. Cost calculations were highly dependent on assumptions of flue gas volume and fuel use. For comparative purposes, we identified other studies for air pollution-related illness. Assumptions that formed the basis for most of the inputs in the present study, such as duration of illness, medical treatment costs, per person illness in children, and lost wages for working mothers, were similar to those recommended in the literature. Lost wages in sick workers and per capita illness incidence in adults were higher than numbers reported elsewhere. Further advances in cost-benefit analysis (CBA) procedures to evaluate the economic effectiveness of NO2 controls in Tokyo are recommended to estimate impacts and values for additional human health benefits, ecosystem health and productivity effects, and nonliving system effects, as well as benefits of ancillary reductions in other pollutants. The present study suggests that Tokyo's past NO2 control policies in total were economically quite effective.

Acquired zinc deficiency in association with anorexia nervosa: case report and review of the literature.

Zinc deficiency, whether a result of an acquired or inherited abnormality of zinc metabolism, is associated with characteristic cutaneous findings. The inherited variety is known as acrodermatitis enteropathica. We present a case of zinc deficiency secondary to starvation induced by anorexia nervosa. Since the cutaneous stigmata of zinc deficiency and anorexia nervosa can initially be subtle and occasionally overlap, we believe that screening zinc levels in patients with anorexia nervosa with prominent cutaneous findings should be considered.

Acute adult T-cell leukemia/lymphoma presenting with florid cutaneous disease.

Adult T-cell leukemia/lymphoma (ATLL) is characterized by cutaneous disease, hypercalcemia, associated HTLV-I infection, and a fulminant course refractory to therapy. A patient with acute ATLL is described, and the natural history of ATLL is reviewed.

Cutaneous and ocular ramifications of ultraviolet radiation.

In this article,the uses of photobiologic techniques such as ultraviolet B radiation and PUVA are discussed, as is a general review of their potential acute and chronic side effects. The authors then focus, in more extensive detail, on the potential acute and chronic ocular toxicity associated with these modalities.