A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: Ineffectiveness in head-and-neck dermatitis.

BACKGROUND: Evaluation of effectiveness and safety of new systemic treatments for atopic dermatitis (AD) after approval is important. There are few published data exceeding 52-week therapy with dupilumab. OBJECTIVES: To examine the safety, effectiveness and drug survival of dupilumab in a Danish nationwide cohort with moderate-to-severe AD up to 104 weeks exposure. METHODS: We included 347 adult patients with AD who were treated with dupilumab and registered in the SCRATCH registry during 2017-2022. RESULTS: At all visits, we observed improvement in AD severity measured by Eczema Area and Severity Index (EASI) [median (IQR)]. EASI score at baseline was 18.0 (10.6-25.2), at week 4: 6.5 (3.5-11.6), at week 16: 3.7 (1.2-6.2), at week 52: 2.0 (0.8-3.6), at week 104: 1.7 (0.8-3.8). While drug survival was high (week 52: 90%; week 104: 86%), AD in the head-and-neck area remained present in most patients at high levels; proportion with head-and-neck AD at baseline was 76% and 68% at week 104. 35% of patients reported any AE. Conjunctivitis was the most frequent (25% of all patients) and median time to first registration of conjunctivitis was 201 days. CONCLUSIONS: While 2-year drug survival was 86%, dupilumab was unable to effectively treat AD in the head-and-neck area, and conjunctivitis was found in 25% of patients.

Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH): A Danish Real-world Evidence Atopic Dermatitis Treatment Registry.

Data from real-world use of new systemic treatments in atopic dermatitis (AD) is important for assessing safety and efficacy. The aim of this study is to describe the baseline characteristics of adult patients with moderate-to-severe AD enrolled in the Danish nationwide Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH) database, between October 2017 and August 2021. A total of 282 adult patients were included. Most (62%) were men, the median age at baseline was 43 years (interquartile range (IQR) 29-54 years), and median age at onset of AD was 1 year (IQR 0-6 years). The median Eczema Area and Severity Index at treatment initiation was 19.1 (IQR 11.9-25.7); median Patient Oriented Eczema Measure 21.0 (IQR 16.0-25.0); median Dermatology Life Quality Index 13.0 (IQR 7.0-19.0); and median itch and sleep numerical rating scale scores 8.0 (IQR 6.0-9.0) and 6.0 (IQR 4.0-8.0). Differences were found between the sexes. This registry will provide a source for future efficacy and safety studies.

Patient-reported outcome measures (PROMs) and palliative-care clinician reported outcomes (ClinROs) mutually improve pain and other symptoms assessment of hospitalized cancer-patients.

OBJECTIVES: Patients with malignant diseases are known to have a high symptom burden including pain, and insufficient treatment of pain in this population has been frequently documented. To promote the integration of specialized palliative care and hematology and oncology, this study investigated disease, treatment, and comorbidity related symptoms as well as functional capacity and health-related quality of life (HQoL) by patient-reported outcome measures (PROMs) and clinician-reported outcome measures (ClinROs) among inpatients in a comprehensive cancer center. METHODS: This cross-sectional study was carried out in a large comprehensive cancer centre of both oncological and hematological inpatients. It combined the use of PROMs and ClinROs. RESULTS: A high symptom burden was reported with fatigue and appetite loss as the most frequent symptoms, and role function being the most impaired function. Further, a low HQoL score was associated with a high number of symptoms/impairments. More than half of all patients reported pain in the last 24 h. Out of 95 patients with average pain >0 in the last 24 h, 71% were treated with opioids and 24% were treated with adjuvant analgesic (AA) defined as antiepileptics, antidepressants and prednisolone. Out of 57 patients with average pain >0 in the last 24 h and possible neuropathic pain, 33% were treated with AAs. A high odds ratio for moderate/severe pain in patients with possible neuropathic pain mechanisms was observed. CONCLUSIONS AND IMPLICATIONS: This study did not only emphasize the need for systematic use of PROMs to identify symptoms and needs for inpatients, but also displayed why PROMs supported by ClinROs are a prerequisite to deliver truly individualized and high-quality patient-centered care. This study calls for continuous training of health care professionals to deliver high-quality treatment of pain. Further, it contributes to the growing recognition, that palliative care and standard care must be integrated to strengthen patient-centered care.

'Sea of blood': the intended and unintended effects of criminalising humanitarian volunteers assisting migrants in distress at sea.

This paper investigates the impact of the recent criminalisation of humanitarian actors engaged in the search for and rescue of migrants in distress in the Mediterranean Sea, focusing on the impact on the motivation and engagement of humanitarian volunteers in Greece. It argues that criminalisation is aimed at reducing search and rescue (SAR) activities and thus removing perceived 'pull factors' for migrants. The paper locates this phenomenon within the broader trend of policing and punishing those who assist migrants in order to deter them and prevent others from engaging in such endeavours. It finds that efforts to criminalise can have the unintended effects of encouraging and mobilising volunteers, as well as generating public attention and support for migrants. However, the negative consequences of criminalisation are far-reaching, including contributing to a high mortality rate among those crossing the Mediterranean without SAR capabilities and the heightened risk of violence against migrants and those who help them.

Bidirectional association between atopic dermatitis, conjunctivitis, and other ocular surface diseases: A systematic review and meta-analysis.

BACKGROUND: Conjunctivitis and several other ocular surface diseases (OSDs) have been linked to atopic dermatitis (AD) and its treatment. OBJECTIVES: To examine the association between AD, conjunctivitis, and other OSDs. METHODS: A systematic review and meta-analysis was performed. Two authors independently searched EMBASE, PubMed, SCOPUS, and Web of Science and performed title/abstract and full-text review and data abstraction. Pooled random-effects prevalence and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. RESULTS: The search yielded 5719 nonduplicate articles; 134 were included in the quantitative analysis. AD was associated with conjunctivitis compared to reference individuals (OR, 2.78; 95% CI, 2.33-3.32); the prevalences of conjunctivitis in patients with AD and reference individuals were 31.7% (95% CI, 27.7-35.9) and 13.3% (95% CI, 11.0-15.7), respectively. Keratoconus (OR, 3.71; 95% CI, 1.99-6.94) and ocular herpes simplex (OR, 3.65; 95% CI 2.04-6.51) were also associated with AD. LIMITATIONS: Disease definitions differed and often relied on self-reports. Few studies provided data concerning AD phenotype or OSDs other than conjunctivitis. CONCLUSIONS: Conjunctivitis is the most common ocular comorbidity in AD. Signs and symptoms of conjunctivitis and other OSDs in AD may be underreported, making proactive inquiry and examination by physicians treating patients with AD important.

Occupational therapy and physiotherapy interventions in palliative care: a cross-sectional study of patient-reported needs.

INTRODUCTION: An interdisciplinary team approach to patients in specialised palliative care is recommended; however, the composition of the professionals tends to vary, and the roles of physiotherapists and occupational therapists may be underestimated. We aimed to investigate patient-reported unmet needs, which potentially could benefit from physiotherapy and occupational therapy interventions in a specialised palliative care team. METHODS: Adult patients with chronic advanced diseases referred to the Specialised Palliative Care Team at Copenhagen University Hospital, Rigshospitalet were enrolled in the study. The Three-Levels-of-Needs Questionnaire was used as primary outcome to assess symptom/problem intensity, symptom/problem burden and felt needs for 12 commonly reported symptoms/problems for patients referred to a specialised palliative care team. Furthermore, participants' level of distress, fatigue and physical activity, symptoms of anxiety and depression, and barriers towards the rehabilitation programme were registered with other measures. RESULTS: In total, 43 of 67 (64%) patients participated. The majority of participants reported severe symptoms/problems concerning fatigue (81%), impaired physical activities (77%), carrying out work and daily activities (77%), pain (72%), and worries (58%). Furthermore, need for help was expressed concerning physical activities (79%), work and daily activities (77%), fatigue (70%), pain (65%), concentration (58%) and worries (51%). On average the patients characterised 6 (out of 12) symptoms/problems as severe. CONCLUSION: Patients referred to a specialised palliative care team reported extensive unmet needs concerning physical activities, work and daily activities, fatigue, pain, concentration and worries. Unmet needs that potentially could be alleviated by physiotherapists or occupational therapists implemented in the interdisciplinary team.

[Health and healthcare in Greenland].

The Greenlandic society has changed rapidly within the last decades. Most of the population have good housing and access to clean water and sanitation. The neonatal and infant mortality is low, and the physical health of the children is good. Although tuberculosis is still common, lifestyle-related conditions and diseases are now of major public health importance. Sexual health has many challenges, and the suicide rate is extremely high. The healthcare system offers services on an international level, although huge distances and difficult access to advanced medical services is a challenge, which is discussed in this review.

The First Steps Taken to Implement Palliative Care in Advanced Heart Disease: A Position Statement from Denmark.

According to the World Health Organization, palliative care must be available for everyone with life-threatening diseases. However, in daily practice the primary focus worldwide is on cancer patients. The aim of the article was to generate a national position statement as the first step in implementing palliative care in severe heart disease with focus on advanced heart failure, including tools to identify the need for and timing of palliative care and how palliative care could be organized in Denmark. A task force was formed in the Danish Society of Cardiology Heart Failure Working Group, and the position statement was prepared in collaboration with members from a broad group of specialties, including palliative medicine. Because of major gaps in evidence, the position statement was based on small and low-quality studies and clinical practice statements. This position statement was aligned with the European Society of Cardiology recommendation, focusing on relieving suffering from the early disease stages parallel to standard care and supplementing life-prolonging treatment. The statement delivers practical guidance on clinical aspects and managing symptoms during the three stages of advanced heart disease. Furthermore, the statement describes the importance of communication and topics to be broached, including deactivating implantable cardioverter defibrillators. The statement recommends a targeted effort on organizational strategies using high-quality assessment tools and emphasizes multidisciplinary and intersectoral collaboration. Danish cardiologists supported by allied professionals acknowledge the importance of palliative care in advanced heart disease. This national position statement intended to inform and influence policy and practice and can hopefully inspire other countries to take action toward implementing palliative care in advanced heart disease.

Including Life Cycle Assessment for decision-making in controlling wastewater nutrient removal systems.

This paper focuses on the use of Life Cycle Assessment (LCA) to evaluate the performance of seventeen control strategies in wastewater treatment plants (WWTPs). It tackles the importance of using site-specific factors for nutrient enrichment when decision-makers have to select best operating strategies. Therefore, the LCA evaluation is repeated for three different scenarios depending on the limitation of nitrogen (N), phosphorus (P), or both, when evaluating the nutrient enrichment impact in water bodies. The LCA results indicate that for treated effluent discharged into N-deficient aquatic systems (e.g. open coastal areas) the most eco-friendly strategies differ from the ones dealing with discharging into P-deficient (e.g. lakes and rivers) and N&P-deficient systems (e.g. coastal zones). More particularly, the results suggest that strategies that promote increased nutrient removal and/or energy savings present an environmental benefit for N&P and P-deficient systems. This is not the case when addressing N-deficient systems for which the use of chemicals (even for improving N removal efficiencies) is not always beneficial for the environment. A sensitivity analysis on using weighting of the impact categories is conducted to assess how value choices (policy decisions) may affect the management of WWTPs. For the scenarios with only N-limitation, the LCA-based ranking of the control strategies is sensitive to the choice of weighting factors, whereas this is not the case for N&P or P-deficient aquatic systems.

Paradigm of pretest risk stratification before coronary computed tomography.

BACKGROUND: The optimal method of determining the pretest risk of coronary artery disease as a patient selection tool before coronary multidetector computed tomography (MDCT) is unknown. OBJECTIVE: We investigated the ability of 3 different clinical risk scores to predict the outcome of coronary MDCT. METHODS: This was a retrospective study of 551 patients consecutively referred for coronary MDCT on a suspicion of coronary artery disease. Diamond-Forrester, Duke, and Morise risk models were used to predict coronary artery stenosis (>50%) as assessed by coronary MDCT. The models were compared by receiver operating characteristic analysis. The distribution of low-, intermediate-, and high-risk persons, respectively, was established and compared for each of the 3 risk models. RESULTS: Overall, all risk prediction models performed equally well. However, the Duke risk model classified the low-risk patients more correctly than did the other models (P < 0.01). In patients without coronary artery calcification (CAC), the predictive value of the Duke risk model was superior to the other risk models (P < 0.05). Currently available risk prediction models seem to perform better in patients without CAC. Between the risk prediction models, there was a significant discrepancy in the distribution of patients at low, intermediate, or high risk (P < 0.01). CONCLUSIONS: The 3 risk prediction models perform equally well, although the Duke risk score may have advantages in subsets of patients. The choice of risk prediction model affects the referral pattern to MDCT.

Externality and materiality as themes in the history of the human sciences

This article presents and discusses some attempts to overcome the "Cartesian" dualism of "mind versus matter" and "interior versus exterior", in particular the attempts of anthropologist Tim Ingold in his book "The Perception of the Environment" (2000). Central to Ingold's argument is a shift in focus from structure to process (temporality), from design to growth, from the organism in a context to organism and environment as co-evolutionary and co-constitutive entities. Ingold builds on ecological thinking (Bateson and Gibson) and phenomenology (Merleau-Ponty and Heidegger). This article characterises Ingold's position as a neo-romantic reaction to the "linguistic turn" in the human sciences and the "genetic turn" in biology and compares his position to historical romanticism.(AU)

Externality and materiality as themes in the history of the human sciences

This article presents and discusses some attempts to overcome the 'Cartesian' dualism of 'mind versus matter' and 'interior versus exterior', in particular the attempts of anthropologist Tim Ingold in his book 'The Perception of the Environment' (2000). Central to Ingold's argument is a shift in focus from structure to process (temporality), from design to growth, from the organism in a context to organism and environment as co-evolutionary and co-constitutive entities. Ingold builds on ecological thinking (Bateson and Gibson) and phenomenology (Merleau-Ponty and Heidegger). This article characterises Ingold's position as a neo-romantic reaction to the 'linguistic turn' in the human sciences and the 'genetic turn' in biology and compares his position to historical romanticism.(AU)

Assessing health-related quality of life in palliative care: comparing patient and physician assessments.

It is often difficult to recruit patients for palliative care studies and severe attrition must be expected resulting in biased findings. This may be avoided if equivalent information could be obtained from sources other than the patients. Therefore, we investigated whether physician assessments can be used to evaluate the patients' health-related quality of life (HRQOL). Patient and physician assessments of the patients' HRQOL were obtained once a week for up to 13 weeks using EORTC QLQ-C30 items. The agreement between patients and physicians at first contact (N=115) and for the following 13 weeks combined (total N=263) was investigated. Significant differences between patient and physician assessments were observed for all HRQOL domains assessed. Physicians reported patients to have fewer problems/symptoms than patients did for all HRQOL domains except for physical and social functioning. The agreement between patients and physicians was poor. Using physician assessments may bias findings and cannot be recommended as a substitute for patient self-assessment in palliative care.

Training response of adolescent Kenyan town and village boys to endurance running.

To investigate the response to endurance training on physiological characteristics, 10 Nandi town boys and 14 Nandi village boys 16.5 and 16.6 years of age, respectively, from western Kenya performed 12 weeks of running training. The study was performed at altitude (approximately 2000 m.a.s.l. approximately 595 mm Hg). Training heart rate and speed were registered during every training session throughout the entire training period. While town and village boys trained at similar heart rates (172.1 vs. 172.5 beats min(-1)), the training speed of the town boys was 9% lower compared with the village boys (12.4 vs. 13.6 km h(-1), P<0.001). Significant increases in VO2max were observed in the town boys (from 50.3 to 55.6 mL kg(-1) min(-1), P<0.001) and in village boys (from 56.0 to 59.1 mL kg(-1) min(-1), P<0.002). Significant decreases in submaximal heart rate (from 172.4 to 160.3 beats min(-1) (P<0.005)), blood lactate (from 2.7 to 1.4 mmol L(-1) (P<0.005)) and ammonia concentration (from 102.0 to 71.4 micromol L(-1) (P<0.01)) at 9.9 km h(-1) were observed in the town boys, while similar decreases in heart rate (from 170.2 to 159.2 beats min(-1) (P<0.001)), blood lactate (from 2.4 to 1.4 mmol L(-1) (P<0.001)) and ammonia concentration (from 102.5 to 72.7 micromol L(-1) (P<0.001)) at 10.9 km h(-1) were observed in the village boys. The oxygen cost of running was decreased from 221.5 to 211.5 mL kg(-1) km(-1) (P<0.03) in the town boys and from 220.1 to 207.2 mL kg(-1) km(-1) (P<0.01) in the village boys. The 5000 m performance time of the town boys was significantly greater than that of the village boys (20.25 vs. 18.42 min (P = 0.01)). It is concluded that no difference was observed in trainability with respect to VO2max, running economy, submaximal heart rate, and submaximal blood lactate and ammonia concentration between Kenyan Nandi town and village boys. The higher performance level of the village boys was likely due to a higher VO2max of these boys.

Kenyan dominance in distance running.

Critical physiological factors for performance in running are maximal oxygen consumption (VO(2max)), fractional VO(2max) utilization and running economy. While Kenyan and Caucasian elite runners are able to reach very high, but similar maximal oxygen uptake levels, the VO(2max) of black South African elite runners seems to be slightly lower. Moreover, the studies of black and white South African runners indicate that the former are able to sustain the highest fraction of VO(2max) during long distance running. Results on adolescent Kenyan and Caucasian boys show that these boys are running at a similar percentage of VO(2max) during competition. Kenyan elite runners, however, appear to be able to run at a high % of VO(2max) which must then have been achieved by training. A lower energy cost of running has been demonstrated in Kenyan elite runners and in untrained adolescent Kenyan boys compared to their Caucasian counterparts. In agreement with this are the results from studies on black South African elite runners who have shown similar low energy costs during running as the Kenyan elite runners. The good running economy cannot be explained by differences in muscle fibre type as they are the same in Kenyan and Caucasian runners. The same is true when comparing untrained adolescent Kenyan boys with their Caucasian counterparts. A difference exists in BMI and body shape, and the Kenyans long, slender legs could be advantageous when running as the energy cost when running is a function of leg mass. Studies comparing the response to training of Kenyans and Caucasians have shown similar trainability with respect to VO(2max), running economy and oxidative enzymes. Taken all these data together it appears that running at a high fractional VO(2max) and having a good running economy may be the primary factors favouring the good performance of endurance athletes rather than them having a higher VO(2max) than other elite runners. In addition to having the proper genes to shape their bodies and thereby contributing to a good running economy, the Kenyan elite runners have trained effectively and used their potential to be in the upper range both in regard to VO(2max) and to a high utilization of this capacity during endurance running.

Comparison of the combined monitoring-based and modelling-based priority setting scheme with partial order theory and random linear extensions for ranking of chemical substances.

The combined monitoring-based and modelling-based priority setting scheme (COMMPS) used to establish a priority setting list within the EU Water Framework Directive plays a major role in the European environmental policy on chemical substances. The COMMPS procedure can be classified as a so-called scoring method. The applied functional relationship and weight factors are established based on expert judgement, which unfortunately appears to be vulnerable to subjective inputs. In this study an alternative priority setting methods based on partial order theory (POT) and random linear extensions (RLE) is suggested and compared to the COMMPS procedure. The POT/RLE is characterised as being based on fewer assumptions concerning functional relationships and does not apply weighting factors. Using the POT/RLE methodology a different ranking result occur than when using the COMMPS procedure. Eight of the top 20 substances from the COMMPS procedure are not ranked within the top 20 when using POT/RLE. From the viewpoint of environmental protection, especially the substances that have been given low priority in the COMMPS procedure, but a high rank in POT/RLE, are of interest in a regulatory context. These substances are naphthalene, trichloromethane, isoproturon, metolachlor, endosulfan, acenaphthene, alachlor and dichloromethane. An analysis of the ability of the descriptors to separate the single substance discloses that the most significant descriptor is the concentrations detected in the environment. Further, the frequency of detection is not applied as a descriptor in the COMMPS procedure. However, if this descriptor was to be applied the analysis revealed that it would have been the third most significant descriptor.