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Background and purpose — Knowing how to interpret values obtained with patient reported outcome measures (PROMs) is essential. We estimated the substantial clinical benefit (SCB) and patient acceptable symptom state (PASS) for Forgotten Joint Score 12 (FJS) and explored differences depending on methods used for the estimates. Patients and methods — The study was based on 195 knee arthroplasties (KA) performed at a university hospital. We used 1 item from the Knee injury and Osteoarthritis Outcome Score domain quality of life and satisfaction with surgery, obtained 1-year postoperatively, to assess SCB and PASS thresholds of the FJS with anchor-based methods. We used different combinations of anchor questions for SCB and PASS (satisfied, satisfied with no or mild knee difficulties, and satisfied with no knee difficulties). A novel predictive approach and receiver-operating characteristics curve were applied for the estimates. Results — 70 and 113 KAs were available for the SCB and PASS estimates, respectively. Depending on method, SCB of the FJS (range 0–100) was 28 (95% CI 21–35) and 22 (12–45) respectively. PASS was 31 (2–39) and 20 (10–29) for satisfied patients, 40 (31–47) and 38 (32–43) for satisfied patients with no/mild difficulties, and 76 (39–80) and 64 (55–74) for satisfied patients with no difficulties. The areas under the curve ranged from 0.82 to 0.88. Interpretation — Both the SCB and PASS thresholds varied depending on methodology. This may indicate a problem using meaningful values from other studies defining outcomes after KA. This study supports the premise of the FJS as a PROM with good discriminatory ability in patients undergoing KA.

Introduction Autoimmune pancreatitis (AIP) is a special form of pancreatitis that responds well to glucocorticoid (GC) treatment. Relapses of AIP are common. The anti-CD20 antibody rituximab (RTX) has shown promising results in GC refractory cases, but long-term data are scarce. The study aims to determine the clinical and imaging response to RTX and summarize the existing data on RTX therapy in patients with AIP type 1 in the literature. Patients and methods Retrospective analysis of electronic medical records was conducted. Additionally, we conducted a systematic review of the literature concerning RTX use in AIP type 1. Results Twelve (11.7%) of 103 patients with AIP type 1 were treated with RTX during the study period: eight (66.7%) achieved complete and four (33.3%) partial remission. RTX was discontinued in one patient who developed fever and reactivation of latent tuberculosis. None of the remaining 11 patients relapsed during a median follow-up of 17 months. No significant differences were detected in baseline clinical characteristics or history of relapse between the patients who obtained complete and partial remission. Altogether, eight studies with 110 AIP type-1 patients treated with RTX were analyzed. Adverse effects ranged from 11-43% and the relapse-free period during follow-up (range 2-173 months) ranged from 38-94%. Conclusions Our results confirm that RTX is efficacious in the treatment of AIP type 1 by inducing remission and preventing relapse. In addition, there are few adverse effects of the treatment.

Summary This study examines the association between the ASA physical status classification score at hip fracture surgery and severe postoperative complications in patients aged 60 and older. Among both men and women, ASA scores consistently predict a wide range of complications including infections, cardiovascular complications, hospital readmissions, and death. Introduction Hip fractures are common in aging populations and associated with poor prognosis. This study examines how the American Society of Anaesthesiologists (ASA) physical status classification is related to severe complications among hip fracture patients including infections, cardiovascular diseases, hospital readmissions, and death. Methods Based on a linkage of the Swedish National Inpatient Register with the Swedish National Registry for Hip Fractures (RIKSHÖFT), this study includes patients aged 60+ with first hip fracture between 1998 and 2017. We estimated associations between ASA score and complications during the hospital stay and during 1 year after hip fracture using multivariable-adjusted logistic regression and Cox proportional hazard regression. Results The study population included 170,193 hip fracture patients of which 24% died and 39% were readmitted to hospital within 1 year. The most common complications were urinary tract infections, pneumonia, second hip fractures, and heart failure. Among both men and women, higher ASA scores were consistently associated with higher risks for all complications included in this study. The strongest associations were observed for heart failure, myocardial infarction, pneumonia, and death. Conclusion ASA scores are routinely assessed in clinical practice and predict a wide range of postoperative complications among hip fracture patients. Since many complications may be preventable through adequate drug treatment, rehabilitation, and risk awareness, future studies should examine the mechanisms linking ASA scores to complication risk in order to improve preventive strategies. Particularly, the high risk of cardiovascular complications among patients with high ASA scores deserves clinical and scientific attention. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-021-05956-w.

ObjectiveIt has been debated whether the different clinical disease courses in multiple sclerosis (MS) are the consequence of different pathogenic mechanisms, with distinct risk factors, or if all MS clinical phenotypes are variations of similar underlying disease mechanisms. We aimed to study environmental risk factors and their interactions with human leucocyte antigen DRB1*15:01 with regards to relapsing-onset and progressive-onset MS.MethodsWe used two Swedish population-based case–control studies, including 7520 relapsing-onset cases, 540 progressive-onset cases and 11 386 controls matched by age, sex and residential area. Logistic regression was used to estimate ORs with 95% CIs for associations between the different MS phenotypes and a number of environmental and lifestyle factors. Interaction between the DRB1*15:01 allele and environmental risk factors was evaluated on the additive scale.ResultsAll environmental and lifestyle factors associated with risk of developing MS apply to both relapsing-onset and progressive-onset disease. Smoking, obesity and Epstein-Barr virus nuclear antigen-1 (EBNA-1) antibody levels were associated with increased risk of both MS phenotypes, whereas snuff use, alcohol consumption and sun exposure were associated with reduced risk. Additive interactions between DRB1*15:01 and smoking, obesity, EBNA-1 antibody levels and sun exposure, respectively, occurred to increase MS risk regardless of the clinical phenotype.InterpretationOur finding that the same environmental and lifestyle factors affect both relapsing-onset and progressive-onset MS supports the notion that the different clinical phenotypes share common underlying disease mechanisms.

Background and purpose — Studies regarding hip fractures in young patients are rare since the patient population is small. We assessed clinical outcomes 4 months after hip fracture in patients < 50 years of age and whether there were differences between sexes and different age groups. Patients and methods — We included adult patients < 50 years with a hip fracture between January 1, 2014 and December 31, 2018. Baseline data were extracted from the Swedish Registry for Hip Fracture Patients and Treatment (RIKSHÖFT) and mortality data was obtained from Statistics Sweden. The outcome variables were change of walking ability, pain in fractured hip, use of analgesics, living conditions, and mortality rate at 4 months. Results — Of the 905 patients included, 72% were men and femoral neck fractures were most common (58%). 4 months after surgery, 23% used a walking aid and 7% reported severe pain. Women reported slightly more pain and higher usage of analgesics. Patients aged 40–49 reported higher usage of analgesics than patients aged 15–39, although the latter group reported more pain. Nearly all of those who lived independently before fracture did so at 4 months. The mortality rate was < 1%. Interpretation — Most patients did not use any walking aid and few had severe pain at 4 months. Furthermore, a hip fracture is not a life-threatening event in a patient < 50 years. The living conditions did not change for those who lived independently before the fracture.

INTRODUCTION Both echocardiography and CMR imaging are used to quantify longitudinal function. Inter-method variability for mitral (MAPSE) and tricuspid (TAPSE) annular plane systolic excursion, and variability between directly measured MAPSE and TAPSE and as based on atrioventricular plane displacement (AVPD) analysis by CMR, are, however, not known. This study, therefore, assessed inter-method variability and variability between annular plane systolic excursion and AVPD-based values in a healthy adult population. METHODS Echocardiography and CMR were performed in 111 adults (35 [32-38] years). Method comparisons were assessed with Deming regression, Bland-Altman analysis and coefficient of variation. Observer reproducibility was assessed by the concordance correlation coefficient. RESULTS Echocardiography and semi-automatic CMR agreed on MAPSE (17 ± 2 mm vs. 17 ± 2 mm, p = 0.1) and TAPSE (25 ± 3 mm vs. 25 ± 3 mm, p = 0.5), correlated highly between methods (fitted-slope 1.22 [95% CI 1.07-1.38] and 1.12 [95% CI 0.95-1.29]) and showed low bias (0.42 [95% CI - 2.05 to 2.88] and - 0.18 [95% CI - 4.78 to 4.43]). Intra-/inter-observer reproducibility was high for both methods for both MAPSE (echocardiography 0.96/0.86; CMR 0.87/0.85) and TAPSE (echocardiography 0.96/0.95; CMR 0.97/0.96). MAPSE (16 ± 2 mm vs. 17 ± 2 mm; p

Studies using cotinine levels to define smokers have generally failed to detect an association between smoking and multiple sclerosis (MS). Using a Swedish population-based case-control study, we show that associations in relation to MS risk and progression differ considerably depending on how smoking is measured. The risk of conversion into secondary progressive disease was increased among smokers when self-reported smoking history, but not presumed cotinine levels, was used to define smokers. Defining smoking by cotinine levels without distinguishing between different sources of nicotine may lead to severely biased estimates of the association between smoking and both MS risk and progression.

Background The aim of this study was to adapt the instrument and evaluate the psychometric properties of the Swedish version of the Swallowing Quality of Care questionnaire (S-SWAL-CARE) in patients with oropharyngeal dysphagia. Methods Translation and adaptation of the original SWAL-CARE into Swedish was performed according to established international guidelines. Field testing was performed using 100 patients with oropharyngeal dysphagia due to multiple reasons such as head and neck cancer and neurologic/neuromuscular disease, who had undergone swallowing evaluation within 6 months prior to the study. The patients answered the S-SWAL-CARE, the Quality from the Patient’s Perspective (QPP) and the Swallowing Quality of Life (SWAL-QOL). Test–retest was performed in 20% of the participants. The reliability and validity of the S-SWAL-CARE were assessed by Pearson correlation coefficient and Cronbach’s alpha as well as convergent and discriminative validity, respectively. Results The field testing of the S-SWAL-CARE resulted in sufficient reliability, with Cronbach’s alpha values exceeding 0.90 for all domains. All items correlated strongly to their own domain, with weaker correlations to the other domains, indicating proper scale structure. Results also indicate sufficient convergent and discriminant validity when tested for association to the QPP domains and the SWAL-QOL Total score. The test–retest reliability of the S-SWAL-CARE demonstrated sufficient intraclass correlation coefficient (ICC) for the General advice domain (0.73) and Clinical advice domain (0.82). The ICC for the Patient satisfaction domain was lower (0.44). Conclusion The S-SWAL-CARE can be considered a reliable and valid tool to assess the dysphagia-related quality of care in a mixed Swedish dysphagia patient population.

Publisher's version (útgefin grein), Background: Rheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibodies in the RA subset that is traditionally defined as seronegative. Methods: Anti-CCP2 IgG, 19 ACPA fine-specificities, IgM/IgG/IgA RF, anti-carbamylated-protein (CarP) antibodies, and 17 other autoantibodies, were analysed in 2755 RA patients and 370 controls. Antibody prevalence, levels, and co-occurrence were examined, and associations with risk factors and disease activity during 5 years were investigated for different antibody-defined RA subsets. Results: Autoantibodies were detected in a substantial proportion of the traditionally defined seronegative RA subset, with ACPA fine-specificities found in 30%, IgA/IgG RF in 9.4%, and anti-CarP antibodies in 16%, with a 9.6% co-occurrence of at least two types of RA-associated autoantibodies. HLA-DRB1 shared epitope (SE) associated with the presence of ACPA in anti-CCP2-negative RA; in anti-CCP2-positive RA, the SE association was defined by six ACPA fine-specificities with high co-occurrence. Smoking associated with RF, but not with ACPA, in anti-CCP2-negative RA. Presence of ACPA and RF, but not anti-CarP antibodies, in conventionally defined "seronegative"RA, associated with worse clinical outcome. Conclusions: "Seronegative"RA is not truly a seronegative disease subset. Additional screening for ACPA fine-specificities and IgA/IgG RF defines a group of patients that resembles seropositive patients with respect to risk factors and clinical picture and may contribute to earlier diagnosis for a subset of anti-CCP2-/IgM RF- patients with a high need for active treatment., This work was supported by grants from the Swedish Research Council (2017-01696); King Gustav V:s 80-year foundation (FAI-2016-0273); the EU funded consortia TRIGGER (FP7-Health-2013-306029); and the EU/EFPIA Innovative Medicines Initiative Joint Undertaking BeTheCure (grant n° 115142), and RTCure (grant n° 777357). Open access funding provided by Karolinska Institute.

Timing and indication for pulmonary valve replacement (PVR) in patients with repaired Tetralogy of Fallot (rToF) and pulmonary regurgitation (PR) are uncertain. To improve understanding of pumping mechanics, we investigated atrioventricular coupling before and after surgical PVR. Cardiovascular magnetic resonance was performed in patients ( n = 12) with rToF and PR > 35% before and after PVR and in healthy controls ( n = 15). Atrioventricular plane displacement (AVPD), global longitudinal peak systolic strain (GLS), atrial and ventricular volumes, and caval blood flows were analyzed. Right ventricular (RV) AVPD and RV free wall GLS were lower in patients before PVR compared with controls ( P < 0.0001; P < 0.01) and decreased after PVR ( P < 0.0001 for both). Left ventricular AVPD was lower in patients before PVR compared with controls ( P < 0.05) and decreased after PVR ( P < 0.01). Left ventricular GLS did not differ between patients and controls ( P > 0.05). Right atrial reservoir volume and RV stroke volume generated by AVPD correlated in controls ( r = 0.93; P < 0.0001) and patients before PVR ( r = 0.88; P < 0.001) but not after PVR. In conclusion, there is a clear atrioventricular coupling in patients before PVR that is lost after PVR, possibly because of loss of pericardial integrity. Impaired atrioventricular coupling complicates assessment of ventricular function after surgery using measurements of longitudinal function. Changes in atrioventricular coupling seen in patients with rToF may be energetically unfavorable, and long-term effects of surgery on atrioventricular coupling is therefore of interest. Also, AVPD and GLS cannot be used interchangeably to assess longitudinal function in rToF. NEW & NOTEWORTHY There is a clear atrioventricular coupling in patients with Tetralogy of Fallot (ToF) and pulmonary regurgitation before surgical pulmonary valve replacement (PVR) that is lost after operation, possibly because of loss of pericardial integrity. The impaired atrioventricular coupling complicates assessment of ventricular function after surgery when using measurements of longitudinal function. Left ventricular atrioventricular plane displacement (AVPD) found differences between patients and controls and changes after PVR that longitudinal strain could not detect. This indicates that AVPD and strain cannot be used interchangeably to assess longitudinal function in repaired ToF.

ObjectivesPatient e-services are increasingly launched globally to make healthcare more efficient and digitalised. One area that is digitalised is medical advice, where patients asynchronously chat with nurses and physicians, with patients having filled in a form with predefined questions before the chat. This study aimed to explore how occupational professionalism and the possibility of professional judgement are affected when clinical patient contact is digitalised. The study’s overall question concerns whether and how the scope of the healthcare staff’s professional judgement and occupational professionalism are affected by digitalisation.Design and settingA qualitative study of healthcare professionals working in a pilot project with a chat programme for patients in a medical advice setting in Sweden.Participants and analysisContextual inquiries and 17 interviews with nurses (n=9) and physicians (n=8). The interviews were thematically analysed. The analysis was inductive and based on theories of decision making.ResultsThree themes emerged: (1) Predefined questions to patients not tailored for healthcare professionals’ work, (2) reduced trust in written communication and (3) reduced opportunity to obtain information through chat communication.ConclusionsThe results indicate that asynchronous chat with patients might reduce the opportunity for nurses and physicians to obtain and use professional knowledge and discretionary decision making. Furthermore, the system’s design increases uncertainty in assessments and decision making, which reduces the range of occupational professionalism.

Aging is associated with a progressive decline in skeletal muscle mass, strength and function (sarcopenia). We have investigated whether a mixture of algae oil (25%) and extra virgin olive oil (75%) could exert beneficial effects on sarcopenia. Young (3 months) and old (24 months) male Wistar rats were treated with vehicle or with the oil mixture (OM) (2.5 mL/kg) for 21 days. Aging decreased gastrocnemius weight, total protein, and myosin heavy chain mRNA. Treatment with the OM prevented these effects. Concomitantly, OM administration decreased the inflammatory state in muscle, it prevented the increase of pro-inflammatory interleukin-6 (IL-6) and the decrease in anti-inflammatory interleukin-10 (IL-10) in aged rats. The OM was not able to prevent aging-induced alterations in either the insulin-like growth factor I/protein kinase B (IGF-I/Akt) pathway or in the increased expression of atrogenes in the gastrocnemius. However, the OM prevented decreased autophagy activity (ratio protein 1A/1B-light chain 3 (LC3b) II/I) induced by aging and increased expression of factors related with muscle senescence such as histone deacetylase 4 (HDAC-4), myogenin, and IGF-I binding protein 5 (IGFBP-5). These data suggest that the beneficial effects of the OM on muscle can be secondary to its anti-inflammatory effect and to the normalization of HDAC-4 and myogenin levels, making this treatment an alternative therapeutic tool for sarcopenia.

BackgroundCritical illness myopathy (CIM) is a debilitating condition characterized by the preferential loss of the motor protein myosin. CIM is a byproduct of critical care, attributed to impaired recovery, long‐term complications, and mortality. CIM pathophysiology is complex, heterogeneous and remains incompletely understood, however loss of mechanical stimuli contributes to critical illness associated muscle atrophy and weakness. Passive mechanical loading (ML) and electrical stimulation (ES) therapies augment muscle mass and function. While having beneficial outcomes, the mechanistic underpinning of these therapies is less known. Therefore, here we aimed to assess the mechanism by which chronic supramaximal ES ameliorates CIM in a unique experimental rat model of critical care.MethodsRats were subjected to 8 days critical care conditions entailing deep sedation, controlled mechanical ventilation, and immobilization with and without direct soleus ES. Muscle size and function were assessed at the single cell level. RNAseq and Western blotting were employed to understand the mechanisms driving ES muscle outcomes in CIM.ResultsFollowing 8 days of controlled mechanical ventilation and immobilization, soleus muscle mass, Myosin:Actin ratio and single muscle fiber maximum force normalized to cross-sectional area (specific force) were reduced by 40-50% (p< 0.0001). ES significantly reduced the loss of soleus muscle fiber cross-sectional area (CSA) and Myosin:Actin ratio by approximately 30% (p< 0.05) yet failed to effect specific force. RNAseq pathway analysis revealed downregulation of insulin signaling in the soleus muscle following critical care and GLUT4 trafficking was reduced by 55% leading to an 85% reduction of muscle glycogen content (p< 0.01). ES promoted phosphofructokinase and insulin signaling pathways to control levels (p< 0.05), consistent with the maintenance of GLUT4 translocation and glycogen levels. AMPK, but not AKT, signaling pathway was stimulated following ES, where the downstream target TBC1D4 increased 3 logFC (p= 0.029) and AMPK-specific P-TBC1D4 levels were increased approximately 2-fold (p= 0.06). Reduction of muscle protein degradation rather than protein synthesis promoted soleus CSA, as ES reduced E3 ubiquitin proteins, Atrogin-1 (p= 0.006) and MuRF1 (p= 0.08) by approximately 50%, downstream of AMPK-FoxO3.ConclusionsES maintained GLUT4 translocation through increased AMPK-TBC1D4 signaling leading to improved muscle glucose homeostasis. Soleus CSA and myosin content was promoted through reduced protein degradation via AMPK-FoxO3 E3 ligases, Atrogin-1 and MuRF1. These results demonstrate chronic supramaximal ES reduces critical care associated muscle wasting, preserved glucose signaling and reduced muscle protein degradation in CIM.

Previous studies have observed an inverse association between alcohol consumption and multiple sclerosis (MS) risk. We aimed to investigate possible interactions between alcohol consumption, MS-associated human leukocyte antigen (HLA) genes and smoking regarding MS risk. We used a Swedish population-based case–control study (2059 incident cases, 2887 controls) matched by age, sex, and residential area. Subjects with different genotypes and alcohol consumption habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals using logistic regression models. Interaction on the additive scale between non-drinking and both genotype and smoking were assessed by calculating the attributable proportion due to interaction (AP). There was a dose-dependent inverse association between alcohol consumption and MS risk (p for trend

Objective To study white-coat hypertension (WCHT, blood pressure ≥140/90 mmHg in a clinic and normal blood pressure

Inflammation induces a wide response of the neuroendocrine system, which leads to modifications in all the endocrine axes. The hypothalamic–growth hormone (GH)–insulin-like growth factor-1 (IGF-1) axis is deeply affected by inflammation, its response being characterized by GH resistance and a decrease in circulating levels of IGF-1. The endocrine and metabolic responses to inflammation allow the organism to survive. However, in chronic inflammatory conditions, the inhibition of the hypothalamic–GH–IGF-1 axis contributes to the catabolic process, with skeletal muscle atrophy and cachexia. Here, we review the changes in pituitary GH secretion, IGF-1, and IGF-1 binding protein-3 (IGFBP-3), as well as the mechanism that mediated those responses. The contribution of GH and IGF-1 to muscle wasting during inflammation has also been analyzed.

Background and purpose — Having patients self-evaluate the outcome is an important part of the follow-up after knee arthroplasty. The Forgotten Joint Score-12 (FJS-12) introduced joint awareness as a new approach, suggested to be sensitive enough to differentiate well-functioning patients. This study evaluated the Swedish translation of the FJS-12 and investigated the validity, reliability, and interpretability in patients undergoing knee arthroplasty Patients and methods — We included 109 consecutive patients 1 year after primary knee arthroplasty to assess construct validity (Pearson’s correlation coefficient, r), internal consistency (Cronbach’s alpha [CA]), floor and ceiling effects, and score distribution. The Knee injury and Osteoarthritis Outcome Score (KOOS) was the comparator instrument for the analyses. Further, 31 patients preoperatively and 22 patients postoperatively were included to assess test–retest reliability (intraclass correlation coefficient [ICC]). Results — Construct validity was moderate to excellent (r = 0.62–0.84). The FJS-12 showed a high degree of internal consistency (CA = 0.96). The ICC was good preoperatively (0.76) and postoperatively (0.87). Ceiling effects were 2.8% in the FJS-12 and ranging between 0.9% and 10% in the KOOS. Interpretation — The Swedish translation of the FJS-12 showed good validity and reliability and can be used to assess outcome after knee arthroplasty. Moreover, the FJS-12 shows promising results in its ability to differentiate well-functioning patients. Future studies on unidimensionality, scale validity, interpretability, and responsiveness are needed for a more explicit analysis of the psychometric properties.

Background Biliary complications during pregnancy is an important issue. The aim of this study was to examine if there is an increased risk to perform cholecystectomy during pregnancy in patients with previous bariatric surgery in comparison to other females subjected to cholecystectomy. Methods The Nationwide Swedish Registry for Gallstone Surgery (GallRiks) and the Scandinavian Obesity Surgery Registry (SOReg) were combined. Female patients 18–45 years old were included. The study group was patients with a history of bariatric surgery whom were pregnant at the time of cholecystectomy. This group was compared with pregnant patients without previous bariatric surgery and non-pregnant with and without previous bariatric surgery. Results In total, 21,314 patients were included and 292 underwent surgery during pregnancy. From 1282 patients identified in both registers, 16 patients were pregnant at the time of cholecystectomy. Acute cholecystectomy was performed in 5922 (28%) non-pregnant and 199 (68%) pregnant (p p = 0.031) and length of stay (p = 0.043), but no differences were seen when only comparing patients with an acute indication for surgery. There was no difference in complications comparing pregnant patients with previous bariatric surgery with non-pregnant, both with and without previous bariatric surgery. Conclusions Cholecystectomy during pregnancy in patients with previous bariatric surgery seems to be safe. The increased risk seen in the non-pregnant group after previous bariatric surgery is not seen in pregnancy, possibly due to an optimization of the circumstances at surgery.

Background Previous studies investigating the relationship between insomnia and mortality have been inconsistent. Purpose We aimed to assess whether nocturnal insomnia symptoms and non-restorative sleep are associated with all-cause mortality and whether they modify the associations between short and long sleep duration and all-cause mortality. Patients and methods The present report is based on a prospective cohort study of 39,139 participants with a mean follow-up time of 19.6 years. Cox proportional hazard models with attained age as timescale were used to estimate overall mortality hazard ratios (HRs) with 95% confidence intervals (CI) for different categories of sleep duration and insomnia symptoms. Results Both difficulty initiating sleep and daytime sleepiness were independently associated with increased mortality among those with sleep duration of 9 hrs or more (HR 1.51, 95% CI 1.11-2.07 and HR 1.37, 95% CI 1.03-1.82). Mortality increased with increasing severity of difficulties initiating sleep (p for trend 0.04) and daytime sleepiness (p for trend 0.01) among the long sleepers. None of the insomnia symptoms were associated with mortality among those who reported sleep duration of 8 hrs or less. Conclusion Long sleep in combination with difficulties initiating sleep and daytime sleepiness, possibly due to psychiatric or physical disorders, was thus associated with increased mortality, whereas long sleep without difficulties falling asleep or daytime sleepiness was not associated with mortality. Our study emphasizes the need to take nocturnal insomnia symptoms and daytime sleepiness into consideration when assessing the influence of sleep duration on mortality. Additional research is needed to elucidate the relationship between long sleep, insomnia and related psychiatric and physical disorders.

Background and purpose — The incidence of manipulation under anesthesia (MUA) after knee arthroplasty surgery has been reported to vary between 0.5% and 10%. We evaluated the incidence of MUA after primary knee arthroplasty in Sweden, the demographics of the patients and the risk of revision. Patients and methods — Between 2009 and 2013, 64,840 primary total and unicompartmental knee arthroplasties (TKA and UKA) were registered in the Swedish Knee Arthroplasty Register (SKAR). MUAs performed between 2009 and 2014 were identified through the in- and outpatient registers of the Swedish National Board of Health and Welfare. Pertinent data were verified through medical records and patient demographics and revisions were obtained from the SKAR. Results — 1,258 MUAs were identified. Of these, 1,078 were 1st-time MUAs, performed within 1 year after the primary knee arthroplasty. The incidence of MUA was 1.7% and the incidence varied between hospitals from 0% to 5%. The majority were performed after TKA (98%), in younger patients (65% < 65 years), women (64%), and relatively healthy persons (88% had ASA ≤ 2). The cumulative risk of revision at 10 years was 10% (95% CI 8.6–12), similar for men and women. Interpretation — In Sweden, MUA is a rather uncommon measure after knee arthroplasty, especially after UKA. The CRR at 10 years was doubled compared to the general knee arthroplasty population. The frequency of the procedure varies between hospitals but in general it is performed more frequently in healthier and younger patients.

Background: Patients with certain autoimmune diseases (AID) have an increased risk of developing diffuse large B-cell lymphoma (DLBCL). However, the occurrence of AID in patients with DLBCL as well ...

Summary Limited visualization of the fetal heart and vessels by fetal ultrasound due to suboptimal fetal position, patient habitus and skeletal calcification may lead to missed diagnosis, overdiagnosis and parental uncertainty. Counselling and delivery planning may in those cases also be tentative. The recent fetal cardiac magnetic resonance (CMR) reconstruction method utilizing tiny golden‐angle iGRASP (iterative Golden‐angle RAdial Sparse Parallel MRI) allows for cine imaging of the fetal heart for use in clinical practice. This case describes an unbalanced common atrioventricular canal where limited ultrasound image quality and visibility of the aortic arch precluded confirming or ruling out presence of a ventricular septal defect. Need of prostaglandins or neonatal intervention was thus uncertain. Cardiovascular magnetic resonance imaging confirmed ultrasound findings and added value by ruling out a significant ventricular septal defect and diagnosing arch hypoplasia. This confirmed the need of patient relocation for delivery at a paediatric cardiothoracic surgery centre and prostaglandins could be initiated before the standard postnatal ultrasound. The applied CMR method can thus improve diagnosis of complicated fetal cardiac malformation and has direct clinical impact.

Aging is associated with increased visceral adiposity and a decrease in the amount of brown adipose tissue and muscle mass, known as sarcopenia, which results in the development of metabolic alterations such as insulin resistance. In this study, we aimed to analyze whether 3-week supplementation with a phenolic-rich olive leaf extract (OLE) to 24 months-old male Wistar rats orally (100 mg/kg) attenuated the aging-induced alterations in body composition and insulin resistance. OLE treatment increased brown adipose tissue and attenuated the aging-induced decrease in protein content and gastrocnemius weight. Treatment with OLE prevented the aging-induced increase in the expression of PPAR-γ in visceral and brown adipose tissues, while it significantly increased the expression of PPAR-α in the gastrocnemius of old rats and reduced various markers related to sarcopenia such as myostatin, HDAC-4, myogenin and MyoD. OLE supplementation increased insulin sensitivity in explants of gastrocnemius and epididymal visceral adipose tissue from aged rats through a greater activation of the PI3K/Akt pathway, probably through the attenuation of inflammation in both tissues. In conclusion, supplementation with OLE prevents the loss of muscle mass associated with aging and exerts anti-inflammatory and insulin-sensitizing effects on adipose tissue and skeletal muscle.

Highlights • Prostheses result in lower pain than osteosyntheses in pathological hip fractures. • Surgeons in sarcoma centers generally use prostheses for pathological hip fractures. • Both methods use similar healthcare resources and effectively restore ambulation., Aims How endoprosthetic replacement compares to osteosynthesis in the treatment of pathologic hip fractures as far as functional outcome and use of healthcare resources is concerned remains largely unknown. We aimed to investigate this in a nationwide registry. Methods We analyzed the functional outcome after surgery for a pathological fracture of the hip in terms of post-operative pain and ambulatory capacity. The preferred surgical method depending on the level of the treating unit was also examined. Furthermore, we documented the length of hospital stay and the patterns of discharge and compared them between these two methods. Results Patients operated with an endoprosthesis reported significantly lower pain at follow-up. Both methods (endoprosthetic replacement and osteosynthesis) were equally effective in restoring the ambulatory capacity and demanded a similar length of stay in hospital. Orthopaedic surgeons working in hospitals with dedicated sarcoma teams were more likely to use a prosthesis rather than osteosynthesis, when compared to surgeons working at other university hospitals or emergency hospitals. Conclusion Endoprosthetic replacement results in a better functional outcome in terms of post-operative pain without consuming more healthcare resources. Orthopaedic surgeons working in hospitals with sarcoma centers are more likely to use prostheses as compared to surgeons working at hospitals where dedicated musculoskeletal oncology teams are not available.

Key Points Question Does fetal cardiovascular magnetic resonance improve prenatal diagnosis of complex congenital heart defects when fetal echocardiography is insufficient? Findings In this cohort study of 31 fetuses referred for fetal cardiovascular magnetic resonance imaging, additional clinically useful information regarding cardiovascular anatomy and function was obtained in 84% of referred cases, covering a wide spectrum of congenital heart defects. This information affected choice of mode of delivery, planning of early postnatal care, and parental counseling. Meaning These findings suggest that fetal cardiovascular magnetic resonance imaging can add important diagnostic information and affect clinical decision-making and parental counseling., This cohort study assesses the clinical utility of fetal cardiovascular magnetic resonance imaging when fetal echocardiography could not visualize all relevant anatomy., Importance Prenatal diagnosis of complex congenital heart defects reduces mortality and morbidity in affected infants. However, fetal echocardiography can be limited by poor acoustic windows, and there is a need for improved diagnostic methods. Objective To assess the clinical utility of fetal cardiovascular magnetic resonance imaging in cases in which fetal echocardiography could not visualize all relevant anatomy. Design, Setting, and Participants This cohort study was conducted between January 20, 2017, and June 29, 2020, at Skåne University Hospital (Lund, Sweden), a tertiary center for pediatric cardiology and thoracic surgery. Participants were fetuses referred for fetal cardiovascular magnetic resonance examination by a pediatric cardiologist after an inconclusive echocardiograph. Exposures Fetal cardiovascular magnetic resonance examination requested by the patient’s pediatric cardiologist. Main Outcomes and Measures Any change in patient management because of diagnostic information gained from fetal cardiovascular magnetic resonance imaging. Results A total of 31 fetuses underwent cardiovascular magnetic resonance examination at a median gestational age of 36 weeks (range, 31-39 weeks). Overall, fetal cardiovascular magnetic resonance imaging had clinical utility, affecting patient management and/or parental counseling in 26 cases (84%). For aortic arch anatomy including signs of coarctation (20 fetuses), fetal cardiovascular magnetic resonance imaging added diagnostic information in 16 cases (80%). For assessment of univentricular vs biventricular outcome in borderline left ventricle, unbalanced atrioventricular septal defect, and pulmonary atresia with intact ventricular septum (15 fetuses), fetal cardiovascular magnetic resonance imaging visualized intracardiac anatomy and ventricular function, allowing assessment of outcome in 13 cases (87%). In 4 fetuses with hypoplastic left heart syndrome, fetal cardiovascular magnetic resonance imaging helped delivery planning in 3 cases (75%). Finally, fetal cardiovascular magnetic resonance imaging provided valuable information for parental counseling in 21 cases (68%). Conclusions and Relevance In this cohort study, fetal cardiovascular magnetic resonance imaging added clinically useful information to what was available from echocardiography. These findings suggest that fetal CMR has the potential to affect clinical decision-making in challenging cases of congenital heart defects with inconclusive data from echocardiography. Fetal cardiovascular magnetic resonance imaging showed an association with clinical decision-making, including mode of delivery and early postnatal care, as well as with parental counseling.

Background Hospital length of stay (LoS) is believed to be associated with higher mortality in hip fracture patients; however, previous research has shown conflicting results. We aimed to explore the association between LoS and 4-month mortality in different groups of hip fracture patients. Methods The study population in this Swedish register-based cohort study was 47 811 patients 65 years or older with a first hip fracture during 2012–2016, followed up for 4 months after discharge. LoS was categorized by cubic splines, and the association between LoS and mortality was analyzed with Cox regression models, adjusted for sociodemographic- and health-related factors. Results Mean LoS was 11.2 ± 5.9 days and 12.3% of the patients died within 4 months. Both a shorter and a longer LoS, compared to the reference 9–12 days, were associated with higher mortality (hazard ratio [95% confidence interval]): 2–4 days 2.15 (1.98–2.34), 5–8 days 1.58 (1.47–1.69), and 24+ days 1.29 (1.13–1.46). However, in fully adjusted models, only the association with a long LoS remained: 13–23 days 1.08 (1.00–1.17) and 24+ days 1.42 (1.25–1.61). Stratifying by living arrangement revealed that the increased risk for a short LoS was driven by the group living in care homes. For patients living at home, a short LoS was associated with lower risk: 0.65 (0.47–0.91) and 0.85 (0.74–0.98) for 2–4 and 5–8 days, respectively. Conclusions A long LoS after a hip fracture is associated with increased 4-month mortality risk even after considering patient characteristics. The association between mortality and a short LoS, however, is explained by individuals coming from care homes (with higher mortality risk), being discharged early.

Introduction Despite advances in new surgical techniques and improvements in medical care of the last decades a considerable number of patients will not regain their ability to walk after a hip fracture. Aims To further identify risk factors associated with non-walking 4-months after a hip fracture. Material and Methods Register-based, longitudinal study with a 4-month follow-up. The collected data from the Swedish hip fracture registry, RIKSHOFT, contained all hip fracture between 2013-01-01–2015-12-31 in Sweden. All patients older than 50 years with a non-pathological fracture and who were able to walk before the fracture were included. The association of sex, age, general health, dementia and type of discharge with complete loss of walking after a hip fracture were investigated using a multivariate analysis. Results Included were 23,759 patients. At the 4-month follow-up, 10% were unable to walk. Twenty-five per cent of patients with dementia lost their ability to walk compared to 7% of those with no cognitive dysfunction. Adjusted odds ratio (OR) for factors associated with loss of walking ability were; discharge to institutionalized care rather than their own home or a rehabilitation unit (OR=1.91; 95% CI=1.67-2.18), dementia (OR=1.80; 95% CI=1.57-2.06), male gender (OR=1.59; 95% CI=1.40-1.81) and ASA score grade III-V (OR=1.37; 95% CI=1.20-1.55) but not age (OR=1.01; 95% CI=1.00-1.02). Conclusions An important factor associated with a complete loss of walking ability after a hip fracture is the discharge to institutionalized care. This factor might be influenced either by favouring rehabilitation units or by improving the rehabilitation protocols.

Background Charlson Comorbidity Index (CCI) has been suggested to be associated with mortality in hip fracture patients, to the same extent as more expensive and time-consuming tools. However, even CCI might be too time-consuming in a clinical setting. Aim To investigate whether the American Society of Anaesthesiologists score (ASA score), a simple grading from the anaesthesiologist’s examination, is comparable with CCI in the association with 1-year mortality after a hip fracture. Methods The study population was patients 60 + years registered in the Swedish Hip Fracture Registry with a first-time hip fracture between 1997 and 2017 (N = 165,596). The outcome was 1-year mortality, and the exposures were ASA score and CCI. The association between comorbidity and mortality was described with Kaplan–Meier curves and analyzed with Cox proportional hazards models. Results The Kaplan–Meier curves showed a stepwise increase in mortality for increasing values of both ASA and CCI. The Hazard Ratios (HRs) for the highest ASA (4–5) were 3.8 (95% Confidence Interval 3.5–4.2) for women and 3.2 (2.8–3.6) for men in the fully adjusted models. Adjusted HRs for the highest CCI (4 +) were 3.6 (3.3–3.9) for women and 2.5 (2.3–2.7) for men. Reference was the lowest score value for both tools. The correlation between the tools was moderate. Conclusions Both ASA and CCI show a similar stepwise association with 1-year mortality in hip fracture patients, despite measuring different factors and capturing different individuals at risk. Since the ASA score is already accessible for health care staff, it might be preferable to aid in prioritizing vulnerable hip fracture patients at risk of adverse outcomes.

The presence of SARS-CoV-2 RNA in wastewater was first reported in March 2020. Over the subsequent months, the potential for wastewater surveillance to contribute to COVID-19 mitigation programmes has been the focus of intense national and international research activities, gaining the attention of policy makers and the public. As a new application of an established methodology, focused collaboration between public health practitioners and wastewater researchers is essential to developing a common understanding on how, when and where the outputs of this non-invasive community-level approach can deliver actionable outcomes for public health authorities. Within this context, the NORMAN SCORE “SARS-CoV-2 in sewage” database provides a platform for rapid, open access data sharing, validated by the uploading of 276 data sets from nine countries to-date. Through offering direct access to underpinning meta-data sets (and describing its use in data interpretation), the NORMAN SCORE database is a resource for the development of recommendations on minimum data requirements for wastewater pathogen surveillance. It is also a tool to engage public health practitioners in discussions on use of the approach, providing an opportunity to build mutual understanding of the demand and supply for data and facilitate the translation of this promising research application into public health practice. Validerad;2021;Nivå 2;2021-05-21 (alebob);Finansiär: För finansiärsinformation se Acknowledgements https://www.sciencedirect.com/science/article/pii/S0043135421003651?via%3Dihub#ack0001 DRIZZLE

Study Objectives The relationship between insomnia and suicide risk is not completely understood. We aimed to investigate the influence of insomnia on suicide risk, taking both sleep duration and depression into consideration. Methods The present study is based on a Swedish prospective cohort study of 38,786 participants with a mean follow-up time of 19.2 years. Cox proportional hazards models with attained age as time-scale were used to estimate hazard ratios (HRs) of death by suicide with 95% confidence intervals (CI) for participants categorized by frequency of insomnia symptoms. Causal mediation analysis was performed to assess to what extent the relationship between insomnia and suicide risk is mediated by depression. Results Insomnia was only associated with suicide risk among short sleepers, whereas no significant association was observed among those who slept 7 h/night or more. The total effect of insomnia in the context of short sleep on suicide risk, expressed on the HR scale, was 2.85 (95% CI 1.42–5.74). The direct effect was 2.25 (95% CI 1.12–4.54) and the indirect effect, mediated by depression, was 1.27 (95% CI 1.05–1.53). Of the total effect, 32% was mediated by depression. The association between insomnia and suicide risk became more pronounced with decreasing depressive symptoms (p value for trend Conclusions Insomnia in the context of short sleep increases suicide risk, both directly and indirectly by affecting the risk of depression. Abnormalities of sleep duration and insomnia symptoms should be evaluated when assessing suicide risk.

Olive leaves are rich in bioactive substances which exert anti-inflammatory, antioxidant, insulin-sensitizing and antihypertensive effects. The aim of this study was to analyze the possible beneficial effects of an olive leaf extract (OLE) rich in secoiridoids and phenolic compounds on the aging-induced metabolic and vascular alterations. Three experimental groups of rats were used: 3-month-old rats, 24-month-old rats and 24-month-old rats supplemented 21 days with OLE (100 mg/kg). Administration of OLE to aged rats decreased the weight of adrenal glands and prevented the aging-induced loss of body weight and muscle mass. In the serum, OLE reduced the circulating levels of LDL-cholesterol and IL-6 and increased the concentrations of leptin and adiponectin. In the liver OLE attenuated the decreased gene expression of SOD-1, GSR, GCK and GSK-3β and reduced the aging-induced overexpression of NOX-4, Alox-5, iNOS and TNF-α. In aorta segments, OLE prevented endothelial dysfunction and vascular insulin resistance and improved vasoconstriction in response to KCl and NA. Improvement in vascular function was associated with the attenuation of the alterations in the gene expression of COX-2, IL-6, GPx, NOX-1 and IL-10. In conclusion, OLE exerts anti-inflammatory and antioxidant effects in aged rats and attenuates the alterations in vascular function associated with aging., This project was funded by the call “Doctorados Industriales 2017” (IND2017/BIO7701), a grant from Community of Madrid (Spain). This program aims to promote the effective collaboration between Universities and Companies and provides funding for both, the development of the research project in the University and the Company, and to hire a PhD student (Daniel González-Hedström) over a three-year period by the Company (Pharmactive Biotech Products S.L.). Community of Madrid also funded the contract of María de la Fuente-Fernández through the Youth Employment Program (PEJ-2018-AI/SAL-11315).

ObjectivesPrevious studies have investigated the association between socioeconomic characteristics and fractures among children, producing different results. In a population-based study, we previously found an increased risk of fractures among children living in an urban municipality compared with rural municipalities. This study aimed to evaluate the importance of socioeconomic variables for the incidence of fractures among 0–17 year olds.Setting, design and outcome measureWe present a longitudinal, observational study of a population 0–17 years of age. Data from an injury database were linked with additional socioeconomic data for the population at risk. These were 55 758 individuals residing within the primary catchment area of a regional hospital in northern Sweden. Using the number of fractures as the outcome, we fitted a generalised linear mixed model for a Poisson response with socioeconomic variables at the family level as independent variables while controlling for age, sex and place of residence.ResultsWe found a significant association between higher levels of family income and the risk of fracture, rate ratio 1.40 (1.28–1.52) pConclusionOur results indicate that children from families with higher income and with siblings are at greater risk of sustaining fractures.

Routine follow-up for diffuse large B-cell lymphoma have been shortened to 2 years when event-free survival at 24 months (EFS24) emerged as a new milestone. In the present study, we aimed to determine whether the achievement of this milestone affected overall survival (OS). We compared OS to that of an age- and sex-matched population, analysed other factors governing OS, and reviewed the causes of death. Data were collected from the Swedish Cancer Registry and from individual patient's records. We included 1169 adult patients from five counties between the years 2001 and 2014. The median (range) age was 64·6 (18-91) years, 56·6% were men and the median follow-up was 82·3 months. For early stages, the achievement of EFS12 did not improve OS. More than two-thirds of the patients (n = 837, 71·6%) achieved EFS24, of which 190 (22·7%) died during follow-up. Lymphoma (20%), cardiovascular disease (22·4%) and malignancies (16%) contributed to causes of death. Patients aged 60 years significantly affected OS after EFS24 compared with the standard population. We concluded that follow-up beyond EFS24 should be considered for patients aged >60 years. Amal Abu Sabaa and Charlott Mörth share first authorship

Objective Previous studies investigating the association between nightmares and suicide have yielded different results. We aimed to investigate whether nightmares, directly or indirectly, influence the incidence of suicide. Methods We used a prospective cohort study, based on 40,902 participants with a mean follow-up duration of 19.0 years. Cox proportional hazards models with attained age as time-scale were fitted to estimate hazard ratios (HR) of suicide with 95% confidence intervals (CI) as a function of the presence or absence of depression and nightmares. Mediation analysis was used to asses to what extent the relationship between nightmares and the incidence rate of suicide could be mediated by depression. Results No association was observed between nightmares and the incidence of suicide among participants without depression. Compared with non-depressed participants without nightmares, the incidence of suicide among participants with a diagnosis of depression was similar among those with and without nightmares (HR 12.3, 95% CI 5.55–27.2 versus HR 13.2, 95% CI 7.25–24.1). The mediation analysis revealed no significant effects of nightmares on suicide incidence. However, the incidence of depression during follow-up was higher among those who suffered from nightmares than among those who did not (p Conclusions Our findings indicate that nightmares have no influence on the incidence rate of suicide, but may reflect pre-existing depression. This is supported by a recent discovery of a strong genetic correlation of nightmares with depressive disorders, with no evidence that nightmares would predispose to psychiatric illness or psychological problems. Interventions targeting both depression and nightmares, when these conditions co-occur, may provide additional therapeutic benefit.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in https://doi.org/10.1016/j.sleep.2020.11.018. The duplicate article has therefore been withdrawn.The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Background and Aim Caloric restriction (CR) improves insulin sensitivity and is one of the dietetic strategies most commonly used to enlarge life and to prevent aging-induced cardiovascular alterations. The aim of this study was to analyze the possible beneficial effects of caloric restriction (CR) preventing the aging-induced insulin resistance in the heart of male Wistar rats. Methods and results Three experimental groups were used: 3 months old rats (3m), 24 months old rats (24m) and 24 months old rats subjected to 20% CR during their three last months of life (24m-CR). After sacrifice hearts were mounted in a perfusion system (Langendorff) and heart function in basal conditions and in response to accumulative doses of insulin (10−9-10−7 M), in the presence or absence of Wortmannin (10−6 M), was recorded. CR did not attenuate the aging-induced decrease in coronary artery vasodilation in response to insulin administration, but it prevented the aging-induced downregulation of cardiac contractility (dp/dt) through activation of the PI3K/Akt intracellular pathway. Insulin stimulated in a greater extent the PI3K/Akt pathway vs the activation of the MAPK pathway and increased the protein expression of IR, GLUT-4 and eNOS in the hearts of 3m and 24m-CR rats, but not in the hearts of 24m rats. Furthermore, CR prevented the aging induced increase in endothelin-1 protein expression in myocardial tissue. Conclusion In conclusion CR partially improves cardiac insulin sensitivity and prevents the aging induced decrease in myocardial contractility in response to insulin administration through activation of PI3K/Akt pathway.

Background and purpose — Waiting time to surgery for patients with hip fractures and its potential association with mortality has been frequently studied with the hypothesis that longer waiting time is associated with adverse outcomes. However, despite numerous studies, there is no consensus regarding which time frames are appropriate, and whether some patients are more vulnerable to waiting than others. We explored the association between waiting time to surgery and short-term mortality and whether sex, age, surgical method, and comorbidity (ASA) modified this association. Patients and methods — This is a nationwide cohort study of 59,675 patients undergoing hip fracture surgery between January 1, 2013 and December 31, 2017 with a 4-month follow-up of mortality. Data were extracted from the Swedish Registry for Hip Fracture Patients and Treatment (RIKSHÖFT) and mortality was obtained from Statistics Sweden. Results — Unadjusted analyses revealed an association between waiting more than 24 hours for surgery and increased mortality, primarily for women. However, when stratifying for ASA grade, an association persisted only among patients with ASA 3 and 4. Furthermore, the absolute differences in mortality risk between those waiting less or longer than 24 hours were small. Age, fracture type, and surgical method did not modify the association between waiting time and mortality. Interpretation — This study suggests that there may be a need for new guidelines, which take into account the heterogeneity of the patient population.

Background According to the European evidence-based consensus, published by European Crohn's and Colitis Organization (ECCO), diseases of the pancreas are included as extra-intestinal manifestations in IBD in the forms of acute pancreatitis (AP), chronic pancreatitis (CP), autoimmune pancreatitis (AIP), pancreatic duct abnormalities and pancreatic exocrine insufficiency (PEI). Presence of pancreatic autoantibodies directed against the exocrine of the pancreas has been reported in about one-third of CD. However, association between CD and PEI is not fully elucidated. Methods Patients with a diagnosis of CD were recruited at the Department for Digestive Diseases at Karolinska University Hospital in Stockholm, Sweden. Demographic, clinical and laboratory data were analyzed. Fecal elastase-1 (FE-1) measurements were performed using the enzyme-linked immunosorbent assay (ELISA) method. Results There were 20 patients included in the study, 13 (65%) males and 7 (35%) females, mean age 48.3±1.4 years (range 29-67 years). Mean duration of CD was 15.7±2.1 years (range 1-40 years). There were 11 (55%) patients without history of bowel surgery and 9 (45%) patients after ileocecal resection. FE-1 test was normal in all patients, among them 15 (75%) patients with the values of FE-1>500. Conclusions Fecal elastase-1 level was normal in all patients with CD strongly indicated absence of PEI in this group of patients.

Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system, characterized by localized areas of inflammation, demyelination, and axonal loss. It is widely accepted that su...

BACKGROUND AND PURPOSE A femoral neck fracture (FNF) may have long term effects on the patient's health related quality of life (HRQoL) and mortality, especially in patients younger than 70 years. These long-term effects are unknown since most studies have a short follow-up. The aim of this study was to investigate self-assessed hip function, HRQoL and factors associated with 10-years mortality after a FNF. PATIENTS AND METHODS A prospective multicenter study with a 10-year follow-up of patients aged 20-69 years with a displaced and non-displaced FNF treated with closed reduction and internal fixation. The self-administered questionnaires EuroQol 5 Dimension (EQ-5D) and Hip Disability Outcome Score (HOOS) were used. Results of EQ-5D and HOOS was compared to sex and age matched general population data of Sweden. All patients that were deceased had their death date recorded. Factors associated with mortality were assessed by regression analysis of the baseline data including age, gender, harmful alcohol consumption according to AUDIT, co-morbidity measured by ASA-grade, body mass index, osteoporosis measured by dual energy x-ray absorptiometry (DXA) and smoking. Prevalence of co-morbidities and smoking was compared to general population data. RESULTS From initial 182 included patients, 55 were deceased at 10-year follow-up, 4 were deregistered from public record and 35 declined participations. A total of 88 patients participated through self-administrated questionnaires. There were no significant differences in HOOS between gender and fracture type and the results were equivalent to general population data. The EQ-5D continued to improve compared to a 24-month follow-up (p = 0.006) but did not recover to pre-fracture level (p

The cause of obesity in narcolepsy type 1 (NT1) patients is not fully understood. The present study investigated if a reduced physical activity could explain weight gain in NT1. Seventy-nine patients were included in this retrospective study and divided into an NT1 group (n = 56) and a non-NT1 group (n = 23), including NT2 and idiopathic hypersomnia (IH). Accelerometry-derived measures of physical activity, total energy expenditure and skin temperature were collected from patients during seven consecutive days without medication. In addition, results from multiple sleep latency tests and the Epworth Sleepiness Scale questionnaire, body weight, height and CSF orexin/hypocretin were acquired. Three measurements of physical activity, including metabolic equivalent of task (MET), the average time of physical activity and step count, were compared without differences between groups. Neither could we find a significant difference in total energy expenditure or skin temperature. Thus, by analysing accelerometric data, we could not find any differences in the amount of physical activity or total energy expenditure explaining overweight in NT1.

Intracardiac hemodynamic forces have been proposed to influence remodeling and be a marker of ventricular dysfunction. We aimed to quantify the hemodynamic forces in patients with repaired tetralogy of Fallot (rToF) to further understand the pathophysiological mechanisms as this could be a potential marker for pulmonary valve replacement (PVR) in these patients. Patients with rToF and pulmonary regurgitation (PR) > 20% ( n = 18) and healthy control subjects ( n = 15) underwent MRI, including four-dimensional flow. A subset of patients ( n = 8) underwent PVR and MRI after surgery. Time-resolved hemodynamic forces were quantified using 4D-flow data and indexed to ventricular volume. Patients had higher systolic and diastolic left ventricular (LV) hemodynamic forces compared with control subjects in the lateral-septal/LV outflow tract ( P = 0.011 and P = 0.0031) and inferior-anterior ( P < 0.0001 and P < 0.0001) directions, which are forces not aligned with blood flow. Forces did not change after PVR. Patients had higher RV diastolic forces compared with control subjects in the diaphragm-right ventricular (RV) outflow tract (RVOT; P < 0.001) and apical-basal ( P = 0.0017) directions. After PVR, RV systolic forces in the diaphragm-RVOT direction decreased ( P = 0.039) to lower levels than in control subjects ( P = 0.0064). RV diastolic forces decreased in all directions ( P = 0.0078, P = 0.0078, and P = 0.039) but were still higher than in control subjects in the diaphragm-RVOT direction ( P = 0.046). In conclusion, patients with rToF and PR had LV hemodynamic forces less aligned with intraventricular blood flow compared with control subjects and higher diastolic RV forces along the regurgitant flow direction in the RVOT and that of tricuspid inflow. Remaining force differences in the LV and RV after PVR suggest that biventricular pumping does not normalize after surgery. NEW & NOTEWORTHY Biventricular hemodynamic forces in patients with repaired tetralogy of Fallot and pulmonary regurgitation were quantified for the first time. Left ventricular hemodynamic forces were less aligned to the main blood flow direction in patients compared with control subjects. Higher right ventricular forces were seen along the pulmonary regurgitant and tricuspid inflow directions. Differences in forces versus control subjects remain after pulmonary valve replacement, suggesting that altered biventricular pumping does not normalize after surgery.

PurposeWe endeavored to investigate whether previous findings of an association between antemortem exposure to selective serotonin re-uptake inhibitors (SSRI) and method of suicide could be replicated.MethodsUsing the Swedish National Board of Forensic Medicines toxicology database and the Swedish National Board of Health and Welfares national registries of causes of death and prescriptions, 10,002 incidents of suicide were retrieved. Risks of violent suicide conferred by SSRIs, expressed as odds ratios (ORs) with 95% confidence intervals (CIs), were estimated using logistic regression. In accordance with previous work, suicide by violent meanscaseswere defined as death attributable to causes designated by ICD-10 codes X70-X83 and Y20-Y33; and suicide by non-violent meanscontrolsby codes X60-X69 and Y10-Y19.ResultsOur results imply that SSRI exposure confers a risk of violent suicide for shorter treatment durations; and that antemortem exposure to other substances (including illegal drugs) confounds estimates of risk. After adjustment for age, sex, and other substances, SSRIs treatment not exceeding 28days conferred an almost fourfold risk of violent suicide (OR 3.6 [95% CI 1.9-6.8]), a finding partly in line with a recent Swedish study that employed a case-crossover design.ConclusionsAlthough risks associated with shorter treatment duration may reflect latencies to onset of therapeutic effect, it is unclear how latencies would influence the choice of suicide method, unless conditions for which SSRIs are prescribed are themselves associated with violent suicide. Finally, in the total dataset, SSRIs were not associated with an increased risk of violent suicide; however, by adjusting for other substances, we avoided the spurious conclusion that the effect of medications in this regard is protective.

[Background] High reproducibility and low intra- and interobserver variability are important strengths of cardiac magnetic resonance (CMR). In clinical practice a significant learning curve may however be observed. Basic CMR courses offer an average of 1.4 h dedicated to lecturing and demonstrating left ventricular (LV) function analysis. The purpose of this study was to evaluate the effect of initial teaching on complete and intermediate beginners’ quantitative measurements of LV volumes and function by CMR., [Methods] Standard clinical cine CMR sequences were acquired in 15 patients. Five observers (two complete beginners, one intermediate, two experienced) measured LV volumes. Before initial evaluation beginners read the SCMR guidelines on CMR analysis. After initial evaluation, beginners participated in a two-hour teaching session including cases and hands-on training, representative for most basic CMR courses, after which it is uncertain to what extent different centres provide continued teaching and feedback in-house. Dice Similarity Coefficient (DSC) assessed delineations. Agreement, accuracy, precision, repeatability and reliability were assessed by Bland-Altman, coefficient of variation, and intraclass correlation coefficient methods., [Results] Endocardial DSC improved after teaching (+0.14 ± 0.17;p, [Conclusions] Initial teaching to complete beginners increases accuracy for assessment of LV volumes, however with high bias and low precision even after standardised teaching as offered in most basic CMR courses. Even though the intermediate beginner showed quite high accuracy already before teaching, precision did generally not improve after standardised teaching. To maintain CMR as a technique known for high accuracy and reproducibility and low intra- and inter-observer variability for quantitative measurements, internationally standardised training should be encouraged including high-quality feedback mechanisms. Objective measurements of training methods, training duration and, above all, quality of assessments are required., This work was supported by a European Union Grant (224495); the British Heart Foundation (Research Excellence Award RE/08/003 and FS/10/029/ 28253); the Biomedical Research Centre (BRC-CTF 196); the Wellcome Trust and EPSRC (WT 088641/Z/09/Z); Lund University Medical Faculty and Lund University Hospital, Sweden; the Foundation BLANCEFLOR BoncompagniLudovisi, née Bildt, Sweden; and the Swedish societies of Medicine, Cardiology, and Radiology; the Erasmus Mundus + Programme of the European Union (Framework Agreement number: 2013–0040); and the German Centre for Cardiovascular Research (DZHK).

Background and purpose - The number of revision total knee arthroplasties (TKA) is continuously increasing, leading to a growing need for reliable management of metaphyseal bone loss. We evaluated patients operated with a TKA using metal metaphyseal sleeves for bone defects with a minimum 5-year follow-up. Patients and methods - 37 patients had been operated on. 3 patients died and 3 patients were lost during follow-up. Of the 31 remainders (20 women), 9 had been operated on with a primary TKA and 22 with a revision TKA at the index surgery. The mean age at surgery was 69 (54-89) years and the mean follow-up time was 7.4 (5-12) years. Bone defects were classified according to the Anderson Orthopaedic Research Institute classification (tibia: type I n = 9, type II n = 5 and type III n = 17; femur: type I n = 12, type II n = 3 and type III n = 16). Results - At final follow-up one-third experienced an improvement concerning walking aids and walking distance. Except for 1 patient, all had full extension and a mean knee flexion of 110 (90-140) degrees. VAS pain at rest was 13 (SD 25) and on movement 30 (SD 31). 7 patients were reoperated due to: infection (n = 4), periprosthetic fracture (n = 1), skin necrosis (n = 1), and wound rupture (n = 1). The cumulative 5-year survival rate for reoperation was 77% (CI 63-92) and for revision 97% (CI 91-100). At the time of final follow-up, the sleeves showed good osseointegration with no signs of progressive radiolucency or migration. Interpretation - Titanium sleeves are a promising option in managing difficult cases with metaphyseal bone defects in TKA, providing a stable construct with good medium-term radiographic outcome.

Background and purpose Prospective studies on patient related outcome in patients Patients and methods 182 patients, 20–69 years with a FNF treated with internal fixation were prospectively included in a multicenter study. Follow up included radiographic and clinical examination at 4, 12 and 24 months. Collected data were hip function using Harris Hip Score (HHS), HRQoL (EQ-5D and SF-36), fracture healing and re-operations. Results At 24 months, HHS was good or excellent in 73% of the patients with a displaced fracture and 85% of the patients with a non-displaced fracture (p = 0.15). Of the patients with displaced fracture (n = 120), 23% had a non-union (NU) and 15% had an avascular necrosis (AVN) with a 28% re-operation rate. None of the patients with non-displaced fracture (n = 50) had an NU, 12% had a radiographic AVN and 8% needed a re-operation. The mean EQ-5Dindex in patients with displaced fracture decreased from 0.81 to 0.59 at 4 months, 0.63 at 12 months and 0.65 at 24 months (p Interpretation Two thirds of the patients with displaced femoral neck fracture healed after one operation and three quarters reported good or excellent functional outcome at 24 months. However, they did not regain their pre-fracture level of HRQoL.

Background: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. Methods: Cases with onset Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p −16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated ( p avg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p −16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA–DRB1*15:01 and HLA–A*02. Conclusion: Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA–DRB1*15:01 and HLA–A*02 are also associated with POMS.

Dysphagia is a common and severe toxicity after oncological treatment of head and neck cancer (HNC). The study aim was to investigate relationships between patient-reported dysphagia and clinically measured swallowing function in HNC after modern curative radiotherapy with or without chemotherapy to identify possible alarm symptoms for clinically manifest dysphagia. Patients with tumors of the tonsil, base of tongue, hypopharynx, and larynx treated in 2007–2015 were assessed for dysphagia post-treatment by telephone interview and videofluoroscopy (VFS). A study-specific categorized symptom score was used to determine patient-reported dysphagia (DESdC = presence of Drinking, Eating, Swallowing difficulties, and Coughing when eating/drinking (any combination); scores between 0 and 4 with 0 = no symptom); the penetration–aspiration scale (PAS) to determine swallowing function by VFS. Swallowing difficulties were defined as DESdC ≥ 1 and PAS ≥ 2. Relationships between clinically relevant cut-offs for DESdC and PAS were determined by Pearson’s correlation coefficient (Pr). Swallowing difficulties according to DESdC were reported by 89% of the patients and according to PAS by 60% at a median of 7 months post-treatment. Averaged correlations between DESdC score 1/2/3/4 and PAS were 0.16/0.10/0.27/0.18. Almost one in two patients with DESdC score ≥3 had severe swallowing difficulties according to PAS. Correlations between individual DESdC:s were highest for swallowing and eating (Pr = 0.53) and lowest for swallowing and coughing (Pr = 0.11). Our data suggest that if a patient reports having swallowing difficulties, it is likely that he or she also has eating difficulties but not necessarily coughing problems when eating/drinking. However, if all these three symptoms are reported, it is likely that the patient will present with moderate or severe impaired swallowing function according to PAS and thus should be referred for further evaluation and treatment.

Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We used six independent case–control studies from five different countries (Sweden, Denmark, Norway, Serbia, United States). A pooled analysis was performed for replication of previous observations (7190 cases, 8876 controls). Refined detailed analyses were carried out by combining the genetically similar populations from the Nordic studies (6265 cases, 8401 controls). In both the pooled analyses and in the combined Nordic material, interactions were observed between HLA-DRB*15 and absence of HLA-A*02 and between smoking and each of the genetic risk factors. Two way interactions were observed between each combination of the three variables, invariant over categories of the third. Further, there was also a three way interaction between the risk factors. The difference in MS risk between the extremes was considerable; smokers carrying HLA-DRB1*15 and lacking HLA-A*02 had a 13-fold increased risk compared with never smokers without these genetic risk factors (OR 12.7, 95% CI 10.8–14.9). The risk of MS associated with HLA genotypes is strongly influenced by smoking status and vice versa. Since the function of HLA molecules is to present peptide antigens to T cells, the demonstrated interactions strongly suggest that smoking alters MS risk through actions on adaptive immunity. Electronic supplementary material The online version of this article (doi:10.1007/s10654-017-0250-2) contains supplementary material, which is available to authorized users.