Age-specific differences in breast cancer treatment between screen-detected and non-screen-detected breast cancers in women aged 40-74 years at diagnosis in Sweden 2008-2017.

BACKGROUND AND PURPOSE: We have recently demonstrated that screen-detected invasive breast cancers had more favourable tumour characteristics than non-screen-detected. The objective of the study was to analyse differences in breast cancer treatment between screen-detected and non-screen-detected cases by age at diagnosis, with and without adjustment for tumour (T) and nodal (N) status, within a nationwide, population-based mammography screening programme utilising register data. MATERIAL AND METHODS: Data spanning 2008-2017 were collected from the National Quality Register for Breast Cancer. Multivariable logistic regression analysis was used to estimate odds ratios and 95% confidence intervals for treatment disparities between screen-detected and non-screen-detected breast cancer. RESULTS: Among 46,481 women diagnosed with invasive breast cancer aged 40-74 and invited for mammography screening, significant differences in treatment were observed. Screen-detected cases showed higher likelihoods of partial mastectomy compared to mastectomy, endocrine therapy, and radiotherapy, whereas chemotherapy and antibody therapy were less likely compared to non-screen-detected cases. However, when adjusting for surgery type, screen-detected cases showed lower likelihoods of radiotherapy. Age at diagnosis significantly influenced treatment odds ratios, with interactions observed for all treatments except radiotherapy adjusted for surgery. Differences increased with age, except for endocrine therapy. Radiotherapy adjusted for surgery type showed no age-related interaction. Adjusting for T and N did not alter these patterns. INTERPRETATION: In general, screen-detected cases received less aggressive treatment, such as mastectomy, chemotherapy, and antibody therapy, compared to non-screen-detected cases. Disparities increased with age, except for endocrine therapy and radiotherapy adjusted for surgery. Differences persisted after adjusting for T and N, suggesting that these factors cannot solely explain the results.

Age-specific differences in tumour characteristics between screen-detected and non-screen-detected breast cancers in women aged 40-74 at diagnosis in Sweden from 2008 to 2017.

OBJECTIVE: To analyze differences between screen-detected and non-screen-detected invasive breast cancers by tumour characteristics and age at diagnosis in the nationwide population-based mammography screening program in Sweden. METHODS: Data were retrieved from the National Quality Register for Breast Cancer for 2008-2017. Logistic regression analysis was used to estimate the likelihood for a tumour to be screen-detected by tumour characteristics and age group at diagnosis. RESULTS: In total there were 51,429 invasive breast cancers in the target age group for mammography screening of 40-74 years. Likelihood of screen detection decreased with larger tumour size, lymph node metastases, higher histological grade and distant metastasis. Odds ratios (ORs) for negative oestrogen (ER) and progesterone (PgR) were 0.41 and 0.57; for positive HER2, 0.62; for Ki-67 high versus low, 0.49. Molecular sub-types had OR of 0.56, 0.40 and 0.28, respectively, for luminal B-like, HER2-positive and triple negative versus luminal A-like. Adjusting for tumour size (T), lymph node status (N), age, year and county at diagnosis slightly elevated the ORs. Statistically significant interactions between tumour characteristics and age were found (p < 0.05) except for ER and PgR. The age group 40-49 deviated most from the other age groups. CONCLUSIONS: Our study demonstrates that screen-detected invasive breast cancers had more favourable tumour characteristics than non-screen-detected after adjusting for age, year and county of diagnosis, and even after adjusting for T and N. The trend towards favourable tumour characteristics was less pronounced in the 40-49 age group compared to the other age groups, except for ER and PgR.

Maternal mortality decline in Zimbabwe, 2007/2008 to 2018/2019: findings from mortality surveys using civil registration, vital statistics and health system data.

BACKGROUND: Sustainable Development Goal (SDG) 3.1 target is to reduce the global maternal mortality ratio (MMR) to less than 70 maternal deaths per 100 000 live births by 2030. In the Ending Preventable Maternal Mortality strategy, a supplementary target was added, that no country has an MMR above 140 by 2030. We conducted two cross-sectional reproductive age mortality surveys to analyse changes in Zimbabwe's MMR between 2007-2008 and 2018-2019 towards the SDG target. METHODS: We collected data from civil registration, vital statistics and medical records on deaths of women of reproductive ages (WRAs), including maternal deaths from 11 districts, randomly selected from each province (n=10) using cluster sampling. We calculated weighted mortality rates and MMRs using negative binomial models, with 95% CIs, performed a one-way analysis of variance of the MMRs and calculated the annual average reduction rate (ARR) for the MMR. RESULTS: In 2007-2008 we identified 6188 deaths of WRAs, 325 pregnancy-related deaths and 296 maternal deaths, and in 2018-2019, 1856, 137 and 130, respectively. The reproductive age mortality rate, weighted by district, declined from 11 to 3 deaths per 1000 women. The MMR (95% CI) declined from 657 (485 to 829) to 217 (164 to 269) deaths per 100 000 live births at an annual ARR of 10.1%. CONCLUSIONS: Zimbabwe's MMR declined by an annual ARR of 10.1%, against a target of 10.2%, alongside declining reproductive age mortality. Zimbabwe should continue scaling up interventions against direct maternal mortality causes to achieve the SDG 3.1 target by 2030.

Changes in causes of pregnancy-related and maternal mortality in Zimbabwe 2007-08 to 2018-19: findings from two reproductive age mortality surveys.

BACKGROUND: Reducing maternal mortality is a priority of Sustainable Development Goal 3.1 which requires frequent epidemiological analysis of trends and patterns of the causes of maternal deaths. We conducted two reproductive age mortality surveys to analyse the epidemiology of maternal mortality in Zimbabwe and analysed the changes in the causes of deaths between 2007-08 and 2018-19. METHODS: We performed a before and after analysis of the causes of death among women of reproductive ages (WRAs) (12-49 years), and pregnant women from the two surveys implemented in 11 districts, selected using multi-stage cluster sampling from each province of Zimbabwe (n=10); an additional district selected from Harare. We calculated mortality incidence rates and incidence rate ratios per 10000 WRAs and pregnant women (with 95% confidence intervals), in international classification of disease groups, using negative binomial models, and compared them between the two surveys. We also calculated maternal mortality ratios, per 100 000 live births, for selected causes of pregnancy-related deaths. RESULTS: We identified 6188 deaths among WRAs and 325 PRDs in 2007-08, and 1856 and 137 respectively in 2018-19. Mortality in the WRAs decreased by 82% in diseases of the respiratory system and 81% in certain infectious or parasitic diseases' groups, which include HIV/AIDS and malaria. Pregnancy-related deaths decreased by 84% in the indirect causes group and by 61% in the direct causes group, and HIV/AIDS-related deaths decreased by 91% in pregnant women. Direct causes of death still had a three-fold MMR than indirect causes (151 vs. 51 deaths per 100 000) in 2018-19. CONCLUSION: Zimbabwe experienced a decline in both direct and indirect causes of pregnancy-related deaths. Deaths from indirect causes declined mainly due to a reduction in HIV/AIDS-related and malaria mortality, while deaths from direct causes declined because of a reduction in obstetric haemorrhage and pregnancy-related infections. Ongoing interventions ought to improve the coverage and quality of maternal care in Zimbabwe, to further reduce deaths from direct causes.

Association of education and feedback on hypertension management with risk for stroke and cardiovascular disease.

PURPOSE: Education and feedback on hypertension management has been associated with improved hypertension control. This study aimed to assess the effectiveness of such interventions to reduce the risk of stroke and cardiovascular events. MATERIALS AND METHODS: Individuals ≥18 years with a blood pressure (BP) recording in Västerbotten or Södermanland County during the study period 2001 to 2009 were included in 108 serial cohort studies, each with 24 months follow-up. The primary outcome was risk of first-ever stroke in Västerbotten County (intervention) compared with Södermanland County (control). Secondary outcomes were first-ever major adverse cardiovascular event (MACE), myocardial infarction, and heart failure, as well as all-cause and cardiovascular mortality. All outcomes were analysed using time-to-event data included in a Cox proportional hazards model adjusted for age, sex, hypertension, diabetes, coronary artery disease, atrial fibrillation, systolic BP at inclusion, marital status, and disposable income. RESULTS: A total of 121 365 individuals (mean [SD] age at inclusion 61.7 [16.3] years; 59.9% female; mean inclusion BP 142.3/82.6 mmHg) in the intervention county were compared to 131 924 individuals (63.6 [16.2] years; 61.2% female; 144.1/81.1 mmHg) in the control county. A first-ever stroke occurred in 2 823 (2.3%) individuals in the intervention county, and 3 584 (2.7%) individuals in the control county (adjusted hazard ratio 0.96, 95% CI 0.90 to 1.03). No differences were observed for MACE, myocardial infarction or heart failure, whereas all-cause mortality (HR 0.91, 95% CI 0.87 to 0.95) and cardiovascular mortality (HR 0.91, 95% CI 0.85 to 0.98) were lower in the intervention county. CONCLUSIONS: This study does not support an association between education and feedback on hypertension management to primary care physicians and the risk for stroke or cardiovascular outcomes. The observed differences for mortality outcomes should be interpreted with caution.

Breast cancer screening with mammography in women aged 40-49 years: Impact of length of screening interval on effectiveness of the program.

OBJECTIVES: To estimate the impact on the effectiveness of Swedish breast cancer screening program in women aged 40-49 years of shortening the screening interval from 21 months to 18 or 12 months. METHODS: The reduction in breast cancer mortality among participants in screening with mammography was previously estimated in the Swedish SCReening of Young women (SCRY) study to be 29%. The expected increased effectiveness with a hypothetical shorter screening interval than the average of 21 months in SCRY was calculated using data about the women who died from breast cancer even though they participated in the SCRY program. RESULTS: During the study period, 547 women who participated in the index screening round died from breast cancer. Shortening the screening interval to 18 months led to an improved effectiveness of 0.7-3.9% considering interval cancers only and of 1.3-7.6% considering screening-detected cancers only, and for both interval and screening-detected cancers the improvement was 1.9-11.5% when the assumed mortality reduction for the deceased cases varied from 5% to 30%. Shortening the screening interval to 12 months increased the effectiveness by 1.6-9.8% for interval cancers and by 2.9-17.4% for both interval and screening-detected cancers. CONCLUSION: Shortening the screening interval for women aged 40-49 years to 18 or 12 months might further reduce the breast cancer mortality rate.

Effectiveness of Population-Based Service Screening with Mammography for Women Aged 70-74 Years in Sweden.

BACKGROUND: Consensus has been reached on the effectiveness of inviting women aged 50 to 69 years to mammography screening, but for older women, the evidence is scarce. The aim of this study was to estimate the marginal effectiveness of inviting women to mammography screening with an upper age limit of 74 years versus stopping at age 69 using data from the Swedish service-screening program. METHODS: A cohort design was used to compare the breast cancer mortality in the period 1986 to 2012 between geographic areas and periods where women were invited to screening up to the age of 74 years (study group) with those where women were invited up to age 69 (control group). The study group and the control group were compared using the incidence-based breast cancer mortality rate ratio where only breast cancer deaths in cases diagnosed at 70 to 74 years of age were counted. RESULTS: After 20 years of follow-up, there were 1,040 and 1,173 breast cancer deaths in the study and the control group, respectively. The breast cancer mortality rate ratio for women invited up to age 74 versus women invited up to age 69 was 0.80 [95% confidence interval (CI): 0.75-0.85] after bias adjustments. The corresponding rate ratio for participating women was 0.73 (95% CI: 0.66-0.81). CONCLUSIONS: Continuing to screen women up to 74 years of age is effective compared with stopping screening at 69 years. IMPACT: This large long-term study will add to the knowledge of the effect of mammography screening for women 70 to 74 years.

Monitoring and evaluation of breast cancer screening programmes: selecting candidate performance indicators.

BACKGROUND: In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection. METHODS: The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries. RESULTS: A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers > 20 mm, cancers ≤10 mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate. CONCLUSION: This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality.

Development and use of health outcome descriptors: a guideline development case study.

BACKGROUND: During healthcare guideline development, panel members often have implicit, different definitions of health outcomes that can lead to misunderstandings about how important these outcomes are and how to balance benefits and harms. McMaster GRADE Centre researchers developed 'health outcome descriptors' for standardizing descriptions of health outcomes and overcoming these problems to support the European Commission Initiative on Breast Cancer (ECIBC) Guideline Development Group (GDG). We aimed to determine which aspects of the development, content, and use of health outcome descriptors were valuable to guideline developers. METHODS: We developed 24 health outcome descriptors related to breast cancer screening and diagnosis for the European Commission Breast Guideline Development Group (GDG). Eighteen GDG members provided feedback in written format or in interviews. We then evaluated the process and conducted two health utility rating surveys. RESULTS: Feedback from GDG members revealed that health outcome descriptors are probably useful for developing recommendations and improving transparency of guideline methods. Time commitment, methodology training, and need for multidisciplinary expertise throughout development were considered important determinants of the process. Comparison of the two health utility surveys showed a decrease in standard deviation in the second survey across 21 (88%) of the outcomes. CONCLUSIONS: Health outcome descriptors are feasible and should be developed prior to the outcome prioritization step in the guideline development process. Guideline developers should involve a subgroup of multidisciplinary experts in all stages of development and ensure all guideline panel members are trained in guideline methodology that includes understanding the importance of defining and understanding the outcomes of interest.

Association of Physician Education and Feedback on Hypertension Management With Patient Blood Pressure and Hypertension Control.

Importance: Elevated systolic blood pressure (SBP) is the most important risk factor for premature death worldwide. However, hypertension detection and control rates continue to be suboptimal. Objective: To assess the association of education and feedback to primary care physicians with population-level SBP and hypertension control rates. Design, Setting, and Participants: This pooled series of 108 population-based cohort studies involving 283 079 patients used data from primary care centers in 2 counties (Västerbotten and Södermanland) in Sweden from 2001 to 2009. Participants were individuals aged 18 years or older who had their blood pressure (BP) measured and recorded in either county during the intervention period. All analyses were performed in February 2019. Exposures: An intervention comprising education and feedback for primary care physicians in Västerbotten County (intervention group) compared with usual care in Södermanland County (control group). Main Outcomes and Measures: Difference in mean SBP levels between counties and likelihood of hypertension control in the intervention county compared with the control county during 24 months of follow-up. Results: A total of 136 541 unique individuals (mean [SD] age at inclusion, 64.6 [16.1] years; 57.0% female; mean inclusion BP, 142/82 mm Hg) in the intervention county were compared with 146 538 individuals (mean [SD] age at inclusion, 65.7 [15.9] years; 58.3% female; mean inclusion BP, 144/80 mm Hg) in the control county. Mean SBP difference between counties during follow-up, adjusted for inclusion BP and other covariates, was 1.1 mm Hg (95% CI, 1.0-1.1 mm Hg). Hypertension control improved by 8.4 percentage points, and control was achieved in 37.8% of participants in the intervention county compared with 29.4% in the control county (adjusted odds ratio, 1.30; 95% CI, 1.29-1.31). Differences between counties increased during the intervention period and were more pronounced in participants with higher SBP at inclusion. Results were consistent across all subgroups. Conclusions and Relevance: This study suggests that SBP levels and hypertension control rates in a county population may be improved by educational approaches directed at physicians and other health care workers. Similar strategies may be adopted to reinforce the implementation of clinical practice guidelines for hypertension management.

Breast Cancer Screening and Diagnosis: A Synopsis of the European Breast Guidelines.

Description: The European Commission Initiative for Breast Cancer Screening and Diagnosis guidelines (European Breast Guidelines) are coordinated by the European Commission's Joint Research Centre. The target audience for the guidelines includes women, health professionals, and policymakers. Methods: An international guideline panel of 28 multidisciplinary members, including patients, developed questions and corresponding recommendations that were informed by systematic reviews of the evidence conducted between March 2016 and December 2018. GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests by enhancing transparency. Questions and recommendations, expressed as strong or conditional, focused on outcomes that matter to women and provided a rating of the certainty of evidence. Recommendations: This synopsis of the European Breast Guidelines provides recommendations regarding organized screening programs for women aged 40 to 75 years who are at average risk. The recommendations address digital mammography screening and the addition of hand-held ultrasonography, automated breast ultrasonography, or magnetic resonance imaging compared with mammography alone. The recommendations also discuss the frequency of screening and inform decision making for women at average risk who are recalled for suspicious lesions or who have high breast density.

Association between changes in waist circumferences and disability among older adults: WHO-INDEPTH study on global ageing and adult health (SAGE) in Indonesia.

BACKGROUND: There is a lack of evidence regarding the impact of changes in waist circumference on disability among older populations in low- and middle-income countries (LMICs). This research examines the association between changes in waist circumference with disability in the older populations of Indonesia, and whether the associations are dependent on wealth or baseline abdominal obesity levels. METHODS: In 2007 the INDEPTH-WHO Study on global AGEing and adult health (SAGE) was conducted among 11,753 individuals aged 50 years and older in Purworejo District, Central Java Province, Indonesia. Of these, a total of 8,089 were followed up in 2010. On both occasions, individuals' waist circumferences were measured and the 12-item version of the WHO Disability Assessment Schedule version 2 (WHODAS-II) was implemented to measure disability. RESULTS: A significant positive association was observed between waist circumference and disability at the baseline (ß=0.066; p<0.001), and between the increase in waist circumference and the level of disability during the three-year follow-up period (ß=0.094; p<0.001) after adjusting for baseline variables. This association was also significant among the poor, non-obese men, as well as poor and rich obese women. Among the non-obese women, a decrease in waist circumference was associated with more disabilities. CONCLUSIONS: An increase in waist circumference is associated with increased disability among older people in Purworejo, Indonesia. Health promotion programmes aiming to prevent obesity could have positive effects in preventing and reducing disability among older adults.

Flawed conclusions on the Västerbotten Intervention Program by San Sebastian et .al.

An evaluation of Västerbotten Intervention Programme (VIP) was recently conducted by San Sebastian et al. (BMC Public Health 19:202, 2019). Evaluation of health care interventions of this kind require 1) an understanding of both the design and the nature of the intervention, 2) correct definition of the target population, and 3) careful choice of the appropriate evaluation method. In this correspondence, we review the approach used by San Sebastian et al. as relates to these three criteria. Within this framework, we suggest important explanations for why the conclusions drawn by these authors contradict a large body of research on the effectiveness of the VIP.

Methods for Development of the European Commission Initiative on Breast Cancer Guidelines: Recommendations in the Era of Guideline Transparency.

Neither breast cancer prevention and early-detection programs, nor their outcomes, are uniform across Europe. This article describes the rationale, methods, and process for development of the European Commission (EC) Initiative on Breast Cancer Screening and Diagnosis Guidelines. To be consistent with standards set by the Institute of Medicine and others, the EC followed 6 general principles. First, the EC selected, via an open call, a panel with broad representation of areas of expertise. Second, it ensured that all recommendations were supported by systematic reviews. Third, the EC separately considered important subgroups of women, included patient advocates in the guidelines development group, and focused on good communication to inform women's decisions. Fourth, EC rules on conflicts of interest were followed and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests. Fifth, it focused its recommendations on outcomes that matter to women, and certainty of the evidence is rated for each. Sixth, the EC elicited stakeholder feedback to ensure that the recommendations remain up to date and relevant to practice. This article describes the approach and highlights ways of disseminating and adapting the recommendations both within and outside Europe, using innovative information technology tools.

Waist Circumference and All-Cause Mortality among Older Adults in Rural Indonesia.

Waist circumference, a measure of abdominal obesity, is associated with all-cause mortality in general adult population. However, the link between abdominal obesity with all-cause mortality in the studies of older adults is unclear. This study aims to determine the association between waist circumference and all-cause mortality in older adults in Indonesia. The association between waist circumference and all-cause mortality was examined in 10,997 men and women aged 50 years and older, in the World Health Organization (WHO) and International Network of field sites for continuous Demographic Evaluation of Populations and their Health in developing countries (INDEPTH) collaboration Study on global AGEing and adult health (SAGE) in Purworejo District Central Java, Indonesia during 2007⁻2010. Multivariate Cox regression analysis with restricted cubic splines was used to assess the non-linear association between waist circumference and all-cause mortality. During the 3-year follow-up, a total of 511 men and 470 women died. The hazard ratio plot shows a pattern of U-shape relationship between waist circumference and all-cause mortality among rich women, though the result was significant only for women in the lower end of waist circumference distribution (p < 0.05). Poor men with a low waist circumference (5th percentile) have a two times higher mortality risk (HR = 2.1; 95% CI = 1.3, 3.3) relative to those with a waist circumference of 90 cm. Poor women with a low waist circumference (25th percentile) have a 1.4 times higher mortality risk (HR = 1.4; 95% CI = 1.1, 1.8) relative to those with a waist circumference of 80 cm. This study shows a significant association between low waist circumference measure and mortality, particularly among poor men and women. Though the association between large waist circumference and mortality was not significant, we observed a trend of higher mortality risk particularly among rich women with large waist circumference measure. Public health intervention should include efforts to improve nutritional status among older people and promoting healthy lifestyle behaviours including healthy food and active lifestyle.

Use of a criteria-based audit to optimize uptake of cesarean delivery in a low-resource setting.

OBJECTIVE: To evaluate the impact of a criteria-based audit (CBA) of obstructed labor and fetal distress on cesarean delivery and perinatal outcomes. METHODS: A cross-sectional study was performed at a tertiary referral hospital in Tanzania. Data were collected before and after CBA (January 2013-November 2013 and July 2015-June 2016). Outcomes of fetal distress (baseline CBA, n=248; re-audit, n=251) and obstructed labor (baseline CBA, n=260; re-audit n=250) were assessed using a checklist. Additionally, 27 960 parturients were assessed using the Robson classification. RESULTS: Perinatal morbidity and mortality decreased from 42 of 260 (16.2%) to 22 of 250 (8.8%) among patients with obstructed labor after CBA (P=0.012). Cesarean delivery rate decreased for referred term multiparas with induced labor or prelabor cesarean delivery (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.09-0.82). Cesarean delivery rate for preterm pregnancies increased among both referred (OR 1.28, 95% CI 1.02-1.63) and non-referred (OR 2.78, 95% CI 1.98-3.90) groups. Neonatal distress rate decreased for referred term multiparas (OR 0.72, 95% CI 0.56-0.92), referred preterm pregnancies (OR 0.32, 95% CI 0.25-0.39), and non-referred preterm pregnancies (OR 0.26, 95% CI 0.18-0.36). CONCLUSION: Use of CBA reduced poor perinatal outcomes of obstructed labor and increased uptake of cesarean delivery.

Overdiagnosis in the population-based organized breast cancer screening program estimated by a non-homogeneous multi-state model: a cohort study using individual data with long-term follow-up.

BACKGROUND: Overdiagnosis, defined as the detection of a cancer that would not become clinically apparent in a woman's lifetime without screening, has become a growing concern. Similar underlying risk of breast cancer in the screened and control groups is a prerequisite for unbiased estimates of overdiagnosis, but a contemporary control group is usually not available in organized screening programs. METHODS: We estimated the frequency of overdiagnosis of breast cancer due to screening in women 50-69 years old by using individual screening data from the population-based organized screening program in Stockholm County 1989-2014. A hidden Markov model with four latent states and three observed states was constructed to estimate the natural progression of breast cancer and the test sensitivity. Piecewise transition rates were used to consider the time-varying transition rates. The expected number of detected non-progressive breast cancer cases was calculated. RESULTS: During the study period, 2,333,153 invitations were sent out; on average, the participation rate in the screening program was 72.7% and the average recall rate was 2.48%. In total, 14,648 invasive breast cancer cases were diagnosed; among the 8305 screen-detected cases, the expected number of non-progressive breast cancer cases was 35.9, which is equivalent to 0.43% (95% confidence interval (CI) 0.10%-2.2%) overdiagnosis. The corresponding estimates for the prevalent and subsequent rounds were 15.6 (0.87%, 95% CI 0.20%-4.3%) and 20.3 (0.31%, 95% CI 0.07%-1.6%), respectively. The likelihood ratio test showed that the non-homogeneous model fitted the data better than an age-homogeneous model (P <0.001). CONCLUSIONS: Our findings suggest that overdiagnosis in the organized biennial mammographic screening for women 50-69 in Stockholm County is a minor phenomenon. The frequency of overdiagnosis in the prevalent screening round was higher than that in subsequent rounds. The non-homogeneous model performed better than the simpler, traditional homogeneous model.

Estimation of overdiagnosis in breast cancer screening using a non-homogeneous multi-state model: A simulation study.

OBJECTIVES: Overdiagnosis is regarded as a harm of screening. We aimed to develop a non-homogeneous multi-state model to consider the age-specific transition rates for estimation of overdiagnosis, to validate the model by a simulation study where the true frequency of overdiagnosis can be calculated, and to compare our estimate with the cumulative incidence method. METHODS: We constructed a four-state model to describe the natural history of breast cancer. The latent disease progression and the observed states for each individual were simulated in a trial with biennial screening of women aged 51-69 and a control group of the same size without screening. We performed 100 repetitions of the simulation with one million women to evaluate the performance of estimates. A sensitivity analysis with reduced number of controls was performed to imitate the data from the service screening programme. RESULTS: Based on the 100 repetitions, the mean value of the true frequency of overdiagnosis was 12.5% and the average estimates by the cumulative incidence method and the multi-state model were 12.9% (interquartile range: 2.46%) and 13.4% (interquartile range: 2.16%), respectively. The multi-state model had a greater bias of overdiagnosis than the cumulative incidence method, but the variation in the estimates was smaller. When the number of unscreened group was reduced, the variation of multi-state model estimates increased. CONCLUSIONS: The multi-state model produces a proper estimate of overdiagnosis and the results are comparable with the cumulative incidence method. The multi-state model can be used in the estimation of overdiagnosis, and might be useful for the ongoing service screening programmes.

Socioeconomic inequality in abdominal obesity among older people in Purworejo District, Central Java, Indonesia - a decomposition analysis approach.

BACKGROUND: Obesity has become a global health challenge as its prevalence has increased globally in recent decades. Studies in high-income countries have shown that obesity is more prevalent among the poor. In contrast, obesity is more prevalent among the rich in low- and middle-income countries, hence requiring different focal points to design public health policies in the latter contexts. We examined socioeconomic inequalities in abdominal obesity in Purworejo District, Central Java, Indonesia and identified factors contributing to the inequalities. METHODS: We utilised data from the WHO-INDEPTH Study on global AGEing and adult health (WHO-INDEPTH SAGE) conducted in the Purworejo Health and Demographic Surveillance System (HDSS) in Purworejo District, Indonesia in 2010. The study included 14,235 individuals aged 50 years and older. Inequalities in abdominal obesity across wealth groups were assessed separately for men and women using concentration indexes. Decomposition analysis was conducted to assess the determinants of socioeconomic inequalities in abdominal obesity. RESULTS: Abdominal obesity was five-fold more prevalent among women than in men (30% vs. 6.1%; p < 0.001). The concentration index (CI) analysis showed that socioeconomic inequalities in abdominal obesity were less prominent among women (CI = 0.26, SE = 0.02, p < 0.001) compared to men (CI = 0.49, SE = 0.04, p < 0.001). Decomposition analysis showed that physical labour was the major determinant of socioeconomic inequalities in abdominal obesity among men, explaining 47% of the inequalities, followed by poor socioeconomic status (31%), ≤ 6 years of education (15%) and current smoking (11%). The three major determinants of socioeconomic inequalities in abdominal obesity among women were poor socio-economic status (48%), physical labour (17%) and no formal education (16%). CONCLUSION: Abdominal obesity was more prevalent among older women in a rural Indonesian setting. Socioeconomic inequality in abdominal obesity exists and concentrates more among the rich population in both sexes. The inequality gap is less prominent among women, indicating a trend towards obesity being more common in poor women. Policies to address social determinants of health need to be developed to address the socioeconomic inequality gaps in obesity, with particular focus on addressing the existing burden of obesity among the better-off population group, while preventing the imminent burden of obesity among the worst-off group, particularly among women.

Reduced breast cancer mortality after 20+ years of follow-up in the Swedish randomized controlled mammography trials in Malmö, Stockholm, and Göteborg.

Objective To analyze the age- and trial-specific effects of the breast cancer screening trials with mammography in Malmö, Stockholm, and Göteborg. Methods The original trial files were linked to the Swedish Cancer and Cause of Death Registers to obtain date of breast cancer diagnosis and date and cause of death. Relative risks and 95% confidence intervals were calculated using the evaluation model (only breast cancers diagnosed between date of randomization and date when the first screening round of the control group was completed were included in the analysis). Results Women aged 40-70 at randomization in the Malmö I and II, Stockholm, and Göteborg trials were followed-up for an average of 30, 22, 25, and 24 years, respectively. The overview of all trials resulted in a significant decrease of 15% in breast cancer mortality. The variation by consecutive 10-year age group at randomization was small-from 21% in the age group 40-49 to 11% in the age group 50-59. After adjustment for age, there was a significant reduction in breast cancer mortality in the Göteborg trial (26%), and a non-significant reduction in the Malmö I and II and Stockholm trials (12%, 15%, and 5.8%, respectively). Conclusions The overview showed a 15% significant relative reduction in breast cancer mortality due to invitation to mammography screening. Heterogeneity in age, trial time, attendance rates, and length of screening intervals may have contributed to the variation in effect between the trials.