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Funding European Commission (DG-SANCO) , the International Agency for Research on Cancer (IARC) , MRC Early Career Fellowship (MR/M501669/1) ., Background Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas emissions, substantial land use, and adverse health such as cancer and mortality. To assess the potential co-benefits from shifting to more sustainable diets, we aimed to investigate the associations of dietary greenhouse gas emissions and land use with all-cause and cause-specific mortality and cancer incidence rates. Methods Using data from 443 991 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a multicentre prospective cohort, we estimated associations between dietary contributions to greenhouse gas emissions and land use and all-cause and cause-specific mortality and incident cancers using Cox proportional hazards regression models. The main exposures were modelled as quartiles. Co-benefits, encompassing the potential effects of alternative diets on all-cause mortality and cancer and potential reductions in greenhouse gas emissions and land use, were estimated with counterfactual attributable fraction intervention models, simulating potential effects of dietary shifts based on the EAT–Lancet reference diet. Findings In the pooled analysis, there was an association between levels of dietary greenhouse gas emissions and allcause mortality (adjusted hazard ratio [HR] 1·13 [95% CI 1·10–1·16]) and between land use and all-cause mortality (1·18 [1·15–1·21]) when comparing the fourth quartile to the first quartile. Similar associations were observed for cause-specific mortality. Associations were also observed between all-cause cancer incidence rates and greenhouse gas emissions, when comparing the fourth quartile to the first quartile (adjusted HR 1·11 [95% CI 1·09–1·14]) and between all-cause cancer incidence rates and land use (1·13 [1·10–1·15]); however, estimates differed by cancer type. Through counterfactual attributable fraction modelling of shifts in levels of adherence to the EAT–Lancet diet, we estimated that up to 19–63% of deaths and up to 10–39% of cancers could be prevented, in a 20-year risk period, by different levels of adherence to the EAT–Lancet reference diet. Additionally, switching from lower adherence to the EAT–Lancet reference diet to higher adherence could potentially reduce food-associated greenhouse gas emissions up to 50% and land use up to 62%. Interpretation Our results indicate that shifts towards universally sustainable diets could lead to co-benefits, such as minimising diet-related greenhouse gas emissions and land use, reducing the environmental footprint, aiding in climate change mitigation, and improving population health., European Commission European Commission Joint Research Centre, World Health Organization, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/M501669/1

Background Cisplatin-based chemotherapy (CBCT) in testicular cancer (TC) is associated with elevated venous thromboembolism (VTE) risk, but trials evaluating the safety and efficacy of thromboprophylaxis are lacking. Objective To evaluate the arterial thromboembolism (ATE) and VTE incidence and risk factors during first-line CBCT for metastatic TC, and the effect of thromboprophylaxis on VTE and bleeding. Design, setting, and participants In a population-based study, 506 men administered first-line CBCT during 2000–2014 at three university hospitals in Norway were included. Clinical variables were retrieved from medical records. Outcome measurements and statistical analysis Patients with ATE and VTE diagnosed at initiation of or during CBCT until 3 mo after completion were registered. Age-adjusted logistic regression was performed to identify possible VTE risk factors. Results and limitations Overall, 69 men (13.6%) were diagnosed with 70 thromboembolic events. Twelve men (2.4%) experienced ATE. Overall, 58 men (11.5%) experienced VTE, of whom 13 (2.6%) were prevalent at CBCT initiation, while 45 (8.9%) were diagnosed with incident VTE. Age-adjusted logistic regression identified retroperitoneal lymph node metastasis >5 cm (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01–3.91), central venous access (OR 2.84, 95% CI 1.46–5.50), and elevated C-reactive protein (>5 mg/l; OR 2.38, 95% CI 1.12–5.07) as incident VTE risk factors. Thromboprophylaxis (n = 84) did not influence the risk of VTE (VTE incidence with or without prophylaxis 13% vs 8%, p = 0.16). The incidence of bleeding events was significantly higher among those who received thromboprophylaxis than among those without thromboprophylaxis (14.5% vs 1.1%, p, Take Home Message We found a high rate of thromboembolism (13.6%) during cisplatin-based chemotherapy for metastatic testicular cancer. Prevalent venous thromboembolism (VTE) was more frequent in men with retroperitoneal lymph nodes >5 cm, intermediate/poor prognosis disease, poor performance status, and elevated C-reactive protein. Consequently, we advise to examine these patients closely with regard to VTE. Central venous access and large retroperitoneal lymph node metastases were associated with an increased risk of incident VTE in age-adjusted analysis. Patients without any risk factors had 5% incidence of VTE, indicating a thrombotic potential of cisplatin-based chemotherapy. Prophylactic treatment against thromboses did not reduce the thrombosis frequency, but it resulted in a high incidence of bleeding events.

Background Mothers with diabetes are less likely to achieve successful breastfeeding. Antenatal breastmilk expression (ABE) may facilitate earlier breastfeeding, but feasibility of introducing ABE and its acceptance among Scandinavian women have previously not been investigated. Methods This observational trial was conducted between the 1 January 2019 and the 12 March 2020 in Tromsø, Norway. We aimed to determine the feasibility of ABE in terms of practicality and acceptability among women with medically (metformin or insulin) treated diabetes. Women were invited to participate during antenatal visits from 32 weeks gestation. Participants received instruction and started ABE from gestation week 37 + 0. Participants, and their infants, were followed until 6–8 weeks after birth. We collected data on breastfeeding rates, infant hypoglycemia, transfer to the neonatal unit, and the women’s overall experience and satisfaction with antenatal breastmilk expression. Results Twenty-eight of 34 (82%) invited women consented to participate. All started ABE from week 37 + 0, and continued until hospital admission. No women reported any discomfort or side effects. Labor was induced at 38 weeks gestation. Twenty-four women brought harvested colostrum to the maternity ward, which was given to their infants during the first 24 h of life. Breastfeeding rates at discharge were 24/28 (86%) and 21/27 (78%) at 6–8 weeks after delivery. Seven (25%) infants were transferred to the neonatal unit; four because of hypoglycemia. Maternal satisfaction assessed 6–8 weeks after delivery revealed that all participants felt positive about the ABE, but one woman would not recommend it to other pregnant women. Conclusions Implementing a structured ABE guideline for women with medically treated diabetes was feasible. The intervention was associated with high level of satisfaction among study participants. No obvious side effects were observed, and breastfeeding rates at discharge and 6–8 weeks after delivery were higher than in comparable studies. Trial registration The study was registered at the research study registry at the University Hospital of North Norway (Nr 2018/7181).

Objective The basis of thyroid nodule diagnostics is ultrasound-guided fine needle biopsy with cytological evaluation (FNC) if ultrasound appearance is not clearly benign. The aim of this study was to investigate the predictive potential of dedicated, expert high-resolution ultrasound, to see if histopathological entities of thyroid nodules can be diagnosed without invasive FNC biopsies. Design Prospective case-cohort study. Methods 187 patients with 221 thyroid nodules were examined with ultrasound and prospectively assigned to the expected histopathological diagnosis: colloid nodule, adenomatoid colloid nodule, follicular adenoma, follicular carcinoma, follicular variant of papillary thyroid carcinoma, papillary thyroid carcinoma, or other thyroid cancer. In 101 of these, we later obtained histopathological reports for comparison. Results Overall accuracy for classification into discrete histopathological categories by expert ultrasound was 71.3% and Cohen’s Kappa was 0.62. The sensitivity and specificity for detecting malignancy were 97.3% and 78.1%. The diagnostic accuracy for malignancy was 85.1%. ACR-TIRADS scores for the same nodules had a sensitivity of 97.3%, specificity of 26.6%, and accuracy of 52.5%. Conclusion Dedicated expert high-resolution ultrasound without FNC can reliably distinguish benign vs malignant nodules, but also differentiate between several histopathological entities in thyroid nodules. There is potential for a reduction in the number of invasive FNC biopsies and diagnostic operations.

Objectives - The aim of the study was to assess the prevalence of symptoms indicative of temporomandibular disorders (TMD) in an adult population in Troms County in Northern Norway, as well as the associations between TMD and socio-demographic factors, dental status, self-reported general, and oral health as well as oral health related quality of life (OHQoL). Methods - Data were collected from a structured questionnaire and a clinical examination of a random sample of almost 2000 adults, 20–79-year-old, in Troms County in Northern Norway. Results - Women had a higher prevalence of all self-reported and clinical signs of pain and dysfunction in the temporomandibular complex compared to men. For both genders, sounds from the temporomandibular joint (TMJ) upon clinical examination was the most common symptom, followed by pain to palpation of jaw muscles. Headache was the most common of the self-reported symptoms and sounds from the TMJ the second most common. Young women had a higher prevalence of self-reported headache and jaw- and face pain compared to middle-aged and elderly women. TMD-related symptoms of pain were significantly associated with poor self-reported general health and correlated with OHQoL as assessed by the oral health impact profile 14 questionnaire. Conclusion - Being women and having moderate to poor self-reported general health were associated with clinical signs and self-reported symptoms of pain in the jaw, face and head region. Self-reported symptoms of TMD correlated more strongly with OHQoL than clinical signs.

Advances in neonatology have led to improved survival for periviable infants. Immaturity still carries a high risk of short- and long-term harms, and uncertainty turns provision of life support into an ethical dilemma. Shared decision-making with parents has gained ground. However, the need to start immediate life support and the ensuing difficulty of withdrawing treatment stands in tension with the possibility of a fair decision-making process. Both the parental “instinct of saving” and “withdrawal resistance” involved can preclude shared decision-making. To help health care personnel and empower parents, we propose a novel approach labeled “postponed withholding.” In the absence of a prenatal advance directive, life support is started at birth, followed by planned redirection to palliative care after one week, unless parents, after a thorough counseling process, actively ask for continued life support. Despite the emotional challenges, this approach can facilitate ethically balanced decision-making processes in the gray zone.

Background Physiological adaptation in pregnancy is characterized by remodeling of endocrine, cardiovascular and renal functions leading to fluid retention, volume expansion, altered cardiac loading conditions and hyperdynamic circulation. Natriuretic peptides have been used as biomarkers of cardiovascular function, but their associations with gestational age-related changes in maternal cardiac, endothelial and renal function have not been elucidated. The aim of this study was to establish longitudinal reference values for maternal plasma atrial natriuretic peptide (proANP) and C-type natriuretic peptide (CNP) and investigate their temporal association with cardiovascular and renal function in the second half of pregnancy. Methods This study was a prospective longitudinal study of 53 low-risk pregnancies. Women were examined every 3–5 weeks during 22–40 weeks of gestation (252 observations). Fasting maternal blood samples were obtained to measure proANP, CNP, creatinine, cystatin C, uric acid, and fibrinogen levels. Cardiac function and systemic hemodynamics were assessed noninvasively by impedance cardiography (ICG) and vascular endothelial function by flow-mediated vasodilation of brachial artery (FMD). Results The plasma proANP (R2adj = 0.79; P = 0.007), CNP (R2adj = 0.54; P = 0.005) decreased between 22 and 40 weeks. The creatinine (R2adj = 0.90; P 2adj = 0.93; P = 2adj = 0.83; P 2adj = 0.93; P 2adj = 0.79; P 2adj = 0.50; P 2adj = 0.62; P 2adj = 0.62; P = 0.438) and thoracic fluid content (R2adj = 0.72; P = 0.132) did not change significantly with gestation. The proANP was associated with thoracic fluid content (R2adj = 0.74; P 2adj = 0.78; P = 0.034) but not with other variables of systemic hemodynamics, endothelial function, or renal function. The CNP was not associated significantly with parameters of cardiovascular or renal function. Conclusion Longitudinal reference values for maternal plasma proANP and CNP were established. These natriuretic peptides decreased slightly with advancing gestation, but they did not reflect the temporal physiological changes in maternal systemic hemodynamics, vascular endothelial function and renal function during the second half of pregnancy. The proANP correlated with the thoracic fluid content reflecting volume load in pregnancy.

Background There is little evidence-based guidance on how to optimize methadone dosages among patients with opioid addiction undergoing methadone maintenance treatment (MMT). This study aims to investigate whether self-perceived opioid withdrawal symptoms, adverse effects, and self-reported substance use in patients on MMT are related to serum methadone concentrations and the role that these variables could play in clinical decisions on dose adjustments. Methods This naturalistic prospective cohort study included clinical and laboratory measurements from 83 patients undergoing MMT in outpatient clinics in Bergen, Norway, from May 2017 to January 2020. Information on age, gender, methadone daily doses and serum concentrations, subjective opioid withdrawal symptoms using 16 items Subjective Opioid Withdrawal Scale (SOWS) questionnaire, self-reported adverse effects, and substance use was obtained. Linear mixed modelling was used for analyzing the data. Results The mean age of the participants was 45 years, and 33% were women. Almost half reported mild to moderate subjective opioid withdrawal symptoms, and all had experienced at least one subjective adverse effect. The use of at least one substance was reported by 88% of the participants. Serum concentration-to-dose ratios were lower among those who had reported subjective opioid withdrawal symptoms (p) = 0.039). The total SOWS score (p p = 0.004), bone and muscle aches (p = 0.003), restlessness (p = 0.017), and (slightly) shaking (p = 0.046), also use of heroin (p = 0.015) and alcohol (p = 0.011) were associated with lower methadone concentrations. Cannabis use was slightly related to higher methadone concentrations (p = 0.049). Conclusions The findings suggest that the patient’s self-perceived symptoms and current clinical condition are related to the serum concentrations of methadone. This interpretation supports dose adjustments based on patient-reported symptoms. In some aberrant cases, measurement of serum concentrations together with other individual assessments may be considered to support the clinical decision.

Oral tongue squamous cell carcinoma (OTSCC) is one of the most common cancers worldwide and is characterized by early metastasis and poor prognosis. Recently, we reported that extracellular interleukin‐17F (IL‐17F) correlates with better disease‐specific survival in OTSCC patients and has promising anticancer effects in vitro. Vasculogenic mimicry (VM) is the formation of an alternative vasculogenic system by aggressive tumor cells, which is implicated in treatment failure and poor survival of cancer patients. We sought to confirm the formation of VM in OTSCC and to investigate the effect of IL‐17F on VM formation. Here, we showed that highly invasive OTSCC cells (HSC‐3 and SAS) form tube‐like VM on Matrigel similar to those formed by human umbilical vein endothelial cells. Interestingly, the less invasive cells (SCC‐25) did not form any VM structures. Droplet‐digital PCR, FACS, and immunofluorescence staining revealed the presence of CD31 mRNA and protein in OTSCC cells. Additionally, in a mouse orthotopic model, HSC‐3 cells expressed VE‐cadherin (CD144) but lacked Von Willebrand Factor. We identified different patterns of VM structures in patient samples and in an orthotopic OTSCC mouse model. Similar to the effect produced by the antiangiogenic drug sorafenib, IL‐17F inhibited the formation of VM structures in vitro by HSC‐3 and reduced almost all VM‐related parameters. In conclusion, our findings indicate the presence of VM in OTSCC and the antitumorigenic effect of IL‐17F through its effect on the VM. Therefore, targeting IL‐17F or its regulatory pathways may lead to promising therapeutic strategies in patients with OTSCC., In this study, we first confirmed the presence of the vasculogenic mimicry (VM) phenomenon in oral cancer patients, in vitro and in vivo, which exhibited different molecular patterns and markers. Next, we reported a novel therapeutic effect of IL‐17F against VM formation in highly aggressive cancer cells. Overall, targeting IL‐17F or its regulatory pathways could lead to promising therapeutic strategies in patients with oral cancer and other solid tumors as well.

We aimed to assess the impact of POLG disease on mental health and quality of life in 15 patients using the Symptom Checklist-90-R (SCL-90-R) and Short-Form 36 Health Survey (RAND-36). We found increased scores in all nine subscales of SCL-90-R, particularly phobic anxiety, depression and somatization. Further, patients reported considerably lower scores in all RAND-36 domains. This study revealed a global decline in mental health and poor quality of life in patients with POLG disease and highlights the need for increased awareness and systematic assessment in order to improve their quality of life and mental health. © 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license.

Immune aggregates organized as tertiary lymphoid structures (TLS) are observed within the kidneys of patients with systemic lupus erythematosus and lupus nephritis (LN). Renal TLS was characterized in lupus-prone New Zealand black × New Zealand white F1 mice analyzing cell composition and vessel formation. RNA sequencing was performed on transcriptomes isolated from lymph nodes, macrodissected TLS from kidneys, and total kidneys of mice at different disease stages by using a personal genome machine and RNA sequencing. Formation of TLS was found in anti–double-stranded DNA antibody–positive mice, and the structures were organized as interconnected large networks with distinct T/B cell zones with adjacent dendritic cells, macrophages, plasma cells, high endothelial venules, supporting follicular dendritic cells network, and functional germinal centers. Comparison of gene profiles of whole kidney, renal TLS, and lymph nodes revealed a similar gene signature of TLS and lymph nodes. The up-regulated genes within the kidneys of lupus-prone mice during LN development reflected TLS formation, whereas the down-regulated genes were involved in metabolic processes of the kidney cells. A comparison with human LN gene expression revealed similar up-regulated genes as observed during the development of murine LN and TLS. In conclusion, kidney TLS have a similar cell composition, structure, and gene signature as lymph nodes and therefore may function as a kidney-specific type of lymph node.

Early urinary incontinence remains a major source of morbidity for patients undergoing robotic prostatectomy. The purpose of the study was to determine whether the introduction of a suspension stitch would improve early urinary continence rates in patients undergoing robotic prostatectomy for localized prostate cancer at our department. We retrospectively reviewed patients undergoing robotic prostatectomy with either suspension (n = 119) or figure-of-eight (n = 48) stitching of the dorsal venous complex. The patients submitted EPIC-26 questionnaires before surgery and after 3 and 18 months, respectively. Logistic regression analysis was run to determine the effect of the suspension stitch, nerve-sparing, posterior reconstruction, prostate volume, age and body mass index on early continence rate. The odds ratio of experiencing urinary leaks was 2.1 times higher (95% CI 1.0–4.3) in the figure-of-eight stitch group compared to the suspension stitch group 3 months after surgery (p p p = 0.1). Ordinal regression analysis identified the suspension stitch, bilateral nerve-sparing and body mass index as independent predictors of urinary continence at 3 months. The association between urinary continence and either unilateral nerve-sparing, posterior reconstruction, prostate volume or age did not reach statistical significance. Our results suggest that the suspension stitch improved early urinary continence following robotic prostatectomy.

BackgroundWe examined the association between active and passive smoking and lung cancer risk and the population attributable fraction (PAF) of lung cancer due to active smoking, in the Norwegian Women and Cancer Study, a nationally representative prospective cohort study.MethodsWe followed 142,508 women, aged 31–70 years, who completed a baseline questionnaire between 1991 and 2007, through linkages to national registries through December 2015. We used Cox proportional hazards models, to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We calculated PAF to indicate what proportion of lung cancer cases could have been prevented in the absence of smoking.ResultsDuring the more than 2.3 million person-years of observation, we ascertained 1507 lung cancer cases. Compared with never smokers, current (HR 13.88, 95% CI 10.18–18.91) smokers had significantly increased risk of lung cancer. Female never smokers exposed to passive smoking had a 1.3-fold (HR 1.34, 95% CI 0.89–2.01) non- significantly increased risk of lung cancer, compared with never smokers. The PAF of lung cancer was 85.3% (95% CI 80.0–89.2).ConclusionMore than 8 in 10 lung cancer cases could have been avoided in Norway, if the women did not smoke.

The underlying neural mechanisms of transcranial direct current stimulation (tDCS), especially beyond the primary motor cortex, remain unclear. Several studies examined tDCS effects on either functional activity, neurotransmitters or behavior but few investigated those aspects together to reveal how the brain responds to tDCS. The objective is to elucidate the underlying mechanisms of tDCS using a multimodal approach that extends from behavioral to neurotransmitter levels of explanation. Thirty-two healthy participants performed an auditory dichotic listening task at two visits, one session with sham and one session with real tDCS (2 mA) while simultaneously undergoing functional magnetic resonance imaging (fMRI). The anode and cathode were placed over the left temporo-parietal cortex (TPC) and dorsolateral prefrontal cortex, respectively. Before and after simultaneous dichotic listening/fMRI/tDCS, combined glutamate and glutamine (Glx) and myo-inositol levels were assessed in the stimulated areas. While fMRI and dichotic listening showed expected functional activity and behavioral effects, neither method demonstrated differences between real and sham stimulation. Glx only showed a statistical trend towards higher levels after real tDCS in both stimulated brain areas. There were no significant correlations between behavior and Glx. Despite a reasonable sample size, electrical field strength, and replication of behavioral and functional activity results, tDCS had little to no effect on dichotic listening, Glx, and functional activity. The study emphasizes that findings about the underlying neural mechanisms of the primary motor cortex cannot simply be generalized to other brain areas. Particularly, the TPC might be less sensitive to tDCS. Moreover, the study demonstrates the general feasibility of multimodal approaches. publishedVersion

Objectives This study aimed to investigate whether inpatient multimodal occupational rehabilitation (I-MORE) reduces sickness absence (SA) more than outpatient acceptance and commitment therapy (O-ACT) among individuals with musculoskeletal and mental health disorders. Methods Individuals on sick leave (2-12 months) due to musculoskeletal or common mental health disorders were randomized to I-MORE (N=86) or O-ACT (N=80). I-MORE lasted 3.5 weeks in which participants stayed at the rehabilitation center. I-MORE included ACT, physical exercise, work-related problem solving and creating a return to work plan. O-ACT consisted mainly of 6 weekly 2.5 hour group-ACT sessions. We assessed the primary outcome cumulative SA within 6 and 12 months with national registry-data. Secondary outcomes were time to sustainable return to work and self-reported health outcomes assessed by questionnaires. Results SA did not differ between the interventions at 6 months, but after one year individuals in I-MORE had 32 fewer SA days compared to O-ACT (median 85 [interquartile range 33–149] versus 117 [interquartile range 59–189)], P=0.034). The hazard ratio for sustainable return to work was 1.9 (95% confidence interval 1.2–3.0) in favor of I-MORE. There were no clinically meaningful between-group differences in self-reported health outcomes. Conclusions Among individuals on long-term SA due to musculoskeletal and common mental health disorders, a 3.5-week I-MORE program reduced SA compared with 6 weekly sessions of O-ACT in the year after inclusion. Studies with longer follow-up and economic evaluations should be performed. This work is licensed under a Creative Commons Attribution 4.0 International License. CC-BY.

Background and purpose - The COVID-19 pandemic caused by infection with SARS-CoV-2 has led to a global shortage of personal protective equipment (PPE). Various alternatives to ordinary PPE have been suggested to reduce transmission, which is primarily through droplets and aerosols. For many years orthopedic surgeons have been using surgical helmets as personal protection against blood-borne pathogens during arthroplasty surgery. We have investigated the possibility of using the Stryker Flyte surgical helmet as a respiratory protective device against airborne- and droplet-transmitted disease, since the helmet shares many features with powered air-purifying respirators. Materials and methods - Using an aerosol particle generator, we determined the filtration capacity of the Stryker Flyte helmet by placing particle counters measuring the concentrations of 0.3, 0.5, and 5 µm particles inside and outside of the helmet. Results - We found that the helmet has insufficient capacity for filtrating aerosol particles, and, for 0.3 µm sized particles, we even recorded an accumulation of particles inside the helmet. Interpretation - We conclude that the Stryker Flyte surgical helmet should not be used as a respiratory protective device when there is a risk for exposure to aerosol containing SARS-CoV-2, the virus causing COVID-19, in accordance with the recommendation from the manufacturer

Background Learning from routine healthcare data is important for the improvement of the quality of care. Providing feedback on clinicians’ performance in comparison to their peers has been shown to be more efficient for quality improvements. However, the current methods for providing feedback do not fully address the privacy concerns of stakeholders. Methods The paper proposes a distributed architecture for providing feedback to clinicians on their clinical performances while protecting their privacy. The indicators for the clinical performance of a clinician are computed within a healthcare institution based on pseudonymized data extracted from the electronic health record (EHR) system. Group-level indicators of clinicians across healthcare institutions are computed using privacy-preserving distributed data-mining techniques. A clinician receives feedback reports that compare his or her personal indicators with the aggregated indicators of the individual’s peers. Indicators aggregated across different geographical levels are the basis for monitoring changes in the quality of care. The architecture feasibility was practically evaluated in three general practitioner (GP) offices in Norway that consist of about 20,245 patients. The architecture was applied for providing feedback reports to 21 GPs on their antibiotic prescriptions for selected respiratory tract infections (RTIs). Each GP received one feedback report that covered antibiotic prescriptions between 2015 and 2018, stratified yearly. We assessed the privacy protection and computation time of the architecture. Results Our evaluation indicates that the proposed architecture is feasible for practical use and protects the privacy of the patients, clinicians, and healthcare institutions. The architecture also maintains the physical access control of healthcare institutions over the patient data. We sent a single feedback report to each of the 21 GPs. A total of 14,396 cases were diagnosed with the selected RTIs during the study period across the institutions. Of these cases, 2924 (20.3%) were treated with antibiotics, where 40.8% (1194) of the antibiotic prescriptions were narrow-spectrum antibiotics. Conclusions It is feasible to provide feedback to clinicians on their clinical performance in comparison to peers across healthcare institutions while protecting privacy. The architecture also enables monitoring changes in the quality of care following interventions.

Objective Although exercise is recommended in the treatment of axial spondyloarthritis (axSpa), the focus has been on flexibility, and the effect of high-intensity exercises is unknown. The purpose of this study was to investigate the effect of high-intensity exercises on fatigue, sleep, and mood in patients with axSpA. Methods In this secondary analysis of a randomized controlled trial, participants were recruited from outpatient clinics at 4 hospitals in Scandinavia. A total of 100 patients with axSpA were randomized to either an exercise group (n = 50) or a control group (n = 50). High-intensity exercise was provided 3 times per week for 3 months and supervised by a physical therapist. The controls received no intervention. Measurements were self-reported at baseline, 3 months, and 12 months: fatigue, using the Fatigue Severity Scale (range = 0–7, 7 = worst, ≥5 = severe); vitality, using the RAND 36-item short-form health survey (SF-36, range = 0–100, 100 = best); sleep, using the Pittsburgh Sleep Quality Index (range = 0–21, 21 = worst, >5 = poor quality); mood, using the General Health Questionnaire 12 (range = 0–36, 36 = worst); and general health, using the EUROQoL (range = 0–100, 100 = best). Results A total of 38 participants (76%) in the exercise group followed ≥80% of the exercise protocol. At 3 months, there was a significant beneficial effect on fatigue (mean group differences = −0.4, 95% CI = −0.7 to −0.1), vitality (5.0, 95% CI = 1.1 to 10.5), mood (−2, 95% CI = −3.7 to −0.04), and general health (9.0, 95% CI = 3.3 to 14.7) but no effect on sleep (−1.1, 95% CI = −2.1 to 0.2). Compared with the control group, the exercise group had a reduced rate of severe fatigue and poor sleep. No differences were seen between the groups at 12 months. Conclusions A 3-month exercise program had a beneficial effect on fatigue, sleep, mood, and general health in patients with axSpA at the end of the intervention; however, no long-term effects were seen. Impact High-intensity cardiorespiratory and strength exercises should be considered as important in exercise programs for patients with axSpA.

Background Few reports are available on the contribution of general and abdominal obesity to the progression of carotid atherosclerosis in late adulthood. This study investigated the impact of four simple anthropometric measures of general and abdominal obesity on the progression of carotid atherosclerosis and the extent to which the association between adiposity and the progression of plaque burden is mediated by cardiometabolic markers. Methods Four thousand three hundred forty-five adults (median age 60) from the population-based Tromsø Study were followed over 7 years from the first carotid ultrasound screening to the next. The progression of carotid atherosclerosis was measured in three ways: incidence of plaques in previously plaque-free participants; change in the number of plaques; and total plaque area (TPA). We used generalised linear models to investigate the association between each adiposity measure – body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) – and each outcome. Models were adjusted for potential confounders (age, sex, smoking, education, physical activity). The pathways through which any associations observed might operate were investigated by further adjusting for cardiometabolic mediators (systolic blood pressure, cholesterol, and HbA1c). Results There was little evidence that adiposity was related to the formation of new plaques during follow-up. However, abdominal adiposity was associated with TPA progression. WHtR showed the largest effect size (mean change in TPA per one standard deviation (SD) increase in WHtR of 0.665 mm2, 95% confidence interval 0.198, 1.133) while BMI showed the smallest. Effect sizes were substantially reduced after the adjustment for potential mediators. Conclusions Abdominal obesity indirectly measured with WC seems more strongly associated with the progression of TPA than general obesity. These associations appear to be largely mediated by known cardiometabolic markers.

The gut microbiome contributes to the variation of blood lipid levels, and secondary bile acids are associated with the effect of statins. Yet, our knowledge of how statins, one of our most common drug groups, affect the human microbiome is scarce. We aimed to characterize the effect of rosuvastatin on gut microbiome composition and inferred genetic content in stool samples from a randomized controlled trial (n = 66). No taxa were significantly altered by rosuvastatin during the study. However, rosuvastatin-treated participants showed a reduction in the collective genetic potential to transport and metabolize precursors of the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO, p p p

Aim - To study whether a simple targeted intervention could reduce unwarranted antibiotic treatment in near‐term and term neonates with suspected, but not confirmed early‐onset sepsis. Methods - A quality improvement initiative in three Norwegian neonatal intensive care units. The intervention included an inter‐hospital clinical practice guideline for discontinuing antibiotics after 36‐48 hours if sepsis was no longer suspected and blood cultures were negative in neonates ≥ 34+0 weeks of gestation. Two units used procalcitonin in decision‐making. We compared data 12‐14 months before and after guideline implementation. The results are presented as median with interquartile ranges. Results - A total of 284 infants (2.5% of all births ≥ 34+0 weeks of gestation) received antibiotics before and 195 (1.8%) after guideline implementation (P = .0018). The two units that used procalcitonin discontinued antibiotics earlier after guideline implementation than the unit without procalcitonin. Neonates not diagnosed with sepsis were treated 49 (31‐84) hours before and 48 (36‐72) hours after guideline implementation (P = .68). In all infants, including those diagnosed with sepsis, antibiotic treatment duration was reduced from 108 (60‐144) to 96 (48‐120) hours (P = .013). Conclusion - Antibiotic treatment duration for suspected, but not confirmed early‐onset sepsis did not change. However, treatment duration for all infants and the proportion of infants commenced on antibiotics were reduced.

Til opplæring (OA) LiseA Background: Chronic obstructive pulmonary disease (COPD) is associated with risk of venous thromboembolism (VTE). It remains unknown whether individual respiratory symptoms and lowered oxygen saturation (SpO2), individually and in combination with COPD, affect the risk of VTE. Objectives: To investigate whether measures of respiratory impairments including respiratory symptoms and SpO2, individually and combined with COPD, were associated with an increased risk of VTE. Methods: Spirometry, SpO2, and self-reported respiratory symptoms were collected in 8686 participants from the fifth (2001-2002) and sixth (2007-2008) surveys of the Tromsø Study. Incident VTE events were registered from the date of inclusion to December 31, 2016. Cox regression models with exposures and confounders as time-varying covariates (for repeated measurements) were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for VTE. Results: During a median follow-up of 9.1 years, 330 participants developed incident VTE. Subjects with SpO2 ≤ 96% (lowest 20th percentile) had a 1.5-fold higher risk of VTE (adjusted HR, 1.48; 95% CI, 1.13-1.93) compared with those with SpO2 ≥ 98%. Severe respiratory symptoms (dyspnea, cough, and phlegm) were associated with a 1.4- to 2.0-fold higher risk of VTE compared with no such symptoms. COPD, combined with respiratory symptoms or lowered SpO2, had an additive effect on the VTE risk. Conclusions: Lowered SpO2 and severe respiratory symptoms were associated with increased VTE risk. COPD combined with respiratory impairments had an additive effect on VTE risk, and may suggest particular attention on VTE preventive strategies in COPD patients with respiratory impairments.

Findings are presented from a study examining the effects of the home-based intervention ‘Growing: Birth to Three’ (GBT) on children born prematurely at a regional hospital in Norway over a four-year period. Nineteen children received the intervention, while 17 children comprised the control group. Results indicate that GBT had a positive effect on development at 18 months, as measured by the Bayley Scale of Infant Development. However, by 36 months both the intervention and control groups were in the normal range on this measure. A post-test comparison of language performance at 36 months found significantly higher expressive language scores among children in the intervention group on the Reynell Developmental Language Scale. Parental anxiety at the end of the intervention was also measured. The benefits of implementing the GBT programme are discussed in relation to public health and the early childhood education and care systems in Norway.

Introduction There is limited evidence for effect of interventional treatment, and pragmatic studies are needed to assess these interventions within a clinical setting. The aim of this study was to describe patients referred to an interventional pain clinic and investigate responses after spinal intervention in general and for radiofrequency ablation (RFA) and transforaminal epidural corticosteroid administration (TECA), specifically. Methods This is a prospective, non-controlled study of patients with chronic spinal pain. The procedures were performed in accordance with the Spine Intervention Society recommendations. Outcome data after a median of 4.5 months are presented, and for those treated with RFA also after 6 and 12 months. Results Among 815 patients, 190 patients underwent diagnostic blocks only and 625 interventional treatment, of these 94 RFA and 246 TECA. Of the whole sample 70% reported pain reduction, for 49% ≥ 50%, while 9% were pain free (p p p p p p p p p p p p p Conclusion The study demonstrates substantial short-term responses after spinal intervention and long-lasting improvement for a subsample of the RFA treated patients. We observed larger proportions reporting pain reduction among those treated with cervical RFA. Implementation Quality assessment should be implemented in interventional pain clinics to improve treatment quality.

This is a non-final version of an article published in final form in Lipcsey, Tenhunen, Pischke, Kuitunen, Flaatten, De Geer, Sjölin, Frithiof, Chew, Bendel, Kawati, Larsson, Mollnes, Tønnessen, Rubertsson. Endotoxin removal in septic shock with the Alteco LPS Adsorber was safe but showed no benefit compared to placebo in the double-blind randomized controlled trial - the Asset Study. Shock. 2020;54(2):224-231. Purpose: Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco LPS Adsorber for LPS removal in early gram-negative septic shock was feasible and safe. Also, effects on endotoxin level, inflammatory response, and organ function were assessed. Methods: A pilot, double-blinded, randomized, Phase IIa, feasibility clinical investigation was undertaken in six Scandinavian intensive care units aiming to allocate 32 septic shock patients with abdominal or urogenital focus on LPS Adsorber therapy or a Sham Adsorber, therapy without active LPS binding. The study treatment was initiated within 12 h of inclusion and given for 6 h daily on first 2 days. LPS was measured in all patients. Results: The investigation was terminated after 527 days with eight patients included in the LPS Adsorber group and seven in the Sham group. Twenty-one adverse effects, judged not to be related to the device, were reported in three patients in the LPS Adsorber group and two in the Sham group. Two patients in the Sham group and no patients in the LPS Adsorber group died within 28 days. Plasma LPS levels were low without groups differences during or after adsorber therapy. The changes in inflammatory markers and organ function were similar in the groups. Conclusions: In a small cohort of patients with presumed gram-negative septic shock, levels of circulating endotoxin were low and no adverse effects within 28 days after LPS adsorber-treatment were observed. No benefit compared with a sham device was seen when using a LPS adsorber in addition to standard care.

Background A commonly applied control condition in trials evaluating complex interventions in rehabilitation research is “usual care.” The main challenge is to ensure that the control group receives genuine usual care as delivered in everyday clinical practice. The assessment interviews and dialogues with the data collectors may influence the control group participants’ reflections on their condition and adjustments. This represents a threat to the internal validity of the trial. Thus, the aim of this study was to explore the perceived study-induced influence of assessment interviews on the adjustment of the members of a control group in a randomized clinical trial. The aim of the trial was to test a dialogue-based psychosocial intervention aiming at promoting the psychosocial well-being and adjustment of stroke survivors. Methods Fifteen participants in the control group of a multicenter stroke rehabilitation trial participated in narrative semi-structured interviews. Ricoeur’s interpretation theory guided the analysis. Results The perceived study-induced influence of the assessment interviews on the adjustment process of members of the control group varied considerably. The results demonstrated that the assessment interviews facilitated some participants’ feelings of control and their ability to cope. Other participants’ statements indicate that they relied on their existing personal capacity to cope and adjust and that the assessment interviews did not make any difference either on their coping ability or on their process of adjustment. Five themes were identified that described the perceived study-induced influence of the assessment interviews in the control group. The themes illustrated that the assessments served as a safety net, enhanced awareness and understanding, encouraged seeking support, allowed the opportunity to vent disappointment, or did not make any difference either way. Conclusions RCT assessment interviews may influence the adjustment process and represent a serious problem in measuring interventions over time in trials of complex interventions in rehabilitation research. To uphold rigor and stringency, the usual care control conditions should be thoroughly assessed and described. Informing participants only about the treatment they were allocated to receive might counteract the potential to dilute the difference between the two arms of the trial. Trial registration ClinicalTrials.gov NCT02338869. Registered on October 4, 2014

Source at https://www.tannlegetidende.no/i/2021/11/m-255. Medlemmer i Munn- og halskreftforeningen mottok et spørreskjema for å kartlegge erfaringer med økonomiske refusjonsordninger for tannbehandling og kostnader til tannbehandling hos personer som er behandlet for hode-halskreft i Norge. I tillegg kartla vi utviklingen i Folketrygdens honorartakster for tannbehandling i perioden 2015-2020, og sammenlignet honorartakstene for 2021 med takstene for voksenbehandling i Den offentlige tannhelsetjenesten i Troms og Finnmark. Av de 216 som besvarte spørreskjemaet rapporterte halvparten kostnader til tannbehandling etter kreftdiagnose, og en fjerdedel hadde hatt utlegg på 10 000 kroner eller mer. De med moderat og dårlig tannhelse rapporterte betydelig høyere kostnader enn de med god tannhelse. Andelen som oppga at de hadde fått god hjelp av tannlege til å få den økonomiske støtten de hadde krav på var høyest blant dem med store utgifter. Funnene indikerer at honorartakstene til Folketrygden ikke gjenspeiler prisene for tannbehandling av voksne i Norge. Mens konsumprisindeksen økte med 14 % mellom januar 2015 og desember 2020, økte Folketrygdens honorartakster for tannbehandling i gjennomsnitt med 5-6 %, og takstene for 2021 lå gjennomsnittlig nesten 40 % under takstene for voksenbehandling i Den offentlige tannhelsetjenesten i Troms og Finnmark. Tross rettigheter gjennom folketrygdloven kan derfor hode-halskreftpasienter oppleve økonomiske barrierer for å motta nødvendig tannhelsehjelp.

Aims: Rewarming from accidental hypothermia and therapeutic temperature management could be complicated by cardiac dysfunction. Although pharmacologic support is often applied when rewarming these patients, updated treatment recommendations are lacking. There is an underlying deficiency of clinical and experimental data to support such interventions and this prevents the development of clinical guidelines. Accordingly, we explored the clinical effects of epinephrine during hypothermic conditions.Materials and methods: Anesthetized pigs were immersion cooled to 32°C. Predetermined variables were compared at temperature/time-point baseline, after receiving 30 ng/kg/min and 90 ng/kg/min epinephrine infusions: (1) before and during hypothermia at 32°C, and after rewarming to 38°C (n = 7) and (2) a time-matched (5 h) normothermic control group (n = 5).Results: At 32°C, both stroke volume and cardiac output were elevated after 30 ng/kg/min administration, while systemic vascular resistance was reduced after 90 ng/kg/min. Epinephrine infusion did not alter blood flow in observed organs, except small intestine flow, and global O2 extraction rate was significantly reduced in response to 90 ng/kg/min infusion. Electrocardiographic measurements were unaffected by epinephrine infusion.Conclusion: Administration of both 30 ng/kg/min and 90 ng/kg/min at 32°C had a positive inotropic effect and reduced afterload. We found no evidence of increased pro-arrhythmic activity after epinephrine infusion in hypothermic pigs. Our experiment therefore suggests that β₁-receptor stimulation with epinephrine could be a favorable strategy for providing cardiovascular support in hypothermic patients, at core temperatures >32°C.

BackgroundCancer genomic studies often include data collected from several omics platforms. Each omics data source contributes to the understanding of the underlying biological process via source specific (“individual”) patterns of variability. At the same time, statistical associations and potential interactions among the different data sources can reveal signals from common biological processes that might not be identified by single source analyses. These common patterns of variability are referred to as “shared” or “joint”. In this work, we show how the use of joint and individual components can lead to better predictive models, and to a deeper understanding of the biological process at hand. We identify joint and individual contributions of DNA methylation, miRNA and mRNA expression collected from blood samples in a lung cancer case–control study nested within the Norwegian Women and Cancer (NOWAC) cohort study, and we use such components to build prediction models for case–control and metastatic status. To assess the quality of predictions, we compare models based on simultaneous, integrative analysis of multi-source omics data to a standard non-integrative analysis of each single omics dataset, and to penalized regression models. Additionally, we apply the proposed approach to a breast cancer dataset from The Cancer Genome Atlas.ResultsOur results show how an integrative analysis that preserves both components of variation is more appropriate than standard multi-omics analyses that are not based on such a distinction. Both joint and individual components are shown to contribute to a better quality of model predictions, and facilitate the interpretation of the underlying biological processes in lung cancer development.ConclusionsIn the presence of multiple omics data sources, we recommend the use of data integration techniques that preserve the joint and individual components across the omics sources. We show how the inclusion of such components increases the quality of model predictions of clinical outcomes.

Background Trauma-induced coagulopathy in patients with traumatic brain injury (TBI) is associated with high rates of complications, unfavourable outcomes and mortality. The mechanism of the development of TBI-associated coagulopathy is poorly understood. Methods This analysis, embedded in the prospective, multi-centred, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, aimed to characterise the coagulopathy of TBI. Emphasis was placed on the acute phase following TBI, primary on subgroups of patients with abnormal coagulation profile within 4 h of admission, and the impact of pre-injury anticoagulant and/or antiplatelet therapy. In order to minimise confounding factors, patients with isolated TBI (iTBI) (n = 598) were selected for this analysis. Results Haemostatic disorders were observed in approximately 20% of iTBI patients. In a subgroup analysis, patients with pre-injury anticoagulant and/or antiplatelet therapy had a twice exacerbated coagulation profile as likely as those without premedication. This was in turn associated with increased rates of mortality and unfavourable outcome post-injury. A multivariate analysis of iTBI patients without pre-injury anticoagulant therapy identified several independent risk factors for coagulopathy which were present at hospital admission. Glasgow Coma Scale (GCS) less than or equal to 8, base excess (BE) less than or equal to − 6, hypothermia and hypotension increased risk significantly. Conclusion Consideration of these factors enables early prediction and risk stratification of acute coagulopathy after TBI, thus guiding clinical management.

IntroductionCardiovascular dysfunction is a potentially lethal complication of hypothermia. Due to a knowledge gap, pharmacological interventions are not recommended at core temperatures below 30°C. Yet, further cooling is induced in surgical procedures and survival of accidental hypothermia is reported after rewarming from below 15°C, advocating a need for evidence-based treatment guidelines. In vivo studies have proposed vasodilation and afterload reduction through arteriole smooth muscle cGMP-elevation as a favorable strategy to prevent cardiovascular dysfunction in hypothermia. Further development of treatment guidelines demand information about temperature-dependent changes in pharmacological effects of clinically relevant vasodilators.Materials and MethodsHuman phosphodiesterase-enzymes and inverted erythrocytes were utilized to evaluate how vasodilators sildenafil and vardenafil affected cellular efflux and enzymatic breakdown of cAMP and cGMP, at 37°C, 34°C, 32°C, 28°C, 24°C, and 20°C. The ability of both drugs to reach their cytosolic site of action was assessed at the same temperatures. IC50- and Ki-values were calculated from dose–response curves at all temperatures, to evaluate temperature-dependent effects of both drugs.ResultsBoth drugs were able to reach the intracellular space at all hypothermic temperatures, with no reduction compared to normothermia. Sildenafil IC50 and Ki-values increased during hypothermia for enzymatic breakdown of both cAMP (IC50: 122 ± 18.9 μM at 37°C vs. 269 ± 14.7 μM at 20°C, p < 0.05) and cGMP (IC50: 0.009 ± 0.000 μM at 37°C vs. 0.024 ± 0.004 μM at 32°C, p < 0.05), while no significant changes were detected for vardenafil. Neither of the drugs showed significant hypothermia-induced changes in IC50 and Ki–values for inhibition of cellular cAMP and cGMP efflux.ConclusionSildenafil and particularly vardenafil were ableto inhibit elimination of cGMP down to 20°C. As the cellular effects of these drugs can cause afterload reduction, they show potential in treating cardiovascular dysfunction during hypothermia. As in normothermia, both drugs showed higher selectivity for inhibition of cGMP-elimination than cAMP-elimination at low core temperatures, indicating that risk for cardiotoxic side effects is not increased by hypothermia.

Background As part of political and professional development with increased focus on including service users within mental health services, these services are being transformed. Specifically, they are shifting from institutional to noninstitutional care provision with increased integration of the use of electronic health and digitalization. In the period from March to May 2020, COVID-19 restrictions forced rapid changes in the organization and provision of mental health services through the increased use of digital solutions in therapy. Objective The aim of this study was to develop and advance comprehensive knowledge about how therapists experience the use of video consultation (VC). To reach this objective, we evaluated therapists’ experiences of using VC in specialized mental health services in the early phase of COVID-19 restrictions. The following questions were explored through interviews: Which opportunities and challenges appeared when using VC during the period of COVID-19 restrictions? In a short-term care pathway, for whom does VC work and for whom does it not work? Methods This study employed a qualitative approach based on an abductive strategy and hermeneutic-phenomenological methodology. Therapists and managers in mental health departments in a hospital were interviewed via Skype for Business from March to May 2020, using a thematic interview guide that aimed to encourage reflections on the use of VC during COVID-19 restrictions. Results Therapists included in this study experienced advantages in using VC under circumstances that did not permit face-to-face consultations. The continuity that VC offered the service users was seen as a valuable asset. Various negative aspects concerning the therapeutic environment such as lack of safety for the most vulnerable service users and topics deemed unsuitable for VC lowered the therapists’ overall impression of the service. The themes that arose in the data analysis have been categorized in the following main topics: (1) VC—“it’s better than nothing”; (2) VC affects therapists’ work situation—opportunities and challenges in working conditions; and (3) challenges of VC when performing professional assessment and therapy on the screen. Conclusions Experiences with VC in a mental health hospital during COVID-19 restrictions indicate that there are overall advantages to using VC when circumstances do not permit face-to-face consultations. Nevertheless, various negative aspects in the use of VC lowered the therapists’ overall impression of VC. Further qualitative research is needed, and future studies should focus on service users’ experiences, cocreation between different stakeholders, and how to scale up the use of VC while ensuring that the service provided is appropriate, safe, and available.

Aim: The combination of iron deficiency and anaemia is a major health problem, and adolescents are an at- risk group. The main aim of this study was to explore the mag-nitude of these conditions among adolescents aged 15–19 and identify possible as-sociated risk factors. Methods: This population- based longitudinal study of adolescents in North Norway was conducted in 2010–2011, with a follow-up two years later. Repeated measure-ments of iron deficiency and anaemia and its possible risk factors were studied in 309 girls and 273 boys. Results: Iron deficiency and anaemia were found in 18.1% and 19.9% of girls and 1.6% and 2.9% of boys in the first study and about half of the cases were chronic two years later. Most girls had moderate iron deficiency (14.5%) and mild anaemia (16.0%). Daily milk consumption was associated with increased iron deficiency in girls (odds ratio 2.3, 95% confidence interval 1.1–4.9), and the most physically active girls had the lowest levels of iron deficiency (odds ratio 0.4, 95% confidence intervaI 0.2–0.9). Iron deficiency was the most important risk factor for chronic anaemia in girls. Conclusion: The results of this study highlight the importance of iron deficiency screening and treatment for adolescent girls.

Objectives: To assess the use of three commonly prescribed psychotropic medications in youth placed in residential care (RC). Methods: Participants were youth aged 0–20 years placed in RC institutions at least once during 2016. Data on filled prescriptions were taken from the Norwegian Prescription Database to compare the use of antidepressants, antipsychotics, and stimulants in RC with the age- and gender-adjusted general child population (GenPop) and how this co-varied with reasons for RC placement, age, and gender. Results: One thousand eight hundred fifty-six children and adolescents were identified in RC, with mean age 14 (range 0–20 years), 46% girls, 81% ≥ 13 years. Among those, 423 or 23% used any of the 3 psychotropics, which was significantly more than the 3.7% in GenPop. The prevalence ratios RC/GenPop were 6.6 for antidepressants, 17.9 for antipsychotics, and 4.4 for stimulants. The median number of days per year for the dispensed defined daily doses varied from 8.3 to 244.0 for the different antipsychotics, indicating short time use for most of the people. Polypharmacy was not frequent in RC, as only 26% used ≥2 classes of medication, but still significantly more frequent than the 10% in GenPop. Youth placed in RC for serious behavior problems had significantly higher use of stimulants than those with other placement reasons. Psychotropics were not used below age 6 years, and although the use of antidepressants and antipsychotics overall increased with age, stimulants were mostly used by 6–16-year olds. The girl/boy ratio for any psychotropic medication use in RC was 1.4 (95% confidence interval [95% CI]: 1.1–1.6), significantly higher than the corresponding ratio in GenPop: 1.0 (95% CI: 0.9–1.0). Conclusion: The present findings do not necessarily suggest an overtreatment with medication in RC. However, the frequent short-term use of antipsychotics, presumably for non-psychotic symptoms, is a concern, as it may reflect that the youth are not provided with the recommended first-line psychological treatments.

BackgroundThe use of information technology can make pulmonary rehabilitation interventions in people with chronic obstructive pulmonary disease (COPD) more flexible and thereby has the potential to reach a larger proportion of the population. However, the success of using information technology in pulmonary rehabilitation is dependent on the end-user’s competence in information technology and access to the Internet. The aim was to describe the access to, and the use, knowledge, and preferences of information technology and technical equipment among people with COPD.MethodsTelephone interviews were conducted using a standardised questionnaire on information technology and technical devises addressing the household, access to and usage of the Internet, contact with authorities, e-commerce, security, the workplace, digital competence, and disabilities. Questions were also posed regarding participants’ views on a future eHealth tool for COPD, appropriate content, and the potential likelihood for them to use an eHealth tool for exercise training.ResultsIn total 137 persons agreed to participate, 17 dropped out resulting in 120 included participants (response rate 88%). The participants (86 women) were aged 51 to 92 years (mean: 72.5), and all severity grades of COPD according to GOLD A-D were represented. Over 90% had access to the Internet. Smartphones were used by 81%, and over 90% used apps. Participants had high knowledge of how to use the Internet, 91% had used the Internet during the last 3 months, 85% almost every day. The most common requests for a future eHealth tool for COPD were evidence-based and trustworthy information on COPD, (including medication, exercise training, inhalation and breathing techniques), communication (chat) with others and with health carers. Access to individually adjusted exercise training, and support, (motivation via prompts, chat rooms, digital information board) was also desired.ConclusionsThe present study showed that people with COPD in Sweden have high access and ability to use the Internet and information technology. They are frequent users and most of them take part in the digital society, even to a higher extent than the general population. The results show that the use of an eHealth tool could be a suitable strategy for people with COPD.

Background Adverse childhood experiences (ACE) are related to adverse physical and mental health outcomes. However, few larger studies based on a general population sample with age groups ranging from young adults to elderly have investigated whether parental alcohol problems increase the risk of offspring subjective reports of ACE both during childhood and current adult adversities. The purpose of this study was to examine the associations between parental alcohol problems and adversities during childhood and later in adulthood. Methods The 28,047 respondents were adults (> 18 years old) from the general population who participated in the Norwegian Counties Public Health Survey. The study had a cross-sectional design and included respondents’ evaluations of childhood experiences and current adult adversities. The short version of the Children of Alcoholics Screening Test (CAST-6, cut-off ≥3) measured parental alcohol problems. Multivariable logistic regression was adjusted for gender, age, and education. Results Growing up with parental alcohol problems strongly increased the risk of experiencing a dysfunctional family environment during childhood (odds ratio [OR] 6.84; 95% confidence interval [CI] 6.36–7.36), perceiving childhood as difficult (OR 5.01; 95% CI 4.58–5.49), and reporting a lack of support from a trusted adult (OR 3.07; 95% CI 2.86–3.29). Parental alcohol problems were associated with a modestly increased risk of harmful alcohol use (OR 1.38; 95% CI 1.29–1.48), but the association with struggling with bad memories was strong (OR 4.56; 95% CI 4.17–4.98). Conclusions Parental alcohol problems increased the risk of offspring experiencing adversities during both childhood and adulthood. Providing supportive services to these children and their families and addressing this issue as part of treatment is important to prevent alcohol related harm.

Fatigue is the most commonly noted symptom among people living with human immunodeficiency virus (PLHIV). The aim of this study was to investigate the prevalence and predictors of fatigue among PLHIV in Norway. Two hundred and forty-four people were recruited from two hospitals to participate in a survey, which contained seven instruments used to investigate mental health, addiction, quality of life, and fatigue. More than a third of the participants (38.5%) suffered from fatigue. Predictors of fatigue were the presence of mental distress (adjusted odds ratio [AOR] 8.98, 95%CI 3.81, 21.15), multimorbidity (AOR 5.13, 95%CI 1.40, 18.73), living alone (AOR 2.99, 95%CI 1.36, 6.56), trouble sleeping (AOR 2.67, 95%CI 1.06, 6.71), and increased body pain (AOR 1.44, 95%CI 1.25, 1.67). To improve the quality of life for many PLHIV, the continuum of HIV care must address fatigue and its predictors.

The last decade has witnessed the development of sophisticated biobehavioral and genetic, ambulatory, and other measures that promise unprecedented insight into psychiatric disorders. As yet, clinical sciences have struggled with implementing these objective measures and they have yet to move beyond “proof of concept.” In part, this struggle reflects a traditional, and conceptually flawed, application of traditional psychometrics (i.e., reliability and validity) for evaluating them. This paper focuses on “resolution,” concerning the degree to which changes in a signal can be detected and quantified, which is central to measurement evaluation in informatics, engineering, computational and biomedical sciences. We define and discuss resolution in terms of traditional reliability and validity evaluation for psychiatric measures, then highlight its importance in a study using acoustic features to predict self-injurious thoughts/behaviors (SITB). This study involved tracking natural language and self-reported symptoms in 124 psychiatric patients: (a) over 5–14 recording sessions, collected using a smart phone application, and (b) during a clinical interview. Importantly, the scope of these measures varied as a function of time (minutes, weeks) and spatial setting (i.e., smart phone vs. interview). Regarding reliability, acoustic features were temporally unstable until we specified the level of temporal/spatial resolution. Regarding validity, accuracy based on machine learning of acoustic features predicting SITB varied as a function of resolution. High accuracy was achieved (i.e., ~87%), but only when the acoustic and SITB measures were “temporally-matched” in resolution was the model generalizable to new data. Unlocking the potential of biobehavioral technologies for clinical psychiatry will require careful consideration of resolution.

Background and purpose — In Norway all compensation claims based on healthcare services are handled by a government agency (NPE, Norsk Pasientskade Erstatning). We provide an epidemiological overview of claims within pediatric orthopedics in Norway, and identify the most common reasons for claims and compensations. Patients and methods — All compensation claims handled by NPE from 2012 to 2018 within pediatric orthopedics (age 0 to 17 years) were reviewed. Data were analyzed with regard to patient demographics, diagnoses, type of injury, type of treatment, reasons for granted compensation, and total payouts. Results — 487 compensation claims (259 girls, 228 boys) within orthopedic surgery in patients younger than 18 years at time of treatment were identified. Mean age was 12 years (0–17). 150 out of 487 claims (31%) resulted in compensation, including 79 compensations for inadequate treatment, 58 for inadequate diagnostics, 12 for infections, and 1 based on the exceptional rule. Total payouts were US$8.45 million. The most common primary diagnoses were: upper extremity injuries (26%), lower extremity injuries (24%), congenital malformations and deformities (12%), spine deformities (11%), disorders affecting peripheral joints (9%), chondropathies (6%), and others (12%). Interpretation — Most claims were submitted and granted for mismanagement of fractures in the upper and lower extremity, and mismanagement of congenital malformations and disorders of peripheral joints. Knowledge of the details of malpractice claims should be implemented in educational programs and assist pediatric orthopedic surgeons to develop guidelines in order to improve patient safety and quality of care.

Whether chronic inflammation mirrored by high levels of systemic inflammatory markers such as high sensitive‐CRP (hs‐CRP) and white blood cell count (WBC) are associated with prostate cancer development remains unclear. In the Prostate Cancer Study throughout Life (PROCA‐life), a prospective population‐based cohort study, 7,356 men were included. Prediagnostic WBC and hs‐CRP were assessed from blood collected at study entry; 2,210 participants also had a second CRP measure during follow‐up. During a mean 11.8 years follow‐up, 509 men developed prostate cancer (mean age at diagnosis 71.7 years). Multivariable Cox proportional hazard regression models were used to study whether individual biomarkers (WBC, hs‐CRP), a combined score based on analyte tertiles (score range 2–6), or change in CRP were associated with risk and severity of prostate cancer. We observed a positive dose–response relationship between hs‐CRP and prostate cancer risk with a Hazard Ratio (HR) per mg/l of 1.3, 95% CI 1.00–1.07. Men with an increase in hs‐CRP between two measurements (Δhs‐CRP) of ≥1.00 mg/l had a 36% increased risk of prostate cancer (HR 1.36, 95% CI 1.02–1.82), compared to men with no change or decrease in hs‐CRP. Men with a systemic inflammatory score of 5 or 6 had a 68% higher risk of being diagnosed with metastatic disease (HR 1.68, 95% CI, 1.04–2.73) compared to men with lower scores. Our study supports that hs‐CRP including repeated measurements alone or in combination with WBC may be a useful inflammation‐related biomarker for prostate cancer risk and prognosis.

Reduced sexual function may have negative implications on health related quality of life among lymphoma survivors. A national cross-sectional study among long-term lymphoma survivors after high-dose therapy with autologous stem-cell transplantation auto-SCT treated during 1987–2008 was conducted in 2012–2014. The current study explored sexual functioning among these survivors. Sixty-six percent (n = 159) of eligible men with complete questionnaire data were included, median age was 55 years. The Brief Sexual Function Inventory (BSFI) was used to assess sexual function and sexual satisfaction, compared with age-matched controls. In addition, sexual problems were defined based on predetermined cutoff values for BSFI domain scores. Sexual drive and erections firm enough to have sexual intercourse were reported to be present only a few days or less last month among 30% and 41% of survivors, respectively. Sexual satisfaction was reported by 39% of survivors. The survivors had significantly lower scores on all BSFI domains and an increased risk of problems with sexual drive and erection compared with controls. In multivariable models, cardiovascular disease was significantly associated with worse erectile function, while age > 55 years, chronic fatigue, and physical inactivity were significantly associated with lower sexual functioning overall. Chronic fatigue and anxiety were related to lower sexual satisfaction.

Venous thromboembolism (VTE) is a frequent complication in patients with cancer. Homozygous carriers of the fibrinogen gamma gene (FGG) rs2066865 have a moderately increased risk of VTE, but the effect of the FGG variant in cancer is unknown. We aimed to investigate the effect of the FGG variant and active cancer on the risk of VTE. Cases with incident VTE (n=640) and a randomly selected age-weighted sub-cohort (n=3,734) were derived from a population-based cohort (the Tromsø study). Cox-regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for VTE according to categories of cancer and FGG. In those without cancer, homozygosity at the FGG variant was associated with a 70% (HR 1.7, 95% CI: 1.2–2.3) increased risk of VTE compared to non-carriers. Cancer patients homozygous for the FGG variant had a two-fold (HR 2.0, 95% CI: 1.1–3.6) higher risk of VTE than cancer patients without the variant. Moreover, the six-months cumulative incidence of VTE among cancer patients was 6.4% (95% CI: 3.5–11.6) in homozygous carriers of FGG and 3.1% (95% CI: 2.3–4.7) in those without risk alleles. A synergistic effect was observed between rs2066865 and active cancer on the risk of VTE (synergy index: 1.81, 95% CI: 1.02–3.21, attributable proportion: 0.43, 95% CI: 0.11–0.74). In conclusion, homozygosity at the FGG variant and active cancer yielded a synergistic effect on the risk of VTE. Copyright© 2020 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.

The aim of this study was to examine the associations between self-harm and suicidal behavior in indigenous Sami and non-Sami adolescents and mental health and social outcomes in young adulthood. Data were obtained by linking the Norwegian Patient Registry (2008–2012), the National Insurance Registry (2003–2013), and the Norwegian Arctic Adolescent Health Study, a school-based survey inviting all 10th grade students in North Norway (2003–2005). In total, 3987 (68%) of all 5877 invited participants consented to the registry linkage, of whom 9.2% were indigenous Sami. Multivariable logistic regression was used to explore the associations between self-harm only, suicidal ideation with and without self-harm, and suicide attempts in adolescence (≤16-year-old), and later mental health disorders, long-term medical, social welfare benefit receipt, or long-term unemployment in young adulthood. Self-harm and suicidal behavior in Sami and non-Sami adolescents were associated with increased risk of later mental health disorders, long-term welfare benefit receipt, and long-term unemployment. These associations were attenuated by adolescent psychosocial problems. No major differences between the indigenous Sami participants and their non-Sami peers were found. Young suicide attempters experienced the highest risk, with adolescent suicide attempts being significantly associated with all four adult outcomes after adjustment. Self-harm and suicidal behavior in adolescence are markers of mental health disorders and unfavorable social outcomes in young adulthood, mostly accounted for by adolescent psychosocial problems. In contrast to other indigenous peoples, no indigenous health disparities were found, indicating that the indigenous Sami adolescents were not worse off.

Gap junctions consist of arrays of intercellular channels that enable adjacent cells to communicate both electrically and metabolically. Gap junctions have a wide diversity of physiological functions, playing critical roles in both excitable and non-excitable tissues. Gap junction channels are formed by integral membrane proteins called connexins. Inherited or acquired alterations in connexins are associated with numerous diseases, including heart failure, neuropathologies, deafness, skin disorders, cataracts and cancer. Gap junctions are highly dynamic structures and by modulating the turnover rate of connexins, cells can rapidly alter the number of gap junction channels at the plasma membrane in response to extracellular or intracellular cues. Increasing evidence suggests that ubiquitination has important roles in the regulation of endoplasmic reticulum-associated degradation of connexins as well as in the modulation of gap junction endocytosis and post-endocytic sorting of connexins to lysosomes. In recent years, researchers have also started to provide insights into the physiological roles of connexin ubiquitination in specific tissue types. This review provides an overview of the advances made in understanding the roles of connexin ubiquitination in the regulation of gap junction intercellular communication and discusses the emerging physiological and pathophysiological implications of these processes.

The prometastatic stroma generated through tumor cells/host cells interaction is critical for metastatic growth. To elucidate the role of ICAM-1 on the crosstalk between tumor and primary liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), implicated in tumor adhesion and angiogenesis, we performed in vitro cocultures and an in vivo model of liver metastasis of colorectal cancer (CRC). ICAM-1 blockade in the LSECs decreased the adhesion and transmigration of tumor cells through an LSEC in vitro and vivo. Cocultures of C26 cells and LSECs contained higher amounts of IL-1 beta, IL-6, PGE-2, TNF-alpha and ICAM-1 than monocultures. C26 cells incubated with sICAM-1 secreted higher amounts of PGE-2, IL-6, VEGF, and MMPs, while enhanced the migration of LSECs and HSCs. HSCs cultures activated by media from C26 cells pretreated with sICAM-1 contained the largest amounts of VEGF and MMPs. C26 cell activation with sICAM-1 enhanced their metastasizing potential in vivo, while tumor LFA-1 blockade reduced tumor burden and LSECs and HSC-derived myofibroblasts recruitment. In vivo ICAM-1 silencing produced similar results. These findings uncover LSEC ICAM-1 as a mediator of the CRC metastatic cascade in the liver and identifies it as target for the inhibition of liver colonization and metastatic progression. This work has been supported by a predoctoral grant from the University of the Basque Country to the principal author and from the Department of Industry and Research of the Basque Government SAIOTEK S-PE12UN075 and S-PE11UN043 to BA, and IT-487-09 to EO.

Background To determine the serum levels of the lectin pathway proteins early in the disease course and 17 years after disease onset and to correlate the protein levels to markers of disease activity in participants from a population-based Nordic juvenile idiopathic arthritis (JIA) cohort. Additionally, to assess the predictive value of lectin pathway proteins with respect to remission status. Methods A population-based cohort study of consecutive cases of JIA with a disease onset from 1997 to 2000 from defined geographical areas of Finland, Sweden, Norway and Denmark with 17 years of follow-up was performed. Clinical characteristics were registered and H-ficolin, M-ficolin, MASP-1, MASP-3, MBL and CL-K1 levels in serum were analyzed. Results In total, 293 patients with JIA were included (mean age 23.7 ± 4.4 years; mean follow-up 17.2 ± 1.7 years). Concentrations of the lectin protein levels in serum were higher at baseline compared to the levels 17 years after disease onset (p ≤ 0.006, n = 164). At baseline, the highest level of M-ficolin was observed in systemic JIA. Further, high M-ficolin levels at baseline and at 17-year follow-up were correlated to high levels of ESR. In contrast, high MASP-1 and MASP-3 tended to correlate to low ESR. CL-K1 showed a negative correlation to JADAS71 at baseline. None of the protein levels had prognostic abilities for remission status 17 years after disease onset. Conclusion We hypothesize that increased serum M-ficolin levels are associated with higher disease activity in JIA and further, the results indicate that MASP-1, MASP-3 and CL-K1 are markers of inflammation.

This is the peer reviewed version of the following article: Småbrekke, B., Rinde, L., Evensen, L., Morelli, V., Hveem, K., Gabrielsen, M., ... Hansen, J. (2019). Impact of prothrombotic genotypes on the association between family history of myocardial infarction and venous thromboembolism. Journal of Thrombosis and Haemostasis, 17(8), 1363-1371., which has been published in final form at https://doi.org/10.1111/jth.14493 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Background: Family history of myocardial infarction (FHMI) is known to increase the risk of venous thromboembolism (VTE). Objectives: To investigate the effect of prothrombotic genotypes on the association between FHMI and VTE in a case‐cohort recruited from a general population. Methods: Cases with a first VTE (n = 1493) and a subcohort (n = 13 072) were sampled from the Tromsø study (1994‐2012) and the Nord‐Trøndelag health (HUNT) study (1995‐2008). The DNA samples were genotyped for rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11). Participants with missing information on risk alleles (n = 175), FHMI (n = 2769), and BMI (n = 52) were excluded. Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for VTE. To explore the role of prothrombotic genotypes for the association between FHMI and VTE, we (a) included the genotypes in the multivariable‐adjusted models and (b) assessed the joint effects between FHMI and genotypes on VTE risk. Results: The FHMI was associated with a 1.3‐fold increased risk of VTE (HR 1.32, 95% CI 1.16‐1.50) and 1.5‐fold increased risk of unprovoked VTE (HR 1.47, 95% CI 1.22‐1.78). The risk of VTE by FHMI did not alter after adjustment for the five genotypes. The combination of FHMI and the different prothrombotic genotypes did not result in an excess VTE risk (i.e. no biological interaction). Conclusions: Our findings suggest that the risk of VTE by FHMI is not explained by rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11). The combination of FHMI with prothrombotic genotypes had an additive effect on VTE risk.

Roar Dyrkorn,1 Harald Christian Langaas,2 Trude Giverhaug,3 Ketil Arne Espnes,1 Debra Rowett,4 Olav Spigset1,51Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway; 2Regional Medicines Information and Pharmacovigilance Centre (RELIS), Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway; 3Regional Medicines Information and Pharmacovigilance Centre (RELIS), University Hospital of North-norway, Tromsoe, North-Norway; 4Repatriation General Hospital, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia; 5Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, NorwayCorrespondence: Roar DyrkornDepartment of Clinical Pharmacology, St. Olav University Hospital, 7006 Trondheim, NorwayEmail roar.dyrkorn@stolav.noIntroduction: Academic detailing is an interactive educational outreach to prescribers to present unbiased, non-commercial, evidence-based information, mostly about medications, with the goal of improving patient care. Academic detailing in Norway is an approach for providing continuing medical education to general practitioners (GPs). The basis of academic detailing is a one-to-one discussion between a trained health professional (the academic detailer) and the GP at the GP’s workplace.Method: Our first campaign was named “Better use of non-steroidal anti-inflammatory drugs (NSAIDs)”, which aim was to reduce the use of diclofenac due to the risk of serious cardiovascular adverse events. At the same time we advised the GPs to use naproxen as the drug of choice if an NSAID was needed. We did a one-to-one intervention in two cities, where a trained academic detailer met the GP during office hours. A total of 247 GPs were invited to participate and 213 visits (86%) were completed. This article reviews the theoretical framework underlying the method and describes the development and implementation of academic detailing to GPs in Norway.Results: More than 90% the participating GPs considered academic detailing a suitable method for providing up-to-date evidence-based, manufacturer-independent information, and nearly all would most likely or probably welcome another visit. After the intervention there was a reduction of diclofenac prescribing of 16% and 18%, respectively, in the two cities.Conclusion: We consider that academic detailing is a suitable method to bring the best available evidence to the point at which care is delivered, to achieve the best for the patients. According to the Norwegian GPs’ evaluation, it is a key supplement to other methods of continuing medical education. To have maximum impact, it is important that academic detailing is practiced according to the consensus that has evolved in the USA and Australia.Keywords: academic detailing, educational outreach visits, general practitioners, general practice, quality improvement

Purpose - Few studies investigated roles of body mass index (BMI) on gastric cancer (GC) risk according to Helicobacter pylori infection status. This study was conducted to evaluate associations between BMI and GC risk with consideration of H. pylori infection information. Materials and Methods - We performed a case-cohort study (n=2,458) that consists of a subcohort, (n=2,193 including 67 GC incident cases) randomly selected from the Korean Multicenter Cancer Cohort (KMCC) and 265 incident GC cases outside of the subcohort. H. pylori infection was assessed using an immunoblot assay. GC risk according to BMI was evaluated by calculating hazard ratios (HRs) and their 95% confidence intervals (95% CIs) using weighted Cox hazard regression model. Results - Increased GC risk in lower BMI group (< 23 kg/m2) with marginal significance, (HR, 1.32; 95% CI, 0.98 to 1.77) compared to the reference group (BMI of 23-24.9 kg/m2) was observed. In the H. pylori non-infection, both lower (< 23 kg/m2) and higher BMI (≥ 25 kg/m2) showed non-significantly increased GC risk (HR, 10.82; 95% CI, 1.25 to 93.60 and HR, 11.33; 95% CI, 1.13 to 113.66, respectively). However, these U-shaped associations between BMI and GC risk were not observed in the group who had ever been infected by H. pylori. Conclusion - This study suggests the U-shaped associations between BMI and GC risk, especially in subjects who had never been infected by H. pylori.

This is a post-peer-review, pre-copyedit version of an article published in Community Mental Health Journal. The final authenticated version is available online at: https://doi.org/10.1007/s10597-019-00411-x. Accurate prediction of risk-states in Serious Mental Illnesses (SMIs) is critical for reducing their massive societal burden. Risk-state assessments are notably inaccurate. Recent innovations, including widely available and inexpensive mobile technologies for ambulatory “biobehavioral” data, can reshape risk assessment. To help understand and accelerate clinician involvement, we surveyed 90 multi-disciplinary clinicians serving SMI populations in various settings to evaluate how risk assessment is conducted and can improve. Clinicians reported considerable variability in conducting risk assessment, and few clinicians explicated their procedures beyond tying it to broader mental status examinations or interviews. Very few clinicians endorsed using currently-available standardized risk measures, and most reported low confidence in their utility. Clinicians also reported spending approximately half the time conducting individual risk assessments than optimally needed. When asked about improvement, virtually no clinicians acknowledged biobehavioral, objective technologies, or ambulatory recording. Overall, clinicians seemed unaware of meaningful ways to improve risk assessment.