Modeling geographic vaccination strategies for COVID-19 in Norway.

Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic.

Metacognitions in patients with chronic obstructive pulmonary disease: a psychometric study of the metacognitions questionnaire-30.

The metacognitions questionnaire-30 (MCQ-30) was developed for the assessment of metacognitive beliefs and processes that are central components of the metacognitive model of emotional disorders. Anxiety and depression commonly occur in patients with chronic obstructive pulmonary disease (COPD). Testing such a model for anxiety and depression in patients with COPD is warranted. However, the psychometric properties of the MCQ-30 in COPD patients are unknown. Therefore, in this study we aimed to examine these properties in COPD patients. The MCQ-30 was administered to 203 COPD patients referred to a rehabilitation unit in respiratory medicine. Confirmatory factor analysis (CFA) was used to test the five-factor as well as the bi-factor models of MCQ-30. Exploratory factor analyses were also performed. Both models did not meet the criteria for an acceptable fit on Comparative Fit Index (CFI) of 0.810 and 0.858 vs. criterion of ≥0.9, but the Root Mean Square Error of Approximation (RMSEA) criterion ≤0.08 was acceptable for both models with RMSEA = 0.074 and 0.066, respectively. The factors were mostly moderately correlated (0.41-0.58) with acceptable reliability coefficients (0.73-0.87). The exploratory factor analysis identified three of the five factors originally described in the five-factor model of the MCQ-30. These data show that the factor structure of the MCQ-30 appears to differ from that of the original instrument in COPD patients and further studies are needed to confirm its validity and reliability in this patient group.

Antibiotic Consumption in a Cohort of Hospitalized Adults with Viral Respiratory Tract Infection.

Development of antibiotic resistance, a threat to global health, is driven by inappropriate antibiotic usage. Respiratory tract infections (RTIs) are frequently treated empirically with antibiotics, despite the fact that a majority of the infections are caused by viruses. The purpose of this study was to determine the prevalence of antibiotic treatment in hospitalized adults with viral RTIs, and to investigate factors influencing the antibiotic decision-making. We conducted a retrospective observational study of patients ≥ 18 years, hospitalized in 2015-2018 with viral RTIs. Microbiological data were taken from the laboratory information system and information on antibiotic treatment drawn from the hospital records. To investigate decisions for prescribing antibiotic treatment, we evaluated relevant factors such as laboratory and radiological results, in addition to clinical signs. In 951 cases without secondary bacterial RTIs (median age 73 years, 53% female), 720 (76%) were prescribed antibiotic treatment, most frequently beta-lactamase-sensitive penicillins, but cephalosporins were prescribed as first-line in 16% of the cases. The median length of treatment (LOT) in the patients treated with antibiotics was seven days. Patients treated with antibiotics had an average of two days longer hospital stay compared to patients with no such treatment, but no difference in mortality was found. Our study revealed that there is still a role for antimicrobial stewardship to further improve antibiotic use in patients admitted for viral RTIs in a country with relatively low antibiotic consumption.

A real-time regional model for COVID-19: Probabilistic situational awareness and forecasting.

The COVID-19 pandemic is challenging nations with devastating health and economic consequences. The spread of the disease has revealed major geographical heterogeneity because of regionally varying individual behaviour and mobility patterns, unequal meteorological conditions, diverse viral variants, and locally implemented non-pharmaceutical interventions and vaccination roll-out. To support national and regional authorities in surveilling and controlling the pandemic in real-time as it unfolds, we here develop a new regional mathematical and statistical model. The model, which has been in use in Norway during the first two years of the pandemic, is informed by real-time mobility estimates from mobile phone data and laboratory-confirmed case and hospitalisation incidence. To estimate regional and time-varying transmissibility, case detection probabilities, and missed imported cases, we developed a novel sequential Approximate Bayesian Computation method allowing inference in useful time, despite the high parametric dimension. We test our approach on Norway and find that three-week-ahead predictions are precise and well-calibrated, enabling policy-relevant situational awareness at a local scale. By comparing the reproduction numbers before and after lockdowns, we identify spatially heterogeneous patterns in their effect on the transmissibility, with a stronger effect in the most populated regions compared to the national reduction estimated to be 85% (95% CI 78%-89%). Our approach is the first regional changepoint stochastic metapopulation model capable of real time spatially refined surveillance and forecasting during emergencies.

Molecular epidemiology and antibiotic resistance profiles of invasive Haemophilus influenzae from Norway 2017-2021.

Invasive Haemophilus influenzae (Hi) disease has decreased in countries that included Hi type b (Hib) vaccination in their childhood immunization programs in the 1990s. Non-typeable (NT) and non-b strains are now the leading causes of invasive Hi disease in Europe, with most cases reported in young children and the elderly. Concerningly, no vaccines toward such strains are available and beta-lactam resistance is increasing. We describe the epidemiology of invasive Hi disease reported to the Norwegian Surveillance System for Communicable Diseases (MSIS) (2017-2021, n = 407). Whole-genome sequencing (WGS) was performed on 245 isolates. We investigated the molecular epidemiology (core genome phylogeny) and the presence of antibiotic resistance markers (including chromosomal mutations associated with beta-lactam or quinolone resistance). For isolates characterized with both WGS and phenotypic antibiotic susceptibility testing (AST) (n = 113) we assessed correlation between resistance markers and susceptibility categorization by calculation of sensitivity, specificity, and predictive values. Incidence rates of invasive Hi disease in Norway ranged from 0.7 to 2.3 per 100,000 inhabitants/year (mean 1.5 per 100,000) and declined during the COVID-19 pandemic. The bacterial population consisted of two major phylogenetic groups with subclustering by serotype and multi-locus sequence type (ST). NTHi accounted for 71.8% (176). The distribution of STs was in line with previous European reports. We identified 13 clusters, including four encapsulated and three previously described international NTHi clones with bla TEM-1 (ST103) or altered PBP3 (rPBP3) (ST14/IIA and ST367/IIA). Resistance markers were detected in 25.3% (62/245) of the isolates, with bla TEM-1 (31, 50.0%) and rPBP3 (28, 45.2%) being the most frequent. All isolates categorized as resistant to aminopenicillins, tetracycline or chloramphenicol possessed relevant resistance markers, and the absence of relevant substitutions in PBP3 and GyrA/ParC predicted susceptibility to cefotaxime, ceftriaxone, meropenem and quinolones. Among the 132 WGS-only isolates, one isolate had PBP3 substitutions associated with resistance to third-generation cephalosporins, and one isolate had GyrA/ParC alterations associated with quinolone resistance. The detection of international virulent and resistant NTHi clones underlines the need for a global molecular surveillance system. WGS is a useful supplement to AST and should be performed on all invasive isolates.

Clinical Outcome of Viral Respiratory Tract Infections in Hospitalized Adults in Norway: High Degree of Inflammation and Need of Emergency Care for Cases With Respiratory Syncytial Virus.

Background: The clinical features and outcomes of viral respiratory tract infections (RTIs) in adults have not been thoroughly studied, especially the respiratory syncytial virus (RSV) disease burden. It has become apparent that outbreaks of RSV in the elderly are associated with increased hospitalization rates. However, little data exists on the severity of such viral RTIs in adults, particularly the need for hospitalization, respiratory support and intensive care. Methods: We conducted a retrospective observational single-center study at Østfold Hospital Trust, Norway, during three winter seasons 2015-2018. Patients ≥18 years with either influenza A, influenza B, RSV A/B, human metapneumovirus, parainfluenza virus 1-4 or adenovirus detected in respiratory specimens were included, if they were hospitalized 14 days prior or following the detection date, with signs of RTI. Hospital records on treatment and outcome were investigated, as well as mortality of all causes up to 30 days from discharge. Results: Of the 1222 infection events that were included, influenza A was the most frequent virus detected (39%), while 179 infection events (14.6%) were due to RSV. Influenza B counted for 24% of the infection events, human metapneumovirus 13%, parainfluenza virus 9% and adenovirus 1%. Patients admitted with RSV more often suffered from COPD and congestive heart failure than patients with influenza A. In addition, RSV patients were overrepresented in the urgent response NEWS score (National Early Warning Score) category ≥5. RSV patients also showed signs of more severe inflammation, with WBC ≥11.1 × 109/L and CRP >100 mg/L, and they were more often treated with antibiotic agents during their hospital stay. However, we found no differences in the need for ICU admission or mortality. Conclusion: Patients with RSV had more often high values for markers of inflammation and elevated NEWS score when compared to patients hospitalized with other common respiratory viruses. Taken into account that they suffered more frequently from comorbidities like COPD, these patients needed hospitalization more urgently. These findings highlight the need for further investigations on RSV disease in adults and the elderly.

Mucosal Gene Transcript Signatures in Treatment Naïve Inflammatory Bowel Disease: A Comparative Analysis of Disease to Symptomatic and Healthy Controls in the European IBD-Character Cohort.

BACKGROUND: Studies of the mucosal transcriptomic landscape have given new insight into the pathogenesis of inflammatory bowel disease (IBD). Recently, the predictive biomarker potential of gene expression signatures has been explored. To further investigate the mucosal gene expression in IBD, we recruited a cohort of treatment naïve patients and compared them to both symptomatic and healthy controls. METHODS: Altogether, 323 subjects were included: Crohn's disease (N = 75), ulcerative colitis (N = 87) and IBD unclassified (N = 3). Additionally, there were two control groups: symptomatic controls (N = 131) and healthy controls (N = 27). Mucosal biopsies were collected during ileocolonoscopy and gene expression in inflamed and non-inflamed mucosa was explored. Gene expression profiling was performed using Agilent G3 Human Gene Expression 860K v3 One-Color microarray. We recorded information about treatment escalation to anti-TNF agents or surgery, and anti-TNF response, to explore predictive opportunities of the mucosal transcriptome. RESULTS: Gene expression profiles in symptomatic controls in whom IBD had been excluded resembled that of IBD patients and diverged from that of healthy controls. In non-inflamed Crohn's disease and ulcerative colitis, gene set enrichment analysis revealed dysregulation of pathways involved in basic cellular biological processes. Mitochondria-associated pathways were dysregulated both in non-inflamed and inflamed Crohn's disease and ulcerative colitis (>2.6 normalized enrichment scores <-1.8). Gene expression signatures of Crohn's disease and ulcerative colitis did not predict time for treatment escalation (p = 0.175). No significant association was found between gene expression signatures and anti-TNF response. CONCLUSION: Non-inflamed samples are probably superior to inflamed samples when exploring gene expression signatures in IBD and might reveal underlying mechanisms central for disease initiation. The gene expression signatures of the control groups were related to if they were symptomatic or not, which may have important implications for future study designs.

Increased transmissibility of the alpha SARS-CoV-2 variant: evidence from contact tracing data in Oslo, January to February 2021.

BACKGROUND: Information about the contagiousness of new SARS-CoV-2 variants, including the alpha lineage, and how they spread in various locations is essential. Country-specific estimates are needed because local interventions influence transmissibility. METHODS: We analysed contact tracing data from Oslo municipality, reported from January through February 2021, when the alpha lineage became predominant in Norway and estimated the relative transmissibility of the alpha lineage with the use of Poisson regression. RESULTS: Within households, we found an increase in the secondary attack rate by 60% (95% CI 20-114%) among cases infected with the alpha lineage compared to other variants; including all close contacts, the relative increase in the secondary attack rate was 24% (95% CI -6%-43%). There was a significantly higher risk of infecting household members in index cases aged 40-59 years who were infected with the alpha lineage; we found no association between transmission and household size. Overall, including all close contacts, we found that the reproduction number among cases with the alpha lineage was increased by 24% (95% CI 0%-52%), corresponding to an absolute increase of 0.19, compared to the group of index cases infected with other variants. CONCLUSION: Our study suggests that households are the primary locations for rapid transmission of the new lineage alpha.

Stool dynamics after extrinsic nerve injury during right colectomy with extended D3-mesenterectomy.

INTRODUCTION: To improve oncological outcome in right colon cancer surgery, an extended mesenterectomy (D3) is under evaluation. In this procedure, all tissue anterior and posterior to the superior mesenteric vessels from the middle colic to ileocolic artery origin is removed, causing injury to the superior mesenteric nerve plexus. The aim was to study the effects of this injury on bowel dynamics and quality of life (QoL). METHODS: Patients undergoing right colectomy with conventional D2- and extended D3-mesenterectomy were asked to record stool number and consistency for 60 d after surgery and complete questionnaires regarding QoL and bowel function (BF) before and after recovery from surgery. We compared early postoperative stool dynamics and long-term QoL in the groups and presented graphs depicting the temporal profile of stool numbers and consistency. RESULTS: Thirty-three patients operated with a D3-resection and 12 patients with a D2-resection participated. The results revealed significantly higher stool numbers in the D3-group until day 26, with significantly more loose-watery stools until day 40. The most pronounced difference was found on day 9 (Mean difference in the total number of stools: 2.25 stools/day, p=.004. Mean difference in loose-watery stools/day: 2.81 p<.001). About 25% in the D2- and 69.7% in the D3-group reported having more than three stools/day in the early postoperative phase. There were no differences in long-term QoL and BF between the groups except in stool consistency (p=.039). DISCUSSION/CONCLUSIONS: Denervation following extended D3-mesenterectomy leads to transitory reduced consistency and increased frequency. It does not affect long-term QoL or BF.

Hypophosphatemia after high-dose intravenous iron treatment in patients with inflammatory bowel disease: Mechanisms and possible clinical impact.

BACKGROUND: High-dose intravenous iron is an effective treatment option for iron deficiency (ID) or ID anaemia (IDA) in inflammatory bowel disease (IBD). However, treatment with ferric carboxymaltose (FCM) has been associated with the development of hypophosphatemia. AIM: To investigate mechanisms behind the development of hypophosphatemia after intravenous iron treatment, and disclose symptoms and clinical manifestations related to hypophosphatemia short-term. METHODS: A prospective observational study of adult IBD patients with ID or IDA was conducted between February 1, 2017 and July 1, 2018 at two separate university hospitals in the southeast region of Norway. Patients received one dose of 1000 mg of either FCM or ferric derisomaltose (FDI) and were followed for an observation period of at least 7 wk. Blood and urine samples were collected for relevant analyses at baseline, week 2 and at week 6. Clinical symptoms were assessed at the same timepoints using a respiratory function test, a visual analogue scale, and a health-related quality of life questionnaire. RESULTS: A total of 106 patients was available for analysis in this study. The FCM treatment group consisted of 52 patients and hypophosphatemia was present in 72.5% of the patients at week 2, and in 21.6% at week 6. In comparison, the FDI treatment group consisted of 54 patients and 11.3% of the patients had hypophosphatemia at week 2, and 3.7% at week 6. The difference in incidence was highly significant at both week 2 and 6 (P < 0.001 and P < 0.013, respectively). We observed a significantly higher mean concentration of intact fibroblast growth factor 23 (P < 0.001), a significant rise in mean urine fractional excretion of phosphate (P = 0.004), a significant decrease of 1,25-dihydroxyvitamin D (P < 0.001) and of ionised calcium levels (P < 0.012) in the FCM-treated patients compared with patients who received FDI. No clinical symptoms could with certainty be related to hypophosphatemia, since neither the respiratory function test, SF-36 (36-item short form health survey) or the visual analogue scale scores resulted in significant differences between patients who developed hypophosphatemia or not. CONCLUSION: Fibroblast growth factor 23 has a key role in FCM induced hypophosphatemia, probably by inducing loss of phosphate in the urine. Short-term clinical impact of hypophosphatemia was not demonstrated.

Accuracy of breast MRI in patients receiving neoadjuvant endocrine therapy: comprehensive imaging analysis and correlation with clinical and pathological assessments.

PURPOSE: To assess the accuracy of magnetic resonance imaging (MRI) measurements in locally advanced oestrogen receptor-positive and human epidermal growth factor receptor 2-negative breast tumours before, during and after neoadjuvant endocrine treatment (NET) for evaluation of tumour response in comparison with clinical and pathological assessments. METHODS: This prospective study enrolled postmenopausal patients treated neoadjuvant with letrozole and exemestane given sequentially in an intra-patient cross-over regimen. Fifty-four patients were initially recruited, but only 35 fulfilled the inclusion criteria and confirmed to participate with a median age of 77. Tumours were scanned with MRI prior to treatment, during the eighth week of treatment and prior to surgery. Additionally, changes in longest diameter on clinical examination (CE) and tumour size at pathology were determined. Pre- and post-operative measurements of tumour size were compared in order to evaluate tumour response. RESULTS: The correlation between post-treatment MRI size and pathology was moderate and higher with a correlation coefficient (r) 0.64 compared to the correlation between CE and pathology r = 0.25. Post-treatment MRI and clinical results had a negligible bias towards underestimation of lesion size. Tumour size on MRI and CE had 0.82 cm and 0.52 cm lower mean size than tumour size measured by pathology, respectively. CONCLUSIONS: The higher correlation between measurements of residual disease obtained on MRI and those obtained with pathology validates the accuracy of imaging assessment during NET. MRI was found to be more accurate for estimating complete responses than clinical assessments and warrants further investigation in larger cohorts to validate this finding.

Patient affect, physician liking for the patient, physician behavior, and patient reported outcomes: A modeling approach.

OBJECTIVE: To determine associations between patient affect and physician liking of the patient, and their associations with physician behavior and patient-reported outcomes. METHODS: Structural equation modeling based on coding of 497 videotaped hospital encounters, with questionnaires assessing pre-visit patient affect, post-visit patient affect and encounter evaluations, and physician liking of the patient, involving 71 physicians. RESULTS: In first visits, patient reported outcomes were strongly correlated with physician behavior and less so with physician liking, while in later visits, patient reported outcomes were directly related to physician liking and not mediated by physician behavior. Physician liking predicted physician behavior, more for female physicians in first visits. Patient negative affect before the visit was negatively associated with male physicians' liking. When acquainted, both patient positive and negative affect were associated with physician liking. CONCLUSION: Physician liking of the patient plays a dynamic role in a consultation, is influenced by patient pre-encounter affect, and influences physician behavior. The dynamics are different in first and later visits, and influenced by physician gender. PRACTICE IMPLICATIONS: Physicians should be aware how patient affect influences their behavior, and administrators should take any prior relationship between patient and physician into account when evaluating patient reported outcomes.

Incidence of hypophosphatemia in patients with inflammatory bowel disease treated with ferric carboxymaltose or iron isomaltoside.

BACKGROUND: Iron deficiency and iron deficiency anaemia are common complications in inflammatory bowel disease (IBD). In patients with moderate-to-severe anaemia, oral iron intolerance or ineffectiveness of oral iron, ferric carboxymaltose and iron isomaltoside are widely used. Hypophosphatemia is a side effect of both preparations. AIMS: To investigate the occurrence of hypophosphatemia in IBD patients with iron deficiency/iron deficiency anaemia treated with high-dose intravenous iron. METHODS: A prospective observational study of adult IBD patients with iron deficiency/iron deficiency anaemia was conducted at two study sites where patients received 1000 mg of ferric carboxymaltose or iron isomaltoside. At baseline, weeks 2 and 6, blood and faecal samples were collected. The primary endpoint was to determine the incidence of moderate-to-severe hypophosphatemia. Secondary endpoints included the total incidence of hypophosphatemia, possible risk factors for hypophosphatemia, and response to single-dose intravenous iron. RESULTS: One hundred and thirty patients were included. In the per-protocol set, 52 patients received ferric carboxymaltose and 54 patients received iron isomaltoside. Ferric carboxymaltose treatment had a significantly higher incidence of moderate-to-severe hypophosphatemia compared with iron isomaltoside at week 2 (56.9% vs 5.7%, P < 0.001) and a higher incidence at week 6 (13.7% vs 1.9%, P = 0.054).The overall incidence of hypophosphatemia was significantly higher with ferric carboxymaltose compared with iron isomaltoside treatment at weeks 2 (72.5% vs 11.3%, P < 0.001) and 6 (21.6% vs 3.7%, P = 0.013). CONCLUSIONS: In IBD patients with iron deficiency/iron deficiency anaemia, ferric carboxymaltose was associated with higher incidence, severity and persistence of hypophosphatemia compared with iron isomaltoside. The presence of moderate-to-severe hypophosphatemia beyond 6 weeks is a clinical concern that requires further investigation.

Interventional study to improve adherence to phosphate binder treatment in dialysis patients.

BACKGROUND: Adherence to phosphate binder treatment is important to prevent high serum phosphate level in chronic dialysis patients. We therefore wanted to investigate patient knowledge, beliefs about and adherence to phosphate binders among these patients and assess whether one-to-one pharmacist-led education and counselling enhance adherence and lead to changes in serum phosphate levels. METHODS: A descriptive, interventional, single arm, pre-post study was performed at a hospital in Norway, including chronic dialysis patients aged 18 years or more using phosphate binders. The primary end-point was change in the proportion of patients with serum phosphate below 1.80 mmol/L and the secondary end-points included change in the patient's knowledge, beliefs and adherence after the intervention measured by completion of questionnaires 'Patient Knowledge', Medication Adherence Report Scale (MARS- 5) and Beliefs about Medicines Questionnaire (BMQ). Data was collected both prior to and after one-to-one pharmacist-led education and counselling about their phosphate binders. Other medicines used by the patient was also registered. RESULTS: A total of 69 patients were enrolled in the study. After intervention, the probability of serum phosphate being below the target threshold 1.80 mmol/L (5.58 mg/dL) increased, although no significant change in mean serum phosphate levels was seen. On the other hand, the knowledge regarding phosphate binder treatment and the patients' beliefs about the necessity of the treatment increased, while the concerns decreased (BMQ). This effect did not lead to increase in self-reported adherence measured by MARS-5. However the scores were high before the intervention. CONCLUSIONS: Short term one-to-one individualized pharmacist-led education and counselling about phosphate binders increased the probability of serum phosphate concentrations being below the target threshold level 1.80 mmol/L (5.58 mg/dL), although not statistically significant. However, it did not decrease the mean serum phosphate level or increase the patients' self-reported adherence. The patients increased their knowledge about the phosphate binder and their understanding of adherence, and were less concerned about the side effects of the medication. TRIAL REGISTRATION: ISRCTN52852596 , registered 11 April 2019. The trial was registered retrospectively.

Bowel Motility After Injury to the Superior Mesenteric Plexus During D3 Extended Mesenterectomy.

BACKGROUND: Improvement of lymphadenectomy in right colectomy requires removal of all tissue surrounding the superior mesenteric vessels beneath the pancreatic notch. Short- and long-term bowel motility disorders after D3 extended mesenterectomy with consecutive superior mesenteric plexus transection are studied. METHODS: Patients without pre-existing motility disorders undergoing D3 extended mesenterectomy were examined 3 times using the wireless motility capsule: before, at 3 wk, and 6 mo after surgery. Segmental transit times and contractility were analyzed using mixed effect modeling. Correlation between contractility and transit time was assessed by the Pearson correlation coefficient. RESULTS: Fifteen patients (4 men), with median age 62 y, were included. Mean values for the three consecutive examinations are as follows. Gastric transit time increased from 237 to 402 and 403 min, respectively. Small bowel transit time decreased from 246 to 158 (P < 0.01) and 199 (P = 0.03) min, respectively. Colonic transit time decreased from 1742 to 1450 and 1110 (P = 0.02) min, respectively. Gastric contractions per minute (CPM) varied from 1.73 to 1.05 (P = 0.01) and 2.47 (P < 0.01), respectively. Small bowel CPM decreased from 3.43 to 2.68 and 3.34, respectively. Colonic CPM ranged from 1.59 to 1.45 and 1.91 (P = 0.08), respectively. Correlation between small bowel (SB) transit time and CPM was -0.45 (P = 0.09) preoperatively, and -0.03 (P = 0.91) 6 mo postoperatively. CONCLUSIONS: Extrinsic SB denervation leads to significantly accelerated SB transit, reduced contractility, and disturbed correlation between transit time and contractility early after denervation. Both number of contractions and transit time in the denervated SB show a clear tendency toward normalization at 6 mo.

Vitamin D supplementation and neurofilament light chain in multiple sclerosis.

OBJECTIVES: The effect of vitamin D supplementation on the disease course of multiple sclerosis (MS) is not established. Neurofilament light chain (NFL) is a sensitive marker of axonal degeneration. The aim of this study was to establish whether high-dose vitamin D supplementation reduces serum levels of NFL. MATERIALS AND METHODS: We have performed a 96 weeks placebo-controlled randomized study of weekly supplementation with 20 000 IU vitamin D3 in 71 patients with relapsing remitting MS (RRMS). Serum levels of NFL were measured at baseline, week 48 and week 96 with a single molecule (Simoa) assay in 69 of these patients. RESULTS: Serum levels of 25-hydroxyvitamin D more than doubled in the vitamin D group. Compared to placebo, vitamin D supplementation had no overall effect on the change in serum levels of NFL from baseline (P = 0.93 at week 48 and P = 0.56 at week 96). In the subgroup of patients not receiving disease-modifying therapy, NFL decreased by 30.9% to week 48% and 32.6% to week 96 from baseline in the vitamin D group as compared to the placebo group (P = 0.06 for both time points). CONCLUSION: With a possible exception for patients not treated with disease-modifying drugs, weekly supplementation with 20 000 IU vitamin D3 did not affect NFL levels in these RRMS patients.

The prevalence and transcriptional activity of the mucosal microbiota of ulcerative colitis patients.

Active microbes likely have larger impact on gut health status compared to inactive or dormant microbes. We investigate the composition of active and total mucosal microbiota of treatment-naïve ulcerative colitis (UC) patients to determine the microbial picture at the start-up phase of disease, using both a 16S rRNA transcript and gene amplicon sequencing. DNA and RNA were isolated from the same mucosal colonic biopsies. Our aim was to identify active microbial members of the microbiota in early stages of disease and reveal which members are present, but do not act as major players. We demonstrated differences in active and total microbiota of UC patients when comparing inflamed to non-inflamed tissue. Several taxa, among them the Proteobacteria phyla and families therein, revealed lower transcriptional activity despite a high presence. The Bifidobacteriaceae family of the Actinobacteria phylum showed lower abundance in the active microbiota, although no difference in presence was detected. The most abundant microbiota members of the inflamed tissue in UC patients were not the most active. Knowledge of active members of microbiota in UC patients could enhance our understanding of disease etiology. The active microbial community composition did not deviate from the total when comparing UC patients to non-IBD controls.

Hospitals implementing changes in law to protect children of ill parents: a cross-sectional study.

BACKGROUND: Norway is one of the first countries to require all health professionals to play a part in prevention for children of parents with all kinds of illnesses (mental illness, drug addiction, or severe physical illness or injury) in order to mitigate their increased risk of psychosocial problems. Hospitals are required to have child responsible personnel (CRP) to promote and coordinate support given by health professionals to patients who are parents and to their children. METHODS: This study examined the extent to which the new law had been implemented as intended in Norwegian hospitals, using Fixsen's Active Implementation Framework. A stratified random sample of managers and child responsible personnel (n = 167) from five Hospitals filled in an adapted version of the Implementation Components Questionnaire (ICQ) about the implementation of policy changes. Additional information was collected from 21 hospital coordinators (H-CRP) from 16 other hospitals. RESULTS: Significant differences were found between the five hospitals, with lowest score from the smallest hopitals. Additional analysis, comparing the 21 hospitals, as reported by the H-CRP, suggests a clear pattern of smaller hospitals having less innovative resources to implement the policy changes. Leadership, resources and system intervention (strategies to work with other systems) were key predictors of a more successful implementation process. CONCLUSIONS: Legal changes are helpful, but quality improvements are needed to secure equal chances of protection and support for children of ill parents. TRIAL REGISTRATION: The study is approved by the Regional Committee on Medical and Health Research Etics South-East (reg.no. 2012/1176 ) and by the Privacy Ombudsmann.

Somatic EP300-G211S mutations are associated with overall somatic mutational patterns and breast cancer specific survival in triple-negative breast cancer.

PURPOSE: We have compared the mutational profiles of human breast cancer tumor samples belonging to all major subgroups with special emphasis on triple-negative breast cancer (TNBC). Our major goal was to identify specific mutations that could be potentially used for clinical decision making in TNBC patients. PATIENTS AND METHODS: Primary tumor specimens from 149 Norwegian breast cancer patients were available. We analyzed the tissue samples for somatic mutations in 44 relevant breast cancer genes by targeted next-generation sequencing. As a second confirmatory technique, we performed pyrosequencing on selected samples. RESULTS: We observed a distinct subgroup of TNBC patients, characterized by an almost completely lack of pathogenic somatic mutations. A point mutation in the adenoviral E1A binding protein p300 (EP300-G211S) was significantly correlated to this TNBC subgroup. The EP300-G211S mutation was exclusively found in the TNBC patients and its presence reduced the chance for other pathological somatic mutations in typical breast cancer genes investigated in our gene panel by 94.9% (P < 0.005). Interestingly, the EP300-G211S mutation also predicted a lower risk for relapses and decreased breast cancer-specific mortality during long-term follow-up of the patients. CONCLUSION: Next-generation sequencing revealed specific mutations in EP300 to be associated with the mutational patterns in typical breast cancer genes and long-term outcome of triple-negative breast cancer patients.