Women's excess unhealthy life years: disentangling the unhealthy life years gap.

BACKGROUND: Compared to men, women live longer but have more years with disability. We assessed the contribution of gender differences in mortality and disability, total and by cause, to women's excess unhealthy life years (ULYs). METHODS: We used mortality data for France 2008 from Eurostat, causes of death from the CépiDc-INSERM-database; and disability and chronic conditions data from the French Disability Health Survey 2008-09. ULYs were calculated by the Sullivan method. The contributions of mortality and disability differences to gender differences in ULY were based on decomposition analyses. RESULTS: Life expectancy of French women aged 50 was 36.3 years of which 19.0 were ULYs; life expectancy of men was 30.4 years of which 14.2 were ULYs. Of the 4.8 excess ULYs in women, 4.0 years were due to lower mortality. Of these 4.0 ULYs, 1.8 ULY originated from women's lower mortality from cancer, 0.8 ULY from heart disease and 0.3 ULY from accidents. The remaining 0.8 excess ULY in women were from higher disability prevalence, including higher disability from musculoskeletal diseases (+1.8 ULY) and anxiety-depression (+0.6 ULY) partly offset by lower disability from heart diseases (-0.8 ULY) and accidents (-0.3 ULY). CONCLUSION: Lower mortality and higher disability prevalence contributed to women's longer life expectancy with disability. Women's higher disability prevalence due to non-fatal disabling conditions was partly offset by lower disability from heart disease and accidents. Conditions differentially impact gender differences in ULY, depending on whether they are mainly life-threatening or disabling. The conclusions confirm the health-survival paradox.

Chronic-active antibody-mediated rejection with or without donor-specific antibodies has similar histomorphology and clinical outcome - a retrospective study.

Chronic-active antibody-mediated rejection (c-aABMR) is defined as histological evidence of chronic endothelial injury (cg), also known as transplant glomerulopathy, and either microvascular inflammation (MVI) or positivity for C4d. Importantly, the presence of donor-specific antibodies (DSA) is currently still mandatory for the diagnosis of c-aABMR. This retrospective study of 41 c-aABMR patients investigates whether cases suspicious for c-aABMR (DSA negative, n = 24) differ from cases of c-aABMR (DSA positive, n = 17) with respect to renal histology, allograft function and long-term graft survival. All included patients had progressive loss of allograft function and were diagnosed by for cause biopsy and scored according to the Banff '15 criteria. In all DSApos cases, DSA were de novo and the majority was directed against HLA-II being mostly anti-HLA-DQ antibodies. There were no statistically significant differences in clinical characteristics, decline in allograft function and renal allograft survival in cases with or without DSAs. All cases showed chronic histomorphological damage and inflammation, irrespective of the presence of DSA. Renal histology and clinical outcome of patients suspicious for c-aABMR (DSAneg) do not significantly differ from patients with a diagnosis of c-aABMR (DSApos). We believe that our study adds to the ongoing debate regarding the need for DSAs to be present for the diagnosis of c-aABMR.

Craniofacial and extracraniofacial anomalies in craniofacial microsomia: a multicenter study of 755 patients'

PURPOSE: Craniofacial microsomia (CFM) is a congenital malformation of structures derived from the first and second pharyngeal arches leading to underdevelopment of the face. However, besides the craniofacial underdevelopment, extracraniofacial anomalies including cardiac, renal and skeletal malformation have been described. The aim of this study is to analyse a large population of patients with regard to demographics, typical phenotypes including craniofacial and extracraniofacial anomalies, and the correlations between the different variables of this condition. MATERIAL AND METHODS: A retrospective study was conducted in patients diagnosed with CFM with available clinical and/or radiographic images. All charts were reviewed for information on demographic, radiographic and diagnostic criteria. The presence of cleft lip/palate and extracraniofacial anomalies were noted. Pearson correlation tests and principal component analysis was performed on the phenotypic variables. RESULTS: A total of 755 patients were included. The male-to-female ratio and right-to-left ratio were both 1.2:1. A correlation was found among Pruzansky-Kaban, orbit and soft tissue. Similar correlations were found between ear and nerve. There was no strong correlation between phenotype and extracraniofacial anomalies. Nevertheless, extracraniofacial anomalies were more frequently seen than in the 'normal' population. Patients with bilateral involvement had a more severe phenotype and a higher incidence of extracraniofacial and cleft lip/palate. CONCLUSION: Outcomes were similar to those of other smaller cohorts. Structures derived from the first pharyngeal arch and the second pharyngeal arch were correlated with degree of severity. Extracraniofacial anomalies were positively correlated with CFM. The findings show that bilaterally affected patients are more severely affected and should be approached more comprehensively.

The effect of population-based mammography screening in Dutch municipalities on breast cancer mortality: 20 years of follow-up.

Long-term follow-up data on the effects of screening are scarce, and debate exists on the relative contribution of screening versus treatment to breast cancer mortality reduction. Our aim was therefore to assess the long-term effect of screening by age and time of implementation. We obtained data on 69,630 breast cancer deaths between 1980 and 2010 by municipality (N = 431) and age of death (40-79) in the Netherlands. Breast cancer mortality trends were analyzed by defining the municipality-specific calendar year of introduction of screening as Year 0. Additionally, log-linear Poisson regression was used to estimate the turning point in the trend after Year 0, per municipality, and the annual percentage change (APC) before and after this point. Twenty years after introduction of screening breast cancer mortality was reduced by 30% in women aged 55-74 and by 34% in women aged 75-79, compared to Year 0. A similar and significant decrease was present in municipalities that started early (1987-1992) and late (1995-1997) with screening, despite the difference in availability of effective adjuvant treatment. In the age groups 55-74 and 75-79, the turning point in the trend in breast cancer mortality was estimated in Years 2 and 6 after the introduction of screening, respectively, after which mortality decreased significantly by 1.9% and 2.6% annually. These findings show that the implementation of mammography screening in Dutch municipalities is associated with a significant decline in breast cancer mortality in women aged 55-79, irrespective of time of implementation.

Motor problems in children with neurofibromatosis type 1.

BACKGROUND: Children with the neurogenetic disorder neurofibromatosis type 1 (NF1) often have problems with learning and behaviour. In both parent reports and neuropsychological assessment, motor problems are reported in approximately one third to one half of the children with NF1. Studies using broad motor performance test batteries with relatively large groups of children with NF1 are limited. The aim of this cross-sectional observational study was to describe the severity of motor problems in children with NF1 and to explore the predictive value of demographics, intelligence, and behavioural problems. METHODS: From 2002 to 2014, 69 children with NF1, aged 4 to 16 years (age = 9.5 ± 2.8 years; 29 girls) had a motor, psychological, and neurological evaluation in an NF1 expertise centre. Data were collected about (1) motor performance (M-ABC: Movement Assessment Battery for Children), (2) intelligence, and (3) emotional and behavioural problems as rated by parents. RESULTS: Sixty-one percent of these children scored within the clinical range of the M-ABC. In ordinal logistic regression analyses, motor problems were associated with symptoms of attention-deficit/hyperactivity disorder (ADHD), symptoms of autism spectrum disorder (ASD), and externalising behavioural problems. Motor outcome was not predicted by age, intelligence, scoliosis, hypotonia, nor hypermobility. CONCLUSIONS: Motor problems are among the most common comorbid developmental problems in children with NF1, and these problems do not diminish with age. Because of their impact on daily functioning, motor problems need to be specifically addressed in diagnosis, follow-up, and treatment of NF1.

Cervical cancer incidence after normal cytological sample in routine screening using SurePath, ThinPrep, and conventional cytology: population based study.

Objective To compare the cumulative incidence of cervical cancer diagnosed within 72 months after a normal screening sample between conventional cytology and liquid based cytology tests SurePath and ThinPrep.Design Retrospective population based cohort study.Setting Nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), January 2000 to March 2013.Population Women with 5 924 474 normal screening samples (23 833 123 person years).Exposure Use of SurePath or ThinPrep versus conventional cytology as screening test.Main outcome measure 72 month cumulative incidence of invasive cervical cancer after a normal screening sample for each screening test. Cox regression analyses assessed the hazard ratios, adjusted for calendar time, age, screening history, and socioeconomic status and including laboratories as random effects.Results The 72 month cumulative cancer incidence was 58.5 (95% confidence interval 54.6 to 62.7) per 100 000 normal conventional cytology samples, compared with 66.8 (56.7 to 78.7) for ThinPrep and 44.6 (37.8 to 52.6) for SurePath. Compared with conventional cytology, the hazard of invasive cancer was 19% lower (hazard ratio 0.81, 95% confidence interval 0.66 to 0.99) for SurePath, mainly caused by a 27% lower hazard (0.73, 0.57 to 0.93) of a clinically detected cancer. For ThinPrep, the hazard was on average 15% higher (hazard ratio 1.15, 0.95 to 1.38), mainly caused by a 56% higher hazard of a screen detected cancer (1.56, 1.17 to 2.08).Conclusions These findings should provoke reconsideration of the assumed similarity in sensitivity to detect progressive cervical intraepithelial neoplasia between different types of liquid based cytology and conventional cytology.

Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study.

BACKGROUND: Biologics are a safe and efficacious therapy for psoriasis. The drug survival of biologics may be disappointing, primarily due to loss of efficacy. Therefore, safe combination treatments are sought to improve their clinical response. OBJECTIVE: To assess the efficacy, safety and tolerability of the combination therapy of etanercept with fumarates versus etanercept monotherapy. METHODS: Thirty-three patients with psoriasis were randomized 1:1 to receive etanercept combined with fumarates or etanercept monotherapy. The primary outcome measure was the difference in PASI-75 response after 24 weeks; additionally, a longitudinal analysis was performed. An important secondary outcome measure was the proportion of patients with a Physician Global Assessment (PGA) of clear or almost clear. Adverse events were collected throughout the study. RESULTS: In the combination therapy group, 78% (14 out of 18 patients) reached PASI-75 at week 24 versus 57% (8 out of 14 patients) in the monotherapy group (p = 0.27). The longitudinal analysis showed a PASI reduction of 5.97% per week for the combination therapy group and of 4.76% for the monotherapy group (p = 0.11). In the combination therapy group, 94% (17 out of 18 patients) of patients had a PGA of clear/almost clear versus 64% (9 out of 14 patients) in the monotherapy group (p = 0.064). The incidence of mild gastrointestinal complaints was higher in the combination group than in the monotherapy group. CONCLUSION: Using the PGA, combination therapy showed a trend towards faster improvement in the first 24 weeks. The difference in the PASI score between the two groups was not statistically significant. Addition of fumarates to etanercept for 48 weeks appeared safe with an acceptable tolerability.

Sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial.

OBJECTIVE: To investigate whether mammalian target of rapamycin complex 1 (mTORC1) inhibitors could reduce seizure frequency in children with tuberous sclerosis complex (TSC). METHODS: Due to slow inclusion rate, target inclusion of 30 children was not reached. Twenty-three children with TSC and intractable epilepsy (age 1.8-10.9 years) were randomly assigned (1:1) to open-label, add-on sirolimus treatment immediately or after 6 months. Sirolimus was titrated to trough levels of 5-10 ng/mL. Primary endpoint was seizure frequency change during the sixth month of sirolimus treatment. RESULTS: Intention-to-treat analysis showed sirolimus treatment resulted in 41% seizure frequency decrease (95% confidence interval [CI] -69% to +14%; p = 0.11) compared to the standard-care period. Per protocol analysis of 14 children who reached sirolimus target trough levels in the sixth sirolimus month showed a seizure frequency decrease of 61% (95% CI -86% to +6%; p = 0.06). Cognitive development did not change. All children had adverse events. Five children discontinued sirolimus prematurely. CONCLUSIONS: We describe a randomized controlled trial for a non-antiepileptic drug that directly targets a presumed causal mechanism of epileptogenesis in a genetic disorder. Although seizure frequency decreased, especially in children reaching target trough levels, we could not show a significant benefit. Larger trials or meta-analyses are needed to investigate if patients with TSC with seizures benefit from mTORC1 inhibition. This trial was registered at trialregister.nl (NTR3178) and supported by the Dutch Epilepsy Foundation. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that sirolimus does not significantly reduce seizure frequency in children with TSC and intractable epilepsy. The study lacked the precision to exclude a benefit from sirolimus.

Towards a standardised informed consent procedure for live donor nephrectomy: the PRINCE (Process of Informed Consent Evaluation) project-study protocol for a nationwide prospective cohort study.

INTRODUCTION: Informed consent is mandatory for all (surgical) procedures, but it is even more important when it comes to living kidney donors undergoing surgery for the benefit of others. Donor education, leading to informed consent, needs to be carried out according to certain standards. Informed consent procedures for live donor nephrectomy vary per centre, and even per individual healthcare professional. The basis for a standardised, uniform surgical informed consent procedure for live donor nephrectomy can be created by assessing what information donors need to hear to prepare them for the operation and convalescence. METHODS AND ANALYSIS: The PRINCE (Process of Informed Consent Evaluation) project is a prospective, multicentre cohort study, to be carried out in all eight Dutch kidney transplant centres. Donor knowledge of the procedure and postoperative course will be evaluated by means of pop quizzes. A baseline cohort (prior to receiving any information from a member of the transplant team in one of the transplant centres) will be compared with a control group, the members of which receive the pop quiz on the day of admission for donor nephrectomy. Donor satisfaction will be evaluated for all donors who completed the admission pop-quiz. The primary end point is donor knowledge. In addition, those elements that have to be included in the standardised format informed consent procedure will be identified. Secondary end points are donor satisfaction, current informed consent practices in the different centres (eg, how many visits, which personnel, what kind of information is disclosed, in which format, etc) and correlation of donor knowledge with surgeons' estimation thereof. ETHICS AND DISSEMINATION: Approval for this study was obtained from the medical ethical committee of the Erasmus MC, University Medical Center, Rotterdam, on 18 February 2015. Secondary approval has been obtained from the local ethics committees in six participating centres. Approval in the last centre has been sought. RESULTS: Outcome will be published in a scientific journal. TRIAL REGISTRATION NUMBER: NTR5374; Pre-results.

Changes in mortality inequalities over two decades: register based study of European countries.

OBJECTIVE: To determine whether government efforts in reducing inequalities in health in European countries have actually made a difference to mortality inequalities by socioeconomic group. DESIGN: Register based study. DATA SOURCE: Mortality data by level of education and occupational class in the period 1990-2010, usually collected in a census linked longitudinal study design. We compared changes in mortality between the lowest and highest socioeconomic groups, and calculated their effect on absolute and relative inequalities in mortality (measured as rate differences and rate ratios, respectively). SETTING: All European countries for which data on socioeconomic inequalities in mortality were available for the approximate period between years 1990 and 2010. These included Finland, Norway, Sweden, Scotland, England and Wales (data applied to both together), France, Switzerland, Spain (Barcelona), Italy (Turin), Slovenia, and Lithuania. RESULTS: Substantial mortality declines occurred in lower socioeconomic groups in most European countries covered by this study. Relative inequalities in mortality widened almost universally, because percentage declines were usually smaller in lower socioeconomic groups. However, as absolute declines were often smaller in higher socioeconomic groups, absolute inequalities narrowed by up to 35%, particularly among men. Narrowing was partly driven by ischaemic heart disease, smoking related causes, and causes amenable to medical intervention. Progress in reducing absolute inequalities was greatest in Spain (Barcelona), Scotland, England and Wales, and Italy (Turin), and absent in Finland and Norway. More detailed studies preferably using individual level data are necessary to identify the causes of these variations. CONCLUSIONS: Over the past two decades, trends in inequalities in mortality have been more favourable in most European countries than is commonly assumed. Absolute inequalities have decreased in several countries, probably more as a side effect of population wide behavioural changes and improvements in prevention and treatment, than as an effect of policies explicitly aimed at reducing health inequalities.

Second-Look Colonoscopies and the Impact on Capacity in FIT-Based Colorectal Cancer Screening.

OBJECTIVES: Fecal immunochemical testing (FIT) and colonoscopy are tandem procedures in colorectal cancer (CRC) screening. A positive FIT predicts advanced neoplasia (AN) that requires endoscopic detection and removal. En bloc or piecemeal resection of AN is associated with a significant rate of residual or recurrent neoplasia. Second-look colonoscopies are indicated to assess completeness of removal of AN. These colonoscopies can make a substantial demand on colonoscopy capacity and health-care system. This study is the first to evaluate the demand and risk factors for second-look colonoscopy in FIT CRC screening. METHODS: All colonoscopies after a positive FIT, in subjects aged 50-74 years approached for 3 rounds of FIT screening, were prospectively registered. Second-look colonoscopies were defined as any colonoscopy within 1 year following a colonoscopy after positive FIT. RESULTS: Out of 1,215 FIT-positive screenees undergoing colonoscopy, 105 (8.6%) patients underwent a second-look colonoscopy, of whom 30 (2.5%) underwent more than one colonoscopy (range 2-9), leading to a total of 149 (12.3%) additional colonoscopies. Main reasons for second-look colonoscopies were assessment of complete AN removal (41.9%) and need for additional polypectomy (34.3%). Risk factors were advanced adenomas and poor bowel preparation (P<0.001). High fecal hemoglobin concentration was the only predictor of a second-look colonoscopy before index colonoscopy (P<0.001). CONCLUSIONS: Second-look colonoscopies have substantial impact on colonoscopy resources, increasing the demand with 12%. The main reasons for these second-look colonoscopies were previous incomplete polypectomy and control of completeness of removal of neoplastic lesions. A high fecal hemoglobin concentration as measured by FIT can help to identify patients at risk of a second-look colonoscopy.

Gender Differences in Fecal Immunochemical Test Performance for Early Detection of Colorectal Neoplasia.

BACKGROUND & AIMS: Fecal immunochemical tests (FITs) are used widely in colorectal cancer screening. Programs use the same fecal hemoglobin threshold for colonoscopy referral for men and women, but it is unclear whether FIT performs equally in both sexes. We therefore assessed FIT performance in men and women. METHODS: A prospective cohort study was performed, in which a total of 10,008 average-risk subjects (age, 50-74 y) were invited for first-round screening and 8316 average-risk subjects (age, 51-74 y) were invited for second-round screening with a single FIT. Subjects with a hemoglobin (Hb) level of 10 µg hemoglobin (Hb)/g (or ≥50 ng/mL) feces or higher were referred for colonoscopy. The test characteristics were assessed by sex for a range of FIT cut-off values. RESULTS: In total, 59.8% of men and 64.6% of women participated in the first round (P < .001). At a cut-off level of 10 µg Hb/g feces, the positivity rate was significantly higher among men (10.7%) compared with women (6.3%; P < .001) in the first round. The detection rate of advanced neoplasia was 4.4% for men and 2.2% for women (P < .001) in the first round. The positive predictive value for advanced neoplasia in the first round was 42% for men and 37% for women (P = .265). A significantly higher false-positive rate in men (6.3%) than in women (4.1%; P < .001) was found. Similar differences in these test characteristics were seen in the second round. CONCLUSIONS: At a cut-off level of 10 µg Hb/g feces the FIT positivity rate was higher in men, reflected by both a higher detection rate and a higher false-positive rate. The use of the same cut-off value in men and women in FIT screening is recommended based on equal test performance in terms of positive predictive value.

Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival.

OBJECTIVES: We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. BACKGROUND: Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. METHODS: Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. RESULTS: One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98). CONCLUSIONS: The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

A prospective assessment of the natural course of the exocrine pancreatic function in patients with a pancreatic head tumor.

INTRODUCTION: In cancer of the pancreatic head region, exocrine insufficiency is a well-known complication, leading to steatorrhea, weight loss, and malnutrition. Its presence is frequently overlooked, however, because the primary attention is focused on cancer treatment. To date, the risk of developing exocrine insufficiency is unspecified. Therefore, we assessed this function in patients with tumors of the pancreatic head, distal common bile duct, or ampulla of Vater. METHODS: Between March 2010 and August 2012, we prospectively included patients diagnosed with cancer of the pancreatic head region at our tertiary center. To preclude the effect of a resection, we excluded operated patients. Each month, the exocrine function was determined with a fecal elastase test. Furthermore, endocrine function, steatorrhea-related symptoms, and body weight were evaluated. Patients were followed for 6 months, or until death. RESULTS: Thirty-two patients were included. The tumor was located in the pancreas in 75%, in the bile duct in 16%, and in the ampullary region in 9%, with a median size of 2.5 cm. At diagnosis, the prevalence of exocrine insufficiency was 66%, which increased to 92% after a median follow-up of 2 months (interquartile range, 1 to 4 mo). DISCUSSION: Most patients with cancer of the pancreatic head region were already exocrine insufficient at diagnosis, and within several months, this function was impaired in almost all cases. Given this high prevalence, physicians should be focused on diagnosing and treating exocrine insufficiency, to optimize the nutritional status and physical condition, especially for those patients undergoing palliative chemotherapy and/or radiotherapy.

Cohort Profile: Understanding socioeconomic inequalities in health and health behaviours: the GLOBE study.

The main aim of the Gezondheid en Levens Omstandigheden Bevolking Eindhoven en omstreken (GLOBE) study (the letters of whose name represent the first letters of the Dutch acronym for Health and Living Conditions of the Population of Eindhoven and surroundings) is to quantitatively assess mechanisms and factors explaining socio-economic inequalities in health in the Netherlands. Baseline data for the study were collected by postal survey in 1991 among 18,973 respondents ranging in age from 15-75 years from the city of Eindhoven and its surrounding municipalities. Subsamples (total N=5667) were interviewed and/or surveyed in 1991, 1997, 2004 (also including a new sample), and most recently in 2011. Information was asked on indicators of socio-economic position, a range of potential explanatory factors (material, behavioural, psychosocial, and environmental) and health outcomes. From 2004 onwards, special emphasis was given to the identification of physical, social, and cultural environmental factors in the explanation of socio-economic inequalities in health behaviours. Information from the baseline postal survey onwards can and has been linked to several registries of causes of death, hospital admissions, and cancer. Researchers are cordially invited to contact the project leader (f.vanlenthe@erasmusmc.nl) to propose research based on the data.

The prevalence of Helicobacter pylori infection in the Netherlands.

BACKGROUNDS: The prevalence of Helicobacter pylori has been declining in the developed countries, as it has the incidence of distal gastric carcinoma. Monitoring this decline and identifying populations not benefiting from this decline is a fit task for public health authorities, with blood donors an obvious source of sera. MATERIALS AND METHODS: We tested 1550 randomly selected blood donors, spread over 5-10 year age cohorts, from four regions in the southern half of The Netherlands, for the presence of antibodies against H. pylori and the CagA antigen. These donors were drawn from an area comprising 46% of the native Dutch population, but did not include non-European immigrants. RESULTS: We observed an age specific decline in the mean seroprevalence of H. pylori from 48% for donors born between 1946 and 1935 to 16% for those born between 1987 and 1977. In H. pylori positive donors, the CagA seroprevalence declined from 38% to 14% in the same age cohorts. There were no significant differences between regions in either prevalence. CONCLUSIONS: Our results are compatible with a persistent age-cohort phenomenon for H. pylori prevalence, with the most pronounced decline of CagA+ strains. Nevertheless, almost one in six of the young native Dutch population remains H. pylori positive, implying that, without specific intervention, this bacterium will remain common over the coming decades.

Democratization and life expectancy in Europe, 1960-2008.

Over the past five decades, two successive waves of political reform have brought democracy to, first, Spain, Portugal and Greece, and, more recently, Central and Eastern European countries. We assessed whether democratization was associated with improvements in population health, as indicated by life expectancy and cause-specific mortality rates. Data on life expectancy at birth, age-standardized total and cause-specific mortality rates, levels of democracy and potential time-variant confounding variables were collected from harmonized international databanks. In two pooled cross-sectional time-series analyses with country-fixed effects, life expectancy and cause-specific mortality were regressed on measures of current and cumulative democracy, controlling for confounders. A first analysis covered the 1960-1990 period, a second covered the 1987-2008 period. In the 1960-1990 period, current democracy was more strongly associated with higher life expectancy than cumulative democracy. The positive effects of current democracy on total mortality were mediated mainly by lower mortality from heart disease, pneumonia, liver cirrhosis, and suicide. In the 1987-2008 period, however, current democracy was associated with lower, and cumulative democracy with higher life expectancy, particularly among men. The positive effects of cumulative democracy on total mortality were mediated mainly by lower mortality from circulatory diseases, cancer of the breast, and external causes. Current democracy was associated with higher mortality from motor vehicle accidents in both periods, and also with higher mortality from cancer and all external causes in the second. Our results suggest that in Europe during these two periods democratization has had mixed effects. That short-term changes in levels of democracy had positive effects in the first but not in the second period is probably due to the fact that democratization in Central and Eastern Europe was part of a complete system change which caused major societal disruptions.

Weight change before and after the introduction of solids: results from a longitudinal birth cohort.

We studied the association, and its direction, between the introduction of solids and weight-for-height (WFH) change between birth and 45 months. Pregnant women were asked to participate in a birth cohort during their first antenatal visit. Data from 3184 children were used. The timing of the introduction of solids was reported by the mother from a questionnaire at 12 months postpartum, and categorised into very early (0-3 months), early (3-6 months) and timely (after 6 months) introduction of solids. Anthropometric data were collected during standardised child health centre visits. WFH was converted into a z-score. Repeated-measurements analyses with splines positioned according to the moments of solid introduction were used to obtain estimates for WFH change before and after the introduction of solids. Analyses were adjusted for educational level, ethnicity, smoking during pregnancy, mother's BMI, breast-feeding, history of food allergy and infant's hospital admission. Before solids were introduced, weight gain was higher in children introduced to solids early (z= 0.65, 95 % CI 0.34, 0.95) than in children introduced to solids very early (z= 0.02, 95 % CI -0.03, 0.08) and timely (z= -0.04, 95 % CI -0.05, -0.03). Shortly after the introduction of solids, children introduced to solids very early and early showed a relative decrease in WFH. WFH change did not differ between the solid introduction groups after 12 months, and at that time, weight change was as expected (i.e. z= 0). We therefore conclude that differences in WFH in childhood are not the result of early introduction to solids.

Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening.

OBJECTIVE: Colorectal cancer screening by means of faecal immunochemical tests (FITs) requires successive screening rounds for an optimal preventive effect. However, data on the influence of the length of the screening interval on participation and diagnostic yield are lacking. Repeated FIT screening was therefore performed in a population-based trial comparing various repeat intervals. DESIGN: 7501 Dutch individuals aged 50-74 years were randomly selected and invited for two 1-sample FIT screening rounds (haemoglobin (Hb) concentration ≥ 50 ng/ml, corresponding to 10 µg Hb/g faeces) with intervals of 1 (group I), 2 (group II) or 3 years (group III). RESULTS: In group I, participation was 64.7% in the first screening round and 63.2% in the second. The corresponding percentages for groups II and III were 61.0% vs 62.5% and 62.0% vs 64.0%. Triennial screening resulted in a higher participation rate in the second screening round compared with annual screening (p=0.04). The overall positivity rate in the second screening round was significantly lower compared with the first round (6.0% vs 8.4%; OR 0.69, 95% CI 0.58 to 0.82) and did not depend on interval length (p=0.23). Similarly, the overall detection rate of advanced neoplasia was significantly lower in the second round compared with the first screening round (1.9% vs 3.3%; OR 0.57, 95% CI 0.43 to 0.76) and also did not depend on interval length (p=0.62). The positive predictive value of the FIT did not significantly change over time (41% vs 33%; p=0.07). CONCLUSION: The total number of advanced neoplasia found at repeat FIT screening is not influenced by the interval length within a range of 1-3 years. Furthermore, there is a stable and acceptably high participation in the second screening round. This implies that screening intervals can be tailored to local resources.