Angiomotin isoform 2 promotes binding of PALS1 to KIF13B at primary cilia and regulates ciliary length and signaling.

The kinesin-3 motor KIF13B functions in endocytosis, vesicle transport and regulation of ciliary length and signaling. Direct binding of the membrane-associated guanylate kinase (MAGUK) DLG1 to the MAGUK-binding stalk domain of KIF13B relieves motor autoinhibition and promotes microtubule plus-end-directed cargo transport. Here, we characterize angiomotin (AMOT) isoform 2 (p80, referred to as Ap80) as a novel KIF13B interactor that promotes binding of another MAGUK, the polarity protein and Crumbs complex component PALS1, to KIF13B. Live-cell imaging analysis indicated that Ap80 is concentrated at and recruits PALS1 to the base of the primary cilium, but is not a cargo of KIF13B itself. Consistent with a ciliary function for Ap80, its depletion led to elongated primary cilia and reduced agonist-induced ciliary accumulation of SMO, a key component of the Hedgehog signaling pathway, whereas Ap80 overexpression caused ciliary shortening. Our results suggest that Ap80 activates KIF13B cargo binding at the base of the primary cilium to regulate ciliary length, composition and signaling.

Construction of the ETECFinder database for the characterization of enterotoxigenic Escherichia coli (ETEC) and revision of the VirulenceFinder web tool at the CGE website.

The identification of pathogens is essential for effective surveillance and outbreak detection, which lately has been facilitated by the decreasing cost of whole-genome sequencing (WGS). However, extracting relevant virulence genes from WGS data remains a challenge. In this study, we developed a web-based tool to predict virulence-associated genes in enterotoxigenic Escherichia coli (ETEC), which is a major concern for human and animal health. The database includes genes encoding the heat-labile toxin (LT) (eltA and eltB), heat-stable toxin (ST) (est), colonization factors CS1 through 30, F4, F5, F6, F17, F18, and F41, as well as toxigenic invasion and adherence loci (tia, tibAC, etpBAC, eatA, yghJ, and tleA). To construct the database, we revised the existing ETEC nomenclature and used the VirulenceFinder webtool at the CGE website [VirulenceFinder 2.0 (dtu.dk)]. The database was tested on 1,083 preassembled ETEC genomes, two BioProjects (PRJNA421191 with 305 and PRJNA416134 with 134 sequences), and the ETEC reference genome H10407. In total, 455 new virulence gene alleles were added, 50 alleles were replaced or renamed, and two were removed. Overall, our tool has the potential to greatly facilitate ETEC identification and improve the accuracy of WGS analysis. It can also help identify potential new virulence genes in ETEC. The revised nomenclature and expanded gene repertoire provide a better understanding of the genetic diversity of ETEC. Additionally, the user-friendly interface makes it accessible to users with limited bioinformatics experience. IMPORTANCE: Detecting colonization factors in enterotoxigenic Escherichia coli (ETEC) is challenging due to their large number, heterogeneity, and lack of standardized tests. Therefore, it is important to include these ETEC-related genes in a more comprehensive VirulenceFinder database in order to obtain a more complete coverage of the virulence gene repertoire of pathogenic types of E. coli. ETEC vaccines are of great importance due to the severity of the infections, primarily in children. A tool such as this could assist in the surveillance of ETEC in order to determine the prevalence of relevant types in different parts of the world, allowing vaccine developers to target the most prevalent types and, thus, a more effective vaccine.

Cost-effectiveness of proactive health support-telephone-based self-management support compared with standard care for persons at risk of hospital admission.

BACKGROUND: A small share of patients account for a large proportion of costs to the healthcare system in Denmark as in many Western countries. A telephone-based self-management support, proactive health support (PaHS), was suggested for prevention of hospitalisations for persons at risk of hospital admission. These persons have chronic diseases, unplanned hospitalisations and age ≥ 65 years. However, evidence is limited on whether this type of intervention is cost-effective. AIM: The aim of this study was to assess the incremental cost-utility ratio (ICER) of PaHS, compared with standard care. METHODS: The economic evaluation was nested within a randomised controlled trial, and was based on a health system perspective, with follow-up and time horizon of 12 months. We measured incremental costs per quality-adjusted life years (QALY) gained. Total average costs per patient included PaHS programme costs, and costs in hospitals, primary care and municipalities. We analysed differences by generalised linear models with Gamma distribution for costs and mixed models for QALY. RESULTS: We analysed data on 6,139 patients, where 3,041 received PaHS and 3,098 received usual care. We found no difference in healthcare costs, and programme costs were on average €1,762 per patient, providing incremental costs of €2,075. Incremental effects on QALY were 0.007, resulting in an ICER of €296,389 per QALY gained. CONCLUSION: We found no evidence of PaHS being cost-effective in this study, but the results will be used to identify new ways to organise similar interventions and identify patients with the objective to reduce health system costs per patient.

Consistency in contouring of organs at risk by artificial intelligence vs oncologists in head and neck cancer patients.

BACKGROUND: In the Danish Head and Neck Cancer Group (DAHANCA) 35 trial, patients are selected for proton treatment based on simulated reductions of Normal Tissue Complication Probability (NTCP) for proton compared to photon treatment at the referring departments. After inclusion in the trial, immobilization, scanning, contouring and planning are repeated at the national proton centre. The new contours could result in reduced expected NTCP gain of the proton plan, resulting in a loss of validity in the selection process. The present study evaluates if contour consistency can be improved by having access to AI (Artificial Intelligence) based contours. MATERIALS AND METHODS: The 63 patients in the DAHANCA 35 pilot trial had a CT from the local DAHANCA centre and one from the proton centre. A nationally validated convolutional neural network, based on nnU-Net, was used to contour OARs on both scans for each patient. Using deformable image registration, local AI and oncologist contours were transferred to the proton centre scans for comparison. Consistency was calculated with the Dice Similarity Coefficient (DSC) and Mean Surface Distance (MSD), comparing contours from AI to AI and oncologist to oncologist, respectively. Two NTCP models were applied to calculate NTCP for xerostomia and dysphagia. RESULTS: The AI contours showed significantly better consistency than the contours by oncologists. The median and interquartile range of DSC was 0.85 [0.78 - 0.90] and 0.68 [0.51 - 0.80] for AI and oncologist contours, respectively. The median and interquartile range of MSD was 0.9 mm [0.7 - 1.1] mm and 1.9 mm [1.5 - 2.6] mm for AI and oncologist contours, respectively. There was no significant difference in ΔNTCP. CONCLUSIONS: The study showed that OAR contours made by the AI algorithm were more consistent than those made by oncologists. No significant impact on the ΔNTCP calculations could be discerned.

Mental well-being and patient activation during the first eight months of the COVID-19 pandemic in Denmark - a cohort study among 710 Danish adults with chronic conditions.

BACKGROUND: COVID-19 has highlighted the importance of patient activation in managing chronic conditions and promoting resilience during times of crisis. Patient activation refers to an individual's knowledge, skills, and confidence in managing their own health and healthcare. Previous research has shown that people with higher levels of patient activation are better prepared to navigate the challenges of chronic illness and are more likely to engage in healthy behaviors. However, the impact of patient activation on COVID-19-related concerns and mental well-being among people with chronic conditions during the pandemic remains unclear. This study aims to investigate the possible role of patient activation in shaping COVID-19-related concerns and to describe changes in mental well-being among Danish adults with one or more chronic conditions during the early months of the pandemic. METHODS: Danish adults with chronic conditions (e.g. diabetes, coronary heart disease, obstructive pulmonary lung disease, cancer) who had participated in a municipal health education program prior to the COVID-19 outbreak were asked to participate in this prospective questionnaire study in May 2020 and November 2020. Sociodemographic (sex, age, living status, educational attainment, employment status) and disease-related information (diagnosis, one or more chronic conditions) along with the Patient Activation Measure were collected before the outbreak and were obtained from a clinical database used for monitoring and evaluation of municipal health education programs. In contrast, the two questionnaires collected six months apart consisted of single items related to concerns about COVID-19 and the WHO-5 well-being index. RESULTS: A total of 710 people with chronic conditions (mean age 60.9 years; 55.8% female) participated at both time points. In bivariate analyses, patient activation was associated with COVID-19-related concern and well-being. At follow-up, participants experienced a significant decrease in well-being. The decrease was associated with poorer well-being measured six months earlier, a greater perception that it had become more challenging to take care of one's health due to the pandemic, and finally, feeling lonely. The association between patient activation and well-being ceased to be significant in the multivariate regression model. CONCLUSIONS: A considerable proportion of people with chronic conditions participating in this study have been mentally burdened during COVID-19. Although lower levels of patient activation were associated with greater COVID-19-related concerns, it did not have a significant impact on mental well-being over time.

Implementation through translation: a qualitative case study of translation processes in the implementation of quality improvement collaboratives.

BACKGROUND: Quality improvement collaboratives (QICs) are used extensively to implement quality improvement in healthcare, and current research is demonstrating positive yet varying evidence. To interpret the effectiveness results, it is necessary to illuminate the dynamics of QIC implementation in specific contexts. Using Scandinavian institutionalist translation theory as a theoretical framework, this study aims to make two contributions. First, we provide insights into the dynamics of the translation processes inherent in QIC implementation. Second, we discuss the implications of the translation processes as experienced by participating actors. METHODS: We used empirical data from a qualitative case study investigating the implementation of QICs as an approach to quality improvement within a national Danish healthcare quality program. We included two diverse QICs to allow for exploration of the significance of organizational complexity for the translation processes. Data comprised qualitative interviews, participant observation and documentary material. RESULTS: Translation was an inherent part of QIC implementation. Key actors at different organizational levels engaged in translation of their implementation roles, and the QIC content and methodology. They drew on different translation strategies and practices that mainly materialized as kinds of modification. The translations were motivated by deliberate, strategic, and pragmatic rationales, contingent on combinations of features of the actors' organizational contexts, and the transformability and organizational complexity of the QICs. The findings point to a transformative power of translation, as different translations led to various regional and local QIC versions. Furthermore, the findings indicate that translation affects the outcomes of the implementation process and the QIC intervention. Translation may positively affect the institutionalization of the QICs and the creation of professional engagement and negatively influence the QIC effects. CONCLUSION: The findings extends the current research concerning the understanding of the dynamics of the translation processes embedded in the local implementation of QICs, and thus constitute a valuable contribution to a more sustainable and effective implementation of QICs in healthcare improvement. For researchers and practitioners, this highlights translation as an embedded part of the QIC implementation process, and encourages detailed attention to the implications of translation for both organizational institutionalization and realisation of the expected intervention outcomes.

Nurses' perspectives on challenges and facilitators when implementing a self-management support intervention as an everyday healthcare practice: A qualitative study.

AIM: To explore registered nurses' perspectives on challenges and facilitators to implementing a telephone-based self-management support (SMS) intervention (Proactive Health Support) as an everyday healthcare practice, during the early stages of implementation. DESIGN: Data were collected using a qualitative research design involving focus-group interviews and participant observations. METHODS: We conducted participant observation following nine nurses and four focus group interviews with 14 nurses. Data were analysed using thematic analyses. RESULTS: Proactive Health Support was implemented in units organized independently of the existing organizational units within healthcare services. This independent organization, along with the intervention's generic (non-disease specific) design, empowered nurses to become autonomous practitioners capable of prioritizing the operationalization of SMS as an everyday healthcare practice. However, unlearning already embedded medical practices and establishing new nursing roles necessary to accommodate the intervention in practice was experienced a challenge. Education and supervision were identified as valuable tools for successful implementation. CONCLUSION: Our study highlights the significance of organizational context and autonomy in successful SMS implementation. Balancing external factors like organizational context, priority and time is vital, but navigating the internal shift in professional practice is equally crucial. Role transition processes can constitute challenges demanding accommodation. IMPLICATIONS FOR THE PROFESSION: From a nursing perspective, this study highlights that practising SMS requires substantial training and education. Generic SMS interventions can introduce higher levels of contingency due to their versatile nature. Thus, equipping nurses with competencies that enable them to navigate this unpredictability flexibly is crucial. IMPACT: Policymakers and administrators should allocate resources and support implementation processes in ways that accommodate both internal and external conditions to facilitate nurses in delivering effective SMS. REPORTING METHOD: This study adheres to the SRQR guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

A Novel Nanocomposite Material for Optically Stimulated Luminescence Dosimetry.

Radiotherapy is a well-established and important treatment for cancer tumors, and advanced technologies can deliver doses in complex three-dimensional geometries tailored to each patient's specific anatomy. A 3D dosimeter, based on optically stimulated luminescence (OSL), could provide a high accuracy and reusable tool for verifying such dose delivery. Nanoparticles of an OSL material embedded in a transparent matrix have previously been proposed as an inexpensive dosimeter, which can be read out using laser-based methods. Here, we show that Cu-doped LiF nanocubes (nano-LiF:Cu) are excellent candidates for 3D OSL dosimetry owing to their high sensitivity, dose linearity, and stability at ambient conditions. We demonstrate a scalable synthesis technique producing a material with the attractive properties of a single dosimetric trap and a single near-ultraviolet emission line well separated from visible-light stimulation sources. The observed transparency and light yield of silicone sheets with embedded nanocubes hold promise for future 3D OSL-based dosimetry.

Development in life expectancy with good and poor cognitive function in the elderly European Population from 2004-05 to 2015.

BACKGROUND: Living not just longer, but also cognitively healthier, and more independent lives is essential if European countries are to cope with the financial challenges that the shifting age composition of Europe's population presents. Here we investigate the change in life expectancy (LE) spent with good and poor cognitive function among older adults across Europe. METHODS: LE with good/poor cognitive function was estimated by the Sullivan Method. Cross-sectional data on cognitive functioning was obtained from 23,213 (wave 1, 2004-05) and 40,874 (wave 6, 2015) 50+-year-olds of the Survey of Health, Ageing and Retirement in Europe (SHARE). Information on mortality was obtained from the Eurostat Database. Results for 70+-year-olds were emphasized. RESULTS: LE with good cognitive function increased with 1.6 years from 10.7 years (95% CI: 10.6-10.9) in 2004-05 to 12.4 years (95% CI: 12.3-12.5) in 2015 for 70+-year-olds. Disparity was observed across sex and region. In 2004-05, a 70+-year-old woman could expect to spend 30.9% (95% CI: 29.4-32.4) of her remaining LE with poor cognitive function compared to 27.7% (95% CI: 26.0 -29.4) for men. In 2015, women (24.4% (95% CI: 23.4-25.3)) had considerably caught up with men (24.8% (95% CI:23.7.25.8)), shifting the pattern in favor of women. In 2004-05 and 2015, Northern Europeans had the lowest LE with poor cognitive function while Southern Europeans had the highest, but made the most improvement during the period. CONCLUSIONS: Overall we find that LE with poor cognitive function has been compressed in the European population of 70+-year-olds.

Proactive Health Support: a randomised controlled trial of telephone-based self-management support for persons at risk of hospital admission.

BACKGROUND: Persons with frequent hospital admissions have a disease burden that may exceed their self-management skills. The evidence base of telephone-based interventions to support self-management is poor with mixed results. The aim of this study is to evaluate the effect of Proactive Health Support (PaHS): telephone-based self-management support for persons with risk of hospitalizations. METHODS: This study is a national randomised controlled trial of PaHS versus usual universal tax-funded healthcare. Participants were persons at risk of emergency hospital admissions. The intervention began with a physical start-up session followed by telephone sessions of self-management support. The two co-primary outcomes were Health-Related Quality of Life (HRQoL) (Mental Health Component Summary Score of SF36v2) analysed with mixed models and hospital admissions analysed with Poisson regression at 6 months. Secondary outcomes were at 3- and 12-month follow-up and disease subgroup analyses. RESULTS: During the study period, 6,402 persons were randomised (3,190 intervention, 3,212 control). HRQoL was significantly improved at 6 months (Est. 1.4992, P = <0.0001) and at 3 and 12 months on all 10 scales. There was no overall effect on hospital admissions at 6 months with an adjusted estimate of 0.0074 (P = 0.8691). Persons with diabetes had significant improvement of HRQoL and reduced hospital admissions. CONCLUSIONS: The PaHS intervention improved HRQoL for all participants and reduced hospital admissions for persons with diabetes only.

Healthy life expectancy by frailty state in Europe from 2004 to 2015: findings from SHARE.

BACKGROUND: As populations age, the possible consequences of increased frailty are a major concern for the health sector. Here, we investigate how life expectancy with and without frailty has changed during a 10-11-year-period across Europe. METHODS: The Sullivan method was used to investigate changes in life expectancy with and without frailty in 10 European countries. Frailty status (non-frail, pre-frail and frail) was determined by use of the Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI). Data on frailty prevalence was obtained from 21 698 individuals in wave 1 (2004-05) and 38 859 individuals in wave 6 (2015) of the SHARE. Information on mortality was obtained from the Eurostat Database. RESULTS: In 2015, women aged 70 spent 25.0% (95% CI: 24.0-26.1) of their remaining life expectancy in a frail state, and the number for men was 11.5% (95% CI: 10.7-12.3). Southern Europeans spent 24.2% (95% CI: 22.9-25.4) of their remaining life expectancy in a frail state and the numbers for Central Europeans and Northern Europeans were 17.0% (95% CI: 16.0-17.9) and 12.2% (95% CI: 10.9-13.5), respectively. From 2004-05 to 2015, life expectancy increased by 1.1 years (from 15.3 to 16.4 years) for 70-year-old Europeans. Similarly, non-frail life expectancy increased by 1.1 years (95% CI: 0.8-1.4), whereas no significant changes in life expectancy in frail states were observed. CONCLUSIONS: This study suggests that Europeans today spend more years in a non-frail state than Europeans did 10-11 years ago. Our findings reflect a considerable inequality by gender and region.

The in vitro effect of antirheumatic drugs on platelet function.

Several antirheumatic drugs lower the cardiovascular risk among rheumatoid arthritis patients. It is, however, unknown whether inhibition of platelet function contributes to this risk reduction. Only few studies have investigated the potential role of platelets as a target of antirheumatic drugs. In this study, platelet function was tested in vitro in samples from 24 healthy individuals spiked with antirheumatic drugs in clinically relevant concentrations or vehicle. Platelet aggregation was tested with 96-well light transmission aggregometry (LTA), and when an effect ≥20% compared to vehicle was observed, flow cytometric platelet aggregation and activation were evaluated and closure time was measured by Platelet Function Analyzer (PFA-200). When evaluated by LTA, teriflunomide (the active metabolite of leflunomide), tocilizumab, and prednisolone reduced ADP- and collagen-induced platelet aggregation ≥20%, while adalimumab increased TRAP-induced platelet aggregation ≥20%. Using flow cytometry, agonist-induced platelet aggregation with teriflunomide or vehicle was mean ± standard deviation (SD); 30.7% ± 5.8 vs. 41.7% ± 6.5, p = 0.02 using ADP, and 34.7% ± 13.9 vs. 55.8% ± 3.9, p = 0.01 using collagen. Results indicate that teriflunomide, prednisolone, and tocilizumab inhibit, and adalimumab increases platelet aggregation. The study suggests that the majority of antirheumatic drugs mainly reduced cardiovascular risk through indirect effects (e.g., reducing inflammation).

Mobile X-ray outside the hospital: a scoping review.

BACKGROUND: For several years mobile X-ray equipment has been routinely used for imaging in patients too unwell within the hospital, when transportation to the radiology department was inadvisable. Now, mobile X-ray examinations are also used outside the hospital. The literature describes that fragile patients may benefit from mobile X-ray, but we need to provide insights into the breadth, depth and gaps in a body of literature. METHODS: The scoping review was performed by searching PubMed, Cinahl, Embase, EconLit and Health Technology Assessment. English-, Danish-, Norwegian-, German-, Italian-, French- and Swedish-language studies, published 1.1.2009-1.5.2020 about mobile X-ray outside the hospital were included. Participants were patients examined using mobile X-ray as the intervention. PRISMA was used when eligible to build up the review. To extract data from the selected articles, we used a structured summary table. RESULTS: We included 12 studies in this scoping review. The results were divided into four topics:1. Target population 2. Population health 3. Experience of care and 4. Cost effectiveness. The main findings are that target population could be larger for instance including hospice patients for palliative care, group dwelling for people with intellectual disabilities, or psychiatric patients, population health may be improved, image quality seems to be good and mobile X-ray may be cost effective. Limitations of language, databases and grey literature may have resulted in studies being missed. CONCLUSIONS: Mobile X-ray may be used outside hospital. There seems to be potential benefits to both patients and health care staff. Based on the published studies it is not possible to draw a final conclusion if mobile X-ray examination is a relevant diagnostic offer and for whom. Further studies are needed to assess the feasibility of use in fragile patients, also regarding staff, relatives and societal consequences and therefore the topic mobile X-ray needs more research.

Exploring patient experiences of participating in a telephone-based self-management support intervention: Proactive Health Support (PaHS).

AIM: Proactive Health Support is a telephone-based self-management intervention that is carried out in Denmark by Registered Nurses who provide self-management support to people at risk of hospital admission. We aimed to explore participants' experiences of Proactive Health Support and to identify what the participants find important and meaningful during the intervention process. DESIGN: Qualitative design involving semi-structured interview. METHODS: Using a phenomenological-hermeneutical framework, we conducted semi-structured interviews with 62 participants in their own homes (32 women, 30 men; aged 20-81 years) in spring and fall 2018. RESULTS: The participants felt confident that they could discuss every matter with the nurses. Participants benefitted from accessibility to the nurses' professional and medical competences and they felt relief that the nurses contacted them via the telephone due to their multiple health conditions. The participants felt that the nurses were available and helped them to navigate the healthcare system. CONCLUSION: The participants valued the intervention because they benefitted from the nurses' holistic approach. They described the nurses' knowledge and professionalism in relation to their symptoms, treatments, and medicine as important and meaningful. Accordingly, the intervention seemed to promote feelings of independence and self-management among the participants. IMPACT: From a nursing perspective, the study highlights that it is possible to establish a close relationship and behavioural change among participants through regular telephone contact.

Iterative Development of a Digital Game-Based Learning Concept: Introduction of Veterinary Herd Health Management in a Virtual Pig Herd.

A growing interest in the use of digital game-based learning has been identified in veterinary education. Projects in the development of veterinary game-based environments and scenarios are mostly initiated by veterinary institutions, faculties, or instructors; however, the process of development is complex and often involves expertise from a variety of disciplines. In the collaboration between professionals, discussions often arise about content, and how specific elements should be implemented or edited. As discussions are based on the individual experts' varied disciplines, it can be difficult to achieve a common language, and this leads to blockage and frustration in the development process. In 2012, the University of Copenhagen launched a project on digital game-based learning aimed at veterinary and agriculture students. The overall goal was to develop learning games for herd health management in pig production. The project was carried out in a collaboration between professional game developers, educational/didactic experts, and veterinarians. From early in the process, we identified a need to communicate across disciplines. Therefore, the framework of the Serious Game Development Triangle (SDT) was developed as a tool to facilitate a common language for solving complex issues. The SDT consists of three orientations: games, school, and professionalism. These three orientations are topics that are required considerations when developing a serious game that seeks to teach skills for a specific profession. The SDT contributed to improved understanding across disciplines and made the development process more progressive.

Altered excitability of small cutaneous nerve fibers during cooling assessed with the perception threshold tracking technique.

BACKGROUND: There is a need for new approaches to increase the knowledge of the membrane excitability of small nerve fibers both in healthy subjects, as well as during pathological conditions. Our research group has previously developed the perception threshold tracking technique to indirectly assess the membrane properties of peripheral small nerve fibers. In the current study, a new approach for studying membrane excitability by cooling small fibers, simultaneously with applying a slowly increasing electrical stimulation current, is evaluated. The first objective was to examine whether altered excitability during cooling could be detected by the perception threshold tracking technique. The second objective was to computationally model the underlying ionic current that could be responsible for cold induced alteration of small fiber excitability. The third objective was to evaluate whether computational modelling of cooling and electrical simulation can be used to generate hypotheses of ionic current changes in small fiber neuropathy. RESULTS: The excitability of the small fibers was assessed by the perception threshold tracking technique for the two temperature conditions, 20 °C and 32 °C. A detailed multi-compartment model was developed, including the ionic currents: NaTTXs, NaTTXr, NaP, KDr, KM, KLeak, KA, and Na/K-ATPase. The perception thresholds for the two long duration pulses (50 and 100 ms) were reduced when the skin temperature was lowered from 32 to 20 °C (p < 0.001). However, no significant effects were observed for the shorter durations (1 ms, p = 0.116; 5 ms p = 0.079, rmANOVA, Sidak). The computational model predicted that the reduction in the perception thresholds related to long duration pulses may originate from a reduction of the KLeak channel and the Na/K-ATPase. For short durations, the effect cancels out due to a reduction of the transient TTX resistant sodium current (Nav1.8). Additionally, the result from the computational model indicated that cooling simultaneously with electrical stimulation, may increase the knowledge regarding pathological alterations of ionic currents. CONCLUSION: Cooling may alter the ionic current during electrical stimulation and thereby provide additional information regarding membrane excitability of small fibers in healthy subjects and potentially also during pathological conditions.

Does closed incision negative wound pressure therapy in non-traumatic major lower-extremity amputations improve survival rates?

Closed incision negative pressure wound therapy (CINPWT) has been shown to be clinically effective compared with the traditional gauze dressing, reducing surgical site infections and wound complications. We evaluated the effect of CINPWT compared with gauze dressing on the need for revision surgery and survival after non-traumatic major lower amputation. We included 309 patients undergoing 403 major lower amputations in a retrospective study from January 1, 2010 to November 23, 2017. A total of 139 patients received CINPWT, and 170 patients received stump bandage. There was no statistically significant difference between the two groups regarding the need for revision surgery (P = .45). Fourteen stump bandage patients and 15 CINPWT patients died in hospital (P = .57). One year after amputation, 55 CINPWT patients and 66 stump bandage patients had died (P = .82). Survival probabilities adjusted for age and gender 2 years after amputation were .52 (.43-.61) and .49 (.42-.58), respectively, and 3 years after amputation were .36 (.25-.50) and .39 (.32-.47), respectively. We also found no significant difference in the need for revision surgery in survival probabilities up till 3 years after amputation between patients treated with CINPWT and patients treated with gauze bandage postoperatively.

Termination of pregnancy following a prenatal diagnosis of Down syndrome: A qualitative study of the decision-making process of pregnant couples.

INTRODUCTION: In Denmark, first trimester screening has a very high uptake (>90%). If Down syndrome is diagnosed, termination rates are high (>95%). The aim of this study was to investigate the timing of the decision to terminate pregnancy following a diagnosis of Down syndrome and the factors influencing this decision. MATERIAL AND METHODS: Semi-structured, qualitative interview study with 21 couples who had received a prenatal diagnosis of Down syndrome and decided to terminate the pregnancy. Participants were recruited from obstetric departments between February 2016 and July 2017. Data were analyzed using thematic analysis. RESULTS: Five themes were identified: "initial decision-making", "consolidating the decision", "reasons and concerns shaping the termination of pregnancy decision", "the right decision is also burdensome", and "perceived influences in decision-making". For most couples, the initial decision to terminate pregnancy was made before or during the diagnostic process, but it was re-addressed and consolidated following the actual diagnosis. Imagining a family future with a severely affected Down syndrome child was the main factor influencing the termination of pregnancy decision. The decision was articulated as "right" but also as existentially burdensome for some, due to fear of regret and concern about ending a potential life. The decision to terminate pregnancy was considered a private matter between the couple, but was refined through interactions with clinicians and social networks. CONCLUSION: All couples made an initial decision prior to receiving the Down syndrome diagnosis. Knowledge of the couple's initial decision may facilitate patient-centered communication during and after the diagnostic process. Couples may benefit from counseling to deal with grief and existential concerns.

Parental response to severe or lethal prenatal diagnosis: a systematic review of qualitative studies.

OBJECTIVE: A severe or lethal prenatal diagnosis places great demands on prospective parents, who face choices of far-reaching consequences, such as continuing or terminating the pregnancy. How best to support these parents is a clinical challenge. This systematic review aimed to identify and synthesize the qualitative evidence regarding prospective parents' responses to such prenatal diagnoses. METHODS: Following PRISMA guidelines, four databases were systematically searched and 28 studies met the inclusion criteria. Thematic analysis guided data extraction and synthesis of findings. The Confidence in the Evidence for Reviews of Qualitative research assessment tool was utilized to assess confidence in the findings. RESULTS: Prospective parents experienced multiple losses, for example, of the healthy child, normal pregnancy and envisioned future. After diagnosis, they requested timely and reliable information and empathetic continued interaction with clinicians. Prospective parents who continued the pregnancy wished to be acknowledged as parents and engaged in planning to obtain a sense of meaning and control. Selective disclosure and concerns about negative responses were issues both for the parents who terminated and those who continued a pregnancy. CONCLUSION: Clinicians can support parental coping following a severe prenatal diagnosis through continued dialogue and collaboration. Further research is needed on the experiences of parents who choose to terminate a pregnancy following prenatal diagnosis. © 2017 John Wiley & Sons, Ltd.

Experiences and expectations in the first trimester of pregnancy: a qualitative study.

BACKGROUND: A dominant context for pregnant women in the Western world is medical technologies such as ultrasound and screening. It has been argued that such technologies may result in tentative pregnancies, which may be particularly prominent in the first trimester. However, little is known about how women experience early pregnancy. OBJECTIVE: To explore the everyday experiences and expectations of first trimester pregnant women in a medicalized context of comprehensive and routine prenatal screening. DESIGN: Qualitative, semi-structured interviews analysed using thematic analysis. SETTING: Between May 2015 and January 2016, participants were recruited from two general practices and one obstetric ultrasound unit in Aarhus, Denmark. PARTICIPANTS: Twenty, first trimester pregnant women (15 primiparae, five multiparae) aged 21-39 years. RESULTS: Early pregnancy is often kept secret in the first trimester due to a higher risk of miscarriage. However, the pregnancy is very real in the lives of the pregnant women who make it meaningful through practices of information seeking, listening to the body and anticipating the different milestones in pregnancy. First trimester screening represents one such milestone that is expected to mark a new and more certain phase in the pregnancy. A majority expects to terminate following a prenatal diagnosis, but this does not seem to influence their engagement with the pregnancy. CONCLUSIONS: The pregnant women use medical technologies to mark a milestone in pregnancy but do not expect all concerns to disappear upon a normal screening result. The majority of women acknowledge that pregnancy involves simultaneous feelings of happiness and worry.