Academia is the life for me, I'm sure.
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Academic Medical Centers↗
Biomedical subjects
Charles N Ellis
Publications and source records attributed to Charles N Ellis.
Clinical e-mail in an academic dermatology setting.
BACKGROUND: Use of e-mail among patients and physicians is limited by reservations over issues such as medicolegal aspects, reimbursement, and time-management. OBJECTIVE: Our purpose was to identify the content of patient-related e-mails in an academic dermatology practice and determine whether clinical questions could be answered by e-mail. METHODS: The first 100 e-mails received each year that related to patients from January 1, 2000 to June 1, 2005 (plus any messages received in e-mail threads started in the original 100) were studied (N = 614). E-mails were sent by patients, potential patients, or physicians in reference to a patient. E-mails were divided into 8 categories on the basis of content. E-mails were subdivided as relating to new (patients who had never been seen in-person) or established patients. All clinical questions were categorized as to whether they were answered by e-mail. The average number of e-mails received per e-mail thread was tallied. RESULTS: E-mails were distributed as follows: clinical question from a physician (20%), clinical question from a patient (17%), appointment request (18%), request for referral to another physician (7%), prescription refill (3%), research inquiry (2%), thank-you correspondence (31%), other (17%). Percentages do not equal 100 because some e-mails contained more than one subject. Clinical questions were more likely to be answered when posed by physicians (100%) than patients (70%; P = .001), and when from established (79%) versus new patients (60%; P = .02). There were fewer e-mails per thread for queries from physicians (1.6 messages received) versus patients (2.2; P < .001) and for established (1.6) versus new patients (2.2; P < .001). LIMITATIONS: This study was limited to the experience of one dermatologist in an academic setting. CONCLUSION: E-mail broadens communication between patients and their dermatologist. E-mail may facilitate consultation with other physicians and management of patients with chronic disease. "Thank-you" responses engage a substantial amount of e-mail resources.
Dermatology↗
Thiazolidinediones: potential as therapeutics for psoriasis and perhaps other hyperproliferative skin disease.
The thiazolidinediones constitute a family of synthetic compounds that act as high-affinity ligands for persoxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor family. Although originally developed to facilitate glucose control in patients with Type 2 diabetes, a number of studies showed that these agents effectively inhibited epithelial cell proliferation and tissue inflammation. Many of the initial cell growth inhibition studies were conducted with malignant epithelial cells from various sites; however, in addition to malignant epithelial cells, other studies showed that rapidly proliferating epidermal keratinoctyes in culture were also sensitive to the growth-inhibiting action of these moieties. Additional studies subsequently demonstrated that some patients with plaque psoriasis responded to treatment with one or another member of the thiazolidinedione family. Due to the potential therapeutic benefit of these compounds in diseases such as psoriasis, studies have been conducted to elucidate mechanisms by which growth inhibition is achieved. Interference with a number of growth-influencing signalling pathways has been demonstrated. Of interest, some of the growth-inhibiting effects are seen under conditions in which PPAR-gamma activation may not be responsible for the activity. Based on therapeutic potential, additional ongoing studies are aimed at developing novel thiazolidinediones that may have better efficacy than the currently available agents. Other studies are aimed at identifying optimal ways to use these agents in the treatment of hyperplastic skin diseases such as psoriasis.
Animals↗
Cost effectiveness of management of mild-to-moderate atopic dermatitis with 1% pimecrolimus cream in children and adolescents 2-17 years of age.
INTRODUCTION: Atopic dermatitis (AD) has the potential to cause a long-term economic impact on patients, their families, and the healthcare system. OBJECTIVE: To determine if 1% pimecrolimus cream is cost-effective in treating mild-to-moderate AD in patients 2-17 years of age. METHODS: Data on the efficacy of AD management with 1% pimecrolimus cream (Elidel, Novartis Pharma GmbH, Wehr, Germany) were obtained from a 12-month, randomized, double-blind, multinational, controlled clinical trial comparing pimecrolimus and conventional therapy. Markov modeling was used for the economic model, based on: (i) Investigator's Global Assessment scores assessed at each visit during the clinical trial; (ii) estimated costs for medication and physician visits for each level of disease severity; and (iii) utility values for each level of disease severity. The perspective was that of a third-party payer. RESULTS: In 2004 US dollars, the incremental cost-effectiveness of 1% pimecrolimus cream was 38,231 US dollars per quality-adjusted life year (QALY) gained compared with conventional therapy. Sensitivity analyses showed a range of 27,299 US dollarsto 63,457 US dollars per QALY gained. CONCLUSION: With an incremental cost-effectiveness ratio of <50,000 US dollars per QALY gained, 1% pimecrolimus cream offers a cost-effective therapeutic option in the management of AD.
Administration, Topical↗
BP-1107 [{2-[4-(2,4-dioxo-thiazolidin-5-ylmethyl)-phenoxy]-ethyl}-methyl-amide]: a novel synthetic thiazolidinedione that inhibits epidermal hyperplasia in psoriatic skin-severe-combined immunodeficient mouse transplants after topical application.
Recent studies have demonstrated that orally administered thiazolidinedione ligands of the peroxisome proliferator-activated receptor-gamma can ameliorate clinical features of psoriasis in humans. Thiazolidinediones also inhibit the proliferation of psoriatic keratinocytes in monolayer and organ culture, and at least one of these agents (troglitazone) inhibits epidermal hyperplasia of human psoriatic skin transplanted to severe-combined immunodeficient (SCID) mice. In the present study, we show that a novel, synthetic, thiazoladinedione derivative, BP-1107 ({2-[4-(2,4-dioxo-thiazolidin-5-ylmethyl)-phenoxy]-ethyl}-methyl-amide), is capable of inhibiting psoriatic hyperplasia in the SCID mouse transplant model after topical application. Like other thiazolidinediones, BP-1107 inhibits proliferation of rapidly growing keratinocytes in monolayer culture, but compared with these agents, the effective dose of BP-1107 needed to suppress keratinocyte proliferation is much lower. Concentrations of BP-1107 that effectively inhibit keratinocyte function have no detrimental effect on dermal fibroblasts. These data suggest that effective topical antipsoriatic therapy may be provided with this agent.
Adamantane↗
Histologic evaluation of melanomas.
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Humans↗
Psychiatric evaluation of the dermatology patient.
Over one third of dermatologic disorders have significant psychiatric comorbidity. The impact of the skin disorder on quality of life, the role of psychosocial stressors, and use of substances should be assessed. Major depressive disorder is the most frequently encountered psychiatric disorder in dermatology and is often associated with suicide risk. Other psychiatric syndromes comorbid with dermatologic disorders include obsessive-compulsive disorder, social phobia, posttraumatic stress disorder associated with dissociation and conversion symptoms, body image pathologies, delusional disorder, and a wide range of personality disorders. This article reviews psychiatric guidelines that may be used to assess psychopathology in the dermatology patient.
Humans↗
Consumers appropriately self-treat based on labeling for over-the-counter hydrocortisone.
BACKGROUND: Over-the-counter (OTC) topical corticosteroids, such as hydrocortisone cream (HC), are commonly used for the treatment of minor dermatological conditions. The safety and efficacy of such products are well documented, but details on patterns of use and self-treatment with HC in the OTC environment remain scarce. OBJECTIVE: We sought to determine compliance with label directions of OTC HCs by examining self-reported patterns of OTC HC use in adults and children. METHODS: A random digit-dialed telephone survey was conducted with 2000 US adults. Following identification of users of OTC HC in the last 6 months, respondents were asked questions about the conditions being treated with OTC HC and the frequency and duration of use in both adults and children. RESULTS: Of adults completing the survey, 20% (n = 396) had used OTC HC. In 83% of cases, the conditions treated were consistent with the OTC label. Use was limited; HC was applied < or =4 times daily in 98% of adult users and lasted < or =7 days in 92%. Patterns of pediatric use were similar and almost always consistent with the labeling. Of households with children, 25% (n = 168) had used OTC HC to treat pediatric dermatological conditions. Of child users, 93% were 2 years of age or older, treatment was limited (97% applied HC < or =4 times daily and 94% of treatments lasted < or =7 days), and the conditions treated were appropriate in 86% of cases. LIMITATIONS: This telephone survey relied on respondents' recall and self-reporting. Our data on pediatric use of OTC HC are skewed toward treatment of younger children. CONCLUSION: The data suggest that OTC HC products are used for self-treatment in a limited and appropriate fashion that is likely to be safe in both adults and children.
Adolescent↗
Psoriasis--recent advances in understanding its pathogenesis and treatment.
Although not completely understood, there is clearly a genetic component in the development of psoriasis. Twin studies show a 67% concordance for monozygotic twins versus 18% for dizygotic twins. This lack of complete concordance in monozygotic twins suggests multifactorial inheritance and interaction between genetic predisposition and the environment. At present, 8 different psoriasis susceptibility loci have been identified in genome-wide linkage scans, including locations on 15 different chromosomes. Genetic connections have been made between psoriasis and other diseases, including atopic dermatitis, rheumatoid arthritis, and Crohn's disease. A variety of approaches are available for the treatment of psoriasis, ranging from topical agents for milder forms of the disease to phototherapy and systemic agents for severe psoriasis. Despite the importance of systemic therapies and recent advances represented by biologic agents, topical treatments will probably remain the mainstay of psoriasis therapy for most patients. The advent of new, cosmetically attractive vehicles may enhance compliance, add to the use of topical agents, and potentially improve patient outcomes.
Anti-Inflammatory Agents↗
Pimecrolimus in dermatology: atopic dermatitis and beyond.
Pimecrolimus is a calcineurin inhibitor developed for the topical therapy of inflammatory skin diseases, particularly atopic dermatitis (AD). Pimecrolimus selectively targets T cells and mast cells. Pimecrolimus inhibits T-cell proliferation, as well as production and release of interleukin-2 (IL-2), IL-4, interferon-gamma and tumour necrosis factor-alpha. Moreover, pimecrolimus inhibits mast cell degranulation. In contrast to tacrolimus, pimecrolimus has no effects on the differentiation, maturation and functions of dendritic cells. In contrast to corticosteroids, pimecrolimus does not affect endothelial cells and fibroblasts and does not induce skin atrophy. Given the low capacity of pimecrolimus to permeate through the skin, it has a very low risk of systemic exposure and subsequent systemic side-effects. In different randomised controlled trials, topical pimecrolimus as cream 1% (Elidel) has been shown to be effective, well tolerated and safe in both adults and children with mild to moderate AD. In addition, pimecrolimus has been successfully used in inflammatory skin diseases other than AD, including seborrheic dermatitis, intertriginous psoriasis, lichen planus and cutaneous lupus erythematosus.
Dermatitis↗
Alpha-Lipoic acid-based PPARgamma agonists for treating inflammatory skin diseases.
Novel thiazolidinedione derivatives of the potent antioxidant, alpha-lipoic (thioctic, 1,2-dithiolane) acid, were prepared. The prototype N-(2-[4-[2,4-dioxo(1,3-thiazolidin-5-yl)methyl]phenoxy]ethyl)-5-(1,2-dithiolan-3-yl)- N-methylpentanamide (designated BP-1003), and dithioester derivatives thereof were shown to be potent activators of peroxisome proliferator-activated receptor gamma (PPARgamma) (EC(50) range 15-101 nM) and modest activators of PPARalpha (EC(50) 5 microM). Both the relatively hydrophobic dithiolane prototype, BP-1003, and its water-soluble dithioglycinate derivative, BP-1017, were shown to inhibit the proliferation of human keratinocytes and suppress the production of interleukin-2 by human peripheral lymphocytes to a greater extent than the antidiabetic thiazolidinedione, rosiglitazone. Both oral and topical administration of BP-1017 showed significant antiinflammatory effects in the oxazolone-sensitized mouse model of allergic contact dermatitis (ACD). These findings suggest that water-soluble lipoic acid-based thiazolidinediones may be efficacious as oral and topical agents for treating inflammatory skin conditions such as contact dermatitis, atopic dermatitis, and psoriasis.
3T3-L1 Cells↗
Evaluating psoriasis with Psoriasis Area and Severity Index, Psoriasis Global Assessment, and Lattice System Physician's Global Assessment.
BACKGROUND: Reliable assessment of severity in psoriasis is essential to document treatment responses in clinical research. The reliability of current clinical outcome measures is uncertain. OBJECTIVE: To quantify the relative variation in commonly used outcome measures (the Psoriasis Area and Severity Index [PASI] and one version of the Psoriasis Global Assessment [PGA]), and a newer measure, the Lattice System Physician's Global Assessment (LS-PGA). METHODS: Physicians who were experienced (53%; 9/17) or inexperienced (47%; 8/17) in using PASI and PGA evaluated 35 patients with psoriasis in random order twice with each rating system. We assessed the variation in scoring psoriasis severity within (intrarater) and among (interrater) physicians. RESULTS: PASI, PGA, and LS-PGA were highly correlated (r > 0.8 for all comparisons) and had high overall reliability (Cronbach's alpha > 0.9 for each). PGA and LS-PGA had lower intrarater variation than PASI. LS-PGA had a 55% higher concordance coefficient between the two evaluations than did PGA. Interrater variation was lower for PGA and LS-PGA than for PASI both before and after correction for measurement error. Experience was beneficial in reducing variation in PASI scores but was not required with PGA or LS-PGA. CONCLUSION: The LS-PGA, which is standardized, does not require experience, and provides discrete word-based scores with intrinsic meaning, is a reliable measure of therapeutic effect in psoriasis, and would allow comparisons across different clinical trials.
Adult↗
Rosiglitazone inhibits proliferation, motility, and matrix metalloproteinase production in keratinocytes.
This study was undertaken to evaluate the effects of thiazolidinediones (TZD) on keratinocyte proliferation, motility, and matrix metalloproteinase (MMP) production. Rosiglitazone (a potent TZD) inhibited both proliferation and motility as well as elaboration of MMP-1 and MMP-9. Inhibition was obtained with keratinocytes in monolayer culture and human skin in organ culture. There were significant concentration-response differences in sensitivity of the three keratinocyte responses to treatment with rosiglitazone. In contrast to keratinocytes, dermal fibroblasts were resistant to the effects of rosiglitazone. Treatment of keratinocytes with rosiglitazone did not suppress epidermal growth factor receptor autophosphorylation, but inhibited signaling through the extracellular regulated kinase mitogen-activated protein kinase pathway without a concomitant effect on pathways that lead to c-jun activation. Pioglitazone, another TZD, also suppressed keratinocyte proliferation, although it was less effective than rosiglitazone. An experimental TZD (BP-1107) inhibited keratinocyte proliferation at a much lower concentration than either rosiglitazone or pioglitazone. Because enhanced keratinocyte motility and increased MMP production as well as increased keratinocyte proliferation are thought to contribute to the phenotype of psoriatic lesional skin, we propose that interference with these keratinocyte responses contributes to the previously reported antipsoriatic activity of TZD.
Adult↗
Repeat courses of intravenous alefacept in patients with chronic plaque psoriasis provide consistent safety and efficacy.
BACKGROUND: Psoriasis is a chronic, relapsing skin disease that may require multiple treatment courses. Alefacept targets the memory T cells implicated in psoriasis pathogenesis. This open-label study evaluated the safety and tolerability, efficacy, and pharmacodynamics of repeat courses of alefacept in men and women with chronic plaque psoriasis. This article reports the interim results of this ongoing study. METHODS: Patients (n = 174) who participated in previous phase II studies of alefacept were included in this retreatment study. Intravenous alefacept (7.5 mg) was administered once weekly for 12 weeks followed by 12 weeks of observation. Initial and subsequent retreatment courses were only given when, in the opinion of the investigators, disease had returned and necessitated treatment; CD4+ T-cell counts had to be at or above the lower limit of normal. RESULTS: Adverse events were similar regardless of the retreatment course. No opportunistic infections, rebound of disease, or flares were reported. Low titers of anti-alefacept antibodies occurred in a few patients without related safety issues. Sixty-six per cent of patients achieved a >/= 50% reduction in the Psoriasis Area and Severity Index (PASI) at any time after the first dose of retreatment course 1. Patients who received two retreatment courses (n = 50) had consistent or improved responses after the second course; 64% and 68% of these patients achieved a >/= 50% PASI improvement at any time after the first dose of retreatment courses 1 and 2, respectively. Alefacept selectively reduced memory T cells without cumulative effects. CONCLUSIONS: Repeat courses of alefacept were well tolerated, and subsequent retreatment courses were at least as effective as the initial course of therapy.
Aged↗
Cost-effectiveness analysis of tacrolimus ointment versus high-potency topical corticosteroids in adults with moderate to severe atopic dermatitis.
BACKGROUND: Few cost-effectiveness analyses have been conducted on topical therapies for atopic dermatitis. OBJECTIVE: We sought to compare cost-effectiveness of high-potency topical corticosteroids (HPTCs) and tacrolimus ointment for the treatment of moderate to severe atopic dermatitis for patients who are not responsive to or not well controlled with mid-potency topical corticosteroids. METHODS: A Markov model represented the cyclic nature of atopic dermatitis. Clinical outcomes were derived from published literature. "Efficacy" was defined as disease-controlled days on which patients experienced a greater than 75% improvement in their disease. Resource use and changes in management were on the basis of opinions of a physician panel; secondary treatment was an oral antibiotic with topical corticosteroids. Sensitivity analyses were conducted for all variables. RESULTS: The model was sensitive to duration of continuous treatment with HPTCs. HPTCs, when limited to 2-week treatment cycles, were associated with the highest total costs ($1682 per year) and the least efficacy (185 disease-controlled days). HPTCs in 4-week treatment intervals and tacrolimus ointment were similar in total costs and efficacy ($1317 vs $1323 for 194 vs 190 disease-controlled days, respectively). Although primary drug costs were higher for patients treated with tacrolimus ointment, patients treated with regimens of HPTCs incurred higher secondary drug costs. CONCLUSION: In the base case analyses, tacrolimus ointment was more cost-effective than HPTCs administered in 2-week treatment cycles, and similar in cost-effectiveness to 4-week cycles of HPTCs.
Administration, Topical↗
Validation of expert opinion in identifying comorbidities associated with atopic dermatitis/eczema.
BACKGROUND: The use of expert opinion is widespread in economic studies of healthcare utilisation; however, few studies have attempted to assess the validity of assumptions derived from such sources. OBJECTIVE: To examine the use of such expert opinion in determining comorbidities associated with atopic dermatitis/eczema (AD/E), which were assessed as part of a recent third-party payer cost-of-illness study. DESIGN: To identify the disease-related comorbidities that would represent costs associated with AD/E, physicians on an expert panel were asked individually and then collectively to group all International Classification of Diseases, 9(th) Edition-Clinical Modification (ICD-9-CM) diagnosis codes as 'most likely', 'possibly' or 'definitely not' related to the costs of identifying and treating patients with AD/E. Claims representing $US464 million in payer reimbursements from nearly 125 000 patients with AD/E were identified within two separate claims databases (1997 values). Over 850 ICD-9-CM diagnosis codes were identified in the first-listed position from these claims. For each group of 'most likely', 'possibly' and 'definitely not' related diagnosis codes, prevalence rates were compared within AD/E and non-AD/E populations from the two historical payer claims databases. Adjusted and non-adjusted odds ratios were calculated by comparing prevalence rates between AD/E and non-AD/E patients in the same payer population. RESULTS: The mean prevalence rate of any diagnosis code in the AD/E population was 0.65 +/- 1.82% (SD) with a mean odds ratio of 1.81 +/- 0.96. Comorbidities considered by the expert panel 'most likely' to be associated with AD/E had higher prevalence rates (3.28 +/- 3.63%) and odds ratios (2.14 +/- 1.14). Comorbidities considered to be 'possibly' related to AD/E had prevalence rates and odds ratios of 3.01 +/- 5.06% and 1.84 +/- 0.82, respectively. Comorbidities considered to be 'definitely not' related to AD/E had the lowest prevalence rates (0.45 +/- 1.09%) and odds ratios (1.80 +/- 0.97). CONCLUSIONS: Comparing the result of consensus panels with actual claims histories validated the use of expert opinion in determining comorbidities associated with AD/E. Expert opinion yielded valid results in terms of identifying comorbidities that manifested frequently and disproportionately in the AD/E population. Limited statistical measurements of comorbidities would have been less specific than expert opinion. Future cost-of-illness studies should consider alternative data sources and methodologies to enhance the validity and importance of expert opinion and to corroborate their findings.
Comorbidity↗
Effects of alefacept on health-related quality of life in patients with psoriasis: results from a randomized, placebo-controlled phase II trial.
INTRODUCTION: Chronic plaque psoriasis has a profound impact on patient quality of life (QOL), including adverse psychosocial effects, impaired daily activities, anxiety, and depression. OBJECTIVE: To assess health-related QOL in a randomized phase II trial of alefacept (human LFA-3/IgG(1) fusion protein), a selective immunomodulator for psoriasis. STUDY DESIGN: Multicenter, randomized, placebo-controlled, double-blind trial. METHODS: 229 patients with moderate to severe psoriasis were randomized to alefacept (0.025, 0.075, or 0.150 mg/kg) or placebo by 30-second intravenous bolus once weekly for 12 weeks and followed for 12 additional weeks. Patients completed a general (SF-36) Health Survey) and dermatology-specific (Dermatology Life Quality Index [DLQI] and Dermatology Quality Of Life Scales [DQOLS]) QOL surveys at each study visit. RESULTS: Patients treated with alefacept had significantly greater improvements on dermatology-specific QOL scales compared with patients receiving placebo (p < 0.05). Patients who achieved a >or=50% or a >or=75% reduction in Psoriasis Area and Severity Index (PASI) reported similar improvement in QOL, which was significantly greater than that of other patients. CONCLUSIONS: The clinical effect of alefacept on psoriasis is associated with an improvement in patients' QOL. Among patients with moderate to severe psoriasis, an improvement in PASI of 50% or more is associated with better QOL scores.
Adult↗
Cost-effectiveness comparison of therapy for psoriasis with a methotrexate-based regimen versus a rotation regimen of modified cyclosporine and methotrexate.
BACKGROUND: Because health care resources are limited, therapeutic regimens should be assessed for their relative costs and effectiveness. OBJECTIVE: We assessed cost-effectiveness for treating psoriasis using two strategies: one consisted principally of methotrexate and the other was principally a rotational schedule of modified cyclosporine (Neoral) with methotrexate. METHODS: We performed a cost-effectiveness analysis using a computerized decision analytic model of simulated patients with moderate to severe psoriasis. Patients were randomly assigned to receive treatment with one of the two strategies. Direct costs included acquisition of medications, laboratory and physician fees, and costs of treating side effects. Because of uncertainty regarding rates of clearing of psoriasis, the relative efficacy of methotrexate and cyclosporine was varied over a wide range in a sensitivity analysis. RESULTS: In the base case over a 10-year treatment period, the methotrexate strategy cost $33,000 and provided approximately 2 years clear of psoriasis compared with $38,000 and approximately 4 years clear of psoriasis for the rotational strategy. When the relative effectiveness of cyclosporine to methotrexate in clearing psoriasis varied from approximately 1 to 20, the rotational strategy cost from $4100 to $2700 per incremental clear year. CONCLUSION: In selecting therapies for psoriasis patients, both costs and effectiveness should be considered. In this simulation, patients could obtain additional periods clear of psoriasis at an incremental cost by using cyclosporine in rotation with methotrexate. If even a small utility gain accompanies the complete clearing of psoriasis, such a strategy may be a worthwhile investment of resources comparable to other healthcare interventions.
Cost-Benefit Analysis↗