Coverage determinants of breast cancer screening in Flanders: an evaluation of the past decade.

BACKGROUND: Breast cancer (BC) is the most common cancer in women in the developed world. In order to find developing cancers in an early stage, BC screening is commonly used. In Flanders, screening is performed in and outside an organized breast cancer screening program (BCSP). However, the determinants of BC screening coverage for both screening strategies are yet unknown. OBJECTIVE: To assess the determinants of BC screening coverage in Flanders. METHODS: Reimbursement data were used to attribute a screening status to each woman in the target population for the years 2008-2016. Yearly coverage data were categorized as screening inside or outside BCSP or no screening. Data were clustered by municipality level. A generalized linear equation model was used to assess the determinants of screening type. RESULTS: Over all years and municipalities, the median screening coverage rate inside and outside BCSP was 48.40% (IQR: 41.50-54.40%) and 14.10% (IQR: 9.80-19.80%) respectively. A higher coverage rate outside BSCP was statistically significantly (P < 0.001) associated with more crowded households (OR: 3.797, 95% CI: 3.199-4.508), younger age, higher population densities (OR: 2.528, 95% CI: 2.455-2.606), a lower proportion of unemployed job seekers (OR: 0.641, 95% CI: 0.624-0.658) and lower use of dental care (OR: 0.969, 95% CI: 0.967-0.972). CONCLUSION: Coverage rate of BC screening is not optimal in Flanders. Women with low SES that are characterized by younger age, living in a high population density area, living in crowded households, or having low dental care are less likely to be screened for BC in Flanders. If screened, they are more likely to be screened outside the BCSP.

Flemish breast cancer screening programme: 15 years of key performance indicators (2002-2016).

BACKGROUND: We examined 15 years of key performance indicators (KPIs) of the population-based mammography screening programme (PMSP) in Flanders, Belgium. METHODS: Individual screening data were linked to the national cancer registry to obtain oncological follow-up. We benchmarked crude KPI results against KPI-targets set by the European guidelines and KPI results of other national screening programmes. Temporal trends were examined by plotting age-standardised KPIs against the year of screening and estimating the Average Annual Percentage Change (AAPC). RESULTS: PMSP coverage increased significantly over the period of 15 years (+ 7.5% AAPC), but the increase fell to + 1.6% after invitation coverage was maximised. In 2016, PMSP coverage was at 50.0% and opportunistic coverage was at 14.1%, resulting in a total coverage by screening of 64.2%. The response to the invitations was 49.8% in 2016, without a trend. Recall rate decreased significantly (AAPC -1.5% & -5.0% in initial and subsequent regular screenings respectively) while cancer detection remained stable (AAPC 0.0%). The result was an increased positive predictive value (AAPC + 3.8%). Overall programme sensitivity was stable and was at 65.1% in 2014. In initial screens of 2015, the proportion of DCIS, tumours stage II+, and node negative invasive cancers was 18.2, 31.2, and 61.6% respectively. In subsequent regular screens of 2015, those proportions were 14.0, 24.8, and 65.4% respectively. Trends were not significant. CONCLUSION: Besides a suboptimal attendance rate, most KPIs in the Flemish PMSP meet EU benchmark targets. Nonetheless, there are several priorities for further investigation such as a critical evaluation of strategies to increase screening participation, organising a biennial radiological review of interval cancers, analysing the effect that preceding opportunistic screening has on the KPI for initial screenings, and efforts to estimate the impact on breast cancer mortality.

Does First Nations ancestry modify the association between gestational diabetes and subsequent diabetes: a historical prospective cohort study among women in Manitoba, Canada.

BACKGROUND: Over the past 30 years, the prevalence of diabetes has steadily increased among Canadians, and is particularly evident among First Nations (FN) women. The interplay between FN ancestry, gestational diabetes and the development of subsequent diabetes among mothers remains unclear. METHODS: After excluding known pre-existing diabetes, we explored whether FN ancestry may modify the association between gestational diabetes and post-partum diabetes among women in Manitoba (1981-2011) via a historical prospective cohort database study. We analysed administrative data in the Population Health Research Data Repository using Kaplan-Meier survival analysis and Cox proportional hazards regression. RESULTS: Gestational diabetes was diagnosed in 11 906 of 404 736 deliveries (2.9%), 6.7% of FN and 2.2% of non-FN pregnant women (P < 0.0001). Post-partum diabetes during ≤ 30 years follow-up was more than three times higher among FN women than among non-FN women (P < 0.0001). Diabetes developed in 76.0% of FN and 56.2% of non-FN women with gestational diabetes within the follow-up period. The hazard ratio of gestational diabetes for post-partum diabetes was 10.6 among non-FN women and 5.4 among FN women. Other factors associated with a higher risk of diabetes included lower family income among FN and non-FN women and rural/remote residences among FN women. Among non-FN women, urban residence was associated with a higher risk of diabetes. CONCLUSION: Gestational diabetes increases post-partum diabetes in FN and non-FN women. FN women had substantially more gestational diabetes or post-partum diabetes than non-FN women, partially due to socio-economic and environmental barriers. Reductions in gestational diabetes and socio-economic inequalities are required to prevent diabetes in women, particularly in FN population.

First results of the Flemish colorectal cancer screening program : start-up- period late 2013.

BACKGROUND AND AIMS: Investigation of the first participation rate and follow-up results of the Flemish colorectal cancer screening program. PATIENTS AND METHODS: In 2013 five age cohorts with an even age between 66 and 74 year old (n=243 335) were invited by mail to return a completed iFOBT. Participants who tested positive (≥75ng/ml) were referred to a follow-up colonoscopy. RESULTS: Participation rate was 48.4% (n=117 774). Overall positivity rate was 10.1%, and 78.1% of those tested positive underwent a colonoscopy. The positive predictive value of colonoscopy for CRC was 8.2%, for advanced adenoma 16.9% and for non-advanced adenoma 36.5%. CONCLUSIONS: Based on the EU-guidelines 35% was expected as participation for a first screening round, thus a participation rate of 48.4% is more than acceptable for a first screening year. The high positivity rate can partly be explained by including only the older ages in the start-up-period and by the first year of mass screening in Flanders. (Acta gastroenterol. belg., 2016, 79, 421-428).

Budd-Chiari syndrome: reassessment of a step-wise treatment strategy.

BACKGROUND AND STUDY AIMS: The Budd-Chiari syndrome is a rare disorder characterized by hepatic venous outflow obstruction. A step-wise management was recently proposed. The aim of this study is to reassess our treatment approach and long-term outcome. PATIENTS AND METHODS: The data of 37 Budd-Chiari patients, seen in our unit, were critically analyzed and compared with the ENVIE (European Network For Vascular Disorders of the Liver) data. RESULTS: Most patients had multiple prothrombotic conditions (41%), of which an underlying myeloproliferative neoplasm was the most frequent (59%). The JAK2V617F mutation was associated with more complete occlusion of all hepatic veins (JAK2 mutation +: 70% vs JAK2 mutation -: 23% and a higher severity score. The step-wise treatment algorithm used in our unit, in function of the severity of the liver impairment and the number and the extension of hepatic veins occluded, resulted in the following treatments: only anticoagulation (n = 7.21%), recanalization procedure (n = 4.21%), portosystemic shunts (n = 9.26%) and liver transplantation (n = 14.44%). This resulted in a 10 year survival rate of 90%. Treatment of the underlying hemostatic disorder offered a low recurrence rate. None of the 21 patients with a myeloproliferative neoplasm died in relation to the hematologic disorder. CONCLUSIONS: An individualized treatment regimen consisting of anticoagulation and interventional radiology and/or transplantation when necessary and strict follow-up of the underlying hematologic disorder, provided an excellent long-term survival, which confirm the data of the ENVIE study.

Long-term benefits of full-day kindergarten: a longitudinal population-based study.

In the first longitudinal, population-based study of full-day kindergarten (FDK) outcomes beyond primary school in Canada, we used linked administrative data to follow 15 kindergarten cohorts (n ranging from 112 to 736) up to grade 9. Provincial assessments conducted in grades 3, 7, and 8 and course marks and credits earned in grade 9 were compared between FDK and half-day kindergarten (HDK) students in both targeted and universal FDK programmes. Propensity score matched cohort and stepped-wedge designs allowed for stronger causal inferences than previous research on FDK. We found limited long-term benefits of FDK, specific to the type of programme, outcomes examined, and subpopulations. FDK programmes targeted at low-income areas showed long-term improvements in numeracy for lower income girls. Our results suggest that expectations for wide-ranging long-term academic benefits of FDK are unwarranted.

Small bioactive molecules as dual functional co-dopants for conducting polymers.

Biological responses to neural interfacing electrodes can be modulated via biofunctionalisation of conducting polymer (CP) coatings. This study investigated the use of small bioactive molecules with anti-inflammatory properties. Specifically, anionic dexamethasone phosphate (DP) and valproic acid (VA) were used to dope the CP poly(ethylenedioxythiophene) (PEDOT). The impact of DP and VA on material properties was explored both individually and together as a codoped system, compared to the conventional dopant p-toluenesulfonate (pTS). Electrical properties of DP and VA doped PEDOT were reduced in comparison to PEDOT/pTS, however co-doping with both DP and VA was shown to significantly improve the electroactivity of PEDOT in comparison the individually doped coatings. Similarly, while the individually doped PEDOT coatings were mechanically friable, the inclusion of both dopants during electropolymerisation was shown to attenuate this response. In a whole-blood model of inflammation all DP and VA doped CPs retained their bioactivity, causing a significant reduction in levels of the pro-inflammatory cytokine TNF-α. These studies demonstrated that small charged bioactive molecules are able act as dopants for CPs and that co-doping with ions of varied size and doping affinity may provide a means of addressing the limitations of large bulky bimolecular dopants.

Risk factors associated with an outbreak of dengue fever/dengue haemorrhagic fever in Hanoi, Vietnam.

Dengue fever/dengue haemorrhagic fever (DF/DHF) appears to be emerging in Hanoi in recent years. A case-control study was performed to investigate risk factors for the development of DF/DHF in Hanoi. A total of 73 patients with DF/DHF and 73 control patients were included in the study. The risk factor analysis indicated that living in rented housing, living near uncovered sewers, and living in a house discharging sewage directly into to ponds were all significantly associated with DF/DHF. People living in rented houses were 2·2 times more at risk of DF/DHF than those living in their own homes [adjusted odds ratio (aOR) 2·2, 95% confidence interval (CI) 1·1-4·6]. People living in an unhygienic house, or in a house discharging sewage directly to the ponds were 3·4 times and 4·3 times, respectively, more likely to be associated with DF/DHF (aOR 3·4, 95% CI 1-11·7; aOR 4·3, 95% CI 1·1-16·9). These results contribute to the understanding of the dynamics of dengue transmission in Hanoi, which is needed to implement dengue prevention and control programmes effectively and efficiently.

Follicular lymphoma presenting with hypercalcaemia: an unusual mechanism of hypercalcaemia.

Hypercalcaemia is a frequent finding in patients with cancer. In up to 30% of malignancies, the disease course is complicated with hypercalcaemia. For hospitalized patients, cancer is the most common cause of hypercalcaemia. In normal physiological circumstances, the ionized calcium is kept in check by the influence of two important hormones, parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D). However, cancer can misbalance the calcium homeostasis by generating certain humoural mediators. Overproduction of parathyroid hormone-related peptide (PTH-rp), intact PTH, 1,25(OH)2D, and cytokines all cause hypercalcaemia. Hypercalcaemia is frequent in certain haematological cancers such as multiple myeloma and aggressive lymphomas. But hypercalcaemia is rare in patients with indolent lymphomas such follicular lymphoma. This case illustrates as a first to our knowledge the involvement of cytokines and chemokines in the pathophysiology of lymphoma-related hypercalcaemia. A pathophysiological mechanism is offered based upon the current understanding of cytokines and chemokines related to follicular lymphoma.

Quantifying independent risk factors for failing to rescreen in a breast cancer screening program in Flanders, Belgium.

BACKGROUND: Mammographic screening may reduce breast cancer mortality by about 20%, provided participation is high and women screen regularly. We quantified independent risk factors for failing to rescreen and built a model to predict how rescreening rates change if these risk factors would be modified. METHODS: Multivariate analysis was used to analyze data from a prospective study which included a self-administered questionnaire and rescreening status 30months after a t0 mammogram, using a random sample of women 50-67years (Belgium 2010-2013). RESULTS: A false positive result at the most recent past mammogram (Odds Ratio=5.0, 95% Confidence Interval 3.6-6.8), an interval until new invitation greater than 25months (Odds Ratio=4.8 for >29months, 95% Confidence Interval 2.9-8.1), waiting times in the mammography unit >1h (Odds Ratio=2.1, 95% Confidence Interval 1.2-3.7) and difficulties in reaching the unit (Odds Ratio=2.5, 95% Confidence Interval 1.4-4.4) were the strongest independent predictors for failing to rescreen. The area under the curve of the receiver operating characteristic analysis was 0.705 for the model development stage and 0.717 for the validation stage and goodness-of-fit was good. CONCLUSIONS: Maintaining an invitation cycle of maximum 25months, limiting waiting time in the mammography unit and lowering the number of false positives could increase breast cancer screening compliance.

A next generation enzymatic magnesium assay on the Abbott ARCHITECT chemistry system meets performance goals based on biological variation.

OBJECTIVE: To evaluate the performance of the Abbott ARCHITECT enzymatic assay for magnesium (3P68) in serum/plasma and urine against analytical goals based on biological variation. METHODS: Analytical performance was evaluated according to CLSI protocols. Precision was examined using commercial chemistry controls. Accuracy was assessed against NIST SRM 956c, electrolytes in human serum. Correlation with the arsenazo Mg assay (7D70) was completed using patient samples (plasma, N = 101; urine, N = 90). Common interferences were examined in pooled patient specimens with high and low magnesium concentrations. RESULTS: The enzymatic Mg assay displayed imprecision of 1.7% at 0.72 mmol/L and 1.4% at 1.80 mmol/L (20 days, one calibration, one reagent lot). The linear range was verified between 0.18-7.0 mmol/L (plasma) and 0.01-10.69 mmol/L (urine). Results of the enzymatic assay (x) correlated well with the predicate assay (y) with the relationships y = 0.891x + 0.035, R = 0.967 (plasma) and y = 1.181x + 0.086, R = 0.997 (urine). Mean bias of the NIST SRM 956 c samples was -1.4%. This method showed minimal interference by hemoglobin (3g/L as hemolysate), lipemia (20 g/L Intralipid), unconjugated bilirubin (531 µmol/L), and ascorbate (680 µmol/L). CONCLUSIONS: The ARCHITECT Magnesium assay 3P68 achieved the desirable analytical quality specification of 4.8% for total allowable error. In comparison to the 7D70 assay, notable improvements are seen in precision, 30-day calibration stability, and minimal interference by hemolyzed and lipemic samples.

False-positive results in mammographic screening for breast cancer in Europe: a literature review and survey of service screening programmes.

OBJECTIVE: To estimate the cumulative risk of a false-positive screening result in European mammographic screening programmes, and examine the rates and procedures of further assessment. METHODS: A literature review was conducted to identify studies of the cumulative risk of a false-positive result in European screening programmes (390,000 women). We then examined aggregate data, cross-sectional information about further assessment procedures among women with positive results in 20 mammographic screening programmes from 17 countries (1.7 million initial screens, 5.9 million subsequent screens), collected by the European Network for Information on Cancer project (EUNICE). RESULTS: The estimated cumulative risk of a false-positive screening result in women aged 50-69 undergoing 10 biennial screening tests varied from 8% to 21% in the three studies examined (pooled estimate 19.7%). The cumulative risk of an invasive procedure with benign outcome ranged from 1.8% to 6.3% (pooled estimate 2.9%). The risk of undergoing surgical intervention with benign outcome was 0.9% (one study only). From the EUNICE project, the proportions of all screening examinations in the programmes resulting in needle biopsy were 2.2% and 1.1% for initial and subsequent screens, respectively, though the rates differed between countries; the corresponding rates of surgical interventions among women without breast cancer were 0.19% and 0.07%. CONCLUSION: The specific investigative procedures following a recall should be considered when examining the cumulative risk of a false-positive screening result. Most women with a positive screening test undergo a non-invasive assessment procedure. Only a small proportion of recalled women undergo needle biopsy, and even fewer undergo surgical intervention.

Mammographic screening programmes in Europe: organization, coverage and participation.

OBJECTIVES: To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe. METHODS: We used the European Network for Information on Cancer (EUNICE), a web-based data warehouse (EUNICE Breast Cancer Screening Monitoring, EBCSM) for breast cancer screening, to obtain information on programme characteristics, coverage and participation from its initial application in 10 national and 16 regional programmes in 18 European countries. RESULTS: The total population targeted by the screening programme services covered in the report comprised 26.9 million women predominantly aged 50-69. Most of the collected data relates to 2005, 2006 and/or 2007. The average participation rate across all programmes was 53.4% (range 19.4-88.9% of personally invited); or 66.4% excluding Poland, a large programme that initiated personal invitations in 2007. Thirteen of the 26 programmes achieved the European Union benchmark of acceptable participation (>70%), nine achieved the desirable level (>75%). Despite considerable invitation coverage across all programmes (79.3%, range 50.9-115.2%) only 48.2% (range 28.4-92.1%) of the target population were actually screened. The overall invitation and examination coverage excluding Poland was 70.9% and 50.3%, respectively. CONCLUSIONS: The results demonstrate the feasibility of European-wide screening monitoring using the EBCSM data warehouse, although further efforts to refine the system and to harmonize standards and data collection practices will be required, to fully integrate all European countries. The more than three-fold difference in the examination coverage should be taken into account in the evaluation of service screening programmes.

Degradable, click poly(vinyl alcohol) hydrogels: characterization of degradation and cellular compatibility.

The aim of this research was to understand the influence of functional group density on degradation and cell survival within injectable poly(vinyl alcohol) (PVA) hydrogels crosslinked through hydrazone bonds. For this purpose, PVA was modified with aldehyde and hydrazide functional groups. The click reaction between these two macromers, performed under physiologic conditions, led to hydrogel formation in less than 3 min. The influence of the crosslinking density on the gelation time, volumetric swelling ratio and mass loss of the hydrogels was investigated. These systems were slowly degradable as they maintained their gel-like state for more than 120 days. However, these networks also exhibited unusual degradation behaviour that could be the result of a breaking-forming bond phenomenon, attributable to the reversible nature of the hydrazone bond. This study also demonstrated that these networks maintained their mechanical strength while degrading, and cell encapsulation revealed the cytocompatibility of these systems.

Immunoisolating semi-permeable membranes for cell encapsulation: focus on hydrogels.

Cell-based medicine has recently emerged as a promising cure for patients suffering from various diseases and disorders that cannot be cured/treated using technologies currently available. Encapsulation within semi-permeable membranes offers transplanted cell protection from the surrounding host environment to achieve successful therapeutic function following in vivo implantation. Apart from the immunoisolation requirements, the encapsulating material must allow for cell survival and differentiation while maintaining its physico-mechanical properties throughout the required implantation period. Here we review the progress made in the development of cell encapsulation technologies from the mass transport side, highlighting the essential requirements of materials comprising immunoisolating membranes. The review will focus on hydrogels, the most common polymers used in cell encapsulation, and discuss the advantages of these materials and the challenges faced in the modification of their immunoisolating and permeability characteristics in order to optimize their function.

Safety and feasibility of nasopharyngeal evaporative cooling in the emergency department setting in survivors of cardiac arrest.

AIM: Mild therapeutic hypothermia improves survival and neurologic recovery in primary comatose survivors of cardiac arrest. Cooling effectivity, safety and feasibility of nasopharyngeal cooling with the RhinoChill device (BeneChill Inc., San Diego, USA) were determined for induction of therapeutic hypothermia. METHODS: Eleven emergency departments and intensive care units participated in this multi-centre, single-arm descriptive study. Eighty-four patients after successful resuscitation from cardiac arrest were cooled with nasopharyngeal delivery of an evaporative coolant for 1h. Subsequently, temperature was controlled with systemic cooling at 33 degrees C. Cooling rates, adverse events and neurologic outcome at hospital discharge using cerebral performance categories (CPC; CPC 1=normal to CPC 5=dead) were documented. Temperatures are presented as median and the range from the first to the third quartile. RESULTS: Nasopharyngeal cooling for 1h reduced tympanic temperature by median 2.3 (1.6; 3.0) degrees C, core temperature by 1.1 (0.7; 1.5) degrees C. Nasal discoloration occurred during the procedure in 10 (12%) patients, resolved in 9, and was persistent in 1 (1%). Epistaxis was observed in 2 (2%) patients. Periorbital gas emphysema occurred in 1 (1%) patient and resolved spontaneously. Thirty-four of 84 patients (40%) patients survived, 26/34 with favorable neurological outcome (CPC of 1-2) at discharge. CONCLUSIONS: Nasopharyngeal evaporative cooling used for 1h in primary cardiac arrest survivors is feasible and safe at flow rates of 40-50L/min in a hospital setting.

Primary birthing attendants and birth outcomes in remote Inuit communities--a natural "experiment" in Nunavik, Canada.

BACKGROUND: There is a lack of data on the safety of midwife-led maternity care in remote or indigenous communities. In a de facto natural "experiment", birth outcomes were assessed by primary birthing attendant in two sets of remote Inuit communities. METHODS: A geocoding-based retrospective birth cohort study in 14 Inuit communities of Nunavik, Canada, 1989-2000: primary birth attendants were Inuit midwives in the Hudson Bay (1529 Inuit births) vs western physicians in Ungava Bay communities (1197 Inuit births). The primary outcome was perinatal death. Secondary outcomes included stillbirth, neonatal death, post-neonatal death, preterm, small-for-gestational-age and low birthweight birth. Multilevel logistic regression was used to obtain the adjusted odds ratios (aOR) controlling for maternal age, marital status, parity, education, infant sex and plurality, community size and community-level random effects. RESULTS: The aORs (95% confidence interval) for perinatal death comparing the Hudson Bay vs Ungava Bay communities were 1.29 (0.63 to 2.64) for all Inuit births and 1.13 (0.48 to 2.47) for Inuit births at > or =28 weeks of gestation. There were no statistically significant differences in the crude or adjusted risks of any of the outcomes examined. CONCLUSION: Risks of perinatal death were somewhat but not significantly higher in the Hudson Bay communities with midwife-led maternity care compared with the Ungava Bay communities with physician-led maternity care. These findings are inconclusive, although the results excluding extremely preterm births are more reassuring concerning the safety of midwife-led maternity care in remote indigenous communities.

Haemolytic anaemia caused by piperacillin-tazobactam.

We report a case of haemolytic due to the use of piperacillin-tazobactam in a 50-year-old woman. Since 2002 4 other cases were reported. Either the presence of piperacillin as tazobactam can induce haemolysis. In all cases discontinuating the drugs resolves the haemolysis. Although drug-induced haemolytic anaemia due to piperacillin-tazobactam is rare, the common use of this antibioticum in the critical care setting should alert the physician as a possible culprit in cases of haemolytic anaemia.

Stroke surveillance in Manitoba, Canada: estimates from administrative databases.

This study investigated the use of population-based administrative databases for stroke surveillance. First, a meta-analysis was conducted of four studies, identified via a PubMed search, which estimated the sensitivity and specificity of hospital data for ascertaining cases of stroke when clinical registries or medical charts were the gold standard. Subsequently, case-ascertainment algorithms based on hospital, physician and prescription drug records were developed and applied to Manitoba's administrative data, and prevalence estimates were obtained for fiscal years 1995/96 to 2003/04 by age group, sex, region of residence and income quintile. The meta-analysis results revealed some over-ascertainment of stroke cases from hospital data when the algorithm was based on diagnosis codes for any type of cerebrovascular disease (Mantel-Haenszel Odds-Ratio [OR] - 1.70 [95% confidence interval (CI): 1.53 - 1.88]). Analyses of Manitoba administrative data revealed that while the total number of stroke cases varied substantially across the algorithms, the trend in prevalence was stable regardless of the algorithm adopted.