Search

Abstract Background Cytokines and growth factors (GF) have been implicated in the development of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD). We hypothesize that even small coordinated changes in inflammatory proteins or GFs may reveal changes in underlying regulating mechanisms that do not induce obvious changes in concentration of individual proteins. We therefore applied correlation network analysis of serum factors to determine early characteristics of these conditions. Methods Concentrations of 17 cytokines and five GFs were measured and analysed in blood samples from cord blood, on day one and during the following month in 72 extremely preterm infants. Spearman’s correlation networks distinguishing BPD and severe ROP patients from non-affected were created. Results Most cytokine concentrations correlated positively with each other and negatively with GFs. Very few individual cytokines differed between patients with and without ROP or BPD. However, networks of differently correlated serum factors were characteristic of the diseases and changed with time. In ROP networks, EPO, G-CSF and IL-8 (cord blood), BDNF and VEGF-A (first month) were prominent. In BPD networks, IL-1β, IGF-1 and IL-17 (day one) were noted. Conclusions Network analysis identifies protein signatures related to ROP or BPD in extremely preterm infants. The identified interactions between serum factors are not evident from the analysis of their individual levels, but may reveal underlying pathophysiological mechanisms in the development of these diseases.

Abstract Introduction The role of the complement inhibitory proteins CD46 and CD59 in the immune response to an acute coronary syndrome (ACS) is unknown. We investigated the relationships between the shedding of CD46 and CD59 into the circulation, reflected by plasma levels of soluble CD46 and CD59, and the risk for post-ACS complications. Methods We measured plasma sCD46 and sCD59 in a cohort of 546 ACS patients within 24 h after hospital admission, and after 6-weeks in a subgroup of 114 patients. Study outcomes were incident heart failure (HF), major adverse cardiovascular events (MACE) and mortality during a median follow-up period of up to 3.3 years. Echocardiography at 1-year was performed in the follow-up subgroup. Results Elevated sCD46 and sCD59 were correlated with increased levels of inflammatory mediators and metalloproteinases in plasma, and were associated with increased risk for MACE in Cox proportional hazard models adjusted for cardiovascular risk factors and revascularization [HR 95% CI 1.24 (1.02–1.52), p = 0.034 for sCD46 and 1.18 (1.00–1.38), p = 0.049 for sCD59]. Elevated sCD59 was also associated with higher incidence of HF [HR 95% CI 1.41 (1.15–1.74), p = 0.001], and with lower left ventricular ejection fraction at 1-year post-ACS (Spearman r = − 0.234, p = 0.020). We found no associations between plasma levels of the proteins at 6 weeks and outcomes. Conclusions Shedding of the complement regulators CD46 and CD59 in plasma in the acute phase of ACS is associated with a negative prognosis. Plasma sCD46 and sCD59 could reflect the degree of local immune activation and serve as prognostic biomarkers in ACS patients.

Abstract Background Hospitalization indicates the presence of severe disease and constitutes a leading cost in health care. We aimed to prospectively assess if prevalent diabetes mellitus contributes to excess all-cause and cause-specific hospital admissions and mortality at the population level. Methods We used a Swedish prospective population-based cohort, including 25,642 individuals of whom 4.2% had prevalent diabetes at baseline (mean age 61.2 ± 6.8 years, age range 44.8–73.4 years). We compared the number of hospitalizations and mortality classified according to the main chapters of the 10th revision of the International Classification of Diseases (ICD-10) during follow-up using nationwide inpatient registries, comparing individuals with and without prevalent diabetes, using multivariate adjusted negative binomial regression (incidence rate ratio, IRR) and Cox regression, respectively. Results During a median follow-up of 19 years, 18,904 subjects were hospitalized at least once [median 3 (IQR 2–6)] and 6767 (26.4%) individuals died. Overall, subjects with diabetes were hospitalized (IRR 1.83, p

Abstract Background and aim Common mental disorders are common reasons for long-term sick leave, especially among women. Return to work is often complex and unsuccessful, why more knowledge is needed regarding women’s health and psychological well-being in the return-to-work process. Therefore, the aim was to describe women’s health and psychological well-being in the return-to-work process, from women’s and first-line managers’ perspectives. Methods Individual interviews were conducted with 17 women and 16 first-line managers. Qualitative content analysis was performed based on the content areas “Women’s health (i.e. overall well-being, both physical and psychological) throughout the whole RTW process” and “Women’s psychological well-being (happiness, meaning and a sense of being significant) at work after work resumption” Themes and categories were created. Results Women and managers had similar descriptions, i.e. that women’s health and psychological well-being depend on the individual characteristics of women themselves, their private life, work and other stakeholders. However, women described relational work tasks (e.g. meeting patients) as beneficial for health, and highlighted small stressors in the work environment, which the managers did not. Having work that was compatible with private life, being in good health, having stimulating work tasks and strengthening relationships at work were important for the women’s psychological well-being. Conclusions Based on women’s and first-line managers experiences, promotion of women’s health and psychological well-being during the return-to-work process requires individually adapted assessments and actions involving women’s entire life situation. First-line managers should know that relational work tasks (e.g., meeting patients) can be beneficial for women’s health as well as that minor stressor in the work environment can put their health at risk.

Abstract Background Breastfeeding is a powerful public health intervention that produces long-term health benefits. However, in high-income countries such as Denmark, breastfeeding rates are suboptimal and unequally distributed across socio-economic positions. The ‘Breastfeeding – a good start together’ intervention, to promote longer duration of exclusive breastfeeding and reduce social inequity, was implemented in a cluster-randomised trial during 2022–2023 across 21 municipalities in two Danish regions. A process evaluation was conducted to assess the implementation, mechanisms of impact, and possible contextual factors affecting the intervention. Methods The study was guided by the Medical Research Council’s guidance for conducting process evaluations and employed a mixed-methods approach in a convergence design. Quantitative data: contextual mapping survey (n = 20), health visitor survey (n = 284), health visitor records from 20 clusters and intervention website statistics. Qualitative data: dialogue meetings (n = 7), focus groups (n = 3) and interviews (n = 8). Results Overall, the intervention was delivered as planned to intended recipients, with few exceptions. Health visitors responded positively to the intervention, noting that it fitted well within their usual practice and enhanced families’ chances of breastfeeding. Mothers expressed having received the intervention with few exceptions, and reacted positively to the intervention. Although health visitors were concerned about the potential stigmatisation of mothers receiving the intensified intervention, none of the interviewed mothers felt stigmatised. Contextual factors impacting the intervention implementation and mechanisms included staff and management turnover, project infrastructure and mothers’ context, such as resources, social networks and previous experiences. The overall fidelity of the intervention delivery was high. Conclusions Health visitors and families responded well to the intervention. Interventions aimed at enabling health care providers to deliver simplified and structured breastfeeding support, in alignment with support provided in other sectors of the health care system, may increase breastfeeding rates and reduce social inequity in breastfeeding, even in international contexts. Trial registration Clinical Trials: NCT05311631. First posted April 5, 2022.

Abstract Background Plant mutagenesis creates novel alleles, thereby increasing genetic and phenotypic diversity. The availability of the faba bean (Vicia faba L.) reference genome and a growing set of additional genomic resources has increased the scientific and practical value of mutant collections. We aimed to genotype and morphologically phenotype a historical faba bean mutant collection developed and characterized by Jan Sjödin (1934–2023) over half a century ago in order to increase its value to researchers. The collection was genotyped using high-throughput single-primer enrichment technology (SPET) assays. Results We used 11,073 informative single nucleotide polymorphism (SNP) markers spanning the faba bean genome to genotype 52 mutant lines along with the background line, cv. Primus. A range of flower, seed, leaf, and stipule mutations were observed. The analysis of population structure revealed a shallow structure with no major subpopulations. Principal component and cluster analyses revealed, to a minor extent, that the mutants clustered by their phenotype. Conclusions The mutants’ phenotypic variation and shallow structure indicate that the Sjödin faba bean collection has the potential to play a significant role in faba bean breeding and in genetic and functional studies.

Abstract Purpose To study the trend of delayed sequential bilateral cataract surgery (DSBCS) in Sweden in the past decade. Methods This register-based cohort study utilized data from the Swedish National Cataract Register (NCR) from 2010 through 2019. Register files from patients who underwent cataract surgery in both eyes during the study period were linked using their social security numbers. Bilateral surgeries on different days were classified as DSBCS. The study investigated the association between DSBCS within 3 months and several variables with stratification and multivariate logistic regression. The following variables were used: operation year, region, private or public unit, age, sex, indication for surgery, type of intraocular lens (IOL), preoperative visual acuity, ocular comorbidity, posterior capsule rupture and perioperative difficulties. Results During the study period, 368,106 patients underwent DSBCS, of which 62.6% (n = 230,331) had bilateral surgery within 3 months. The median time between the surgeries was 61 days (interquartile range 26–161 days), showing regional variations. Better visual acuity in the fellow eye, presence of ocular comorbidity, various perioperative events and complications were associated with longer time to surgery of the second eye. Conversely, cataract surgery in more recent years, private clinic, increasing age, anisometropia and multifocal IOL were associated with shorter timespan between surgeries. Conclusions The majority of DSBCS were conducted within a 3-month timeframe, with the interval between surgeries decreasing throughout the study period. Several rational factors were associated with the time difference, in addition to regional variations. Many patients would probably benefit from less time between the surgeries, and we encourage a clinical practice taking the whole patient’s visual function into account.

Abstract Background Breastfeeding is the ideal nutrition for infants and protects infants and mothers from a range of adverse health outcomes during their lifespan. In Denmark, while the breastfeeding initiation rate is high, only 14% of mothers meet the World Health Organization’s recommendation of exclusive breastfeeding at six months. Furthermore, a notable social inequity exists among those who achieve this recommendation. Knowledge of effective interventions to reduce breastfeeding inequity is limited. A previous hospital-based intervention succeeded in increasing breastfeeding duration. However, most breastfeeding support is provided in Danish municipalities by health visitors. This called for adapting the intervention to the health visiting program and developing an intensified intervention addressing the social inequity in breastfeeding. This article describes the adaptation and development process of a municipality-based intervention. Methods During a 15-month period in 2020–21, the municipal intervention was iteratively developed using a three-stage framework for developing complex health interventions described by Hawkins et al. The three stages were 1) need assessment and stakeholder consultation, 2) co-production and 3) prototyping. The process was inspired by O’Cathain et al.’s principles for a user-centred, co-created and theory- and evidence-based approach, involving parents and health visitors. Results In stage 1, we identified the needs and priorities of the target groups of the intervention. In stage 2, the intervention was developed through action research design and inspired by Duus’ ‘learning cycles’ as the method to enhance motivation and ownership and to strengthen the implementation process by creating a joint room for learning and reflection with health visitors and developers. In stage 3, the intervention was tested for feasibility and usefulness during a 2.5-month period accompanied by monthly dialogue meetings with health visitors and developers. In this period, the intervention was refined based on the gathered experiences and was subsequently prepared for evaluation. Conclusion The description of the development of this complex intervention, aimed at increasing breastfeeding duration and reducing inequity, offers breastfeeding practitioners and researchers a transparent foundation for continuously improving breastfeeding support and a methodology for complex intervention development. Trial registration Registered at Clinical Trials NCT05311631.

Abstract Background We sought to analyze, in well-defined clinical setting, the first 100 patients treated at the intraoperative MRI (iMRI) hybrid surgical theatre at our facility in a population-based setting to evaluate which pathologies are best approached with iMRI assisted surgeries, as this is not yet clearly defined. Methods Patients undergoing surgery in the 3T iMRI hybrid surgical theatre at our neurosurgical department between December 2017 to May 2021 were included after informed consent. Demographic, clinical, surgical, histological, radiological and outcome parameters, as well as variables related to iMRI, were retrospectively collected and analyzed. Patients were subdivided into adult and pediatric cohorts. Results Various neurosurgical procedures were performed; resection of tumors and epileptic foci, endoscopic skull base procedures including pituitary lesions, deep brain stimulation (DBS) and laser interstitial thermal therapy (LITT). In total, 41 patients were pediatric. An iMRI scan was carried out in 96% of cases and led to continuation of surgery in 50% of cases, mainly due to visualized remaining pathological tissue (95.2%). Median time to iMRI from intubation was 280 min and median total duration of surgery was 445 min. The majority of patients experienced no postoperative complications (70%), 13 patients suffered permanent postoperative deficits, predominantly visual. Conclusion Herein, we demonstrate the first 100 patients undergoing neurosurgery aided by iMRI at our facility since introduction. Indications for surgery differed between pediatric and adult patients. The iMRI was utilized for tumor surgeries, particularly adult low-grade gliomas and pediatric tumors, as well as for epilepsy surgery and DBS. In this heterogenous population, iMRI led to continuation of surgery in 50%. To establish the benefit in maximizing the extent of resection in these brain pathologies future studies are recommended. Clinical trial number Not applicable.

Abstract Background A team-based, individualised rehabilitation approach may be required to meet the complex needs of people with dementia. This randomised controlled pilot trial evaluated the feasibility of a person-centred multidimensional interdisciplinary rehabilitation programme for community-dwelling older people with dementia and their informal primary caregivers. Methods Participants with dementia were randomised to an intervention group (n = 31, mean age (SD) 78.4 (6.0) years) or usual care (n = 30, mean age 79.0 (7.1)). The rehabilitation programme consisted of a 20-week rehabilitation period containing assessments and interventions based on each individual’s goals, and group-based physical exercise plus social interaction twice a week for 16 weeks at a rehabilitation unit. After 5 and 14 months, the interdisciplinary team followed up participants over two four-week periods. For both groups, dates of deaths and decision to move to nursing home over three years, as well as interventions for the relevant periods, were collected. Blinded assessors measured physical functions, physical activity, activities of daily living, cognitive functions, nutritional status, and neuropsychiatric symptoms at baseline and at 5, 12, 24, and 36 months. Results Participants in the intervention group received a mean of 70.7 (20.1) interventions during the 20-week rehabilitation period, delivered by all ten team professions. The corresponding figures for the control group were 5.8 (5.9). In the intervention group, all but one participated in rehabilitation planning, including goal setting, and attendance in the exercise and social interaction groups was 74.8%. None of the adverse events (n = 19) led to any manifest injury or disease. Cox proportional hazard regression showed a non-significant lower relative risk (HR = 0.620, 95% CI 0.27–1.44) in favour of the intervention for moving to nursing home or mortality during the 36-month follow-up period. Linear mixed-effect models showed non-significant but potentially clinically meaningful between-group differences in gait, physical activity, and neuropsychological symptoms in favour of the intervention. Conclusions The rehabilitation programme seems feasible among community-dwelling older people with dementia. The overall results merit proceeding to a future definitive randomised controlled trial, exploring effects and cost-effectiveness. One could consider to conduct the programme earlier in the course of dementia, adding cognitive training and a control attention activity. Trial registration The study protocol, ISRCTN59155421 , was registered online 4/11/2015.

Abstract Background Most women experience vasomotor symptoms (VMS) during the menopausal transition. A 15-week resistance training intervention (RTI) significantly reduced moderate-to-severe VMS (MS-VMS) and improved health-related quality of life (HRQoL) and cardiovascular risk markers in postmenopausal women. Whether a short RTI could have long-term effects is unknown. We aimed to investigate whether there were intervention-dependent effects two years after a 15-week RTI on MS-VMS frequency, HRQoL, and cardiovascular risk markers in postmenopausal women. Methods This observational prospective cohort study is a follow-up to a randomized controlled trial (RCT) on a 15-week RTI in postmenopausal women (n = 57). The control group had unchanged low physical activity during these first 15 weeks. At the follow-up contact two years post-intervention, 35 women agreed to participate in an additional physical visit at the clinic with clinical testing, blood sampling, and magnetic resonance imaging, identical to the protocol at the baseline visit at the start of the RCT. Results Although all women showed reduced MS-VMS and increased moderate-to-vigorous physical activity (MVPA) over the 2-year follow-up compared to baseline, the groups from the original RCT (intervention group; IG, control group; CG) changed differently over time (p

Abstract Background The Nova Scotia Duck Tolling Retriever (NSDTR) has previously been highlighted as a breed at risk for developing immune mediated diseases and cancer. The immune response is of great importance for the development of neoplastic disease and a dysregulated immune response may predispose to cancer. Two of the commonly seen immune mediated diseases in NSDTRs are immune mediated rheumatic disease (IMRD), which bears similarities to systemic lupus erythematosus (SLE) affecting humans, and steroid-responsive meningitis-arteritis (SRMA), which is a non-infectious inflammation of the meninges and the leptomeningeal vessels. The aim of this survey study was to investigate the lifetime prevalence of immune mediated diseases and tumors among Swedish NSDTRs based on owners’ information. The study design was cross-sectional. A questionnaire was sent to 4102 persons who owned or had previously owned a NSDTR. The questions concerned information about the dog and its overall health status as well as specific diseases. Results The response rate was 30%, including 935 live NSDTRs, corresponding to approximately 20% of the current population registered in Sweden (n = 4564), and 177 dead dogs. The surveyed dogs were spread over different ages and sex and corresponded to the typical demographic profile of the general dog population. Of the 935 individuals that were alive, 28 dogs (3%) were reported as previously diagnosed with IMRD and 33 dogs (3.5%) were reported as previously diagnosed with SRMA, one dog was reported to have been diagnosed with both SRMA and IMRD. There were 129 dogs (14%) reported to have or have had a neoplasia of some kind. For the dead dogs (n = 177), almost 40% of the owners reported neoplasia as the main reason for death/euthanasia. Conclusion This study reports an estimated lifetime prevalence of IMRD and SRMA, in the studied population of Swedish NSDTRs, of 3.0 and 3.5% respectively. In this study, 14% of the living dogs (n = 935) were reported to have a neoplasia of some kind and almost 40% of the deceased dogs (n = 177) were euthanized due to neoplasia or suspicion of it.

Abstract Background Assessment of undergraduate students using assessment instruments in the clinical setting is known to be complex. The aim of this study was therefore to examine whether two different assessment instruments, containing learning objectives (LO`s) with similar content, results in similar assessments by the clinical supervisors and to explore clinical supervisors’ experiences of assessment regarding the two different assessment instruments. Method A mixed-methods approach was used. Four simulated care encounter scenarios were evaluated by 50 supervisors using two different assessment instruments. 28 follow-up interviews were conducted. Descriptive statistics and logistic binary regression were used for quantitative data analysis, along with qualitative thematic analysis of interview data. Result While significant differences were observed within the assessment instruments, the differences were consistent between the two instruments, indicating that the quality of the assessment instruments were considered equivalent. Supervisors noted that the relationship between the students and supervisors could introduce subjectivity in the assessments and that working in groups of supervisors could be advantageous. In terms of formative assessments, the Likert scale was considered a useful tool for evaluating learning objectives. However, supervisors had different views on grading scales and the need for clear definitions. The supervisors concluded that a complicated assessment instrument led to limited very-day usage and did not facilitate formative feedback. Furthermore, supervisors discussed how their experiences influenced the use of the assessment instruments, which resulted in different descriptions of the experience. These differences led to a discussion of the need of supervisor teams to enhance the validity of assessments. Conclusion The findings showed that there were no significant differences in pass/fail gradings using the two different assessment instruments. The quantitative data suggests that supervisors struggled with subjectivity, phrasing, and definitions of the LO´s and the scales used in both instruments. This resulted in arbitrary assessments that were time-consuming and resulted in limited usage in the day-to-day assessment. To mitigate the subjectivity, supervisors suggested working in teams and conducting multiple assessments over time to increase assessment validity.

Abstract Purpose Achilles tendon ruptures (ATRs) close to the insertion, in high-level athletes, and in patients at high risk of re-rupture, may be better suited to operative repair. Minimally Invasive Repair (MIR) of the Achilles tendon has excellent outcome and low complication rates. Traditionally MIR has showed lower repair strength, failing due to suture pull-out from the distal tendon stump. The aim of this study was to describe the outcome of ATR patients who received transosseous distal suture placement using a standard technique as a reference. Methods Following ATR, patients were evaluated for pre-injury activity level, body weight, location of the tear and size of the distal Achilles tendon stump. Patients considered to be at high-risk of re-rupture: Tegner level ≥ 8, body weight ≥ 105Kg and distal ATR, received transosseous (TO) distal suture placement (n = 20) rather than the usual transtendinous (TT) technique (n = 55). Patient reported outcome measures and functional evaluation was performed at 12 months following repair. Results At 12 months follow up both methods resulted in good median (IQR) Achilles tendon Total Rupture Score TO 83.8 (74-88.3) vs. TT 90 (79–94), low increased relative Achilles Tendon Resting Angle TO -3.5˚ (3.6) vs. TT -3.5˚ (3.3) and mean (SD) Single leg Heel-Rise Height Index TO 88.2% (9.9) vs. TT 85.6% (9.9) (n.s.). There were 4 re-ruptures in the high-risk group and 2 in the group receiving TT distal suture placement. All but one of these were traumatic in nature. The mode of failure following TO distal suture placement was proximal suture pull out. Conclusions To distal suture placement during minimally-invasive Achilles tendon repair for higher-risk patients can lead to results equivalent to those in lower-risk patients treated with a standard TT MIR technique, except for the re-rupture rate which remained higher. There may be factors that have greater influence on outcome other than suture placement following ATR.

Abstract Introduction Digital technologies have enabled new possibilities to assess dietary intake and have shown promise in terms of decreased participant burden, improved accuracy and lower costs. However, their potential and validity in pregnant populations are scarcely explored. Objectives This study aimed to (a) validate energy intakes obtained from a web-based dietary recall method developed for national surveys (RiksmatenFlex) against total energy expenditure (TEE) by means of the doubly labelled water (DLW) method, and (b) to compare intakes of macronutrients, key unhealthy and healthy foods as well as adherence to food-based dietary guidelines between RiksmatenFlex and repeated 24 h telephone dietary recalls in healthy Swedish pregnant women. Methods This study was conducted as a nested validation within the HealthyMoms trial. Intakes of foods, macronutrients and energy were assessed during three days through RiksmatenFlex and 24 h telephone dietary recalls, and Swedish Healthy Eating Index (SHEI) scores were also calculated for both methods (n = 52). For 24 women, TEE was also assessed through the DLW method. Paired Samples T-tests and Wilcoxon Signed Ranks Tests were used to identify differences between means for foods, macronutrients, energy and SHEI scores. Pearson correlation coefficient or Spearman’s rho were performed to identify relationships between variables. To compare energy intake (RiksmatenFlex) with TEE (DLW method) and 24 h telephone dietary recalls, Bland and Altman plots were constructed. Results Average energy intake from RiksmatenFlex (10,015 [SD 2004] kJ) was not statistically different from TEE (10,252 [SD 1197] kJ) (p = 0.596) (mean difference: -237 kJ/24 h). Correspondingly, there were small mean differences between average intakes of key unhealthy and healthy foods and average SHEI scores between RiksmatenFlex and 24 h telephone dietary recalls. However, the Bland and Altman plots showed wide limits of agreement for all dietary variables (e.g., for energy intake using RiksmatenFlex versus TEE: ±4239 kJ/24 h). High correlations between the investigated dietary variables for the two dietary methods were observed (r = 0.751 to 0.931; all p

Abstract Background Bladder cancer (BC) and Renal cell carcinoma (RCC) are the most common urogenital cancers among both sexes, with a yearly global incidence of around 500 000 each. Both BC and RCC have been linked to diabetes. Poor glycemic control (malglycemia) is a serious consequence of diabetes and a possible consequence of systemic treatments used in BC and RCC. The objective of this study was to investigate the prevalence of diabetes and use of hospital-based care for malglycemia in people with BC or RCC. Methods This Swedish retrospective population-based register study used national health-data registers for longitudinal data on cancer incidence covering 15 years, use of hospital-based health care, and filled prescriptions of outpatient medications. Study endpoints included co-prevalence of diabetes in individuals with BC/RCC, healthcare resource utilization due to malglycemia, use of systemic corticosteroids, and changes in diabetes management for people with concomitant type 2 diabetes. Results We identified 36,620 and 15,581 individuals diagnosed with BC and RCC, respectively, between 2006 and 2019. The proportion of individuals registered with diabetes was 24% in BC and 23% in RCC. An association between BC/RCC and poor glycemic control was found, although the number of malglycemic events in hospital-based care were few (65/59 per 1000 individuals with diabetes and BC/RCC respectively with at least one event). An earlier switch to insulin-based diabetes management was observed in BC/RCC compared to matched individuals with type 2 diabetes but no cancer. The results also indicated an association between steroid treatment and poor glycemic control, and that systemic corticosteroids were more common among people with BC/RCC compared to diabetes controls. Conclusion The high prevalence of diabetes and increased use of systemic corticosteroid treatment observed in this large national study highlights the need for specific clinical management, risk-assessment, and monitoring of individuals with BC/RCC and diabetes.

Abstract Background Care transitions are high-risk processes, especially for people with complex or chronic illness. Discharge letters are an opportunity to provide written information to improve patients’ self-management after discharge. The aim of this study is to determine the impact of discharge letter content on unplanned hospital readmissions and self-rated quality of care transitions among patients 60 years of age or older with chronic illness. Methods The study had a convergent mixed methods design. Patients with chronic obstructive pulmonary disease or congestive heart failure were recruited from two hospitals in Region Stockholm if they were living at home and Swedish-speaking. Patients with dementia or cognitive impairment, or a “do not resuscitate” statement in their medical record were excluded. Discharge letters from 136 patients recruited to a randomised controlled trial were coded using an assessment matrix and deductive content analysis. The assessment matrix was based on a literature review performed to identify key elements in discharge letters that facilitate a safe care transition to home. The coded key elements were transformed into a quantitative variable of “SAFE-D score”. Bivariate correlations between SAFE-D score and quality of care transition as well as unplanned readmissions within 30 and 90 days were calculated. Lastly, a multivariable Cox proportional hazards model was used to investigate associations between SAFE-D score and time to readmission. Results All discharge letters contained at least five of eleven key elements. In less than two per cent of the discharge letters, all eleven key elements were present. Neither SAFE-D score, nor single key elements correlated with 30-day or 90-day readmission rate. SAFE-D score was not associated with time to readmission when adjusted for a range of patient characteristics and self-rated quality of care transitions. Conclusions While written summaries play a role, they may not be sufficient on their own to ensure safe care transitions and effective self-care management post-discharge. Trial registration Clinical Trials. giv, NCT02823795, 01/09/2016.

Abstract Background Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype. Methods Participants from a large, prospective, population-based, Swedish study were included (n = 3,229). Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA1c), different lipid levels, physical activity, alcohol consumption, smoking, education, APOE genotype, age and sex. All models were adjusted for follow-up time and basic demographics, and, in a second step, all significant predictors were included to examine independent effects. Follow-up outcomes were memory and attention/executive functions. Results The mean age at baseline was 56.1 (SD 5.7) years and 59.7% were women. The mean follow-up time was 17.4 (range 14.3–20.8) years. When examining independent effects, APOE ε4 genotype(p

Abstract Background Studies suggest that cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)42 and Aβ40 present a circadian rhythm. However sustained sampling of large volumes of CSF with indwelling intrathecal catheters used in most of these studies might have affected CSF dynamics and thereby confounded the observed fluctuations in the biomarker levels. Methods We included 38 individuals with either normal (N = 20) or abnormal (N = 18) CSF Aβ42/Aβ40 levels at baseline. CSF and plasma were collected at two visits separated by an average of 53 days with lumbar punctures and venipunctures performed either in the morning or evening. At the first visit, sample collection was performed in the morning for 17 participants and the order was reversed for the remaining 21 participants. CSF and plasma samples were analyzed for Alzheimer’ disease (AD) biomarkers, including Aβ42, Aβ40, GFAP, NfL p-tau181, p-tau217, p-tau231 and t-tau. CSF samples were also tested using mass spectrometry for 22 synaptic and endo-lysosomal proteins. Results CSF Aβ42 (mean difference [MD], 0.21 ng/mL; p = 0.038), CSF Aβ40 (MD, 1.85 ng/mL; p

Abstract Background Suicide prevention media campaigns are one way of reaching people at increased suicide risk who would otherwise not seek help. This is the first study of a Norwegian campaign directed both at individuals at risk for suicide and at their social network. Methods We evaluated a media campaign consisting of outdoor posters, feature articles, film clips, and online banners in print, digital, and social media spread across the Mid-Norway region in late autumn 2022. This campaign material consisted of information about how to seek help for suicide thoughts and mental health problems and how to help a friend in similar situations. Before and after this campaign, 1149 adult individuals living in Mid-Norway participated in a survey on attitudes to suicide, mental ill health, and help-seeking. Results There were only marginal changes in attitudes and help-seeking literacy after the campaign. This result was sustained when controlling for age, sex, and campaign visibility. For males, there were a few changes in the negative direction, i.e. lack of willingness to seek help from family and friends, after the campaign. Conclusion We conclude that the campaign did not seem to have the desired effect and suggest ways of improving future regional Norwegian media campaigns.

Abstract Background A person’s sense of coherence (SoC) is likely to affect coping when exposed to a life changing event like the COVID -19 pandemic, which impacted the older population especially hard, an age group that already suffers from a lot of mental illness. Thus, the aim of this study was to investigate the associations between SoC and mental health in older adults using both screening scales and hair cortisol concentrations (HCC). Method A cross-sectional design studying a cohort of 70–80 years old, N = 260, set in Swedish primary care during the pandemic years 2021–2022. Instruments used are sense of coherence 13 (SoC-13), EQ-5D-3L, Geriatric depression scale 20 (GDS-20), Hospital anxiety and depression scale (HADS), and Perceived stress scale 10 (PSS-10). Sociodemography and factors concerning SoC, and mental health are explored. HCC are measured using radioimmunoassay. Outcome measures are factors independently associated with SoC. Linear regression models were performed with SoC as dependent variable, and priory path analyses explored whether associations with SoC were direct, or indirect via anxiety. Results SoC was significantly associated with anxiety (p

Abstract Background The molecular pathways linking short and long sleep duration with incident diabetes mellitus (iDM) and incident coronary heart disease (iCHD) are not known. We aimed to identify circulating protein patterns associated with sleep duration and test their impact on incident cardiometabolic disease. Methods We assessed sleep duration and measured 78 plasma proteins among 3336 participants aged 46–68 years, free from DM and CHD at baseline, and identified cases of iDM and iCHD using national registers. Incident events occurring in the first 3 years of follow-up were excluded from analyses. Tenfold cross-fit partialing-out lasso logistic regression adjusted for age and sex was used to identify proteins that significantly predicted sleep duration quintiles when compared with the referent quintile 3 (Q3). Predictive proteins were weighted and combined into proteomic scores (PS) for sleep duration Q1, Q2, Q4, and Q5. Combinations of PS were included in a linear regression model to identify the best predictors of habitual sleep duration. Cox proportional hazards regression models with sleep duration quintiles and sleep-predictive PS as the main exposures were related to iDM and iCHD after adjustment for known covariates. Results Sixteen unique proteomic markers, predominantly reflecting inflammation and apoptosis, predicted sleep duration quintiles. The combination of PSQ1 and PSQ5 best predicted sleep duration. Mean follow-up times for iDM (n = 522) and iCHD (n = 411) were 21.8 and 22.4 years, respectively. Compared with sleep duration Q3, all sleep duration quintiles were positively and significantly associated with iDM. Only sleep duration Q1 was positively and significantly associated with iCHD. Inclusion of PSQ1 and PSQ5 abrogated the association between sleep duration Q1 and iDM. Moreover, PSQ1 was significantly associated with iDM (HR = 1.27, 95% CI: 1.06–1.53). PSQ1 and PSQ5 were not associated with iCHD and did not markedly attenuate the association between sleep duration Q1 with iCHD. Conclusions We here identify plasma proteomic fingerprints of sleep duration and suggest that PSQ1 could explain the association between very short sleep duration and incident DM.

Abstract Background Globally as well as in Sweden, diseases that are caused by unhealthy lifestyle habits are the most common causes of death and disability. Even though there are guidelines that oblige all health-care professionals to counsel patients about lifestyle, studies have shown that it is not prioritized within healthcare. One reason for this among nurses has been shown to be lack of confidence in knowledge and counselling skills. This study aimed to develop, and quality assess the psychometric properties of an instrument to measure self-efficacy in lifestyle counselling. Methods An instrument inspired by an American instrument, following Bandura’s recommendations for development of self-efficacy measures, was developed according to Swedish national guidelines for disease-prevention. The instrument was revised after cognitive interviews with nursing students, university teachers within health sciences, and clinical experts, then administrated to 310 nursing students at different levels in their education. The instrument was tested with Rasch Measurement Theory, with focus on dimensionality, local dependency, targeting, reliability, response category functioning, Rasch model fit, and differential item functioning by age, gender, educational level and previous health care education. Results The development of the instrument resulted in 20 + 20 items, 20 items about self-efficacy in knowledge, and 20 items about self-efficacy in ability to counsel persons about their lifestyle. The analyses showed that knowledge and ability are two different, but related, constructs, where ability is more demanding than knowledge. The findings provide support (considering dimensionality and local dependency) for that all 20 items within the knowledge construct as well as the 20 items within the ability construct can be summed, achieving two separate but related total scores, where knowledge (reliability 0.81) is a prerequisite for ability (reliability 0.84). Items represented lower self-efficacy than reported by the respondents. Response categories functioned as expected, Rasch model fit was acceptable, and there was no differential item functioning. Conclusions The SELC 20 + 20 was found to be easy to understand with an acceptable respondent burden and the instrument showed good measurement properties.

Abstract Background With access to antiretroviral therapy (ART) HIV infection is a chronic manageable condition and non-sexually transmissible. Yet, many people living with HIV still testify about experiencing HIV-related stigma and discrimination. It is well-documented that HIV-related stigma and discrimination continue to be critical barriers to prevention, treatment, care and quality of life. From an individual stigma-reduction intervention perspective, it is essential to identify individual and interpersonal factors associated with HIV-related stigma manifestations. To address this issue and to expand the literature, the aim of this study was to assess the prevalence of HIV-related stigma manifestations and their associated factors among a diverse sample of people living with HIV in Sweden. Method Data from 1 096 participants were derived from a nationally representative, anonymous cross-sectional survey ”Living with HIV in Sweden”. HIV-related stigma manifestations were assessed using the validated Swedish 12-item HIV Stigma Scale encompassing four HIV-related stigma manifestations: personalised stigma, concerns with public attitudes towards people living with HIV, concerns with sharing HIV status, and internalized stigma. Variables potentially associated with the HIV-related stigma manifestations were divided into four categories: demographic characteristics, clinical HIV factors, distress and ART adherence, and available emotional HIV-related support. Four multivariable hierarchical linear regression analyses were employed to explore the associations between multiple contributors and HIV-related stigma manifestations. Results The most dominating stigma feature was anticipation of HIV-related stigma. It was manifested in high scores on concerns with sharing HIV status reported by 78% of the participants and high scores on concerns about public attitudes towards people living with HIV reported by 54% of the participants. High scores on personalised stigma and internalized stigma were reported by around one third of the participants respectively. Between 23 and 31% of the variance of the four reported HIV-related stigma manifestations were explained mainly by the same pattern of associated factors including female gender, shorter time since HIV diagnosis, feelings of hopelessness, non-sharing HIV status, and lack of available emotional HIV-related support. Conclusion The most dominating stigma feature was anticipation of stigma. Female gender, shorter time since HIV diagnosis, feelings of hopelessness, non-sharing HIV status, and lack of available emotional HIV-related support constituted potential vulnerability factors of the four HIV-related stigma manifestations. Our findings highlight the vital necessity to support people living with HIV to increase their resilience to stigma in its different forms. Exploring associated factors of HIV-related stigma manifestations may give an indication of what circumstances may increase the risk of stigma burden and factors amenable to targeted interventions. As individual stigma-reductions interventions cannot be performed isolated from HIV-related stigma and discrimination in society, a key challenge is to intensify anti-stigma interventions also on the societal level.

Abstract Background The advancement of sequencing technologies results in the rapid release of hundreds of new genome assemblies a year providing unprecedented resources for the study of genome evolution. Within this context, the significance of in-depth analyses of repetitive elements, transposable elements (TEs) in particular, is increasingly recognized in understanding genome evolution. Despite the plethora of available bioinformatic tools for identifying and annotating TEs, the phylogenetic distance of the target species from a curated and classified database of repetitive element sequences constrains any automated annotation effort. Moreover, manual curation of raw repeat libraries is deemed essential due to the frequent incompleteness of automatically generated consensus sequences. Results Here, we present an example of a crowd-sourcing effort aimed at curating and annotating TE libraries of two non-model species built around a collaborative, peer-reviewed teaching process. Manual curation and classification are time-consuming processes that offer limited short-term academic rewards and are typically confined to a few research groups where methods are taught through hands-on experience. Crowd-sourcing efforts could therefore offer a significant opportunity to bridge the gap between learning the methods of curation effectively and empowering the scientific community with high-quality, reusable repeat libraries. Conclusions The collaborative manual curation of TEs from two tardigrade species, for which there were no TE libraries available, resulted in the successful characterization of hundreds of new and diverse TEs in a reasonable time frame. Our crowd-sourcing setting can be used as a teaching reference guide for similar projects: A hidden treasure awaits discovery within non-model organisms.

Abstract Background Home visiting programmes aiming to support parents and promote more equal health amongst young children have grown in Sweden and in other countries. These programmes involve interprofessional teams. Teamwork in interprofessional contexts often requires setting boundaries, but professionals’ boundary work in the home setting is unexplored. Therefore, this article focuses on interprofessional teams comprising child healthcare nurses, midwives, social workers, and dental hygienists in a home visiting programme for first-time parents in Sweden; it aims to explore how the professionals performed boundary work that enabled collaboration and to investigate important contextual conditions for this kind of boundary work. Methods The data were drawn from semi-structured interviews with twelve professionals from the four different disciplines. Content analysis was used to explore their boundary work. Results The findings show that the professionals performed three forms of collaborative boundary work. They maintained boundaries by clarifying their distinct roles and expertise. However, the differences were viewed as complementary, and the professionals worked together humbly to complement each other’s knowledge and perspectives. Lastly, they tended to drop perceptions of prestige and blurred the boundaries to accommodate their overlapping knowledge. Important conditions for the success of collaborative boundary work were meetings prior to the home visits, the opportunities for discussion and reflection after the home visits, and the informal character of the home setting. Consequently, the professionals were able to jointly contribute to a holistic view of the visited families, which increased the possibilities to meet these families’ needs. Conclusions This study contributes knowledge on boundary work in interprofessional collaborations in the home setting. The informal character of the home setting seemed to facilitate collaboration and contributed to creating informal professional roles. The findings suggest that having interprofessional teams in the home setting enabled collaboration as well as reinforced support for first-time parents, which emphasizes the merit of home visit programmes.

Abstract Background Patients’ ideas, concerns, and expectations are three important concepts in consultation techniques. Limited studies on these concepts include responses from both health care providers and care recipients of the same consultation. Highlighting both perspectives provides an increased understanding of the consultation. This study aims to explore the perspectives of patients and health care professionals about patients’ expectations of primary health care during consultations with primary care physicians and compare the two sets of perspectives. Methods A cross-sectional study. Patients (n = 113) and physicians (n = 67) from five primary health care centers completed a questionnaire after planned consultations. Their responses to open-ended questions about patients’ expectations, from patients’ and physicians’ perspectives were analyzed with qualitative content analyses. Results The patients expected a personal journey, through the primary health care system where they were the subject of interest. A journey, with ready access to a health care provider followed by a consultation with the physician, medical measures administered, their outcomes discussed, and a plan developed for continued health care. The physicians observed patients’ expectations to concern the responsibilities placed on primary health care where patients were the object of interest. Patients’ short-term expectations were described in a similar way by both patients and physicians. Patients expressed their long-term expectations as more personal and interpersonal whereas physicians observed them from a more professional and organizational standpoint. Conclusions Patients and physicians have different views of what patients expect of primary health care. While patients’ short-term expectations were perceived by physicians, their long-term expectations were not. Patients expected more of a personal journey through the primary health care system while physicians observed patients’ expectations to concern the responsibilities placed on primary health care. Identifying and meeting patients’ expectations is an important part of patient-centered care, and a better understanding of patients’ expectations is needed to improve health professionals’ consultation skills.

Abstract Background Device-related bacterial infections account for a large proportion of hospital-acquired infections. The ability of bacteria to form a biofilm as a protective shield usually makes treatment impossible without removal of the implant. Topographic surfaces have attracted considerable attention in studies seeking antibacterial properties without the need for additional antimicrobial substances. As there are still no valid rules for the design of antibacterial microstructured surfaces, a fast, reproducible production technique with good resolution is required to produce test surfaces and to examine their effectiveness with regard to their antibacterial properties. Methods In this work various surfaces, flat and with microcylinders in different dimensions (flat, 1, 3 and 9 μm) with a surface area of 7 × 7 mm were fabricated with a nanoprinter using two-photon lithography and evaluated for their antibiofilm effect. The microstructured surfaces were cultured for 24 h with different strains of Pseudomonas aeruginosa and Staphylococcus aureus to study bacterial attachment to the patterned surfaces. In addition, surface wettability was measured by a static contact angle measurement. Results Contact angles increased with cylinder size and thus hydrophobicity. Despite the difference in wettability, Staphylococcus aureus was not affected by the microstructures, while for Pseudomonas aeruginosa the bacterial load increased with the size of the cylinders, and compared to a flat surface, a reduction in bacteria was observed for one strain on the smallest cylinders. Conclusions Two-photon lithography allowed rapid and flexible production of microcylinders of different sizes, which affected surface wettability and bacterial load, however, depending on bacterial type and strain.

Abstract Background Polycystic ovary syndrome (PCOS) has previously been associated with several comorbidities that may have shared genetic, epigenetic, developmental or environmental origins. PCOS may be influenced by prenatal androgen excess, poor intrauterine or childhood environmental factors, childhood obesity and learned health risk behaviors. We analyzed the association between PCOS and several relevant comorbidities while adjusting for early-life biological and socioeconomic conditions, also investigating the extent to which the association is affected by familial risk factors. Methods This total-population register-based cohort study included 333,999 full sisters, born between 1962 and 1980. PCOS and comorbidity diagnoses were measured at age 17-45 years through national hospital register data from 1997 to 2011, and complemented with information on the study subjects´ early-life and social characteristics. In the main analysis, sister fixed effects (FE) models were used to control for all time-invariant factors that are shared among sisters, thereby testing whether the association between PCOS and examined comorbidities is influenced by unobserved familial environmental, social or genetic factors. Results Three thousand five hundred seventy women in the Sister sample were diagnosed with PCOS, of whom 14% had obesity, 8% had depression, 7% had anxiety and 4% experienced sleeping, sexual and eating disorders (SSE). Having PCOS increased the odds of obesity nearly 6-fold (adjusted OR (aOR): 5.9 [95% CI:5.4-6.5]). This association was attenuated in models accounting for unobserved characteristics shared between full sisters, but remained considerable in size (Sister FE: aOR: 4.5 [95% CI: 3.6-5.6]). For depression (Sister FE: aOR: 1.4 [95% CI: 1.2-1.8]) and anxiety (Sister FE: aOR: 1.5 [95% CI: 1.2-1.8), there was a small decrease in the aORs when controlling for factors shared between sisters. Being diagnosed with SSE disorders yielded a 2.4 aOR (95% CI:2.0-2.6) when controlling for a comprehensive set of individual-level confounders, which only decreased slightly when controlling for factors at the family level such as shared genes or parenting style. Accounting for differences between sisters in observed early-life circumstances influenced the estimated associations marginally. Conclusion Having been diagnosed with PCOS is associated with a markedly increased risk of obesity and sleeping, sexual and eating disorders, also after accounting for factors shared between sisters and early-life conditions.

Abstract Background Even though there has been a cultural change within residential aged care to a more person-centered care, there remain improvements to be made for a more consistent way of working. Using a salutogenic approach along with person-centered care is a potential way to promote it. This study aimed to describe nurses’ experiences of combining person-centered care with a salutogenic approach at a nursing home for older people. Methods Nine nurses, specially trained in salutogenesis and Sense of coherence, were individually interviewed using a semi-structured interview approach. Data was analysed through qualitative content analysis. Results The nurses experienced that the residential aged care was improved by using salutogenesis and Sense of coherence as a complement to person-centered care. Core aspects of person-centered care were thereby promoted, as the resources of the older persons were emphasized, and aged care became more holistic. In addition to improved residential aged care, the results indicate that this manner of working also contributed to enhanced work satisfaction of the care personnel themselves. Conclusions The results suggest that a salutogenic approach facilitates the implementation of person-centered care by focusing on the older persons’ resources and maintaining health. The organization needs to prioritize training staff in salutogenesis and person-centered care, as it supports working toward a common goal and benefits both the older persons and the staff.

Abstract Background Adolescent mental health problems are on the rise globally, including in Sweden. One indicator of this trend is increased psychosomatic symptoms (PSS) over time. Lifestyle factors such as physical activity (PA), diet, smoking, and alcohol consumption may influence the time trends in PSS; however, the evidence base is scarce. The aim of this study was to investigate associations between time trends in PSS and lifestyle factors. Methods The study was based on data collected from a nationally representative sample of 9,196 fifteen-year-old boys and girls in Sweden using the Health Behavior in School-aged Children (HBSC) symptom checklist. The sample comprised nearly equal proportions of girls (50.5%) and boys. The lifestyle factors examined in this study included PA, regular breakfast intake, consumption of fruits, vegetables, sweets, or soft drinks, smoking, and alcohol drunkenness. We used data from 2002 to 2018 and stratified by family affluence scale (FAS) to demonstrate how the associations varied among the FAS groups. We fitted separate regression models for the high- and low-FAS groups, where interaction terms between the year of survey and each lifestyle factor were used to estimate the level and direction of associations between the factors and trends in PSS. Results There was a generally increasing trend in PSS mean scores from 2.26 in 2002 to 2.49 in 2018 (p

Abstract Background Out-of-hospital cardiac arrest (OHCA) is a leading cause of death, and survival outcomes vary across countries and regions. To improve survival, the European Resuscitation Council Guidelines encourage the implementation of technologies like smartphone applications to alert voluntary first responders (VFRs) who are near a suspected OHCA. VFRs are of great importance in the ´chain of survival´, but there is still a lack of knowledge about their experiences; especially of those operating in rural areas. Understanding those experiences is crucial in developing appropriate interventions to train, encourage, and safeguard VFRs in their mission. Therefore, the aim of this study was to describe VFRs´ experiences of being dispatched to suspected OHCA in rural areas. Methods The study used an inductive design. The data were collected using individual interviews with 16 VFRs and analysed using qualitative content analysis. Results The results are presented in terms of six generic categories ‘‘Being motivated and prepared’’, ‘‘Having strategies to undertake the mission’’, ‘‘Collaborating with others’’, ‘‘Being ethically aware’’, ‘‘Supporting the family members’’, and ‘‘Coping with the mission’’, which formed the basis of the main category ‘Desire to save lives and help others’. The findings showed that VFRs had a genuine desire to contribute to save lives in this rural area. Regardless of the circumstances, they were prepared to leave everything and act to the best for the victim and their family members. In theirs’ missions they collaborated with others at the scene and were guided by ethics while they acted in complex circumstances. Conclusions VFRs dispatched in rural areas express a desire to save lives. In their missions, they acted in complex situations and experienced both emotional and ethical challenges. The design, implementation, and evaluation of support interventions directed at VFRs should be prioritised, especially in rural areas, as it can contribute to more people becoming and remaining VFRs, which in turn could contribute to sustainable development.

Abstract Background Reports at the beginning of the COVID-19 pandemic suggested differences in COVID-19-associated mortality between individuals with serious mental disorders (SMD) and the population at large. Aim To compare the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden over the two main pandemic years. Methods We compared the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden during 2020 and 2021. For SMD, we included psychotic disorder, bipolar disorder, and severe depression. The analysis was based on summary data from the Swedish Board of Health and Welfare covering the entire adult Swedish population. Results The overall relative risk (RR) for experiencing a COVID-19-associated death was 1.66 (CI 1.50–1.83; p

Abstract Background Mental health problems among older people are large public health concerns but often go unrecognized and undertreated. During COVID − 19 several restrictions regarding social contacts were launched, primarily for the old. The objective of this study is to investigate which factors that had the main negative affect on mental health in the older population during the pandemic. Method A cross-sectional cohort study set in Swedish primary care during the pandemic years 2021–2022. The population constitutes of 70–80-years-old, N = 260. Instruments used are Geriatric depression scale 20 (GDS20); Hospital anxiety and depression scale (HADS), and Perceived stress scale 10 (PSS10). Sociodemography and risk factors are explored. Outcome measures are factors independently associated with decreased mental health. Analyses were performed for the group as a whole and with logistic regression models comparing individuals who stated they were mentally affected by the pandemic to individuals who stated they were not. Results Participants who stated they were mentally affected by the COVID − 19 pandemic reported significantly higher levels of anxiety (p

Abstract Introduction A chronic Achilles tendon rupture (ATR) is defined as an ATR that has been left untreated for more than four weeks following rupture. This systematic review aims to summarize the outcomes of chronic ATR treated using either a gastrocnemius aponeurosis flap or semitendinosus tendon graft. Methods A systematic search was conducted in three databases (PubMed, Scopus and Cochrane), for studies describing outcomes after surgical treatment of chronic ATR using gastrocnemius aponeurosis flaps or semitendinosus tendon grafts with more than 10 patients included. The studies were assessed for quality and risk of bias using the Methodological Items used to assess risk of bias in Non-Randomized Studies (MINORS). Results Out of the 818 studies identified with the initial search, a total of 36 studies with 763 individual patients were included in this systematic review. Gastrocnemius aponeurosis flap was used in 21 and semitendinosus tendon graft was used in 13 of the studies. The mean (SD) postoperative Achilles tendon Total Rupture Score (ATRS) for patients treated with a gastrocnemius aponeurosis flap was 83 (14) points and the mean (SD) American Orthopaedic Foot and Ankle Score (AOFAS) was 96 (1.7) points compared with ATRS 88 (6.9) points and AOFAS 92 (5.6) points for patients treated with a semitendinosus tendon graft. The included studies generally had low-quality according to MINORS, with a median of 8 (range 2–13) for all studies. Conclusion Both gastrocnemius aponeurosis flaps and semitendinosus tendon grafts give acceptable results with minimal complications and are valid methods for treating chronic ATR. The main difference is more wound healing complications in patients treated with a gastrocnemius aponeurosis flap and more sural nerve injuries in patients treated with a semitendinosus grafts. The current literature on the subject is of mainly low quality and the absence of a patient-related outcome measure validated for chronic ATR makes comparisons between studies difficult. Level of evidence Level IV.

Abstract Background Mucosal vaccines have the potential to induce protective immune responses at the sites of infection. Applying CRISPR/Cas9 editing, we aimed to develop a probiotic-based vaccine candidate expressing the HIV-1 envelope membrane-proximal external region (MPER) on the surface of E. coli Nissle 1917. Results The HIV-1 MPER epitope was successfully introduced in the porin OmpF of the E. coli Nissle 1917 (EcN-MPER) and the modification was stable over 30 passages of the recombinant bacteria on the DNA and protein level. Furthermore, the introduced epitope was recognized by a human anti-HIV-1 gp41 (2F5) antibody using both live and heat-killed EcN-MPER, and this antigenicity was also retained over 30 passages. Whole-cell dot blot suggested a stronger binding of anti-HIV-1 gp41 (2F5) to heat-killed EcN-MPER than their live counterpart. An outer membrane vesicle (OMV) – rich extract from EcN-MPER culture supernatant was equally antigenic to anti-HIV-1 gp41 antibody which suggests that the MPER antigen could be harboured in EcN-MPER OMVs. Using quantitative ELISA, we determined the amount of MPER produced by the modified EcN to be 14.3 µg/108 cfu. Conclusions The CRISPR/Cas9 technology was an effective method for establishment of recombinant EcN-MPER bacteria that was stable over many passages. The developed EcN-MPER clone was devoid of extraneous plasmids and antibiotic resistance genes which eliminates the risk of plasmid transfer to animal hosts, should this clone be used as a vaccine. Also, the EcN-MPER clone was recognised by anti-HIV-1 gp41 (2F5) both as live and heat-killed bacteria making it suitable for pre-clinical evaluation. Expression of OmpF on bacterial surfaces and released OMVs identifies it as a compelling candidate for recombinant epitope modification, enabling surface epitope presentation on both bacteria and OMVs. By applying the methods described in this study, we present a potential platform for cost-effective and rational vaccine antigen expression and administration, offering promising prospects for further research in the field of vaccine development.

Abstract Background Amyloid and tau aggregates are considered to cause neurodegeneration and consequently cognitive decline in individuals with Alzheimer’s disease (AD). Here, we explore the potential of cerebrospinal fluid (CSF) proteins to reflect AD pathology and cognitive decline, aiming to identify potential biomarkers for monitoring outcomes of disease-modifying therapies targeting these aggregates. Method We used a multiplex antibody-based suspension bead array to measure the levels of 49 proteins in CSF from the Swedish GEDOC memory clinic cohort at the Karolinska University Hospital. The cohort comprised 148 amyloid- and tau-negative individuals (A-T-) and 65 amyloid- and tau-positive individuals (A+T+). An independent sample set of 26 A-T- and 26 A+T+ individuals from the Amsterdam Dementia Cohort was used for validation. The measured proteins were clustered based on their correlation to CSF amyloid beta peptides, tau and NfL levels. Further, we used support vector machine modelling to identify protein pairs, matched based on their cluster origin, that reflect AD pathology and cognitive decline with improved performance compared to single proteins. Results The protein-clustering revealed 11 proteins strongly correlated to t-tau and p-tau (tau-associated group), including mainly synaptic proteins previously found elevated in AD such as NRGN, GAP43 and SNCB. Another 16 proteins showed predominant correlation with Aβ42 (amyloid-associated group), including PTPRN2, NCAN and CHL1. Support vector machine modelling revealed that proteins from the two groups combined in pairs discriminated A-T- from A+T+ individuals with higher accuracy compared to single proteins, as well as compared to protein pairs composed of proteins originating from the same group. Moreover, combining the proteins from different groups in ratios (tau-associated protein/amyloid-associated protein) significantly increased their correlation to cognitive decline measured with cognitive scores. The results were validated in an independent cohort. Conclusions Combining brain-derived proteins in pairs largely enhanced their capacity to discriminate between AD pathology-affected and unaffected individuals and increased their correlation to cognitive decline, potentially due to adjustment of inter-individual variability. With these results, we highlight the potential of protein pairs to monitor neurodegeneration and thereby possibly the efficacy of AD disease-modifying therapies.

Abstract Deposition of amyloid beta (Aβ) into plaques is a major hallmark of Alzheimer’s disease (AD). Different amyloid precursor protein (APP) mutations cause early-onset AD by altering the production or aggregation properties of Aβ. We recently identified the Uppsala APP mutation (APPUpp), which causes Aβ pathology by a triple mechanism: increased β-secretase and altered α-secretase APP cleavage, leading to increased formation of a unique Aβ conformer that rapidly aggregates and deposits in the brain. The aim of this study was to further explore the effects of APPUpp in a transgenic mouse model (tg-UppSwe), expressing human APP with the APPUpp mutation together with the APPSwe mutation. Aβ pathology was studied in tg-UppSwe brains at different ages, using ELISA and immunohistochemistry. In vivo PET imaging with three different PET radioligands was conducted in aged tg-UppSwe mice and two other mouse models; tg-ArcSwe and tg-Swe. Finally, glial responses to Aβ pathology were studied in cell culture models and mouse brain tissue, using ELISA and immunohistochemistry. Tg-UppSwe mice displayed increased β-secretase cleavage and suppressed α-secretase cleavage, resulting in AβUpp42 dominated diffuse plaque pathology appearing from the age of 5–6 months. The γ-secretase cleavage was not affected. Contrary to tg-ArcSwe and tg-Swe mice, tg-UppSwe mice were [11C]PiB-PET negative. Antibody-based PET with the 3D6 ligand visualized Aβ pathology in all models, whereas the Aβ protofibril selective mAb158 ligand did not give any signals in tg-UppSwe mice. Moreover, unlike the other two models, tg-UppSwe mice displayed a very faint glial response to the Aβ pathology. The tg-UppSwe mouse model thus recapitulates several pathological features of the Uppsala APP mutation carriers. The presumed unique structural features of AβUpp42 aggregates were found to affect their interaction with anti-Aβ antibodies and profoundly modify the Aβ-mediated glial response, which may be important aspects to consider for further development of AD therapies.

Abstract Immunotherapies with antibody–drug-conjugates (ADC) and CAR-T cells, targeted at tumor surface antigens (surfaceome), currently revolutionize clinical oncology. However, target identification warrants a better understanding of the surfaceome and how it is modulated by the tumor microenvironment. Here, we decode the surfaceome and endocytome and its remodeling by hypoxic stress in glioblastoma (GBM), the most common and aggressive brain tumor in adults. We employed a comprehensive approach for global and dynamic profiling of the surfaceome and endocytosed (endocytome) proteins and their regulation by hypoxia in patient-derived GBM cultures. We found a heterogeneous surface-endocytome profile and a divergent response to hypoxia across GBM cultures. We provide a quantitative ranking of more than 600 surface resident and endocytosed proteins, and their regulation by hypoxia, serving as a resource to the cancer research community. As proof-of-concept, the established target antigen CD44 was identified as a commonly and abundantly expressed surface protein with high endocytic activity. Among hypoxia induced proteins, we reveal CXADR, CD47, CD81, BSG, and FXYD6 as potential targets of the stressed GBM niche. We could validate these findings by immunofluorescence analyses in patient tumors and by increased expression in the hypoxic core of GBM spheroids. Selected candidates were finally confronted by treatment studies, showing their high capacity for internalization and ADC delivery. Importantly, we highlight the limited correlation between transcriptomics and proteomics, emphasizing the critical role of membrane protein enrichment strategies and quantitative mass spectrometry. Our findings provide a comprehensive understanding of the surface-endocytome and its remodeling by hypoxia in GBM as a resource for exploration of targets for immunotherapeutic approaches in GBM.

Abstract Background Automated measurement of blood pressure (BP) in designated BP kiosks have in recent years been introduced in primary care. If kiosk blood pressure (BP) monitoring provides results equivalent to in-office BP or daytime ambulatory BP monitoring (ABPM), follow-up of adult patients could be managed primarily by self-checks. We therefore designed a comparative trial and evaluated the diagnostic performance of kiosk- and office-based BP (nurse- versus physician-measured) compared with daytime ABPM. Methods A trial of automated BP monitoring in three settings: a designated BP kiosk, by nurses and physicians in clinic, and by ABPM. The primary outcome was systolic and diastolic BP, with respective diagnostic thresholds of ≥135 mmHg and/or ≥ 85 mmHg for daytime ABPM and kiosk BP and ≥ 140 mmHg and/or ≥ 90 mmHg for office BP (nurse- and physician-measured). Results Compared with daytime ABPM, mean systolic kiosk BP was higher by 6.2 mmHg (95% confidence interval [CI] 3.8–8.6) and diastolic by 7.9 mmHg (95% CI 6.2–9.6; p

Abstract Background Amyloid beta (Aβ) deposits and hyperphosphorylated tau (p-tau) accumulation have been identified in the retina of Alzheimer’s disease (AD) patients and transgenic AD mice. Previous studies have shown that retinal microglia engulf Aβ, but this property decreases in AD patients. Whether retinal microglia also take up p-tau and if this event is affected in AD is yet not described. In the current study, we use the p-tau-specific thiophene-based ligand bTVBT2 to investigate the relationship between disease progression and p-tau uptake by microglia in the retina of AD patients and App NL−F/NL−F knock-in mice, an AD mouse model known to demonstrate extracellular Aβ plaques and dystrophic neurites in the brain from 6 months of age. Methods Evaluation of bTVBT2 specificity and its presence within microglia was assessed by immunofluorescent staining of hippocampal sections and flat-mount retina samples from non-demented controls, AD patients, 3-, 9-, and 12-month-old App NL−F/NL−F knock-in mice and 12- and 18-month-old wild type (WT) mice. We used ImageJ to analyze the amount of bTVBT2 inside Iba1-positive microglia. Co-localization between the ligand and p-tau variant Ser396/Ser404 (PHF-1), Aβ, phosphorylated TAR DNA binding protein 43 (pTDP-43), and islet amyloid polypeptide (IAPP) in the brain and retina was analyzed using confocal imaging. Results Confocal imaging analysis showed that bTVBT2 binds to PHF-1- and AT8-positive aggregates inside retinal microglia, and not to Aβ, pTDP-43, or IAPP. The density of bTVBT2-positive microglia was higher in cases with a high Aβ load compared to those with a low Aβ load. This density correlated with the neurofibrillary tangle load in the brain, but not with retinal levels of high molecular weight (aggregated) Aβ40 or Aβ42. Analysis of App NL−F/NL−F knock-in mouse retina further showed that 50% of microglia in 3-month-old App NL−F/NL−F knock-in mice contained bTVBT2. The percentage significantly increased in 9- and 12-month-old mice. Conclusion Our study suggests that the microglial capability to uptake p-tau in the retina persists and intensifies with AD progression. These results also highlight bTVBT2 as a ligand of interest in future monitoring of retinal AD pathology.

Abstract Background Reactive oxidative stress is a critical player in the amyloid beta (Aβ) toxicity that contributes to neurodegeneration in Alzheimer’s disease (AD). Damaged mitochondria are one of the main sources of reactive oxygen species and accumulate in Aβ plaque-associated dystrophic neurites in the AD brain. Although Aβ causes neuronal mitochondria reactive oxidative stress in vitro, this has never been directly observed in vivo in the living mouse brain. Here, we tested for the first time whether Aβ plaques and soluble Aβ oligomers induce mitochondrial oxidative stress in surrounding neurons in vivo, and whether this neurotoxic effect can be abrogated using mitochondrial-targeted antioxidants. Methods We expressed a genetically encoded fluorescent ratiometric mitochondria-targeted reporter of oxidative stress in mouse models of the disease and performed intravital multiphoton microscopy of neuronal mitochondria and Aβ plaques. Results For the first time, we demonstrated by direct observation in the living mouse brain exacerbated mitochondrial oxidative stress in neurons after both Aβ plaque deposition and direct application of soluble oligomeric Aβ onto the brain, and determined the most likely pathological sequence of events leading to oxidative stress in vivo. Oxidative stress could be inhibited by both blocking calcium influx into mitochondria and treating with the mitochondria-targeted antioxidant SS31. Remarkably, the latter ameliorated plaque-associated dystrophic neurites without impacting Aβ plaque burden. Conclusions Considering these results, combination of mitochondria-targeted compounds with other anti-amyloid beta or anti-tau therapies hold promise as neuroprotective drugs for the prevention and/or treatment of AD.

Abstract Background Delayed neurocognitive recovery and neurocognitive disorder are common postoperative complications among older adults. The assessment of these complications traditionally relies on analog neurocognitive tests, predominantly using the test battery from the ISPOCD-study as the standard approach. However, analog tests are time-consuming and necessitate trained staff which poses limitations. The potential availability of a digital neurocognitive test as an alternative to the ISPOCD remains unknown. We conducted a comparative study between the analog test battery from ISPOCD and the self-administrated digital test battery developed by Mindmore. Methods We conducted a crossover study with 50 cognitively healthy older adults ≥ 60 years of age recruited in Stockholm Sweden, between February and April 2022. The primary outcome focused on measuring comparability between the two test batteries. Our secondary outcomes included assessing participants’ perceptions and attitudes about the tests with qualitative interviews and their usability experiences. Results Fifty older adults, mean age 76, female 56%, with a university or college degree 48% participated in the study. The sub tests in two test batteries demonstrated a medium–large correlation (r = 0.3–0.5), except for one measure. For four out of six measures, significant differences were found with medium to large effect sizes, ranging from 0.57–1.43. Two categories were recognized in the qualitative analysis: self-competing in a safe environment, and experience with technology. Participants expressed feeling safe and at ease during the assessment, with some preferring the digital test over the analog. Participants reported a high level of usability with the digital test and a majority participants (n = 47) reported they would undergo the digital test for a potential future surgery. Conclusions The digital test battery developed by Mindmore offers several advantages, including rapid access to test results, easy comprehension, and use for participants, thereby increased accessibility of cognitive screening. Trial registration number NCT05253612; ClinicalTrials.gov, 24/02/2022.

Abstract Background We have previously reported on the design and efficacy of two cluster-randomized multi-level workplace interventions, attempting to decrease sedentary behavior (SED) or increase moderate to vigorous physical activity (MVPA) among office workers to improve mental health outcomes. The aim of this study was to investigate intervention effects on mental health outcomes, i.e., mental wellbeing, depression or anxiety symptoms, and stress immediately after the 6-month intervention period. Methods Teams of 263 office workers were cluster-randomized to one of two interventions or a waitlist control group. The PA intervention (iPA) focused on increasing MVPA and the SED intervention (iSED) on reducing SED. Both multi-level interventions targeted individual office workers and their social, physical, and organizational work environment, incorporating counseling based on cognitive behavioral therapy and motivational interviewing. Mental health outcomes were assessed using validated questionnaires before and immediately after the intervention. Intervention effects were analyzed using linear mixed effects models. Results Participants were mostly female and highly educated, with a mean age of 42 years and had favorable levels of mental health at baseline. Mental wellbeing improved for the iSED group (β = 8, 95% CI 1 to 15, p = 0.030) but not for the iPA group (β = 6, 95% CI -1 to 12, p = 0.072) compared to the control group. No effects were found for depression or anxiety symptoms or stress. Conclusions The multi-level interventions improved mental wellbeing among this population of office workers, reaching statistical significance in the iSED group. The size of the effect can be regarded meaningful, considering favorable mental health and high PA level at baseline. Thus, workplace interventions that provide support on multiple levels appear to have potential for improving mental wellbeing, but not reducing ill-health variables, among healthy office workers. More research is needed to understand the mechanisms through which such improvements can be achieved and to identify the most effective intervention components. Trial registration ISRCTN92968402 (27 February 2018).

Abstract Research Impact Assessment (RIA) represents one of a suite of policies intended to improve the impact generated from investment in health and medical research (HMR). Positivist indicator-based approaches to RIA are widely implemented but increasingly criticised as theoretically problematic, unfair, and burdensome. This commentary proposes there are useful outcomes that emerge from the process of applying an indicator-based RIA framework, separate from those encapsulated in the metrics themselves. The aim for this commentary is to demonstrate how the act of conducting an indicator-based approach to RIA can serve to optimise the productive gains from the investment in HMR. Prior research found that the issues regarding RIA are less about the choice of indicators/metrics, and more about the discussions prompted and activities incentivised by the process. This insight provides an opportunity to utilise indicator-based methods to purposely optimise the research impact. An indicator-based RIA framework specifically designed to optimise research impacts should: focus on researchers and the research process, rather than institution-level measures; utilise a project level unit of analysis that provides control to researchers and supports collaboration and accountability; provide for prospective implementation of RIA and the prospective orientation of research; establish a line of sight to the ultimate anticipated beneficiaries and impacts; Include process metrics/indicators to acknowledge interim steps on the pathway to final impacts; integrate ‘next’ users and prioritise the utilisation of research outputs as a critical measure; Integrate and align the incentives for researchers/research projects arising from RIA, with those existing within the prevailing research system; integrate with existing peer-review processes; and, adopt a system-wide approach where incremental improvements in the probability of translation from individual research projects, yields higher impact across the whole funding portfolio. Optimisation of the impacts from HMR investment represents the primary purpose of Research Impact policy. The process of conducting an indicator-based approach to RIA, which engages the researcher during the inception and planning phase, can directly contribute to this goal through improvements in the probability that an individual project will generate interim impacts. The research project funding process represents a promising forum to integrate this approach within the existing research system.

Abstract Background Clinical practice gives medical students opportunities to develop clinical skills and to gain insight into their future profession as a physician. Students in the medical programme at Karolinska Institutet in Sweden had clinical practice in primary health care in nine of their 11 semesters. The aim of this study was to explore medical students’ perceptions of learning from patient encounters in a primary health care context. Methods The study was a qualitative inductive interview study. The 21 participating medical students were from their 3rd, 4th and 5th (final year) year of the study programme. A semi-structured interview guide was used. The data analysis was performed with qualitative content analysis. Results The overarching theme of the study was: The individual patient encounters are the key to learning in primary health care. The patient encounters presented both useful opportunities and challenges that could contribute to the students’ professional development. The following four categories were found: 1. Patient encounters in are instructive, rewarding and challenging. Practising in primary health care provided experience in meeting and communicating with a wide variety of patients. Students described it being challenging to trust in their own clinical competence and feeling a responsibility towards the patients. 2. Encounters with patients in primary health care provide opportunities for gradual professional development. Students had the opportunity of increasing independence based on their level of clinical competence. They experienced a progression in their professional development after each period in primary health care. 3. A committed supervisor plays a significant role in learning. Committed supervisors who set aside time for supervision, offered support, and encouraged the student, played an important role in the student’s learning. 4. Learning in primary health care and learning in hospitals complement one another. It could be difficult for the students to sort out exactly where they learnt different things as they perceived that learning in primary health care and in hospitals complemented one another. Conclusions The students’ encounters with authentic patients in primary health care gave them recurring opportunities to develop communication skills and to be trusted to work on their own under supervision, giving them guidance on their way to becoming future physicians.

Abstract Introduction Synaptic loss is closely associated with tau aggregation and microglia activation in later stages of Alzheimer’s disease (AD). However, synaptic damage happens early in AD at the very early stages of tau accumulation. It remains unclear whether microglia activation independently causes synaptic cleavage before tau aggregation appears. Methods We investigated 104 participants across the AD continuum by measuring 14-3-3 zeta/delta ( $$\upzeta /\updelta$$ ζ / δ ) as a cerebrospinal fluid biomarker for synaptic degradation, and fluid and imaging biomarkers of tau, amyloidosis, astrogliosis, neurodegeneration, and inflammation. We performed correlation analyses in cognitively unimpaired and impaired participants and used structural equation models to estimate the impact of microglia activation on synaptic injury in different disease stages. Results 14-3-3 $$\upzeta /\updelta$$ ζ / δ was increased in participants with amyloid pathology at the early stages of tau aggregation before hippocampal volume loss was detectable. 14-3-3 $$\upzeta /\updelta$$ ζ / δ correlated with amyloidosis and tau load in all participants but only with biomarkers of neurodegeneration and memory deficits in cognitively unimpaired participants. This early synaptic damage was independently mediated by sTREM2. At later disease stages, tau and astrogliosis additionally mediated synaptic loss. Conclusions Our results advertise that sTREM2 is mediating synaptic injury at the early stages of tau accumulation, underlining the importance of microglia activation for AD disease propagation.