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.

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.

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.

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.

High level of circulating vitamin D during neoadjuvant therapy may lower risk of metastatic progression in high-risk rectal cancer.

BACKGROUND: Following curative-intent neoadjuvant therapy in locally advanced rectal cancer, metastatic progression is still dominant. We investigated if patients' circulating 25-hydroxyvitamin D [25(OH)D] levels were associated with outcome. METHODS: Serum 25(OH)D concentration was assessed by liquid chromatography-mass spectrometry in samples collected from 84 patients at baseline, completion of the neoadjuvant therapy, and treatment evaluation before surgery, and analyzed with respect to season, disease presentation, and treatment effects. RESULTS: In the cohort of patients residing at latitude 58-62°N, baseline 25(OH)D differed significantly over the seasons, with highest measures (mean of 71.2 ± 5.6 nmol/L) in summer and lowest (48.7 ± 4.5 nmol/L) in spring, and changed over the three-month neoadjuvant period till response evaluation solely owing to season. The patient subgroup with slightly reduced performance status, anemia, and T4 disease that did not respond to the neoadjuvant therapy (ypT4 cases), had significantly lower baseline 25(OH)D (below 50 nmol/L) than T4 cases with response (ypT0-3) and T2-3 cases (above 60 nmol/L). Compared to the T4 patients with levels above 50 nmol/L, regarded as sufficient for a healthy bone status, those presenting levels below had significantly heightened risk of disease progression (mainly metastasis) and death, with hazard ratio of 3 and 17, respectively, on adjustment for age, sex, body mass index, and season. CONCLUSION: Rectal cancer T4 cases had high risk of metastatic progression and death if circulating 25(OH)D levels were insufficient but obtained short-term and long-term outcome to neoadjuvant treatment no worse than patients with T2-3 disease when 25(OH)D was sufficient. TRIAL REGISTRATION: ClinicalTrials.gov NCT00278694 ; registration date: 16 January 2006, retrospective to enrollment of the first 10 patients of the current report.

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 NEOLETEXE trial: a neoadjuvant cross-over study exploring the lack of cross resistance between aromatase inhibitors.

The aromatase inhibitor letrozole (Femar®/Femara®) and the aromatase inactivator exemestane (Aromasin®) differ in their biochemical effect on the aromatase enzyme. Letrozole is a competitive aromatase inhibitor while exemestane binds irreversibly to the aromatase enzyme. This pharmacological difference is of clinical interest since a lack of cross-resistance has been documented. It has been demonstrated in several clinical trials that exemestane may cause a disease regression following resistance to nonsteroidal aromatase inhibitors. The exact mechanism(s) behind this phenomenon is yet unknown. Here, we present the NEOLETEXE trial with the aim of exploring the individual mechanisms involved behind the observed lack of cross resistance. Clinical trial registration: The trial has been approved by the Regional Ethics Committee of South-East Norway (project number 2015/84).

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.

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics.

BACKGROUND: The majority of breast cancer cases are steroid dependent neoplasms, with hormonal manipulation of either CYP19/aromatase or oestrogen receptor alpha axis being the most common therapy. Alternate pathways of steroid actions are documented, but their interconnections and correlations to BC subtypes and clinical outcome could be further explored. METHODS: We evaluated selected steroid receptors (Androgen Receptor, Oestrogen Receptor alpha and Beta, Glucocorticoid Receptor) and oestrogen pathways (steroid sulfatase (STS), 17ß-hydroxysteroid dehydrogenase 2 (17ßHSD2) and aromatase) in a cohort of 139 BC cases from Norway. Using logistic and cox regression analysis, we examined interactions between these and clinical outcomes such as distant metastasis, local relapse and survival. RESULTS: Our principal finding is an impact of STS expression on the risk for distant metastasis (p<0.001) and local relapses (p <0.001), HER2 subtype (p<0.015), and survival (p<0.001). The suggestion of a beneficial effect of alternative oestrogen synthesis pathways was strengthened by inverted, but non-significant findings for 17ßHSD2. CONCLUSIONS: Increased intratumoural metabolism of oestrogens through STS is associated with significantly lower incidence of relapse and/or distant metastasis and correspondingly improved prognosis. The enrichment of STS in the HER2 overexpressing subtype is intriguing, especially given the possible role of HER-2 over-expression in endocrine resistance.

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.

Targeted Interdisciplinary Model for Evaluation and Treatment of Neuropsychiatric Symptoms: A Cluster Randomized Controlled Trial.

OBJECTIVE: To determine the effectiveness of the Targeted Interdisciplinary Model for Evaluation and Treatment of Neuropsychiatric Symptoms (TIME) for treatment of moderate to severe agitation in people with dementia. METHODS: In a single-blinded, cluster randomized controlled trial in 33 nursing homes (clusters) from 20 municipalities in Norway, 229 patients (104 patients in 17 nursing homes and 125 patients in 16 nursing homes) were randomized to an intervention or control group, respectively. The intervention group received TIME, and the control group received a brief education-only intervention. TIME is an interdisciplinary multicomponent intervention and consists of a comprehensive assessment of the patient with the goal to create and put into action a tailored treatment plan. The primary outcome was the between-group difference in change at the agitation/aggression item of the Neuropsychiatric Inventory Nursing Home version between baseline and 8 weeks. Secondary outcomes were the between-group difference in change at the agitation/aggression between baseline and 12 weeks in other neuropsychiatric symptoms, quality of life, and use of psychotropic and analgesic medications between baseline and 8 and 12 weeks. RESULTS: A significant between-group difference in reduction of agitation at both 8 weeks (1.1; 95% confidence interval: 0.1-2.1; p = 0.03) and 12 weeks (1.6; 95% confidence interval: 0.6-2.7; p = 0.002) in favor of the TIME intervention was found. CONCLUSION: The implementation of TIME resulted in a significant reduction of agitation among nursing homes patients with dementia. These results should inform training programs for care staff in Norway and internationally.

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.

Effect of high-dose vitamin D3 supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis.

BACKGROUND: Elevated antibody levels against Epstein-Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology. OBJECTIVES: To examine effects of high-dose oral vitamin D3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS. METHODS: Serum 25-hydroxyvitamin D3 (25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385-420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3 supplementation (20,000 IU/week) (NCT00785473). RESULTS: The mean 25(OH)D level more than doubled in the vitamin D group and was significantly higher than in the placebo group at study conclusion (123.2 versus 61.8 nmol/L, p < 0.001). Compared to the placebo group, both anti-EBNA1 protein and fragment antibody levels decreased in the vitamin D group from baseline to week 48 ( p = 0.038 and p = 0.004, respectively), but not from baseline to week 96. Vitamin D3 supplementation did not affect antibodies against VCA, CMV or VZV. CONCLUSION: The results indicate that high-dose oral vitamin D3 supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.

High dose vitamin D supplementation does not affect biochemical bone markers in multiple sclerosis - a randomized controlled trial.

BACKGROUND: People with multiple sclerosis have high risk of osteoporosis and fractures. A poor vitamin D status is a risk factor for MS, and vitamin D supplementation has been recommended both to prevent MS progression and to maintain bone health. METHODS: We assessed the effect of 20,000 IU vitamin D3 weekly compared to placebo on biochemical markers of bone metabolism in 68 persons with relapsing remitting multiple sclerosis. RESULTS: Serum levels of 25-hydroxyvitamin D more than doubled in the vitamin D group, and parathyroid hormone decreased in the vitamin D group compared to the placebo group at week 48 and week 96. There was however no effect on bone formation as measured by procollagen type I N propeptide (PINP), or on bone resorption as measured by C-terminal cross-linking telopeptide of type I collagen (CTX1). Neither PINP nor CTX1 predicted bone loss from baseline to week 96. CONCLUSIONS: These findings corroborate the previously reported lack of effect of weekly high dose vitamin D supplementation on bone mass density in the same patients, and suggest that such vitamin D supplementation does not prevent bone loss in persons with MS who are not vitamin D deficient. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov on April 4 2008, registration number NCT00785473 .

Psychometric properties of the Norwegian version of the Evidence-Based Practice Attitude Scale (EBPAS): to measure implementation readiness.

BACKGROUND: Attitudes can be a precursor to the decision of whether or not to try a new practice. In order to tailor the implementation of evidence-based practices (EBPs) in mental health settings, we must first consider practitioner attitudes towards EBP adoption. To assess these attitudes, the Evidence-Based Practice Attitude Scale (EBPAS) was developed. The purpose of this study was to investigate the psychometric properties of the Norwegian version of the EBPAS, and to examine differences in attitudes towards implementing EBPs among mental health practitioners. METHODS: The EBPAS was translated into Norwegian and administered to 294 practitioners from seven primary and 22 specialized mental care units within a defined geographical area of Norway. RESULTS: The EBPAS showed good psychometric properties. The less clinical experience the practitioner had, the more positive their attitude toward EBPs. Primary care practitioners reported more positive attitudes towards implementing EBPs that were required of them than specialized care practitioners. CONCLUSIONS: The Norwegian version of the EBPAS is a promising tool for measuring implementation readiness in mental health services, and can be used in clinical practice to tailor implementation efforts. TRIAL REGISTRATION: The study was approved by the regional committees for medical and health research ethics [ REK 2013/2035 ] on 25(th) of May, 2014.

Are Users Satisfied with Assertive Community Treatment in Spite of Personal Restrictions?

The purpose of this explorative study was to examine satisfaction among 70 users of 12 Norwegian Assertive Community Treatment teams. The study was carried out among a group of 70 service users, and reveals generally high levels of satisfaction with the service, with satisfaction also being high in comparison to other ACT satisfaction studies. Users under a Community Treatment Order were more satisfied, while users with an alcohol use disorder were less satisfied. Younger service users were less positive than older users. There was no difference in satisfaction between the genders. This study's positive result may reflect the ACT model's focus on user involvement, recovery and building relationships, and the fact that this service has a more holistic approach than previous services that users have experienced.

Seasonally adjusted birth frequencies follow the Poisson distribution.

BACKGROUND: Variations in birth frequencies have an impact on activity planning in maternity wards. Previous studies of this phenomenon have commonly included elective births. A Danish study of spontaneous births found that birth frequencies were well modelled by a Poisson process. Somewhat unexpectedly, there were also weekly variations in the frequency of spontaneous births. Another study claimed that birth frequencies follow the Benford distribution. Our objective was to test these results. MATERIAL AND METHOD: We analysed 50,017 spontaneous births at Akershus University Hospital in the period 1999-2014. To investigate the Poisson distribution of these births, we plotted their variance over a sliding average. We specified various Poisson regression models, with the number of births on a given day as the outcome variable. The explanatory variables included various combinations of years, months, days of the week and the digit sum of the date. RESULTS: The relationship between the variance and the average fits well with an underlying Poisson process. A Benford distribution was disproved by a goodness-of-fit test (p < 0.01). The fundamental model with year and month as explanatory variables is significantly improved (p < 0.001) by adding day of the week as an explanatory variable. Altogether 7.5% more children are born on Tuesdays than on Sundays. The digit sum of the date is non-significant as an explanatory variable (p = 0.23), nor does it increase the explained variance. INERPRETATION: Spontaneous births are well modelled by a time-dependent Poisson process when monthly and day-of-the-week variation is included. The frequency is highest in summer towards June and July, Friday and Tuesday stand out as particularly busy days, and the activity level is at its lowest during weekends.

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.