Work Disability and Return to Work After Treatment for Acute Lymphoblastic Leukemia: A Danish Nationwide Cohort Study.

Purpose: Most adult patients diagnosed with acute lymphoblastic leukemia (ALL) are below retirement age. The overall survival of patients with ALL has improved with implementation of high intensity pediatric-inspired treatment protocols. However, this treatment comes with a risk of long-term complications, which could affect the ability to work. The aim of this study was to investigate the risk of disability pension (DP) and return to work (RTW) for patients with ALL. Patients and Methods: Patients aged 18-60 years diagnosed with ALL between 2005 and 2019 were identified in the Danish National Acute Leukemia Registry. Each patient was matched with five comparators from the general population on birth year, sex, and Charlson Comorbidity Index. The Aalen-Johansen estimator was used to calculate the cumulative risk of DP for patients and comparators from index date (defined as 1 year after diagnosis) with competing events (transplantation or relapse, death, retirement pension, or early retirement pension). Differences in cumulative incidences were calculated using Gray's test. RTW was calculated as proportions one, three, and five years after the index date for patients holding a job before diagnosis. Results: A total of 154 patients with ALL and 770 matched comparators were included. The 5-year cumulative risk of DP was increased fivefold for patients with ALL compared with the general population. RTW was 41.7%, 65.7%, and 60.7% one, three, and five years after the index date, respectively. Conclusion: The risk of DP in patients with ALL increased significantly compared with the general population. Five years after the index date, RTW was 60.7% for patients with ALL.

Online Physical Exercise and Group Sessions to Increase and Maintain Physical Activity in Individuals with Type 2 Diabetes: A Single-Arm Feasibility Study.

Current physical activity interventions for individuals with Type 2 diabetes do not accommodate the needs of the individual in terms of content, time, and location. The aim of this study was to evaluate the feasibility and acceptability of an 8-week high intensity online physical exercise intervention combined with online group meetings and supported by an activity watch in individuals with Type 2 diabetes. This study was designed as a one-armed feasibility study and the intervention was developed using a co-creation approach. A total of 19 individuals with Type 2 diabetes participated in eight weeks of 30 min online physical exercise intervention followed by 30 min online group meetings in smaller groups once a week. Outcomes included pre-defined research progression criteria, secondary measurements of health parameters, and participant feedback. Most research progression criteria reached a level of acceptance, with the exception of participant recruitment, burden of objectively measured physical activity, and adverse events, where changes are needed before continuing to an RCT. Combining online physical exercise with online group meetings supported by an activity watch is feasible and acceptable in individuals with Type 2 diabetes with a higher educational level compared to the general population with Type 2 diabetes.

DNA methyltransferase inhibition promotes recruitment of myeloid-derived suppressor cells to the tumor microenvironment through induction of tumor cell-intrinsic interleukin-1.

DNA methyltransferase (DNMT) inhibitors are used for treatment of certain hematological malignancies and exert anti-cancer activity through diverse mechanisms, including reexpression of tumor suppressor genes and anti-viral responses triggered by expression of endogenous retroviruses. Despite advances in the pharmacokinetic properties of DNMT inhibitors, the efficacy of these drugs in solid cancers remains low. Here, we show in cell lines and clinical and experimental tumors across multiple cancer types that DNMT inhibition induces the expression of interleukin-1 (IL-1), a cytokine with proinflammatory and protumorigenic properties. Specifically, this tumor-intrinsic IL-1 expression modulates the chemokine landscape of tumors and leads to the recruitment of monocytic myeloid-derived suppressor cells to the tumor microenvironment, processes that can be blocked by IL-1 antagonists. Molecular analysis demonstrates complex patterns of IL-1 and interferon activation and crosstalk in response to DNMT inhibition, which depend on the integrity of IRF- and NF-κB-mediated antiviral pathways and may determine the outcome of DNMT-inhibitor treatment. Together, our results show that DNMT inhibitors may negatively affect the microenvironment of a large subset of tumors and suggest that co-treatment with IL-1 antagonists may be a favorable combination for these patients.

COVID-19 as moral breakdown: Entangled ethical demands experienced by hospital-based nurses in the early onset of the pandemic.

2020 saw the rapid onset of a global pandemic caused by the SARS-CoV-2 virus. For healthcare systems worldwide, the pandemic called upon quick organization ensuring treatment and containment measures for the new virus disease. Nurses were seen as constituting a vital instrumental professional component in this study. Due to the pandemic's unpredictable and potentially dangerous nature, nurses have faced unprecedented risks and challenges. Based on interviews and free text comment from a survey, this study explores how ethical challenges related to "being a nurse" during the COVID-19 pandemic was experienced and understood by Danish hospital-based nurses. Departing from anthropologist Jarett Zigon's notion of moral breakdown, the study demonstrates how the rapid onset of the pandemic constitutes a moral breakdown raising ethical demands for nurses. Analytically we identify three different ethical demands experienced by the nurses. These ethical demands are Nursing and societal ethical demands, Nursing and personal ethical demands, and Nursing and conflicting ethical demands. These demands represent not only very different understandings of ethical demands but also different understandings of ethical acts that are seen as necessary to respond to these demands.

Mental Fatigue, Activities of Daily Living, Sick Leave and Functional Status among Patients with Long COVID: A Cross-Sectional Study.

Studies suggest that persistent symptoms after COVID-19 (long COVID) influence functioning and activities of daily living (ADL). However, it is still uncertain how and to what extent. This study aimed to describe patient-reported mental fatigue, ADL problems, ADL ability, sick leave and functional status among patients with long COVID. In this cross-sectional study, 448 patients, ≥18 years old and referred to occupational therapy at a Danish Post-COVID-19 Clinic, were included. Mental fatigue was measured by the Mental Fatigue Scale, ADL problems and ability were measured by the Canadian Occupational Performance Measure, sick leave was self-reported and functional status was evaluated by the Post-COVID-19 Functional Status Scale. Mean age was 46.8 years, 73% of the patients were female, and 75% suffered from moderate to severe mental fatigue. The majority reported difficulties performing productive and leisure activities. The median performance and satisfaction scores were 4.8 and 3, respectively. In total, 56% of the patients were on sick leave, and 94% were referred to rehabilitation. A decrease in functional status was found between pre-COVID-19 and assessment. Conclusively, the patients were highly affected in their everyday life and had distinct rehabilitation needs. Future research is needed to address causalities and rehabilitation for this patient group.

Opsonophagocytosis of Chlamydia pneumoniae by Human Monocytes and Neutrophils.

The human respiratory tract pathogen Chlamydia pneumoniae, which causes mild to severe infections, has been associated with the development of chronic inflammatory diseases. To understand the biology of C. pneumoniae infections, several studies have investigated the interaction between C. pneumoniae and professional phagocytes. However, these studies have been conducted under nonopsonizing conditions, making the role of opsonization in C. pneumoniae infections elusive. Thus, we analyzed complement and antibody opsonization of C. pneumoniae and evaluated how opsonization affects chlamydial infectivity and phagocytosis in human monocytes and neutrophils. We demonstrated that IgG antibodies and activation products of complement C3 and C4 are deposited on the surface of C. pneumoniae elementary bodies when incubated in human serum. Complement activation limits C. pneumoniae infectivity in vitro and has the potential to induce bacterial lysis by the formation of the membrane attack complex. Coculture of C. pneumoniae and freshly isolated human leukocytes showed that complement opsonization is superior to IgG opsonization for efficient opsonophagocytosis of C. pneumoniae in monocytes and neutrophils. Neutrophil-mediated phagocytosis of C. pneumoniae was crucially dependent on opsonization, while monocytes retained minor phagocytic potential under nonopsonizing conditions. Complement opsonization significantly enhanced the intracellular neutralization of C. pneumoniae in peripheral blood mononuclear cells and neutrophils and almost abrogated the infectious potential of C. pneumoniae In conclusion, we demonstrated that complements limit C. pneumoniae infection in vitro by interfering with C. pneumoniae entry into permissive cells by direct complement-induced lysis and by tagging bacteria for efficient phagocytosis in both monocytes and neutrophils.

Lactate level, aetiology and mortality of adult patients in an emergency department: a cohort study.

BACKGROUND: Increased lactate is associated with high mortality among patients with suspected infection or trauma in the emergency department (ED), but the association with patients with other aetiologies is less well described. The aim of this study was to describe the relation between lactate, aetiology and 7-day mortality in adult ED patients. METHODS: A retrospective cohort study of all adult patients who had a lactate measured within 4 h after arrival to the ED at Odense University Hospital between June 2012 and May 2013. The categorisation of suspected aetiology was based on discharge diagnoses. RESULTS: 5360 patients were included; 51.7% were men, and the median age was 67 years (IQR 50-79). 77.2% had low lactate (0-1.9 mmol/L), 16.2% intermediate lactate (2-3.9 mmol/L), and 6.6% high lactate (≥4 mmol/L). 7-day mortality was 2.9% (95% CI 2.4% to 3.5%) for patients with low lactate, 7.8% (95% CI 6.1% to 9.8%) for patients with intermediate lactate, and 23.9% (95% CI 19.6% to 28.8%) for patients with high lactate. The association between lactate level and mortality varied across different diagnostic groups. Based on Area Under the Curve in receiver operating characteristic analysis, lactate level showed to be useful in patients with infection (0.78, 95% CI 0.73 to 0.84), trauma (0.78, 95% CI 0.65 to 0.92), cardiac diseases (0.83, 95% CI 0.75 to 0.91) and gastrointestinal diseases (0.83, 95% CI 0.68 to 0.98). Lactate level was not useful in neurological (0.58, 95% CI 0.50 to 0.67) and respiratory disease (0.64, 95% CI 0.55 to 0.74), and of uncertain value in the remaining diagnostic groups. CONCLUSIONS: Among adult ED patients, the prognostic value of lactate varies between diagnostic groups.

Long-Term Effect of Interactive Online Dietician Weight Loss Advice in General Practice (LIVA) Protocol for a Randomized Controlled Trial.

Background. Internet-based complex interventions aiming to promote weight loss and optimize healthy behaviors have attracted much attention. However, evidence for effect is lacking. Obesity is a growing problem, resulting in an increasing demand for cost efficient weight loss programs suitable for use on a large scale, for example, as part of standard primary care. In a previous pilot project by Brandt et al. (2011) without a control group, we examined the effects of online dietician counseling and found an average weight loss of 7.0 kg (95% CI: 4.6 to 9.3 kg) after 20 months. Aims and Methods. To analyze the effects of a complex intervention using trained dieticians in a general practice setting combined with internet-based interactive and personalized weight management support compared with conventional advice with a noninteractive internet support as placebo treatment in 340 overweight patients during a 2-year period. Primary endpoints are weight loss and lowering of cholesterol (LDL). We will also explore patients' sociodemographics and use of the intervention as well as the health professionals' views and perceptions of the intervention (their role and the advice and support that they provide). Perspective. The project will generate knowledge on the cost-effectiveness of a complex internet-based intervention in a general practice setting and on barriers and acceptability among professionals and patients.