Prevalence and population characteristics associated with frailty in a rural low socioeconomic area in Denmark: the Lolland-Falster Health Study.

BACKGROUND: Frailty is a major geriatric syndrome that predicts increased vulnerability to minor stressor events and adverse outcomes such as falls, fractures, disability and death. The prevalence of frailty among individuals above the age of 65 varies widely with an overall weighted prevalence of 10.7%. OBJECTIVES: The purpose of this study was to examine the prevalence of prefrailty and frailty in community-dwelling older adults from the regions of Lolland-Falster, which is one of the most socioeconomically disadvantaged areas of Denmark with lower income and lower life expectancy compared with the general Danish population. Moreover, the objective was to find selected individual characteristics associated with frailty. DESIGN: An observational, cross-sectional registry-based population study with data from the regions of Lolland-Falster collected between February 2016 and February 2020. RESULTS: The study included 19 000 individuals. There were 10 154 above the age of 50 included for analysis. Prevalence of frailty in the age group of 50-64 years was 4.7% and 8.7% in the age group of 65 years and above.The study demonstrates associations between frailty and high age, female gender, low education level, low income, smoking, living alone, frequency of seeing one's children and getting help when needed. These associations are comparable with findings from other studies. CONCLUSION: The syndrome of frailty consists of not only physiological and medical issues but also education, life conditions such as living alone and living in poverty and how you evaluate your own health.

Development and validation of a simple general population lung cancer risk model including AHRR-methylation.

INTRODUCTION: Screening reduces lung cancer mortality of high-risk populations. Currently proposed screening eligibility criteria only identify half of those individuals, who later develop lung cancer. This study aimed to develop and validate a sensitive and simple model for predicting 10-year lung cancer risk. METHODS: Using the 1991-94 examination of The Copenhagen City Heart Study in Denmark, 6,820 former or current smokers from the general population were followed for lung cancer within 10 years after examination. Logistic regression of baseline variables (age, sex, education, chronic obstructive pulmonary disease, family history of lung cancer, smoking status and cumulative smoking, secondhand smoking, occupational exposures to dust and fume, body mass index, lung function, plasma C-reactive protein, and AHRR(cg05575921) methylation) identified the best predictive model. The model was validated among 3,740 former or current smokers from the 2001-03 examination, also followed for 10 years. A simple risk chart was developed with Poisson regression. RESULTS: Age, sex, education, smoking status, cumulative smoking, and AHRR(cg05575921) methylation identified 65 of 88 individuals who developed lung cancer in the validation cohort. The highest risk group, consisting of less educated men aged >65 with current smoking status and cumulative smoking >20 pack-years, had absolute 10-year risks varying from 4% to 16% by AHRR(cg05575921) methylation. CONCLUSION: A simple risk chart including age, sex, education, smoking status, cumulative smoking, and AHRR(cg05575921) methylation, identifies individuals with 10-year lung cancer risk from below 1% to 16%. Including AHRR(cg05575921) methylation in the eligibility criteria for screening identifies smokers who would benefit the most from screening.

Changing Smoking Behavior and Epigenetics: A Longitudinal Study of 4,432 Individuals From the General Population.

BACKGROUND: Hypomethylation of the aryl hydrocarbon receptor repressor (AHRR) gene indicates long-term smoking exposure and might therefore be a monitor for smoking-induced disease risk. However, studies of individual longitudinal changes in AHRR methylation are sparse. RESEARCH QUESTION: How does the recovery of AHRR methylation depend on change in smoking behaviors and demographic variables? STUDY DESIGN AND METHODS: This study included 4,432 individuals from the Copenhagen City Heart Study, with baseline and follow-up blood samples and smoking information collected approximately 10 years apart. AHRR methylation at the cg05575921 site was measured in bisulfite-treated leukocyte DNA. Four smoking groups were defined: participants who never smoked (Never-Never), participants who formerly smoked (Former-Former), participants who quit during the study period (Current-Former), and individuals who smoked at both baseline and follow-up (Current-Current). Methylation recovery was defined as the increase in AHRR methylation between baseline and follow-up examination. RESULTS: Methylation recovery was highest among participants who quit, with a median methylation recovery of 5.58% (interquartile range, 1.79; 9.15) vs 1.64% (interquartile range, -1.88; 4.96) in the Current-Current group (P < .0001). In individuals who quit smoking, older age was associated with lower methylation recovery (P < .0001). In participants who quit aged > 65 years, methylation recovery was 5.9% at 5.6 years after quitting; methylation recovery was 8.5% after 2.8 years for participants who quit aged < 55 years. INTERPRETATION: AHRR methylation recovered after individuals quit smoking, and recovery was more pronounced and occurred faster in younger compared with older interim quitters.

Lung function in Lolland-Falster Health Study (LOFUS).

BACKGROUND: COPD prevalence in Denmark is estimated at 18% based on data from urban populations. However, studies suggest that using the clinical cut-off for airway obstruction in population studies may overestimate prevalence. The present study aims to compare estimated prevalence of airway obstruction using different cut-offs and to present lung function data from the Lolland-Falster Health Study, set in a rural-provincial area. METHODS: Descriptive analysis of participant characteristics and self-reported respiratory disease and of spirometry results in the total population and in subgroups defined by these characteristics. Airway obstruction was assessed using previously published Danish reference values and defined according to either FEV1 /FVC below lower limit of normal (LLN) 5% (as in clinical diagnosis) or 2.5% (suggested for population studies), or as FEV1 /FVC < 70%. RESULTS: Using either FEV1 /FVC < 70% or LLN 5% cut-off, 19.0% of LOFUS participants aged 35 years or older had spirometry, suggesting airway obstruction. By the LLN 2.5% criterion, the proportion was considerably lower, 12.2%. The prevalence of airway obstruction was higher among current smokers, in participants with short education or reporting low leisure-time physical activity and in those with known respiratory disease. Approximately 40% of participants reporting known respiratory disease had normal spirometry, and 8.7% without known respiratory disease had airway obstruction. CONCLUSION: Prevalence of airway obstruction in this rural population was comparable to previous estimates from urban Danish population studies. The choice of cut-off impacts the estimated prevalence, and using the FEV1 /FVC cut-off may overestimate prevalence. However, many participants with known respiratory disease had normal spirometry in this health study.

Frequency of missed or delayed diagnosis in dementia is associated with neighborhood socioeconomic status.

Introduction: Underdetection of dementia in areas with low socioeconomic status (SES) may interfere with findings concerning associations between SES and dementia. Methods: Using administrative registers we assessed the associations between age- and sex-adjusted dementia incidence and neighborhood socioeconomic status (nSES) in 94 Danish municipalities. Wealth was divided into income quartiles and other nSES variables were dichotomized into high versus low according to the median. Results: High population density (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.18-1.24), higher proportion of inhabitants in higher income quartiles (P for trend < .0001), and high educational level (OR 1.19, 95% CI 1.15-1.22) were associated with higher incidence of dementia. High proportion of residents above 65 years was associated with lower age-adjusted dementia incidence (OR 0.86, 95% CI 0.84-0.89). Discussion: Low nSES municipalities have a lower age-adjusted incidence of dementia diagnosis. These findings corroborate prior concerns that a large number of dementia diagnoses may be missed in municipalities characterized by low SES.

AHRR (cg05575921) Methylation Safely Improves Specificity of Lung Cancer Screening Eligibility Criteria: A Cohort Study.

BACKGROUND: Screening reduces lung cancer mortality, but specificities of eligibility criteria are low. We tested if leukocyte AHRR(cg05575921) methylation improves specificity of lung cancer screening eligibility criteria. METHODS: A total of 9,206 and 5,370 individuals of the 1991 to 1994 and 2001 to 2003 examinations of the Copenhagen City Heart Study, Denmark, were followed for lung cancer within 5 years after examination and mortality. Screening eligibility criteria (DANTE, DLCST, ITALUNG, LUSI, NELSON, NLST, and PLCOM2012) were evaluated, and AHRR (cg05575921) methylation extent at different methylation cut points was added. The model with the lowest number of eligible individuals per 5-year lung cancer was validated within the 2001 to 2003 examination. RESULTS: Eligibility criteria identified risk-groups ranging from 3,182 (DANTE) to 1,641 (ITALUNG) individuals. The positive predictive value was highest for PLCOM2012 (3.2%), while DANTE showed the highest negative predictive value (99.7%). Adding AHRR (cg05575921) methylation led to higher specificities for all criteria. Number of eligible individuals per 5-year lung cancer varied from 38 (NELSON) to 27 (NLST) with AHRR (cg05575921) methylation <55%. This last model led to a 21.9% lower screening burden and increased (P < 0.05) specificity of 84.0%. Findings were reproduced among the 5,334 individuals of the 2001 to 2003 examination. CONCLUSIONS: Adding AHRR (cg05575921) methylation on top of current eligibility criteria for lung cancer screening improves specificity by excluding those individuals with the lowest risk. IMPACT: The results point toward a potential clinical use of AHRR (cg05575921) methylation, which is a cost-effective measurement compared with lung CT scanning, to provide additional predictive risk information to identify eligible smokers for lung cancer screening. See related commentary by Hung, p. 698.

Predictive validity of PRISMA-7 as a screening instrument for frailty in a hospital setting.

OBJECTIVES: Frailty is a major clinical geriatric syndrome associated with serious adverse events including functional disability, falls, hospitalisation, increased morbidity and mortality. The aim of this study was to study the associations between frailty defined as Program of Research to Integrate Services for the Maintenance of Autonomy (PRISMA-7) score ≥3 and use of healthcare resources in hospital and in the municipality as well as association between frailty and mortality. DESIGN: Register-based retrospective study. SETTING: The target population consists of patients aged 75 years or above who, during hospital stay, were assessed by a physiotherapist, and at discharge from hospital were prescribed further physical training in the community. PARTICIPANTS: 973 individuals aged 75+ years were included. OUTCOME MEASURES: We examined associations between frailty and use of healthcare resources in hospital and in the municipality as well as the association between frailty and mortality. RESULTS: 973 individuals aged 75+ years were included. Of these, 63.9% had a PRISMA-7 score ≥3 and were thus defined as frail. Frail individuals were older compared with non-frail with mean ages of 84.6 and 80.4 years, respectively, p>0.001. Age and gender-adjusted mortality after 1 year was higher among the frail (OR 2.46, 95% CI 1.53 to 3.97). Use of healthcare services in the municipality as well as hospital admissions was significantly higher among frail individuals. CONCLUSIONS: Based on these findings we consider PRISMA-7 to be useful in an in-hospital setting as a screening tool to identify frail elderly patients who may profit from further geriatric assessment during hospital stay. TRIAL REGISTRATION NUMBER: ID REG-070-2017.

Hormone replacement therapy and mammographic density: a systematic literature review.

PURPOSE: Hormone replacement therapy (HRT) is used to reduce climacteric symptoms of menopause and prevent osteoporosis; however, it increases risk of breast cancer. Mammographic density (MD) is also a strong risk factor for breast cancer. We conducted this review to investigate the association between HRT use and MD and to assess the effect of different HRT regimens on MD. METHODS: Two of authors examined articles published between 2002 and 2019 from PubMed, Embase, and OVID using Covidence systematic review platform. Any disagreements were discussed until consensus was reached. The protocol used in this review was created in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Quality of each eligible study was assessed using the Oxford Center for Evidence-Based Medicine (OCEBM) hierarchy. RESULTS: Twenty-two studies met the inclusion criteria. Six studies showed that using estrogen plus progestin (E + P) HRT was associated with higher MD than estrogen alone. Four studies reported that continuous estrogen plus progestin (CEP) users had higher MD than sequential estrogen plus progestin (SEP) and estrogen alone users. However, two studies showed that SEP users had slightly higher MD than CEP users and estrogen alone users. CONCLUSIONS: Epidemiological evidence is rather consistent suggesting that there is a positive association between HRT use and MD with the highest increase in MD among current users, and CEP users. Our results suggest that due to increase in MD and masking effect, current E + P users may require additional screening procedures, shorter screening intervals, or using advanced imaging techniques.

Influence of sample centrifugation on plasma platelet count and activated partial thromboplastin time using patient samples.

BACKGROUND: Diagnostic coagulation testing is vulnerable to factors of the pre-analytical phase such as sample centrifugation. Despite this, centrifugation conditions differ widely among European laboratories. Here we use samples from patients referred for Activated partial thromboplastin time (APTT) testing to investigate if different centrifugation conditions result in platelet-poor plasma (PPP) (plasma platelet count < 10 × 109/L) and how the variation in centrifugation conditions affect APTT measurements. METHODS: Centrifugation of 2000g (10 min) were compared with 3000g (10 min) using samples from patients referred for APTT testing (n = 70). Plasma platelet count and APTT were measured to investigate the influence of the centrifugation conditions. Differences were evaluated using Bland Altman Plots and Student's t-test. RESULTS: Centrifugation at 3000g for 10 min produced PPP for more of the samples (64%) than centrifugation at 2000g (6%) (p < 0.001). No statistically significant difference for APTT (p = 0.265) was found for samples with APTT < 37 s while samples with prolonged APTT (>37 s) showed a statistically significant difference (p = 0.025). The Bland Altman plot did not reveal a clinically significant difference (mean difference 0.30 s/0.68%) when compared to a maximum acceptable bias of 10%. CONCLUSION: None of the centrifugation conditions used in this study adequately secured PPP for all samples. Despite a statistically significant difference between samples with prolonged APTT, no clinically significant difference was observed when comparing all APTT measurements.

Comparison of the Quantum Blue® reader Point-of-Care system versus ELISA technique for therapeutic drug monitoring of Infliximab levels.

BACKGROUND: Infliximab (IFX) is a monoclonal antibody used to treat patients with inflammatory bowel disease (IBD). For IFX therapeutic drug monitoring (TDM), the most commonly used analysis is enzyme-linked immunosorbent assays (ELISA) which do not allow results to be provided in real-time. The aim of this study was to compare the in-house ELISA (Promonitor IFX) with the much faster assay Quantum Blue® IFX (QB) for quantification of serum IFX concentration among IBD patients in maintenance IFX therapy. METHODS: We studied 30 serum samples from outpatients in IFX maintenance therapy at Copenhagen University Hospital Hvidovre, Denmark. Samples were used to compare IFX measurements from Promonitor IFX with QB. Therapeutic intervals of <3 µg/mL, 3-7 µg/mL and >7 µg/mL were equally covered. Differences were evaluated using Bland-Altman plots and Student t-test. Correlation was evaluated using x,y-plot and Pearson's correlation coefficient. The intermediate imprecision (CV%) of QB was measured at two levels (3 µg/mL and 7 µg/mL). For qualitative comparison, weighted kappa statistics (κ) were determined after stratification of results by therapeutic interval. RESULTS: Promonitor IFX and QB were strongly correlated (r = 0.92, p < 0.001). The mean difference between Promonitor IFX and QB was -0.57 µg/mL (p = 0.2). The CV% of QB was 16.3% at 3 µg/mL and 16.7% at 7 µg/mL. Classification of results according to therapeutic interval showed almost perfect agreement (κ = 0.81). CONCLUSIONS: QB is a suitable alternative to Promonitor IFX for TDM in patients treated with IFX for IBD. The results revealed a strong correlation between methods, in particular at lower IFX concentrations, representing the most interesting clinical range. When the samples were stratified according to the therapeutic interval, an almost perfect agreement between the methods was observed.

Associations between the SHARE frailty phenotype and common frailty characteristics: evidence from a large Danish population study.

OBJECTIVES: Frailty is a major clinical geriatric syndrome associated with serious adverse events including functional disability, falls, hospitalisation, increased morbidity and mortality. The aim of this study was to study associations between a frailty phenotype and frailty characteristics well known from the literature. DESIGN: Registry-based cross-sectional study. SETTING: The target population consists of inhabitants above the age of 50 living in the Danish municipalities of Lolland and Guldborgsund. Excluded are incapacitated people, inhabitants unable to understand Danish or English and inhabitants without a permanent residence. PARTICIPANTS: 7327 individuals aged 50+ years were included. OUTCOME MEASURES: We examined associations between the frailty measurement and factors known to be associated with frailty: sex, age, income insufficiency, education, comorbidity, self-assessed health, morbidity and mortality. RESULTS: 7327 individuals aged 50+ years were included. Of these, 6.5% had ≥3 frailty components (frail), 46.7% had 1-2 components (prefrail) and 46.9% had none (non-frail). Those who were frail were older and more likely female than those who were non-frail or prefrail. There was a stepwise decrease in educational level, and in self-assessed health with increasing frailty status, and a stepwise increase in difficulty in making ends meet, number of hospital contacts and mortality with increasing frailty status, p<0.0001 for each comparison. Compared with individuals who were non-frail, mortality was higher among those who were prefrail (HR: 2.90; 95% CI: 1.30 to 6.43) or frail (HR: 8.21; 95% CI: 3.37 to 20.0). CONCLUSIONS: Based on these findings, we consider the Lolland-Falster Health Study frailty assessment a valid instrument demonstrating the same characteristics as other validated frailty measures concerning associations with sex, age, income insufficiency, education, comorbidity, self-assessed health, morbidity and mortality. TRIAL REGISTRATION NUMBER: NCT02482896.

Is a discard tube necessary, when drawing blood for P-Ionized calcium analysis?

BACKGROUND: Deviation in blood collection procedures is a central source of preanalytical variation affecting overall analytical and diagnostic precision. The procedure of venous blood collection for ionized calcium is hypothesized to affect analytical results. Here, we evaluate the effect of blood collection with and without a discard tube, and storage duration on results of P-Ionized Calcium (pH adjusted = 7.4). METHODS: We collected 100 paired venous blood tubes from randomly selected outpatients using a winged blood collection. No discard tube was drawn before the first tube. The samples were divided in five subsamples, stored at 4°-6 °C at 24 (n = 20), 48 (n = 20), 72 (n = 20), 96 (n = 20) and 120 h (n = 20) after venipuncture, and analyzed for P-Ionized Calcium (pH adjusted = 7.4) on Konelab 60i (Thermo Scientific, Finland). Differences between first and second tubes were evaluated for all samples (n = 100) and for subsamples divided by storage duration, using Bland-Altman plot and Wilcoxon's rank-sum test. RESULTS: P-Ionized Calcium (pH adjusted = 7.4) results ranged from 1.13 to 1.37 mmol/L. We observed no statistical significant differences between the first and the second tube when comparing all samples. Dividing samples by storage duration, a statistically significant difference was found (p = .0068) after 120 h, but the difference of individual samples was not clinically relevant. CONCLUSIONS: Our study has shown no significant difference between P-Ionized Calcium (pH adjusted = 7.4) values for the first and second tubes. Hence, the use of a discard tube is not required. A statistically significant difference was found on samples stored 120 h but was not considered clinically relevant.

Order of draw practices in venous blood sampling at clinical biochemistry departments in the Danish health care system.

BACKGROUND: Deviation in blood collection procedures is a central source of preanalytical variation affecting overall analytical and diagnostic precision. The order of draw of venous sampling is suspected to affect analytical results, in particular for coagulation analysis. Here we compare the procedures in venous blood sampling among clinical biochemistry departments to assess the uniformity of order of blood draw and adherence to international guidelines in the Danish health care system. METHODS: We collected venous order of draw procedures from 49 clinical biochemistry departments at 22 public hospitals in Denmark. Procedures were compared to the international guidelines fromthe Clinical Laboratory Standards Institute (CLSI) and World Health Organization (WHO), and assessed in relation to department ISO 15189:2012 accreditation. RESULTS: We observed seven different order of draw procedures related to citrate, serum, heparin, and EDTA tubes, and the use of discard tubes in relation to coagulation assays. 31 departments (63.3%) were found to adhere to CLSI and WHO guidelines. A majority of departments instructs the use of discard tubes before collection for coagulation assays in citrate tubes (44 departments; 89.8%). The citrate tube was the first sample tube to be drawn for most departments (35 departments; 75.5%); and the preferred order of non-citrate tubes was serum-heparin-EDTA (36 departments; 73.5%). Adherence to the CLSI and WHO guidelines was not associated with department ISO 15189:2012 accreditation (p = .57). CONCLUSIONS: Venous order of draw procedures is diverse at Danish clinical biochemistry departments and show moderate adherence to international guidelines.

Alcohol consumption and mammographic density in the Danish Diet, Cancer and Health cohort.

PURPOSE: We examined the association between alcohol consumption and mammographic density (MD) considering in detail the time of exposure and the type of alcohol. METHODS: Of 5,356 women (4,489 post-menopausal) from the Danish Diet, Cancer and Health cohort (1993-1997) who attended mammographic screening in Copenhagen (1993-2001), we used MD (mixed/dense or fatty) assessed at the first screening after cohort entry. Alcohol consumption was assessed at the time of recruitment. Logistic regression was used to estimate associations [odds ratios (OR), 95% confidence intervals (CI)] between alcohol consumption and MD. RESULTS: The mean age was 56.2 years, 56.5% of women had mixed/dense MD, and 91.8% were alcohol consumers. There was no association between current alcohol consumption and MD at baseline (age 50-65, on average 1 year before MD assessment) neither between age at drinking initiation and MD, in the fully adjusted model. There was a borderline statistically significantly increased OR of having mixed/dense MD in women who consumed > 7 drinks/week at age 20-29 (1.31, 95% CI 1.00-1.72) compared to non-drinkers in this age group, and no effect of drinking at age 30-39, 40-49 or after > 50 years, when adjusting for current drinking. However, when considering different types of alcohol, drinking spirits at age 20-29 was positively associated with mixed/dense breast (3-7 drinks/week: OR 1.74, 95% CI 1.12-2.72); >7 drinks/week: (OR 1.76, 95% CI 0.73-4.23). No consistent pattern was found with beer, wine, or fortified wine. CONCLUSIONS: We found higher MD among women with high alcohol consumption in early adulthood (ages 20-29), in those drinking spirits.

Impact of invitation schemes on breast cancer screening coverage: A cohort study from Copenhagen, Denmark.

Background The purpose of mammography screening is to decrease breast cancer mortality. To achieve this a high coverage by examination is needed. Within an organized screening programme, we examined the impact of changes in the invitation schedule on the interplay between coverage and participation. Method We studied nine cohorts aged 50-51 when first targeted by mammography screening in Copenhagen, Denmark. Population data were retrieved from the Danish Civil Registration System; invitation and attendance data from the screening programme database. Data were linked using unique personal identification numbers. Coverage by invitation was defined as (number of invited women/number of targeted women), coverage by examination as (number of screened women/number of targeted women), and participation rate as (number of screened women/number of invited women). Results Coverage by invitation was close to or above 95% for all newly recruited cohorts. In subsequent invitation rounds, both technical errors and changes in the invitation scheme affected the coverage by invitation. Coverage by examination at first invitation was 72.5% for the first cohort, but dropped to 64.2% for the latest cohort. Furthermore, coverage by examination dropped by increasing invitation number and with omission of re-invitation of previous non-attenders. Participation rate closely reflected changes in the invitation scheme. Conclusion Changes in the invitation schemes influenced coverage by invitation, coverage by examination, and participation rate. We observed a considerable gap between coverage by examination and participation rate, strongly indicating that the latter cannot without reservations, be taken as an indicator of the first.

Cigarette smoking and mammographic density in the Danish Diet, Cancer and Health cohort.

PURPOSE: Smoking before first childbirth increases breast cancer risk, but the biological mechanism remains unknown and may involve mammographic density (MD), one of the strongest biomarkers of breast cancer risk. We aimed to examine whether active smoking and passive smoking were associated with MD. METHODS: For the 5,356 women (4,489 postmenopausal) from the Danish Diet, Cancer and Health cohort (1993-1997) who attended mammographic screening in Copenhagen (1993-2001), we used MD (mixed/dense or fatty) assessed at the first screening after cohort entry. Active smoking (status, duration, and intensity) and passive smoking were assessed at cohort baseline (1993-1997) via questionnaire, together with other breast cancer risk factors. Logistic regression was used to estimate associations (odds ratios, 95 % confidence intervals) between smoking and MD, adjusting for confounders. RESULTS: Two thousand and twenty-six (56.5 %) women had mixed/dense MD, 2,214 (41.4 %) were current, and 1,175 (21.9 %) former smokers. Current smokers had significantly lower odds (0.86, 0.75-0.99) of having mixed/dense MD compared to never smokers, while former smoking was not associated with MD. Inverse association between smoking and MD was strongest in women who initiated smoking before age of 16 years (0.79, 0.64-0.96), smoked ≥15 cigarettes/day (0.83, 0.71-0.98), smoked ≥5 pack-years (0.62, 0.43-0.89), smoked >30 years (0.86, 0.75-0.99), and smoked ≥11 years before first childbirth (0.70, 0.51-0.96). Association between smoking and MD diminished after smoking cessation, with increased odds of having mixed/dense breasts in women who quit smoking >20 years ago as compared to current smokers (1.37, 1.01-1.67). There was no association between passive smoking and MD. CONCLUSIONS: We found an inverse association between active smoking and MD.

Seventeen-years overview of breast cancer inside and outside screening in Denmark.

BACKGROUND: Long-term data on breast cancer detection in mammography screening programs are warranted to better understand the mechanisms by which screening changes the breast cancer pattern in the population. We aimed to analyze 17 years of breast cancer detection rates inside and outside screening in two Danish regions, emphasizing the influence of organizational differences of screening programs on the outcomes. MATERIAL AND METHODS: We used data from two long-standing population-based mammography screening programs, Copenhagen and Fyn, in Denmark. Both programs offered biennial screening to women aged 50-69 years. We identified targeted, eligible, invited and participating women. We calculated screening detection and interval cancer rates for participants, and breast cancer incidence in non-screened women (= targeted women excluding participants) by biennial invitation rounds. Tumor characteristics were tabulated for each of the three groups of cancers. RESULTS: Start of screening resulted in a prevalence peak in participants, followed by a decrease to a fairly stable detection rate in subsequent invitation rounds. A similar pattern was found for breast cancer incidence in non-screened women. In Fyn, non-screened women even had a higher rate than screening participants during the first three invitation rounds. The interval cancer rate was lower in Copenhagen than in Fyn, with an increase over time in Copenhagen, but not in Fyn. Screen-detected cancers showed tumor features related with a better prognosis than tumors detected otherwise, as more than 80% were smaller than 20 mm and estrogen receptor positive. CONCLUSION: Data from two long-standing population-based screening programs in Denmark illustrated that even if background breast cancer incidence and organization were rather similar, performance indicators of screening could be strongly influenced by inclusion criteria and participation rates. Detection rates should be interpreted with caution as they may be biased by selection into the screening population.

Performance indicators for participation in organized mammography screening.

BACKGROUND: A population's acceptance of a screening programme is reflected by its participation. Participation can be measured by cross-section, in an individual screening round, or by cumulative examination rate, which covers participation in numerous rounds at a pre-specified frequency. To establish an informed overview of programme performance, the relationship between these measures was analysed. METHODS: The Central Population Register (CPR) of Denmark was used to define the total population. The data sources were mammography screening programmes in Copenhagen (1991-2008) and Funen (1993-2008) and participation and coverage rates were calculated according to European guidelines. Long-term adherence was defined as the cumulative examination rate. RESULTS: The participation rates were 71% in Copenhagen and 91% in Funen. The cumulative examination rates across all invitation rounds were between 21 and 24% lower than the average participation rates. CONCLUSIONS: If the cumulative examination rate across all, or the majority of, invitation rounds is substantially lower than the average participation rate it may suggest that standard cross-sectional performance indicators overestimate the level of protection provided to the women targeted by the programme. Consequently, it may prove valuable to include cumulative examination rate as a performance indicator of mammography screening.