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Purpose: The aim of this study was to gain a deeper understanding of the experiences and perspectives of care professionals in multidisciplinary and cross-sectorial collaboration, and their experiences of interactions with childbearing families within the context of the FACAM project., Methods: Eight focus groups were conducted with 32 multidisciplinary care professionals working with childbearing families in vulnerable positions. A thematic analysis was conducted, with positioning theory as the theoretical framework focusing on storylines, positioning and speech-acts., Results: Two overall themes were constructed. Theme one: Cross-sectorial collaboration and the influence on the care provided. Theme two: Interaction with and assessment of women and families' care needs and their influence on the care provided, with three subthemes; a) Establishment of a trustful relationship, b) Assessments of vulnerable positions in relation to function in everyday life, c) Interactions with the woman or family depending on their needs., Conclusion: Care professionals found needs-adapted and tailored care meaningful. Well-functioning multidisciplinary and cross-sectorial collaboration was important to support the families.

Objectives: Current guidelines provide limited evidence for cardiovascular screening in ANCA-associated vasculitis (AAV). This study aimed to investigate the prevalence of electrocardiogram (ECG) abnormalities and associations between no, minor or major ECG abnormalities with cardiovascular mortality in AAV patients compared with matched controls., Method: Using a risk-set matched cohort design, patients diagnosed with granulomatosis with polyangiitis or microscopic polyangiitis with digital ECGs were identified from Danish registers from 2000-2021. Patients were matched 1:3 to controls without AAV on age, sex, and year of ECG measurement. Associated hazards of cardiovascular mortality according to ECG abnormalities were assessed in Cox regression models adjusted for age, sex, and comorbidities, with subsequent computation of 5-year risk of cardiovascular mortality standardized to the age- and sex-distribution of the sample., Results: A total of 1431 AAV patients were included (median age: 69 years, 52.3% male). Median follow-up was 4.8 years. AAV was associated with higher prevalence of left ventricular hypertrophy (17.5% vs 12.5%), ST-T deviations (10.1% vs 7.1%), atrial fibrillation (9.6% vs 7.5%), and QTc prolongation (5.9% vs 3.6%). Only AAV patients with major ECG abnormalities demonstrated significantly elevated risk of cardiovascular mortality [HR 1.99 (1.49-2.65)] compared with controls. This corresponded to a 5-year risk of cardiovascular mortality of 19.14% (16-22%) vs 9.41% (8-11%)., Conclusion: Patients with AAV demonstrated a higher prevalence of major ECG abnormalities than controls. Notably, major ECG abnormalities were associated with a significantly increased risk of cardiovascular mortality. These results advocate for the inclusion of ECG assessment into routine clinical care for AAV patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In this case report, a 19-year-old woman suffered a high-energy trauma to her left side with multiple left-sided fractures, including ribs 8-12, with no pneumothorax on the left side, but a large right-sided pneumothorax. Contralateral pneumothorax is extremely rare in primarily unilateral trauma, especially when no contralateral rib fractures are present. A possible explanation is that of a barotrauma due to increased intrathoracic pressure with external compression. Careful examination of both sides of the body is necessary when evaluating patients with unilateral trauma, as serious organ injury may occur contralaterally., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Introduction: We tested the feasibility of adding a potassium binder to enable increased renin angiotensin aldosterone system inhibition (RAASi) and reduce albuminuria in patients with chronic kidney disease (CKD). In a controlled trial design, a potassium binder was introduced exclusively in patients developing hyperkalemia after intensified RAASi, thereby mirroring clinical decision-making., Methods: We planned to include 140 patients aged 18 to 80 years with estimated glomerular filtration rate (eGFR) 25 to 60 ml/min per 1.73 m 2 , albuminuria, and a history of hyperkalemia to an open-label, randomized trial comparing treatment with or without patiromer alongside maximally tolerated RAASi. Patients were randomized only if developing a documented P-potassium >5.5 mmol/l during run-in with intensified RAASi (losartan/spironolactone). The primary end point was change in urine albumin-creatinine ratio (UACR)., Results: Screening among 800,000 individuals with available laboratory results yielded just 317 candidates meeting major selection criteria during 18⅔ months, with 75 ultimately included. Among them, only 23 developed P-potassium >5.5 mmol/l, qualifying for randomization. Consequently, only 20 participants completed the study, falling short of the planned 98, precluding a significant effect on the primary outcome. Inclusion and randomization challenges stemmed from a limited pool of eligible patients for intensified RAASi at risk of hyperkalemia, along with a lower than expected incidence of hyperkalemia during run-in., Conclusion: Despite extensive screening efforts, few eligible patients were identified, and fewer developed hyperkalemia during run-in. Hence, a trial design limited to CKD patients at high hyperkalemia risk and including a run-in phase appears unlikely to provide evidence for a potential renal benefit from additional use of potassium binders., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Health inequality can have a profound impact on a child's life. Maternal mental health challenges can hinder bonding, leading to impaired functioning and poorer child outcomes. To provide extra support for vulnerable pregnant women, the FACAM intervention offers the services of a health nurse or family therapist from pregnancy until the child starts school. This study examined the effects of FACAM intervention on pregnant women in vulnerable positions and their children until the child turned two years old. We randomly assigned 331 pregnant women to either FACAM intervention or care as usual and assessed them at baseline and when the infant was 3-6, 12-13.5, and 24 months old. The primary outcome was maternal sensitivity measured by Coding Interactive Behavior (CIB). Secondary outcomes included the parent-child relationship, child social-emotional development, child developmental progress, parent-child interaction, and child development. Our findings indicate that care-as-usual children were significantly more involved than FACAM children when the child was 4-6 months old (b = -0.25, [-0.42; -0.08] d = -0.42). However, we suspect this result is due to a biased dropout. We did not find any significant differences in any other outcomes. Therefore, the study suggests that the FACAM intervention is not superior to care as usual regarding child development and parent-child interaction outcomes.

Objective: To examine whether patients with ANCA-associated vasculitis (AAV) have an increased risk of cardiovascular disease in the months prior to diagnosis of AAV., Methods: Using a nested case-control framework, patients with granulomatosis with polyangiitis and microscopic polyangiitis were identified through the Danish Nationwide Registries from 1996 to 2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV diagnosis) as their corresponding case. Conditional logistic regression was used to compute adjusted hazard ratios (HRs) for major adverse cardiovascular events (MACE), ischaemic heart disease, coronary angiogram, heart failure, venous thromboembolism, atrial fibrillation, ischaemic stroke, pericarditis and ventricular arrhythmias/implantable cardioverter defibrillator implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before index date., Results: A total of 2371 patients with AAV (median age 63 years, 53.7% male) were matched with 7113 controls. The prevalence of any cardiovascular outcome and MACE within 12 months preceding index date were 10.3% and 2.4% for AAV, compared with 3.8% [HR 3.05 (95% CI 2.48-3.75)] and 1.3% [HR 1.98 (95% CI 1.39-2.82)] of controls. The risk of cardiovascular outcomes was similarly increased in temporal proximity to the diagnosis, with the highest HR at 1 month prior to index date: any cardiovascular outcome [HR 10.73 (95% CI 7.05-16.32)] and MACE [HR 5.78 (95% CI 2.67-12.52)]. In individual analysis, a significantly higher rate was observed for all outcomes (excluding VA/ICD/CA)., Conclusions: AAV disease is associated with an increased risk of cardiovascular disease in the months preceding diagnosis, which underlines the importance of early clinical vigilance towards cardiovascular disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To examine long-term cardiovascular outcomes and temporal trends among patients with ANCA-associated vasculitis (AAV) using Danish nationwide registries., Methods: Using a cohort design, we examined patients with granulomatosis with polyangiitis (ICD-10: DM31.3) and microscopic polyangiitis (ICD-10: DM3.17) in Denmark from 1996-2018. Hazard ratios (HRs) of cardiovascular outcomes were compared between patients with AAV and age and gender-matched controls. Counterfactual G-estimation of HRs was performed to estimate 5-year absolute risks. Temporal trends were obtained by grouping cohorts into evenly distributed tertiles according to inclusion year., Results: A total of 2306 patients with AAV (median age: 62.9yrs, 52.6% male) were matched with 6918 controls. Median follow-up was 9.5yrs. Patients with AAV had a higher rate of ischaemic heart disease [HR 1.86 (1.62-2.15)], myocardial infarction [HR 1.62 (1.26-2.09)], coronary angiogram [HR 1.64 (1.37-1.96)], percutaneous coronary intervention [HR 1.56 (1.17-2.07)] and ventricular arrhythmias/implantable-cardioverter-defibrillator (ICD)-implantations [HR 2.04 (1.16-3.57)]. Similarly, an increased rate of heart failure [HR 2.12 (1.77-2.54)], deep vein thrombosis [HR 3.13 (2.43-4.05)], pulmonary embolism [HR 4.04 (3.07-5.32)], atrial fibrillation [HR 2.08 (1.82-2.39)], ischaemic stroke [HR 1.58 (1.31-1.90)] and in-hospital cardiac arrest [HR 2.27 (1.49-3.48)] was observed. The 5-year risk of all outcomes were significantly higher (excluding ventricular arrhythmia/ICD-implantations). For temporal trends among patients with AAV, a decreased 3-year risk of cardiovascular mortality was observed over time., Conclusions: Patients with AAV are at increased risk of heart failure, atrial-/ventricular arrhythmias, venous thrombotic events, ischaemic stroke and myocardial infarction. Furthermore, patients with AAV were more frequently examined with coronary procedures and underwent more coronary revascularizations. No temporal changes in ischaemic cardiovascular outcomes were observed, albeit the cardiovascular mortality has decreased over time., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Calculating changes in protein stability (ΔΔG) has been shown to be central for predicting the consequences of single amino acid substitutions in protein engineering as well as interpretation of genomic variants for disease risk. Structure-based calculations are considered most accurate, however the tools used to calculate ΔΔGs have been developed on experimentally resolved structures. Extending those calculations to homology models based on related proteins would greatly extend their applicability as large parts of e.g. the human proteome are not structurally resolved. In this study we aim to investigate the accuracy of ΔΔG values predicted on homology models compared to crystal structures. Specifically, we identified four proteins with a large number of experimentally tested ΔΔGs and templates for homology modeling across a broad range of sequence identities, and selected three methods for ΔΔG calculations to test. We find that ΔΔG-values predicted from homology models compare equally well to experimental ΔΔGs as those predicted on experimentally established crystal structures, as long as the sequence identity of the model template to the target protein is at least 40%. In particular, the Rosetta cartesian_ddg protocol is robust against the small perturbations in the structure which homology modeling introduces. In an independent assessment, we observe a similar trend when using ΔΔGs to categorize variants as low or wild-type-like abundance. Overall, our results show that stability calculations performed on homology models can substitute for those on crystal structures with acceptable accuracy as long as the model is built on a template with sequence identity of at least 40% to the target protein., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Aims: To explore how consultation exercises were described in a convenience sample of recent scoping reviews., Design: Critical literature review., Data Sources: We searched PsycINFO, Embase, CINAHL and PubMed in July 2020. Our inclusion criterion was a peer-reviewed journal article reporting a scoping review in Danish, English, Norwegian or Swedish., Review Methods: We identified a convenience sample of articles (n = 66) reporting a consultation exercise as part of a scoping review. The descriptions of the consultation were charted, summarized and critically discussed., Results: The current analysis showed no widely accepted consensus on how to approach and report a consultation exercise in the sample of scoping reviews. The reports of stakeholder consultation processes were often brief and general, and often there were no reports of the effects of the stakeholder consultation processes. Further, there was no discussion of the principal theoretical problems mixing stakeholder voices and review findings., Conclusion: The finding that conventional research ethics and research methods often were suspended could indicate that the stakeholder consultants were in a precarious position because of power imbalances between researchers and stakeholder consultants. We suggest that a consultation exercise should only be included when it genuinely invites participation and reports on the effect of alternative voices., Impact: Scoping reviews are common across a range of disciplines, but they often lack definitional and methodological clarity. In their influential approach to scoping studies, Arksey and O'Malley introduced an optional 'consultation exercise', which has been heralded as a valuable tool that can be used to strengthen the process and outcome of a scoping study and to support the dissemination of the study's findings and its implications. However, there is no clear outline on about how to operationalize consultations of stakeholders in scoping studies/reviews. This article includes recommendations for consultation exercises, including encouraging an aspirational move from 'consultation' to 'participation'., (© 2022 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Background: Inequality in health can have profound short- and long-term effects on a child's life. Infants develop in a responsive environment, and the relationship between mother and infant begins to develop during pregnancy. The mother's ability to bond with the fetus and newborn child may be challenged by mental health issues which can cause impaired functioning and poorer health outcomes. Families with complex problems need interdisciplinary interventions starting in early pregnancy to be prepared for motherhood and to ensure healthy child development. This study aims to examine the effects of an early and coordinated intervention (the Family Clinic and Municipality (FACAM) intervention) offered to vulnerable pregnant women during pregnancy and the child's first year of life on the mother-child relationship, maternal social functioning, mental health, reflective functioning, well-being, parental stress, and the development and well-being of the child., Methods: The study is a prospective randomized controlled trial where we will randomize 320 pregnant women enrolled to receive antenatal care at the family clinic at Odense University Hospital, to either FACAM intervention or usual care. The FACAM intervention consists of extra support by a health nurse or family therapist during pregnancy and until the child starts school. The intervention is most intensive in the first 12 months and also includes attachment-based support provided either individually or in groups. The participants are assessed at baseline, and when the infant is 3 and 12 months old. The primary outcome is maternal sensitivity measured by the Coding Interactive Behavior (CIB) instrument. Secondary outcomes include prenatal parental reflective functioning, mental well-being, depressive symptoms, breastfeeding duration, maternal satisfaction, child development, parent competence, parental stress, and activities with the child., Discussion: The trial is expected to contribute knowledge about the effect of early coordinated support in antenatal and postnatal care for vulnerable pregnant women and their families., Trial Registration: ClinicalTrials.gov NCT03659721 . Registered on September 6, 2018., (© 2022. The Author(s).)

Germline mutations in the folliculin (FLCN) tumor suppressor gene are linked to Birt-Hogg-Dubé (BHD) syndrome, a dominantly inherited genetic disease characterized by predisposition to fibrofolliculomas, lung cysts, and renal cancer. Most BHD-linked FLCN variants include large deletions and splice site aberrations predicted to cause loss of function. The mechanisms by which missense variants and short in-frame deletions in FLCN trigger disease are unknown. Here, we present an integrated computational and experimental study that reveals that the majority of such disease-causing FLCN variants cause loss of function due to proteasomal degradation of the encoded FLCN protein, rather than directly ablating FLCN function. Accordingly, several different single-site FLCN variants are present at strongly reduced levels in cells. In line with our finding that FLCN variants are protein quality control targets, several are also highly insoluble and fail to associate with the FLCN-binding partners FNIP1 and FNIP2. The lack of FLCN binding leads to rapid proteasomal degradation of FNIP1 and FNIP2. Half of the tested FLCN variants are mislocalized in cells, and one variant (ΔE510) forms perinuclear protein aggregates. A yeast-based stability screen revealed that the deubiquitylating enzyme Ubp15/USP7 and molecular chaperones regulate the turnover of the FLCN variants. Lowering the temperature led to a stabilization of two FLCN missense proteins, and for one (R362C), function was re-established at low temperature. In conclusion, we propose that most BHD-linked FLCN missense variants and small in-frame deletions operate by causing misfolding and degradation of the FLCN protein, and that stabilization and resulting restoration of function may hold therapeutic potential of certain disease-linked variants. Our computational saturation scan encompassing both missense variants and single site deletions in FLCN may allow classification of rare FLCN variants of uncertain clinical significance., Competing Interests: The authors have declared that no competing interests exist.

A suicide attempt is a significant burden on the suicidal person, the family, and the community. The psychosocial strain on parents after their offspring's suicide attempt is significant. The aim of this study was to gain insight into how a parent's relationship with a partner was affected after their son or daughter's suicide attempt or serious suicide threats. Individual in-depth interviews were made of 19 parents recruited through a Danish non-governmental organisation in 2013. Data were analysed using a generic thematic analysis. A key category "Sense of solidarity" and two sub-categories "Challenges to the relationship" and "Responding to different reactions and coping strategies" were constructed. Sense of solidarity was important for the parents' co-parenting and how they engaged with the situation as a couple. The group of participants was heterogeneous and had learned to manage the stressful situation in different ways. Interventions to support parents of sons or daughters who have attempted suicide should include a stronger focus on parents' co-parenting abilities in the family system in order to support the well-being of the whole family.

Background & Aims: Intestinal insufficiency and intestinal failure are conditions associated with malabsorption of micro- and macronutrients. Consequently, malnutrition and ensuing alterations in body composition are common in this context and patients may have an increased risk of progressive loss of skeletal muscle mass and function (i.e. sarcopenia). We investigated the prevalence of sarcopenia in patients with intestinal insufficiency and intestinal failure and identified associated risk factors., Methods: This was a cross-sectional study including 113 clinically stable outpatients with intestinal insufficiency or intestinal failure. Body composition was assessed using bioelectrical impedance analysis and muscle function (strength or performance) using a handheld dynamometer and a timed up-and-go test. Sarcopenia was classified using the European Working Group on Sarcopenia in Older People criteria. Several parameters, including smoking, alcohol, and concurrent morbidities, were analyzed for association with sarcopenia., Results: The prevalence of sarcopenia was 53.1% (95% CI; 43.8 to 62.2) in the combined patient group. In patients with intestinal failure the prevalence of sarcopenia was 72.7% (95% CI; 59.3 to 83.0) compared to 34.5% (95% CI; 23.3 to 47.8) in those with intestinal insufficiency (OR 5.07 [95% CI; 2.27 to 11.31]; p < 0.001). Excessive alcohol consumption (OR 7.69 [95% CI; 1.50 to 39.34]; p = 0.014), intestinal failure (OR 4.16 [95% CI; 1.69 to 10.28]; p = 0.002), and inflammatory activity (OR 3.83 [95% CI; 1.06 to 12.84]; p = 0.041), were identified as independent risk factors of sarcopenia. A trend was observed for hypermetabolism in multivariate analysis (OR 7.55 [95% CI; 0.79 to 72.03]; p = 0.079)., Conclusions: Patients with intestinal insufficiency and intestinal failure are at immense risk of developing sarcopenia. Associated risk factors are excessive alcohol consumption, intestinal failure, and inflammatory activity., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Intestinal insufficiency and intestinal failure are associated with malabsorption of micro- and macronutrients that may negatively influence bone metabolism and increase the risk for developing osteoporosis. However, information regarding prevalence and contribution of individual risk factors is scarce. We investigated the prevalence of osteoporosis in patients with intestinal insufficiency and intestinal failure and identified associated risk factors., Methods: This was a retrospective cross-sectional study including 167 clinically stable outpatients with intestinal insufficiency or intestinal failure. Bone mineral density (BMD) was measured by dual X-ray absorptiometry and the prevalence of osteoporosis was compared to a gender and age matched population. Several clinical and demographic parameters, including body mass index (BMI), vitamin-D, smoking habits and medications, were analyzed for association with BMD., Results: The prevalence of osteoporosis was 56.9% in the combined patient group compared to 24.1% in the control group (OR 4.2 [95% CI, 2.3 to 7.7]; p < 0.001). BMD in the hip was independently associated with BMI (0.13 [95% CI, 0.09 to 0.18]; p < 0.001) and vitamin-D levels (-0.41 [95% CI, -0.76 to -0.06]; p = 0.03). Similar associations were seen for BMD in the spine (0.15 [95% CI, 0.08 - 0.22]; p < 0.001) and (-0.60 [95% CI, -0.76 to -0.06]; p = 0.02), respectively. Trends for low BMD were observed in smokers, and in patients using glucocorticoids, opioids, and proton pump inhibitors., Conclusions: Patients with intestinal insufficiency and intestinal failure are at immense risk of developing osteoporosis. Low BMI and vitamin-D deficiency were identified as independent risk factors., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)