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Efficacy and Safety of CT-P13 in Inflammatory Bowel Disease after Switching from Originator Infliximab: Exploratory Analyses from the NOR-SWITCH Main and Extension Trials
Get PDFBackground: The NOR-SWITCH main and extension trials demonstrated that switching from originator to biosimilar infliximab (CT-P13) is efficacious and safe across six diseases. However, a subgroup analysis of Crohn's disease (CD) in the main trial displayed a close to significant difference favouring originator infliximab, and more scientific data have therefore been requested. Objective: The aim was to assess treatment efficacy, safety, and immunogenicity in an explorative subgroup analysis in CD and ulcerative colitis (UC) in the NOR-SWITCH trials. Patients and methods: The 52-week, randomised, non-inferiority, double-blind, multicentre, phase 4 NOR-SWITCH study was followed by a 26-week open extension trial where all patients received treatment with CT-P13. Treatment efficacy, safety, and immunogenicity in CD and UC were assessed throughout the 78-week study period. Results: The main and extension trials included 155 and 93 patients with CD and 93 and 80 patients with UC, respectively. Demographic and baseline characteristics were comparable in both treatment arms within patient groups. There were no differences in the main and extension trials regarding changes in activity indices, C-reactive protein, faecal calprotectin, patient's and physician's global assessment of disease activity and patient-reported outcome measures in CD and UC. Moreover, comparable results were also demonstrated for trough serum levels, presence of anti-drug antibodies, and reported adverse events. Conclusion: Efficacy, safety, and immunogenicity of both the originator and biosimilar infliximab were comparable in CD and UC in the NOR-SWITCH main and extension trials. These explorative subgroup analyses confirm that there are no significant concerns related to switching from originator infliximab to CT-P13 in CD and UC.Open Access funding provided by Akershus University Hospital (AHUS). This work was supported by the Norwegian Ministry of
Health and Care Services.publishedVersio
Do direct oral anticoagulants (DOACs) cause delayed surgery, longer length of hospital stay, and poorer outcome for hip fracture patients?
Get PDFPurpose: The perioperative consequences of direct oral anticoagulants (DOACs) in hip fracture patients are not sufficiently investigated. The primary aim of this study was to determine whether DOAC-users have delayed surgery compared to non-users. Secondarily, we studied whether length of hospital stay, mortality, reoperations and bleeding complications were influenced by the use of DOAC.
Methods: The medical records of 314 patients operated for a hip fracture between 2016 and 2017 in a single trauma center were assessed. Patients aged < 60 and patients using other forms of anticoagulation than DOACs were excluded. Patients were followed from admission to 6 months postoperatively. Surgical delay was defined as time from admission to surgery. Secondary outcomes included length of hospital stay, transfusion rates, perioperative bleeding loss, postoperative wound ooze, mortality and risk of reoperation. The use of general versus neuraxial anaesthesia was registered. Continuous outcomes were analysed using Students t test, while categorical outcomes were expressed by Odds ratios.
Results: 47 hip fracture patients (15%) were using DOACs. No difference in surgical delay (29 vs 26 h, p = 0.26) or length of hospital stay (6.6 vs 6.1 days, p = 0.34) were found between DOAC-users and non-users. DOAC-users operated with neuraxial anaesthesia had longer surgical delay compared to DOAC-users operated with general anaesthesia (35 h vs 22 h, p < 0.001). Perioperative blood loss, transfusion rate, risk of bleeding complications and mortality were similar between groups.
Conclusion: Hip fracture patients using DOAC did not have increased surgical delay, length of stay or risk of reported bleeding complications than patients without anticoagulation prior to surgery. The increased surgical delay found for DOAC-users operated with neuraxial anaesthesia should be interpreted with caution.publishedVersio
Itch and Mental Health in Dermatological Patients across Europe: A Cross-Sectional Study in 13 Countries
Get PDFItch is a highly prevalent and multidimensional symptom. We aimed to analyze the association between itch and mental health in dermatological patients. This multicenter study is observational and cross-sectional and was conducted in dermatological clinics across 13 European countries. A total of 3,530 patients and 1,094 healthy controls were included. Patients were examined clinically. Outcome measures were itch (presence, chronicity, and intensity), the Hospital Anxiety and Depression Scale, EQ-5D visual analogue scale, sociodemographics, suicidal ideation, and stress (negative life events and economic difficulties). Ethical approval was obtained. Results showed significant association between the presence of itch in patients and clinical depression (odds ratio, 1.53; 95% confidence interval, 1.15-2.02), suicidal ideation (odds ratio, 1.27; 95% confidence interval, 1.01-1.60), and economic difficulties (odds ratio, 1.24; 95% confidence interval, 1.10-1.50). The mean score of reported generic health status assessed by the EQ-5D visual analogue scale was 65.9 (standard deviation = 20.1) in patients with itch, compared with 74.7 (standard deviation = 18.0) in patients without itch (P < 0.001) and 74.9 (standard deviation = 15.7) in controls with itch compared with 82.9 (standard deviation = 15.6) in controls without itch (P < 0.001). Itch contributes substantially to the psychological disease burden in dermatological patients, and the management of patients should include access to multidisciplinary care.publishedVersio
PS-DeVCEM: Pathology-sensitive deep learning model for video capsule endoscopy based on weakly labeled data
No full textWe propose a novel pathology-sensitive deep learning model (PS-DeVCEM) for frame-level anomaly detection and multi-label classification of different colon diseases in video capsule endoscopy (VCE) data. Our proposed model is capable of coping with the key challenge of colon apparent heterogeneity caused by several types of diseases. Our model is driven by attention-based deep multiple instance learning and is trained end-to-end on weakly labeled data using video labels instead of detailed frame-by-frame annotation. This makes it a cost-effective approach for the analysis of large capsule video endoscopy repositories. Other advantages of our proposed model include its capability to localize gastrointestinal anomalies in the temporal domain within the video frames, and its generality, in the sense that abnormal frame detection is based on automatically derived image features. The spatial and temporal features are obtained through ResNet50 and residual Long short-term memory (residual LSTM) blocks, respectively. Additionally, the learned temporal attention module provides the importance of each frame to the final label prediction. Moreover, we developed a self-supervision method to maximize the distance between classes of pathologies. We demonstrate through qualitative and quantitative experiments that our proposed weakly supervised learning model gives a superior precision and F1-score reaching, 61.6% and 55.1%, as compared to three state-of-the-art video analysis methods respectively. We also show our model’s ability to temporally localize frames with pathologies, without frame annotation information during training. Furthermore, we collected and annotated the first and largest VCE dataset with only video labels. The dataset contains 455 short video segments with 28,304 frames and 14 classes of colorectal diseases and artifacts. Dataset and code supporting this publication will be made available on our home page.publishedVersio
Sulfhydryl groups as targets of mercury toxicity
Get PDFThe present study addresses existing data on the affinity and conjugation of sulfhydryl (thiol; -SH) groups of low- and high-molecular-weight biological ligands with mercury (Hg). The consequences of these interactions with special emphasis on pathways of Hg toxicity are highlighted. Cysteine (Cys) is considered the primary target of Hg, and link its sensitivity with thiol groups and cellular damage. In vivo, Hg complexes play a key role in Hg metabolism. Due to the increased affinity of Hg to SH groups in Cys residues, glutathione (GSH) is reactive. The geometry of Hg(II) glutathionates is less understood than that with Cys. Both Cys and GSH Hg-conjugates are important in Hg transport. The binding of Hg to Cys mediates multiple toxic effects of Hg, especially inhibitory effects on enzymes and other proteins that contain free Cys residues. In blood plasma, albumin is the main Hg-binding (Hg2+, CH3Hg+, C2H5Hg+, C6H5Hg+) protein. At the Cys34 residue, Hg2+ binds to albumin, whereas other metals likely are bound at the N-terminal site and multi-metal binding sites. In addition to albumin, Hg binds to multiple Cys-containing enzymes (including manganese-superoxide dismutase (Mn-SOD), arginase I, sorbitol dehydrogenase, and δ-aminolevulinate dehydratase, etc.) involved in multiple processes. The affinity of Hg for thiol groups may also underlie the pathways of Hg toxicity. In particular, Hg-SH may contribute to apoptosis modulation by interfering with Akt/CREB, Keap1/Nrf2, NF-κB, and mitochondrial pathways. Mercury-induced oxidative stress may ensue from Cys-Hg binding and inhibition of Mn-SOD (Cys196), thioredoxin reductase (TrxR) (Cys497) activity, as well as limiting GSH (GS-HgCH3) and Trx (Cys32, 35, 62, 65, 73) availability. Moreover, Hg-thiol interaction also is crucial in the neurotoxicity of Hg by modulating the cytoskeleton and neuronal receptors, to name a few. However, existing data on the role of Hg-SH binding in the Hg toxicity remains poorly defined. Therefore, more research is needed to understand better the role of Hg-thiol binding in the molecular pathways of Hg toxicology and the critical role of thiols to counteract negative effects of Hg overload. Keywords: Apoptosis; Conjugates; Cysteine; Mercury; S-mercuration.R01 ES007331/ES/NIEHS NIH HHS/United States
R01 ES010563/ES/NIEHS NIH HHS/United States
R01 ES020852/ES/NIEHS NIH HHS/United StatesacceptedVersio
TECLA—an innovative technical approach for prostate cancer registries
Get PDFObjective: To present a code-driven, electronic database for patients TrEated with robotic-assisted radiCaL prostAtectomy (TECLA), developed at Innlandet Hospital (IH), Trust, Norway, for research, local quality control and to deliver data to the National Cancer Registry of Norway (CRN). Clinical data are directly extracted from the structured documentation in the electronic medical record (EMR). Materials and methods: The urological department at IH treats about 200 patients with robotic-assisted radical prostatectomy (RARP) annually. All consenting patients registered with the procedure code for RARP are included in TECLA. Clinical data are obtained automatically from the EMR, by structured forms. Patient-reported outcome and experience measures (PROMs and PREMs) are filled in by the patients on an iPad or a smartphone. Results: The basic construct of TECLA is presented. From August 2017 to June 2018, 200 men were treated with RARP, of which 182 (91%) provided consent for inclusion in the register. Of these, 97% completed the PROM survey before treatment and 91% at 3 months follow-up. PREMs were completed by 78%. All clinical variables for the hospital stay and for the 6-week follow-up were more than 95% complete. Conclusion: This entirely electronic surgical quality register is easy to use, both for patients and clinicians, and has a high capture rate. The data collection is linked to the clinicians’ workflow, without double data entry, so entering data does not add any extra work. The register design can be used by other hospitals for various surgical procedures.acceptedVersio
Trauma in childhood and adolescence and impaired executive functions are associated with uncertain reflective functioning in mothers with substance use disorder
Get PDFAims: Impairments in reflective functioning are known to have adverse effects on the ability to display sensitive parenting as a caregiver. Several factors are associated with impairments in reflective functioning, such as impaired executive functioning and experienced trauma. We investigated how these factors contribute to an impaired reflective functioning style, such as pathological certain or uncertain reflective functioning. Extreme scores on these two subscales reflect two kinds of impairments in reflective functioning. We assessed executive functions, reflective functioning, and trauma in 43 mothers diagnosed with substance use disorders (SUD). Methods: Certain or uncertain reflective functioning were assessed using the Reflective Functioning Questionnaire 8 (RFQ-8). Executive functions and trauma were assessed by administering various questionnaires, interviews and neuropsychological tests. Results: High uncertain reflective functioning was more than six times as common (odds ratio) in mothers reporting high amounts of trauma in childhood and adolescence compared with mothers reporting low amounts of trauma. Impaired executive functions were also significantly associated with high uncertain reflective functioning. Certain reflective functioning did, however, not show any significant associations. Conclusion: When the SUD mothers give information about relational trauma in childhood and adolescence, it might therefore be worth investigating and addressing the potential tendency to have an uncertain reflective functioning style.publishedVersio
The feasibility of the Ages and Stages Questionnaire for the assessment of child development in a community setting in Nepal
Get PDFBackground: The Ages and Stages Questionnaire Third Edition (ASQ-3) may be a feasible and cost-effective tool to screen children's development in resource poor settings. We have assessed the feasibility of the ASQ-3 "home procedure" when conducted by fieldworkers in a community-based nutritional interventional trial on early child development in Nepal.
Method: Six hundred children aged 6-11 months at risk of stunting were assessed by trained fieldworkers in their homes by the ASQ-3. Three fieldworkers performed standardization exercises and were double scored with a gold standard during the study period. Intraclass correlations (ICCs) were calculated to measure the interrater agreement. The internal consistency was expressed by standardized Cronbach's alphas. The association between total ASQ score and gestation, low birth weight, and stunted children is presented to give an estimate of the construct validity of the tool.
Result: Mean scores of the 600 Nepalese children were consistently lower than in the American norm sample. The ICCs from the standardization exercises were initially good to excellent but declined throughout the study period. The standardized alphas for the total score in the different age groups indicate good internal consistency but varied in the subscales. Children who were preterm, children with low birth weight, and children who were stunted scored substantially lower on the total ASQ score than those who were not.
Conclusion: Although the ASQ-3 "home procedure" is low at cost and easily accessible in a Nepalese context, the tool requires rigorous and stringent training to achieve acceptable interrater agreement. Further adjustment is required to achieve satisfactory internal consistency.GC Rieber Funds
Thrasher Research Fund. Grant Number: 11512acceptedVersio
Reproducibility of semiautomated body composition segmentation of abdominal computed tomography: a multiobserver study
Get PDFBackground: Segmentation of computed tomography (CT) images provides quantitative data on body tissue composition, which may greatly impact the development and progression of diseases such as type 2 diabetes mellitus and cancer. We aimed to evaluate the inter- and intraobserver variation of semiautomated segmentation, to assess whether multiple observers may interchangeably perform this task.
Methods: Anonymised, unenhanced, single mid-abdominal CT images were acquired from 132 subjects from two previous studies. Semiautomated segmentation was performed using a proprietary software package. Abdominal muscle compartment (AMC), inter- and intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were identified according to pre-established attenuation ranges. The segmentation was performed by four observers: an oncology resident with extensive training and three radiographers with a 2-week training programme. To assess interobserver variation, segmentation of each CT image was performed individually by two or more observers. To assess intraobserver variation, three of the observers did repeated segmentations of the images. The distribution of variation between subjects, observers and random noise was estimated by a mixed effects model. Inter- and intraobserver correlation was assessed by intraclass correlation coefficient (ICC).
Results: For all four tissue compartments, the observer variations were far lower than random noise by factors ranging from 1.6 to 3.6 and those between subjects by factors ranging from 7.3 to 186.1. All interobserver ICC was ≥ 0.938, and all intraobserver ICC was ≥ 0.996.
Conclusions: Body composition segmentation showed a very low level of operator dependability. Multiple observers may interchangeably perform this task with highly reproducible results.The study received no external funding and was carried out with the
resources of the author affiliated institutions.publishedVersio
A family‐oriented intervention programme to curtail obesity from five years of age had no effect over no intervention
Get PDFAim: To examine the effect of a family-oriented multidisciplinary intervention pro-gramme to curtail weight increase in young children with obesity.Methods: Children who weighed more than one kilogram above the 97th percentile for height at the preschool assessment in Oppland County, Norway, were identified. Parents residing in one part of the county were invited to participate in a group-based three-year intervention programme while the rest had no interventions. Body mass index (BMI) and family characteristics at entry and measurements at birth were explanatory variables, and change in BMI standard deviation score (SDS) the outcome measure. For the intervention group, outcome was also related to skinfold thicknesses, waist-to-height ratio and physical ability.Results: The programme was completed by 31 families in the intervention and 33 in the control group. At entry, the respective median (interquartile) age was 5.83 (0.36) and 5.74 (0.66) years, and the BMI SDS 2.35 (1.06) and 1.95 (0.49), P = .012. The median decrease in BMI SDS was 0.19 in both groups. The decline increased with increasing BMI SDS at entry, but irrespective of group. Social or behavioural factor or other anthropometric measures were not associated with outcome.Conclusion: The intervention programme had no effect on BMI SDS.The South-Eastern Norway Regional Health Authority (Helse Sør Øst)
Innlandet Hospital TrustpublishedVersio