Cervical cancer incidence in Denmark: Disentangling determinants of time trend.

Cervical cancer is a preventable disease. Nevertheless, stagnation has been seen in incidence rates also in countries with well-functioning healthcare. On this basis, we investigated associations between control interventions and changes in cervical cancer incidence in Denmark from 2009 to 2022. Data on human papillomavirus (HPV)-vaccination were retrieved from Staten's Serum Institute; on screening recommendations from Danish Health Authority, on screening performance from Danish Quality Database for Cervical Screening; and on cervical cancer incidence from Nordcan and Danish Cancer Register. We reported coverage with HPV vaccination (1+ dose); coverage with cervical cell samples; number of women with primary HPV tests; proportion of non-normal cell samples without timely follow-up; number of conizations; and cervical cancer incidence rates. In 2022, all women aged ≤29 had been offered childhood HPV vaccination with coverage of 80%-90%. By 2020-2022, the cervical cancer incidence rate in women aged 20-29 was 3 per 100,000; at level of disease elimination. In 2017, women aged 70+ were offered a one-time HPV screening, and by 2020-2022, the old-age peak in cervical cancer incidence had largely disappeared. From 2009 to 2022, proportion of non-normal cell samples without timely follow-up decreased from 20% to 10%, and conventional cytology was largely replaced by SurePath liquid-based cytology; these factors could explain the steady decrease in cervical cancer incidence rate. Implementation of primary HPV screening in women aged 30-59 in 2021 was reflected in a, probably temporary, increase in the 2022 cervical cancer incidence rate. In conclusion, combined interventions with childhood HPV vaccination; one-time HPV screening of elderly women; and better management of screening broke previous stagnation in cervical cancer incidence rate.

Non-participation in breast screening in Denmark: Sociodemographic determinants.

BACKGROUND: Internationally, non-participation in breast screening increased with decreasing level of education indicating importance of information campaigns to enhance awareness of screening. However, in Denmark in the 1990s the association between education and non-participation was U-shaped. We therefore analyzed recent Danish data. METHODS: Data derived from the Capital Region of Denmark, biennial, organized breast screening program 2008-2020, where women aged 50-69 were personally invited to screening. Non-participation was measured as number of women with no participation out of women eligible for at least three invitations. Sociodemographic determinants were identified by linkage to public registers. Results were reported as age adjusted odds ratios (OR) of non-participation including 95% confidence intervals (CI). RESULTS: Among 196,085 women, 86% participated. Using women with low education as baseline, the OR for professional bachelors was 0.64; and for academics 0.75. The strongest determinants of non-participation were being non-married OR 2.03; born outside Denmark OR 2.04; being self-employed OR 1.67; retired OR 3.12; on public support OR 3.66; or having co-morbidity OR 1.56. CONCLUSION: The U-shaped association between education and non-participation in breast screening prevailed. The data further indicated that screening participation was low in women with pertinent health and social problems.

Long-term exposure to air pollution and road traffic noise and incidence of dementia in the Danish Nurse Cohort.

INTRODUCTION: We examined the association of long-term exposure to air pollution and road traffic noise with dementia incidence in the Danish Nurse Cohort. METHODS: Female nurses were followed for dementia incidence (hospital contact or medication prescription) from 1993/1999 to 2020. Air pollution and road traffic noise levels were estimated at nurses' residences, and their associations with dementia were examined using Cox regression models. RESULTS: Of 25,233 nurses 1409 developed dementia. Particulate matter with a diameter of ≤2.5 µm (PM2.5) was associated with dementia incidence, after adjusting for lifestyle, socioeconomic status, and road traffic noise (hazard ratio [95% confidence interval] 1.35 [1.15-1.59] per interquartile range of 2.6 µg/m3). There was no association of PM2.5 with dementia in physically active nurses. Association with road traffic noise diminished after adjusting for PM2.5 (1.02 [0.93-1.11] per 7.6 dB). DISCUSSION: Long-term exposure to air pollution increases risk of dementia, and physical activity may moderate this risk. HIGHLIGHTS: Long-term exposure to air pollution was associated with increased risk of dementia among female nurses from the Danish Nurse Cohort. Association of air pollution with dementia was independent of road traffic noise. Association of road traffic noise with dementia diminished after adjusting for air pollution. Physical activity moderated adverse effects of air pollution on dementia.

Breast density and risk of breast cancer.

Early studies reported a 4- to 6-fold risk of breast cancer between women with extremely dense and fatty breasts. As most early studies were case-control studies, we took advantage of a population-based screening program to study density and breast cancer incidence in a cohort design. In the Capital Region, Denmark, women aged 50 to 69 are invited to screening biennially. Women screened November 2012 to December 2017 were included, and classified by BI-RADS density code, version 4, at first screen after recruitment. Women were followed up for incident breast cancer, including ductal carcinoma in situ (DCIS), to 2020 in nationwide pathology data. Rate ratios (RRs) and 95% confidence intervals (CI) were compared across density groups using Poisson-regression. We included 189 609 women; 1 067 282 person-years; and 4110 incident breast cancers/DCIS. Thirty-three percent of women had BI-RADS density code 1; 38% code 2; 24% code 3; 4.7% code 4; and missing 0.3%. Using women with BI-RADS density code 1 as baseline; women with code 2 had RR 1.69 (95% CI 1.56-1.84); women with code 3, RR 2.06 (95% CI 1.89-2.25); and women with code 4, RR 2.37 (95% CI 1.05-2.74). Results differed between observations accumulated during screening and above screening age. Our results indicated less difference in breast cancer risk across level of breast density than normally stated. Translated into absolute risk of breast cancer after age 50, we found a 6.2% risk for the one-third of women with lowest density, and 14.7% for the 5% of women with highest density.

Long-term exposure to air pollution and risk of SARS-CoV-2 infection and COVID-19 hospitalisation or death: Danish nationwide cohort study.

BACKGROUND: Early ecological studies have suggested links between air pollution and risk of coronavirus disease 2019 (COVID-19), but evidence from individual-level cohort studies is still sparse. We examined whether long-term exposure to air pollution is associated with risk of COVID-19 and who is most susceptible. METHODS: We followed 3 721 810 Danish residents aged ≥30 years on 1 March 2020 in the National COVID-19 Surveillance System until the date of first positive test (incidence), COVID-19 hospitalisation or death until 26 April 2021. We estimated residential annual mean particulate matter with diameter ≤2.5 µm (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) in 2019 by the Danish DEHM/UBM model, and used Cox proportional hazards regression models to estimate the associations of air pollutants with COVID-19 outcomes, adjusting for age, sex, individual- and area-level socioeconomic status, and population density. RESULTS: 138 742 individuals were infected, 11 270 were hospitalised and 2557 died from COVID-19 during 14 months. We detected associations of PM2.5 (per 0.53 µg·m-3) and NO2 (per 3.59 µg·m-3) with COVID-19 incidence (hazard ratio (HR) 1.10 (95% CI 1.05-1.14) and HR 1.18 (95% CI 1.14-1.23), respectively), hospitalisations (HR 1.09 (95% CI 1.01-1.17) and HR 1.19 (95% CI 1.12-1.27), respectively) and death (HR 1.23 (95% CI 1.04-1.44) and HR 1.18 (95% CI 1.03-1.34), respectively), which were strongest in the lowest socioeconomic groups and among patients with chronic respiratory, cardiometabolic and neurodegenerative diseases. We found positive associations with BC and negative associations with O3. CONCLUSION: Long-term exposure to air pollution may contribute to increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection as well as developing severe COVID-19 disease requiring hospitalisation or resulting in death.

Stringency of COVID-19 Containment Response Policies and Air Quality Changes: A Global Analysis across 1851 Cities.

The COVID-19 containment response policies (CRPs) had a major impact on air quality (AQ). These CRPs have been time-varying and location-specific. So far, despite having numerous studies on the effect of COVID-19 lockdown on AQ, a knowledge gap remains on the association between stringency of CRPs and AQ changes across the world, regions, nations, and cities. Here, we show that globally across 1851 cities (each more than 300 000 people) in 149 countries, after controlling for the impacts of relevant covariates (e.g., meteorology), Sentinel-5P satellite-observed nitrogen dioxide (NO2) levels decreased by 4.9% (95% CI: 2.2, 7.6%) during lockdowns following stringent CRPs compared to pre-CRPs. The NO2 levels did not change significantly during moderate CRPs and even increased during mild CRPs by 2.3% (95% CI: 0.7, 4.0%), which was 6.8% (95% CI: 2.0, 12.0%) across Europe and Central Asia, possibly due to population avoidance of public transportation in favor of private transportation. Among 1768 cities implementing stringent CRPs, we observed the most NO2 reduction in more populated and polluted cities. Our results demonstrate that AQ improved when and where stringent COVID-19 CRPs were implemented, changed less under moderate CRPs, and even deteriorated under mild CRPs. These changes were location-, region-, and CRP-specific.

Risk of precancerous cervical lesions in women using a hormone-containing intrauterine device and other contraceptives: a register-based cohort study from Denmark.

STUDY QUESTION: Is the risk of high-grade precancerous cervical lesions and/or is the risk of lesion progression increased in users of a hormone-containing intrauterine device (HIUD) compared with users of other contraceptive methods. SUMMARY ANSWER: Women starting use of HIUD had the same subsequent risk of cervical intraepithelial neoplasia 3+ (CIN3+) as copper IUD (CIUD) users, and both groups tended to have lower risks than oral contraceptives (OC) users. WHAT IS KNOWN ALREADY: HIUDs may cause inflammatory and immunosuppressive changes that may potentially affect the risk of persistent human papillomavirus infection and precancerous cervical lesions. STUDY DESIGN, SIZE, DURATION: A Danish population-based cohort study was conducted using register data from 2008 to 2011 on 26-50-year-old users of HIUD (n = 60 551), CIUD (n = 30 303), or OC (n = 165 627). PARTICIPANTS/MATERIALS, SETTING, METHODS: Within each user group, women were divided into two groups; normal cytology or abnormal diagnosis before start of contraceptive use (baseline). Follow-up histology and cytology diagnoses were registered during the 5 years after baseline. Adjusted relative risks (aRR) and 95% CI were calculated for precancerous cervical lesions in HIUD users compared with CIUD and OC users. MAIN RESULTS AND THE ROLE OF CHANCE: Women with normal cytology at baseline: at follow-up HIUD users had the same risk of CIN3 or higher (3+) as CIUD users; aRR 1.08 (95% CI 0.94-1.22). For the HIUD and CIUD groups compared with OCs, the risks of CIN3+ were lower: aRR 0.63 (95% CI 0.57-0.69) and aRR 0.58 (95% CI 0.52-0.65), respectively. The same was observed for CIN2 risks: aRR 0.86 (95% CI 0.76-0.96) and aRR 0.68 (95% CI 0.58-0.79) for HIUD and CIUD groups, respectively. Women with abnormal diagnosis at baseline: a lower progression risk, except for CIN2+ at baseline, was observed in HIUD users compared with OC users. Similar progression risks were found in HIUD and CIUD users. There were no differences between the three contraceptive groups in persistence or regression of present lesions. LIMITATIONS, REASONS FOR CAUTION: We adjusted for age, education, and region of residence as a proxy for socio-economic factors. Data on smoking and sexual behavior were not available thus we cannot exclude some differences between the three user groups. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that women may safely use HIUDs. STUDY FUNDING/COMPETING INTEREST(S): A.P. Møller Foundation for the Advancement of Medical Science, Else and Mogens Wedell-Wedellborgs Fund, Direktør Emil C. Hertz og Hustru Inger Hertz Fund, and the Fund for Development of Evidence Based Medicine in Private Specialized Practices. EL is principle investigator for a study with HPV-test-kits provided by Roche. The other authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Reference intervals for 12 clinical laboratory tests in a Danish population: The Lolland-Falster Health Study.

Reference intervals (RIs), developed as part of the Nordic Reference Interval Project 2000 (NORIP) are widely used in most European laboratories. We aimed to examine the validity of the NORIP RIs by establishing RIs for 12 frequently used laboratory tests based on data from a local Danish population and compare these local RIs with the NORIP RIs. Using an a posteriori direct sampling approach, blood sample data were assessed from 11,138 participants aged 18+ years in the Lolland-Falster Health Study (LOFUS), of whom 2154 turned out to meet criteria for being healthy for inclusion in establishing RIs according to the NORIP methodology. The 2.5th and 97.5th percentiles were calculated for alanine aminotransferase (ALAT), albumin, alkaline phosphatase, bilirubin, creatinine, hemoglobin, high-density lipoprotein cholesterol, iron, low-density lipoprotein cholesterol, thrombocytes, total cholesterol, and triglycerides. When comparing our estimates with the NORIP, the lower reference limits (RLs) for bilirubin and iron were lower, and higher for ALAT, thrombocytes and triglycerides. Upper RLs were lower for albumin (males and females ≥70 years), bilirubin and iron, but higher for alkaline phosphatase, triglycerides and for creatinine in men. In LOFUS, approximately 20% of the participants were healthy and qualified for inclusion in the establishment of RIs. Several of the local RIs differed from the NORIP RIs.

Breast cancer mortality and overdiagnosis after implementation of population-based screening in Denmark.

INTRODUCTION: Service breast cancer screening is difficult to evaluate because there is no unscreened control group. Due to a natural experiment, where 20% of women were offered screening in two regions up to 17 years before other women, Denmark is in a unique position. We utilized this opportunity to assess outcome of service screening. MATERIALS AND METHODS: Screening was offered in Copenhagen from 1991 and Funen from 1993 to women aged 50-69 years. We used difference-in-differences methodology with a study group offered screening; a historical control group; a regional control group; and a regional-historical control group, comparing breast cancer mortality and incidence, including ductal carcinoma in situ, between study and historical control group adjusted for changes in other regions, and calculating ratios of rate ratios (RRR) with 95% confidence intervals (CI). Data came from Central Population Register; mammography screening databases; Cause of Death Register; and Danish Cancer Register. RESULTS: For breast cancer mortality, the study group accumulated 1,551,465 person-years and 911 deaths. Long-term breast cancer mortality in Copenhagen was 20% below expected in absence of screening; RRR 0.80 (95% CI 0.71-0.90), and in Funen 22% below; RRR 0.78 (95% CI 0.68-0.89). Combined, cumulative breast cancer incidence in women followed 8+ years post-screening was 2.3% above expected in absence of screening; RRR 1.023 (95% CI 0.97-1.08). DISCUSSION: Benefit-to-harm ratio of the two Danish screening programs was 2.6 saved breast cancer deaths per overdiagnosed case. Screening can affect only breast cancers diagnosed in screening age. Due to high breast cancer incidence after age 70, only one-third of breast cancer deaths after age 50 could potentially be affected by screening. Increasing upper age limit could be considered, but might affect benefit-to-harm ratio negatively.

High-grade cervical lesions after vaccination against human papillomavirus: A Danish cohort study.

INTRODUCTION: It is pertinent to evaluate the impact of vaccination against human papillomavirus (HPV) in real life. The aim of the study was to evaluate the real-life impact of HPV vaccination in the first birth cohort of Danish women offered free HPV vaccination as girls and invited to screening at the age of 23 years. MATERIAL AND METHODS: Women born in 1993 were offered free HPV vaccination at the age of 15 years but women born in 1983 have never been offered free HPV vaccination. We followed these two birth cohorts for 10 years from the age of 15 to after their first invitation to screening, and compared the risk of high-grade cervical intraepithelial neoplasia (CIN). Data were obtained from Danish national health registers. RESULTS: Vaccination coverage was 91% in the 1993 birth cohort and <0.1% in the 1983 cohort. Screening coverage was close to 80% in both cohorts. CIN2+ was detected in 4% of the 15 748 screened women born in 1983 and in 3% of the 19 951 screened women born in 1993. The risk of high-grade CIN was reduced by about 30% in the 1993 cohort compared with the 1983 cohort; for CIN2+ relative risk 0.74 (95% CI 0.66-0.82) and for CIN3+ relative risk 0.68 (95% CI 0.58-0.79). CONCLUSIONS: This study investigated the real-life impact of quadrivalent HPV vaccination by comparing a cohort of women offered HPV vaccination with a cohort of women not offered HPV vaccination. The observed decrease in the detection of high-grade cervical lesions following HPV vaccination is in line with results from the randomized trials and has important implications for future cervical screening of HPV vaccinated cohorts.

Burden of prediabetes, undiagnosed, and poorly or potentially sub-controlled diabetes: Lolland-Falster health study.

BACKGROUND: This study aimed to investigate prevalence and risk factors for prediabetes, undiagnosed diabetes mellitus, poorly and potentially sub-controlled diabetes in a rural-provincial general adult population in Denmark. METHODS: Using cross-sectional data from the Lolland-Falster Health Study, we examined a total of 10,895 individuals aged 20 years and above. RESULTS: Prevalence of prediabetes was 5.8% (men: 6.1%; women: 5.5%); of undiagnosed diabetes 0.8% (men: 1.0%; women: 0.5%); of poorly controlled diabetes 1.2% (men: 1.5%; women: 0.8%); and of potentially sub-controlled diabetes 2% (men: 3.0%; women: 1.3%). In total, 9.8% of all participants had a diabetes-related condition in need of intervention; men at a higher risk than women; RR 1.41 (95% CI 1.26-1.58); person aged + 60 years more than younger; RR 2.66 (95% CI 2.34-3.01); obese more than normal weight person, RR 4.51 (95% CI 3.79-5.38); smokers more than non-smokers, RR 1.38 (95% CI 1.19-1.62); persons with self-reported poor health perception more than those with good, RR 2.59 (95% CI 2.13-3.15); low leisure time physical activity more than those with high, RR 2.64 (95% CI 2.17-3.22); and persons with self-reported hypertension more than those without, RR 3.28 (95% CI 2.93-3.68). CONCLUSIONS: In the Lolland-Falster Health Study, nearly 10% of participants had prediabetes, undiagnosed diabetes, poorly controlled, or potentially sub-controlled diabetes. The risk of these conditions was more than doubled in persons with self-reported poor health perception, self-reported hypertension, low leisure time physical activity, or measured obesity, and a large proportion of people with diabetes-related conditions in need of intervention can therefore be identified relatively easily.

Change in mammographic density across birth cohorts of Dutch breast cancer screening participants.

High mammographic density is a well-known risk factor for breast cancer. This study aimed to search for a possible birth cohort effect on mammographic density, which might contribute to explain the increasing breast cancer incidence. We separately analyzed left and right breast density of Dutch women from a 13-year period (2003-2016) in the breast cancer screening programme. First, we analyzed age-specific changes in average percent dense volume (PDV) across birth cohorts. A linear regression analysis (PDV vs. year of birth) indicated a small but statistically significant increase in women of: 1) age 50 and born from 1952 to 1966 (left, slope = 0.04, p = 0.003; right, slope = 0.09, p < 0.0001); 2) age 55 and born from 1948 to 1961 (right, slope = 0.04, p = 0.01); and 3) age 70 and born from 1933 to 1946 (right, slope = 0.05, p = 0.002). A decrease of total breast volume seemed to explain the increase in PDV. Second, we compared proportion of women with dense breast in women born in 1946-1953 and 1959-1966, and observed a statistical significant increase of proportion of highly dense breast in later born women, in the 51 to 55 age-groups for the left breast (around a 20% increase in each age-group), and in the 50 to 56 age-groups for the right breast (increase ranging from 27% to 48%). The study indicated a slight increase in mammography density across birth cohorts, most pronounced for women in their early 50s, and more marked for the right than for the left breast.

Does closed incision negative wound pressure therapy in non-traumatic major lower-extremity amputations improve survival rates?

Closed incision negative pressure wound therapy (CINPWT) has been shown to be clinically effective compared with the traditional gauze dressing, reducing surgical site infections and wound complications. We evaluated the effect of CINPWT compared with gauze dressing on the need for revision surgery and survival after non-traumatic major lower amputation. We included 309 patients undergoing 403 major lower amputations in a retrospective study from January 1, 2010 to November 23, 2017. A total of 139 patients received CINPWT, and 170 patients received stump bandage. There was no statistically significant difference between the two groups regarding the need for revision surgery (P = .45). Fourteen stump bandage patients and 15 CINPWT patients died in hospital (P = .57). One year after amputation, 55 CINPWT patients and 66 stump bandage patients had died (P = .82). Survival probabilities adjusted for age and gender 2 years after amputation were .52 (.43-.61) and .49 (.42-.58), respectively, and 3 years after amputation were .36 (.25-.50) and .39 (.32-.47), respectively. We also found no significant difference in the need for revision surgery in survival probabilities up till 3 years after amputation between patients treated with CINPWT and patients treated with gauze bandage postoperatively.

Impact of HPV vaccination on outcome of cervical cytology screening in Denmark-A register-based cohort study.

4vHPV vaccination has been tested in randomized controlled trials under almost ideal conditions, and studies of real-life use have compared outcome between vaccinated and unvaccinated women from the same birth cohort and mostly before screening age. Here we present the first-to our knowledge-evaluation of the impact of the 4vHPV vaccination in real life without selection bias in the reported data. The study has been carried out by comparing the results after first cervical screening between an HPV-vaccinated and an unvaccinated birth cohort, consisting of women born in Denmark in 1993 and 1983, respectively. Cytology data covering an 8-year period, from the age of 15 (age of HPV-vaccination) to age 23 (age of invitation to first cervical screening), were retrieved from the Danish National Pathology Register. Abnormal cytology, defined as atypical squamous cell of undetermined significance and worse (ASCUS+) was detected in 9.4% of women born in 1993 as compared with 9.0% of women born in 1983; RR = 1.04 (95% CI 0.96-1.12), p = .29. Detection of high-grade squamous intraepithelial lesion (HSIL) was statistically significantly lower in the 1993 than in the 1983 cohort, RR = 0.6 (95% CI 0.5-0.7), p < .0001, while the opposite pattern was seen for ASCUS RR = 1.4 (95% CI 1.2-1.6), p < .0001. The decrease in HSIL means that more women can be spared referral for colposcopy and biopsy. The increase of ASCUS could be explained by transition from conventional to liquid-based cytology, but this observation requires further monitoring.

Screening mammography: benefit of double reading by breast density.

PURPOSE: The currently recommended double reading of all screening mammography examinations is an economic burden for screening programs. The sensitivity of screening is higher for women with low breast density than for women with high density. One may therefore ask whether single reading could replace double reading at least for women with low density. We addressed this question using data from a screening program where the radiologists coded their readings independently. METHODS: Data include all screening mammography examinations in the Capital Region of Denmark from 1 November 2012 to 31 December 2013. Outcome of screening was assessed by linkage to the Danish Pathology Register. We calculated sensitivity, specificity, number of interval cancers, and false positive-tests per 1000 screened women by both single reader and consensus BI-RADS density code. RESULTS: In total 54,808 women were included. The overall sensitivity of double reading was 72%, specificity was 97.6%, 3 women per 1000 screened experienced an interval cancer, and 24 a false-positive test. Across all BI-RADS density codes, single reading consistently decreased sensitivity as compared with consensus reading. The same was true for specificity, apart from results across BI-RADS density codes set by reader 2. CONCLUSIONS: Single reading decreased sensitivity as compared with double reading across all BI-RADS density codes. This included results based on consensus BI-RADS density codes. This means that replacement of double with single reading would have negative consequences for the screened women, even if density could be assessed automatically calibrated to the usual consensus level.

Self-Reported Health as Predictor of Allostatic Load and All-Cause Mortality: Findings From the Lolland-Falster Health Study.

Objectives: The aim was to determine the association between self-reported health (SRH), allostatic load (AL) and mortality. Methods: Data derived from the Lolland-Falster Health Study undertaken in Denmark from 2016-2020 (n = 14,104). Median follow-up time for death was 4.6 years where 456 participants died. SRH was assessed with a single question and AL by an index of ten biomarkers. Multinomial regression analysis were used to examine the association between SRH and AL, and Cox regression to explore the association between SRH, AL and mortality. Results: The risk of high AL increased by decreasing level of SRH. The ratio of relative risk (RRR) of having medium vs. low AL was 1.58 (1.11-2.23) in women reporting poor/very poor SRH as compared with very good SRH. For men it was 1.84 (1.20-2.81). For high vs. low AL, the RRR was 2.43 (1.66-3.56) in women and 2.96 (1.87-4.70) in men. The hazard ratio (HR) for all-cause mortality increased by decreasing SRH. For poor/very poor vs. very good SRH, the HR was 6.31 (2.84-13.99) in women and 3.92 (2.12-7.25) in men. Conclusion: Single-item SRH was able to predict risk of high AL and all-cause mortality.

Clinical Significance of Combined Density and Deep-Learning-Based Texture Analysis for Stratifying the Risk of Short-Term and Long-Term Breast Cancer in Screening.

Assessing a woman's risk of breast cancer is important for personalized screening. Mammographic density is a strong risk factor for breast cancer, but parenchymal texture patterns offer additional information which cannot be captured by density. We aimed to combine BI-RADS density score 4th Edition and a deep-learning-based texture score to stratify women in screening and compare rates among the combinations. This retrospective study cohort study included 216,564 women from a Danish populations-based screening program. Baseline mammograms were evaluated using BI-RADS density scores (1-4) and a deep-learning texture risk model, with scores categorized into four quartiles (1-4). The incidence rate ratio (IRR) for screen-detected, interval, and long-term cancer were adjusted for age, year of screening and screening clinic. Compared with subgroup B1-T1, the highest IRR for screen-detected cancer were within the T4 category (3.44 (95% CI: 2.43-4.82)-4.57 (95% CI: 3.66-5.76)). IRR for interval cancer was highest in the BI-RADS 4 category (95% CI: 5.36 (1.77-13.45)-16.94 (95% CI: 9.93-30.15)). IRR for long-term cancer increased both with increasing BI-RADS and increasing texture reaching 5.15 (4.31-6.16) for the combination of B4-T4 compared with B1-T1. Deep-learning-based texture analysis combined with BI-RADS density categories can reveal subgroups with increased rates beyond what density alone can ascertain, suggesting the potential of combining texture and density to improve risk stratification in breast cancer screening.

Correlation between allostatic load index and cumulative mortality: a register-based study of Danish municipalities.

OBJECTIVES: The aim of this study was to examine population-based allostatic load (AL) indices as an indicator of community health across 14 municipalities in Denmark. DESIGN: Register-based study. SETTING: Data derived from: the Lolland-Falster Health Study, the Copenhagen General Population Study and the Danish General Suburban Population Study. Nine biomarkers (systolic blood pressure, diastolic blood pressure, pulse rate, total serum cholesterol, high-density lipoprotein cholesterol, waist-to-hip ratio, triglycerides, C-reactive protein and serum albumin) were divided into high-risk and low-risk values based on clinically accepted criteria, and the AL index was defined as the average between the nine values. All-cause mortality data were obtained from Statistics Denmark. PARTICIPANTS: We examined a total of 106 808 individuals aged 40-79 years. PRIMARY OUTCOME MEASURE: Linear regression models were performed to investigate the association between mean AL index and cumulative mortality risk. RESULTS: Mean AL index was higher in men (range 2.3-3.3) than in women (range 1.7-2.6). We found AL index to be strongly correlated with the cumulative mortality rate, correlation coefficient of 0.82. A unit increase in mean AL index corresponded to an increase in the cumulative mortality rate of 19% (95% CI 13% to 25%) for men, and 16% (95% CI 8% to 23%) for women but this difference was not statistically significant. The overall mean increase in cumulative mortality rate for both men and women was 17% (95% CI 14% to 20%). CONCLUSIONS: Our findings indicate the population-based AL index to be a strong indicator of community health, and suggest identification of targets for reducing AL.

Introduction of one-view tomosynthesis in population-based mammography screening: Impact on detection rate, interval cancer rate and false-positive rate.

OBJECTIVE: To assess performance endpoints of a combination of digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) compared with FFDM only in breast cancer screening. MATERIALS AND METHODS: This was a prospective population-based screening study, including eligible (50-69 years) women attending the Capital Region Mammography Screening Program in Denmark. All attending women were offered FFDM. A subgroup was consecutively allocated to a screening room with DBT. All FFDM and DBT underwent independent double reading, and all women were followed up for 2 years after screening date or until next screening date, whichever came first. RESULTS: 6353 DBT + FFDM and 395 835 FFDM were included in the analysis and were undertaken in 196 267 women in the period from 1 November 2012 to 12 December 2018. Addition of DBT increased sensitivity: 89.9% (95% confidence interval (CI): 81.0-95.5) for DBT + FFDM and 70.1% (95% CI: 68.6-71.6) for FFDM only, p < 0.001. Specificity remained similar: 98.2% (95% CI: 97.9-98.5) for DBT + FFDM and 98.3% (95% CI: 98.2-98.3) for FFDM only, p = 0.9. Screen-detected cancer rate increased statistically significantly: 11.18/1000 for DBT + FFDM and 6.49/1000 for FFDM only, p < 0.001. False-positive rate was unchanged: 1.75% for DBT + FFDM and 1.73% for FFDM only, p = 0.9. Positive predictive value for recall was 39.0% (95% CI: 31.9-46.5) for DBT + FFDM and 27.3% (95% CI: 26.4-28.2), for FFDM only, p < 0.0005. The interval cancer rate decreased: 1.26/1000 for DBT + FFDM and 2.76/1000 for FFDM only, p = 0.02. CONCLUSION: DBT + FFDM yielded a statistically significant increase in cancer detection and program sensitivity.

Long-Term Exposure to Air Pollution and Risk of Acute Lower Respiratory Infections in the Danish Nurse Cohort.

Rationale: Air pollution is a major risk factor for chronic cardiorespiratory diseases, affecting the immune and respiratory systems' functionality, but epidemiological evidence in respiratory infections remains sparse. Objectives: We aimed to assess the association of long-term exposure to ambient air pollution with the risk of developing new and recurrent acute lower respiratory infections (ALRIs), characterized by persistently severe symptoms necessitating hospital contact, and identify the potential susceptible populations by socioeconomic status, smoking, physical activity status, overweight, and comorbidity with chronic lung disease. Methods: We followed 23,912 female nurses from the Danish Nurse Cohort (age >44 yr) from baseline (1993 or 1999) until 2018 for incident and recurrent ALRIs defined by hospital contact (inpatient, outpatient, and emergency room) data from the National Patient Register. Residential annual mean concentrations of fine particulate matter, nitrogen dioxide (NO2), and black carbon were modeled using the Danish Eulerian Hemispheric Model/Urban Background Model/Air Geographic Information System. We used marginal Cox models with time-varying exposures to assess the association of 3-year running mean air pollution level with incident and recurrent ALRIs and examined effect modification by age, socioeconomic status, smoking, physical activity, body mass index, and comorbidity with asthma or chronic obstructive pulmonary disease (COPD). Results: During a 21.3-year mean follow-up, 4,746 ALRIs were observed, of which 2,553 were incident. We observed strong positive associations of all three pollutants with incident ALRIs, with hazard ratios and 95% confidence intervals of 1.19 (1.08-1.31) per 2.5 µg/m3 for fine particulate matter, 1.17 (1.11-1.24) per 8.0 µg/m3 for NO2, and 1.09 (1.05-1.12) per 0.3 µg/m3 for black carbon, and slightly stronger associations with recurrent ALRIs. Associations were strongest in patients with COPD and nurses with low physical activity. Conclusions: Long-term exposure to air pollution at low levels was associated with risks of new and recurrent ALRIs, with patients with COPD and physically inactive subjects most vulnerable.