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It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [C-11]DASB and [C-11]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response. Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission; Riksbankens Jubileumsfond-the Swedish Foundation for Humanities and Social Sciences; Kjell and Marta Beijer Foundation

Introduction As compared to younger adults, older people have a greater risk of domestic accidents, such as burns, and their prognosis is worsened by a diminished physiological ability to face a thermal trauma. The in-hospital mortality is adversely affected by old age and burn size, whereas less is known about the long-term-survival in elderly patients who survive a burn injury. The aim of this study was to investigate if elderly burn patients after discharge from a Swedish National Burn Centre have a shorter remaining life compared to the national population, by using calculated remaining Life Expectancy (rLE). Methods In this retrospective study we included all patients who were admitted for burns to the Linkoping Burn Centre during 1993–2016 and who were 60 years or older and alive, at the time of discharge. The control group was extracted from Statistics Sweden, the national statistics database, and consisted of all individuals from the Swedish population matched for each patient in the study group, by sex and age at the year of discharge. The proportion who died before reaching the rLE was compared between the study population and the control group by calculating risk ratio. Results The study group consisted of 111 former patients and 77 of them (69%) died before reaching the rLE, with mean 4.7 years of life lost (YLL), which was 33% more than that (52%) of the control group (RR 1.33, 95% CI 1.18–1.51). Burn related factors, such as TBSA % or FTB % were not found to account for this effect. Conclusion We found that the long-time survival of elderly patients after burns is shorter than that of a national control, the magnitude of which is quantitatively important. The current study does not support that burn related factors account for this effect and the reason should therefore be sought in other factors, such as e.g., co-morbidity or psychosocial issues.

Background This study was performed to develop and validate a cardiac surgical intensive care risk adjustment model for mixed cardiac surgery based on a few preoperative laboratory tests, extracorporeal circulation time, and measurements at arrival to the intensive care unit. Methods This was a retrospective study of admissions to 5 cardiac surgical intensive care units in Sweden that submitted data to the Swedish Intensive Care Registry. Admissions from 2008 to 2014 (n = 21,450) were used for model development, whereas admissions from 2015 to 2016 (n = 6463) were used for validation. Models were built using logistic regression with transformation of raw values or categorization into groups. Results The final model showed good performance, with an area under the receiver operating characteristics curve of 0.86 (95% confidence interval, 0.83-0.89), a Cox calibration intercept of –0.16 (95% confidence interval, –0.47 to 0.19), and a slope of 1.01 (95% confidence interval, 0.89-1.13) in the validation cohort. Conclusions Eleven variables available on admission to the intensive care unit can be used to predict 30-day mortality after cardiac surgery. The model performance was better than those of general intensive care risk adjustment models used in cardiac surgical intensive care and also avoided the subjective assessment of the cause of admission. The standardized mortality ratio improves over time in Swedish cardiac surgical intensive care.

Objective: To compare the assessments of 10-year probability by patients and their physicians of cardiovascular complications of hypertension with actual outcomes. Design: Patients with uncomplicated hypertension treated with at least one antihypertensive drug at inclusion were followed for 10 years through mandatory national health registers. Setting: 55 primary health care centres, 11 hospital outpatient clinics in Sweden Patients: 848 patient, 212 physicians. Main outcome measures: Patients and physicians estimated the probability of hypertension-related complications with treatment (death, heart failure, acute myocardial infarction/AMI, and stroke) for each patient in 848 pairs. Estimates were compared with the clinical outcomes 10 years later using data from the Mortality Register and the National Patient Register. Results: Patients were significantly better (p p Conclusions: Patients were better than their physicians in estimating the average probability of morbidity due to hypertension. Both the patients and their attending physicians had difficulty in estimating the individual patient’s risk of complications. The results support the use of evidence-based tools in consultations for assessing the risk of cardiovascular complications associated with hypertension.Key points • Shared decision making relies on a common understanding of risks and benefits. Tools for risk assessment of hypertension have been introduced in the last two decades. • Without tools for risk assessment, both patients and physicians had difficulties in estimating the individual patient’s risk of cardiovascular morbidity. • Patients were better than physicians in estimating actual average cardiovascular morbidity due to hypertension during a follow-up of 10 years. • The results support the use of evidence-based tools in consultations for assessing the risk of cardiovascular complications associated with hypertension. • Shared decision making relies on a common understanding of risks and benefits. Tools for risk assessment of hypertension have been introduced in the last two decades. • Without tools for risk assessment, both patients and physicians had difficulties in estimating the individual patient’s risk of cardiovascular morbidity. • Patients were better than physicians in estimating actual average cardiovascular morbidity due to hypertension during a follow-up of 10 years. • The results support the use of evidence-based tools in consultations for assessing the risk of cardiovascular complications associated with hypertension.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for development of type 2 diabetes mellitus (T2DM). We aimed to evaluate whether conventional histological grading of steatosis and accurate quantification of fat content in liver biopsies using stereological point counting (SPC) can predict mortality and future development of T2DM in NAFLD patients. METHODS: 129 patients with biopsy proven NAFLD, enrolled between 1988 and 1992, were re-evaluated on two occasions, after 13.7 (±1.5) and 23.2 (±6.8) years. In patients accepting to undergo the procedure, repeat liver biopsies were performed on each follow-up and were evaluated with conventional histopathological methodology and SPC. RESULTS: Of the 106 patients without T2DM at baseline, 66 (62%) developed T2DM during a mean follow-up of 23.2 (± 6.8) years. Steatosis grade and liver fat measured with SPC independently (adjusted for age, BMI, fibrosis stage) predicted development of T2DM with an aHR of 1.60 per grade and 1.03 for each SPC percentage increase, respectively. Overall mortality and development of T2DM was more common in patients with grade 3 steatosis compared to lower grades of steatosis. Liver fat measured with SPC was significant for overall mortality (aHR 1.04). In patients that underwent repeat biopsy, reduction of liver fat measured with SPC was associated with decreased risk of developing T2DM (aHR 0.91 for each SPC percentage decrease). CONCLUSION: Steatosis grade and liver fat measured with SPC predict mortality and the risk of developing T2DM in NAFLD. Reduction of liver fat decreases the risk of developing T2DM.

Background Frailty is a multidimensional syndrome characterised by a loss of reserve and an increased risk of adverse outcomes. Objective To study the impact of frailty on mortality in unselected intensive care patients, and to compare its discriminatory ability to an established model for outcome prediction in intensive care. Design A prospective study with a comparison of two prediction models. Setting A tertiary mixed ICU, from January 2017 to June 2018. Patients and main outcome measures Data on premorbid frailty (clinical frailty scale; CFS), severity of illness (the simplified acute physiology score, third version; SAPS3), therapeutic procedures, limitations of care and outcome were collected in 872 adult ICU patients. A cut-off level of CFS for predicting death within 30 days was identified and unadjusted and adjusted analyses were used to evaluate the association of frailty to outcome. Results The receiver operating curve, area under the curve of CFS [0.74 (95% confidence interval, 0.69 to 0.79)] did not differ significantly from that of SAPS3 [0.79 (0.75 to 0.83), P = 0.53], whereas combining the two resulted in an improved discriminatory ability [area under the curve = 0.82 (0.79 to 0.86), CFS + SAPS3 vs. SAPS3 alone, P = 0.02]. The correlation of CFS to SAPS3 was moderate (r = 0.4). A cut-off level was identified at CFS at least 5, defining 43% (n=375) of the patients as frail. Frail patients were older with higher SAPS3 and more comorbidities. Treatment in the ICU was more often withheld or withdrawn in frail patients, and mortality was higher. After adjustment for SAPS3, comorbidities, limitations of treatment, age and sex, frailty remained a strong predictor of death within 30 days [hazard ratio 2.12 (95% confidence interval, 1.44 to 3.14), P Conclusion Premorbid frailty was common in general ICU patients and was an independent predictor of death. Our study suggests that frailty could be a valuable addition in outcome prediction in intensive care.

ObjectivesThe aim of this study was to identify prehospital and early hospital risk factors associated with 30-day mortality in patients with blood culture-confirmed community-acquired bloodstream infection (CA-BSI) in Sweden.MethodsA retrospective case–control study of 1624 patients with CA-BSI (2015–2016), 195 non-survivors satisfying the inclusion criteria were matched 1:1 with 195 survivors for age, gender and microorganism. All forms of contact with a healthcare provider for symptoms of infection within 7 days prior CA-BSI episode were registered. Logistic regression was used to analyse risk factors for 30-day all-cause mortality.ResultsOf the 390 patients, 61% (115 non-survivors and 121 survivors) sought prehospital contact. The median time from first prehospital contact till hospital admission was 13 hours (6–52) for non-survivors and 7 hours (3–24) for survivors (p24 hours from first contact remained an important risk factor for 30-day all-cause mortality due to CA-BSI OR=6.17 (95% CI: 2.19 to 17.38), pConclusionPrehospital delay and inappropriate empirical antibiotic therapy were found to be important risk factors for 30-day all-cause mortality associated with CA-BSI. Increased awareness and earlier detection of BSI in prehospital and early hospital care is critical for rapid initiation of adequate management and antibiotic treatment.

AIM This study described the basic characteristics of children aged 0-16 years who were treated in intensive care units (ICUs) and paediatric ICUs (PICUs), compared their outcomes and examined any causes of death. METHODS This was a retrospective cohort study of admissions to 74 ICUs and three PICUs in Sweden that were recorded in the Swedish Intensive Care Registry from January 1, 2008 to December 31, 2012. RESULTS We retrieved data on 12 756 children who were admitted 17 003 times. The case mix differed between the ICUs, which were mainly admissions for injuries, accidents and observation, and PICUs, which were mainly admissions for malformations, genetic abnormalities and respiratory problems (p

Background There is still no consensus about the association between working in dampness-damaged buildings and new onset of asthma among adults. The purpose of this study was to assess asthma in the staff of two psychiatric clinics where some premises were suffering from dampness. Methods A 20-year retrospective cohort study was performed using questionnaires. Results Incidence rate ratios (IRR) for asthma were non-significantly elevated (IRR = 2.3) among exposed individuals. The risk was greater among females (IRR = 3.5, 95% CI 1.0-16). IRR for non-atopic women was 8.8 (95% CI 1.4-196). Adjusting for smoking habits weakened the risks marginally (IRR = 7.3, 95% CI 1.1-167). The number of male participants was too low to draw conclusion regarding the risk for men. Conclusion The results suggest that working in dampness-damaged buildings might be a possible health hazard. This finding is most pronounced in non-atopic females.

Background Current evidence for the conduct of rapid sequence induction (RSI) is weak. This increases the risk of clinicians modifying the RSI procedure according to personal preferences. Checklists may help increase compliance to best practice guidelines and reduce complication rates. Their value during RSI, a critical procedure in anaesthesia, is unknown. The aim of this study was to investigate compliance to local guidelines and frequency of RSI-related complications before and after introduction of an RSI checklist. Methods This was a prospective, observational, pre- and post-intervention study conducted at two hospitals. There were two interventions: the first was a standardized educational lecture to all staff at both hospitals, consisting of an educational instruction of the checklist and general information about RSI, and the second intervention was the introduction of a RSI checklist. The checklist consisted of 16 items. Compliance to guidelines was categorized as high, moderate and low, and was assessed pre- and post-intervention. The frequency of RSI-related complications was also measured. Results We registered 811 RSI procedures of which 412 were pre-intervention. After intervention, the proportion of procedures with high compliance to RSI guidelines increased from 49% to 70% (P < .001). The proportion with partial and low compliance decreased from 37% to 26% (P < .001) and 13% to 3.3% (P < .001) respectively. No change in RSI-related complication rates was detectable post-intervention (16.6%-16.7% P = .56). Conclusion The introduction of a structured RSI checklist significantly increased compliance to RSI guidelines. A change in RSI-related complications could not be detected due to the size of the study. A checklist may be a useful tool to reduce variance during the RSI procedure. Funding Agencies|Healthcare region of Ostergotland; departments of Anaesthesiology of University hospital of Linkoping and Vrinnevisjukhuset, Norrkoping, Region Ostergotland, Sweden

Neuroimaging studies using PET and SPECT to evaluate neurofunctional differences between patients with anxiety- and stress-related disorders and healthy controls were reviewed. At rest, patients with social anxiety disorder display increased serotonin synthesis rate and upregulated serotonin transporter expression, whereas studies targeting dopamine have yielded mixed results. Posttraumatic stress disorder is associated with a compromised benzodiazepine receptor function. In panic disorder, both benzodiazepine receptors and serotonergic (5-hydroxytryptamine 1A (5HT1A)) receptors are downregulated. Across the anxiety disorders, there is downregulation of both benzodiazepine and 5HT1A receptors. Symptom provocation studies, where regional cerebral blood flow is measured, support that activity in the brain’s fear circuit is altered with increased reactivity in the amygdala, the midbrain, and possibly also the insular cortex, whereas activity in emotion-regulating areas in the prefrontal cortex such as the subgenual anterior cingulate cortex and the orbitofrontal cortex is compromised in the symptomatic state, predominantly in phobic disorders. Some studies demonstrate a coupling between individual differences in neurotransmission and fear network activity. Treatment studies suggest that reductions of neural activity in the amygdala may be a final common pathway for successful therapeutic interventions, thereby linking neurotransmission to plasticity in the core fear network of the brain.

IntroductionA coeliac disease (CD) diagnosis is likely in children with levels of tissue transglutaminase autoantibodies (anti-TG2) >10 times the upper reference value, whereas children with lower anti-TG2 levels need an intestinal biopsy to confirm or rule out CD. A blood sample is easier to obtain than an intestinal biopsy sample, and stabilised blood is suitable for routine diagnostics because transcript levels are preserved at sampling. Therefore, we investigated gene expression in stabilised whole blood to explore the possibility of gene expression-based diagnostics for the diagnosis and follow-up of CD.DesignWe performed RNA sequencing of stabilised whole blood from active CD cases (n=10), non-CD cases (n=10), and treated CD cases on a gluten-free diet (n=10) to identify diagnostic CD biomarkers and pathways involved in CD pathogenesis.ResultsNo single gene was differentially expressed between the sample groups. However, by using gene set enrichment analysis (GSEA), significantly differentially expressed pathways were identified in active CD, and these pathways involved the inflammatory response, negative regulation of viral replication, translation, as well as cell proliferation, differentiation, migration, and survival. The results indicate that there are differences in pathway regulation in CD, which could be used for diagnostic purposes. Comparison between GSEA results based on stabilised blood with GSEA results based on small intestinal biopsies revealed that type I interferon response, defence response to virus, and negative regulation of viral replication were identified as pathways common to both tissues.ConclusionsStabilised whole blood is not a suitable sample for clinical diagnostics of CD based on single genes. However, diagnostics based on a pathway-focused gene expression panel may be feasible, but requires further investigation.

Spider phobia is characterized by exaggerated fear of situations where spiders could be present, resulting in avoidance of such situations and compromised quality of life. An important component in psychological treatment of spider phobia is exposure to phobic situations that reduces avoidance behaviors. At the neural level, amygdala responses to phobic material are elevated, but normalizes following exposure treatment. To what extent amygdala activity decreases during a session of repeated phobic stimulation, and whether activity decrease is related to subsequent avoidance is not well studied. We hypothesized reduced amygdala activity during the course of repeated exposure to spider pictures, and that the degree of reduction would predict subsequent avoidance of spider pictures. To test our hypothesis, functional magnetic resonance imaging was performed in 45 individuals with spider fear during repeated exposure to spider pictures. Results showed that repeated exposure to spider stimuli attenuated amygdala reactivity and individual differences in activity reductions predicted subsequent avoidance behavior to spider pictures in an incentive-conflict task, with larger attenuations predicting less avoidance. At 6-month follow up, initial reductions in amygdala activation still predicted avoidance. This result demonstrates that reduction in amygdala responses is related to clinically meaningful outcomes in human anxiety, and suggests that within-session reductions in amygdala responses could be an important mechanism explaining the clinical effects of exposure therapy. De två sista författarna delar sistaförfattarskapet

Background: The outcome and tolerability of palliative second line chemotherapy for advanced pancreatic cancer (APC) in real life patients are largely unknown. Prognostic parameters for risk stratification and treatment guidance are lacking. Materials and Methods: A population based multicenter retrospective cohort study was conducted, covering all APC patients who received palliative second-line chemotherapy between 2011 and 2018 at any cancer center in the South East Region of Sweden. Primary outcome was overall survival after second-line therapy (OS2). Time to treatment failure after second-line therapy (TTF2), hematological toxicity, and unplanned hospitalizations were key secondary outcomes. A number of baseline potentially prognostic parameters were assessed. Results: A total of 509 patients received first-line palliative chemotherapy, and of these 167 (33%) received at least one dose of second-line therapy and formed the final study population. Median OS2 was 5.2 months (95% CI = 4.7–5.7) and median TTF2 was 1.9 months (1.5–2.2). OS2 and TTF2 were similar regardless regimen, including comparison of the two most common regimens (fluoropyrimidine monotherapy vs. fluoropyrimidine/oxaliplatin doublet). Multivariate analysis revealed that normal plasma albumin (≥35) and serum CA-19-9 above median (>1,550) were independent predictors for OS2 (HR = 0.21, p < 0.001 and HR = 2.03, p = 0.009) and TTF2 (HR = 0.22, p < 0.001 and HR = 2.03, p = 0.01), while ECOG performance status >1 was predictive for TTF2 (HR = 2.05, p = 0.032). Grade 3–4 hematological toxicity was registered in 17 patients (10%). 50 (30%) had at least one event of hospitalization. Conclusion: The real world outcome of second line palliative chemotherapy for refractory APC remains dismal. Baseline plasma albumin, serum CA-19-9, and performance status emerge as key prognostic factors, and should be further studied as tools for individualized treatment decisions. Funding Agencies|Futurum, Academy for Health and Care Jonkoping County Council [695491]; Medical Research Council of Southeast Sweden [FORSS-751541]; ALF grants Region Ostergotland [LIO-697991, LIO-707011, LIO-697461]; Sveriges Gastro-Onkologiska Forening (GOF); CKOC grants Region Ostergotland

Background: The aim of this study was to validate a translated Swedish version of the lymphoedema-specific quality of life questionnaire (LYMQOL) in a cohort of Swedish cancer patients with secondary lymphoedema of the limbs after cancer treatment. Material and methods: We recruited 102 patients with lymphoedema of the arms or legs after cancer treatment who were visiting lymphoedema therapists at the departments of oncology at the university hospitals in Linköping and Umeå. The LYMQOL questionnaires were translated forward and backward from English to Swedish. Content and face validity were evaluated. The construct validity was assessed by comparing the LYMQOL with the Short Form Health Survey (SF-36) and the perceived degree of lymphoedema of the limbs, respectively. Reliability was determined through test-retest. The internal consistency was assessed by determining Cronbach’s alpha and by factor analysis. Results: The content and face validity assessments showed that LYMQOL was an easy, clear and not too long questionnaire to use for patients with lymphoedema. Construct validity was high in both versions when compared with the SF-36. The association between the degrees of perceived lymphoedema and the LYMQOL was only significant in the domains Function and Body Image in the arm version, whereas all domains in the leg version were significant. The reliability was good for the arm version (intra-class-correlation coefficients 0.53–0.87) and very good for the leg version (intra-class-correlation coefficients 0.78–0.90). The internal consistency was acceptable to excellent, with Cronbach’s alpha values between 0.79–0.93 (arm-version) and 0.87–0.94 (leg-version). The factor analysis confirmed the usefulness of the four domains in the LYMQOL versions. Conclusions: This study confirmed the validity of the Swedish version of LYMQOL and demonstrated that LYMQOL may be a simple and useful tool for use in clinical practice and scientific contexts for evaluating QoL in patients with lymphoedema of the limbs. Funding Agencies|Swedish Cancer SocietySwedish Cancer Society [CAN 2013/620]; Linkoping University; County Council of Ostergotland

Background In recent years treatment options for advanced pancreatic cancer have markedly improved, and a combination regimen of gemcitabine and nab-paclitaxel is now considered standard of care in Sweden and elsewhere. Nevertheless, a majority of patients do not respond to treatment. In order to guide the individual patient to the most beneficial therapeutic strategy, simple and easily available prognostic and predictive markers are needed. Methods The potential prognostic value of a range of blood/serum parameters, patient-, and tumour characteristics was explored in a retrospective cohort of 75 patients treated with gemcitabine/nab-paclitaxel (Gem/NabP) for advanced pancreatic ductal adenocarcinoma (PDAC) in the South Eastern Region of Sweden. Primary outcome was overall survival (OS) while progression free survival (PFS) was the key secondary outcome. Result Univariable Cox regression analysis revealed that high baseline serum albumin (> 37 g/L) and older age (> 65) were positive prognostic markers for OS, and in multivariable regression analysis both parameters were confirmed to be independent prognostic variables (HR 0.48, p = 0.023 and HR = 0.47, p = 0.039,). Thrombocytopenia at any time during the treatment was an independent predictor for improved progression free survival (PFS) but not for OS (HR 0.49, p = 0.029, 0.54, p = 0.073), whereas thrombocytopenia developed under cycle 1 was neither related with OS nor PFS (HR 0.87, p = 0.384, HR 1.04, p = 0.771). Other parameters assessed (gender, tumour stage, ECOG performance status, myelosuppression, baseline serum CA19–9, and baseline serum bilirubin levels) were not significantly associated with survival. Conclusion Serum albumin at baseline is a prognostic factor with palliative Gem/NabP in advanced PDAC, and should be further assessed as a tool for risk stratification. Older age was associated with improved survival, which encourages further studies on the use of Gem/NabP in the elderly.

Background Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD). Methods We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18 years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram (20 mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605. Findings Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n = 24) as compared to covert (n = 22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI 10.69–31.65, p, Highlights • Overt surpassed covert SSRI treatment with doubled effect size and tripled response rate on the main social anxiety outcome. • Overt vs. covert SSRI treatment yielded different neural changes in brain areas involved in emotion-cognition interactions. • This study suggests that the presentation of a treatment may be as important as the treatment itself. Using truthful or deceiving verbal instructions, we tested how expectancies influence SSRI efficacy in social anxiety disorder. The number of responders was more than three times higher after open administration of escitalopram 20 mg compared to covert administration of the drug presented as “active placebo” in a cover story. Correct vs. incorrect information about the SSRI also yielded different neural changes in brain areas involved in emotion-cognition interactions. The benefit of SSRI medication seems to be highly affected by psychological factors like positive expectancies traditionally associated with placebo. Our results favor a biopsychosocial over a biomedical explanatory model for SSRI efficacy.

Changes in blood flow influence temperature of surrounding tissues. Since the internal carotid artery (ICA) and internal jugular vein (IJV) neighbor the tympanic membrane, changes in their blood flow most likely determine changes in tympanic membrane temperature (TMT). We sought to evaluate the relationship between changes during a head-up tilt (HUT) induced reduction in cerebral blood flow (CBF) and TMT.Ten male subjects (age 19-28 years) underwent 50° HUT until presyncope. A non-contact infrared sensor in the ear canal targeted the tympanic membrane. Changes in CBF were monitored by transcranial Doppler which determined the mean blood flow velocity in the middle cerebral artery (MCA VDuring HUT, TMT decreased by 0.6 °C (median; range 0.2 to 1.6 °C) related to a decrease in MCA VDuring an orthostatic challenge TMT decreases and the decrease is related to a reduction in CBF as indicated by MCA V

Lymphedema is one of the least studied complications of cancer treatment and a chronic condition with a substantial impact on health-related quality of life (HQoL). Lymphedema of the legs (LLL) constitutes a common adverse side effect of lymphadenectomy LA in gynecologic cancer treatment. Primary treatment of endometrial cancer (EC) comprises hysterectomy and bilateral salpingo-oophorectomy. Pelvic and para-aortic lymphadenectomy is recommended in prognostic high risk groups of EC. This review summarizes the published literature concerning the prevalence of LLL after treatment for EC, methods used for measuring LLL, risk factors and HQoL impact. The main findings are that the reported prevalence of LLL varies significantly between 0% and 50%. This is due to a lack of a generally accepted standardization of terminology in assessment of lymphedema. The studies use different methods to assess and grade lymphedema and often the methodology used for determining LLL is poorly described and lacks baseline measurement. Lymphadenectomy, number of lymph nodes removed, and radiation therapy seems to increase the risk for LLL. All studies dealing with HQoL show that women with LLL have impaired HQoL. The level of evidence in the published studies is generally low. Consequently it is difficult to make clear-cut conclusions about the true prevalence or determination of risk factors. More prospective longitudinal or randomized trials with LLL as the primary outcome are necessary before conclusions can be drawn regarding prevalence of LLL and risk factor determination in EC. An internationally accepted standardization for terminology and methodology in lymphedema in research is needed.

As widely reported, the progress in burn care during recent decades has reduced the hospital mortality. The effect of the burns on long-term outcome has not received so much attention, and more study is indicated. The aim of this retrospective study was to investigate the long-time survival among patients who had been treated for burns.We studied 1487 patients who were discharged alive from the Linköping University Hospital Burn Centre during the period 1993 until the end of December 2012. We used Cox's regression analysis to study the effect of burns on long-term survival after adjustment for different factors.Age and a full-thickness burn were significantly associated with mortality after discharge (p0.001), whereas percentage of total body surface area burned (TBSA %), need for mechanical ventilation, and gender were not. Less than 1% of the patients with burns (13/1487) died within 30 days of discharge and a total of 176/1487 (12%) died during follow-up.Age and full-thickness burns reduce the long-time survival after discharge from the Burn Centre, whereas the effect of TBSA% and need for artificial ventilation ends with discharge.

Background: Quality of care has gained increased attention in IBD. The questionnaire Quality of Care Through the Patient’s Eyes – Inflammatory Bowel Disease (QUOTE-IBD) was the first published vali...

Innate immunity is a first line defense against Mycobacterium tuberculosis infection where inflammasome activation and secretion of the pro-inflammatory cytokine IL-1beta, plays a major role. Thus, genetic polymorphisms in innate immunity-related genes such as CARD8 and NLRP3 may contribute to the understanding of why most exposed individuals do not develop infection. Our aim was to investigate the association between polymorphisms in CARD8 and NLRP3 and active tuberculosis (TB) as well as their relationship to treatment outcome in a high-endemic setting for TB. Polymorphisms in CARD8 (C10X) and NLRP3 (Q705K) were analysed in 1190 TB patients and 1990 healthy donors (HD). There was a significant association between homozygotes in the CARD8 polymorphism and extrapulmonary TB (EPTB), which was not the case for pulmonary TB or HDs. Among TB-patients, there was an association between poor treatment outcome and the NLRP3 (Q705K) polymorphism. Our study shows that inflammasome polymorphisms are associated with EPTB and poor clinical outcome in active TB in Ethiopia. The practical implications and determining causal relationships on a mechanistic level needs further study. Funding Agencies|Research Council of South East of Sweden (FORSS); Swedish International Development Cooperation Agency (SIDA); Heart and Lung Foundation; Swedish Research Council

Background: After intensive care unit treatment, patients often have prolonged impairments that affect their physical, cognitive and mental health. Family members can face overwhelming and emotionally challenging situations and their concerns and needs must be addressed. Objective: We investigated the outcomes of pilot randomised control trial, a nurse-led family intervention, Health Promoting Conversations, which focused on family functioning and wellbeing in families with a critically ill member. Study design: This randomised controlled pilot study used a pre-test, post-test design with intervention and control groups to investigate the outcomes of the nurse-led intervention in 17 families. Outcome measures: The Health Promoting Conversations intervention was evaluated using validated instruments that measure family functioning and family wellbeing: the General Functioning sub-scale from the McMaster Family Assessment Device; the Family Sense of Coherence, the Herth Hope Index, and the Medical Outcome Short-Form Health Survey. Descriptive and analytical statistical methods were used to analyse the data. Results: After 12 months, the intervention group reported better family functioning than the control group. The intervention group also had better social functioning and mental health after 12 months. Conclusion: This intervention may improve family wellbeing by improving family function, reducing stress, and promoting better mental health. (C) 2018 Elsevier Ltd. All rights reserved. Funding Agencies|Medical Research Council of Southeast Sweden [FORSS 466311]; Department of Anaesthesiology and Intensive Care; Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden

Objectives: To assess how women in Sweden with breast cancer (BC), endometrial cancer (EC), and/or pulmonary embolism (PE) were dispensed menopausal hormone therapy (HT). Study design: A retrospective study of Swedish women aged 40 years or more on 31 December 2005 (n = 2,863,643), followed through to December 2011. The study analysed three mandatory national healthcare registries: the Swedish Prescribed Drug Register, the National Inpatient Register and the Cancer Register. New users were defined as having a first dispensation after at least a 9-month break, and thus were possible to identify from April 2006. New users with at least one of the diagnoses BC, EC or PE before the first dispensation were classified as having a relative or absolute contraindication for HT. Main outcome measures: The relative risks of having HT dispensed after being diagnosed with BC, EC and/or PE. Results: In total, 171,714 women had at least one of the diagnoses BC, EC or PE. The relative risk of having hormone therapy dispensed (current and new users) after being diagnosed with any of the diagnoses was significantly lower (PE, IRR 0.11, 95% CI 0.10-0.12;/ BC, IRR 0.12, 95% CI 0.11-0.13; EC, IRR 0.43, CI 0.40-0.46) than for women without these diagnoses. Conclusions: One in about 250 women started treatment with HT after being diagnosed with BC, PE or EC. Swedish prescribers seem to be well aware of the recommendations for HT use in women with contraindications. A few women, however, are prescribed HT despite having BC, EC or PE, possibly after careful evaluation of the risks and benefits and giving informed consent. Women with a history of PE were prescribed transdermal HT to a larger extent than women in general, in line with results from observational studies. Funding Agencies|County Council of Ostergotland, Sweden [LiO-11877, LiO-31321, LiO-79951]

Objectives The aim was to examine health-related quality of life (HRQoL), patient characteristics and reasons for visits to general practitioners (GPs) by frequent attenders (FAs) and a comparison group (CG) in primary care. Methods Patients aged 18–64 years were eligible for the study. Medical records were scrutinised concerning reasons for visits. Questionnaires including short-form health survey (SF-36) were mailed to 331 FAs (≥5 visits at GPs during 2000) and 371 patients in a CG randomly selected from two healthcare centres and returned by 49% and 57%, respectively. FAs’ SF-36 health profiles were compared both to CG and general Swedish population norms. Results FAs report lower HRQoL than CG and below the general Swedish population norms in all eight SF-36 domains including both mental and physical component summary scores (MCS and PCS). Effect sizes (ESs) for differences between FAs and norms ranged from 0.79 to 1.08 for specific domains and was 0.94 for PCS and 0.71 for MCS. ESs of FAs versus CG ranged between 0.60 and 0.95 for the domains and was 0.76 for PCS and 0.49 for MCS. There were no significant differences between the FAs and CG with regard to sex, being married or cohabiting, number of children in household or educational level. FAs were more often unemployed, obese, slightly older and used complementary medicine more frequently. Except for injuries, all health complaints as classified in 10 categories were more common among FAs than CG, particularly musculoskeletal pain and psychosocial distress related to compromised HRQoL. Conclusion The HRQoL is compromised in FAs, both when compared with patients who do not often seek care and to general Swedish population norms. Commonly reported reasons for visiting GPs among FAs were musculoskeletal pain and psychosocial distress. Thus, perceived ill health, particularly pain and distress, seems important for high utilisation of healthcare resources. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Early appropriate antimicrobial therapy is crucial in patients with sepsis and septic shock. Studies often focus on time to first dose of appropriate antibiotics, but subsequent dosing is equally important. Our aim was to investigate the impact of fulfillment of early treatment, with focus on appropriate administration of first and second doses of antibiotics, on 28-day mortality in patients with community-onset severe sepsis and septic shock. A retrospective study on adult patients admitted to the emergency department with community-onset sepsis and septic shock was conducted 2012–2013. The criterion “early appropriate antibiotic treatment” was defined as administration of the first dose of adequate antibiotics within 1 h, and the second dose given with less than 25% delay after the recommended dose interval. A high-risk patient was defined as a septic patient with either shock within 24 h after arrival or red triage level on admittance according to the Medical Emergency Triage and Treatment System Adult. Primary endpoint was 28-day mortality. Of 90 patients, less than one in four (20/87) received early appropriate antibiotic treatment, and only one in three (15/44) of the high-risk patients. The univariate analysis showed a more than threefold higher mortality among high-risk patients not receiving early appropriate antibiotic treatment. Multivariable analysis identified early non-appropriate antibiotic treatment as an independent predictor of mortality with an odds ratio for mortality of 10.4. Despite that the importance of early antibiotic treatment has been established for decades, adherence to this principle was very poor. Electronic supplementary material The online version of this article (10.1007/s10096-019-03529-8) contains supplementary material, which is available to authorized users.

Standardised Mortality Ratio (SMR) based on generic mortality predicting models is an established quality indicator in critical care. Burn-specific mortality models are preferred for the comparison among patients with burns as their predictive value is better. The aim was to assess whether the sum of age (years) and percentage total body surface area burned (which constitutes the Baux score) is acceptable in comparison to other more complex models, and to find out if data collected from a separate burn centre are sufficient for SMR based quality assessment. The predictive value of nine burn-specific models was tested by comparing values from the area under the receiver-operating characteristic curve (AUC) and a non-inferiority analysis using 1% as the limit (delta). SMR was analysed by comparing data from seven reference sources, including the North American National Burn Repository (NBR), with the observed mortality (years 1993-2012, n=1613, 80 deaths). The AUC values ranged between 0.934 and 0.976. The AUC 0.970 (95% CI 0.96-0.98) for the Baux score was non-inferior to the other models. SMR was 0.52 (95% CI 0.28-0.88) for the most recent five-year period compared with NBR based data. The analysis suggests that SMR based on the Baux score is eligible as an indicator of quality for setting standards of mortality in burn care. More advanced modelling only marginally improves the predictive value. The SMR can detect mortality differences in data from a single centre.

Background To our knowledge this is the first published estimate of the charges of the care of burns in Sweden. The Linkoping Burn Interventional Score has been used to calculate the charges for each burned patient since 1993. The treatment of burns is versatile, and depends on the depth and extension of the burn. This requires a flexible system to detect the actual differences in the care provided. We aimed to describe the model of burn care that we used to calculate the charges incurred during the acute phase until discharge, so it could be reproduced and applied in other burn centres, which would facilitate a future objective comparison of the expenses in burn care. Methods All patients admitted with burns during the period 2010–15 were included. We analysed clinical and economic data from the daily burn scores during the acute phase of the burn until discharge from the burn centre. Results Total median charge/patient was US$ 28 199 (10th–90th centiles 4668-197 781) for 696 patients admitted. Burns caused by hot objects and electricity resulted in the highest charges/TBSA%, while charges/day were similar for the different causes of injury. Flame burns resulted in the highest mean charges/admission, probably because they had the longest duration of stay. Mean charges/patient increased in a linear fashion among the different age groups. Conclusion Our intervention-based estimate of charges has proved to be a valid tool that is sensitive to the procedures that drive the costs of the care of burns such as large TBSA%, intensive care, and operations. The burn score system could be reproduced easily in other burn centres worldwide and facilitate the comparison regardless of the differences in the currency and the economic circumstances.

Cardiac dysfunction is a well-known complication of sepsis, but its long-term consequences and implications for patients remain unclear. The aim of this study was to investigate cardiac outcome in sepsis by assessing causes of death up to 2 years after treatment in an Intensive Care Unit (ICU) in a nationwide register-based cohort collected from the Swedish Intensive Care Registry.A cohort of 13 669 sepsis and septic shock ICU patients from 2008 to 2014 was collected together with a non-septic control group, matched regarding age, sex and severity of illness (n = 6582), and all without preceding severe cardiac disease. For a large proportion of the severe sepsis and septic shock patients (n = 7087), no matches were found. Information on causes of death up to 2 years after ICU admission was sought in the Swedish National Board of Health and Welfare's Cause of Death Registry.Intensive Care Unit mortality was nearly identical in a matched comparison of sepsis patients to controls (24% in both groups) but higher in more severely ill sepsis patients for whom no matches were found (33% vs 24%, P 0.001). There was no association of sepsis to cardiac deaths in the first month (OR 1.03, 95%CI 0.87 to 1.20, P = 0.76) nor up to 2 years after ICU admission (OR 1.01, 95%CI 0.82 to 1.25, P = 0.94) in an adjusted between-group comparison.There was no association with an increased risk of death related to cardiac disease in patients with severe sepsis or septic shock when compared to other ICU patients with similar severity of illness.

Background: The interpretation of changes in injury-related mortality over time requires an understanding of changes in the incidence of the various types of injury, and adjustment for their severity. Our aim was to investigate changes over time in incidence of hospital admission for injuries caused by falls, traffic incidents, or assaults, and to assess the risk-adjusted short-term mortality for these patients.less thanbr /greater thanMethods: All patients admitted to hospital with injuries caused by falls, traffic incidents, or assaults during the years 2001-11 in Sweden were identified from the nationwide population-based Patient Registry. The trend in mortality over time for each cause of injury was adjusted for age, sex, comorbidity and severity of injury as classified from the International Classification of diseases, version 10 Injury Severity Score (ICISS).less thanbr /greater thanResults: Both the incidence of fall (689 to 636/100000 inhabitants: p = 0.047, coefficient - 4.71) and traffic related injuries (169 to 123/100000 inhabitants: p less than 0.0001, coefficient - 5.37) decreased over time while incidence of assault related injuries remained essentially unchanged during the study period. There was an overall decrease in risk-adjusted 30-day mortality in all three groups (OR 1.00; CI95% 0.99-1.00). Decreases in traffic (OR 0.95; 95% CI 0.93 to 0.97) and assault (OR 0.93; 95% CI 0.87 to 0.99) related injuries was significant whereas falls were not during this 11-year period.less thanbr /greater thanDiscussion: Risk-adjustment is a good way to use big materials to find epidemiological changes. However after adjusting for age, year, sex and risk we find that a possible factor is left in the pre- and/or in-hospital care.less thanbr /greater thanConclusions: The decrease in risk-adjusted mortality may suggest changes over time in pre- and/or in-hospital care. A non-significantdecrease in risk-adjusted mortality was registered for falls, which may indicate that low-energy trauma has not benefited for the increased survivability as much as high-energy trauma, ie traffic- and assault related injuries.

Surgery for hip fractures is associated with high mortality and morbidity. The causes of poor outcome are not fully understood and may be related to other factors than the surgery itself. The relative contributions of patient, surgical, anaesthetic and structural factors have seldom been studied together. This study, a retrospective registry-based cohort study of 14 932 patients undergoing hip fracture surgery in Sweden from 1st of January 2014 to 31st of December 2016, aimed to identify important predictors of mortality post-surgery. The independent predictive power of our included variables was examined using Cox proportional hazards modeling with all-cause mortality at longest follow-up as the outcome. Twelve independent variables were considered as interrelated exposures and their individual adjusted effect within a single model were evaluated. Kaplan-Meier curves were also generated. Crude mortality rates were 8.2% at 30 days (95% CI 7.7-8.6%) and 23.6% at 365 days (95% CI 22.9-24.2%). Of the 12 factors entered into the Cox regression analysis, age (aHR1.06, p amp;lt; 0.001), male gender (aHR 1.45, p amp;lt; 0.001), ASA-PS-class (ASA 1amp;2 reference; ASA 3 aHR 2.12; ASA 4 aHR 4.79; ASA 5 aHR 12.57 respectively, p amp;lt; 0.001) and PACU-LOS (aHR 1.01, p amp;lt; 0.001) were significantly associated with mortality at longest follow-up (up to 3 years). University hospital status was protective (aHR 0.83, p amp;lt; 0.001) in the same model. Age, gender and ASA-PS-class were strong predictors of mortality after surgery for hip fractures in Sweden. University hospital status and length of stay in the postoperative care unit were also identified as modifiable risk factors after multivariable adjustment and require confirmation in future studies. Funding Agencies|Region Ostergotland County Council

Establishing a celiac disease (CD) diagnosis can be difficult, such as when CD-specific antibody levels are just above cutoff or when small intestinal biopsies show low-grade injuries. To investigate the biological pathways involved in CD and select potential biomarkers to aid in CD diagnosis, RNA sequencing of duodenal biopsies from subjects with either confirmed Active CD (n=20) or without any signs of CD (n=20) was performed. Gene enrichment and pathway analysis highlighted contexts, such as immune response, microbial infection, phagocytosis, intestinal barrier function, metabolism, and transportation. Twenty-nine potential CD biomarkers were selected based on differential expression and biological context. The biomarkers were validated by real-time polymerase chain reaction of eight RNA sequencing study subjects, and further investigated using an independent study group (n=43) consisting of subjects not affected by CD, with a clear diagnosis of CD on either a gluten-containing or a gluten-free diet, or with low-grade intestinal injury. Selected biomarkers were able to classify subjects with clear CD/non-CD status, and a subset of the biomarkers (CXCL10, GBP5, IFI27, IFNG, and UBD) showed differential expression in biopsies from subjects with no or low-grade intestinal injury that received a CD diagnosis based on biopsies taken at a later time point. A large number of pathways are involved in CD pathogenesis, and gene expression is affected in CD mucosa already in low-grade intestinal injuries. RNA sequencing of low-grade intestinal injuries might discover pathways and biomarkers involved in early stages of CD pathogenesis. Funding Agencies|Futurum-the Academy for Health and Care, Region Jonkoping County; Medical Research Council of Southeast Sweden; National Genomics Infrastructure - Swedish Research Council

Aim The aim of the study is to investigate if cognitive behavioral therapy given in a group setting affects anxiety and depression, stress, pain, coping strategies during daily life, and health‐related quality of life (HRQoL), among frequent attenders (FAs) in primary care. Methods Cognitive behavioral therapy was offered to 331 FAs between 18 and 65 years of age, of whom 89 accepted and 54 completed all steps in the protocol; patients were assigned to 1 of 3 groups: 0, 6, and 12‐month waiting time. The therapy consisted of 12 sessions administered in group format. Outcome measures were Beck's Anxiety Inventory (BAI), Beck's Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Everyday Life Stress (ELS), Coping Strategy Questionnaire, Multidimensional Pain Inventory‐Swedish version, and Short Form‐36. Results Mean age among patients who completed cognitive behavioral therapy was 49.9 years, with a female majority (79.6%). Anxiety and depression scores were reduced after treatment (BAI 16.7 vs 13.6; BDI 16.3 vs 15.7; HADS‐Anxiety 8.41 vs 6.05; HADS‐Depression 7.09 vs 5.69). Because waiting time itself did not affect symptoms, differences reflect treatment effects. Stress ratings were not affected by treatment. Use of nonadaptive coping strategies like praying and hoping and catastrophizing decreased. Frequent attenders experienced a higher sense of life control. Frequent attenders reported significantly lower HRQoL than general Swedish population norms in all 8 Short Form‐36 domains including mental and physical component summary scores (MCS and PCS), and all domains were unaffected by treatment. Conclusion Cognitive behavioral therapy exerts some beneficial effects in FAs. Content of treatment addressed musculoskeletal pain, stress, anxiety, and depression. This broad approach resulted in reduced anxiety, depression, and impact of pain because of enhanced life control., Aim: The aim of the study is to investigate if cognitive behavioral therapy given in a group setting affects anxiety and depression, stress, pain, coping strategies during daily life, and health‐related quality of life (HRQoL), among frequent attenders (FAs) in primary care. Methods: Cognitive behavioral therapy was offered to 331 FAs between 18 and 65 years of age, of whom 89 accepted and 54 completed all steps in the protocol; patients were assigned to 1 of 3 groups: 0, 6, and 12‐month waiting time. The therapy consisted of 12 sessions administered in group format. Outcome measures were Beck's Anxiety Inventory (BAI), Beck's Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Everyday Life Stress (ELS), Coping Strategy Questionnaire, Multidimensional Pain Inventory‐Swedish version, and Short Form‐36. Results: Mean age among patients who completed cognitive behavioral therapy was 49.9 years, with a female majority (79.6%). Anxiety and depression scores were reduced after treatment (BAI 16.7 vs 13.6; BDI 16.3 vs 15.7; HADS‐Anxiety 8.41 vs 6.05; HADS‐Depression 7.09 vs 5.69). Because waiting time itself did not affect symptoms, differences reflect treatment effects. Stress ratings were not affected by treatment. Use of nonadaptive coping strategies like praying and hoping and catastrophizing decreased. Frequent attenders experienced a higher sense of life control. Frequent attenders reported significantly lower HRQoL than general Swedish population norms in all 8 Short Form‐36 domains including mental and physical component summary scores (MCS and PCS), and all domains were unaffected by treatment. Conclusion: Cognitive behavioral therapy exerts some beneficial effects in FAs. Content of treatment addressed musculoskeletal pain, stress, anxiety, and depression. This broad approach resulted in reduced anxiety, depression, and impact of pain because of enhanced life control.

SummaryWe aimed to identify biomarkers to guide the decision to add selective serotonin reuptake inhibitors (SSRI) to psychological treatment for social anxiety disorder (SAD). Forty-eight patients with SAD underwent functional magnetic resonance imaging and collection of clinical and demographic variables before treatment with cognitive–behavioural therapy, combined on a double-blind basis with either escitalopram or placebo for 9 weeks. Pre-treatment neural reactivity to aversive faces in the dorsal anterior cingulate cortex (ACC), but not clinical/demographic variables, moderated clinical outcomes. Cross-validated individual-level predictions accurately identified 81% of responders/non-responders. Dorsal ACC reactivity is thus a potential biomarker for SAD treatment selection.Declaration of interestNone.

Background and rationale for the study: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e. fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. Methods: In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (± 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. Main results: NAFLD patients had an increased mortality compared with the reference population (HR 1.29, CI 1.04-1.59, p=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, p=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, p=0.001), infectious disease (HR 2.71, CI 1.02-7.26, p=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, p=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, p=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, p

The Linkoping burn score has been used for two decades to calculate the cost to the hospital of each burned patient. Our aim was to validate the Burn Score in a dedicated Burn Centre by analysing the associations with burn-specific factors: percentage of total body surface area burned (TBSA%), cause of injury, patients referred from other (non-specialist) centres, and survival, to find out which of these factors resulted in higher scores. Our second aim was to analyse the variation in scores of each category of care (surveillance, respiration, circulation, wound care, mobilisation, laboratory tests, infusions, and operation). We made a retrospective analysis of all burned patients admitted during the period 2000-15. Multivariable regression models were used to analyse predictive factors for an increased daily burn score, the cumulative burn score (the sum of the daily burn scores for each patient) and the total burn score (total sum of burn scores for the whole group throughout the study period) in addition to sub-analysis of the different categories of care that make up the burn score. We retrieved 22301 daily recordings for inpatients. Mobilisation and care of the wound accounted for more than half of the total burn score during the study. Increased TBSA% and age over 45 years were associated with increased cumulative (model R2 0.43, p

The Simplified Acute Physiology 3 outcome prediction model has a narrow time window for recording physiologic measurements. Our objective was to examine the prevalence and impact of missing physiologic data on the Simplified Acute Physiology 3 model's performance.Retrospective analysis of prospectively collected data.Sixty-three ICUs in the Swedish Intensive Care Registry.Patients admitted during 2011-2014 (n = 107,310).None.Model performance was analyzed using the area under the receiver operating curve, scaled Brier's score, and standardized mortality rate. We used a recalibrated Simplified Acute Physiology 3 model and examined model performance in the original dataset and in a dataset of complete records where missing data were generated (simulated dataset). One or more data were missing in 40.9% of the admissions, more common in survivors and low-risk admissions than in nonsurvivors and high-risk admissions. Discrimination did not decrease with one to two missing variables, but accuracy was highest with no missing data. Calibration was best in the original dataset with a mix of full records and records with some missing values (area under the receiver operating curve was 0.85, scaled Brier 27%, and standardized mortality rate 0.99). With zero, one, and two data missing, the scaled Brier was 31%, 26%, and 21%; area under the receiver operating curve was 0.84, 0.87, and 0.89; and standardized mortality rate was 0.92, 1.05 and 1.10, respectively. Datasets where the missing data were simulated for oxygenation or oxygenation and hydrogen ion concentration together performed worse than datasets with these data originally missing.There is a coupling between missing physiologic data, admission type, low risk, and survival. Increased loss of physiologic data reduced model performance and will deflate mortality risk, resulting in falsely high standardized mortality rates.

Injury is an important cause of death in all age groups worldwide, and contributes to many losses of human and economic resources. Currently, we know a few data about mortality from injury, particularly among the working population. The aim of the present study was to examine death from injury over a period of 14 years (1999–2012) using the Swedish Cause of Death Registry (CDR) and the National Patient Registry, which have complete national coverage. CDR was used to identify injury-related deaths among adults (18 years or over) during the years 1999–2012. ICD-10 diagnoses from V01 to X39 were included. The significance of changes over time was analyzed by linear regression. The incidence of prehospital death decreased significantly (coefficient −0.22, r 2 = 0.30; p = 0.041) during the study period, while that of deaths in hospital increased significantly (coefficient 0.20, r 2 = 0.75; p

Background: Juvenile idiopathic arthritis (JIA) is considered to be an autoimmune disease, but the etiology is unknown. We decided to study the influence of early nutrition on later development of JIA. Methods: All parents with children born between October 1, 1997 and October 1, 1999 in Southeast Sweden were asked to participate in the ABIS prospective cohort study (All Babies in Southeast Sweden), At 1 year, questionnaires with information on breastfeeding and introduction of foods were completed by 10,565 families. We identified 32 children with JIA and 111 children with non-chronic arthritis with completed questionnaires after delivery and after 1 year. A multivariable logistic regression model, adjusted for relevant factors, was performed to calculate the association between JIA and feeding during the first year of life. Results: An increased risk for JIA was found in children who had breast fed for less than 4 months, as opposed to those who were continued on breast milk beyond 4 months of age (aOR 3.5, 95% CI 1.4-8,5; p = 0.006). A short duration of exclusive as well as total breastfeeding was associated with an increased risk of JIA (aOR 1.3, 95% CI 1.1-1.6; p = 0.008 and aOR 1.2, 95% CI 1.1-1.3; p amp;lt; 0.001). All associations between breastfeeding and JIA persisted after adjustment. There was no relationship between early nutrition and non-chronic arthritis. Conclusions: Our results indicate that there are different disease mechanisms for different types of arthritis in childhood. Longer duration of breastfeeding (both total and exclusive) may protect against development of JIA. Mothers should be encouraged to breast-feed their babies exclusively, if at all possible, for 4 months and continue partial breastfeeding for an extended time when foreign proteins are introduced. Funding Agencies|Research Unit of Kalmar County Council; Swedish Rheumatism Association; Jerring Foundation; Swedish Child Diabetes Foundation (Barndiabetesfonden); Juvenile Diabetes Research Foundation; Medical Research Council of Southeast Sweden (FORSS)

Total duration of stay adjusted for percentage of the total body surface area burned (TBSA%) is a commonly used outcome measure in burn care. However, it has been criticised as it is affected by many factors, some of which are not strictly part of burn care. A division into operative stay and postoperative stay may improve this measure. The aim was to evaluate if operative stay can serve as a more standardised measure by: comparing the variation in operative stay/TBSA% with the variation in total stay/TBSA%, and to study different factors associated with operative stay and postoperative stay. Patients and methods Surgically managed burn patients admitted between 2010–14 were included. Operative stay was defined as the time from admission until the last operation, postoperative stay as the time from the last operation until discharge. The difference in variation was analysed with F-test. A retrospective review of medical records was done to explore reasons for extended postoperative stay. Multivariable regression was used to assess factors associated with operative stay and postoperative stay. Results Operative stay/TBSA% showed less variation than total duration/TBSA% (F test = 2.38, p

Purpose: To assess the independent associations between ability to cope and hopelessness with measures of health-related quality of life (HRQoL) and their effects on mortality up to 3 years after discharge in patients who have been treated in an intensive care unit (ICU). Methods: A prospective, cross-sectional multicenter study of 980 patients. Ability to cope, hopelessness, and HRQoL were evaluated using validated scales. Questionnaires were sent to patients 6, 12, 24, and 36 months after discharge from ICU. Results: After adjustment, low scores for ability to cope and high scores for hopelessness were both related to poorer HRQoL for all subscales (except for coping with bodily pain). Effects were in the same range as coexisting disease for physical subscales, and stronger for social and mental subscales. High scores for hopelessness also predicted mortality up to 3 years after discharge from ICU (p amp;lt; 0.001). Conclusions: The psychological factors ability to cope and hopelessness both strongly affected HRQoL after ICU care, and this effect was stronger than the effects of coexisting disease. Hopelessness also predicted mortality after critical illness. Awareness of the psychological state of patients after a stay in ICU is important to identify which of them are at risk. (C) 2017 Elsevier Inc. All rights reserved.

Objectives: we assessed the incidence, risk factors and outcome of BSI over a 14-year period (2000-2013) in a Swedish county. Methods: retrospective cohort study on culture confirmed BSI among patients in the county of Östergötland, Sweden, with approximately 440,000 inhabitants. A BSI was defined as either community-onset BSI (CO-BSI) or hospital-acquired BSI (HA-BSI). Results: of a total of 11,480 BSIs, 67% were CO-BSI and 33% HA-BSI. The incidence of BSI increased by 64% from 945 to 1,546 per 100,000 hospital admissions per year during the study period. The most prominent increase, 83% was observed within the CO-BSI cohort whilst HA-BSI increased by 32%. Prescriptions of antibiotics in outpatient care decreased with 24% from 422 to 322 prescriptions dispensed/1,000 inhabitants/year, whereas antibiotics prescribed in hospital increased by 67% (from 424 to 709 DDD per 1,000 days of care). The overall 30-day mortality for HA-BSIs was 17.2%, compared to 10.6% for CO-BSIs, with an average yearly increase per 100,000 hospital admissions of 2 and 5% respectively. The proportion of patients with one or more comorbidities, increased from 20.8 to 55.3%. In multivariate analyses, risk factors for mortality within 30 days were: HA-BSI (2.22); two or more comorbidities (1.89); single comorbidity (1.56); CO-BSI (1.21); male (1.05); and high age (1.04). Conclusion: this survey revealed an alarming increase in the incidence of BSI over the 14-year study period. Interventions to decrease BSI in general should be considered together with robust antibiotic stewardship programmes to avoid both over- and underuse of antibiotics. Funding agencies: Ostergotland County Council (Hakan Hanberger ALF)

Summary Objective Most women on combined oral contraceptives (COC) report high levels of satisfaction, but 4–10% complain of adverse mood effects. The aim of this randomized, double-blinded, placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood. A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing. Methods Thirty-four women with previous experience of mood deterioration during COC use were randomized to one treatment cycle with a levonorgestrel-containing COC or placebo. An emotional face matching task (vs. geometrical shapes) was administered during functional magnetic resonance imaging (fMRI) prior to and during the COC treatment cycle. Throughout the trial, women recorded daily symptom ratings on the Cyclicity Diagnoser (CD) scale. Results During the last week of the treatment cycle COC users had higher scores of depressed mood, mood swings, and fatigue than placebo users. COC users also had lower emotion-induced reactivity in the left insula, left middle frontal gyrus, and bilateral inferior frontal gyri as compared to placebo users. In comparison with their pretreatment cycle, the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri, whereas placebo users had decreased reactivity in the right amygdala. Conclusion COC use in women who previously had experienced emotional side effects resulted in mood deterioration, and COC use was also accompanied by changes in emotional brain reactivity. These findings are of relevance for the understanding of how combined oral contraceptives may influence mood. Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality throughout the world. When we began this project our knowledge about the outcome of COPD patients admitted to the ICU in Sweden was scarce.Aims: To investigate the characteristics, survival and health-related quality of life (HRQL) of COPD patients admitted to Swedish ICUs. To investigate how ICU personnel decide whether to use invasive or non-invasive ventilatory treatment (NIV) of the newly admitted COPD patient in need of ventilatory support. To investigate outcome according to mode of ventilation.Material and methods: Detailed data, including HRQL during recovery, from COPD patients admitted to ICUs that participated in the Swedish intensive care registry were analysed. A questionnaire was distributed to personnel in 6 of the participating ICUs in order to define factors deemed important in making the choice between invasive and non-invasive ventilation immediately after admission. The answers were analysed.Results: The proportion of COPD patients admitted to Swedish ICUs in need of ventilatory support is 1.3-1.6 % of all admissions. The patients are around 70 years-old and are severely ill on admission, with high respiratory rates and most have life-threatening disturbances in their acid-base balance and blood gases. There are more women than men. The short- and long-term mortality is high despite intensive care treatment. The majority of patients are treated with NIV. The length of stay on the ICU is shorter when NIV is used. The choice between NIV and invasive ventilation in these patients may be irrational. It is guided by current guidelines, but other non-patient-related factors seem to influence this decision. NIV seems to be preferable to invasive ventilation at admission, not only according to short-term benefits but also to long-term survival. Failure of NIV followed by invasive ventilation does not have a poorer prognosis than directly employing invasive ventilation. The health-related quality of life of COPD patients after treatment on Swedish ICUs is lower than in the general population. However it does not decline between 6 and 24 months after ICU discharge. After 24 months the HRQL is quite similar to that of COPD patients not treated on the ICU.Conclusions: COPD patients in need of ventilatory support admitted to Swedish ICUs are severely ill on admission, and their short- and long-term mortality is high despite ICU care and ventilatory treatment. Non-invasive ventilation should be the first line treatment on admission. NIV has short- and long-term benefits compared to invasive ventilation, without increasing mortality risk in case of failure. After discharge from the ICU and recovery, the HRQL of COPD patients is lower than in the general population, but comparable to COPD patients not treated on the ICU.

OBJECTIVES To examine ICU performance based on the Simplified Acute Physiology Score 3 using 30-day, 90-day, or 180-day mortality as outcome measures and compare results with 30-day mortality as reference. DESIGN Retrospective cohort study of ICU admissions from 2010 to 2014. SETTING Sixty-three Swedish ICUs that submitted data to the Swedish Intensive Care Registry. PATIENTS The development cohort was first admissions to ICU during 2011-2012 (n = 53,546), and the validation cohort was first admissions to ICU during 2013-2014 (n = 57,729). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Logistic regression was used to develop predictive models based on a first level recalibration of the original Simplified Acute Physiology Score 3 model but with 30-day, 90-day, or 180-day mortality as measures of outcome. Discrimination and calibration were excellent for the development dataset. Validation in the more recent 2013-2014 database showed good discrimination (C-statistic: 0.85, 0.84, and 0.83 for the 30-, 90-, and 180-d models, respectively), and good calibration (standardized mortality ratio: 0.99, 0.99, and 1.00; Hosmer-Lemeshow goodness of fit H-statistic: 66.4, 63.7, and 81.4 for the 30-, 90-, and 180-d models, respectively). There were modest changes in an ICU's standardized mortality ratio grouping ( 1.00) when follow-up was extended from 30 to 90 days and 180 days, respectively; about 11-13% of all ICUs. CONCLUSIONS The recalibrated Simplified Acute Physiology Score 3 hospital outcome prediction model performed well on long-term outcomes. Evaluation of ICU performance using standardized mortality ratio was only modestly sensitive to the follow-up time. Our results suggest that 30-day mortality may be a good benchmark of ICU performance. However, the duration of follow-up must balance between what is most relevant for patients, most affected by ICU care, least affected by administrative policies and practically feasible for caregivers.

Background: Pre-existing disease is the most important factor in the prediction of health-related quality of life (HRQoL) after intensive care. We hypothesised that the “inpatient care trajectories ...