Showing papers by "David J. Margolis published in 2018"

Epidemiology of atopic dermatitis in adults: Results from an international survey.

Abstract: Background There are gaps in our knowledge of the prevalence of adult atopic dermatitis (AD). Objective To estimate the prevalence of AD in adults and by disease severity. Methods This international, cross-sectional, web-based survey was performed in the United States, Canada, France, Germany, Italy, Spain, United Kingdom, and Japan. Adult members of online respondent panels were sent a questionnaire for AD identification and severity assessment; demographic quotas ensured population representativeness for each country. A diagnosis of AD required subjects to be positive on the modified UK Working Party/ISAAC criteria and self-report of ever having an AD diagnosis by a physician. The proportion of subjects with AD who reported being treated for their condition was determined and also used to estimate prevalence. Severity scales were Patient-Oriented SCORAD, Patient-Orientated Eczema Measure, and Patient Global Assessment. Results Among participants by region, the point prevalence of adult AD in the overall/treated populations was 4.9%/3.9% in the US, 3.5%/2.6% in Canada, 4.4%/3.5% in the EU, and 2.1%/1.5% in Japan. The prevalence was generally lower for males vs females, and decreased with age. Regional variability was observed within countries. Severity varied by scale and region; however, regardless of the scale or region, proportion of subjects reporting severe disease was lower than mild or moderate disease. Conclusions Prevalence of adult AD ranged from 2.1% to 4.9% across countries. Severe AD represented a small proportion of the overall AD population regardless of measure or region.

Patient burden and quality of life in atopic dermatitis in US adults: A population-based cross-sectional study

Abstract: Background The patient burden and quality of life (QOL) impact of atopic dermatitis (AD) in the United States population is not well established. Objective To elucidate the patient burden of AD in the US population. Methods A cross-sectional, population-based study of 602 adults was performed. Atopic dermatitis was determined using modified UK Diagnostic Criteria for AD. Its severity was assessed using self-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Scoring AD (PO-SCORAD), PO-SCORAD-itch, and sleep. Quality of life was assessed using short-form (SF-)12 mental and physical health scores and Dermatology Life Quality Index (DLQI). Results Adults with AD reported higher proportions of having only fair/poor overall health (25.8% vs. 15.8%), being somewhat/very dissatisfied with life (16.7% vs 11.4%), lower weighted mean (standard deviation [SD]) SF-12 mental (45.9 [9.9] vs 50.9 [9.2]) and physical health subscores (53.0 [2.5] vs 53.5 [2.3]) and higher DLQI (4.9 [6.5] vs 1.1 [2.8]). In multivariable regression models adjusting for sociodemographics and multiple comorbid health disorders, significant stepwise decreases by AD severity (self-reported, POEM, PO-SCORAD) of overall health, life satisfaction, SF-12 mental health, and increases of DLQI scores were seen. The SF-12 physical health scores were only associated with moderate AD. Concurrently, severe PO-SCORAD, POEM, or PO-SCORAD-itch was associated with very low mean SF-12 mental health (34.7) and high DLQI scores (24.7). Atopic dermatitis commonly limited lifestyle (51.3%), led to avoidance of social interaction (39.1%), and impacted activities (43.3%). The most burdensome AD symptoms were itch (54.4%), excessive dryness/scaling (19.6%), and red/inflamed skin (7.2%). Conclusion These data support the heavy burden that AD places on patients, particularly those with moderate and severe AD.

Guidelines of care for the management of cutaneous squamous cell carcinoma

Abstract: Cutaneous squamous cell carcinoma (cSCC) is the second most common form of human cancer and has an increasing annual incidence. Although most cSCC is cured with office-based therapy, advanced cSCC poses a significant risk for morbidity, impact on quality of life, and death. This document provides evidence-based recommendations for the management of patients with cSCC. Topics addressed include biopsy techniques and histopathologic assessment, tumor staging, surgical and nonsurgical management, follow-up and prevention of recurrence, and management of advanced disease. The primary focus of these recommendations is on evaluation and management of primary cSCC and localized disease, but where relevant, applicability to recurrent cSCC is noted, as is general information on the management of patients with metastatic disease.

The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: Posttreatment Controllers Identified From 14 Clinical Studies

Abstract: Author(s): Namazi, Golnaz; Fajnzylber, Jesse M; Aga, Evgenia; Bosch, Ronald J; Acosta, Edward P; Sharaf, Radwa; Hartogensis, Wendy; Jacobson, Jeffrey M; Connick, Elizabeth; Volberding, Paul; Skiest, Daniel; Margolis, David; Sneller, Michael C; Little, Susan J; Gianella, Sara; Smith, Davey M; Kuritzkes, Daniel R; Gulick, Roy M; Mellors, John W; Mehraj, Vikram; Gandhi, Rajesh T; Mitsuyasu, Ronald; Schooley, Robert T; Henry, Keith; Tebas, Pablo; Deeks, Steven G; Chun, Tae-Wook; Collier, Ann C; Routy, Jean-Pierre; Hecht, Frederick M; Walker, Bruce D; Li, Jonathan Z | Abstract: BackgroundHIV posttreatment controllers are rare individuals who start antiretroviral therapy (ART), but maintain HIV suppression after treatment interruption. The frequency of posttreatment control and posttreatment interruption viral dynamics have not been well characterized.MethodsPosttreatment controllers were identified from 14 studies and defined as individuals who underwent treatment interruption with viral loads ≤400 copies/mL at two-thirds or more of time points for ≥24 weeks. Viral load and CD4+ cell dynamics were compared between posttreatment controllers and noncontrollers.ResultsOf the 67 posttreatment controllers identified, 38 initiated ART during early HIV infection. Posttreatment controllers were more frequently identified in those treated during early versus chronic infection (13% vs 4%, P l .001). In posttreatment controllers with weekly viral load monitoring, 45% had a peak posttreatment interruption viral load of ≥1000 copies/mL and 33% had a peak viral load ≥10000 copies/mL. Of posttreatment controllers, 55% maintained HIV control for 2 years, with approximately 20% maintaining control for ≥5 years.ConclusionsPosttreatment control was more commonly identified amongst early treated individuals, frequently characterized by early transient viral rebound and heterogeneous durability of HIV remission. These results may provide mechanistic insights and have implications for the design of trials aimed at achieving HIV remission.

Association of atopic dermatitis with allergic, autoimmune, and cardiovascular comorbidities in US adults.

Abstract: Background Atopic dermatitis (AD) has been associated with multiple comorbid extracutaneous and systemic disorders. The relation between AD severity and disease comorbidities is complex and not fully understood. Objective To determine the complex relation between AD severity and comorbidities. Methods A cross-sectional US population-based study of 8,217 adults who were participants in a nationally representative internet health panel was performed using a structured questionnaire. A diagnosis of AD was determined using modified United Kingdom Working Party Criteria for AD (n = 602). AD severity was assessed using Patient-Oriented Scoring AD, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, and self-reported global AD severity. Logistic regression and structural equation models were used to explore associations of AD with self-reported allergic, cardiometabolic, anxiety and depression, and autoimmune disease. Results In multivariable regression models controlling for sociodemographics, AD was associated with higher odds of asthma (adjusted odds ratio [OR] 2.09, 95% confidence interval [CI] 1.71–2.55), hay fever (OR 4.31, 95% CI 3.27–5.69), food allergy (OR 2.07, 95% CI 1.54–2.77), anxiety and depression (OR 2.34, 95% CI 1.91–2.87), autoimmune disease (OR 3.05, 95% CI 2.31–4.03), obesity (OR 1.37, 95% CI 1.13–1.67), diabetes (OR 1.52, 95% CI 1.16–1.99), high blood pressure (OR 1.46, 95% CI 1.18–1.80), and heart disease (OR 1.94, 95% CI 1.40–2.70) compared with controls (P Conclusion There is a strong relation of AD severity to allergic, autoimmune, and cardiovascular comorbidities.

Association of Inadequately Controlled Disease and Disease Severity With Patient-Reported Disease Burden in Adults With Atopic Dermatitis

Abstract: Importance Real-world data are limited on the patient-reported burden of adult atopic dermatitis (AD). Objective To characterize the patient-reported burden of AD with regard to impact of disease severity and inadequate control in adults from clinical settings. Design, Setting, and Participants In this cross-sectional study using data from 6 academic medical centers in the United States collected by a self-administered internet-based questionnaire, 1519 adult patients with AD were stratified by AD severity as mild or moderate/severe using the Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD). Patients with moderate/severe disease using systemic immunomodulators/phototherapy were further stratified as having adequate or inadequate disease control. Strata were compared for all outcomes. Main Outcomes and Measures Outcomes included validated measures and stand-alone questions assessing itch (pruritus numerical rating scale; PO-SCORAD itch visual analog scale), pain (numerical rating scale), sleep (PO-SCORAD sleep visual analog scale; sleep interference with function), anxiety and depression (Hospital Anxiety and Depression Scale), and health-related quality of life (Dermatology Life Quality Index). Results Among the 1519 adult patients with AD, relative to mild AD (n = 689, 64% women; mean [SD] age, 46.5 [18.0] years), patients with moderate/severe AD (n = 830, 66.8% women; mean [SD] age, 45.1 [16.9] years) reported more severe itching and pain, greater adverse effects on sleep, higher prevalence of anxiety and depression (417 [50.2%] vs 188 [27.3%]), and greater health-related quality-of-life impairment. The 103 patients with moderate/severe AD with inadequate disease control despite treatment with systemic immunomodulators or phototherapy (55.7%) reported higher burdens of itch and sleeping symptoms vs patients with controlled disease including more days per week with itchy skin (5.7 vs 2.7) and higher proportions with itch duration greater than half a day (190 [22.8%] vs 20 [2.9%]). Sleep symptoms included trouble sleeping (3.9 vs 1.1 on the PO-SCORAD VAS), longer sleep latency (38.8 vs 21.6 minutes), more frequent sleep disturbances (2.6 vs 0.4 nights in past week), and greater need for over-the-counter sleep medications (324 [39%] vs 145 [21%]). Conclusions and Relevance Inadequate disease control was common among patients with moderate/severe AD, and was associated with a higher patient-reported burden than patients with controlled disease. Regardless of disease control, the burden of moderate/severe AD was higher than mild AD, suggesting a need for more effective therapies for moderate/severe disease.

Content and construct validity, predictors, and distribution of self-reported atopic dermatitis severity in US adults.

Abstract: Background Atopic dermatitis (AD) is associated with skin lesions, multiple symptoms, and effect of quality of life, all of which factor into disease severity. Self-reported global AD severity may be a valid severity assessment for epidemiologic research. Objective To validate self-reported global AD severity in a representative cohort of adults with AD. Methods Preliminary probing-cognitive interviews were performed (n = 8). Next, a cross-sectional US population-based survey study of adults with AD was performed. AD was diagnosed using an adap/tation of the UK Working Party criteria (n = 602). AD severity was assessed using self-reported global AD severity (mild, moderate, severe), Patient-Oriented Scoring AD (PO-SCORAD), Patient-Oriented Eczema Measure (POEM), Numeric Rating Scale (NRS)–itch, NRS-sleep, NRS-pain, and Hospital Anxiety and Depression Scale (HADS). Results Self-reported global AD severity had good content validity. Self-reported global AD severity had strong correlations with PO-SCORAD (Spearman correlation ρ = 0.61) and objective PO-SCORAD (ρ = 0.61); moderate correlations with POEM (ρ = 0.54), NRS-itch (ρ = 0.44), NRS-pain (ρ = 0.46), and HADS (ρ = 0.41); and weak correlation with NRS-sleep (ρ = .32) (P Conclusion Self-reported AD severity simultaneously assesses multiple AD constructs and appears to be sufficiently valid for assessing AD severity in clinical and epidemiologic studies.

Systematic review of atopic dermatitis disease definition in studies using routinely collected health data.

Abstract: Author(s): Dizon, MP; Yu, AM; Singh, RK; Wan, J; Chren, M-M; Flohr, C; Silverberg, JI; Margolis, DJ; Langan, SM; Abuabara, K | Abstract: BackgroundRoutinely collected electronic health data obtained for administrative and clinical purposes are increasingly used to study atopic dermatitis (AD). Methods for identifying AD patients in routinely collected electronic health data differ, and it is unknown how this might affect study results.ObjectivesTo evaluate how patients with AD have been identified in studies using routinely collected electronic health data, to determine whether these methods were validated and to estimate how the method for identifying patients with AD affected variability in prevalence estimates.MethodsWe systematically searched PubMed, Embase and Web of Science for studies using routinely collected electronic health data that reported on AD as a primary outcome. Studies of localized AD and other types of dermatitis were excluded. The protocol for this review was registered in PROSPERO (CRD42016037968).ResultsIn total, 59 studies met eligibility criteria. Medical diagnosis codes for inclusion and exclusion, number of occasions of a code, type of provider associated with a code and prescription data were used to identify patients with AD. Only two studies described validation of their methods and no study reported on disease severity. Prevalence estimates ranged from 0·18% to 38·33% (median 4·91%) and up to threefold variation in prevalence was introduced by differences in the method for identifying patients with AD.ConclusionsThis systematic review highlights the need for clear reporting of methods for identifying patients with AD in routinely collected electronic health data to allow for meaningful interpretation and comparison of results.

Severity strata for POEM, PO-SCORAD, and DLQI in US adults with atopic dermatitis

Abstract: Background Patient-Oriented Eczema Measure (POEM) is the preferred patient-reported outcome (PRO) for assessing symptoms of atopic dermatitis (AD). Dermatology Life Quality Index (DLQI) is commonly used to assess the burden of skin disease. Previous severity strata were developed for POEM and DLQI in clinical cohorts, which may be biased toward more severe disease. Severity strata were not previously examined in population-based cohorts. Patient-Oriented Scoring AD (PO-SCORAD) is another commonly used PRO for assessing AD symptoms; however, severity strata are not established. Objective We sought to confirm previously developed strata for POEM and DLQI, and to develop strata for the PO-SCORAD in a population-based cohort of adults with AD. Methods A cross-sectional, population-based study of 8,217 adults was performed using a structured questionnaire. A diagnosis of AD was determined using modified UK Diagnostic Criteria for AD (n = 602). AD severity was assessed using self-reported global AD severity (anchoring question), POEM, PO-SCORAD, and DLQI. Strata were selected using an anchoring approach based on patient-reported disease severity. Results We confirmed the existing strata for DLQI (mild = 0-5, moderate = 6-10, severe = 11-30) (kappa = 0.446). However, the preferred strata for POEM was mild = 0-7, moderate = 8-19, and severe = 20-28 (kappa = 0.409) and PO-SCORAD was mild = 1-27, moderate = 28-56, severe = 57-104 (kappa = 0.444). Conclusion Existing strata for DLQI performed well in a population-based cohort of adult AD. The optimal severity strata for the POEM in our AD population varies slightly from those previously published for AD. This may suggest that different strata may be optimal in different study settings and cohorts. Finally, we proposed new strata for PO-SCORAD in adult AD.

Frequency of Treatment Switching for Spironolactone Compared to Oral Tetracycline-Class Antibiotics for Women With Acne: A Retrospective Cohort Study 2010-2016.

Abstract: Background Long-term oral antibiotic use in acne may be associated with a variety of adverse effects including antibiotic resistance, pharyngitis, inflammatory bowel disease, and breast and colon cancer. Spironolactone may represent an effective and safe alternative to oral antibiotics for women with moderate to severe acne, however comparative studies are lacking. Methods Using the OptumInsight™ Clinformatics™ DataMart, we conducted a retrospective analysis of the frequency of switching to a different systemic agent within the first year of therapy among women with acne who were started on either spironolactone or an oral tetracycline-class antibiotic between 2010-2016, after controlling for age, topical retinoid, and oral contraceptive use. Results Among women with acne who were started on spironolactone, 14.4% were prescribed a different systemic agent within one year, compared with 13.4% started on an oral tetracycline-class antibiotic. After adjusting for age, topical retinoid, and oral contraceptive use, the odds ratio for being prescribed a different systemic agent within one year was 1.07 (95% CI 0.99-1.16) for those prescribed spironolactone when compared with oral tetracycline-class antibiotics and the risk difference was 0.007 (95% CI -0.002-0.017). Conclusions Based on the observation of similar switching between the two groups, spironolactone may have similar clinical effectiveness to that of oral tetracycline-class antibiotics. While ultimately large clinical trials are needed to determine the optimal management strategy for women with moderate to severe acne, these results provide additional support that spironolactone represents an effective treatment for women with acne. J Drugs Dermatol. 2018;17(6):632-638.

Decoding cortical brain states from widefield calcium imaging data using visibility graph

Abstract: Widefield optical imaging of neuronal populations over large portions of the cerebral cortex in awake behaving animals provides a unique opportunity for investigating the relationship between brain function and behavior. In this paper, we demonstrate that the temporal characteristics of calcium dynamics obtained through widefield imaging can be utilized to infer the corresponding behavior. Cortical activity in transgenic calcium reporter mice (n=6) expressing GCaMP6f in neocortical pyramidal neurons is recorded during active whisking (AW) and no whisking (NW). To extract features related to the temporal characteristics of calcium recordings, a method based on visibility graph (VG) is introduced. An extensive study considering different choices of features and classifiers is conducted to find the best model capable of predicting AW and NW from calcium recordings. Our experimental results show that temporal characteristics of calcium recordings identified by the proposed method carry discriminatory information that are powerful enough for decoding behavior.

A risk adjustment approach to estimating the burden of skin disease in the United States

Abstract: Direct insurance claims tabulation and risk adjustment statistical methods can be used to estimate health care costs associated with various diseases. In this third manuscript derived from the new national Burden of Skin Disease Report from the American Academy of Dermatology, a risk adjustment method that was based on modeling the average annual costs of individuals with or without specific diseases, and specifically tailored for 24 skin disease categories, was used to estimate the economic burden of skin disease. The results were compared with the claims tabulation method used in the first 2 parts of this project. The risk adjustment method estimated the direct health care costs of skin diseases to be $46 billion in 2013, approximately $15 billion less than estimates using claims tabulation. For individual skin diseases, the risk adjustment cost estimates ranged from 11% to 297% of those obtained using claims tabulation for the 10 most costly skin disease categories. Although either method may be used for purposes of estimating the costs of skin disease, the choice of method will affect the end result. These findings serve as an important reference for future discussions about the method chosen in health care payment models to estimate both the cost of skin disease and the potential cost impact of care changes.

Optogenetic and transcriptomic interrogation of enhanced muscle function in the paralyzed mouse whisker pad

Abstract: The functional state of denervated muscle is a critical factor in the ability to restore movement after injury- or disease-related paralysis. Here we used peripheral optogenetic stimulation and transcriptome profiling in the mouse whisker system to investigate the time course of changes in neuromuscular function following complete unilateral facial nerve transection. While most skeletal muscles rapidly lose functionality after lower motor neuron denervation, optogenetic muscle stimulation of the paralyzed whisker pad revealed sustained increases in the sensitivity, velocity, and amplitude of whisker movements, and reduced fatigability, starting 48 h after denervation. RNA-seq analysis showed distinct regulation of multiple gene families in denervated whisker pad muscles compared to the atrophy-prone soleus, including prominent changes in ion channels and contractile fibers. Together, our results define the unique functional and transcriptomic landscape of denervated facial muscles, and have general implications for restoring movement after neuromuscular injury or disease.

Highlights from the 8th International Workshop on HIV Persistence during Therapy, 12-15 December 2017, Miami, FL, USA.

Abstract: Over 4 days, more than 500 scientists involved in HIV persistence research shared their new unpublished data and designed future perspectives towards ART-free HIV remission. This 8th International Workshop on HIV Persistence followed the format of past conferences but further focused on encouraging participation of young investigators, especially through submission of oral and poster presentations. The topic of the workshop was HIV persistence. Consequently, issues of HIV reservoirs and HIV cure were also addressed. In this article, we report the discussions as closely as possible; however, all the workshop abstracts can be found online at www.viruseradication.com.

Opposing Influence of Sensory and Motor Cortex on Striatal Circuitry and Choice Behavior

Abstract: The striatum is the main input nucleus of the basal ganglia and is a key site of sensorimotor integration. While the striatum receives extensive excitatory afferents from the cerebral cortex, the influence of different cortical areas on striatal circuitry and behavior is unknown. Here we find that corticostriatal inputs from whisker-related primary somatosensory (S1) and motor (M1) cortex differentially innervate projection neurons and interneurons in the dorsal striatum, and exert opposing effects on sensory-guided behavior. Optogenetic stimulation of S1-corticostriatal afferents in ex vivo recordings produced larger postsynaptic potentials in striatal parvalbumin (PV)-expressing interneurons than D1- or D2-expressing spiny projection neurons (SPNs), an effect not observed for M1-corticostriatal afferents. Critically, in vivo optogenetic stimulation of S1-corticostriatal afferents produced task-specific behavioral inhibition, which was bidirectionally modulated by striatal PV-expressing interneurons. M1 input produced the opposite behavioral effect. Thus, our results reveal opposing roles for sensory and motor cortex in behavioral choice via distinct influences on striatal circuitry.

Natural killer cell dysregulation underlies atopic dermatitis

Abstract: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease characterized by dry, itchy rashes that affects 5–10% of the US adults. AD commonly presents in childhood and is known to be complicated by reduced antiviral skin immunity. Although classically thought to be driven by adaptive T H 2 cells, recent work has demonstrated that dysregulation of innate immune cells such as group 2 innate lymphoid cells (ILC2s) and basophils can promote its pathogenesis. However, how these innate immune cells become dysregulated remains unclear. Using paired RNA-Seq of lesional and non-lesional skin in patients, we identified an enrichment for natural killer (NK) cell-associated gene sets in AD skin lesions. NK cells are well-recognized innate effector cells for antiviral and anticancer immunity. However, their role in AD has not been established. We utilized unbiased multidimensional analysis of gene expression and flow cytometry data to identify underlying NK cell dysregulation in AD patients. Further, we demonstrate that NK cells negatively regulate type 2 inflammation in a mouse model of AD. Collectively, these studies reveal previously unrecognized functions of NK cells in cutaneous immune homeostasis.

Optogenetic probing of nerve and muscle function after facial nerve lesion in the mouse whisker system

Abstract: Optogenetic modulation of neural circuits has opened new avenues into neuroscience research, allowing the control of cellular activity of genetically specified cell types. Optogenetics is still underdeveloped in the peripheral nervous system, yet there are many applications related to sensorimotor function, pain and nerve injury that would be of great benefit. We recently established a method for non-invasive, transdermal optogenetic stimulation of the facial muscles that control whisker movements in mice (Park et al., 2016, eLife, e14140)1. Here we present results comparing the effects of optogenetic stimulation of whisker movements in mice that express channelrhodopsin-2 (ChR2) selectively in either the facial motor nerve (ChAT-ChR2 mice) or muscle (Emx1-ChR2 or ACTA1-ChR2 mice). We tracked changes in nerve and muscle function before and up to 14 days after nerve transection. Optogenetic 460 nm transdermal stimulation of the distal cut nerve showed that nerve degeneration progresses rapidly over 24 hours. In contrast, the whisker movements evoked by optogenetic muscle stimulation were up-regulated after denervation, including increased maximum protraction amplitude, increased sensitivity to low-intensity stimuli, and more sustained muscle contractions (reduced adaptation). Our results indicate that peripheral optogenetic stimulation is a promising technique for probing the timecourse of functional changes of both nerve and muscle, and holds potential for restoring movement after paralysis induced by nerve damage or motoneuron degeneration.