Diakonhjemmet Hospital

Schizophrenia patho-etiology may involve endothelial inflammation and blood-brain barrier (BBB) dysregulation with cellular adhesion molecules (CAMs) as important mediators. CAMs are essential for cellular integrity but can show increased levels in inflammation. Cognitive dysfunction precedes and exists independently of psychotic symptoms in schizophrenia patients. CAMs could impact cognition through influence on BBB integrity. To gain insights into disease mechanisms and potential therapeutic targets, we explored the relationship between CAMs protein levels and neurocognitive tests in schizophrenia-spectrum disorders in the BeSt InTro study. Seventy-one in- and out-patients underwent CAMs measurements and neuropsychological testing on a minimum of one time point: baseline, 6, 26, or 52weeks. Cognitive domains included working memory, processing speed, verbal abilities, executive functions, and overall cognition. CAMs analyzed were neural CAMs: junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD); vascular CAMs: intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), and platelet (P)-selectin from fasting blood samples. Linear mixed effects models, adjusted for age, sex, body mass index, smoking, education, and drug naivety, estimated CAMs effect on cognitive outcome measures. N-CAD levels correlated positively with overall cognition (p=0.002), working memory (p=0.034), and executive functions (p=0.0011). ICAM-1 levels correlated positively with overall cognition (p=0.037). Conversely, JAM-A levels correlated negatively with executive functions (p=0.021). Associations between CAMs (N-CAD, ICAM-1, JAM-A) and neurocognitive tests suggest CAMs may impact cognition in schizophrenia. Contrary to our hypothesis, most associations between CAMs levels and cognitive tests were positive. Future research on mechanisms is mandatory.

Brain network architecture is anticipated to influence future grey matter loss in individuals at Clinical High Risk (CHR) for psychosis. However, existing studies on grey matter structural network properties in CHR are scarce and constrained by small sample sizes. Here, we examined network topology differences comparing a) CHR versus healthy controls (HC); b) CHR who transitioned to psychosis (CHR-T) versus those who did not (CHR-NT); and c) different subsyndromes. We included structural scans from 1842 CHR individuals and 1417 HC individuals from 31 sites within the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. At the global level, CHR individuals exhibited lower structural covariance (q < 0.001; Cohen's d = 0.164) and less optimal structural network configuration than HC (lower global efficiency and clustering coefficient, d = 0.100,0.087, qs <= 0.027). Though no global difference between CHR-T and CHR-NT, network distinctiveness of the frontal and temporal surface area networks was higher in CHR-T than CHR-NT (d = 0.223,0.237) and HC (d = 0.208,0.219) (qs < 0.001). Network distinctiveness of the frontal cortical thickness network was lower in CHR-T (d = 0.218, q < 0.001) than CHR-NT and HC (d = 0.165, q < 0.001). Importantly, higher network distinctiveness was associated with worse positive symptoms in CHR-NT (frontal surface area, q = 0.008, R2 = 0.013) and at trend with worse negative symptoms in CHR-T (frontal thickness, q = 0.063, R2 = 0.049). Further, the brief intermittent psychotic syndrome subgroup showed more severe network alterations. Together, brain structural networks inform symptoms and the risk of transition to psychosis in CHR individuals.

Ethyl glucuronide (EtG) and ethyl sulphate (EtS) are non-oxidative metabolites of ethanol, valuable as biomarkers of alcohol consumption in forensic and clinical contexts. This study aims to calculate the elimination half-lives (t₁/₂) of EtG and EtS in apprehended drivers based on two consecutive blood samples, enhancing the reliability of forensic alcohol consumption assessments. Data was extracted from a database including apprehended drivers in Norway from 2019 to 2024. The study included suspected drunk drivers in which ethanol, EtG and EtS were detected in two consecutive blood samples, drawn at least 20 min apart. In cases where the blood alcohol concentration (BAC) was at or below 0.20 g/kg, in at least one sample, the t₁/₂ was estimated using both empirical and Bayesian statistical methods. In 670 cases, ethanol, EtG and EtS were detected in two consecutive samples. In 20 of these, the BAC was below 0.20 g/kg. In these 20 cases, the median time between blood samples was 0.46 h. The empirical calculations of t₁/₂ for cases with declining EtG and EtS concentrations yielded a median of 2.6 h for EtG and 2.4 h for EtS. A strong positive correlation was found between empirical t₁/₂ of EtG and EtS (rs=0.81, p < 0.001). The t₁/₂ values for EtG and EtS in apprehended drivers are comparable to those reported in experimental studies. The findings contribute to forensic alcohol assessments and legal expert reports. Additional research is needed to investigate EtG and EtS elimination kinetics in real-life impaired driving scenarios.

Acute kidney injury (AKI) is a key complication of rhabdomyolysis. Creatine kinase (CK), the standard muscle injury biomarker, has limited predictive value. Myoglobin may be more accurate but has its limitations. The myoglobin-to-CK ratio may be a stronger predictor but lacks prospective validation. We aimed to validate this ratio using admission values, compare it with CK and myoglobin, and identify thresholds for early AKI risk stratification. Prospective multicentre cohort study across four hospitals in Oslo and Akershus, Norway (2019-2022). All adults with CK ≥5000 U/L and/or myoglobin ≥1000 ng/mL at emergency department presentation or within 72 hours thereafter were eligible, irrespective of admission. Primary outcome was AKI. Predictive performance of CK, myoglobin and the myoglobin-to-CK ratio was assessed using logistic regression and receiver operating characteristic (ROC) analysis. In the 310 included patients, 108 (35%) developed AKI. In ROC analysis the myoglobin-to-CK ratio was the strongest predictor of AKI on admission (area under the curve (AUC) 0.84, 95% CI 0.79 to 0.89), followed by myoglobin (AUC 0.73, 95% CI 0.67 to 0.79); CK was a weak predictor (AUC 0.31, 95% CI 0.25 to 0.37). In quartile analysis, 72% of patients in the highest ratio quartile developed AKI, with a ratio ≥0.20 indicating risk. For myoglobin, 65% in the highest quartile developed AKI, with values ≥6372 ng/mL indicating risk. ROC analysis identified optimised cut-offs of 0.48 for the ratio (sensitivity/specificity 79/82%) and 4489 ng/mL for myoglobin (61/76%). Combined, these cut-offs increased sensitivity and negative predictive value to 89% (95% CI 81.3% to 94.4%) and 92% (95% CI 86.2% to 96.0%), respectively, suggesting potential for identification of both high-risk and low-risk patients at admission. The myoglobin-to-CK ratio was the strongest early predictor of AKI. Combined with myoglobin ≥4489 ng/mL, a ratio ≥0.48 identified 89% of AKI cases and ruled out 92% of non-AKI cases, suggesting a potential admission-based tool for early AKI risk stratification in rhabdomyolysis. NCT04118608.

ObjectivesTo explore differences in health-related benefit status over 3 years, focusing on patterns of sick leave, work assessment allowance and disability benefits, between people who underwent rehabilitation and a matched control group.DesignProspective longitudinal multicentre cohort study using registry data over three consecutive years.SettingSecondary specialist rehabilitation services at 17 institutions across Norway.ParticipantsPatients (n=2710), 42% with rheumatic and musculoskeletal diseases, aged 18–65 years referred for multidisciplinary rehabilitation at one of the participating institutions. They were propensity score matched with 37 760 controls from the national sick leave registry, based on sociodemographic factors and health-related benefit status.InterventionMultidisciplinary rehabilitation programmes, commonly lasting 3 weeks (range: 1 week to 6 months), tailored to individual needs.Primary outcome measuresDays on health-related benefits (sick leave, work assessment allowance (WAA) and disability benefits) were quantified as lost workdays per month. Differences between groups were analysed using Generalised Estimating Equations across three consecutive years: the year before rehabilitation, the rehabilitation year and the year after rehabilitation.ResultsThe rehabilitation group had more days on health-related benefits per month than controls throughout the observation period. During the rehabilitation year, they had on average 1.7 more days on sick leave (95 % CI 1.3 to 1.9), 2.3 more WAA days (95% CI 1.9 to 2.7) and 0.2 more days on disability benefits (95% CI 0.1 to 0.3). In the year after rehabilitation, they had 0.6 fewer days on sick leave (95% CI −0.8 to −0.3), but 3.7 more days on WAA (95% CI 3.1 to 4.2) and 0.6 more days on disability benefits (95% CI 0.4 to 0.8). Patterns were similar for the subgroup with rheumatic and musculoskeletal diseases.ConclusionsPeople undergoing rehabilitation had more days on health-related benefits and a greater increase in long-term benefits, even after matching, indicating a higher disease and support burden than controls. Tailoring interventions and health-related benefits is an essential aspect of rehabilitation for people with complex work participation needs. Future research should include longer observation periods to explore long-term outcomes of rehabilitation.Trail registration numberNCT03764982

Fatigue is common in Crohn's disease (CD) and ulcerative colitis (UC), but the pathogenesis remains poorly understood. This study aimed to assess changes in fatigue prevalence during the first year after diagnosis and examine the association between disease course and substantial fatigue (SF) at the 1-year follow-up. Adults with newly diagnosed CD or UC were recruited from the population-based IBSEN III cohort. Fatigue was assessed at diagnosis and the 1-year follow-up using the Fatigue Questionnaire. Associations between SF at the 1-year follow-up and disease-related factors were quantified using multivariate logistic regression adjusted for sex, age and comorbidities. In total, 596 patients were included (CD: 196, UC: 400). SF was present at both baseline and after one year of disease for 46.9% (n = 92/196) and 40.5% (n = 162/400) of patients with CD and UC, respectively. In CD, development of endoscopically non-passable stricture and/or surgically treated stricture within first year of disease (OR = 4.52, 95%CI [1.61;12.68]), self-reported flares since diagnosis (OR = 2.55, 95%CI [1.26;5.16]), female sex (OR = 3.12, 95%CI [1.53;6.37]) and comorbidities (OR = 4.05, 95%CI [1.89;8.69]) were independently associated with SF at the 1-year follow-up. In UC, SF was associated with current biological treatment (OR = 5.14, 95%CI [1.56;16.96]), increasing Mayo endoscopic score at the 1-year follow-up (OR = 1.54, 95%CI [1.01;2.35]), self-reported flares since diagnosis (OR = 2.66, 95%CI [1.24;5.72]) and female sex (OR = 2.20, 95%CI [1.06;4.57]). Fatigue frequently persists through the first year after IBD diagnosis. Clinical factors reflecting a more severe disease course were associated with SF one year after diagnosis in both CD and UC.

ObjectiveProactive therapeutic drug monitoring (pTDM) intends to optimise tumour necrosis factor (TNF) inhibitor treatment through regular assessment of drug and antidrug antibody levels, enabling individualised dosing. However, health economic evidence for this strategy is limited. This study aims to evaluate the health benefits and costs of pTDM with infliximab compared with standard therapy.MethodsBased on the 52-week randomised, controlled, open-label, multicentre Norwegian Drug Monitoring trial (NOR-DRUM) B trial, we estimated the cost-effectiveness of pTDM compared with standard infliximab maintenance therapy in patients with six different immune-mediated inflammatory diseases. For each patient (n=454), we estimated the 12-month healthcare costs, including pharmaceuticals, biochemical tests and other types of resource use. Reported in 2024 Euros, unit costs were based on market prices, diagnosis-related group cost weights and reimbursement schedules. We evaluated health outcomes with quality-adjusted life-years (QALYs), using the EuroQol five-dimension, three-level questionnaire (EQ-5D-3L) and Short Form six-dimension health utility measure (SF-6D). Indicator of cost-effectiveness was the incremental cost-effectiveness ratio, expressed as Euros/QALY, compared with an assumed cost-effectiveness threshold value of €23 755. We assessed sampling uncertainty using the non-parametric bootstrap.ResultsThe mean 1-year cost per patient in the pTDM group was lower than in the standard therapy group, with a difference of €592 (95% CI −1304 to 107), while the QALYs based on EQ-5D-3L were 0.0018 higher (95% CI −0.0126 to 0.0165). Based on the bootstrap results, pTDM has a probability of 95% of being cost-effective. In explorative subgroup analyses, pTDM appeared cost-effective for some, but not all diagnoses.ConclusionpTDM is very likely a cost-effective treatment strategy for patients with immune-mediated inflammatory diseases on infliximab maintenance therapy.Trial registration numberNCT03074656.

The role of estradiol in depression and Alzheimer’s disease – brain disorders that disproportionately affect females – is debated. Results from observational studies are inconsistent and limited by confounding and reverse causation. To overcome these limitations, we perform two-sample Mendelian randomization. We run genome-wide association studies on sex-specific brain age gap, a proxy of brain health, and female-specific estradiol levels using data from the UK Biobank. We test for causal links between genetically-predicted factors related to estradiol exposure (estradiol levels in pre- and postmenopausal samples, reproductive span, age at menarche, age at menopause, number of childbirths) and brain age gap, Alzheimer’s disease and depression as outcomes. We replicate our analyses on estradiol levels in males. Here, we find no significant associations between estradiol exposure and brain health across samples and robust methods, indicating an absence of constant causal effects and suggesting that hormonal fluctuations may drive links between estradiol and brain health.

Research on mental health has traditionally separated the study of ill-being, including clinically defined mental and behavioural disorders and subthreshold problems, from the study of well-being, which encompasses factors such as life satisfaction and positive affect. Although previous reviews of studies primarily using self-report scales indicate that ill-being and well-being are distinct yet interconnected constructs, a deeper examination of their relationship is lacking. In this Perspective, we synthesize genetic, biological, developmental, psychosocial, societal, cultural and clinical research on ill-being and well-being. Our review reveals substantial genetic overlap and similar biological underpinnings for ill-being and well-being. By contrast, environmental factors and societal changes often exert divergent influences. We propose a differentiated multidisciplinary framework in which the shared and unique determinants, predictors, mechanisms and consequences of mental ill-being and well-being vary across levels of analysis, offering a more nuanced understanding of the interconnections.