High mortality among patients with severe COVID-19 and Do Not Intubate orders.

INTRODUCTION: Moderate to severe respiratory distress among patients with COVID-19 is associated with a high mortality. This study evaluated ventilator support and mortality by Do Intubate (DI) or Do Not Intubate (DNI) orders. METHODS: This was a retrospective study of patients with COVID-19 and a supplemental oxygen requirement of ≥ 15 l/min. The patients were divided into two groups corresponding to the first and second wave of COVID-19 and were subsequently further divided according to DI and DNI orders and analysed regarding need of ventilator support and mortality. RESULTS: The study included 178 patients. The mortality was 24% for patients with DI orders (n = 115) and 81% for patients with DNI orders (n = 63) increasing to 98% (n = 46) for patients with DNI orders and very high flow oxygen requirements (≥ 30 l/min.). From the first to the second wave of COVID-19, the use of constant continuous positive airway pressure (cCPAP) increased from 71% to 91% (p less-than 0.001), whereas the use of mechanical ventilation decreased from 54% to 28% (odds ratio = 0.38 (95% confidence interval: 0.17-0.85)). CONCLUSION: The mortality was high for patients with DNI orders and respiratory distress with very high levels in supplemental oxygen in both the first and second wave of COVID-19 despite an increase in use of cCPAP and treatment with dexamethasone and remdesivir during the second wave. Hence, careful evaluation on transition to palliative care must be considered for these patients. FUNDING: none. TRIAL REGISTRATION: The study was approved by the Danish Patient Safety Authority (record no. 31-1521-309) and the Regional Data Protection Centre (record no. P-2020-492).

Risk of work-related hand eczema in relation to wet work exposure.

Objective Albeit a pivotal risk for the development of hand eczema (HE), the exposure-response relationship between wet work and HE remains to be further investigated. Knowledge on exposure-response is important regarding preventive measures, medico-legal regulations and job-counseling. Recently, a job-exposure matrix (JEM) for wet work was developed, providing information on the likelihood of wet work. By combining the JEM with data on HE we aimed to investigate the relationship between extent of wet work and HE. Methods This study is a case-referent study including patients registered in the National Database of Contact Allergy, Denmark, and comprises data on sex, age, atopic dermatitis, HE, face eczema and patch testing results. Patients with HE served as cases and patients with facial eczema served as referents. Information on profession was retrieved from the DOC*X database in accordance with the DISCO-88 classification system. A wet-work-specific JEM provides - for each profession - an estimate for (i) the likelihood of wet work lasting ≥2 hours/day and (ii) the average number of hours of wet work per day. Results After two hours of wet hands and glove wear, the odds ratio (OR) was 3.49 and 3.19, respectively, for females and 2.41 and 1.82, respectively, for males. Females had a higher risk of HE than males with probability of wet hands <75% (OR 2.34, 95% CI 2.12-2.58 compared to males 1.68, 95% CI 1.22-2.31) and regarding glove wear at all exposure levels. Conclusion Our data confirms a close association between wet work and HE. Exposure lasting less than the current definition of wet work (having wet hands for ≥2 hours per day) may be of importance.

[Hand eczema and wet work].

Occupational hand eczema (HE) has continuously been the most frequently recognised occupational disease, comprising > 95% of all recognised occupational skin diseases. Irritant contact dermatitis constitutes > 70%, where wet work is the main eliciting factor. Knowledge on the dose-response relationship between wet work and HE is pivotal concerning preventive interventions, job counselling and medico-legal regulations, which is summarised in this review. New findings indicate a significant risk of having HE at an exposure level of no more than 30 minutes of wet work per day.

A job-exposure matrix addressing hand exposure to wet work.

PURPOSE: The aim of this study was to create a job-exposure matrix (JEM) for wet work. A JEM is a tool used to assess exposure to potential health hazards in occupational epidemiological studies. It can be used when counselling concerning job change/job choice, as a medico-legal tool when recognizing diseases as occupational and when planning interventions regarding prevention of, in this case, occupational hand eczema. METHODS: The study population was based on results from national surveys on working environment performed by the National Research Centre for the Working Environment in Denmark in 2000, 2005, and 2010 (National Research Centre for the Working Environment). We assessed responses on questions regarding wet hands, glove wear and total wet work. For the JEM a cutoff of 2 h total wet work/day was chosen as the exposure measurement. The proportion of responses of 2 h total wet work/day in each profession is illustrated as a number between 0 and 1 equal to 0-100% of the responses. RESULTS: Total wet work was most frequent among cleaners (domestic, office, and hotel cleaning), butchers and fishmongers, cooks, beauticians (hairdressers, barbers, related work) and health care workers (home-based personal workers, dentists, dental assistants). Regarding differences between sexes we found that indifferent of age and profession, women had 78% higher odds of having wet work. CONCLUSION: We found that wet work as an exposure varies among professions depending on whether wet hands or glove wear is assessed. A JEM is a useful tool to assess the extent of the exposure, wet work, independent of prior perceptions of classical wet work professions.

Wet work exposure: comparison of observed and self-reported data.

PURPOSE: Wet work is the most important exposure leading to occupational hand eczema; however, the prevalence and character of wet work in various wet work professions remain not fully covered. Self-reported data are widely used in studies of wet work although the validity of these remains uncertain. The objective of the present study is to provide information on validity of self-reported wet work exposure in different professions by comparing work place observations with self-reported data. METHODS: 114 workers from 15 various wet work professions were observed. The observations covered duration and frequency of wet work activities. The observed population as well as a non-observed population from each work place were given a questionnaire covering the same wet work activities. RESULTS: Correspondence analysis between self-reported and observed wet work showed that misclassification was larger regarding duration than frequency. 29.2% overestimated and 23.9% underestimated total wet work with more than 2 h/day. Professions with high wet work prevalence overestimated duration of wet work activities, but underestimated frequency. Females overestimated frequency, but not duration. The observed group (45%) significantly more often, than the non-observed group (32%), reported having more than 2 h of wet work/day (OR 2.8, 95% CI 1.6-4.9). Sensitivity and specificity of the questionnaire regarding total wet work in the observed population showed 51% sensitivity and 59% specificity. CONCLUSION: Over- and underestimation of wet work were found to be equally distributed. The correspondence analyses illustrate a noticeable misclassification between the estimations and the observations on all wet work variables, but largest for total wet work.

Use of TNF-inhibitors and ustekinumab for psoriasis during pregnancy: A patient series.

From 2002 to 2016 a total of seven women with severe refractory psoriasis were exposed to the TNF-inhibitors infliximab and adalimumab or to the IL12/23 inhibitor ustekinumab during one or more pregnancies. Maternal, fetal or teratogenic toxicity were not detected during pregnancy and puerperium. All pregnancies were uneventful and resulted in delivery of 10 healthy children in total, one of the women is due February 2017. Postpartum, five of the women were lactating, but none of the women or newborns developed adverse reactions. Data on safety of treatment during breastfeeding are sparse, but so far appears to be safe due to the lack of absorption across the gastrointestinal lining. Currently biological therapy with either TNF-inhibitors or ustekinumab is not recommended during pregnancy, however in selected women with severe psoriasis these treatment modalities may be considered.

Discrepant coagulation profile in HIV infection: elevated D-dimer but impaired platelet aggregation and clot initiation.

OBJECTIVES: In HIV infection, cardiovascular disease (CVD) has emerged as a clinical problem, and elevated D-dimer has been reported. The pathophysiologic mechanisms underlying this remain unclear. We aimed to investigate whether untreated HIV-infected individuals display evidence of functional coagulopathy and whether this was associated with microbial translocation. DESIGN: The study population consisted of 50 HIV-infected untreated individuals and 50 HIV-infected individuals on combination antiretroviral therapy (cART). Groups were matched for age, sex and current CD4cell count. METHODS: Coagulation analyses included D-dimer and the functional haemostatic whole blood tests, thromboelastography (TEG) and platelet aggregation (Multiplate, impedance aggregometry). Microbial translocation was assessed by plasma levels of lipopolysaccharide (LPS). RESULTS: A larger proportion of untreated individuals compared with treated individuals had D-dimer above normal reference range (27.7 vs. 2.2%, P = 0.001). In both treated and untreated individuals, delayed clot initiation with TEG R-time above upper reference range (18 and 28%, respectively, both P < 0.001) and TEG angle below lower reference range [14% (P = 0.004) and 24% (P < 0.001), respectively] was found. In untreated individuals, 64.6% had aggregation response below threshold in at least two of four tests compared with 36.7% in treated individuals (P = 0.010). Untreated individuals with increased D-dimer levels were relatively hypercoagulable by thromboelastography. Furthermore, in untreated patients, a negative association between microbial translocation and platelet aggregation was found. CONCLUSION: Elevated D-dimer in untreated HIV-infected individuals was confirmed. However, in both untreated and treated individuals, reduced platelet aggregation and clot initiation was found. The impact of reduced platelet function in HIV infection and a potential role of microbial translocation warrant further investigation.

Microbial translocation in HIV infection is associated with dyslipidemia, insulin resistance, and risk of myocardial infarction.

OBJECTIVE: Microbial translocation has been suggested to be a driver of immune activation and inflammation. It is hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals. DESIGN: Cross-sectional study of 60 HIV-infected patients on combination antiretroviral therapy with viral suppression >2 years and 31 healthy age-matched controls. METHODS: Lipopolysaccharide (LPS) was analyzed by limulus amebocyte lysate colorimetric assay. Lipids, including cholesterol, low-density lipoprotein (LDL), and triglycerides, were measured. Glucose metabolism was determined using an oral glucose tolerance test. Body composition was determined using whole-body dual-energy x-ray absorptiometry scans and magnetic resonance imaging. The Framingham risk score was used to assess risk of cardiovascular disease and myocardial infarction. RESULTS: HIV-infected patients had higher level of LPS compared with controls (64 pg/mL vs. 50 pg/mL, P = 0.002). Likewise, HIV-infected patients had higher triglycerides, LDL, and fasting insulin as well as evidence of lower insulin sensitivity compared with controls. Among HIV-infected patients, high LPS was associated with a higher level of triglycerides and LDL and with lower insulin sensitivity. Importantly, among HIV-infected patients, high LPS was associated with a higher Framingham risk score. CONCLUSIONS: HIV-infected patients with suppressed viral replication had increased level of microbial translocation as measured by LPS. LPS was associated with cardiometabolic risk factors and increased Framingham risk score. Hence, the gastrointestinal mucosal barrier may be a potential therapeutic target to prevent dyslipidemia and future cardiovascular complications in HIV infection.