Incidence and survival of primary metastatic breast cancer in Denmark; implication of breast cancer screening, classification, and staging practice.

BACKGROUND: Primary metastatic breast cancer (pMBC) accounts for 5-10% of annual breast cancers with a median survival of 3-4 years, varying among subtypes. In Denmark, the incidence of breast cancer increased until 2010, followed by a stabilisation. Several factors influencing pMBC incidence and survival, including screening prevalence, staging methods, and classification standards, remain pivotal but inadequately documented. MATERIAL AND METHOD: This retrospective observational study involving pMBC patients diagnosed between 2000 and 2020 encompassed all Danish oncology departments. Data from the Danish Breast Cancer Group database and the National Patient Register included diagnosis specifics, demographics, treatment, and follow-up. RESULTS: Between 2000 and 2020, 3,272 patients were diagnosed with pMBC, a rise from 355 patients in 2000-2004 to 1,323 patients in 2015-2020. The increase was particularly observed in patients aged 70 years or older. Changes in tumour subtypes were observed, notably with a rise in human epidermal growth factor receptor 2 (HER2)-positive cases but a steady distribution of estrogen receptor (ER) status. Diagnostic practices changed over the two decades, with 6% evaluated with PET/CT (positron emission tomography-computed tomography) or CT (computed tomography) with a bone evaluation in 2000-2004 and 65% in 2015-2020. Overall survival (OS) improved from 23 months in 2000-2004 to 33 months in 2015-2020. In patients with ER-positive and HER2-positive disease, the multivariable model showed improved survival by year of diagnosis, and further, patients with ER-negative/HER2-negative disease fared worse the first 2 years after diagnosis. INTERPRETATION: Our study delineates changes in the treatment and survival of pMBC over two decades. Stage migration, screening introduction, and changes in registration practice, however, prevent a valid assessment of a possible causal relationship.

ProTarget: a Danish Nationwide Clinical Trial on Targeted Cancer Treatment based on genomic profiling - a national, phase 2, prospective, multi-drug, non-randomized, open-label basket trial.

BACKGROUND: An increasing number of trials indicate that treatment outcomes in cancer patients with metastatic disease are improved when targeted treatments are matched with druggable genomic alterations in individual patients (pts). An estimated 30-80% of advanced solid tumors harbor actionable genomic alterations. However, the efficacy of personalized cancer treatment is still scarcely investigated in larger, controlled trials due to the low frequency and heterogenous distribution of druggable alterations among different histologic tumor types. Therefore, the overall effect of targeted cancer treatment on clinical outcomes still needs investigation. STUDY DESIGN/METHODS: ProTarget is a national, non-randomized, multi-drug, open-label, pan-cancer phase 2 trial aiming to investigate the anti-tumor activity and toxicity of currently 13 commercially available, EMA-approved targeted therapies outside the labeled indication for treatment of advanced malignant diseases, harboring specific actionable genomic alterations. The trial involves the Danish National Molecular Tumor Board for confirmation of drug-variant matches. Key inclusion criteria include a) measurable disease (RECIST v.1.1), b) ECOG performance status 0-2, and c) an actionable genomic alteration matching one of the study drugs. Key exclusion criteria include a) cancer type within the EMA-approved label of the selected drug, and b) genomic alterations known to confer drug resistance. Initial drug dose, schedule and dose modifications are according to the EMA-approved label. The primary endpoint is objective response or stable disease at 16 weeks. Pts are assigned to cohorts defined by the selected drug, genomic alteration, and tumor histology type. Cohorts are monitored according to a Simon's two-stage-based design. Response is assessed every 8 weeks for the first 24 weeks, then every 12 weeks. The trial is designed similar to the Dutch DRUP and the ASCO TAPUR trials and is a partner in the Nordic Precision Cancer Medicine Trial Network. In ProTarget, serial fresh tumor and liquid biopsies are mandatory and collected for extensive translational research including whole genome sequencing, array analysis, and RNA sequencing. DISCUSSION: The ProTarget trial will identify new predictive biomarkers for targeted treatments and provide new data and essential insights in molecular pathways involved in e.g., resistance mechanisms and thereby potentially evolve and expand the personalized cancer treatment strategy. PROTOCOL VERSION: 16, 09-MAY-2022. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04341181. Secondary Identifying No: ML41742. EudraCT No: 2019-004771-40.

Treatment of urinary incontinence in overweight women by a multidisciplinary lifestyle intervention.

PURPOSE: Urinary incontinence (UI) is a frequent and complex condition that negatively affects women's quality of life (QoL). Weight loss and pelvic floor muscle training (PFMT) are first-line treatments of UI. The study aimed to reduce the symptoms of UI on QoL in overweight women by a multidisciplinary intervention including diet, physical exercise, and PFMT. METHODS: In this non-blinded prospective interventional study, women with stress or mixed UI were included in an intervention combining dietary counseling, physical exercise in groups, and individually planned PFMT. The primary outcome measure was the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). The Patient Global Impression of Improvement (PGI-I) was used at 12 and 36 weeks. Also, anthropometric measures, pelvic floor muscle strength (PFMS), and physical performance were measured at baseline, 12, and 36 weeks. The primary aim of this study was to reduce the ICIQ-UI SF score by minimum of 2.6 points. RESULTS: Thirty-three women participated in the study. Nine dropped out during the intervention. The ICIQ-UI SF score was reduced by 6.8 and 4.5 points at 12 and 36 weeks, respectively. PGI-I revealed satisfaction with the results. Furthermore, weight was reduced by 2.6 and 3.6 kg at 12 and 36 weeks, respectively, and PFMS improved significantly. CONCLUSION: Despite a limited mean weight loss of 3.6 kg, participants reported a significant decrease in the symptoms and the burden of UI. Using PFMT as an integrated part of the intervention might have contributed to the improvements and could be subject to future research.

Alcohol screening in North Denmark Region hospitals: Frequency of screening and experiences of health professionals.

BACKGROUND: Alcohol consumption is a risk factor for disease, disability and death. Approximately 20% of all hospital admissions are alcohol related. In Denmark, hospitalised patients undergo systematic health risk screenings to establish preventive initiatives if the screening detects a risk. The frequency and usability of alcohol screening and health professionals' experiences of the screening is unknown. AIM: To examine the frequency and usability of alcohol screening at North Denmark Region hospitals, as well as health professionals' experiences of screening for alcohol. METHODS: This study consisted of an initial audit of 120 patient records from medical and surgical units at four hospitals assessing information on alcohol screening. This was followed by six focus-group interviews with health professionals (n = 20) regarding their experiences of conducting alcohol screening. RESULTS: Among overall health screenings, screening for alcohol and tobacco smoking was performed most frequently (81.8% and 85%). Alcohol screening scored the lowest percentage for usability (67.7%). Hospital-based alcohol screening was perceived ambiguously leading to a schism between standardised alcohol screening and the individual needs of the patient. Health professionals described different patient types, each with their perceived needs, and screening was associated with taboo and reluctance to engage in alcohol screening of some patient groups. CONCLUSION: This study revealed factors that influence health professionals working with hospital-based alcohol screening. The variation in and complexity of alcohol screening suggests that screening practice is an ambiguous task that needs continuous reflection and development to ensure that health professionals are prepared for the task.

Impact of NaCl reduction in Danish semi-hard Samsoe cheeses on proliferation and autolysis of DL-starter cultures.

Reduction of sodium chloride (NaCl) in cheese manufacturing is a challenge for the dairy industry. NaCl has a profound role on microbial development influencing cheese sensory and technological properties. The purpose of this work was to investigate how proliferation, distribution and autolysis of two commercial DL-starter cultures (C1 and C2) used in the production of Danish semi-hard Samsoe cheeses were affected by reduced NaCl levels. Cheeses containing <0.3% (unsalted), 2.3% (reduced-salt) and 3.4% (normal-salted) (w/v) NaCl in moisture were produced and analyzed during 12 weeks of ripening. Lactic acid bacteria (LAB), distribution of bacteria as single cells or microcolonies, their viability in the cheeses and cell autolysis were monitored during ripening, as well as the impact of NaCl content and autolysis on the formation of free amino acids (FAA). Reduction of NaCl resulted in higher LAB counts at the early stages of ripening, with differences between the two DL-starter cultures. The unsalted cheeses produced with C1 had retained a significantly higher number of the initial LAB counts (cfu/g) after 1 and 2 weeks of ripening (i.e. 58% and 71%), compared to the normal-salted cheeses (i.e. 22% and 21%), whereas no significant difference was found between the reduced-salt (i.e. 31% and 35%) and normal-salted cheeses. At the later stages of ripening (i.e. 7 and 11 weeks) NaCl had no significant influence. For cheeses produced with C2, a significant influence of NaCl was only found in cheeses ripened for 7 weeks, where the unsalted and reduced-salt cheeses had retained a significantly higher number of the initial LAB counts (cfu/g) (i.e. 39% and 38%), compared to the normal-salted cheeses (i.e. 21%). In the Samsoe cheeses, bacteria were organized as single cells, in groups of 2-3 cells or in groups of ≥4 cells. During ripening the decrease in the number of viable bacteria was mainly due to a reduction in the number of viable bacteria organized in groups of ≥4 cells. A negative correlation between NaCl content and PepX activity was observed. At the end of ripening the total FAA content was lower in the unsalted cheeses, compared to the reduced- and normal-salted cheeses. In conclusion, NaCl had a significant influence on proliferation of both DL-starter cultures. However, the influence of NaCl on culture development was more pronounced in cheeses produced with DL-starter culture C1. As both texture and taste are parameters known to be affected by the development of the starter culture, the design of starter cultures for reduced NaCl cheeses is recommended.

Elevated costs and high one-year mortality in patients with diabetic foot ulcers after surgery.

INTRODUCTION: In Denmark, approximately 300,000 patients have a diabetes mellitus diagnosis. Recently published guidelines emphasise that health-care professionals who are in direct contact with citizens should be aware of the importance of prevention and early detection of diabetic foot ulcers. The objective of this study was to evaluate the mortality, length of hospital stay and economic impact on health care in patients with acute diabetic foot ulcers who were hospitalised in the Department of Orthopaedic Surgery, Aalborg University Hospital, Denmark. METHODS: This was a prospective cohort study including all patients admitted with a diagnosis of acute foot ulcer to the Department of Orthopaedic Surgery, Aalborg, Denmark, from September 2011 to February 2012. RESULTS: A total of 48 patients were referred for surgical treatment of a diabetic foot ulcer. The average age on admission was 64 years (35-87 years). The median length of hospital stay was 17 days (3-150 days), and 14 patients were readmitted within the first year. Within the first year of enrolment, 13 patients died, corresponding to a 36% mortality rate. Based on the Danish Diagnosis-Related Groups rates, the median cost associated with a case in the study population was 133,867 DKK. CONCLUSION: Patients referred for surgical revision of diabetic foot ulcers are often severely ill, and the condition is associated with a high one-year mortality rate. Furthermore, the cost of these cases is considerable. Preventive interventions, early diagnosis and treatment and multidisciplinary interventions ­ before and during hospitalisation ­ should be implemented. FUNDING: not relevant. TRIAL REGISTRATION: The Danish Data Protection Agency (J. No. 2008-58-0028) approved the study.

Flaxseed dietary fibers lower cholesterol and increase fecal fat excretion, but magnitude of effect depend on food type.

BACKGROUND: Dietary fibers have been proposed to play a role in cardiovascular risk as well as body weight management. Flaxseeds are a good source of dietary fibers, and a large proportion of these are water-soluble viscous fibers. METHOD: Here, we examine the effect of flaxseed dietary fibers in different food matrices on blood lipids and fecal excretion of fat and energy in a double-blind randomized crossover study with 17 subjects. Three different 7-d diets were tested: a low-fiber control diet (Control), a diet with flaxseed fiber drink (3/day) (Flax drink), and a diet with flaxseed fiber bread (3/day) (Flax bread). Total fat and energy excretion was measured in feces, blood samples were collected before and after each period, and appetite sensation registered 3 times daily before main meals. RESULTS: Compared to control, Flax drink lowered fasting total-cholesterol and LDL-cholesterol by 12 and 15%, respectively, (p < 0.01), whereas Flax bread only produced a reduction of 7 and 9%, respectively (p < 0.05). Fecal fat and energy excretion increased by 50 and 23% with Flax drink consumption compared to control (p < 0.05), but only fecal fat excretion was increased with Flax bread compared to control (p < 0.05). CONCLUSION: Both Flax drink and Flax bread resulted in decreased plasma total and LDL-cholesterol and increased fat excretion, but the food matrix and/or processing may be of importance. Viscous flaxseed dietary fibers may be a useful tool for lowering blood cholesterol and potentially play a role in energy balance. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00953004.