Phase II study of everolimus and temozolomide as first-line treatment in metastatic high-grade gastroenteropancreatic neuroendocrine neoplasms.

BACKGROUND: The optimal treatment for metastatic high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms when Ki-67 ≤55% is unknown. A prospective multi-centre phase 2 study was performed to evaluate the efficacy and safety of everolimus and temozolomide as first-line treatment for these patients. METHODS: Patients received everolimus 10 mg daily continuously and temozolomide 150 mg/m2 for 7 days every 2 weeks. Endpoints included response, survival, safety and quality of life (QoL). Histopathological re-evaluation according to the 2019 WHO classification was performed. RESULTS: For 37 eligible patients, the primary endpoint with 65% disease control rate (DCR) at 6 months (m) was reached. The response rate was 30%, the median progression-free survival (PFS) 10.2 months and the median overall survival (OS) 26.4 months. Considering 26 NET G3 patients, 6 months DCR was 77% vs. 22% among nine NEC patients (p = 0.006). PFS was superior for NET G3 vs. NEC (12.6 months vs. 3.4 months, Log-rank-test: p = 0.133, Breslow-test: p < 0.001). OS was significantly better for NET G3 (31.4 months vs. 7.8 months, p = 0.003). Grade 3 and 4 toxicities were reported in 43% and 38%. QoL remained stable during treatment. CONCLUSION: Everolimus and temozolomide may be a treatment option for selected GEP-NET G3 patients including careful monitoring. Toxicity did not compromise QoL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NTC02248012).

In vitro quality of cold and delayed cold-stored platelet concentrates from interim platelet units during storage for 21 days.

BACKGROUND AND OBJECTIVES: Based on previous success using apheresis platelets, we wanted to investigate the in vitro quality and platelet function in continuously cold-stored and delayed cold-stored platelet concentrates (PCs) from interim platelet units (IPUs) produced by the Reveos system. MATERIALS AND METHODS: We used a pool-and-split design to prepare 18 identical pairs of PCs. One unit was stored unagitated and refrigerated after production on day 1 (cold-stored). The other unit was stored agitated at room temperature until day 5 and then refrigerated (delayed cold-stored). Samples were taken after pool-and-split on day 1 and on days 5, 7, 14 and 21. Swirling was observed and haematology parameters, metabolism, blood gas, platelet activation and platelet aggregation were analysed for each sample point. RESULTS: All PCs complied with European recommendations (EDQM 20th edition). Both groups had mean platelet content >200 × 109 /unit on day 21. The pH remained above 6.4 for all sample points. Glucose concentration was detectable in every cold-stored unit on day 21 and in every delayed cold-stored unit on day 14. The cold-stored group showed a higher activation level before stimulation as measured by flow cytometry. The activation levels were similar in the two groups after stimulation. Both groups had the ability to form aggregates after cold storage and until day 21. CONCLUSION: Our findings suggest that PCs from IPUs are suitable for cold storage from day 1 until day 21 and delayed cold storage from day 5 until day 14.

Seven-year trajectories of body weight, quality of life and comorbidities following Roux-en-Y gastric bypass and sleeve gastrectomy.

BACKGROUND/OBJECTIVES: There is limited long-term data comparing the outcomes of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) for severe obesity, both with respect to body weight, quality of life (QOL) and comorbidities. We aimed to determine 7-year trajectories of body mass index (BMI), QOL, obesity-related comorbidities, biomarkers of glucose and lipid metabolism, and early major complications after SG and RYGB. SUBJECTS/METHODS: Patients scheduled for bariatric surgery at two Norwegian hospitals, preferentially performing either SG or RYGB, were included consecutively from September 2011 to February 2015. Data was collected prospectively before and up to 7 years after surgery. Obesity-specific, generic and overall QOL were measured by the Impact of Weight on Quality of Life-Lite, Short-Form 36 and Cantril's ladder, respectively. Comorbidities were assessed by clinical examination, registration of medication and analysis of glucose and lipid biomarkers. Outcomes were examined with linear mixed effect models and relative risk estimates. RESULTS: Of 580 included patients, 543 (75% women, mean age 42.3 years, mean baseline BMI 43.0 kg/m2) were operated (376 SG and 167 RYGB). With 84.2% of participants evaluable after 5-7 years, model-based percent total weight-loss (%TWL) at 7 years was 23.4 after SG versus 27.3 after RYGB (difference 3.9%, p = 0.001). All levels of QOL improved similarly after the two surgical procedures but remained below reference data from the general population at all timepoints. Remission rates for type 2 diabetes, dyslipidemia, obstructive sleep-apnea and gastroesophageal reflux disease (GERD) as well as the rate of de novo GERD significantly favored RYGB. SG had fewer major early complications, but more minor and major late complications combined over follow-up. CONCLUSION: In routine health care, both SG and RYGB are safe procedures with significant long-term weight-loss, improvement of QOL and amelioration of comorbidities. Long-term weight-loss and remission rates of main obesity-related comorbidities were higher after RYGB.

Dixon T2 imaging of vertebral bone edema: reliability and comparison with short tau inversion recovery.

BACKGROUND: It is uncertain whether T2-weighted Dixon water images (DixonT2w) and short tau inversion recovery (STIR) are interchangeable when evaluating vertebral bone edema, or if one method is superior or visualizes the edema differently. PURPOSE: To compare image quality and Modic change (MC)-related edema between DixonT2w and STIR and estimate inter-observer reliability for MC edema on DixonT2w. MATERIAL AND METHODS: Consecutive patients (n = 120) considered for the Antibiotics in Modic changes (AIM) trial underwent lumbar 1.5-T magnetic resonance imaging with two-point DixonT2w and STIR. Two radiologists assessed MC-related high-signal lesions on DixonT2w and compared image quality and lesion extent with STIR. Cohen's kappa and mean of differences ± limits of agreement were calculated. RESULTS: Fat suppression and artefacts were similar on DixonT2w and STIR in 116 of 120 (97%) patients. Lesion conspicuity was similar in 88, better on STIR in 10, and better on DixonT2w in 9 of 107 patients with MC-related high-signal lesions. Contrast-to-noise ratio for STIR versus DixonT2w was 19.1 versus 17.1 (mean of differences 2.0 ± 8.2). Of 228 lesions L4-S1, 215 (94%) had similar extent on DixonT2w and STIR, 11 were smaller/undetected on STIR, and two were smaller/undetected on DixonT2w. Lesions missed on STIR (n = 9) or DixonT2w (n = 1) had a weak signal increase on the other sequence (≤17%; 0% = vertebral body, 100% = cerebrospinal fluid). Inter-observer reliability (mean kappa L4-S1) was very good for presence (0.87), moderate for height (0.44), and good for volume (0.63) of lesions on DixonT2w. CONCLUSION: DixonT2w provided similar visualization of MC-related vertebral edema as STIR.

The impact of referral letter quality on timely access to specialised mental health care: a quantitative study of the reliability of patient triage.

BACKGROUND: Patients referred to specialised mental health care are usually triaged based on referral information provided by general practitioners. However, knowledge about this system's ability to ensure timely access to and equity in specialised mental health care is limited. We aimed to investigate to the degree to which patient triage, based on referral letter information, corresponds to triage based on a hospital specialist's consultation with the patient, and whether the degree of correspondence is affected by the quality of the referral letter. METHODS: We gathered information from three specialised mental health centres in Norway regarding patients that were referred and offered health care (N = 264). Data consisted of triage decisions for each patient (i.e., the hospital specialist's assessment of maximum acceptable waiting time), which were determined on the basis of a) referral information and b) meeting the patient. Referral letter quality was evaluated using the Quality of Referral information-Mental Health checklist. The reliability of priority setting and the impact of referral letter quality on this measure were investigated using descriptive analyses, binary logistic regression and Nadaraya-Watson kernel regression. RESULTS: In 143 (54%) cases, the triage decision based on referral information corresponded with the decision based on patient consultation. In 70 (27%) cases, the urgency of need for treatment was underestimated when based on referral information compared with that based on information from patient consultation. Referral letter quality could not explain the differences between the two triage decisions. However, when a cut-off value of 7 on the Quality of Referral information-Mental Health scale was used, low-quality letters were found more frequently among patients whose urgency of need was underestimated, compared with those whose need was overestimated. CONCLUSIONS: Deciding the urgency of patient need for specialised mental health care based on referral information is a reliable system in many situations. However, the possibility of under- and overestimation is present, implying risks to patient safety and inappropriate use of resources. Improving the content of referral letters does not appear to reduce this risk when the letters are of acceptable quality. TRIAL REGISTRATION: NCT01374035 .

Can systematic implementation support improve programme fidelity by improving care providers' perceptions of implementation factors? A cluster randomized trial.

BACKGROUND: Investigations of implementation factors (e.g., collegial support and sense of coherence) are recommended to better understand and address inadequate implementation outcomes. Little is known about the relationship between implementation factors and outcomes, especially in later phases of an implementation effort. The aims of this study were to assess the association between implementation success (measured by programme fidelity) and care providers' perceptions of implementation factors during an implementation process and to investigate whether these perceptions are affected by systematic implementation support. METHODS: Using a cluster-randomized design, mental health clinics were drawn to receive implementation support for one (intervention) and not for another (control) of four evidence-based practices. Programme fidelity and care providers' perceptions (Implementation Process Assessment Tool questionnaire) were scored for both intervention and control groups at baseline, 6-, 12- and 18-months. Associations and group differences were tested by means of descriptive statistics (mean, standard deviation and confidence interval) and linear mixed effect analysis. RESULTS: Including 33 mental health centres or wards, we found care providers' perceptions of a set of implementation factors to be associated with fidelity but not at baseline. After 18 months of implementation effort, fidelity and care providers' perceptions were strongly correlated (B (95% CI) = .7 (.2, 1.1), p = .004). Care providers perceived implementation factors more positively when implementation support was provided than when it was not (t (140) = 2.22, p = .028). CONCLUSIONS: Implementation support can facilitate positive perceptions among care providers, which is associated with higher programme fidelity. To improve implementation success, we should pay more attention to how care providers constantly perceive implementation factors during all phases of the implementation effort. Further research is needed to investigate the validity of our findings in other settings and to improve our understanding of ongoing decision-making among care providers, i.e., the mechanisms of sustaining the high fidelity of recommended practices. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03271242 (registration date: 05.09.2017).

Apparent diffusion coefficient values in Modic changes - interobserver reproducibility and relation to Modic type.

BACKGROUND: Modic Changes (MCs) in the vertebral bone marrow were related to back pain in some studies but have uncertain clinical relevance. Diffusion weighted MRI with apparent diffusion coefficient (ADC)-measurements can add information on bone marrow lesions. However, few have studied ADC measurements in MCs. Further studies require reproducible and valid measurements. We expect valid ADC values to be higher in MC type 1 (oedema type) vs type 3 (sclerotic type) vs type 2 (fatty type). Accordingly, the purpose of this study was to evaluate ADC values in MCs for interobserver reproducibility and relation to MC type. METHODS: We used ADC maps (b 50, 400, 800 s/mm2) from 1.5 T lumbar spine MRI of 90 chronic low back pain patients with MCs in the AIM (Antibiotics In Modic changes)-study. Two radiologists independently measured ADC in fixed-sized regions of interests. Variables were MC-ADC (ADC in MC), MC-ADC% (0% = vertebral body, 100% = cerebrospinal fluid) and MC-ADC-ratio (MC-ADC divided by vertebral body ADC). We calculated mean difference between observers ± limits of agreement (LoA) at separate endplates. The relation between ADC variables and MC type was assessed using linear mixed-effects models and by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: The 90 patients (mean age 44 years; 54 women) had 224 MCs Th12-S1 comprising type 1 (n = 111), type 2 (n = 91) and type 3 MC groups (n = 22). All ADC variables had higher predicted mean for type 1 vs 3 vs 2 (p < 0.001 to 0.02): MC-ADC (10- 6 mm2/s) 1201/796/576, MC-ADC% 36/21/14, and MC-ADC-ratio 5.9/4.2/3.1. MC-ADC and MC-ADC% had moderate to high ability to discriminate between the MC type groups (AUC 0.73-0.91). MC-ADC-ratio had low to moderate ability (AUC 0.67-0.85). At L4-S1, widest/narrowest LoA were for MC-ADC 20 ± 407/12 ± 254, MC-ADC% 1.6 ± 18.8/1.4 ± 10.4, and MC-ADC-ratio 0.3 ± 4.3/0.2 ± 3.9. Difference between observers > 50% of their mean value was less frequent for MC-ADC (9% of MCs) vs MC-ADC% and MC-ADC-ratio (17-20%). CONCLUSIONS: The MC-ADC variable (highest mean ADC in the MC) had best interobserver reproducibility, discriminated between MC type groups, and may be used in further research. ADC values differed between MC types as expected from previously reported MC histology.

Fathers' Mental Health and Children's Aggressive Behaviour A Study Based on Data from the Norwegian Mother, Father and Child Cohort Study (MoBa).

The aim of the study was to examine the association between fathers' prenatal psychological distress and children's aggressive behaviour in terms of hitting others, and how children's age, gender and temperament affect this association. The study is based on data from 20,155 fathers and mothers from the Norwegian Mother, Father and Child Cohort Study (MoBa). Fathers and mothers completed questionnaires at 17 or 18 weeks of gestation and mothers at children's age 18 months, and 3 and 5 years. Fathers' prenatal psychological distress was assessed by the 5-item Symptom Checklist (SCL-5), and children's temperament by 12 items from the Emotionality Activity Sociability (EAS) Temperament Survey. Increasing prenatal psychological distress in fathers was associated with an increase of hitting from 18 months to 3 years of age in boys. Children's temperament did not affect the association between fathers' prenatal psychological distress and children's aggressive behaviour.

Effect of leukoreduction and temperature on risk of bacterial growth in CPDA-1 whole blood: A study of Escherichia coli.

BACKGROUND: Collection of non-leukoreduced citrate-phosphate-dextrose-adenine (CPDA-1) whole blood is performed in walking blood banks. Blood collected under field conditions may have increased risk of bacterial contamination. This study was conducted to examine the effects of WBC reduction and storage temperature on growth of Escherichia coli (ATCC® 25922™) in CPDA-1 whole blood. METHODS: CPDA-1 whole blood of 450 ml from 10 group O donors was inoculated with E. coli. Two hours after inoculation, the test bags were leukoreduced with a platelet-sparing filter. The control bags remained unfiltered. Each whole blood bag was then split into three smaller bags for further storage at 2-6°C, 20-24°C, or 33-37°C. Bacterial growth was quantified immediately, 2 and 3 h after inoculation, on days 1, 3, 7, and 14 for all storage temperatures, and on days 21 and 35 for storage at 2-6°C. RESULTS: Whole blood was inoculated with a median of 19.5 (range 12.0-32.0) colony-forming units per ml (CFU/ml) E. coli. After leukoreduction, a median of 3.3 CFU/ml (range 0.0-33.3) E. coli remained. In the control arm, the WBCs phagocytized E. coli within 24 h at 20-24°C and 33-37°C in 9 of 10 bags. During storage at 2-6°C, a slow self-sterilization occurred over time with and without leukoreduction. CONCLUSIONS: Storage at 20-24°C and 33-37°C for up to 24 h before leukoreduction reduces the risk of E. coli-contamination in CPDA-1 whole blood. Subsequent storage at 2-6°C will further reduce the growth of E. coli.

Low birthweight is associated with lower glomerular filtration rate in middle-aged mainly healthy women.

BACKGROUND: Low birthweight (LBW) has been shown to increase the risk of severe kidney disease. Studies have also shown associations between LBW and lower estimated glomerular filtration rate (GFR) in young adults. In this study we investigated whether LBW associates with measured GFR (mGFR) in middle-aged mainly healthy adults. METHODS: We invited individuals with LBW (1100-2300 g) and individuals with normal BW (NBW; 3500-4000 g) ages 41-52 years. GFR was measured using plasma clearance of iohexol. BW and BW for gestational age (BWGA) were obtained from the Medical Birth Registry of Norway and tested as main predictors. GFR was the main outcome. RESULTS: We included 105 individuals (57 LBW and 48 NBW). The mean GFR was 95 ± 14 mL/min/1.73 m2 in the LBW group and 100 ± 13 mL/min/1.73 m2 in the NBW group (P = 0.04). There was a significant sex difference: in women the mean GFR was 90 ± 12 versus 101 ± 14 mL/min/1.73 m2 in the LBW and NBW groups, respectively (P = 0.006), whereas corresponding values for men were 101 ± 15 versus 100 ± 11 mL/min/1.73 m2 (P = 0.7). Using linear regression, we found the GFR was 4.5 mL/min/1.73 m2 higher per 1 kg higher BW for women (P = 0.02), with a non-significant 1.2 mL/min/1.73 m2 lower GFR for men (P = 0.6). In analyses of BWGA, there was also a significant association for women, but not for men. CONCLUSIONS: Middle-aged mainly healthy women with LBW had lower mGFR as compared with women with NBW. No such difference was found for men.

Oedema on STIR modified the effect of amoxicillin as treatment for chronic low back pain with Modic changes-subgroup analysis of a randomized trial.

OBJECTIVE: To evaluate potential MRI-defined effect modifiers of amoxicillin treatment in patients with chronic low back pain and type 1 or 2 Modic changes (MCs) at the level of a previous lumbar disc herniation (index level). METHODS: In a prospective trial (AIM), 180 patients (25-64 years; mean age 45; 105 women) were randomised to receive amoxicillin or placebo for 3 months. Primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (0-24 scale) at 1 year. Mean RMDQ score difference between the groups at 1 year defined the treatment effect; 4 RMDQ points defined the minimal clinically important effect. Predefined baseline MRI features of MCs at the index level(s) were investigated as potential effect modifiers. The predefined primary hypothesis was a better effect of amoxicillin when short tau inversion recovery (STIR) shows more MC-related high signal. To evaluate this hypothesis, we pre-constructed a composite variable with three categories (STIR1/2/3). STIR3 implied MC-related STIR signal increases with volume ≥ 25% and height > 50% of vertebral body and maximum intensity increase ≥ 25% and presence on both sides of the disc. As pre-planned, interaction with treatment was analysed using ANCOVA in the per protocol population (n = 155). RESULTS: The STIR3 composite group (n = 41) and STIR signal volume ≥ 25% alone (n = 45) modified the treatment effect of amoxicillin. As hypothesised, STIR3 patients reported the largest effect (- 5.1 RMDQ points; 95% CI - 8.2 to - 1.9; p for interaction = 0.008). CONCLUSIONS: Predefined subgroups with abundant MC-related index-level oedema on STIR modified the effect of amoxicillin. This finding needs replication and further support. KEY POINTS: • In the primary analysis of the AIM trial, the effect of amoxicillin in patients with chronic low back pain and type 1 or 2 MCs did not reach the predefined cut-off for clinical importance. • In the present MRI subgroup analysis of AIM, predefined subgroups with abundant MC-related oedema on STIR reported an effect of amoxicillin. • This finding requires replication and further support.

Investigating novel biomarkers of immune activation and modulation in the context of sedentary behaviour: a multicentre prospective ischemic stroke cohort study.

BACKGROUND: Sedentary behaviour is associated with disease, but the molecular mechanisms are not understood. Valid biomarkers with predictive and explanatory properties are required. Therefore, we have investigated traditional and novel biomarkers of inflammation and immune modulation and their association to objectively measured sedentary behaviour in an ischemic stroke population. METHODS: Patients admitted to hospital with acute ischemic stroke were included in the multicentre Norwegian Cognitive Impairment After Stroke (Nor-COAST) study (n = 815). For this sub-study (n = 257), sedentary behaviour was registered 3 months after stroke using position transition data from the body-worn sensor, ActivPal®. Blood samples were analysed for high sensitive C-reactive protein (hsCRP), the cytokines interleukin-6 (IL-6) and 10 (IL-10), neopterin, tryptophan (Trp), kynurenine (kyn), kynurenic acid (KA), and three B6 vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and pyridoxic acid (PA). The kynurenine/tryptophan ratio (KTR) and the pyridoxic acid ratio index (PAr = PA: PL + PLP) were calculated. RESULTS: Of the 815 patients included in the main study, 700 attended the three-month follow-up, and 257 fulfilled the inclusion criteria for this study. Sedentary time was significantly associated with levels of hsCRP, IL-6, neopterin, PAr-index, and KA adjusted for age, sex, waist circumference, and creatinine. In a fully adjusted model including all the significant biomarkers except hsCRP (because of missing values), sedentary time was independently positively associated with the PAr-index and negatively with KA. We did not find an association between sedentary behaviour, IL-10, and KTR. CONCLUSIONS: The PAr-index is known to capture several modes of inflammation and has previously shown predictive abilities for future stroke. This novel result indicates that the PAr-index could be a useful biomarker in future studies on sedentary behaviour and disease progression. KA is an important modulator of inflammation, and this finding opens new and exciting pathways to understand the hazards of sedentary behaviour. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted 08/01/2016.

Neopterin and kynurenic acid as predictors of stroke recurrence and mortality: a multicentre prospective cohort study on biomarkers of inflammation measured three months after ischemic stroke.

BACKGROUND: Chronic low-grade inflammation is associated with both ischemic stroke and sedentary behaviour. The aim of this study was to investigate the predictive abilities of biomarkers of inflammation and immune modulation associated with sedentary behaviour for ischemic stroke recurrence and mortality in a stroke population. METHODS: Patients admitted to hospital for acute stroke were recruited to the prospective multicentre cohort study, the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, from May 2015 until March 2017. Patients with ischemic stroke, blood samples available from the three-month follow-up, and no stroke recurrence before the three-month follow-up were included. Serum was analysed for C-reactive protein (CRP) with high-sensitive technique, and plasma for interleukin-6 (IL-6), neopterin, pyridoxic acid ratio index (PAr-index: 4-pyridoxic acid: [pyrioxal+pyridoxal-5'-phosphate]) and kynurenic acid (KA). Ischemic stroke recurrence and death were identified by the Norwegian Stroke Registry and the Cause of Death Registry until 31 December 2018. RESULTS: The study included 354 patients, 57% male, mean age 73 (SD 11) years, mean observation time 2.5 (SD 0.6) years, and median National Institute of Health Stroke Scale of 0 (IQR 1) at three months. CRP was associated with mortality (HR 1.40, CI 1.01, 1.96, p = 0.046), and neopterin was associated with the combined endpoint (recurrent ischemic stroke or death) (HR 1.52, CI 1.06, 2.20, p = 0.023), adjusted for age, sex, prior cerebrovascular disease, modified Rankin Scale, and creatinine. When adding neopterin and KA to the same model, KA was negatively associated (HR 0.57, CI 0.33, 0.97, p = 0.038), and neopterin was positively associated (HR 1.61, CI 1.02, 2.54, p = 0.040) with mortality. Patients with cardioembolic stroke at baseline had higher levels of inflammation at three months. CONCLUSION: Neopterin might be a valuable prognostic biomarker in stroke patients. The use of KA as a measure of anti-inflammatory capacity should be investigated further. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted on 08/01/2016.

Comparison of Performance Score for Female and Male Residents in General Surgery Doing Supervised Real-Life Laparoscopic Appendectomy: Is There a Norse Shield-Maiden Effect?

BACKGROUND: Gender bias may represent a threat to resident assessment during surgical training, and there have been concerns that women might be disadvantaged. There is a lack of studies investigating gender differences in 'entry-level' real-life procedures, such as laparoscopic appendectomy. We aimed to explore potential gender disparities in self-evaluation and faculty evaluation of a basic surgical procedure performed by junior surgical residents in general surgery. METHODS: A structured training program in laparoscopic appendectomy was implemented before undertaking evaluation of real-life consecutive laparoscopic appendectomies by junior residents in general surgery. Resident and faculty gender-pairs were assessed. Intraclass correlation coefficient (ICC) was calculated using a single-rater, consistency, 2-way mixed-effects model. RESULTS: A total of 165 paired sessions were completed to evaluate resident-faculty scores for the procedure. Overall, 19 residents participated (43% women) and 26 faculty (42% women) were involved. The overall correlation between faculty and residents was good (ICC > 0.8). The female-female pairs scored higher for most steps, achieving excellent (ICC ≥ 0.9) for several steps and for overall performance. Female residents were more likely to give a higher self-evaluated score on own performance particularly if evaluated by a female faculty. Also, female trainees had highest correlation-score with male faculty. CONCLUSIONS: This study found higher performance scores in female surgical residents evaluated during real-time laparoscopic appendectomy. No negative gender bias toward women was demonstrated. Better insight into the dynamics of gender-based interaction and dynamics in both training, feedback and influence on evaluation during training is needed when evaluating surgical training programs.

Cold-stored whole blood in a Norwegian emergency helicopter service: an observational study on storage conditions and product quality.

BACKGROUND: Increasing numbers of emergency medical service agencies and hospitals are developing the capability to administer blood products to patients with hemorrhagic shock. Cold-stored whole blood (WB) is the only single product available to prehospital providers who aim to deliver a balanced resuscitation strategy. However, there are no data on the safety and in vitro characteristics of prehospital stored WB. This study aimed to describe the effects on in vitro quality of storing WB at remote helicopter bases in thermal insulating containers. STUDY DESIGN AND METHODS: We conducted a two-armed single-center study. Twenty units (test) were stored in airtight thermal insulating containers, and 20 units (controls) were stored according to routine procedures in the Haukeland University Hospital Blood Bank. Storage conditions were continuously monitored during emergency medical services missions and throughout remote and blood bank storage. Hematologic and metabolic variables, viscoelastic properties, and platelet (PLT) aggregation were measured on Days 1, 8, 14, and 21. RESULTS: Storage conditions complied with the EU guidelines throughout remote and in-hospital storage for 21 days. There were no significant differences in PLT aggregation, viscoelastic properties, and hematology variables between the two groups. Minor significantly lower pH, glucose, and base excess and higher lactate were observed after storage in airtight containers. CONCLUSION: Forward cold storage of WB is safe and complies with EU standards. No difference is observed in hemostatic properties. Minor differences in metabolic variables may be related to the anaerobic conditions within the thermal box.

Blue-blocking glasses as additive treatment for mania: Effects on actigraphy-derived sleep parameters.

Improvement of sleep is a central treatment goal for patients in a manic state. Blue-blocking (BB) glasses as adjunctive treatment hasten overall recovery from mania. This method is an evolvement from dark therapy and builds on the discovery of the blue-light-sensitive retinal ganglion cell that signals daytime to the brain. We report effects of adjunctive BB glasses on actigraphy-derived sleep parameters for manic inpatients as compared to placebo. Hospitalized patients with bipolar disorder in a manic state aged 18-70 years were recruited from five clinics in Norway from February 2012 to February 2015. The participants were randomly allocated to wearing BB glasses or placebo (clear glasses) as an adjunctive treatment from 18:00 to 08:00 hours for seven consecutive nights. Sleep and wake were monitored by actigraphy. From 32 eligible patients, 10 patients in each group qualified for the group analyses. The BB group's mean sleep efficiency was significantly higher at night 5 as compared to the placebo group (92.6% vs. 83.1%, p = .027). The 95% confidence interval (CI) was 89.4%-95.8% in the BB group and 75.9%-90.3% in the placebo group. There were fewer nights of interrupted sleep in the BB group: 29.6% versus 43.8% in the placebo group. The BB group received less-intensive sleep-promoting pharmacological treatment and showed significantly higher sleep efficiency and more consolidated sleep as compared to the placebo group. Our findings suggest sleep-promoting effects through deactivating mechanisms. Adjunctive BB glasses seem to be useful for improving sleep for manic patients in the hospital setting.

Tumour architecture, grade and location remain predictors of non-organ-confined upper tract urothelial carcinoma at time of radical nephroureterectomy: results from a multicenter Norwegian external validation study.

PURPOSE: Selecting patients for intensified treatment for upper tract urothelial carcinoma can be challenging, partly due to the lack of accurate preoperative staging tools. Several preoperative staging models for upper tract urothelial carcinoma have been presented, but none have been externally validated. The aim of the current study was to perform an external validation of the Margulis nomogram for predicting non-organ-confined upper tract urothelial carcinoma at time of nephroureterectomy. METHODS: 209 patients from two high-volume centres in Norway were treated with radical nephroureterectomy during the period 2005-2017. 163 patients with complete data necessary for external validation of the Margulis nomogram were included in the study. All relevant covariates were analysed with uni- and multivariate regression analysis to assess their ability to predict non-organ-confined disease. The Margulis nomogram was applied on the present cohort to calculate predicted risk of non-organ-confined disease. This was compared to the observed risk to assess model calibration. The Margulis nomogram accuracy was measured as the area under the curve in a receiver operator characteristics curve to evaluate model discrimination. RESULTS: Tumour grade (OR 28.1, p = 0.001) and architecture (OR 4.72, p < 0.001) were independent predictors of non-organ-confined disease. There was a high concordance between predicted and observed risk quantified with a Cronbach alpha of 0.96. The Margulis nomogram had an area under the curve of 0.83 in predicting non-organ-confined disease when applied on the current cohort. CONCLUSIONS: We consider the Margulis nomogram validated for clinical use.

Moderate-to-vigorous intensity physical activity is associated with modified fatigue during and after cancer treatment.

PURPOSE: The primary objective was to investigate the association between the amount of time spent in moderate-to-vigorous intensity physical activity (MVPA) and cancer-related fatigue (CRF) before, during, and 2 years after start of treatment. METHODS: The results of the present study are based on data from the study "Early rehabilitation of cancer patients." Two hundred and forty patients (109 females) with one of the following cancer types were included: breast, colorectal, prostate and testicular cancer, and lymphoma. Chalder's fatigue questionnaire (FQ) was used to map CRF at baseline, 4, 8, 12, and 24 months post-inclusion. Baseline was at the time of diagnosis, before treatment start. Physical activity was recorded using SenseWear armband (SWA) at baseline, 4 and 24 months post-inclusion. RESULTS: One hour increased MVPA daily at baseline was associated with lower fatigue with - 0.8 at 4 months' follow-up (p < 0.001), - 0.7 at 8 months' follow-up (p = 0.001), - 0.6 at 12 months' follow-up (p = 0.008), and - 0.5 at 24 months' follow-up (p < 0.043). The participants maintained and improved PA level at the two follow-up points. CONCLUSION: The results imply that the amount of time spent in moderate to vigorous intensity physical activity at baseline can modify cancer related fatigue during and after cancer treatment. The participants managed to maintain and improve their activity level at the two follow-up points. Future research should map fatigue and measure activity, with objective measurement units, at several measurement points to map activity level over time and to substantiate these results.

Factors associated with self-rated health in a Norwegian population of older people participating in a preventive home visit program: a cross-sectional study.

BACKGROUND: Assessing self-rated health by preventive home visits of older people can provide information about the person's well-being, quality of life and risk of developing illness. The aim of this study was to examine associations between self-rated health and factors related to demographics, lifestyle, health conditions and medical diagnoses by older people participating in a preventive home visit program. METHODS: A cross-sectional study including 233 participants (age 75-79) from three municipalities of Western Norway was conducted. Data were collected through preventive home visits performed by six nurses, using a questionnaire including self-rated health assessment and questions and tests related to demographics (e.g. education and housing), lifestyle (e.g. social activities, alcohol and smoking), health conditions (e.g. sensory impairment, pain and limited by disease) and medical diagnoses. Descriptive and inferential statistics including linear block-wise regression model were applied. RESULTS: The block-wise regression model showed that the variables Limited by disease and Pain were negatively associated with self-rated health and Use internet was positively associated. The model had a R2 0.432. The variable that contributed to largest change in the model was Limited by disease (R2 Change; 0.297, p-value< 0.001). CONCLUSIONS: In the present study, being limited by disease and pain were strongly associated with poor self-rated health, indicating that these are important factors to assess during a preventive home visit. Also, digital competence (Use internet) was associated with a better self-rated health, suggesting that it could be useful to ask, inform and motivate for the use of digital tools that may compensate for or improve social support, social contact and access to health -related information.

Magnetic resonance radiomics for prediction of extraprostatic extension in non-favorable intermediate- and high-risk prostate cancer patients.

BACKGROUND: To investigate whether magnetic resonance (MR) radiomic features combined with machine learning may aid in predicting extraprostatic extension (EPE) in high- and non-favorable intermediate-risk patients with prostate cancer. PURPOSE: To investigate the diagnostic performance of radiomics to detect EPE. MATERIAL AND METHODS: MR radiomic features were extracted from 228 patients, of whom 86 were diagnosed with EPE, using prostate and lesion segmentations. Prediction models were built using Random Forest. Further, EPE was also predicted using a clinical nomogram and routine radiological interpretation and diagnostic performance was assessed for individual and combined models. RESULTS: The MR radiomic model with features extracted from the manually delineated lesions performed best among the radiomic models with an area under the curve (AUC) of 0.74. Radiology interpretation yielded an AUC of 0.75 and the clinical nomogram (MSKCC) an AUC of 0.67. A combination of the three prediction models gave the highest AUC of 0.79. CONCLUSION: Radiomic analysis combined with radiology interpretation aid the MSKCC nomogram in predicting EPE in high- and non-favorable intermediate-risk patients.