IL17A mRNA Staining Distinguishes Palmoplantar Psoriasis from Hyperkeratotic Palmoplantar Eczema in Diagnostic Skin Biopsies.

Acral dermatoses, including hyperkeratotic palmoplantar eczema (HPE), palmoplantar psoriasis (PP), and mycosis fungoides palmaris et plantaris (MFPP), can be challenging to diagnose clinically and histopathologically. In this setting, cytokine biomarkers may be able to help provide diagnostic clarity. Therefore, we evaluated IL-17A, IFN-γ, and IL-13 expression in PP, HPE, and MFPP and compared their expression profiles with nonacral sites. We used biopsy specimens from the Yale Dermatopathology database, selecting cases of HPE (n = 12), PP (n = 8), MFPP (n = 8), normal acral skin (n = 9), nonacral eczema (n = 10), and nonacral psoriasis (n = 10) with classic clinical and histopathologic features. IL17A mRNA expression by RNA in situ hybridization differentiated PP (median score 63.1 [interquartile range 9.4-104.1]) from HPE (0.8 [0-6.0]; P = 0.003), MFPP (0.6 [0-2.6]; P = 0.003), and normal acral skin (0 [0-0]; P < 0.001). Unexpectedly, both PP and HPE showed co-expression of IFNG and IL13 mRNA. In contrast, nonacral psoriasis and eczema showed divergent patterns of IFNG and IL13 mRNA expression. Taken together, we show that IL17A mRNA expression may be a useful biomarker of PP, and we further show that acral dermatoses exhibit distinct immunology compared to nonacral sites, with implications for clinical management.

Characteristics of Esketamine Prescribers Among Medicare Beneficiaries in the United States, 2019-2020.

This cross-sectional study examines the characteristics and geographic distribution of eskatamine prescribers among Medicare beneficiaries in the US from 2019 to 2020.

Association of sarcoidosis with psoriasis: a cross-sectional study in the All of Us research program.

Psoriasis and sarcoidosis are inflammatory skin and systemic diseases that may share a similar immunopathogenesis involving a Th1 and/or Th17 polarized immune response. Although the coexistence of sarcoidosis and psoriasis in the same individuals has been reported, the potential association between these diseases at a population-level in the United States has not been evaluated. To evaluate this association, we performed a matched cross-sectional study in the All of Us research program database. In the multivariable analysis of 4932 psoriasis cases and 19,728 controls, sarcoidosis was found to be significantly associated with psoriasis (OR 2.37 [95% CI 1.73-3.23], p < 0.001). The relative strength of this association between psoriasis and sarcoidosis may be, in part, explained by overlapping immunopathogenesis and common genetic susceptibility of these diseases. Taken together, these observations underscore the need for screening psoriasis patients for development of new cardiopulmonary symptoms. Further research into the mechanism of this relationship and its implications is warranted.

Autoimmune comorbidities associated with sarcoidosis: a case-control study in the All of Us research program.

Objective: The degree to which sarcoidosis patients are affected by autoimmune diseases is poorly understood. Prior studies of autoimmune co-morbidities in sarcoidosis have focused on populations outside the USA or have been impeded by small sample sizes and limited scope. This case-control study evaluated the association between sarcoidosis and autoimmune diseases in a large, diverse cohort based in the USA. Methods: We used data from the All of Us research programme to conduct a case-control study involving patients ≥18 years old, from 2018 to the present, diagnosed with sarcoidosis. Sarcoidosis cases and age-, sex- and race-matched controls were identified in a 1:4 ratio. Autoimmune co-morbidities were compared between sarcoidosis patients and controls in univariable and multivariable analyses using logistic regression. The degree of association was measured using the odds ratio (OR). Results: A total of 1408 sarcoidosis cases and 5632 controls were included in this study. Seven of 24 examined autoimmune diseases were significantly associated with sarcoidosis in our multivariable analysis (P < 0.05). The composite variable of any autoimmune disease was also significantly associated with sarcoidosis (OR = 2.29, P < 0.001). Conclusion: We demonstrate an association between sarcoidosis and multiple autoimmune diseases in a large and diverse cohort based in the USA. These results underscore the need for careful screening of sarcoidosis patients for concomitant autoimmune disease.

Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis.

Sarcoidosis is an idiopathic inflammatory disorder that is commonly treated with glucocorticoids. An imprecise understanding of the immunologic changes underlying sarcoidosis has limited therapeutic progress. Here in this open-label trial (NCT03910543), 10 patients with cutaneous sarcoidosis are treated with tofacitinib, a Janus kinase inhibitor. The primary outcome is the change in the cutaneous sarcoidosis activity and morphology instrument (CSAMI) activity score after 6 months of treatment. Secondary outcomes included change in internal organ involvement, molecular parameters, and safety. All patients experience improvement in their skin with 6 patients showing a complete response. Improvement in internal organ involvement is also observed. CD4+ T cell-derived IFN-γ is identified as a central cytokine mediator of macrophage activation in sarcoidosis. Additional type 1 cytokines produced by distinct cell types, including IL-6, IL-12, IL-15 and GM-CSF, also associate with pathogenesis. Suppression of the activity of these cytokines, especially IFN-γ, correlates with clinical improvement. Our results thus show that tofacitinib treatment is associated with improved sarcoidosis symptoms, and predominantly acts by inhibiting type 1 immunity.

Factors associated with declaration of disability in medical students and junior doctors, and the association of declared disability with academic performance: observational study using data from the UK Medical Education Database, 2002-2018 (UKMED54).

OBJECTIVES: To examine factors associated with declaration of disability by medical students and doctors, and the association of declared disability with academic performance. DESIGN: Observational study using record-linked data collected between 2002 and 2018. SETTING: UK Medical Education Database is a repository of data relating to training of medical students and doctors. Disability and other data are record-linked. PARTICIPANTS: All students starting at a UK medical school between 2002 and 2018 (n=135 930). MAIN OUTCOME MEASURES: Declared disability was categorised by the Higher Education Statistics Authority. Outcomes related to undergraduate academic performance included scores in the educational performance measure (EPM), prescribing safety assessment and situational judgement test. Performance in postgraduate examinations was studied, as well as prior attainment in school examinations and aptitude tests. RESULTS: Specific learning disability (SLD) was the most commonly declared disability (3.5% compared with the next most commonly declared disability at 1.0% of n=129 345 all cases in the study), and during the period covered by the data, SLD declarations increased from 1.4% (n=6440 for students starting in 2002) to 4.6% (n=8625 for students starting in 2018). In a logistic regression, the following factors predicted recording of SLD on entry to medical school ((exp(B)±95% CI), p<0.0001 unless otherwise stated): attendance at a fee-paying school (2.306±0.178), graduate status (1.806±0.205), participation of local areas quintile (1.089±0.030), age (1.034±0.012). First year medical students were less likely to declare SLD if they were from a non-white ethnic background (Asian/Asian British 0.324±0.034, black/black British 0.571±0.102, mixed 0.731±0.108, other ethnic groups 0.566±0.120), female (0.913±0.059; p=0.007) or from a low index of multiple deprivation quintile (0.963±0.029); p=0.017. In univariate analysis with Bonferroni corrections applied for multiple tests, no significant difference was observed in the recording of SLD according to socioeconomic class (χ2=5.637, p=1), whether or not a student's parents had a higher education (χ2=0.140, p=1), or whether or not a student had received a United Kingdom Clinical Aptitude Test (UKCAT) bursary (χ2=7.661, p=0.068). Students who declared SLD at some point in medical school (n=4830) had lower EPM normalised deviate values (-0.390) than those who did not (-0.119) (F=189.872, p<0.001). Those for whom SLD was recorded were as likely to complete the course successfully as those who did not declare disability (93.0% successful completion by those for whom SLD declared from year 1 (n=2480), 92.2% by those for whom SLD declared after year 1 (n=2350), 91.6% by those for whom SD not declared at any point (n=85 180)) (χ2=6.905, p=0.032). Of 3580 first year students who declared SLD, 43.1% had not sat the UKCAT Special Educational Needs aptitude test (which gives extra time for those with special educational needs), while 28% of 2400 registrants for whom SLD was recorded as medical students did not declare it at General Medical Council registration. CONCLUSIONS: Substantial increases in declaration of SLD may reflect changes in the social and legal environment during the period of the study. Those who declare SLD are just as likely to gain a primary medical qualification as those who do not. For some individuals, disability declaration appears to depend on context, based on differences in numbers declaring SLD before, during and after medical school.

COVID-19 aerosol transmission modeling in support of company HVAC guideline.

A company COVID-19 Heating, Ventilation, and Air Conditioning Guideline was implemented globally, as part of a larger control measure toolset, to minimize the potential for SARS-CoV-2 aerosol transmission. The COVID-19 Heating, Ventilation, and Air Conditioning Guideline informed and provided the process to optimize existing ventilation systems, set occupancy duration limits, and set clearance periods for a given space. Aerosol transmission modeling was used extensively to determine space limitations to reduce the potential for aerosol transmission in various manufacturing, lab, warehouse, aircraft, and administrative workspaces. This paper focuses on the modeling completed for administrative spaces (e.g., offices, conference rooms, restrooms, elevators) due to their lower ventilation rates, higher occupant densities, and greater vocalization levels. A detailed description of how the Guideline was implemented, with examples showing the evaluation and determinations made for specific spaces, is provided. World-wide implementation of this Guideline, as one of the layers of protection, was a key component in the overall strategy to reduce aerosol transmission of the SARS-CoV-2 virus.

Use of portable air purifiers as local exhaust ventilation during COVID-19.

The purpose of this study was to determine if strategic placement of portable air purifiers would improve effectiveness of aerosol reduction in a space as compared to use as a general room air purifier. Two sizes of portable air purifiers were placed in two different positions intended to function similar to either a local exhaust ventilation hood or an air curtain to determine if strategic placement would lead to a reduction of particles in a worker's position at a desk in an office environment. Particle generators were used to introduce particulate into the air and personal aerosol monitors measured particles during each test condition. Results showed that when the medium room portable air purifiers used in this study were set to high, corresponding to 98 CFM, and placed near the breathing zone of each office worker with the unit's filter cover removed, the particle concentration was reduced 35% beyond the reduction that would be expected if the same units were placed on the floor behind the occupant's workstation. Results also indicated that the larger portable air purifier tested, positioned as close as reasonable to each occupant's breathing zone with the largest capture area possible (i.e., removing the unit's filter cover), delivers the best aerosol reduction performance. The authors concluded that as a layer of protection against transmission of airborne infectious organisms for office occupants, installing a portable air purifier, sized and operated similar to the units tested in this study on the desk 12 inches from the breathing zone of the worker, has the potential to reduce airborne particulate to a greater degree than if the same units were placed outside of the breathing zone, in the general cubicle area.

Slowdown in Mortality Improvement in the Past Decade: A US/UK Comparison.

OBJECTIVES: To investigate the slowdown in mortality improvement in the United States, United Kingdom, and comparator countries observed in the first decade of the twenty-first century and critically evaluate proposed explanations. METHODS: Change-point analysis to identify the year of change in comparison of national mortality trends and linear spline models in the investigation of subnational differences using data from the Human Mortality Database, Global Burden of Disease cause-specific data, and, for the United Kingdom, national statistics data. Consideration of the impact of using different methods to estimate overall mortality is also concluded together with a review of methodological assumptions made in previous studies. RESULTS: The results confirm the slowdown in mortality improvement observed in the early twenty-first century but indicate that proposed explanations for this are inadequate on a range of counts. DISCUSSION: Mortality improvement slowed down in the early twenty-first century but the explanations advanced, such as opioid use in the United States or influenza epidemics and austerity programs in the United Kingdom, seem unlikely to account for this. Further research considering longer-term life course and cohort influences is needed.

Exploring the Ethics of a Nurses' Strike During a Pandemic.

ABSTRACT: It's usually considered a violation of professional ethics for health care workers, including nurses, to refuse to work during mass medical emergencies, especially if their refusal is over concerns like compensation. Strikes and other forms of work stoppage may result in harm to patients and, therefore, violate professional obligations of beneficence. However, in rare circumstances a health care worker's choice to remain on the job despite risk or potential harm to themselves or even their family may be considered beyond their professional obligation. During a pandemic such as COVID-19, the ethical calculus (that is, finding the right balance between beneficence and harm before deciding on a course of action) must take account of a confluence of factors, including the risks to present patients, future patients, and health care workers; the severity and duration of the risks; and the availability of ameliorative or protective steps that reduce risk and harm. The principle of beneficence to both future patients and health care workers may be thwarted if the risk analysis is confined only to short-term concerns (that is, to concerns occurring within a narrow temporal window). If a significantly elevated risk has been demonstrated to affect nurses and other health care workers of color disproportionately, racial justice must also be considered. The purpose of this article is to assess the moral framework of a work stoppage by nurses during a pandemic.