Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cells.

Environmental signals shape host physiology and fitness. Microbiota-derived cues are required to program conventional dendritic cells (cDCs) during the steady state so that they can promptly respond and initiate adaptive immune responses when encountering pathogens. However, the molecular underpinnings of microbiota-guided instructive programs are not well understood. Here, we report that the indigenous microbiota controls constitutive production of type I interferons (IFN-I) by plasmacytoid DCs. Using genome-wide analysis of transcriptional and epigenetic regulomes of cDCs from germ-free and IFN-I receptor (IFNAR)-deficient mice, we found that tonic IFNAR signaling instructs a specific epigenomic and metabolic basal state that poises cDCs for future pathogen combat. However, such beneficial biological function comes with a trade-off. Instructed cDCs can prime T cell responses against harmless peripheral antigens when removing roadblocks of peripheral tolerance. Our data provide fresh insights into the evolutionary trade-offs that come with successful adaptation of vertebrates to their microbial environment.

Exposure to chlorpyrifos and pyrethroid insecticides and symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in preschool children from the Odense Child Cohort.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood psychiatric disorder with severe and lifelong impact on mental health and socioeconomic achievements. Environmental factors may play a role in the increasing incidens rates. Previous studies on associations between prenatal and childhood exposure to organophosphate and pyrethroid insecticides and ADHD symptoms have yielded mixed findings. OBJECTIVES: To investigate associations between prenatal and childhood exposure to chlorpyrifos and pyrethroids and ADHD symptoms in 5-year-old children from the Odense Child Cohort. METHODS: Spot urine samples from pregnant women in gestational week 28 (n = 614) and offspring at 5 years of age (n = 814) were collected and analyzed for the specific metabolite of chlorpyrifos, TCPY (3,5,6-trichloro-2-pyridinol), as well as the generic pyrethroid metabolite, 3-PBA (3-phenoxybenzoic acid). Offspring ADHD symptoms were assessed at age 5 years using the parent reported "ADHD scale" from the "Child Behavior Checklist 1½-5" (n = 1114). Associations between insecticide exposure variables and an ADHD score ≥90th percentile were analyzed using logistic regression for all children and stratified by sex. RESULTS: Most pregnant women had detectable concentrations of 3-PBA (93%) and TCPY (91%) with median concentrations of 0.20 µg/L and 1.62 µg/L, respectively. In children, 3-PBA and TCPY concentrations were detectable in 88% and 82% of the samples, and the median concentrations were 0.17 and 1.16 µg/L. No statistically significant associations were observed between insecticide metabolites and an ADHD score ≥90th percentile at age 5. CONCLUSION: In this relatively large Danish birth cohort study with mainly low dietary insecticide exposure, we found no statistically significant associations between prenatal or childhood exposure to chlorpyrifos or pyrethroids, and excess ADHD-symptom load, in 5-year-old children. Prospective studies with multiple urine samples across vulnerable windows of neurodevelopment is warranted to improve assessment of safe exposure levels, which is particularly relevant for pyrethroids, since their use is increasing.

Quality of life of adolescent and adult survivors of childhood cancer in Europe-A systematic review.

Advances in diagnostics and treatment of childhood cancer during the past few decades have substantially increased survival, resulting in a growing population of survivors of childhood cancer. Somatic and mental late effects of the cancer and the treatment may impact the quality of life (QoL). Previous reviews of QoL in survivors of childhood cancer have shown contradictory findings across studies and the majority of studies included have been based on data from North America and may not be directly comparable to a European setting. The aim of our study was to critically evaluate and summarise the latest evidence on the QoL of childhood cancer survivors in Europe and to identify survivors at particular risk. The eligible studies were published between 2008 and 2022, conducted in Europe and included participants who had survived at least 5 years after diagnosis of a childhood cancer. The main outcome of interest was QoL of survivors which was measured with validated qualitative and quantitative QoL questionnaires. A systematic literature search conducted in PubMed, EMBASE, PsycINFO and CINALH resulted in inclusion of 36 articles with a total of 14 342 survivors of childhood cancer. The majority of included studies found that childhood cancer survivors reported poorer QoL than comparisons. Female gender, treatment with haematopoietic stem cell transplantation and a brain tumour diagnosis were associated with lower QoL. With a growing population of childhood cancer survivors with many years ahead of them, targeted interventions and optimal follow-up care are important to improve the QoL of survivors.

IFNAR signaling in fibroblastic reticular cells can modulate CD8+ memory fate decision.

CD8+ memory T cells (TM ) are crucial for long-term protection from infections and cancer. Multiple cell types and cytokines are involved in the regulation of CD8+ T cell responses and subsequent TM formation. Besides their direct antiviral effects, type I interferons (IFN-I) modulate CD8+ T cell immunity via their action on several immune cell subsets. However, it is largely unclear how nonimmune cells are involved in this multicellular network modulating CD8+ TM formation. Fibroblastic reticular cells (FRCs) form the 3D scaffold of secondary lymphoid organs, express the IFN-I receptor (IFNAR), and modulate adaptive immune responses. However, it is unclear whether and how early IFNAR signals in lymph node (LN) FRCs affect CD8+ TM differentiation. Using peptide vaccination and viral infection, we studied CD8+ TM differentiation in mice with an FRC-specific IFNAR deletion (FRCΔIFNAR ). We show here that the differentiation of CD8+ TCR-transgenic T cells into central memory cells (TCM ) is enhanced in peptide-vaccinated FRCΔIFNAR mice. Conversely, vesicular stomatitis virus infection of FRCΔIFNAR mice is associated with impaired TCM formation and the accumulation of vesicular stomatitis virus specific double-positive CD127hi KLRG-1hi effector memory T cells. In summary, we provide evidence for a context-dependent contribution of FRC-specific IFNAR signaling to CD8+ TM differentiation.

A survey exploring the practices of smoking cessation support among hospital-based healthcare providers.

BACKGROUND: Hospital visits constitute a 'window of opportunity' for initiating smoking cessation attempts, and healthcare providers (HCPs) play an important role in supporting patients to stop smoking. Yet, the current practices of supporting smoking cessation in the hospital setting are largely unexplored. The aim of this study was to explore practices of smoking cessation support among hospital-based HCPs. METHODS: HCPs working in a large hospital in the secondary care sector completed an online, cross-sectional survey, including sociodemographic and work-related factors as well as 21 questions assessing practices of smoking cessation support based on the "five As" framework. Descriptive statistics were computed, and predictors of HCPs giving patients advice to stop smoking were explored using logistic regression analysis. RESULTS: All employees (N = 3998) in the hospital received a survey link; 1645 (41.1%) HCPs with daily patient contact completed the survey. Smoking cessation support in the hospital setting was limited with regard to assessment of smoking; providing information and advice; planning and referral for further support; and follow-up on smoking cessation attempts. Almost half (44.8%) of participating HCPs with daily patient contact never or rarely advise their patients to stop smoking. Physicians were more likely than nurses to advice patients to stop smoking, and HCPs in outpatient clinics were more likely to give advice than inpatient clinic HCPs. CONCLUSION: Smoking cessation support is very limited in the hospital-based healthcare setting. This is problematic, as hospital visits can be windows of opportunity to help patients change their health behaviour. An intensified focus on the implementation of hospital-based smoking cessation support is needed.

Absence of cGAS-mediated type I IFN responses in HIV-1-infected T cells.

The DNA sensor cGAS catalyzes the production of the cyclic dinucleotide cGAMP, resulting in type I interferon responses. We addressed the functionality of cGAS-mediated DNA sensing in human and murine T cells. Activated primary CD4+ T cells expressed cGAS and responded to plasmid DNA by upregulation of ISGs and release of bioactive interferon. In mouse T cells, cGAS KO ablated sensing of plasmid DNA, and TREX1 KO enabled cells to sense short immunostimulatory DNA. Expression of IFIT1 and MX2 was downregulated and upregulated in cGAS KO and TREX1 KO T cell lines, respectively, compared to parental cells. Despite their intact cGAS sensing pathway, human CD4+ T cells failed to mount a reverse transcriptase (RT) inhibitor-sensitive immune response following HIV-1 infection. In contrast, infection of human T cells with HSV-1 that is functionally deficient for the cGAS antagonist pUL41 (HSV-1ΔUL41N) resulted in a cGAS-dependent type I interferon response. In accordance with our results in primary CD4+ T cells, plasmid challenge or HSV-1ΔUL41N inoculation of T cell lines provoked an entirely cGAS-dependent type I interferon response, including IRF3 phosphorylation and expression of ISGs. In contrast, no RT-dependent interferon response was detected following transduction of T cell lines with VSV-G-pseudotyped lentiviral or gammaretroviral particles. Together, T cells are capable to raise a cGAS-dependent cell-intrinsic response to both plasmid DNA challenge or inoculation with HSV-1ΔUL41N. However, HIV-1 infection does not appear to trigger cGAS-mediated sensing of viral DNA in T cells, possibly by revealing viral DNA of insufficient quantity, length, and/or accessibility to cGAS.

Mentalization-oriented psychodynamic group therapy for patients with personality disorders: a naturalistic prospective cohort study.

OBJECTIVES: Patients with personality disorders (PDs) are often treated with non-manualized psychodynamic group therapy (PDT) lasting for several years. Non-manualized PDT often combines a variety of therapeutic approaches from different PDT traditions, including mentalization-based therapy. Currently, little is known about the effect of this long-term, costly treatment. This study investigated the extent to which patients with different PDs benefit from mentalization-oriented PDT as it is implemented in clinical practice in terms of symptom severity, interpersonal problems, and general functioning. METHODS: The design was a naturalistic, prospective cohort study. Seventy-five consecutive PD patients were assessed before treatment with the Symptom Checklist-90 Revised (SCL-90-R) as the primary outcome measure and the Inventory of Interpersonal Problems (IIP) and Global Assessment of Functioning (GAF) as secondary outcome measures. The sample was repeatedly assessed every 12 months for up to 36 months. Paired t-tests were applied to examine the effectiveness of the intervention. RESULTS: Among completers (n = 42; 56%), improvement was observed on the SCL-90-R: Global Severity Index (mean change = -0.45 [95% CI = -0.72, -0.19]; Cohen's d = -0.55), Positive Symptom Distress Index (-0.40 [-0.63, -0.17]; -0.56); Positive Symptoms Total (-10.70 [-17.31, -4.09]; -0.52). Secondary outcomes also improved: IIP-total (mean change = -0.50 [95%CI = -0.74, -0.25]; Cohen's d = -0.66); GAF-Functioning (8.79 [6.32, 11.27]; 1.15); and GAF-Symptoms (10.67 [8.09, 13.25]; 1.34). CONCLUSIONS: Completers improved on symptom severity, interpersonal problems, and general functioning, with within-group effect sizes ranging from medium to large. Approximately half the sample dropped out, suggesting that mentalization-oriented PDT spanning several years may be unrealistic for many patients with PD. Significant outcomesThere are no clear guidelines for psychological interventions targeting personality disorders (PDs), and currently eclectic and non-manualized psychodynamic approaches lasting for up to 3 years are prevailing in some clinical practices.Although this treatment approach may have an effect on compliant patients, the high drop-out rate indicates that it may not be suitable for a large proportion of PD patients since it requires long-term commitment. Furthermore, it is difficult to identify the content of the non-manualized psychodynamic therapy and what helps the patients.More specific clinical guidelines emphasizing the application of evidence-based treatments or at least manualized treatments are warranted for the treatment of emotionally unstable PDs and other PDs. LimitationsThe naturalistic study design, without any control group, limits conclusions about mechanisms of action of the intervention.Since the intervention was not manualized, it is unknown exactly which treatment was actually administered, which reduces external validity.The outcomes are based on completer data of a relatively small sample size with high drop-out rate.

Cognitive performance in hospitalized patients with severe or extreme anorexia nervosa.

PURPOSE: Severe malnourishment may reduce cognitive performance in anorexia nervosa (AN). We studied cognitive functioning during intensive nutritional and medical stabilization in patients with severe or extreme AN and investigated associations between weight gain and cognitive improvement. METHODS: A few days after admission to a specialized hospital unit, 33 patients with severe or extreme AN, aged 16-42 years, completed assessments of memory, cognitive flexibility, processing speed, and attention. Mean hospitalization was 6 weeks. Patients completed the same assessments at discharge (n = 22) following somatic stabilization and follow-up up to 6 months after discharge (n = 18). RESULTS: The patients displayed normal cognitive performance at admission compared to normative data. During nutritional stabilization, body weight increased (mean: 11.3%; range 2.6-22.2%) and memory, attention, and processing speed improved (p values: ≤ 0.0002). No relationship between weight gain and cognitive improvement was observed at discharge or follow-up. CONCLUSIONS: Cognitive performance at hospital admission was normal in patients with severe or extreme AN and improved during treatment although without association to weight gain. Based on these results, which are in line with previous studies, patients with severe or extreme AN need not be excluded from cognitively demanding tasks, possibly including psychotherapy. As patients may have other symptoms that interfere with psychotherapy, future research could investigate cognitive functioning in everyday life in patients with severe AN. TRIAL REGISTRATION NUMBER: The study is registered at clinicaltrials.gov (NCT02502617). LEVEL OF EVIDENCE: Level III, cohort study.

Selective reconstitution of IFN­Î³ gene function in Ncr1+ NK cells is sufficient to control systemic vaccinia virus infection.

IFN-γ is an enigmatic cytokine that shows direct anti-viral effects, confers upregulation of MHC-II and other components relevant for antigen presentation, and that adjusts the composition and balance of complex cytokine responses. It is produced during immune responses by innate as well as adaptive immune cells and can critically affect the course and outcome of infectious diseases, autoimmunity, and cancer. To selectively analyze the function of innate immune cell-derived IFN-γ, we generated conditional IFN-γOFF mice, in which endogenous IFN-γ expression is disrupted by a loxP flanked gene trap cassette inserted into the first intron of the IFN-γ gene. IFN-γOFF mice were intercrossed with Ncr1-Cre or CD4-Cre mice that express Cre mainly in NK cells (IFN-γNcr1-ON mice) or T cells (IFN-γCD4-ON mice), respectively. Rosa26RFP reporter mice intercrossed with Ncr1-Cre mice showed selective RFP expression in more than 80% of the NK cells, while upon intercrossing with CD4-Cre mice abundant RFP expression was detected in T cells, but also to a minor extent in other immune cell subsets. Previous studies showed that IFN-γ expression is needed to promote survival of vaccinia virus (VACV) infection. Interestingly, during VACV infection of wild type and IFN-γCD4-ON mice two waves of serum IFN-γ were induced that peaked on day 1 and day 3/4 after infection. Similarly, VACV infected IFN-γNcr1-ON mice mounted two waves of IFN-γ responses, of which the first one was moderately and the second one profoundly reduced when compared with WT mice. Furthermore, IFN-γNcr1-ON as well as IFN-γCD4-ON mice survived VACV infection, whereas IFN-γOFF mice did not. As expected, ex vivo analysis of splenocytes derived from VACV infected IFN-γNcr1-ON mice showed IFN-γ expression in NK cells, but not T cells, whereas IFN-γOFF mice showed IFN-γ expression neither in NK cells nor T cells. VACV infected IFN-γNcr1-ON mice mounted normal cytokine responses, restored neutrophil accumulation, and showed normal myeloid cell distribution in blood and spleen. Additionally, in these mice normal MHC-II expression was detected on peripheral macrophages, whereas IFN-γOFF mice did not show MHC-II expression on such cells. In conclusion, upon VACV infection Ncr1 positive cells including NK cells mount two waves of early IFN-γ responses that are sufficient to promote the induction of protective anti-viral immunity.

Multiple sclerosis impairment scale and brain MRI in secondary progressive multiple sclerosis.

OBJECTIVE: To examine the Multiple Sclerosis Impairment Scale (MSIS) in secondary progressive MS (SPMS) in relation to the Expanded Disability Status Scale (EDSS), magnetic resonance imaging (MRI) outcomes, and mobility. METHODS: In this observational single-center study, 68 secondary progressive multiple sclerosis (SPMS) patients were examined by MSIS, EDSS, functional mobility tests of upper/lower extremities, and multimodal MRI. Participants had EDSS ≥3.5, a decline in daily activities over the last year unrelated to relapses, and/or 6-month confirmed disability progression. RESULTS: Mean disease duration was 23.1 ± 8.3 years and mean age 54.4 ± 8.1 years. MSIS, EDSS, and their corresponding motor, cerebellar, and sensory subscores correlated (p < .0001). Motor subscores of MSIS correlated stronger with Timed-25-Foot-Walk (T25FW) than pyramidal functional system score (FSS) (p = .03), but EDSS had a stronger correlation to T25FW than the total MSIS score (p = .01). MSIS cerebellar subscore correlated stronger with 9-Hole Peg Test (9-HPT) than cerebellar FSS (p = .04). The sensory MSIS subscore also showed correlation with 9-HPT in contrast to sensory FSS (p = .006). MSIS subscores had stronger correlations with MRI volumetry measures than FSS scores (lesion volume and putamen, thalamus, corpus callosum volumetry, p = .0001-0.0017). CONCLUSION: In patients with SPMS, MSIS correlated with functional motor tests. MSIS showed stronger correlations with atrophy of central nervous system areas, and may be more sensitive to scale cerebellar and sensory function than EDSS.

Health anxiety symptoms in Danish children during the first lockdown period of the COVID-19 pandemic: an Odense Child Cohort study.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has a severe impact on the general population. During the pandemic, children may develop emotional and psychological symptoms, including increased worries about health and illness, known as health anxiety symptoms (HASs). We aimed to explore HAS in 7-9-year-old children from the Danish Odense Child Cohort (OCC) during the first COVID-19 lockdown period in Denmark, and to examine associations with potential risk factors. MATERIAL AND METHODS: OCC is a cohort of children born between 2010 and 2012, which originally recruited 2874 of 6707 pregnancies (43%). Among the current OCC population of 2430 singleton children, 994 participated in this study (response rate 40%). Children and their parents filled out questionnaires about child HAS, family exposure to COVID-19 infection and parental HAS. Adjusted odds ratios (aORs) were calculated between high score child HAS (≥90th percentile) and covariates by use of logistic regression. RESULTS: Most children (n = 686, 69%) reported few worries about their health. Children reporting high score HAS also had higher levels of internalizing symptoms at age 5; aOR 2.15 (1.20;3.85), p = .010, and higher levels of maternal and paternal HAS; aOR 2.40 (1.44;3.97), p = .001, and 2.00 (1.10;3.65), p = .023, whereas no association with child sex or familial exposure to COVID-19 was detected (n = 65, 6.5%). CONCLUSIONS: High score child HAS during the first lockdown period of the COVID-19 pandemic was not associated with family exposure to COVID-19 infection, but to being a more anxious child a priori and to HAS in parents.

Intact Type I Interferon Receptor Signaling Prevents Hepatocellular Necrosis but Not Encephalitis in a Dose-Dependent Manner in Rift Valley Fever Virus Infected Mice.

Rift Valley fever (RVF) is a zoonotic and emerging disease, caused by the RVF virus (RVFV). In ruminants, it leads to "abortion storms" and enhanced mortality rates in young animals, whereas in humans it can cause symptoms like severe hemorrhagic fever or encephalitis. The role of the innate and adaptive immune response in disease initiation and progression is still poorly defined. The present study used the attenuated RVFV strain clone 13 to investigate viral spread, tissue tropism, and histopathological lesions after intranasal infection in C57BL/6 wild type (WT) and type I interferon (IFN-I) receptor I knockout (IFNAR-/-) mice. In WT mice, 104 PFU RVFV (high dose) resulted in a fatal encephalitis, but no hepatitis 7-11 days post infection (dpi), whereas 103 PFU RVFV (low dose) did not cause clinical disease or significant histopathological lesions in liver and the central nervous system (CNS). In contrast, IFNAR-/- mice infected with 103 PFU RVFV developed hepatocellular necrosis resulting in death at 2-5 dpi and lacked encephalitis. These results show that IFNAR signaling prevents systemic spread of the attenuated RVFV strain clone 13, but not the dissemination to the CNS and subsequent fatal disease. Consequently, neurotropic viruses may be able to evade antiviral IFN-I signaling pathways by using the transneuronal instead of the hematogenous route.

Validating the Danish version of the Eating Disorder Quality of Life Scale (EDQLS) in anorexia nervosa.

PURPOSE: The aim of this study was to explore the factor structure of the Danish translation of the eating disorder quality of life scale and evaluate the internal reliability and convergent validity of the scale in a Danish cohort of women with AN. METHODS: The total sample comprised 211 patients diagnosed with anorexia nervosa age 13-40 years. Patients completed questionnaires assessing eating disorder psychopathology, physical and social functioning, and well-being. RESULTS: Factor analyses were not able to support the current division of the scale into 12 factors. We found excellent internal consistency of the eating disorder quality-of-life scale total score. We found relevant associations between quality of life and pre-determined variables. CONCLUSION: This study supports the use of the total score of the eating disorder quality of life scale in assessing quality of life in patients with anorexia nervosa. However, future studies should explore the factor structure of the scale further. LEVEL OF EVIDENCE: III: Evidence obtained from cohort or case-control analytic studies.

Maternal polycystic ovary syndrome and attention deficit hyperactivity disorder in offspring at 3 years of age: Odense Child Cohort.

INTRODUCTION: Previous data suggested a link between maternal polycystic ovary syndrome (PCOS) and offspring attention deficit hyperactivity disorder (ADHD), which could be mediated by higher prenatal androgen exposure. MATERIAL AND METHODS: The study was part of the prospective Odense Child Cohort and included 1776 pregnant women, 165 (9%) with PCOS and 1607 (91%) controls. ADHD symptoms at 3 years of age were defined using the parent-reported questionnaire Child Behavior Checklist/1.5-5 (scores >90th centile of Danish national standard). Maternal blood samples were collected in the third trimester measuring total testosterone by mass spectrometry, sex hormone-binding globulin, and calculated free testosterone. Offspring anogenital distance was measured at 3 months of age. Regression models were performed with presence of ADHD symptoms as the dependent variable and adjusted for maternal age, body mass index, parity, smoking status, educational level, and parental psychiatric diagnoses. RESULTS: ADHD symptoms were present in 105/937 (11%) boys and 72/839 (9%) girls. In boys, maternal PCOS was positively associated with ADHD symptoms (unadjusted odds ratio [OR] 1.91, 95% CI 1.07-3.43, p = 0.03, adjusted OR 2.20, 95% CI 1.20-4.02, p = 0.01), whereas maternal PCOS was not associated with ADHD symptoms in girls. Maternal total testosterone, free testosterone, and offspring anogenital distance were not associated with higher risk of ADHD symptoms in the offspring. CONCLUSIONS: Higher risk of ADHD in boys born of mothers with PCOS were not associated with maternal third-trimester testosterone levels or offspring anogenital distance.

Preoperative risk factors including serum levels of potassium, sodium, and creatinine for early mortality after open abdominal surgery: a retrospective cohort study.

BACKGROUND: In hospitalized patients, abnormal plasma electrolyte concentrations are frequent and have been linked to poor outcomes following acute surgery. The aim of this study was to assess whether preoperative plasma levels of potassium, sodium, and creatinine at the time of admission were associated with 30-day mortality in patients following open abdominal surgery. METHODS: This was a single-center register-based retrospective study. By means of electronic search in a maintained surgery database, all patients (n = 4177) aged ≥ 60 years old undergoing open surgery in our department from January 2000 to May 2013 were identified. Plasma was assessed within 30 days prior to surgery. The primary endpoint was 30-day postoperative mortality. The association between mortality and plasma levels of potassium, sodium, and creatinine were examined using Cox proportional hazard models. RESULTS: A total of 3690 patients were included in the study cohort. The rates of abnormal preoperative plasma levels were 36, 41, and 38% for potassium, sodium, and creatinine, respectively. The overall 30 day mortality was 20%. A predictive algorithm for 30 day mortality following abdominal surgery was constructed by means of logistic regression showing excellent distinction between patients with and without a fatal postoperative outcome. CONCLUSION: Apart from demographic factors (age, sex, and emergency surgery), preoperative imbalance in potassium, sodium and creatinine levels were significant independent predictors of early mortality following open abdominal surgery.

Time trends in treatment modes of anorexia nervosa in a nationwide cohort with free and equal access to treatment.

BACKGROUND: Treating patients with anorexia nervosa (AN) remains a major challenge. The choice between an inpatient or an outpatient care setting is an essential issue for the patients and for their relatives with major health economic implications. However, health services-related studies are lacking. The present study was a descriptive exploration of time-trends in treatment modes of patients with free and equal access to health services. METHODS: The study was based on a nationwide cohort of patients diagnosed for the first time with AN, each followed for 5 years in the registers covering the years 1994-2018. The per patient number of hospital admissions, cumulated number of days of hospitalization and number of outpatient visits during the first 5 years after initial diagnosis were considered. RESULTS: The cohort of patients with AN with at least 5 years of follow-up amounted to N = 7,505. A clear trend was observed in the per patient five-year cumulated number of inpatient days, decreasing by 6% per year after adjustment for age at diagnosis, parental mental diagnosis, and family income. The five-year number of hospital admissions after initial diagnosis decreased by 2% per year, while no trend was observed for outpatient visits. CONCLUSIONS: The per patient number of hospitalizations and cumulated days of hospitalization during 5 years after diagnosis were reduced for patients initially diagnosed with AN while there was no change in the number of outpatient visits. The factors contributing to these changes of treatment modes over time are in need of further study.

Barriers to lifestyle changes for prevention of cardiovascular disease - a survey among 40-60-year old Danes.

BACKGROUND: Elimination of modifiable risk factors including unhealthy lifestyle has the potential for prevention of 80% of cardiovascular disease cases. The present study focuses on disclosing barriers for maintaining specific lifestyle changes by exploring associations between perceiving these barriers and various sociodemographic and health-related characteristics. METHODS: Data were collected through a web-based questionnaire survey and included 962 respondents who initially accepted treatment for a hypothetical cardiovascular risk, and who subsequently stated that they preferred lifestyle changes to medication. Logistic regression was used to analyse associations between barriers to lifestyle changes and relevant covariates. RESULTS: A total of 45% of respondents were identified with at least one barrier to introducing 30 min extra exercise daily, 30% of respondents reported at least one barrier to dietary change, and among smokers at least one barrier to smoking cessation was reported by 62% of the respondents. The perception of specific barriers to lifestyle change depended on sociodemographic and health-related characteristics. CONCLUSION: We observed a considerable heterogeneity between different social groups in the population regarding a number of barriers to lifestyle change. Our study demonstrates that social inequality exists in the ability to take appropriate preventive measures through lifestyle changes to stay healthy. This finding underlines the challenge of social inequality even in populations with equal and cost-free access to health care. Our study suggests supplementing traditional public campaigns to counter cardiovascular disease by using individualized and targeted initiatives.

The microINR portable coagulometer: analytical quality and user-friendliness of a PT (INR) point-of-care instrument.

Regular measurement of prothrombin time as an international normalized ratio PT (INR) is mandatory for optimal and safe use of warfarin. Scandinavian evaluation of laboratory equipment for primary health care (SKUP) evaluated the microINR portable coagulometer (microINR®) (iLine Microsystems S.L., Spain) for measurement of PT (INR). Analytical quality and user-friendliness were evaluated under optimal conditions at an accredited hospital laboratory and at two primary health care centres (PHCCs). Patients were recruited at the outpatient clinic of the Laboratory of Medical Biochemistry, St Olav's University Hospital, Trondheim, Norway (n = 98) and from two PHCCs (n = 88). Venous blood samples were analyzed under optimal conditions on the STA-R®Evolution with STA-SPA + reagent (Stago, France) (Owren method), and the results were compared to capillary measurements on the microINR®. The imprecision of the microINR® was 6% (90% CI: 5.3-7.0%) and 6.3% (90% CI: 5.1-8.3) in the outpatient clinic and PHCC2, respectively for INR ≥2.5. The microINR® did not meet the SKUP quality requirement for imprecision ≤5.0%. For INR <2.5 at PHCC2 and at both levels in PHCC1, CV% was ≤5.0. The accuracy fulfilled the SKUP quality goal in both outpatient clinic and PHCCs. User-friendliness of the operation manual was rated as intermediate, defined by SKUP as neutral ratings assessed as neither good nor bad. Operation facilities was rated unsatisfactory, and time factors satisfactory. In conclusion, quality requirements for imprecision were not met. The SKUP criteria for accuracy was fulfilled both at the hospital and at the PHCCs. The user-friendliness was rated intermediate.

Associations between patients' risk attitude and their adherence to statin treatment - a population based questionnaire and register study.

BACKGROUND: Poor adherence to medical treatment may have considerable consequences for the patients' health and for healthcare costs to society. The need to understand the determinants for poor adherence has motivated several studies on socio-demographics and comorbidity. Few studies focus on the association between risk attitude and adherence. The aim of the present study was to estimate associations between patients' adherence to statin treatment and different dimensions of risk attitude, and to identify subgroups of patients with poor adherence. METHODS: Population-based questionnaire and register-based study on a sample of 6393 persons of the general. Danish population aged 20-79. Data on risk attitude were based on 4 items uncovering health-related as well as financial dimensions of risk attitude. They were collected through a web-based questionnaire and combined with register data on redeemed statin prescriptions, sociodemographics and comorbidity. Adherence was estimated by proportion of days covered using a cut-off point at 80 %. RESULTS: For the dimension of health-related risk attitude, "Preference for GP visit when having symptoms", risk-neutral and risk-seeking patients had poorer adherence than the risk-averse patients, OR 0.80 (95 %-CI 0.68-0.95) and OR 0.83 (95 %-CI 0.71-0.98), respectively. No significant association was found between adherence and financial risk attitude. Further, patients in the youngest age group and patients with no CVD were less adherent to statin treatment. CONCLUSION: We find some indication that risk attitude is associated with adherence to statin treatment, and that risk-neutral and risk-seeking patients may have poorer adherence than risk-averse patients. This is important for clinicians to consider when discussing optimal treatment decisions with their patients. The identified subgroups with the poorest adherence may deserve special attention from their GP regarding statin treatment.

Alarm symptoms of upper gastrointestinal cancer and contact to general practice--A population-based study.

INTRODUCTION: Survival of upper gastrointestinal (GI) cancer depends on early stage diagnosis. Symptom-based guidelines and fast-track referral systems have been implemented for use in general practice. To improve diagnosis of upper GI cancer, knowledge on prevalence of alarm symptoms in the general population and subsequent healthcare-seeking is needed. MATERIAL AND METHODS: A nationwide study of 100,000 adults, who were randomly selected from the general population were invited to participate in an internet-based survey. People aged ≥45 years were included in this study. Items regarding experience of specific and nonspecific alarm symptoms of upper GI cancer within the preceding 4 weeks and contact to general practitioner (GP) were included. RESULTS: Of the 60,562 subjects aged ≥45 years, 33,040 (54.6%) completed the questionnaire. The prevalence of the specific alarm symptoms ranged between 1.1% ("repeated vomiting") and 3.4% ("difficulty swallowing"). Women had higher odds of experiencing "repeated vomiting" and "persistent and recent-onset abdominal pain", but lower odds of experiencing "upper GI bleeding". The proportion of people contacting their GP with each of the four specific alarm symptoms ranged from 24.3% ("upper GI bleeding") to 39.9% ("repeated vomiting"). For each combination of two specific alarm symptoms, at least 52% contacted their GP. CONCLUSION: The specific alarm symptoms of upper GI cancer are not very prevalent in the general population. The proportion of GP contacts with each of the four specific symptoms varied between 24.3% and 39.9%. The proportion of GP contacts was higher in the older age and with combinations of two symptoms.