Sykehuset i Vestfold

Diagnostic delay is common in pediatric inflammatory bowel disease (PIBD), and fecal calprotectin (FCP) is often limited by challenges with sample collection. Therefore, we aimed to identify and validate a blood-based diagnostic protein signature of PIBD. Proteins were analyzed using proximity extension assay in plasma samples from treatment-naïve pediatric patients in a Swedish inception cohort referred for suspected inflammatory bowel disease (IBD) and validated in an independent Norwegian population-based pediatric inception cohort. Diagnostic performance was estimated by the area under the curve (AUC) with 95% confidence intervals (CIs). The discovery cohort included 58 patients with PIBD and 36 symptomatic controls without evidence of IBD, while the validation cohort consisted of 79 patients with PIBD and 37 symptomatic controls. In total, 154 proteins were examined. Univariable analyses identified 26 differentially regulated proteins for PIBD versus symptomatic controls in the discovery cohort (q < 0.05), whereas 29 proteins were differentially regulated in the validation cohort. Using regularized logistic regression, we identified a diagnostic model of 31 proteins that differentiated PIBD from symptomatic controls in the discovery cohort (AUC = 0.83; 95% CI: 0.74-0.90). The protein signature was further reduced to a clinically relevant biomarker consisting of high-sensitivity C-reactive protein (hsCRP) and seven other proteins with diagnostic capacity (AUC = 0.85, 95% CI: 0.78-0.92) outperforming hsCRP in the validation cohort (p = 0.006). We identified and validated a blood-based protein signature for PIBD with superior diagnostic performance compared to hsCRP. Given the challenges of fecal sample collection, further assay development may enable integration of these biomarkers into diagnostic pathways for PIBD. ClinicalTrials.gov identifier: NCT02727959.

Antibiotic use in early childhood may alter the developing microbiome and has been proposed as a risk factor for inflammatory bowel disease (IBD). We conducted a systematic review to examine the association between childhood antibiotic use and subsequent risk of IBD. In a systematic literature search, we identified cohort and case-control studies reporting the association between antibiotic use (exposure age <1 to 17 years) and development of IBD. MEDLINE and EMBASE databases were searched from inception through December 31, 2024. Studies reporting a hazard ratio, odds ratio, or risk ratio (RR) were included. To account for heterogeneity, pooled estimates were calculated using the DerSimonian-Laird random-effects model. Estimates were adjusted for potential confounding as reported in the original studies. We identified 10 studies, of which 8 (n = 2783 cases) reported associations between childhood antibiotics and IBD risk. Additionally, 2 studies on Crohn's disease (CD) and 1 on ulcerative colitis were included in disease-specific analyses. In pooled analyses, antibiotic exposure compared with no exposure was associated with increased risk of IBD (RR, 1.42; 95% confidence interval [CI], 1.23-1.66), CD (RR, 1.59; 95% CI, 1.39-1.81), and ulcerative colitis (RR, 1.23; 95% CI, 1.08-1.40). Heterogeneity was low to moderate (I2 = 0%-35%), and funnel plots did not indicate publication bias (Egger's test, P = .12-.43). Adjustment for infections did not attenuate the association between childhood antibiotic exposure and IBD development. While causal interpretation should be cautious, childhood exposure to antibiotics was associated with an increased risk of later IBD, particularly for CD.

Background: Previous research has linked opioid use disorder (OUD) to neuronal reward systems and impulsivity. The aim of this study was to examine the influence of COMT rs4680 Val158Met polymorphism on impulsivity, hyperactivity and inattention (IHI) in patients with OUD. Methods: Open-label, cross-sectional cohort study was conducted involving individuals, 18 to 65 years, with OUD who either were included in opioid agonist treatment (OAT)—or same group of individuals who were awaiting induction on extended-release naltrexone (XR-NTX). Adult ADHD Self-Report Scale 18-item version was used to score IHI, and saliva samples were collected for genotyping (TaqMan assays). Logistic regression models were used to analyze the data. Results: The data of the entire cohort (n = 206) showed that carriers of one or two Val alleles had a negative association with IHI compared to Met/Met carriers (Val/Met OR = 0.43, p-value = 0.017, and Val/Val OR = 0.29, p-value = 0.005). Individuals included in OAT not waiting for XR-NTX (n = 120) exhibited the same pattern as observed in the entire cohort (Val/Met OR = 0.33, p-value = 0.019, and Val/Val OR = 0.18, p-value = 0.004), but not those who chose XR-NTX (Val/Met OR = 0.60, p-value = 0.353, and Val/Val OR = 0.47, p-value = 2.779). Conclusions: The present study revealed that individuals with OUD carrying the COMT rs4680 Val allele had lower IHI scores than Met/Met carriers. Hence, in individuals with OUD, the COMT rs4680 Met allele is associated with higher IHI symptom burden.

BackgroundCentral retinal artery occlusion can result in permanent vision loss. Effective treatment is lacking.MethodsWe conducted a phase 3, double-blind, double-dummy, randomized, controlled trial involving adults with acute, nonarteritic central retinal artery occlusion who had symptom onset within 4.5 hours before treatment. Patients were assigned, in a 1:1 ratio, to receive intravenous tenecteplase (at a dose of 0.25 mg per kilogram of body weight) and oral placebo or intravenous placebo and oral aspirin (at a dose of 300 mg). The primary end point was vision recovery, defined as a best corrected visual acuity (BCVA) in the affected eye at 30 days of up to 0.7 logMAR (logarithm of the minimum angle of resolution; equivalent to ≥20/100). Key secondary visual end points were a BCVA of up to 0.5 logMAR (equivalent to ≥20/63), mean improvement in BCVA, and perimetry score at 30 days. Key safety end points included symptomatic intracranial hemorrhage, major bleeding, and death.ResultsA total of 78 patients at 16 sites in six countries underwent randomization, with 40 assigned to receive tenecteplase and 38 to receive aspirin. At 30 days, 8 patients (20%) in the tenecteplase group and 9 patients (24%) in the aspirin group had vision recovery (risk difference, −3.7 percentage points; 95% confidence interval, −22.0 to 14.7; P=0.69). The outcomes with regard to the secondary visual end points did not differ substantially between the groups. There was a greater incidence of adverse events in the tenecteplase group, including one fatal intracranial hemorrhage.ConclusionsIntravenous tenecteplase administered within 4.5 hours after onset of central retinal artery occlusion did not result in significantly greater vision recovery at 30 days than oral aspirin but was associated with serious safety concerns. (Funded by Oslo University Hospital and others; TenCRAOS ClinicalTrials.gov number, NCT04526951; EU Clinical Trials number, 2024-517606-29-00.)

A positive surgical margin (PSM) after radical prostatectomy (RP) is considered an adverse surgical feature, but the clinical implications have been debated. Further motive to aim for negative margins (NSM) may be patient anxiety due to PSM, but studies on psychological consequences are lacking. We explored associations between psychological factors and PSM on a consecutive group of men after RP. Men with suspected prostate cancer were invited to a study on psychological factors. Patient reported outcome measurement questionnaires were collected before diagnosis, and at 6, 12 and 24 months from those who underwent RP. Multivariable mixed models and post hoc pairwise comparisons were used to explore associations between PSM and psychological outcomes. In total, 387 men had RP and 94 (24%) had PSM. General psychological outcomes were not associated with margin status. At 12 months, men with PSM considered their personal risk of recurrence 6% (30% vs. 24%) points higher and had clinical fear of recurrence (FoR) 14% (47% vs. 33%) more often than men with NSM. In adjusted and stratified analyses, men with pathological (p-)T2-stage and NSM had less FoR than the rest of the sample. In pT3-disease, PSM had no additional impact on FoR. A limitation was the small size of the pT2 group with PSM and the lack of information on how patients were informed. After RP, PSM was associated with higher FoR, particularly in men with pT2-cancer. Improved counselling and further research into causes and mitigation of FoR, is warranted.

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.

BackgroundImmersive technologies such as virtual reality (VR) that has been developed the recent years, are now increasingly accessible and offers new opportunities for VR environments combined with games that may enhance physical activity. However, these games may require adaptation and further customization for use among older users. In this pilot study, we investigate the experiences of older adults using a head-mounted VR exercise game that was developed in close collaboration with end users.MethodsWe included ten community-dwelling older adults aged 65 years and older who undertook six VR exercise sessions across a two-week period, each session lasting 15 min. Descriptive information included age, gender, mobility (Timed Up and Go test, TUG), and gait speed (10 m walk test), and daily steps from ankle-worn accelerometers. Semi-structured individual interviews were conducted, transcribed verbatim and analyzed by use of reflexive thematic analysis.ResultsWe included four men and six women, age range from 66 to 77 years, with an average gait speed of 1.4 m/sec and an average TUG-time of 7.6 s. Their average activity levels were close to 4200 steps per day. After the trial period, participants’ experiences were that VR is a new and exciting development. They found VR to be more of a game than exercise, and they suggested integrating more challenging activities, physical movement and social engagement to enhance the exercise part of the game. They did not feel that the game facilitated any more physical activity in their daily lives.Discussion/conclusionVR is a promising tool that older adults in this trial enjoyed, but the game was not physically demanding enough for the participants. Future adaptations should include more challenges. Game development should focus on tasks that keep players interested and engaged over longer times, without jeopardizing safety.

ABSTRACTThe aim of this systematic literature review (SLR) of reviews was to update the evidence, established in a 2017 SLR, on the impact of obesity and weight loss by various interventions on health‐related quality of life (HRQoL). In total, eight SLRs and/or meta‐analyses published since 2017 were identified. The results consistently demonstrated a negative association between obesity and HRQoL, with some evidence suggesting poorer HRQoL in people with adverse metabolic profiles. In addition to substantial weight or body mass index reduction, metabolic and bariatric surgery (MBS) or endoscopic bariatric therapies resulted in significant and clinically relevant HRQoL improvements, with pronounced and persistent effects on the physical components in particular. HRQoL typically improved within 1–2 years after MBS and stabilised or deteriorated while remaining above baseline in subsequent years, likely due to weight regain. Evidence for the benefits of exercise interventions on HRQoL was inconclusive. Notably, no SLRs on anti‐obesity medications were identified, limiting conclusions on this emerging treatment area. This updated SLR expands on previous findings from the 2017 SLR, providing additional insights into underexplored areas, including the role of metabolic profiles in HRQoL and trends of HRQoL after MBS. Evidence synthesis remains challenging due to heterogeneity in HRQoL measurements used in this field.

Abstract Background: Depression in older adults is common in general practice, but the optimal approach for identification and treatment is not entirely clear. Aim: To explore physicians’ experiences with a structured collaboration model based on joint consultations between patients, general practitioners (GPs) and geriatric psychiatrists for treating depression in patients aged 65 and older. Methods: A focus group study was conducted with three groups, totalling 13 physicians (10 GPs and 3 psychiatrists) who had participated in the collaborative model and recently had participated in a cluster randomised intervention study. The analysis was performed using the Systematic Text Condensation method. Results: Five main themes emerged from the analysis: 1) Challenges in diagnostics, 2) Advantages of the model, 3) Feasibility, 4) Overdiagnosis and overtreatment, and 5) Adjustments to the model. The GPs identified a challenge in patients’ strong focus on somatic symptoms, often reinforced by GPs due to time constraints and overshadowing depressive symptoms. Both GPs and psychiatrists recognized the structured collaborative model, which strengthened the GP-patient relationship and enabled mutual learning. The GPs’ presence during joint consultations was crucial for patient participation. The model filled a gap where GPs lacked effective interventions and was praised by psychiatrists as highly cost-effective. All participants supported broader implementation of joint consultations in clinical practice. Conclusion: The GPs' enthusiasm for this collaborative approach indicates an unmet need in the treatment of older patients with depression. By strengthening both the doctor-patient relationship and interdisciplinary collaboration between GPs and psychiatrists in a cost-effective manner, the use of such joint consultations should be further investigated.