Clinical supervisors' perceptions and use of the fundamentals of care framework in supervision of nursing students.

AIM: To explore clinical supervisors' perceptions and use of the Fundamentals of Care framework in supervising nursing students in clinical placement in hospital settings. DESIGN: A qualitative study using focus group interviews. Reported in accordance with Consolidated Criteria for Reporting Qualitative Research. METHODS: Twelve clinical nurse supervisors working in medical, surgical or psychiatric wards in hospitals in Denmark participated in four focus groups conducted from September to November 2020. Data were analysed using thematic analysis. RESULTS: Clinical supervisor's perceptions and use of the framework are described in three themes: structuring students' clinical learning, supporting tool for learning what nursing care is and developing own supervision practice. CONCLUSION: Supervisors perceive the Fundamentals of Care framework positively and use it as a supporting tool to structure and facilitate students' reflection on what nursing is and requires. They perceive that having a shared framework across school and clinical setting contributes to a safe and positive learning environment. Furthermore, using the framework develops their own practice as clinical supervisors.

The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 × 2 factorial trial of hydralazine-isosorbide dinitrate in patients with chronic heart failure (H-HeFT) and metformin in patients with chronic heart failure and diabetes or prediabetes (Met-HeFT).

OBJECTIVES: The DANHEART trial is a multicenter, randomized (1:1), parallel-group, double-blind, placebo-controlled study in chronic heart failure patients with reduced ejection fraction (HFrEF). This investigator driven study will include 1500 HFrEF patients and test in a 2 × 2 factorial design: 1) if hydralazine-isosorbide dinitrate reduces the incidence of death and hospitalization with worsening heart failure vs. placebo (H-HeFT) and 2) if metformin reduces the incidence of death, worsening heart failure, acute myocardial infarction, and stroke vs. placebo in patients with diabetes or prediabetes (Met-HeFT). METHODS: Symptomatic, optimally treated HFrEF patients with LVEF ≤40% are randomized to active vs. placebo treatment. Patients can be randomized in either both H-HeFT and Met-HeFT or to only one of these study arms. In this event-driven study, it is anticipated that 1300 patients should be included in H-HeFT and 1100 in Met-HeFT and followed for an average of 4 years. RESULTS: As of May 2020, 296 patients have been randomized at 20 centers in Denmark. CONCLUSION: The H-HeFT and Met-HeFT studies will yield new knowledge about the potential benefit and safety of 2 commonly prescribed drugs with limited randomized data in patients with HFrEF.

Does rocking motion calm delirious patients in ICU? A multicentre randomised clinical trial protocol (RockingICU).

BACKGROUND: Rocking chair therapy has been explored in patients with dementia to promote the feeling of relaxation, but not in Intensive Care Unit (ICU) patients with delirium. AIM: The aim is to investigate the effect of a chair with or without rocking motion on the duration of delirium and intensity of agitation in critically ill patients admitted to the ICU. DESIGN: This is an investigator-initiated pragmatic, multicentre, parallel-grouped, centrally randomised, stratified, data analyst-blinded trial. METHOD: We will include patients for 1:1 web-based randomisation, stratified by site in patients 18 y or older with a positive delirium score identified by a validated tool. We will exclude patients mainly due to mobilisation restrictions, body weight exceeding 130 kg, inability to provide consent, and presence of multiresistant bacteria or viral droplet infections. The intervention group will receive a minimum of 20 min of rocking therapy daily. The control group will be transferred to the same type of chair but without rocking therapy daily. A power calculation with a risk reduction of 20%, a power of 80% with an alpha cut-off on 5% and further 20% inclusion gives 76 patients in intervention and control group reaching a total of n = 152 inclusion in the trial. CONCLUSION: The RockingICU trial will provide important new knowledge and raise research questions regarding nonpharmacological interventions to alleviate delirium in ICU patients.

Associations of health literacy with socioeconomic position, health risk behavior, and health status: a large national population-based survey among Danish adults.

BACKGROUND: Health literacy concerns the ability of citizens to meet the complex demands of health in modern society. Data on the distribution of health literacy in general populations and how health literacy impacts health behavior and general health remains scarce. The present study aims to investigate the prevalence of health literacy levels and associations of health literacy with socioeconomic position, health risk behavior, and health status at a population level. METHODS: A nationwide cross-sectional survey linked to administrative registry data was applied to a randomly selected sample of 15,728 Danish individuals aged ≥25 years. By the short form HLS-EU-Q16 health literacy was measured for the domains of healthcare, disease prevention, and health promotion. Adjusted multinomial logistic regression analyses were used to estimate associations of health literacy with demographic and socioeconomic characteristics, health risk behavior (physical activity, smoking, alcohol consumption, body weight), and health status (sickness benefits, self-assessed health). RESULTS: Overall, 9007 (57.3%) individuals responded to the survey. Nearly 4 in 10 respondents faced difficulties in accessing, understanding, appraising, and applying health information. Notably, 8.18% presented with inadequate health literacy and 30.94% with problematic health literacy. Adjusted for potential confounders, regression analyses showed that males, younger individuals, immigrants, individuals with basic education or income below the national average, and individuals receiving social benefits had substantially higher odds of inadequate health literacy. Among health behavior factors (smoking, high alcohol consumption, and inactivity), only physical behavior [sedentary: OR: 2.31 (95% CI: 1.81; 2.95)] was associated with inadequate health literacy in the adjusted models. The long-term health risk indicator body-weight showed that individuals with obesity [OR: 1.78 (95% CI: 1.39; 2.28)] had significantly higher odds of lower health literacy scores. Poor self-assessed health [OR: 4.03 (95% CI: 3.26; 5.00)] and payments of sickness absence compensation benefits [OR: 1.74 (95% CI: 1.35; 2.23)] were associated with lower health literacy scores. CONCLUSIONS: Despite a relatively highly educated population, the prevalence of inadequate health literacy is high. Inadequate health literacy is strongly associated with a low socioeconomic position, poor health status, inactivity, and overweight, but to a lesser extent with health behavior factors such as smoking and high alcohol consumption.

Risk of atrial fibrillation after pacemaker implantation: A nationwide Danish registry-based follow-up study.

BACKGROUND: The overall risk of atrial fibrillation (AF) among patients with pacemaker (PM) in comparison to control cohort is unknown. PURPOSE: To investigate the risk of AF after implantation of a PM in an AF-naive population in comparison to an age- and sex-matched PM- and AF-free population cohort. METHODS: All patients with a dual chamber PM (DDD) implanted between 2000 and 2014 without a known history of AF were included (n = 17,428). To compare, a general population cohort without pacemaker and a cohort with loop recorder was identified. Outcome was the cumulative incidence of AF within the first 2 years from 3-months after device implantation. RESULTS: At the end of first 3-months after device implantation, 16,383 patients were free of AF and were included in the current study. In comparison to controls (n = 86,167), patients with PM had higher cumulative incidence of AF (5.2% vs 2.7%, P < 0.001)). Due to interaction with age, patients were divided into three age-groups) and the relative risk for the diagnosis of AF were: < 70 years (HR 4.46, 95% CI 3.65-5.44); 70-79 years (HR 2.60, 95% CI 2.27-2.98); and ≥ 80 years (HR 1.29, 95% CI 1.15-1.45). For comparison between PM and loop-recorder cohort (1:1 matching), 2202 patients were available in both groups. The incidence of AF within the first 2-years in the both groups was 7.9% vs. 8.4% (loop vs pacemaker). CONCLUSIONS: Patients with PM have an increased risk of being diagnosed with AF in comparison to general cohort likely due to continuous monitoring.

Exploring nursing students' use of the Fundamentals of Care framework in case-based work.

AIMS AND OBJECTIVES: To explore how nursing students perceive and use the conceptual Fundamentals of Care framework in case-based work in nursing education and furthermore to describe influencing factors on perceptions and use of the framework. BACKGROUND: The Fundamentals of Care framework has been integrated in core courses in two Schools of Nursing in Region North Denmark in response to studies reporting that nursing students and newly graduated nurses lack the knowledge, skills and competencies to meet the challenges of delivering fundamental care in clinical practice. An integration of the framework in case-based work in nursing education has not previously been studied. DESIGN AND METHODS: The study design was focused ethnography. Data were collected using participant observations, focus group interviews and individual interviews. Four groups of four to five nursing students participating in case-based work sessions and three faculty members from two Schools of Nursing were included. The study adhered to COREQ. RESULTS: The results show an uncertainty among the students about how to understand and use the conceptual framework in case-based work. The uncertainties derive from diversities in faculty members' perceptions and curricular planning among others. However, the framework appears to support the students' learning about what nursing is and requires. CONCLUSIONS: The study indicates that integrating Fundamentals of Care framework in case-based work may be one way of teaching nursing students the complexities of integrated fundamental nursing care. However, there is a need to consider how to support students in articulating Fundamentals of Care, and to draw attention to the influence of role models and curricular planning. RELEVANCE TO EDUCATIONAL PRACTICE: The study provides knowledge relevant when customising future educational interventions regarding the integration of Fundamentals of Care in nursing education and may provide valuable knowledge of evaluation strategies.

Integration of Rehabilitation Activities Into Everyday Life Through Telerehabilitation: Qualitative Study of Cardiac Patients and Their Partners.

BACKGROUND: Implementation of cardiac rehabilitation has not been optimal, with patient participation rates below 50%. Factors that contribute to cardiac patients' lack of participation in rehabilitation programs are patient motivation, logistical difficulties in getting to the rehabilitation facilities, lack of psychosocial elements, and individualization of activities in the rehabilitation programs. Telerehabilitation has been proposed as a new way to address the challenge of engaging and motivating cardiac patients and their partners to participate in rehabilitation. OBJECTIVE: The aim of this study was to explore the experiences of cardiac patients and their partners of participating in the Teledialog Telerehabilitation Program (TTP). The Teledialog program consisted of a digital rehabilitation plan, transmission of health data from patient's home to hospital and health care center, and an interactive Web portal with information and training videos. METHODS: This case study used a theoretical approach combining the "community of practice" approach and self-determination theory. A triangulation of data collection techniques was used, including documents, participant observation (72 hours), and qualitative interviews with cardiac patients and their partners enrolled in the telerehabilitation group. A total of 14 cardiac patients, 12 patient spouses/partners, and 1 son participated in the study. The participants were interviewed at enrollment in the telerehabilitation program and after 12 weeks of participation in the program. Interview data were analyzed using NVivo 11.0. RESULTS: Patients and their partners found the Web portal ActiveHeart.dk and the electronic rehabilitation (e-rehabilitation) plan to be helpful tools for health education, coordinating rehabilitation goals, creating an overview of the data, and ensuring continuity in the rehabilitation process. The patients felt that the TTP treated them as individuals, gave them a sense of autonomy, and provided enhanced relatedness to health care professionals and partners and a sense of competence as active participants in their own rehabilitation process. Some patients missed being part of a community of practice with other cardiac patients and did not use the Web forum. Patients' partners found that the telerehabilitation program gave them a sense of security and helped them balance their involvement as a partner to the patient and not push the patient too hard. CONCLUSIONS: Cardiac patients and their partners found telerehabilitation technologies a useful digital toolbox in the rehabilitation process. Telerehabilitation motivated the patients to integrate rehabilitation activities into their work schedule and everyday life and made them feel like unique individuals. Participating in the Teledialog Telerehabilitation Program might not be a suitable strategy for all cardiac patients. Being a patient's partner in the telerehabilitation program was associated with a heightened sense of security, navigation between active involvement in the rehabilitation process, being an equal partner, and not pushing the patient too hard.

SpatTrack: an imaging toolbox for analysis of vesicle motility and distribution in living cells.

The endocytic pathway is a complex network of highly dynamic organelles, which has been traditionally studied by quantitative fluorescence microscopy. The data generated by this method can be overwhelming and its analysis, even for the skilled microscopist, is tedious and error-prone. We developed SpatTrack, an open source, platform-independent program collecting a variety of methods for analysis of vesicle dynamics and distribution in living cells. SpatTrack performs 2D particle tracking, trajectory analysis and fitting of diffusion models to the calculated mean square displacement. It allows for spatial analysis of detected vesicle patterns including calculation of the radial distribution function and particle-based colocalization. Importantly, all analysis tools are supported by Monte Carlo simulations of synthetic images. This allows the user to assess the reliability of the analysis and to study alternative scenarios. We demonstrate the functionality of SpatTrack by performing a detailed imaging study of internalized fluorescence-tagged Niemann Pick C2 (NPC2) protein in human disease fibroblasts. Using SpatTrack, we show that NPC2 rescued the cholesterol-storage phenotype from a subpopulation of late endosomes/lysosomes (LE/LYSs). This was paralleled by repositioning and active transport of NPC2-containing vesicles to the cell surface. The potential of SpatTrack for other applications in intracellular transport studies will be discussed.

Cardiac Patients' Walking Activity Determined by a Step Counter in Cardiac Telerehabilitation: Data From the Intervention Arm of a Randomized Controlled Trial.

BACKGROUND: Walking represents a large part of daily physical activity. It reduces both overall and cardiovascular diseases and mortality and is suitable for cardiac patients. A step counter measures walking activity and might be a motivational tool to increase and maintain physical activity. There is a lack of knowledge about both cardiac patients' adherence to step counter use in a cardiac telerehabilitation program and how many steps cardiac patients walk up to 1 year after a cardiac event. OBJECTIVE: The purpose of this substudy was to explore cardiac patients' walking activity. The walking activity was analyzed in relation to duration of pedometer use to determine correlations between walking activity, demographics, and medical and rehabilitation data. METHODS: A total of 64 patients from a randomized controlled telerehabilitation trial (Teledi@log) from Aalborg University Hospital and Hjoerring Hospital, Denmark, from December 2012 to March 2014 were included in this study. Inclusion criteria were patients hospitalized with acute coronary syndrome, heart failure, and coronary artery bypass grafting or valve surgery. In Teledi@log, the patients received telerehabilitation technology and selected one of three telerehabilitation settings: a call center, a community health care center, or a hospital. Monitoring of steps continued for 12 months and a step counter (Fitbit Zip) was used to monitor daily steps. RESULTS: Cardiac patients walked a mean 5899 (SD 3274) steps per day, increasing from mean 5191 (SD 3198) steps per day in the first week to mean 7890 (SD 2629) steps per day after 1 year. Adherence to step counter use lasted for a mean 160 (SD 100) days. The patients who walked significantly more were younger (P=.01) and continued to use the pedometer for a longer period (P=.04). Furthermore, less physically active patients weighed more. There were no significant differences in mean steps per day for patients in the three rehabilitation settings or in the disease groups. CONCLUSIONS: This study indicates that cardiac telerehabilitation at a call center can support walking activity just as effectively as telerehabilitation at either a hospital or a health care center. In this study, the patients tended to walk fewer steps per day than cardiac patients in comparable studies, but our study may represent a more realistic picture of walking activity due to the continuation of step counter use. Qualitative studies on patients' behavior and motivation regarding step counter use are needed to shed light on adherence to and motivation to use step counters. TRIAL REGISTRATION: ClinicalTrials.gov NCT01752192; https://clinicaltrials.gov/ct2/show/NCT01752192 (Archived by WebCite at http://www.webcitation.org/6fgigfUyV).

Cost-Utility Analysis of a Cardiac Telerehabilitation Program: The Teledialog Project.

BACKGROUND: Cardiac rehabilitation can reduce mortality of patients with cardiovascular disease, but a frequently low participation rate in rehabilitation programs has been found globally. The objective of the Teledialog study was to assess the cost-utility (CU) of a cardiac telerehabilitation (CTR) program. The aim of the intervention was to increase the patients' participation in the CTR program. At discharge, an individualized 3-month rehabilitation plan was formulated for each patient. At home, the patients measured their own blood pressure, pulse, weight, and steps taken for 3 months. MATERIALS AND METHODS: The analysis was carried out together with a randomized controlled trial with 151 patients during 2012-2014. Costs of the intervention were estimated with a health sector perspective following international guidelines for CU. Quality of life was assessed using the 36-Item Short Form Health Survey. RESULTS: The rehabilitation activities were approximately the same in the two groups, but the number of contacts with the physiotherapist was higher among the intervention group. The mean total cost per patient was €1,700 higher in the intervention group. The quality-adjusted life-years (QALYs) gain was higher in the intervention group, but the difference was not statistically significant. The incremental CU ratio was more than €400,000 per QALY gained. CONCLUSIONS: Even though the rehabilitation activities increased, the program does not appear to be cost-effective. The intervention itself was not costly (less than €500), and increasing the number of patients may show reduced costs of the devices and make the CTR more cost-effective. Telerehabilitation can increase participation, but the intervention, in its current form, does not appear to be cost-effective.

Macrophage-mediated nanoparticle delivery to the periodontal lesions in established murine model via Pg-LPS induction.

We established a murine periodontitis model by local injection of lipopolysaccharide of Porphyromonas gingivalis (Pg-LPS) into the gingival sulcus of mandibular left incisor four times with 48-h interval. The histological examination of the periodontal tissues demonstrated that significant loss of periodontal bone and ligaments was observed in the lesion side with abundant inflammatory cell infiltration. Two days after the last injection, Cy5-labelled siRNA/chitosan particles were injected intraperitoneally (ip). The chitosan/siRNA particles were taken up by peritoneal macrophages, which subsequently migrated to the inflamed gingival area evaluated by in vivo imaging. The localization of macrophages in the inflamed region was further confirmed by immunofluorescent staining. The present report demonstrates that intragingival injection of Pg-LPS can be used to create an experimental model of periodontal inflammation in mice and that recruitment of macrophages with chitosan/siRNA nanoparticles to the inflamed area opens the possibility of an RNAi-based therapeutic approach using chitosan as a carrier in periodontitis.

Ficolin B in Diabetic Kidney Disease in a Mouse Model of Type 1 Diabetes.

BACKGROUND: The innate immune system may have adverse effects in diabetes and cardiovascular disease. The complement system seems to play a key role through erroneous complement activation via hyperglycaemia-induced neoepitopes. Recently mannan-binding lectin (MBL) was shown to worsen diabetic kidney changes. We hypothesize that mouse ficolin B exerts detrimental effects in the diabetic kidney as seen for MBL. METHODS: We induced diabetes with streptozotocin in female wild-type mice and ficolin B knockout mice and included two similar nondiabetic groups. Renal hypertrophy and excretion of urinary albumin and creatinine were quantified to assess diabetic kidney damage. RESULTS: In the wild-type groups, the kidney weighed 24% more in the diabetic mice compared to the controls. The diabetes-induced increase in kidney weight was 29% in the ficolin B knockout mice, that is, equal to wild-type animals (two-way ANOVA, P = 0.60). In the wild-type mice the albumin-to-creatinine ratio (ACR) was 32.5 mg/g higher in the diabetic mice compared to the controls. The difference was 62.5 mg/g in the ficolin B knockout mice, but this was not significantly different from the wild-type animals (two-way ANOVA, P = 0.21). CONCLUSIONS: In conclusion, the diabetes-induced effects on kidney weight and ACR were not modified by the presence or absence of ficolin B.

Do educational meetings and group detailing change adherence to drug formularies in hospitals? A cluster randomized controlled trial.

PURPOSE: The aim of this study was to examine whether educational meetings and group detailing could increase the use of drugs from the ward lists or the drug formulary in hospitals. METHODS: Twelve medical wards from two hospitals were randomized into three groups: control, basic and extended intervention. All wards had a ward list review before interventions. Moreover, the basic intervention consisted of an educational meeting, and the extended intervention included two group detailing sessions. The proportion of drugs used from the ward list or hospital drug formulary (HDF) was the primary outcome. Data (defined daily doses [DDDs], numbers and cost [Euros]) on drugs sold to the wards were retrieved from the two hospitals from 1 July 2011 to 31 August 2012. BASELINE DATA: from July to September 2011, and follow-up data: from June to August 2012. RESULTS: The proportion of formulary drugs used increased for the extended intervention group (0.04, range -0.02 to 0.09) and basic intervention group (0.03, range -0.03 to 0.09) in comparison with a decrease in the control group (-0.01, range -0.03 to -0.02). The interventions did not significantly change odds for selecting drugs from the formulary in comparison with the control group (basic intervention: OR 1.09 [95 % CI 0.81 to 1.46]; extended intervention: OR 1.00 [95 % CI 0.75 to 1.35]). CONCLUSIONS: In this study, educational meetings and group detailing do not significantly improve adherence to ward lists or HDF. The adherence to the formularies at baseline was relatively high, which may explain why the interventions did not have a significant effect.

Productivity parameters, antimicrobial consumption, and prevalence of enteric pathogens before and after intramuscular vaccination against Lawsonia intracellularis in naturally infected Danish weaner and finisher pig herds.

In Danish pig production, gastro-intestinal diseases account for most of the antimicrobials (AM) used in growing pigs. Diarrhoea is most frequently caused by Lawsonia intracellularis (LI), Brachyspira pilosicoli (BP), E coli fimbria type F4 (F4) and E. coli fimbria type F18 (F18). With a new LI vaccine available from 2019, it was relevant to investigate the effect of this vaccine in a Danish field study including both weaner and finisher sites. The aim was to evaluate the efficacy of Porcilis® Lawsonia Vet. in naturally LI-infected pig herds by comparing of productivity parameters, AM consumption and dynamics of enteric pathogens over two 6-months periods before and after LI vaccination. Further, faecal sock samples were collected from each site before and after vaccination and analysed by qPCR for excretion levels of LI, BP, F18 and F4. In total, 28 weaner and 41 finisher sites were included in the study. Vaccination reduced Feed Conversion Ratio by 0.12 Feed Unit/kg (p = 0.029) and 0.08 Feed Unit/kg (p = 0.005) in weaners and finishers, respectively. Increased Average Daily Weight Gain of 45.6 gr./day (p < 0.001) was found in the finishers. Mortality risk fell by 8.8% in weaners (RR = 0.912; p < 0.001). AM prescriptions for oral group treatments were reduced by 38.8% active compound/kg pig produced (p = 0.005) or 33.3% Weighted Animal Daily Doses per 100 animals per day in finishers (p = 0.004). LI prevalence was reduced in weaners and finishers (both p < 0.001) and BP prevalence was reduced in finishers (p = 0.043). Mean excretion levels of LI and BP decreased at weaner sites (-1.32 and -1.02 log(10) copies/gr faeces, respectively; both p < 0.001) and at finisher sites (-1.04 and -1.16 log(10) copies/gr faeces, respectively; both p < 0.001). Prevalence and excretion levels of F18 and F4 were unaffected by LI vaccination. In conclusion, vaccination against LI using Porcilis® Lawsonia Vet. improved productivity parameters, cut AM consumption, and reduced prevalence and excretion levels of LI and BP in naturally LI-infected pig herds.

Effect of intramuscular vaccination against Lawsonia intracellularis on production parameters, diarrhea occurrence, antimicrobial treatment, bacterial shedding, and lean meat percentage in two Danish naturally infected finisher pig herds.

Lawsonia intracellularis (LI) is an economically important enteric pathogen in pigs with a worldwide endemic prevalence. The objective of this study was to evaluate the effect of an intramuscularly administrated LI vaccine (Porcilis®Lawsonia Vet.) in Danish finisher pigs (30-115 kg) measured on key production figures, antimicrobial (AB) treatments, occurrence of diarrhea and LI shedding. The study was a group-randomized block-trial with parallel groups in two herds, Herd 1 and Herd 2, experiencing a natural subclinical-clinical LI infection in early finisher period. Vaccination occurred at weaning, but the study focused on the first eight weeks in the finisher period. Further, slaughterhouse data were included. In total, 52 and 50 finisher pens comprising 2184 and 2254 finisher pigs were included in each of two herds, respectively. LI vaccination significantly reduced feed conversion ratio (FCR) by 0.05 and 0.09 FU/kg (p = 0.007 and p < 0.001) alongside a significantly increased average daily weight gain (ADWG) by 31 and 43 gr/day (p = 0.001 and p < 0.001) in each of the herds, respectively. In the vaccinated group, less variation was found in ADWG compared to the control group (p < 0.001 in both herds) as an expression of a more uniform growth, which was further confirmed by less variation in lean meat percent in the vaccinated group in one herd (p = 0.007). No significant difference between groups were found in mortality and pigs excluded due to welfare reasons. AB flock treatment against diarrhea was significantly reduced in Herd 1 with all pens treated in the control group compared to 30.8 % in the vaccinated group (p < 0.001). In Herd 2, the difference was non-significant with 68.0 % in the control group compared to 50.0 % in the vaccination group (p = 0.252). Low levels of individual treatments against diarrhea were seen in both herds (≤ 5.0 %) but still significantly reduced in vaccinated pigs compared to control pigs (p < 0.050 in both herds). Mean diarrheic blot counts were significantly reduced in vaccinated pens compared to control pens (p < 0.001 in both herds). In vaccinated pigs, shedding of LI was reduced in both prevalence (p < 0.001 in both herds), excretion level in positive samples (p < 0.001 in both herds) and, in one herd, also in duration (p = 0.003) when compared to control pigs. In conclusion, pigs vaccinated with Porcilis®Lawsonia Vet against LI in both of two high-health and high-productive finisher herds had, compared to non-vaccinated pigs, significantly improved key production figures, and reduced AB treatment, occurrence of diarrhea, LI shedding, and growth variation.

Evaluation of the establishment of a national task force - A systematic measure to manage critical drug shortages in hospitals.

Introduction: Drug shortages (DSs) have become a well-known challenge in health care, and serious patient safety consequences, such as medication errors and adverse patient outcomes are reported. To meet these challenges, a national task force was established to manage and minimize the impact of critical DSs' on hospitals in Denmark. Objective: To evaluate the establishment of the National Task Force for Critical Drug Shortages (NTF) in terms of quality, patient safety, and resources from different actor perspectives related to critical DS management in Danish hospitals. Methods: Five online focus group interviews were held with participants representing different actor perspectives, all of whom were involved in managing DSs. They represent actors from 1) the NTF; 2) hospital pharmacists not involved in the NTF but who manage DSs locally and/or regionally; 3) the procurement departments of hospital pharmacies; 4) pharmacy technicians performing clinical pharmacy services at a patient level, and 5) the procurement and supply unit at Amgros. Results: The thematic analysis revealed four major themes: 1) centralized management of critical DSs is predominantly considered to be positive, 2) collaboration and professional discussion across actors and actor levels, 3) mixed attitudes toward the current communication platforms and format, and 4) short supply of time. Conclusion: The NTF ensures a consistent and qualified management of critical DSs. The NTF ensures the evaluation of different patient safety aspects related to identification of a suitable alternative. Challenges with the communication platform and transparency of the process from the NTF toward hospital pharmacy were mentioned but overall, the NTF contributes to a successful use of resources in health care.

Prevalences and excretion levels of Lawsonia intracellularis, Brachyspira pilosicoli and Escherichia coli F4 and F18 in fecal sock samples from Danish weaner and finisher pig batches and the association with diarrhea.

BACKGROUND: Bacterial enteritis in growing pigs is a matter of concern in Danish pig production challenging herd health as well as production economy, and antimicrobial usage. The aim of this observational study using fecal sock samples was to determine the prevalence and excretion level of Lawsonia intracellularis (LI), Brachyspira pilosicoli (BP), Escherichia coli F4 (F4) and F18 (F18) and to investigate associations between prevalence or excretion levels of the bacteria and diarrhea. The study was performed in the late weaner and the early finisher period in herds with a history of diarrhea. Every weaner and finisher herd contributed with one sample each. RESULTS: In total, 47 weaner and 59 finisher herds were sampled. The overall prevalence and excretion levels (median and range in log(10) copies/gram of feces) were for LI 84.0% (median 6.2; range 3.0-7.7), for BP 45.2% (median 5.6; range 3.0-6.6), for F18 20.8% (median 5.7; range 4.7-7.7), and for F4 4.7% (median 5.5; range 5.2-6.0). In both diarrheic and non-diarrheic samples, the most prevalent bacteria were either LI alone or LI and BP in combination. In general, no association was found between increasing total bacterial excretion levels and diarrhea, but prevalence (p = 0.04) and excretion (p < 0.01) level of F18 was found to be significantly higher in diarrheic samples. Further, a significant association was found between low LI excretion level and lack of diarrhea in weaner herds (p = 0.03). A significant positive correlation was found between excretion levels of LI and BP in diarrheic weaner herd samples (p = 0.02). CONCLUSION: Enteric pathogens were prevalent in a wide range of bacterial excretion levels in both diarrheic and non-diarrheic samples. Especially LI and BP were frequently found and with a positive correlation between excretion levels. Even in the absence of diarrhea, high prevalence and excretion levels of LI and BP were detected, thus making the status of diarrhea an insufficient tool for assessing the severity of their infections.

A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone.

The objectives were to develop a standardized Ki-67 immunohistochemistry (IHC) method for precise, robust, and reproducible assessment of patients with early breast cancer, and utilize this assay to evaluate patients participating in the monarchE study (NCT03155997). The Ki-67 assay was developed and validated for sensitivity, specificity, repeatability, precision, and robustness using a predefined ≥20% cutoff. Reproducibility studies (intersite and intrasite, interobserver and intraobserver) were conducted at 3 external laboratories using detailed scoring instructions designed for monarchE. Using the assay, patient tumors were classified as displaying high (≥20%) or low (<20%) Ki-67 expression; Kaplan-Meier methods evaluated 2-year invasive disease-free survival rates for these 2 groups among patients treated with endocrine therapy (ET) alone. All analytical validation and reproducibility studies achieved point estimates of >90% for negative, positive, and overall percent agreement. Intersite reproducibility produced point estimate values of 94.7%, 100.0%, and 97.3%. External interobserver reproducibility produced point estimate values of 98.9%, 97.8%, and 98.3%. Among 1954 patients receiving ET alone, 986 (50.5%) had high and 968 (49.5%) had low Ki-67 expression. Patients with high Ki-67 had a clinically meaningful increased risk of developing invasive disease within 2 years compared with those with low Ki-67 [2-y invasive disease-free survival rate: 86.1% (95% confidence interval: 83.1%-88.7%) vs. 92.0% (95% confidence interval: 89.7%-93.9%), respectively]. This standardized Ki-67 methodology resulted in high concordance across multiple laboratories, and its use in the monarchE study prospectively demonstrated the prognostic value of Ki-67 IHC in HR+, HER2- early breast cancer with high-risk clinicopathologic features.

Uncertainty in classification of death from fatal myocardial infarction: A nationwide analysis of regional variation in incidence and diagnostic support.

AIMS: The usefulness of mortality statistics relies on the validity of death certificate diagnosis. However, diagnosing the causal sequence of conditions leading to death is not simple. We examined diagnostic support for fatal acute myocardial infarction (AMI) and investigated its association with regional variation. METHODS AND RESULTS: From Danish nationwide registers, we identified the study population (N = 3,244,051) of whom 36,669 individuals were recorded with AMI as the underlying cause-of-death between 2002 and 2015. We included clinical diagnoses, procedures, and claimed prescriptions related to atherosclerotic disease to evaluate the level of diagnostic support for fatal AMI in three diagnostic groups (Definite; Plausible; Uncertain). Adjusted mortality rates, rate ratios, and odds ratios were estimated for each AMI category, stratified by hospital region using multivariable regression models. More than one-third (N = 12,827, 35%) of deaths reported as fatal AMI had uncertain diagnostic support. The largest regional variation in AMI mortality rate ratios, varying from 1.16 (95%CI:1.02;1.31) to 1.62 (95%CI:1.43;1.83), was found among cases with uncertain diagnostic supportive data. Substantial inter-regional differences in the degree to which death occurs outside hospital [OR: 1.01 (95%CI:0.92;1.12) - 1.49 (95%CI:1.36;1.63)] and general practitioners determining the cause-of-death at home were present. Minor regional differences [OR: 0.96 (95%CI:0.85;1.07) - 1.16 (95%CI:1.04;1.29)] in in-hospital AMI mortality were observed. CONCLUSION: There is significant regional variation associated with recording AMI as a cause-of-death. This variation is predominately based on death certificate diagnoses without diagnostic supportive evidence. Studies of fatal AMI should include a stratification on supportive evidence of the diagnosis.

Level of Physical Activity, Left Ventricular Mass, Hypertension, and Prognosis.

Left ventricular hypertrophy is a strong predictor of prognosis in hypertension. Physical activity is associated with higher left ventricular mass but also reduced risk of cardiovascular outcomes. The aims were to explore whether (1) presence of hypertension modifies the association between physical activity and left ventricular mass; (2) the beneficial association between physical activity and prognostic outcome is modified by left ventricular hypertrophy. Randomly selected number of 3078 persons from the general population underwent echocardiogram. Left ventricular mass was indexed to body surface area. Level of physical activity was self-reported: inactivity, light activity, and moderate/high activity. Blood pressure was measured in rest: normal BP (<140/90 mm Hg) and hypertension (≥140/90 mm Hg or in pharmacological treatment for hypertension). Presence of hypertension modified the association between physical activity and left ventricular mass index significantly (test for interaction: P=0.01): in normal BP, higher levels of physical activity were associated with significantly higher left ventricular mass index (P<0.001), but this was not present in hypertension (P=0.90). Level of physical activity was associated with reduction in mortality and cardiovascular outcome independent of the presence of LVH (Persons with LVH: light activity HR, 0.77 [0.52-1.15], moderate/high activity HR, 0.61 [0.38-0.97]; test for interaction between LVH and level of physical activity P=0.71). In conclusion, persons with normal BP had higher left ventricular mass index at increased levels of physical activity, whereas this association was not present among persons with hypertension. Level of physical activity was associated with better prognosis independent of whether left ventricular hypertrophy was present or not.