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.

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.

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.

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.

Competencies in the context of entry-level registered nurse practice: a collaborative project in Canada.

AIM: To present the process used by professional staff from 10 Canadian jurisdictional regulatory bodies to develop entry-level competencies for registered nurse practice. BACKGROUND: Canada is composed of provinces and territories, commonly referred to as jurisdictions with the governmental legal authority to administer the affairs of the area. Each jurisdiction establishes regulatory bodies with the mandate to protect the public. The Executive Directors of the jurisdictional regulatory bodies initiated this collaborative project to develop entry-level competencies for registered nurses. The purpose of the project was to enhance the consistency of entry-level registered nurse competencies, thereby supporting reciprocity of registration and workforce mobility, within Canada. This was the first time that Canadian nursing regulatory bodies have collaborated in a jurisdictional-driven project of this magnitude for registered nurses exclusively. This initiative has demonstrated how nursing regulatory bodies, working together, can achieve a common goal. PROCESS: The project participants worked from 2004 to 2006, developing and refining the competencies. Multiple methods were used to accomplish the task, including monthly teleconferences, frequent E-mail communications, small group work and face-to-face meetings. At various stages in the project, consultation with registered nurses within several participating jurisdictions occurred, depending on where each jurisdiction was in their jurisdictional competency review. This project spanned a 2-year period and resulted in a comprehensive document that captured the views of the participants and enhanced the resulting document. CONCLUSION: The result is a document stating the core competencies for entry-level registered nurses in the 10 participating jurisdictions and includes several components that establish the context in which entry-level competencies are developed and applied. The 119 competency statements are organized in a standard-based framework of five categories: professional responsibility and accountability; knowledge-based practice; ethical practice; service to the public; and self-regulation. The project team plans to follow up on implementation as each jurisdiction decides how to use the competencies within their particular jurisdiction.

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).

Multicenter, randomized, controlled trial of 150-J biphasic shocks compared with 200- to 360-J monophasic shocks in the resuscitation of out-of-hospital cardiac arrest victims. Optimized Response to Cardiac Arrest (ORCA) Investigators.

BACKGROUND: In the present study, we compared an automatic external defibrillator (AED) that delivers 150-J biphasic shocks with traditional high-energy (200- to 360-J) monophasic AEDs. METHODS AND RESULTS: AEDs were prospectively randomized according to defibrillation waveform on a daily basis in 4 emergency medical services systems. Defibrillation efficacy, survival to hospital admission and discharge, return of spontaneous circulation, and neurological status at discharge (cerebral performance category) were compared. Of 338 patients with out-of-hospital cardiac arrest, 115 had a cardiac etiology, presented with ventricular fibrillation, and were shocked with an AED. The time from the emergency call to the first shock was 8.9+/-3.0 (mean+/-SD) minutes. CONCLUSIONS: The 150-J biphasic waveform defibrillated at higher rates, resulting in more patients who achieved a return of spontaneous circulation. Although survival rates to hospital admission and discharge did not differ, discharged patients who had been resuscitated with biphasic shocks were more likely to have good cerebral performance.

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.

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.

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.

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.

The impact of heat waves and cold spells on mortality rates in the Dutch population.

We conducted the study described in this paper to investigate the impact of ambient temperature on mortality in the Netherlands during 1979-1997, the impact of heat waves and cold spells on mortality in particular, and the possibility of any heat wave- or cold spell-induced forward displacement of mortality. We found a V-like relationship between mortality and temperature, with an optimum temperature value (e.g., average temperature with lowest mortality rate) of 16.5 degrees C for total mortality, cardiovascular mortality, respiratory mortality, and mortality among those [Greater and equal to] 65 year of age. For mortality due to malignant neoplasms and mortality in the youngest age group, the optimum temperatures were 15.5 degrees C and 14.5 degrees C, respectively. For temperatures above the optimum, mortality increased by 0.47, 1.86, 12.82, and 2.72% for malignant neoplasms, cardiovascular disease, respiratory diseases, and total mortality, respectively, for each degree Celsius increase above the optimum in the preceding month. For temperatures below the optimum, mortality increased 0.22, 1.69, 5.15, and 1.37%, respectively, for each degree Celsius decrease below the optimum in the preceding month. Mortality increased significantly during all of the heat waves studied, and the elderly were most effected by extreme heat. The heat waves led to increases in mortality due to all of the selected causes, especially respiratory mortality. Average total excess mortality during the heat waves studied was 12.1%, or 39.8 deaths/day. The average excess mortality during the cold spells was 12.8% or 46.6 deaths/day, which was mostly attributable to the increase in cardiovascular mortality and mortality among the elderly. The results concerning the forward displacement of deaths due to heat waves were not conclusive. We found no cold-induced forward displacement of deaths.

Incidence of physician-diagnosed primary Sjögren syndrome in residents of Olmsted County, Minnesota.

OBJECTIVES: To estimate the incidence of physician-diagnosed primary Sjögren syndrome (SS) among residents of Olmsted County, Minnesota, in the setting of usual medical care and to determine how often objective criteria are available in the medical records of such patients. PATIENTS AND METHODS: We reviewed all medical records of residents in Olmsted County with physician-diagnosed SS from 1976 to 1992 to determine whether they had undergone objective tests for keratoconjunctivitis sicca, salivary dysfunction, or serologic abnormality. Confounding illnesses were excluded. To identify misclassified cases, all records from patients with xerostomia or keratoconjunctivitis sicca were also reviewed. The average annual SS incidence rates were calculated by considering the entire population to be at risk. RESULTS: Of 75 patients with onset of SS during the study period, 53 had primary SS. All patients were white, 51 (96.2%) were women, and the mean +/- SD age was 59+/-15.8 years. The age- and sex-adjusted annual incidence was 3.9 per 100,000 population (95% confidence interval, 2.8-4.9) for patients with primary SS. Eleven patients (20.8%) with physician-diagnosed SS had no documentation of objective eye, mouth, or laboratory abnormalities. Objective evaluations performed most frequently were laboratory and ocular tests and least often were investigations of xerostomia. CONCLUSIONS: The average annual incidence rate for physician-diagnosed primary SS in Olmsted County is about 4 cases per 100,000 population. These data probably underestimate the true incidence because they are based on usual medical care of patients with SS in a community setting, rather than on a case-detection survey. In the future, a true incidence may be possible with a higher index of suspicion, greater attention to objective tests, and increased awareness of new classification criteria for SS. For epidemiological studies based on existing data, application of current criteria may not be feasible, and consensus on criteria for such studies would be useful.

Rapid identification of marker chromosomes using primed in situ labeling (PRINS).

Primed in situ labeling (PRINS) is a relatively new technology with wide-ranging applications in clinical cytogenetics. Using PRINS, we have identified the chromosomal origin of marker chromosomes in three patients. In the first patient with primary amenorrhea, we were able to confirm the marker chromosome as originating from an X. In the second (prenatal) case, PRINS allowed us to determine rapidly the origin of the marker as a Y chromosome. In the third patient with minor anomalies, the marker was identified as derived from a chromosome 18. In all three cases, application of PRINS permitted us to characterize the marker chromosomes within 1 hour after the slides were prepared. The methodology is simple, has added advantages over conventional fluorescence in situ hybridization (FISH), and can be used as a viable and effective alternative to FISH in clinical cytogenetic diagnosis.

Hypertrichosis, pigmentary retinopathy, and facial anomalies: a new syndrome?

We report on a 22-month-old male with congenital hypertrichosis of the face, arms, legs, shoulders, back, and buttocks, abnormal facial appearance, dolichocephaly, and pigmentary retinopathy. Symmetrical hyperpigmentation is present on the sideburn areas of his face, and hyperpigmented streaks are seen on arms and legs. Biopsy of the hyperpigmented' skin showed many separate bundles of smooth muscles in the dermis. No relative had hypertrichosis or other birth defects. To our knowledge, the syndrome of facial anomalies, pigmentary retinopathy, and congenital hypertrichosis has not been reported previously.

Identification of the origin of centromeres in whole-arm translocations using fluorescent in situ hybridization with alpha-satellite DNA probes.

We detected 2 patients with whole-arm translocations resulting in a derivative chromosome consisting of 18q and 21q. Because the breakpoints were near the centromere, classical cytogenetic techniques could not determine the centromeric origin of the derivative chromosomes. Using nonradioactive in situ hybridization with a chromosome 18 alpha-satellite DNA probe (D18Z1), the centromeres in the abnormal chromosomes were determined to be from chromosome 18. The abnormality in one patient resulted in monosomy 18p with a karyotype 45,XX, -18, -21, + der(18)t(18;21) (p11;q11)mat complement. The second patient with a 46,XX, -21, + der(18)t(18;21)(p11;q11) de novo karyotype had complete trisomy of 18q. In both cases the appropriate phenotype was observed.

Characterization of an unbalanced de novo rearrangement by microsatellite polymorphism typing and by fluorescent in situ hybridization.

Unbalanced de novo rearrangements, difficult to characterize by conventional cytogenetic techniques, may be elucidated by molecular approaches. By dinucleotide repeat polymorphism typing and fluorescence in situ hybridization (FISH), we have defined the composition of an unbalanced de novo translocation (46,XX,15p+) in a child with multiple congenital anomalies. Use of a microsatellite repeat D5S208 (localized to 5p15) and polymerase chain reaction (PCR) analysis confirmed that the extra segment originated from the short arm of chromosome 5. Amplification of the patient's DNA with primers for dinucleotide repeats D5S350 and D5S118 showed that the entire 5p (from 5pter to 5q11) was present in 3 copies. FISH confirmed the trisomic status of 5p, and further revealed the presence of centromeres of both chromosomes 5 and 15 on the rearranged chromosome thus delineating its dicentric nature. This information allowed us to redefine the de novo rearrangement in this patient as 46,XX,dic der(15)t(5;15)(q11;p11).

Localization of SRY by primed in situ labeling in XX and XY sex reversal.

Primed in situ labeling (PRINS) can be used to localize DNA segments too small to be detected by fluorescence in situ hybridization. By PRINS we identified the SRY gene in two XX males, a woman with XY gonadal dysgenesis, and an azoospermic male with Xp-Yp interchange. Because PRINS has been used generally in the study of repetitive sequences, we modified the technique for study of the single copy 2. 1-kb SRY sequence. SRY signals were identified at band Yp11.31p11.32 in normal XY males and in the woman with XY gonadal dysgenesis. SRY signals were identified on Xp22 in one XX male but not in the other. They were identified in the corresponding region (Xp22) of the der(X) in the azoospermic male with Xp-Yp interchange. SRY signals were not observed in normal XX females. Presence of SRY in DNA samples from the various subjects was confirmed by polymerase chain reaction. We conclude that PRINS is ideal for rapid localization of single copy genes and small DNA segments in general.