The effect of a pre-scheduled appointment on attendance in a population-based mammography screening programme.

BACKGROUND: Pre-scheduled appointments can increase attendance in breast cancer screening programmes compared to 'open invitations' but relatively few randomized controlled trials exist. We investigated the effect of a pre-scheduled appointment on uptake in the Flemish population-based mammography screening programme. METHODS: Between September and December 2022, a total of 4798 women were randomly assigned to receive either a pre-scheduled appointment or open invitation. The difference in attendance was compared with Poisson regression analysis for the primary endpoint (attendance ≤92 days after date of invitation), yielding relative risks (RRs). This was done separately for three groups: women invited to a mobile unit and a history of nonattendance (group M-NA); women invited to a hospital-based unit and a history of nonattendance (group HB-NA); women invited to a hospital-based unit and a history of irregular attendance (group HB-IA). There were no women invited to a mobile unit and a history of irregular attendance. RESULTS: The RRs in favour of the pre-scheduled appointment were 2.3 [95% confidence interval (CI) 1.80-2.88], 1.8 (95% CI 1.07-2.97) and 1.8 (95% CI 1.43-2.39), for groups M-NA, HB-NA and HB-IA, respectively. We found no statistically significant difference between the various RRs. The respective absolute gains in attendance between pre-scheduled appointment and open invitation were 8.3%, 4.4% and 15.8%. CONCLUSIONS: Sending an invitation with a pre-scheduled appointment is an effective tool to increase screening attendance in both mobile and hospital-based screening units. The pre-scheduled appointment is associated with a considerable absolute gain in attendance which varies depending on the screening history.

Brown Coal and Logwood Combustion in a Modern Heating Appliance: The Impact of Combustion Quality and Fuel on Organic Aerosol Composition.

Residential heating with solid fuels is one of the major drivers for poor air quality in Central and Eastern Europe, and coal is still one of the major fuels in countries, such as Poland, the Czech Republic, and Hungary. In this work, emissions from a single-room heater fueled with brown coal briquettes (BCBs) and spruce logs (SLs) were analyzed for signatures of inorganic as well as semivolatile aromatic and low-volatile organic constituents. High variations in organic carbon (OC) emissions of BCB emissions, ranging from 5 to 22 mg MJ-1, were associated to variations in carbon monoxide (CO) emissions, ranging from 900 to 1900 mg MJ-1. Residential BCB combustion turned out to be an equally important source of levoglucosan, an established biomass burning marker, as spruce logwood combustion, but showed distinct higher ratios to manosan and galactosan. Signatures of polycyclic aromatic hydrocarbons emitted by BCB combustion exhibited defunctionalization and desubstitution with increasing combustion quality. Lastly, the concept of island and archipelago structural motifs adapted from petroleomics is used to describe the fraction low-volatile organic compounds in particulate emissions, where a transition from archipelago to island motifs in relation with decreasing CO emissions was observed in BCB emissions, while emissions from SL combustion exhibited the island motif.

The effect of the Flemish breast cancer screening program on breast cancer-specific mortality: A case-referent study.

BACKGROUND: Breast cancer screening programs were introduced in many countries worldwide following randomized controlled trials in the 1980s showing a reduction in breast cancer-specific mortality. However, their effectiveness remains debated and estimates vary. A breast cancer screening program was introduced in 2001 in Flanders, Belgium where high levels of opportunistic screening practices are observed. The effectiveness of this program was estimated by measuring its effect on breast cancer-specific mortality. METHODS: We performed a case-referent study to investigate the effect of participation in the Flemish population-based mammography screening program (PMSP) on breast cancer-specific mortality from 2005 to 2017. A multiple logistic regression model assessed the association between breast cancer-specific death and screening program participation status in the four years prior to (pseudo)diagnosis (yes/no), with adjustment for potential confounders (individual socio-economic position and calendar year of diagnosis) and stratified for age. In addition, we performed different sensitivity analyses. RESULTS: We identified 1571 cases and randomly selected 6284 referents. After adjustment, women who participated in PMSP had a 51 % lower risk of breast cancer-specific mortality compared to those who did not (adjusted odds ratio [aOR] =0.49, 95 % CI: 0.44-0.55). Sensitivity analyses did not markedly change the estimated associations. Correction for self-selection bias reduced the effect size, but the estimate remained significant. CONCLUSION: Our results indicate that in a context of high opportunistic screening rates, participation in breast cancer screening program substantially reduces breast cancer-specific mortality. For policy, these results should be balanced against the potential harms of screening, including overdiagnosis and overtreatment.

Tumour characteristics of screen-detected and interval cancers in the Flemish Breast Cancer Screening Programme: A mammographic breast density study.

OBJECTIVE: The objective is to investigate tumour prognostic factors versus breast density in screen-detected cancers and interval cancers. The results may highlight the need for more personalised screening protocols based on breast density in organized screening programmes. STUDY DESIGN: A retrospective study was performed of tumour characteristics of screen-detected cancers (n=468) and interval cancers (n=515) of 983 women who participated in the Flemish Breast Cancer Screening Programme in 2009-2010. Breast density was obtained from the screening programme data. Information on nodal invasion and histological grading was taken from the Belgian Cancer Registry. Tumour size and proliferation and receptor expression status were retrieved from pathology reports. The differences in tumour characteristics between screen-detected and interval cancers as well as the variation in these variables with breast density in both groups were studied by logistic regression. RESULTS: A comparison of tumour characteristics between screen-detected cancers and interval cancers systematically showed features of more aggressive tumours in interval cancers: larger tumour size, nodal invasion, grade 3 tumours, and hormone receptor negative phenotype (p<0.05). The analysis of tumour characteristics versus breast density in screen-detected cancers showed higher numbers of aggressive grade 3 tumours in low-density breasts and of the luminal A subtype with good prognosis in high-density breasts (p<0.05). This analysis for interval cancers highlights a high proportion of the difficult-to-treat triple-negative subtype in low-density breasts compared with high-density breasts. In conclusion, the study data support arguments against changes in breast cancer screening programmes with prolongation of screening intervals in low-density breasts.

Effect of Atmospheric Aging on Soot Particle Toxicity in Lung Cell Models at the Air-Liquid Interface: Differential Toxicological Impacts of Biogenic and Anthropogenic Secondary Organic Aerosols (SOAs).

BACKGROUND: Secondary organic aerosols (SOAs) formed from anthropogenic or biogenic gaseous precursors in the atmosphere substantially contribute to the ambient fine particulate matter [PM ≤2.5µm in aerodynamic diameter (PM2.5)] burden, which has been associated with adverse human health effects. However, there is only limited evidence on their differential toxicological impact. OBJECTIVES: We aimed to discriminate toxicological effects of aerosols generated by atmospheric aging on combustion soot particles (SPs) of gaseous biogenic (ß-pinene) or anthropogenic (naphthalene) precursors in two different lung cell models exposed at the air-liquid interface (ALI). METHODS: Mono- or cocultures of lung epithelial cells (A549) and endothelial cells (EA.hy926) were exposed at the ALI for 4 h to different aerosol concentrations of a photochemically aged mixture of primary combustion SP and ß-pinene (SOAßPIN-SP) or naphthalene (SOANAP-SP). The internally mixed soot/SOA particles were comprehensively characterized in terms of their physical and chemical properties. We conducted toxicity tests to determine cytotoxicity, intracellular oxidative stress, primary and secondary genotoxicity, as well as inflammatory and angiogenic effects. RESULTS: We observed considerable toxicity-related outcomes in cells treated with either SOA type. Greater adverse effects were measured for SOANAP-SP compared with SOAßPIN-SP in both cell models, whereas the nano-sized soot cores alone showed only minor effects. At the functional level, we found that SOANAP-SP augmented the secretion of malondialdehyde and interleukin-8 and may have induced the activation of endothelial cells in the coculture system. This activation was confirmed by comet assay, suggesting secondary genotoxicity and greater angiogenic potential. Chemical characterization of PM revealed distinct qualitative differences in the composition of the two secondary aerosol types. DISCUSSION: In this study using A549 and EA.hy926 cells exposed at ALI, SOA compounds had greater toxicity than primary SPs. Photochemical aging of naphthalene was associated with the formation of more oxidized, more aromatic SOAs with a higher oxidative potential and toxicity compared with ß-pinene. Thus, we conclude that the influence of atmospheric chemistry on the chemical PM composition plays a crucial role for the adverse health outcome of emissions. https://doi.org/10.1289/EHP9413.

Genotoxic and inflammatory effects of spruce and brown coal briquettes combustion aerosols on lung cells at the air-liquid interface.

Solid fuel usage in residential heating and cooking is one of the largest sources of ambient and indoor air particulate matter, which causes adverse effects on the health of millions of peoples worldwide. Emissions from solid fuel combustion, such as biomass or coal, are detrimental to health, but toxicological responses are largely unknown. In the present study, we compared the toxicological responses regarding cytotoxicity, inflammation and genotoxicity of spruce (SPR) and brown coal briquette (BCB) combustion aerosols on human alveolar epithelial cells (A549) as well as a coculture of A549 and differentiated human monocytic cells (THP-1) into macrophages exposed at the air-liquid interface (ALI). We included both the high emissions from the first hour and moderate emissions from the third hour of the batch combustion experiment in one ALI system, whereas, in the second ALI system, we exposed the cells during the whole 4-hour combustion experiment, including all combustion phases. Physico-chemical properties of the combustion aerosol were analysed both online and offline. Both SPR and BCB combustion aerosols caused mild cytotoxic but notable genotoxic effects in co-cultured A549 cells after one-hour exposure. Inflammatory response analysis revealed BCB combustion aerosols to cause a mild increase in CXCL1 and CXCL8 levels, but in the case of SPR combustion aerosol, a decrease compared to control was observed.

Toxicity of Water- and Organic-Soluble Wood Tar Fractions from Biomass Burning in Lung Epithelial Cells.

Widespread smoke from wildfires and biomass burning contributes to air pollution and the deterioration of air quality and human health. A common and major emission of biomass burning, often found in collected smoke particles, is spherical wood tar particles, also known as "tar balls". However, the toxicity of wood tar particles and the mechanisms that govern their health impacts and the impact of their complicated chemical matrix are not fully elucidated. To address these questions, we generated wood tar material from wood pyrolysis and isolated two main subfractions: water-soluble and organic-soluble fractions. The chemical characteristics as well as the cytotoxicity, oxidative damage, and DNA damage mechanisms were investigated after exposure of A549 and BEAS-2B lung epithelial cells to wood tar. Our results suggest that both wood tar subfractions reduce cell viability in exposed lung cells; however, these fractions have different modes of action that are related to their physicochemical properties. Exposure to the water-soluble wood tar fraction increased total reactive oxygen species production in the cells, decreased mitochondrial membrane potential (MMP), and induced oxidative damage and cell death, probably through apoptosis. Exposure to the organic-soluble fraction increased superoxide anion production, with a sharp decrease in MMP. DNA damage is a significant process that may explain the course of toxicity of the organic-soluble fraction. For both subfractions, exposure caused cell cycle alterations in the G2/M phase that were induced by upregulation of p21 and p16. Collectively, both subfractions of wood tar are toxic. The water-soluble fraction contains chemicals (such as phenolic compounds) that induce a strong oxidative stress response and penetrate living cells more easily. The organic-soluble fraction contained more polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs and induced genotoxic processes, such as DNA damage.

The Role of Socio-Demographic Factors in the Coverage of Breast Cancer Screening: Insights From a Quantile Regression Analysis.

Background: In Flanders, breast cancer (BC) screening is performed in a population-based breast cancer screening program (BCSP), as well as in an opportunistic setting. Women with different socio-demographic characteristics are not equally covered by BC screening. Objective: To evaluate the role of socio-demographic characteristics on the lowest 10th and highest 90th quantile levels of BC screening coverage. Methods: The 2017 neighborhood-level coverage rates of 8,690 neighborhoods with women aged 50-69 and eligible for BCSP and opportunistic screening were linked to socio-demographic data. The association between socio-demographic characteristics and the coverage rates of BCSP and opportunistic screening was evaluated per quantile of coverage using multivariable quantile regression models, with specific attention to the lowest 10th and highest 90th quantiles. Results: The median coverage in the BCSP was 50%, 33.5% in the 10th quantile, and 64.5% in the 90th quantile. The median coverage of the opportunistic screening was 12, 4.2, and 24.8% in the 10th and 90th quantile, respectively. A lower coverage of BCSP was found in neighborhoods with more foreign residents and larger average household size, which were considered indicators for a lower socioeconomic status (SES). However, a higher average personal annual income, which was considered an indicator for a higher SES, was also found in neighborhoods with lower coverage of BCSP. For these neighborhoods, that have a relatively low and high SES, the negative association between the percentage of foreign residents, average household size, and average personal annual income and the coverage in the BCSP had the smallest regression coefficient and 95% confidence interval (CI) values were -0.75 (95% CI: -0.85, -0.65), -13.59 (95% CI: -15.81, -11.37), and -1.05 (95% CI: -1.18, -0.92), respectively, for the 10th quantile. The neighborhoods with higher coverage of opportunistic screening had a relatively higher average personal annual income, with the largest regression coefficient of 1.72 (95% CI: 1.59, 1.85) for the 90th quantile. Conclusions: Women from relatively low and high SES neighborhoods tend to participate less in the BCSP, whereas women with a relatively high SES tend to participate more in opportunistic screening. For women from low SES neighborhoods, tailored interventions are needed to improve the coverage of BCSP.

A randomized, controlled trial of two strategies of offering the home-based HPV self-sampling test to non- participants in the Flemish cervical cancer screening program.

We conducted a randomized, controlled trial to evaluate different strategies of offering an HPV-self sampling program, and compared this with two control groups. All total of 35,354 women who did not participate in the Flemish cancer screening program were included in the study: 9,118 received a HPV self-collection brush (RIATOL qPCR HPV genotyping test (qPCR [E6/E7]); 9,098 were offered the opportunity to order an HPV-selfsampling brush, 8,830 received the recall letter; 8,849 received no intervention. Within 12 months after the mailing, 18.7% of the women who had received the brush, participated by returning a self-sample sample, while 10.6% women allocated to the opt- in group did so. 10.5% women who received the standard recall letter, had a PAP smear taken within a period of 12 months; while 8% women did so without receiving an intervention at all. Participation in postmenopausal women was higher than in women younger than 50 in both self-sampling arms. Screening by means of the self-sample kit increased by age, contradictory when screening is performed by a PAP smear. Of those testing hrHPV positive (9.5%), 88.9% attended for follow up cytology. The mean DNA concentration, found in the self-sampler, decreased by age, causing a higher number of inconclusive results. Our results support the efficacy of a self-sampling strategy to increase participation in the Flemish screening program. Self-sampling seems particularly acceptable to postmenopausal non-responders. Future research should focus on the performance of different self-sampling devices in post-menopausal women as low DNA concentrations exponentially increased over age.

Screen-detected versus interval cancers: Effect of imaging modality and breast density in the Flemish Breast Cancer Screening Programme.

OBJECTIVES: To investigate if direct radiography (DR) performs better than screen-film mammography (SF) and computed radiography (CR) in dense breasts in a decentralized organised Breast Cancer Screening Programme. To this end, screen-detected versus interval cancers were studied in different BI-RADS density classes for these imaging modalities. METHODS: The study cohort consisted of 351,532 women who participated in the Flemish Breast Cancer Screening Programme in 2009 and 2010. Information on screen-detected and interval cancers, breast density scores of radiologist second readers, and imaging modality was obtained by linkage of the databases of the Centre of Cancer Detection and the Belgian Cancer Registry. RESULTS: Overall, 67% of occurring breast cancers are screen detected and 33% are interval cancers, with DR performing better than SF and CR. The interval cancer rate increases gradually with breast density, regardless of modality. In the high-density class, the interval cancer rate exceeds the cancer detection rate for SF and CR, but not for DR. CONCLUSIONS: DR is superior to SF and CR with respect to cancer detection rates for high-density breasts. To reduce the high interval cancer rate in dense breasts, use of an additional imaging technique in screening can be taken into consideration. KEY POINTS: • Interval cancer rate increases gradually with breast density, regardless of modality. • Cancer detection rate in high-density breasts is superior in DR. • IC rate exceeds CDR for SF and CR in high-density breasts. • DR performs better in high-density breasts for third readings and false-positives.

Impact of the digitalisation of mammography on performance parameters and breast dose in the Flemish Breast Cancer Screening Programme.

OBJECTIVES: To investigate the impact of digitalisation on performance parameters and breast dose of the Flemish Breast Cancer Screening Programme. Both computed (CR) and direct radiography (DR) are compared with screen-film mammography (SFM). METHODS: Data from 975,673 mammographic examinations were collected from units which underwent digitalisation from SFM to CR (41 units) or DR (72 units) in the period 2005-2011. Performance indicators were obtained by consulting the Screening Programme database. Phantom and patient dosimetry data were acquired from the physical technical quality assurance of the programme. RESULTS: Digitalisation induced no significant change in cancer detection rate (CDR), percentage of ductal carcinomas in situ and percentage of breast cancers smaller than 1 cm. A decrease in false-positive results and third readings was observed, which was a time-related observation. After digitalisation, positive predictive value (PPV) increased and recall rates decreased. Compared with SFM, an increase of 30% in mean glandular dose (MGD) was found for CR, while a similar change in the opposite direction was found for DR. CONCLUSIONS: No major differences in performance parameters after digitalisation were found. Transition of SFM to CR resulted in a higher MGD and associated lower detection-over-induction ratio (DIR), while the change to DR induced an improvement of DIR. KEY POINTS: • Performance parameters showed no major differences after digitalisation to CR or DR. • Transition from SFM to CR results in a higher mean glandular dose. • Transition from SFM to DR results in a lower mean glandular dose.

Technical and clinical breast cancer screening performance indicators for computed radiography versus direct digital radiography.

OBJECTIVES: To compare technical and clinical screening performance parameters between computed radiography (CR) and direct digital radiography (DR) systems. METHODS: The number of women screened with CR was 73,008 and with DR 116,945. Technical and patient dose survey data of 25 CR and 37 DR systems were available. Technical performance was expressed by threshold thickness values at the mean glandular dose (MGD) level of routine practice. Clinical indicators included recall rate (RR), cancer detection rate (CDR), percentage of ductal carcinoma in situ (DCIS), percentage of cancers with T-scores smaller than 1 cm and positive predictive value (PPV). RESULTS: Contrast threshold values for the 0.1-mm gold disk were 1.44 µm (SD 0.13 µm) for CR and 1.20 µm (SD 0.13 µm for DR). MGD was 2.16 mGy (SD 0.36 mGy) and 1.35 mGy (SD 0.32 mGy) for CR and DR respectively. We obtained for CR, respectively DR, the following results: RR in the first round of 5.48 % versus 5.61 %; RR in subsequent rounds of 2.52 % versus 2.65 %; CDR of 0.52 % versus 0.53 %; DCIS of 0.08 % versus 0.11 %; a rate of cancers with T-scores smaller than 1 cm of 0.11 % versus 0.11 %; PPV of 18.45 % versus 18.64 %; none of them was significantly different. CONCLUSION: Our screening indicators are reassuring for the use of CR and DR, with CR operating at 60 % higher MGD. KEY POINTS: • Breast cancer screening can employ both computed (CR) and direct digital radiography (DR). • Screening performance parameters for CR and DR technology are not significantly different. • Screening parameters are in accordance with European Guidelines. • Radiation doses employed for CR are generally 60 % greater than for DR.

Strict normoglycaemic blood glucose levels in the therapeutic management of patients within 12h after cardiac arrest might not be necessary.

AIM OF THE STUDY: The admission blood glucose level after cardiac arrest is predictive of outcome. However the blood glucose levels in the post-resuscitation period, that are optimal remains a matter of debate. We wanted to assess an association between blood glucose levels at 12h after restoration of spontaneous circulation and neurological recovery over 6 months. MATERIALS AND METHODS: A total of 234 patients from a multi-centre trial examining the effect of mild hypothermia on neurological outcome were included. According to the serum glucose level at 12h after restoration of spontaneous circulation, quartiles (Q) were generated: Median (range) glucose concentrations were for QI 100 (67-115 mg/dl), QII 130 (116-143 mg/dl), QIII 162 (144-193 mg/dl) and QIV 265 (194-464 mg/dl). RESULTS: In univariate analysis there was a strong non-linear association between blood glucose and good neurological outcome (odds ratio compared to QIV): QI 8.05 (3.03-21.4), QII 13.41 (4.9-36.67), QIII 1.88 (0.67-5.26). After adjustment for sex, age, "no-flow" and "low-flow" time, adrenaline (epinephrine) dose, history of coronary artery disease and myocardial infarction, and therapeutic hypothermia, this association still remained strong: QI 4.55 (1.28-16.12), QII 13.02 (3.29-49.9), QIII 1.37 (0.38-5.64). CONCLUSION: There is a strong non-linear association of survival with good neurological outcome and blood glucose levels 12h after cardiac arrest even after adjusting for potential confounders. Not only strict normoglycaemia, but also blood glucose levels from 116 to 143 mg/dl were correlated with survival and good neurological outcome, which might have an important therapeutic implication.