Treatment with intravenous immunoglobulins and methylprednisolone may significantly decrease loss of renal function in chronic-active antibody-mediated rejection.

BACKGROUND: Chronic-active antibody mediated rejection (c-aABMR) is a major contributor to long-term kidney allograft loss. We conducted a retrospective analysis to establish the efficacy of treatment with intravenous immunoglobulins (IVIG) and pulse methylprednisolone (MP) of patients with c-aABMR. METHODS: Sixty-nine patients, in the period 2005-2017, with the diagnosis (suspicious for) c-aABMR that were treated with IVIG and MP were included. Patients were administered three doses of 1 g intravenous MP combined with a single dose of IVIG (1 g/kg body weight). Primary outcome was the decline in allograft function one year post treatment. Responders to IVIG-MP therapy were defined by an eGFR one year after treatment which was at least 25% above the projected allograft function. RESULTS: Patients showed an average decline in eGFR of 9.8 ml/min/1.73m2 the year prior to treatment. Following treatment, a significant reduction (p < 0.001) in eGFR decline was observed (6.3 ml/min/1.73m2). Furthermore, a significant improvement in proteinuria was observed upon treatment (p < 0.001). Sixty-two percent (n = 43) of the patients were considered a responder and showed considerable slowing of graft function deterioration in the year after treatment (p < 0.001). Three and 5-year graft survival was significantly superior in responders. CONCLUSIONS: More than 60% of patients with c-aABMR with a progressive decline in eGFR respond favorably to treatment with IVIG-MP resulting in a significant improvement of graft survival (Sablik, Am J Transplant 18, 2018).

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.

Contribution of chronic conditions to disability in men and women in France.

Background: Women report more disability than men perhaps due to gender differences in the prevalence of diseases and/or in their disabling impact. We compare the contribution of chronic diseases to disability in men and women in France, using a disability survey conducted in both private households and institutions, and we also examine the effect of excluding the institutionalized population. Methods: Data comprised 17 549 individuals age 50+, who participated in the 2008-09 French Disability Health Survey including people living in institutions. Disability was defined by limitations in activities people usually do due to health problems (global activity limitation indicator). Additive regression models were fitted separately by gender to estimate the contribution of conditions to disability taking into account multi-morbidity. Results: Musculoskeletal diseases caused most disability for both men (10.1%, CI: 8.1-12.0) and women (16.0%, CI 13.6-18.2). The second contributor for men was heart diseases (5.7%, CI: 4.5-6.9%), and for women anxiety-depression (4.0, CI 3.1-5.0%) closely followed by heart diseases (3.8%, CI 2.9-4.7%). Women's higher contribution of musculoskeletal diseases reflected their higher prevalence and disabling impact; women's higher contribution of anxiety-depression and lower contributions of heart diseases reflected gender differences in prevalence. Excluding the institutionalized population did not change the overall conclusions. Conclusions: The largest contributors to the higher disability of women than men are moderately disabling conditions with a high prevalence. Whereas traditional disabling conditions such as musculoskeletal diseases are more prevalent and disabling in women, fatal diseases such as cardiovascular disease are also important contributors in women and men.

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.

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.

Behavioural disinhibition in the general population during the antiretroviral therapy roll-out in Sub-Saharan Africa: systematic review and meta-analysis.

OBJECTIVES: Improved life expectancy and reduced transmission probabilities due to ART may result in behavioural disinhibition - that is an increase in sexual risk behaviour in response to a perceived lower risk of HIV. We examined trends in sexual risk behaviour in the general population of sub-Saharan African countries 1999-2015. METHODS: We systematically reviewed scientific literature of sexual behaviour and reviewed trends in Demographic and Health Surveys. A meta-analysis on four indicators of sexual risk behaviour was performed: unprotected sex, multiple sexual partners, commercial sex and prevalence of sexually transmitted infections. RESULTS: Only two peer-reviewed studies met our inclusion criteria, while our review of DHS data spanned 18 countries and 16 years (1999-2015). We found conflicting trends in sexual risk behaviour. Reported unprotected sex decreased consistently across the 18 countries, for both sexes. In contrast, reporting multiple partners was decreasing over the period 1999 to the mid-2000s, yet has been consistently increasing thereafter. Similar trends were found for reported sexually transmitted infections and commercial sex (men only). CONCLUSIONS: In conclusion, we found no clear evidence of behavioural disinhibition due to expanded access to ART in sub-Saharan Africa. Substantial increases in condom use coincided with increases in reported multiple partners, commercial sex and sexually transmitted infections, especially during the period of ART scale-up. Further research is needed into how these changes might affect HIV transmission.

'Fundamental causes' of inequalities in mortality: an empirical test of the theory in 20 European populations.

The 'fundamental causes' theory stipulates that when new opportunities for lowering mortality arise, higher socioeconomic groups will benefit more because of their greater material and non-material resources. We tested this theory using harmonised mortality data by educational level for 22 causes of death and 20 European populations from the period 1980-2010. Across all causes and populations, mortality on average declined by 2.49 per cent (95%CI: 2.04-2.92), 1.83% (1.37-2.30) and 1.34% (0.89-1.78) per annum among the high, mid and low educated, respectively. In 69 per cent of cases of declining mortality, mortality declined faster among the high than among the low educated. However, when mortality increased, less increase among the high educated was found in only 46 per cent of cases. Faster mortality decline among the high educated was more manifest for causes of death amenable to intervention than for non-amenable causes. The difference in mortality decline between education groups was not larger when income inequalities were greater. While our results provide support for the fundamental causes theory, our results suggest that other mechanisms than the theory implies also play a role.

Multinomial additive hazard model to assess the disability burden using cross-sectional data.

Population aging is accompanied by the burden of chronic diseases and disability. Chronic diseases are among the main causes of disability, which is associated with poor quality of life and high health care costs in the elderly. The identification of which chronic diseases contribute most to the disability prevalence is important to reduce the burden. Although longitudinal studies can be considered the gold standard to assess the causes of disability, they are costly and often with restricted sample size. Thus, the use of cross-sectional data under certain assumptions has become a popular alternative. Among the existing methods based on cross-sectional data, the attribution method, which was originally developed for binary disability outcomes, is an attractive option, as it enables the partition of disability into the additive contribution of chronic diseases, taking into account multimorbidity and that disability can be present even in the absence of disease. In this paper, we propose an extension of the attribution method to multinomial responses, since disability is often measured as a multicategory variable in most surveys, representing different severity levels. The R function constrOptim is used to maximize the multinomial log-likelihood function subject to a linear inequality constraint. Our simulation study indicates overall good performance of the model, without convergence problems. However, the model must be used with care for populations with low marginal disability probabilities and with high sum of conditional probabilities, especially with small sample size. For illustration, we apply the model to the data of the Belgian Health Interview Surveys.

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.

Performance indicators; the association between the quality of preventive care and the prevalence of hospital-acquired skin lesions in adult hospital patients.

AIM: The aim of this study was to explore the relation between the occurrence of pressure ulcers or incontinence dermatitis and the quality of preventive care provided. BACKGROUND: Performance measurements using indicators has become standard practice in recent years. The prevalence of pressure ulcers with or without incontinence dermatitis is widely used as an indicator of the quality of nursing care. DESIGN: Matched case-control study. METHODS: We collected information on 132 patients selected from a prevalence study (April 2010). We matched 88 controls to 44 cases, controlling for duration of hospitalization and type of nursing unit. We wrote 132 patient reports, including patient factors and process criteria, using a chart review. Five expert teams assessed nine processes of care with guideline-based review criteria. The expert teams assessed the reports blinded for outcome. The care process was assessed using a four-point quality score ranging from optimal care to suboptimal care. RESULTS: In a multivariable analysis using conditional logistic regression, the pressure ulcer risk score and the quality score were associated with a poor outcome after adjustment for type of illness, age, care needs prior to hospitalization, intensive care stay during admission and the number of care problems. CONCLUSION: We found that the development of pressure ulcers or incontinence dermatitis was associated with the quality of the preventive care process, indicating that variation in their prevalence reflects variation in the quality of care.

Inequalities in Alcohol-Related Mortality in 17 European Countries: A Retrospective Analysis of Mortality Registers.

BACKGROUND: Socioeconomic inequalities in alcohol-related mortality have been documented in several European countries, but it is unknown whether the magnitude of these inequalities differs between countries and whether these inequalities increase or decrease over time. METHODS AND FINDINGS: We collected and harmonized data on mortality from four alcohol-related causes (alcoholic psychosis, dependence, and abuse; alcoholic cardiomyopathy; alcoholic liver cirrhosis; and accidental poisoning by alcohol) by age, sex, education level, and occupational class in 20 European populations from 17 different countries, both for a recent period and for previous points in time, using data from mortality registers. Mortality was age-standardized using the European Standard Population, and measures for both relative and absolute inequality between low and high socioeconomic groups (as measured by educational level and occupational class) were calculated. Rates of alcohol-related mortality are higher in lower educational and occupational groups in all countries. Both relative and absolute inequalities are largest in Eastern Europe, and Finland and Denmark also have very large absolute inequalities in alcohol-related mortality. For example, for educational inequality among Finnish men, the relative index of inequality is 3.6 (95% CI 3.3-4.0) and the slope index of inequality is 112.5 (95% CI 106.2-118.8) deaths per 100,000 person-years. Over time, the relative inequality in alcohol-related mortality has increased in many countries, but the main change is a strong rise of absolute inequality in several countries in Eastern Europe (Hungary, Lithuania, Estonia) and Northern Europe (Finland, Denmark) because of a rapid rise in alcohol-related mortality in lower socioeconomic groups. In some of these countries, alcohol-related causes now account for 10% or more of the socioeconomic inequality in total mortality. Because our study relies on routinely collected underlying causes of death, it is likely that our results underestimate the true extent of the problem. CONCLUSIONS: Alcohol-related conditions play an important role in generating inequalities in total mortality in many European countries. Countering increases in alcohol-related mortality in lower socioeconomic groups is essential for reducing inequalities in mortality. Studies of why such increases have not occurred in countries like France, Switzerland, Spain, and Italy can help in developing evidence-based policies in other European countries.

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.

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.

The effect of local policy actions on mortality among homeless people: a before-after study.

BACKGROUND: Homeless people have a 3-5-fold increased risk of mortality compared with general populations. After 2005, policy actions being implemented in Rotterdam, the Netherlands, have improved the living conditions of this group. This study examines the effect of policies aimed at improving living conditions on mortality risks of the homeless. METHODS: Register-based 10-year follow-up study of homeless in Rotterdam, the Netherlands. The participants are homeless adults (aged 18+ years) who visited one or more services for homeless people in Rotterdam in 2001. The intervention of local policies after 2005 was to get homeless people into housing, increase their participation in employment and other regular daytime activities, and controlling drug and alcohol addictions. The main outcome measure is mortality rate ratios calculated using Poisson regression. Differences in mortality between the periods 2001-05 vs. 2006-10 were assessed. RESULTS: The cohort of homeless adults in 2001 consisted of 1870 men and 260 women, with a mean age of 40.3 years. During the 10 years of follow-up, 265 persons (232 male and 33 female) died. Adjusted for age and sex, no significant difference in mortality was observed between the periods 2001-05 and 2006-10 (P = 0.9683). A different splitting in periods did not change the results. CONCLUSION: Five years of local policy efforts improved their living conditions, but left the mortality rate of a homeless cohort unchanged. Incomplete reach of the program and long previous histories of homelessness ask for additional policies beyond the provision of housing and other services. Attention to the prevention of homelessness seems needed.

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.

Pancreatic cancer risk in Peutz-Jeghers syndrome patients: a large cohort study and implications for surveillance.

BACKGROUND: Although Peutz-Jeghers syndrome (PJS) is known to be associated with pancreatic cancer (PC), estimates of this risk differ widely. This hampers counselling of patients and implementation of surveillance strategies. We therefore aimed to determine the PC risk in a large cohort of Dutch PJS patients. METHODS: PJS was defined by diagnostic criteria recommended by the WHO, a proven LKB1 mutation, or both. All patients with a presumptive diagnosis of pancreatic, ampullary or distal bile duct cancer were identified. Cases were reviewed clinically, radiologically and immunohistochemically. Cumulative PC risks were calculated by Kaplan-Meier analysis and relative risks by Poisson regression analysis. RESULTS: We included 144 PJS patients (49% male) from 61 families (5640 person years follow-up). Seven (5%) patients developed PC at a median age of 54 years. Four patients (3%) were diagnosed with distal bile duct (n=2) or ampullary cancer (n=2) at a median age of 55 years. The cumulative risk for PC was 26% (95% CI 4% to 47%) at age 70 years and relative risk was 76 (95% CI 36 to 160; p<0.001). The cumulative risk for pancreatico-biliary cancer was 32% (95% CI 11% to 52%) at age 70 years, with a relative risk of 96 (95% CI 53 to 174; p<0.001). CONCLUSIONS: PJS patients have a highly increased risk for pancreatico-biliary cancer. Therefore, patients are eligible for surveillance within well defined research programmes to establish the benefit of such surveillance.

The rise of mortality from mental and neurological diseases in Europe, 1979-2009: observational study.

BACKGROUND: We studied recent trends in mortality from seven mental and neurological conditions and their determinants in 41 European countries. METHODS: Age-standardized mortality rates were analysed using standard methods of descriptive epidemiology, and were related to cultural, economic and health care indicators using regression analysis. RESULTS: Rising mortality from mental and neurological conditions is seen in most European countries, and is mainly due to rising mortality from dementias. Mortality from psychoactive substance use and Parkinson's disease has also risen in several countries. Mortality from dementias has risen particularly strongly in Finland, Iceland, Malta, Netherlands, Spain, Sweden and the United Kingdom, and is positively associated with self-expression values, average income, health care expenditure and life expectancy, but only the first has an independent effect. CONCLUSIONS: Although trends in mortality from dementias have probably been affected by changes in cause-of-death classification, the high level of mortality from these conditions in a number of vanguard countries suggests that it is now among the most frequent causes of death in high-income countries. Recognition of dementias as a cause of death, and/or refraining from life-saving treatment for patients with dementia, appear to be strongly dependent on cultural values.

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.