Exploring content and psychometric validity of newly developed assessment tools for itch and skin pain in atopic dermatitis.

BackgroundAtopic dermatitis (AD) is a common skin disorder characterized by chronic inflammation, altered skin barrier function, and inflammatory cell skin infiltration that decreases health-related quality of life (HRQoL). The study objective was to understand the patient perspective of AD burden and determine suitable patient-reported outcome (PRO) measures.MethodsThis mixed methods study involved the collection of qualitative and quantitative information from adults (≥ 18 years old) and adolescents (12 - 17 years old) with clinician-confirmed AD regarding their experiences of AD symptoms and its impact on HRQoL. The first part of the study included three stages: in-person concept elicitation (CE) interviews, a 2-week daily electronic diary (eDiary) study, and in-person cognitive debriefing (CD) interviews. An Itch numeric rating scale (NRS) (v1.0) and a Skin Pain NRS (v1.0) evaluation during CD interviews required participants to think about their 'worst' itch and 'worst' skin pain in the past 24 h. Other PRO measures allowed for psychometric testing. The second part of the study involved telephone-depth interviews (TDIs) and qualitative feedback from participants who had not participated in the CD interviews. Qualitative data were thematically analyzed. Psychometric evaluation of NRS measures was performed using eDiary data.ResultsIn the CE interviews, itch and/or itching and skin pain were the most prevalent symptoms consistently discussed by participants. Both NRS measures demonstrated strong psychometric reliability and were applicable across ages with suitable concurrent validity. During the CD interviews, some participants focused their answers on their 'average' itch/itching in the past 24 h, rather than their 'worst' itch. Some participants answered the Skin Pain NRS thinking about general pain or other types of pain, rather than skin pain specifically. Consequently, modifications to both measures addressed these issues and re-tested as paper-and-pen versions in subsequent TDIs. Itch NRS (v2.0) modifications helped participants focus on their worst itching. Most participants preferred Skin Pain NRS v2.0b, which included skin pain descriptors.ConclusionsItching and skin pain are the most important and relevant AD symptoms. The Itch NRS (v2.0) and Skin Pain NRS (v2.0b) appear to be appropriate endpoints for the assessment of itching and skin pain severity for clinical trials with adults and adolescents with AD

IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis.

Dupilumab is a fully human antibody to interleukin-4 receptor α that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor α inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus

Life-Expectancy Disparities Among Adults With HIV in the United States and Canada: The Impact of a Reduction in Drug- and Alcohol-Related Deaths Using the Lives Saved Simulation Model.

Improvements in life expectancy among people living with human immunodeficiency virus (PLWH) receiving antiretroviral treatment in the United States and Canada might differ among key populations. Given the difference in substance use among key populations and the current opioid epidemic, drug- and alcohol-related deaths might be contributing to the disparities in life expectancy. We sought to estimate life expectancy at age 20 years in key populations (and their comparison groups) in 3 time periods (2004-2007, 2008-2011, and 2012-2015) and the potential increase in expected life expectancy with a simulated 20% reduction in drug- and alcohol-related deaths using the novel Lives Saved Simulation model. Among 92,289 PLWH, life expectancy increased in all key populations and comparison groups from 2004-2007 to 2012-2015. Disparities in survival of approximately a decade persisted among black versus white men who have sex with men and people with (vs. without) a history of injection drug use. A 20% reduction in drug- and alcohol-related mortality would have the greatest life-expectancy benefit for black men who have sex with men, white women, and people with a history of injection drug use. Our findings suggest that preventing drug- and alcohol-related deaths among PLWH could narrow disparities in life expectancy among some key populations, but other causes of death must be addressed to further narrow the disparities

Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration

Shopping, sex, and lies: Mimong/Sweet Dreams (1936) and the disruptive process of colonial girlhood

In the early Korean film we follow the melodramatic life of an unfaithful housewife. Sweet Dreams situates itself at the heart of the Korean colonial experience with urban Seoul as the backdrop to a narrative of deceit, adultery and consumerism. This article will explore how Sweet Dreams functions both as a warning about the perils of modern womanhood and, simultaneous to this, a vision of consumerist pleasure and delight. This article examines how the actions of lead character Ae-soon constitute a process by which the adult women is rendered girl via her positioning at the locus of female visual pleasure. I use the term girl as a process rather than a static category since, as will be explored, the attributes of girlhood with relation to Sweet Dreams are both expansive and fluid. In this way girlhood can be appropriated for transgressive purposes, not only in terms of a visualization of a desiring femininity, but also as a marker of colonial dissent. I argue that Sweet Dreams uses the interplay between the categories of woman and girl to disrupt the colonial drive towards a productive body in favour of the delights of consumption

IL-4R alpha blockade by dupilumab decreases Staphylococcus aureus colonization and increases microbial diversity in atopic dermatitis

Dupilumab is a fully human antibody to interleukin-4 receptor alpha that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S. aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S. aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S. aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S. aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor alpha inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S. aureus

Functional magnetic resonance imaging in primary hyperparathyroidism

Objective: The neurophysiological mechanisms underlying cognitive dysfunction in primary hyperparathyroidism (PHPT) and the brain regions affected are not clear. We assessed neural activation during cognitive testing (matrix reasoning, paired associates, and logical memory) using functional MRI (fMRI) in 23 patients with PHPT and 23 healthy controls. A subset with PHPT was re-assessed 6 months post-parathyroidectomy (PTX). Design: This is an observational study comparing neural activation by fMRI in patients with PHPT to normative controls. Postmenopausal women were studied at a tertiary referral center. Results: There were no between-group differences in cognitive task performance. Patients with PHPT had lower neural activation vs controls (max Z = 4.02, all P < 0.01) during matrix reasoning in brain regions involved in executive function (left frontal lobe (k = 57) and right medial frontal gyrus (k = 72)) and motor function (right precentral gyrus (k = 51)). During paired associates (verbal memory), those with PHPT had greater activation in the right inferior parietal lobule (language/mathematical operations; k = 65, P < 0.01). Greater activation in this region bilaterally correlated with higher PTH (k = 96, P < 0.01). Post-PTX, activation decreased during matrix reasoning, but in different regions than those affected pre-PTX. Conclusions: PHPT is associated with differences in task-related neural activation patterns, but no difference in cognitive performance. While this may indicate compensation to maintain the same cognitive function, there was no clear improvement in neural activation after PTX. Larger, longitudinal studies that include PHPT patients followed without surgery are needed to determine if PTX could prevent worsening of altered neural activation patterns in PHPT

The relationship of smoking and unhealthy alcohol use to the HIV care continuum among people with HIV in an integrated health care system

INTRODUCTION: Smoking tobacco and unhealthy alcohol use may negatively influence HIV care continuum outcomes but have not been examined in combination. METHODS: Participants were people with HIV (PWH) in Kaiser Permanente Northern California. Predictors included smoking status and unhealthy alcohol use (exceeding daily and/or weekly limits) reported by patients during primary care screening (index date). Outcomes were based on not achieving the following steps in the care continuum: linkage to HIV care (≥1 visit within 90 days of newly identified HIV diagnosis), retention (2+ in-person visits, 60+ days apart) and HIV RNA control (<75 copies/mL). Adjusted odds ratios (ORs) were obtained from separate logistic regression models for each outcome associated with smoking and unhealthy alcohol use independently and combined. RESULTS: The overall sample (N=8,958) had a mean age of 48.0 years; was 91.3% male; 54.0% white, 17.6% Latino, 15.1% black, and 9.6% other race/ethnicity. Smoking was associated with higher odds of not being linked to HIV care (OR=1.60 [95% CI 1.03–2.48]), not retained (OR=1.30 [95% CI 1.13–1.50]), and HIV RNA not in control (OR=1.91 [95% CI 1.60–2.27]). Alcohol measures were not independently associated with outcomes. The combination of unhealthy alcohol use and smoking (versus neither) was associated with higher odds of not being linked to care (OR=2.83 [95% CI 1.40–5.71]), although the interaction did not reach significance (p=0.18). CONCLUSIONS: In this large sample of PWH in an integrated health care system, smoking, both independently and in combination with unhealthy alcohol use, was associated with worse HIV care continuum outcomes

Uranium diagenesis in sediments underlying bottom waters with high oxygen content

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 73 (2009): 2920-2937, doi:10.1016/j.gca.2009.02.014.We measured U in sediments (both pore waters and solid phase) from three locations on the middle Atlantic Bight (MAB) from the eastern margin of the United States: a northern location on the continental shelf off Massachusetts (OC426, 75 m water depth), and two southern locations off North Carolina (EN433-1, 647 m water depth and EN433-2, 2648 m water depth). These sediments underlie high oxygen bottom waters (250-270 μM), but become reducing below the sediment-water interface due to the relatively high organic carbon oxidation rates in sediments (EN433-1: 212 μmol C/cm2/y; OC426: 120±10 μmol C/cm2/y; EN433-2: 33 μmol C/cm2/y). Pore water oxygen goes to zero by 1.4-1.5 cm at EN433-1 and OC426 and slightly deeper oxygen penetration depths were measured at EN433-2 (~4 cm). All of the pore water profiles show removal of U from pore waters. Calculated pore water fluxes are greatest at EN433-1 (0.66±0.08 nmol/cm2/y) and less at EN433-2 and OC426 (0.24±0.05 and 0.13±0.05 nmol/cm2/y, respectively). Solid phase profiles show authigenic U enrichment in sediments from all three locations. The average authigenic U concentrations are greater at EN433-1 and OC426 (5.8±0.7 nmol/g and 5.4±0.2 nmol/g, respectively) relative to EN433-2 (4.1±0.8 nmol/g). This progression is consistent with their relative ordering of ‘reduction intensity’, with greatest reducing conditions in sediments from EN433-1, less at OC426 and least at EN433-2. The authigenic U accumulation rate is largest at EN433-1 (0.47±0.05 nmol/cm2/y), but the average among the three sites on the MAB is ~0.2 nmol/cm2/y. Pore water profiles suggest diffusive fluxes across the sediment-water interface that are 1.4-1.7 times greater than authigenic accumulation rates at EN433-1 and EN433-2. These differences are consistent with oxidation and loss of U from the solid phase via irrigation and/or bioturbation, which may compromise the sequestration of U in continental margin sediments that underlie bottom waters with high oxygen concentrations. Previous literature compilations that include data exclusively from locations where [O2]bw < 150 μM suggest compelling correlations between authigenic U accumulation and organic carbon flux to sediments or organic carbon burial rate. Sediments that underlie waters with high [O2]bw have lower authigenic U accumulation rates than would be predicted from relationships developed from results that include locations where [O2]bw < 150 μM.The authors appreciate the financial support from NSF (JLM, WRM: OCE-0220892; and OCE-0526389 to WRM), Research Corporation (JLM, CMC), Franklin & Marshall College, and the Hackman Summer Research Program (CMC) at F&M