Overweight and obesity result from an imbalance between caloric intake and energy expenditure, including expenditure from spontaneous physical activity (SPA). Changes in SPA and resulting changes in ...non-exercise activity thermogenesis (NEAT) likely interact with diet to influence risk for obesity. However, previous research on the relationship between diet, physical activity, and energy expenditure has been mixed. The neuropeptide orexin is a driver of SPA, and orexin neuron activity can be manipulated using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). We hypothesized that HFD decreases SPA and NEAT, and that DREADD-mediated activation of orexin neuron signaling would abolish this decrease and produce an increase in NEAT instead. To test these ideas, we characterized behaviors to determine the extent to which access to a high-fat diet (HFD) influences the proportion and probability of engaging in food intake and activity. We then measured NEAT following access to HFD and following a DREADD intervention targeting orexin neurons. Two cohorts of orexin-cre male mice were injected with an excitatory DREADD virus into the caudal hypothalamus, where orexin neurons are concentrated. Mice were then housed in continuous metabolic phenotyping cages (Sable Promethion). Food intake, indirect calorimetry, and SPA were automatically measured every second. For cohort 1 (n=8), animals were given access to chow, then switched to HFD. For cohort 2 (n=4/group), half of the animals were given access to HFD, the other access to chow. Then, among animals on HFD, orexin neurons were activated following injections of clozapine n-oxide (CNO). Mice on HFD spent significantly less time eating (p<0.01) and more time inactive compared to mice on chow (p<0.01). Following a meal, mice on HFD were significantly more likely to engage in periods of inactivity compared to those on chow (p<0.05). NEAT was decreased in animals on HFD, and was increased to the NEAT level of control animals following activation of orexin neurons with DREADDs. Food intake (kilocalories) was not significantly different between mice on chow and HFD, yet mice on chow expended more energy per unit of SPA, relative to that in mice consuming HFD. These results suggest that HFD consumption reduces SPA and NEAT, and increases inactivity following a meal. Together, the data suggest a change in the efficiency of energy expenditure based upon diet, such that SPA during HFD burns fewer calories compared to SPA on a standard chow diet.
•A high fat diet decreases spontaneous physical activity and time spent eating.•A high fat diet encourages longer bouts of inactivity, particularly after a meal.•Energy expenditure from SPA (NEAT) is decreased in animals on a high fat diet.•Orexin activation increases previously low levels of NEAT induced by high fat diet.•A high fat diet increases energy efficiency during physical activity.
To identify patterns of self-reported health problems relating to dose and duration of glucocorticoid intake in unselected patients with rheumatoid arthritis from routine practice.
Data from 1066 ...patients were analysed. The clinical status and drug treatment were reported by the physician, health problems during the past 6 months by the patient using a comprehensive list of symptoms. Patients with ongoing glucocorticoid treatment for more than 6 months and current doses of less than 5, 5-7.5 and over 7.5 mg/day prednisone equivalent were compared with a group without any glucocorticoid treatment for at least 12 months.
The frequency of self-reported health problems was lowest in the group without glucocorticoid exposition and increased with dosage. Two distinct dose-related patterns of adverse events were observed. A "linear" rising with increasing dose was found for cushingoid phenotype, ecchymosis, leg oedema, mycosis, parchment-like skin, shortness of breath and sleep disturbance. A "threshold pattern" describing an elevated frequency of events beyond a certain threshold value was observed at dosages of over 7.5 mg/day for glaucoma, depression/listlessness and increase in blood pressure. Dosages of 5 mg/day or more were associated with epistaxis and weight gain. A very low threshold was seen for eye cataract (<5 mg/day).
The associations found are in agreement with biological mechanisms and clinical observations. As there is a paucity of real-life data on adverse effects of glucocorticoids prescribed to unselected groups of patients, these data may help the clinician to adapt therapy with glucocorticoids accordingly and improve the benefit-risk ratio.
Worldwide 2–3 million cases of keratinocyte carcinoma (KC) are diagnosed annually. Sun‐related knowledge is essential for adequate protection against solar ultraviolet radiation (UVR), the main risk ...factor for KC. The goal was (i) to provide an updated overview of primary prevention against KC including skin cancer‐related knowledge, attitudes and sun protection behaviour (SPB) of outdoor workers, the general population and medical professionals as well as (ii) to evaluate the effectiveness and acceptability of sun protection programmes. We conducted a systematic review of articles indexed for MEDLINE on PubMed using selected MeSH terms and keywords related to the studied topic as well as an extensive hand search of publications between 1 January 2012 and 31 December 2018. We identified 51 relevant cross‐sectional studies and 22 interventional studies. Sun‐related knowledge and attitude showed substantial differences with some alarming results, including people who had not even heard about skin cancer before. Reported SPB varied enormously between the included studies, with none of the studies providing an overall sufficient SPB in their examined sun protection measures. However, sun protection programmes using new technologies seem to have great potential to increase sun‐related knowledge and SPB. In countries worldwide, particularly in those where KC is not yet a public health issue, UVR protection should be promoted by healthcare institutions and authorities, politicians, cancer foundations and dermatologists to increase awareness as well as SPB and to decrease the worldwide burden of KC.
Background
Atopic eczema (AE, atopic dermatitis) is one of the most common non‐communicable inflammatory skin diseases affecting 1–5% of the adult population in Europe with marked impairment in ...quality of life. In spite of great progress in understanding the pathophysiology of disturbed skin barrier and immune deviation, AE still represents a problem in daily clinical practice. Furthermore, the true impact of AE on individual suffering is often not recognized.
Objectives
With a large European study, we wanted to provide insights into the actual suffering and individual burden of disease in adult patients with AE.
Methods
A total of 1189 adult patients (18–87 years, 56% female) with moderate to severe AE were recruited in nine European countries by dermatologists or allergists together with the help of patient organizations. A computer‐assisted telephone interview was performed by experienced interviewers between October 2017 and March 2018. The following instruments were used to assess severity or measure quality of life: Patient‐Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS‐D) and a newly developed Atopic Eczema Score of Emotional Consequences (AESEC). Patients were also asked to self‐assess the severity of their disease.
Results
Despite current treatment, 45% of participants still had actual moderate to very severe AE in POEM. Due to their skin disease, 57% missed at least 1 day of work in the preceding year. DLQI showed moderate to extremely large impairment in 55%. According to HADS‐D, 10% scored on or above the threshold of eight points with signs of depressive symptoms. Assessed with AESEC, 57% were emotionally burdened with feelings such as ‘trying to hide the eczema’, ‘feeling guilty about eczema’, having ‘problems with intimacy’ and more. Of persons actually suffering from severe AE, 88% stated that their AE at least partly compromised their ability to face life.
Conclusions
This real‐life study shows that adults with a moderate to severe form of AE are suffering more than what would be deemed acceptable. There is a need for increased awareness of this problem among healthcare professionals, policymakers and the general public to support research in the development of new and more effective treatments and provide access to better and affordable health care for affected patients.
Abstract Background In trauma, most hemorrhagic deaths occur within the first 6 hours. This study examined the effect on survival of high ratios of fresh frozen plasma (FFP) and platelets (PLTs) to ...packed red blood cells (PRBCs) in the first 6 hours. Methods Records of 466 massive transfusion trauma patients (≥10 U of PRBCs in 24 hours) at 16 level 1 trauma centers were reviewed. Transfusion ratios in the first 6 hours were correlated with outcome. Results All groups had similar baseline characteristics. Higher 6-hour ratios of FFP:PRBCs and PLTs:PRBCs lead to improved 6-hour mortality (from 37.3 in the lowest ratio group to 15.7 in the middle ratio group to 2.0% in the highest ratio group and 22.8% to 19.0% to 3.2%, respectively) and in-hospital mortality (from 54.9 to 41.1 to 25.5% and 43.7% to 46.8% to 27.4%, respectively). Initial higher ratios of FFP:PRBCs and PLTs:PRBCs decreased overall PRBC transfusion. Conclusions The early administration of high ratios of FFP and platelets improves survival and decreases overall PRBC need in massively transfused patients. The largest difference in mortality occurs during the first 6 hours after admission, suggesting that the early administration of FFP and platelets is critical.
Background
One of the main risk factors for non‐melanoma skin cancer (NMSC), the most common cancer worldwide, is solar ultraviolet radiation (UVR). This has led to the recognition of NMSC as ...occupational disease for outdoor workers in several countries. However, outdoor professions are a very heterogeneous group with diverse daily activities and associated UVR exposure.
Objective
To compare the prevalence of NMSC and associated risk behaviour in different outdoor professions.
Methods
Cross‐sectional study among outdoor workers (farmers, gardeners, mountain guides) and indoor workers (office employees) as control group using a paper‐based questionnaire on UVR exposure and protective behaviour followed by a skin examination by a dermatologist.
Results
A total of 563 participants (46.9% women, 46.9 ± 13.8 years) consisting of 348 outdoor workers (38.8% farmer, 35.3% gardener, 25.9% mountain guides) and 215 indoor workers were included in the study between March and September 2017. NMSC incl. actinic keratosis was diagnosed in 33.3% of mountain guides, 27.4% of farmers, 19.5% of gardeners and in 5.6% of indoor workers. Significant differences were seen between the outdoor professions with mountain guides at highest risk compared to farmers (OR = 2.6, 95% CI = 1.2–5.7). Substantial differences between the professions were also seen in skin cancer screening attendance rates (indoor worker 61.4%, mountain guides 57.8%, farmers 31.9%, gardeners 27.6%), daily UVR exposure during work and protective behaviour such as sunscreen use during work.
Conclusion
Different outdoor professions have significant different risks for NMSC and show different risk behaviour. Tailoring prevention efforts to different professions based on their individual needs could be the key to lower the global burden of (occupational) NMSC.
To evaluate the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score for serious infections in patients with rheumatoid arthritis (RA).
The RABBIT Risk Score for serious ...infections was developed in 2011 on a cohort of RA patients enrolled in the German biologics register RABBIT between 2001 and 2007. To evaluate this score, we used data from patients enrolled in RABBIT after 1 January 2009. Expected numbers of serious infections and expected numbers of patients with at least one serious infection per year were calculated by means of the RABBIT Risk Score and compared with observed numbers in the evaluation sample.
The evaluation of the score in an independent cohort of 1522 RA patients treated with tumour necrosis factor α (TNFα) inhibitors and 1468 patients treated with non-biological disease-modifying antirheumatic drugs (DMARDs) showed excellent agreement between observed and expected rates of serious infections. For patients exposed to TNF inhibitors, expected as well as observed numbers of serious infections were 3.0 per 100 patient-years (PY). For patients on non-biological DMARDs the expected and observed numbers were 1.5/100 PY and 1.8/100 PY, respectively. The score was highly predictive in groups of patients with low as well as with high infection risk.
The RABBIT Risk Score is a reliable instrument which determines the risk of serious infection in individual patients based on clinical and treatment information. It helps the rheumatologist to balance benefits and risks of treatment, to avoid high-risk treatment combinations and thus to make informed clinical decisions.
Scabies is a World Health Organization‐defined neglected tropical disease, with continuously rising incidence worldwide in recent years. The aim of this study was to provide an update of the ...worldwide prevalence and new treatment approaches of scabies in population‐based settings. MEDLINE (PubMed), Embase and LILACS databases were reviewed for English and German language population‐based studies from October 2014 to March 2022. Two authors independently screened the records for eligibility, extracted all data and one critically appraised the quality of the studies and risk of bias. Systematic review registration: PROSPERO CRD42021247140. Overall, 1273 records were identified through database searching, of which 43 studies were included for the systematic review. Most of the studies (n = 31) examined the scabies prevalence in medium or low human development index countries. The highest prevalence of scabies reported in the general population (children and adults) was recorded in five randomly selected communities in Ghana (71.0%), whereas the highest scabies prevalence in studies, which only examined children (76.9%), was recorded in an Indonesian boarding school. The lowest prevalence was recorded in Uganda (0.18%). The systematic review highlights the prevalence of scabies worldwide, showing that scabies is still a serious, increasing disease that occurs globally and is clustered in developing countries. More transparent data on scabies prevalence are needed to identify risk factors to find new prevention measures.
Background
Atopic dermatitis (AD) is one of the most common chronic skin diseases worldwide, showing various manifestations and having a severe impact on quality of life. As previous studies ...demonstrated, internet search analysis can help identify public interest in diseases and possible influencing factors on search behavior.
Objective
To identify AD‐related topics of interest in Germany using internet search volume.
Methods
Google Ads Keyword Planner was used to identify AD‐related search terms including their search volume in Germany on a national level as well as in 16 selected cities from January 2016 to December 2019. Identified keywords were qualitatively analyzed, and temporal trends as well as the influence of seasonal and environmental factors on search volume were assessed.
Results
Overall, 1222 AD‐related search terms with a search volume of 8 842 360 searches were identified. An increase from 2016 to 2019 and seasonal peaks from January to April of each year were observed. Nationwide, the search volume correlated with mean monthly temperature and sun duration. With increasing temperature and sun duration, a significant decrease in search queries was observed. The most populated cities showed the lowest number of searches per 100 000 inhabitants (Berlin, Hamburg, and Munich). In the eight categories formed (comorbidities, general, influential factors, localization, stage of life, symptoms/severity, therapy/information, and questions on AD), the highest proportion of search queries were assigned to the category “therapy/information” in most cities. In this category, a focus on the topics of “alternative medicine” and “home remedies“ could be observed.
Conclusion
The overall high and increasing search volume indicates a high interest in AD‐related topics, especially regarding treatment and disease education. Information provided by internet search volume analyses can optimize AD therapy and patient‐centered care by providing insight into patient needs and predicting potential climatic trigger factors.
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