Novel drug resistance mechanisms and drug targets in BRAF-mutated peritoneal metastasis from colorectal cancer.

BACKGROUND: Patients with peritoneal metastasis from colorectal cancer (PM-CRC) have inferior prognosis and respond particularly poorly to chemotherapy. This study aims to identify the molecular explanation for the observed clinical behavior and suggest novel treatment strategies in PM-CRC. METHODS: Tumor samples (230) from a Norwegian national cohort undergoing surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C (MMC) for PM-CRC were subjected to targeted DNA sequencing, and associations with clinical data were analyzed. mRNA sequencing was conducted on a subset of 30 samples to compare gene expression in tumors harboring BRAF or KRAS mutations and wild-type tumors. RESULTS: BRAF mutations were detected in 27% of the patients, and the BRAF-mutated subgroup had inferior overall survival compared to wild-type cases (median 16 vs 36 months, respectively, p < 0.001). BRAF mutations were associated with RNF43/RSPO aberrations and low expression of negative Wnt regulators (ligand-dependent Wnt activation). Furthermore, BRAF mutations were associated with gene expression changes in transport solute carrier proteins (specifically SLC7A6) and drug metabolism enzymes (CES1 and CYP3A4) that could influence the efficacy of MMC and irinotecan, respectively. BRAF-mutated tumors additionally exhibited increased expression of members of the novel butyrophilin subfamily of immune checkpoint molecules (BTN1A1 and BTNL9). CONCLUSIONS: BRAF mutations were frequently detected and were associated with particularly poor survival in this cohort, possibly related to ligand-dependent Wnt activation and altered drug transport and metabolism that could confer resistance to MMC and irinotecan. Drugs that target ligand-dependent Wnt activation or the BTN immune checkpoints could represent two novel therapy approaches.

Effects of feeding whole-cracked rapeseeds, nitrate, and 3-nitrooxypropanol on protein composition, minerals, and vitamin B in milk from Danish Holstein cows.

The present study was conducted to assess the individual or combined effects of feeding dietary fat (whole-cracked rapeseed), nitrate, and 3-nitrooxypropanol (3-NOP) on protein profile, mineral composition, B vitamins, and nitrate residues in milk from dairy cows. Forty-eight Danish Holstein cows used in an 8 × 8 incomplete Latin square design were fed 8 factorially arranged diets ((30 or 63 g crude fat/kg DM) × (0 or 10 g nitrate/kg DM) × (0 or 80 mg 3-NOP/kg DM)) over 6 periods of 21 d each. In each period, milk samples were collected from individual cows during the third week by pooling milk obtained from 4 consecutive milkings, and analyzed for protein profile including protein modifications, mineral composition, riboflavin, cobalamin, and presence of nitrate residues. Fat supplementation led to an increase in the phosphorylation degree of αS1-CN by 8.5% due to a decreased relative proportion of αS1-CN 8P and an increased relative proportion of αS1-CN 9P and further to a decrease in the relative proportion of αS2-CN by 2.4%. Additionally, fat supplementation decreased the relative proportions of glycosylated and unglycosylated forms of κ-CN, consequently leading to a 3.6% decrease in total κ-CN. In skim milk, K, Ca, P, and Mg concentrations were altered by individual use of fat, nitrate, and 3-NOP. Feeding nitrate resulted in a 5.4% increase in riboflavin concentration in milk while supplementing 3-NOP increased cobalamin concentration in milk by 21.1%. The nitrate concentration in milk was increased upon feeding nitrate however, this increased concentration was well below the maximum permissible limit of nitrate in milk (<50 mg/L). In conclusion, no major changes were observed in milk protein, and mineral compositions by feeding fat, nitrate, and 3-NOP to dairy cows while the increased riboflavin and cobalamin by nitrate and 3-NOP, respectively, could be of beneficial nutritional value for milk consumers.

The validity of instruments to measure knowledge in population-based cancer screening targeting individuals at average risk - A systematic review.

OBJECTIVES: Relevant knowledge is essential for informed choices about (non)participation in population-based cancer screening. Many instruments have been proposed to assess residents' knowledge about cancer screening programmes but their measurement properties are unknown. This systematic review aims to identify and critically evaluate the measurement properties of instruments to measure knowledge about cancer screening in individuals eligible for population-based screening. METHODS: A literature search was undertaken in PubMed, PsycINFO, Embase, CINAHL, Scopus and Web of Science in August 2023. The review included any study reporting one or more measurement properties of the questionnaire or sub-scale used measuring knowledge of cancer screening including breast, colorectal and/or cervical cancer screening. Studies including males aged 45 or older and females aged 20 or older were included. Two independent reviewers screened the articles and assessed the included articles using the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN). RESULTS: We included 24 instruments, which varied in number and characteristics of items. All instruments were assessed as having an inadequate instrument development. The results of structural validity, internal consistency, criterion validity and reliability were assessed as indeterminate, while construct validity and responsiveness were assessed as sufficient. CONCLUSION: This systematic review identified no instruments to measure knowledge about cancer screening where the measurement properties were sufficiently evaluated. There is a lack of focus on content validity and structural validity, and further validation of the instruments is needed. The results indicate a lack of shared understanding or agreement of what constitutes relevant knowledge about cancer screening.

Differences in the referral process from general practice to resident specialists in gynaecology depending on density of specialists and patients' socioeconomic status.

BACKGROUND: There are significant differences in the densities of resident specialists in gynaecology (RSGs) in various regions of Denmark. It is unclear whether this disparity affects gynaecological patients' experience of the referral process and whether it differs in terms of their socioeconomic status (SES). OBJECTIVE: To examine gynaecological patients' experiences of the referral process to an RSG concerning RSG density and patients' SES. DESIGN: Cross-sectional questionnaire and registry-based study. SETTING: In Denmark, general practitioners (GPs) serve as gatekeepers of secondary care and are responsible for referrals to resident specialists as well as inpatient and outpatient hospital care. SUBJECTS: A total of 2917 patients who consulted an RSG participated in this study. MAIN OUTCOME MEASUREMENTS: Patients' experiences of referral to an RSG, waiting times, involvement, and how they experienced the referral process. RESULTS: Patients who lived in the highest density RSG region were referred to an RSG more promptly after the onset of symptoms, had to visit their GP less frequently to obtain a referral to the RSG, and rarely received a gynaecological examination by their GP compared with those living in regions with lower RSG densities. Moreover, their waiting times were shorter, and more often, the patients themselves proposed to be referred to an RSG. The findings show that RSG density had a greater impact on women's experiences than SES. CONCLUSION: To allow equal access to specialist care, RSG density must be equal across all regions in the country.

Danish women's preferences regarding gynecological examination support international recommendations: A cross-sectional study.

OBJECTIVE: Gynecological examinations (GEs) are challenging for many women. Several recommendations and guidelines have emerged, partly based on common sense and clinicians' consensus. However, there is a lack of knowledge regarding women's opinions. Therefore, this study aimed to describe women's preferences and experiences in relation to GEs and investigate whether they are dependent on their socioeconomic status. METHODS: In Denmark, GEs are typically performed by general practitioners or resident specialists in gynecology (RSGs) in gynecological hospital departments. This cross-sectional questionnaire and register study included approximately 3000 randomly selected patients who visited six RSGs from January 1, 2020, to March 1, 2021. The main outcome measurement involved women's preferences and experiences regarding GEs. RESULTS: Overall, 37% of the women thought that a changing room was important, 20% preferred a garment to cover themselves, 18% preferred a separate examination room, and 13% thought that the presence of a chaperone was important. Compared with working and retired women, more women outside the workforce felt insufficiently informed, considered their experience with RSGs unprofessional, and found GEs painful. CONCLUSION: Our results support existing recommendations regarding GEs and the related environment, confirming that privacy and modesty are factors to take into consideration as they are of concern for a relatively large group of women. Thus, providers should focus on women outside the workforce, because this group appears to feel vulnerable in this environment.

Danish general practitioners as gatekeepers for gynaecological patients in regions with different density of resident specialists in gynaecology: in which situations and to whom do they refer? A cross-sectional study.

BACKGROUND: There are large differences in the density of Resident Specialists in Gynaecology (RSG) in the various regions of Denmark. It is unknown if this inequality affects the General Practitioner (GP) referral patterns of gynaecological patients. OBJECTIVE: To investigate the GP referral patterns of gynaecological patients to the RSG or to the Hospital/Outpatient Clinic (HOC) in specific situations according to the regional density of RSGs. Moreover, to examine whether GPs prefer to refer to the HOC or to the RSG, or whether they were treated by the GP depending on the density of RSGs, specifically, in six benign gynaecological diagnoses. DESIGN: A cross-sectional questionnaire survey. SETTING: In Denmark, GPs serve as gatekeepers to secondary care, being responsible for referrals to resident specialists and in- and outpatient hospital care. SUBJECTS: Five hundred Danish GPs were randomly selected and invited to take part in the questionnaire study. Main outcome measurements: Referral patterns: Own treatment, RSG, or HOC. RESULTS: GPs prefer to refer their gynaecologic patients to RSGs rather than to HOCs. In addition, the study shows the higher the density of RSGs, the more gynaecological patients are referred to the RSG. This also applies to the six diagnoses examined. CONCLUSION: To allow patients' equal access to specialist care, the density of RSGs must be equal all over the country.

The impact of diabetes on cancer detection during the prevalence round of a national screening program for colorectal cancer.

AIMS: Diabetes is associated with a higher risk of colorectal cancer (CRC) and inferior survival after CRC. Screening may enable the early detection of CRC. We aimed to assess the impact of diabetes on cancer detection and disease stage during the prevalence round of a national CRC screening program. METHODS: We performed a register-based cohort study based on the randomized procedure for inviting Danish residents aged 50-74 years to the prevalence round of national CRC screening program in 2014-2017. By comparing the random half of the population who had been invited by 1 May 2016 with the not yet invited half, the effect of screening was assessed by the detection of CRC and disease stage among individuals with and without diabetes. Further, the impact of diabetes on the screening participation rate was calculated. RESULTS: By randomisation, 504,673 individuals had been invited to the CRC screening by 1 May 2016, and 549,359 individuals had not yet been invited. The diabetes prevalence was 10% in both groups. When comparing those not yet invited to those invited, the effect of screening on the number of detected cancers per 100,000 individuals was higher in those with diabetes (from 207 to 494 cancers) than in those without diabetes (from 147 to 364 cancers), and screening resulted in overall higher proportions of stage I cancer. Among those invited to screening, the participation rate was 9.1% lower (95% CI: 8.7%-9.5%) in individuals with versus without diabetes. CONCLUSIONS: Despite a lower participation rate, the effect of CRC screening was higher in individuals with diabetes.

Levels of anxiety in women aged ≥45 years undergoing diagnostic large loop excision of the transformation zone: A longitudinal study.

OBJECTIVE: To measure anxiety levels in women aged ≥45 years undergoing diagnostic large loop excision of the transformation zone (LLETZ) at the first colposcopy visit. DESIGN: Longitudinal study. SETTING: Three colposcopy clinics in the Central Denmark Region. POPULATION: Women aged ≥45 years undergoing diagnostic LLETZ. METHODS: Women completed the State-Trait Anxiety Inventory (STAI) and Short Form 12 (mental and physical health) questionnaires before, immediately after, and at 1 and 6 months after LLETZ. MAIN OUTCOME MEASURES: STAI state anxiety median scores were calculated and stratified by health status, by letter with information about screening result and by LLETZ results. RESULTS: Of 109 eligible women, 11 were excluded, leaving 98 women for the final analyses. Response rates ranged from 84.7% to 100%. Overall, state anxiety levels were low; however, a decrease was observed from before to immediately after the LLETZ (33.4 vs 29.3, p < 0.001). The anxiety levels remained stable up to 6 months after LLETZ. Women with poor mental health were more likely to have higher anxiety levels compared with women with good mental health (before LLETZ, RR 3.77, 95% CI 2.12-6.70; 1 month after LLETZ, RR 3.37, 95% CI 1.59-7.15; 6 months after LLETZ, RR 1.93, 95%CI 1.06-3.51). CONCLUSIONS: Overall, colposcopy and diagnostic LLETZ in women aged ≥45 years were not associated with high levels of anxiety. Anxiety levels were highest before colposcopy, and the women seemed to experience immediate relief afterwards. Women with poor mental health had the highest anxiety levels throughout the study, which might call for special attention.

"It's cancer screening after all". Barriers to cervical and colorectal cancer screening and attitudes to promotion of self-sampling kits upon attendance for breast cancer screening.

OBJECTIVES: To explore barriers to cervical and colorectal cancer screening and attitudes to promotion of self-sampling kits upon attendance for breast cancer screening. METHODS: Interview study with women who had not responded to one or more invitations to cervical or colorectal cancer screening. A semi-structured interview guide was used and interviews were audio recorded and transcribed verbatim. Concepts from Temporal Motivation Theory were used to structure and analyse the data. RESULTS: Twenty-two women were interviewed. Screening was highly valued but the women perceived screening for cervical cancer and colorectal cancer as more troublesome to participate in, compared with participation in breast cancer screening. The lack of a pre-booked appointment or a suggested deadline attenuated the perceived value of cervical and colorectal cancer screening and this further increased procrastination. Promotion of self-sampling kits for cervical and colorectal cancer screening upon attendance for breast cancer screening was considered a feasible way to increase salience of both types of screening. CONCLUSION: A high number of micro steps and absence of a deadline in cervical and colorectal cancer screening diverted attention away from screening participation in cervical and colorectal cancer screening. The main facilitator could be reduction of micro actions, proposing a suggested deadline, and promotion of self-sampling kits when attending breast cancer screening to increase salience and a renewed attention to all three screening programmes.

The impact of pre-notifications and reminders on participation in colorectal cancer screening - A randomised controlled trial.

This study aimed to test whether participation in colorectal cancer (CRC) screening can be increased by combining the standard invitation procedure with a pre-notification and/or an extra reminder. In a non-blinded randomised controlled trial nested in a population-based CRC screening programme employing the faecal immunochemical test, Group I received a three-staged invitation procedure (pre-notification, invitation and one reminder), Group II received a three-staged invitation procedure (invitation and two reminders) and Group III received a four-staged invitation procedure (pre-notification, invitation and two reminders). The control group received the invitation and one reminder (usual procedure). A total of 59,041 participants were included in the analyses. Overall participation rates increased from 66.9% in the control group to 69.8% in the four-staged invitation procedure corresponding to an increase in overall participation rate of 2.9% (95% CI: 1.8 to 4.0). In the age group 50-59 years, the four-staged invitation procedure increased the participation rate by 4.0% (95% CI: 2.4 to 5.6). An extra reminder increased participation with 2.7% (95% CI: 1.1; 4.2) for males compared to 1.1% (95% CI: -0.3; 2.5) for females. In conclusion, the four-staged invitation procedure was the most effective invitation procedure indicating that multiple invitation procedures are most effective, especially in the youngest age group. If a three-staged invitation procedure is applied, a second reminder should be preferred over a pre-notification. Trial registration The project was registered at ClinicalTrials.gov on 26 February 2020 and patient enrolment began in August 2020. ClinicalTrials.gov Identifier: NCT04292366.

Three birds with one stone: a protocol for a randomised intervention study to increase participation in cervical and colorectal cancer screening among women attending breast cancer screening.

INTRODUCTION: The participation rate is higher in breast cancer screening than in cervical cancer (CCU) and colorectal cancer (CRC) screening. In this cluster-randomised study, we aim to evaluate an intervention offering home-based CCU and CRC screening to women when attending breast cancer screening if they are overdue for CCU and/or CRC screening. METHODS AND ANALYSIS: On intervention days, one of the five breast cancer screening units in the Central Denmark Region will be randomly allocated to intervention, whereas the remaining units will serve as control. Women attending breast cancer screening in the intervention unit will be offered information regarding their CCU and CRC screening history, and, if overdue, they will be offered self-sampling screening kits. For CCU screening, women aged 50-64 years will be offered a vaginal self-sampling kit for human papillomavirus testing. For CRC screening, women aged 50-69 years will be offered a kit to obtain a faecal immunochemical test. Women attending the control units will receive only standard care.After the intervention, a survey will be sent to all women in the intervention and control group, asking about their experience while attending breast cancer screening.Primary outcomes will be difference in the coverage in CCU and CRC screening 6 months after intervention between the intervention and the control group, and difference in participation rates 6 months after intervention for those who were overdue for CCU and/or CRC screening at the time of the intervention. ETHICS AND DISSEMINATION: The project is listed in the record of processing activities for research projects in the Central Denmark Region (R. No.: 1-16-02-217-21). According to the Danish Consolidation Act on Research Ethics Review of Health Research Project, this study was not notifiable to the Committee (R. No.: 1-10-72-1-21). The findings will be disseminated in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT05022511.

What can We Learn From High-Performing Screening Programs to Increase Bowel Cancer Screening Participation in Australia?

BACKGROUND: Colorectal cancer (CRC) is the second most diagnosed cancer in men and women and second most common cause of cancer death in Australia; Australia's CRC incidence and mortality are among the world's highest. The Australian National Bowel Cancer Screening Program began in 2006; however, only 33% of those approached for the first time by the Program between 2018 and 2019 returned the kit. Of the 5.7 million kits sent during this period, only 44% were returned. Our aim was to identify practices and features of national bowel cancer screening programs in countries with similar programs but higher screening participation, to identify potential interventions for optimising Australian CRC screening participation. METHODS: We searched published and grey literature for CRC screening programs reporting at least 50% screening participation using postal invitation and free return of iFOBT home kits. Interviews were conducted with cancer registry staff and academic researchers, focused on participant and practitioner engagement in screening. RESULTS: National programs in Netherlands, Scotland, Denmark, and Finland reported over 50% screening participation rates for all invitation rounds. Shared characteristics include small populations within small geographic areas relative to Australia; relatively high literacy; a one-sample iFOBT kit; national registration systems for population cancer screening research; and screening program research including randomised trials of program features. CONCLUSIONS: Apart from the one-sample kit, we identified no single solution to persistent Australian low uptake of screening. Research including randomised trials within the program promises to increase participation. IMPACT: This screening program comparison suggests that within-program intervention trials will lead to increased Australian screening participation.

The importance of an outdoor playground for children with epilepsy and their family during and after hospitalization: A qualitative study of parents' experiences.

OBJECTIVES: To explore parents' experiences of using an outdoor playground during hospitalization with their child with epilepsy. METHOD: The study is based on a qualitative exploratory design. Semi-structured individual interviews were conducted with 10 parents with a child with epilepsy (6-11 years). A phenomenological- hermeneutic approach was taken, inspired by Ricoeur. Data analysis and interpretation have been conducted at three levels: naive reading, structural analysis, and critical interpretation and discussion. RESULTS: During hospitalization the playground was the children's territory, where children felt safe, in control and normality. Parents experienced valuable time with their children through participation, and play facilitated communication and reduced pain and negative emotions. The playground improved parents and children's emotional well-being during hospitalization. Further, it supported coping with epilepsy, and contributed to gain successful experiences thus children developed self-esteem. CONCLUSION: The study indicates that to the parents, an outdoor playground at the hospital environment is valuable for supporting children with epilepsy and their families to cope with hospitalization and everyday life, and it contributes to improve the family's physical, social and emotional well-being. The results emphasize that play at an outdoor playground could be integrated in the care and treatment during hospitalization.

Colorectal cancer mortality after randomized implementation of FIT-based screening - a nationwide cohort study.

OBJECTIVE: Evidence of reduction in colorectal cancer (CRC) mortality following CRC screening based on the faecal immunochemical test (FIT) is insufficient. This study aimed to analyse if CRC mortality was reduced after implementing FIT-based screening. SETTING: The Danish national CRC screening programme. METHODS: This nationwide cohort study included residents aged 50-71 years invited to the prevalence round of the screening programme. Invitation order was decided by randomising on birth month; the first two birth months to be invited were classified as invited and the five last were classified as not-yet-invited and given a pseudo invitation data. Follow-up was from (pseudo)invitation date until 31 December 2017, emigration or death. Relative risk (RR) of CRC death was calculated with 95% confidence intervals (CIs). RESULTS: A total of 897,812 residents were included (29% invited and 71% not-yet-invited). The median follow-up was 3.3 years. The RR of CRC death at end of follow-up was 0.83 (95% CI 0.66; 1.03) among those invited to screening compared with those not yet invited. For men aged 60-71 years, this RR was 0.68 (95% CI 0.49; 0.94). For those participating in screening compared with a similar group of not-yet-invited residents, the RR was 0.71 (95% CI 0.46-1.08). For male participants aged 60-71 years, this RR was 0.49 (95% CI 0.27-0.89). For women and men aged 50-59 years, RRs were small and statistically non-significant. CONCLUSION: This nationwide study showed that even within a median follow-up of only 3.3 years, implementing FIT-based CRC screening reduced CRC mortality among older men.

The relative effectiveness of fecal immunochemical test-based colorectal cancer screening to detect adenomas and cancer in different demographic and socioeconomic groups. A nationwide cohort study.

INTRODUCTION: This study aimed at analyzing the relative effectiveness in removal of adenomas and detection of cancer of implementing colorectal cancer (CRC) screening in different demographic and socioeconomic groups. METHODS: This register-based retrospective cohort study included residents aged 50-72 years. Those randomly selected to be invited for CRC screening from 1 March 2014 to 30 June 2015 were classified as invited; those invited from 1 January 2016 to 31 December 2017 were classified as not yet invited. Strata-specific relative risks (RRs) of having adenomas removed and CRC detected were estimated. RESULTS: A total of 1 343 090 individuals were included. The RR of having adenomas removed were higher among men compared with women [RR women = 6.41 (95% confidence interval [CI]: 5.08-8.09), RR men = 7.74 (95% CI: 6.16-9.73), P < 0.01] and among Danes compared with immigrants [RR Danes = 4.71 (95% CI: 3.73-5.93), RR Western = 4.76 (95% CI: 3.39-6.69), RR non-Western = 3.35 (95% CI: 2.39-4.69), P = 0.03]. Regarding detection of CRC, the effectiveness increased with increasing age ranging from RR = 1.53 (95% CI: 0.93- 2.51) to RR = 1.97 (95% CI: 1.22-3.17) ( P = 0.04) and was higher among men compared with women (RR women = 1.75 (95% CI: 1.10-2.76), RR men = 2.07 (95% CI: 1.32-3.26), P = 0.02. CONCLUSION: Attention must be paid to the potential differences in screening effectiveness among diverse subpopulations; first, by securing equal opportunities for participation across subpopulations and second, by considering sex and age-specific screening programs.

Making decisions on your own: Self-administered decision aids about colorectal cancer screening - A systematic review and meta-analyses.

OBJECTIVE: To provide a systematic review of self-administered decision aids (DAs) for citizens invited to participate in colorectal cancer screening synthesizing the effectiveness of self-administered DAs on informed choice or the components hereof; knowledge, attitudes, and participation. METHODS: The literature search was undertaken in PubMed, CINAHL, PsycINFO, Embase and Scopus and last updated 19 March 2021. Results were presented by narrative synthesis, meta-analyses and vote counting based on direction of effect. RESULTS: Fourteen studies of fair methodological quality were included. One study reported on informed choice and 13 studies reported on the components. Self-administered DAs increased participation and knowledge whereas it was inconclusive with regard to attitudes towards screening. The studies were very heterogeneous with different comparators, outcomes and means of measurement. CONCLUSION: This systematic review showed a potential for self-administered DAs to support informed choice in colorectal cancer screening, especially by increasing knowledge. PRACTICE IMPLICATIONS: It seems reasonable to consider informed choice to be one of the main outcomes of self-administered DAs. Yet there is a need for consensus on how to measure informed choice in cancer screening, especially a validated measurement of knowledge defining what constitutes 'adequate knowledge'.

Prevalence of self-reported abdominal symptoms among 50-74-years-old men and women eligible for colorectal cancer screening -a cross-sectional study.

BACKGROUND: Screening is defined as the identification of unrecognized disease in an apparently healthy population. Symptomatic individuals are recommended to contact a physician instead of participating in screening. However, in colorectal cancer (CRC) screening this approach may be problematic as abdominal symptoms are nonspecific. This study aimed at identifying the prevalence of self-reported abdominal symptoms among screening-eligible men and women aged 50-74 years. METHODS: This cross-sectional survey study included 11,537 individuals aged 50-74 years invited for CRC screening from 9 to 23 September 2019. Descriptive statistics of responders experiencing alarm symptoms of CRC, Low Anterior Resection Syndrome Score (LARS) and the Patient Assessment of Constipation-Symptoms (PAC-SYM) were derived. The association between abdominal symptoms and demographic and socioeconomic variables were estimated by prevalence ratio (PR) using a Poisson regression model with robust variance. RESULTS: A total of 5488 respondents were included. The respondents were more likely women, of older age, Danish, cohabiting and had higher education and income level compared to non-respondents. Abdominal pain more than once a week was experienced by 12.0% of the respondents. Of these, 70.8% had been experiencing this symptom for >1 month. Fresh blood in the stool was experienced by 0.7% and of these 82.1% for >1 month. About one third of those experiencing alarm symptoms more than once a week for >1 month had not consulted a doctor. A total of 64.1% of the respondents had no LARS, 21.7% had minor LARS and 14.2% had major LARS. The median PAC-SYM score was 0.33 (Interquartile range (IQR): 0.17;0.75), the median abdominal score was 0.50 (IQR: 0.00;1.00), median rectal score 0.00 (IQR:0.00;0.33) and median stool score 0.40 (IQR: 0.00;0.80). Men and those aged 65-74 reported less symptoms than women and those aged 50-64 years, respectively. CONCLUSIONS: This study illustrated that abdominal symptoms were frequent among screening-eligible men and women. This should be taken into account when implementing and improving CRC screening strategies. A concerning high number of the respondents experiencing alarm symptoms had not consulted a doctor. This calls for attention to abdominal symptoms in general and how those with abdominal symptoms should participate in CRC screening.

Vitamin B12 and transcobalamin in bovine milk: Genetic variation and genome-wide association with loci along the genome.

In human nutrition, bovine milk is an essential source of bioavailable vitamin B12 and B12-binding proteins, including transcobalamin. In this study, we estimated genetic parameters for milk content of vitamin B12 and transcobalamin using milk samples from 341 and 663 Danish Holstein cows, respectively. Additionally, we conducted whole-genome association analysis to identify SNP and genes associated with vitamin B12 and transcobalamin. Our results indicated moderate to high heritability for vitamin B12 (0.37 ± 0.18) and transcobalamin (0.61 ± 0.13) content in the Danish Holstein. With a significance threshold of -log10 P-value > 5.87, significant associations were detected between SNP in Bos taurus autosome (BTA)17 and the log-transformed transcobalamin content of milk; no significant association was detected for vitamin B12. The significant region in BTA17 was imputed to full sequence for further fine mapping, and the SNP with the most significant associations to transcobalamin were assigned to the transcobalamin 2 (TCN2) gene.

Effectiveness of a decision aid for colorectal cancer screening on components of informed choice according to educational attainment: A randomised controlled trial.

BACKGROUND: The decision to take up colorectal cancer screening has to be made on informed grounds balancing benefits and harms. Self-administered decision aids can support citizens in making an informed choice. A self-administered web-based decision aid targeting citizens with lower educational attainment has been evaluated within the target population. However, the effectiveness in the general screening population remains unexplored. The aim of this study was to evaluate the effectiveness of a web-based decision aid for colorectal cancer screening on components of informed choice among previous non-participants in colorectal cancer screening. METHODS AND FINDINGS: The study was designed as a parallel randomised controlled trial among non-participants in colorectal cancer screening in Central Denmark Region (men and women aged 53-74 years). Respondents to baseline and follow-up questionnaires comprised the study population (n = 1,723). The intervention group received the decision aid electronically along with the second reminder. The control group received only the second reminder. The main outcomes (knowledge, attitudes, uptake and decisional conflict) were obtained through questionnaires data and from the Danish Colorectal Cancer Screening Database. The decision aid increased the uptake rate by 8 percentage points (95% CI: 3.4;12.6) but had no effect on either knowledge (scale score differences: 0.09; 95% CI: -0.05;0.24) or attitudes (0.45; 95% CI: -0.00;0.91). Decisional conflict decreased by 1.69 scale points (95% CI: -3.18;-0.20). The effect was similar across educational attainment levels. CONCLUSIONS: The web-based decision aid offers a feasible way to provide individualised screening information in a "one size fits all" approach that may hold the potential to increase informed CRC screening uptake. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT03253888.

Participation in breast cancer screening among breast cancer survivors -A nationwide register-based cohort study.

The aim of this study was to analyse if breast cancer survivors without other breast imaging surveillance attend population-based screening differently than women not previously diagnosed with breast cancer. Further, to analyse if any differences depended on the women's age and years since previous cancer diagnosis. The study was a register-based retrospective cohort study of all women invited to participate in the national breast cancer screening programme in 2015-2016. Participation rates were calculated for breast cancer survivors without breast imaging within 21 months (2-4 years, 4-6 years, 6-10 years and more than 10 years after diagnosis) and for women without previous breast cancer. Relative differences in participation rates between the two groups were calculated. A total of 679,990 women were included in the study (2.6% breast cancer survivors). For breast cancer survivors, participation rates increased with increasing number of years since the previous cancer diagnosis peaking at 80.3% if the cancer diagnosis was more than 10 years ago. For women with no previous breast cancer, participation rate was 80.3%. The relative difference in participation was highest close to the breast cancer diagnosis and for the youngest women participation rates remained lower among breast cancer survivors even more than 10 years after the diagnosis. In conclusion, regardless of age and years since previous breast cancer diagnosis, breast cancer survivors had lower or similar participation rates than women with no previous cancer diagnosis. This indicated that as many as one fifth of the breast cancer survivors are at risk of inadequate surveillance.