Disease burden of breast cancer and risk factors in Europe 44 countries, 1990-2019: findings of the global burden of disease study 2019.

Background: Breast cancer (BC) represents a significant health challenge in Europe due to its elevated prevalence and heterogeneity. Despite notable progress in diagnostic and treatment methods, the region continues to grapple with rising BC burdens, with comprehensive investigations into this matter notably lacking. This study explores BC burden and potential contributing risk factors in 44 European countries from 1990 to 2019. The aim is to furnish evidence supporting the development of strategies for managing BC effectively. Methods: Disease burden estimates related to breast cancer from the Global Burden of Disease 2019(GBD2019) across Eastern, Central, and Western Europe were examined using Joinpoint regression for trends from 1990 to 2019. Linear regression models examined relationships between BC burden and Socio-demographic Index (SDI), healthcare access and quality (HAQ), and BC prevalence. We utilized disability-adjusted life year(DALY) proportions for each risk factor to depict BC risks. Results: In Europe, the BC burden was 463.2 cases per 100,000 people in 2019, 1.7 times the global burden. BC burden in women was significantly higher and increased with age. Age-standardized mortality and DALY rates of BC in Europe in 2019 decreased by 23.1%(average annual percent change: AAPC -0.92) and 25.9%(AAPC -1.02), respectively, compared to 1990, in line with global trends. From 1990 to 2019, age-standardized DALY declined faster in Western Europe (-34.8%, AAPC -1.49) than in Eastern Europe (-9.4%, AAPC -0.25) and Central Europe (-15.0%, AAPC -0.56). Monaco, Serbia, and Montenegro had the highest BC burden in Europe in 2019. BC burden was negatively correlated with HAQ. In addition, Alcohol use and Tobacco were significant risk factors for DALY. High fasting plasma glucose and obesity were also crucial risk factors that cannot be ignored in DALY. Conclusion: The burden of BC in Europe remains a significant health challenge, with regional variations despite an overall downward trend. Addressing the burden of BC in different regions of Europe and the increase of DALY caused by different risk factors, targeted prevention measures should be taken, especially the management of alcohol and tobacco should be strengthened, and screening services for BC should be popularized, and medical resources and technology allocation should be optimized.

Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition.

BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023.

BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-ß-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla NDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla NDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla NDM-1-carrying-P. stuartii and the third bla NDM-5-carrying-P. stuartii. The bla NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla NDM-1, bla OXA-10, bla CMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.

Association between combination COVID-19-influenza vaccination and long COVID in middle-aged and older Europeans: A cross-sectional study.

The potential impact of combined COVID-19 and influenza vaccination on long COVID remains uncertain. In the present cross-sectional study, we aimed to investigate the plausible association between them in middle-aged and older Europeans based on the Survey of Health, Ageing, and Retirement in Europe (SHARE). A total of 1910 participants were recruited in the analyses. The study outcome was long COVID. Participants were divided into 4 groups through the self-reported status of COVID-19 and influenza vaccination. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. 1397 participants experienced long COVID. After multivariable adjustment, those vaccinated with neither COVID-19 nor influenza vaccine had higher risk of long COVID (OR, 1.72; 95% CI, 1.26-2.35) compared to those vaccinated with both vaccines. Furthermore, adding the 4 statuses of COVID-19 vaccination/influenza vaccination to conventional risk model improved risk reclassification for long COVID (continuous net reclassification improvement was 16.26% [p = .003], and integrated discrimination improvement was 0.51% [p = .005]). No heterogeneity was found in the subgroup analyses (all p-interaction ≥0.05). Our study might provide a strategy for people aged 50 and over to reduce the occurrence of long COVID, that is, to combine the use of the COVID-19 vaccine and influenza vaccines.

Reducing childhood mortality extends mothers' lives.

During the twentieth century, childhood mortality was dramatically reduced globally, falling by more than 90% in the United States and much of Europe. Total fertility also fell, with the combined result that many parents who otherwise would have experienced the loss of a child were spared the trauma and negative health consequences that accompany such a loss. Here I use mathematical modeling to argue that the reduction in the frequency of child death that occurred in the twentieth century indirectly led to a substantial reduction in female mortality, resulting in an extension of female lifespan. I estimate that the reduction in maternal bereavement in the US during the twentieth century indirectly increased mean female lifespan after age 15 by approximately 1 year. I discuss implications for our understanding of the persistence of the sex gap in longevity and approaches to improving maternal health outcomes in countries that still face high levels of childhood mortality.

Association between air pollution and skin cutaneous melanoma: A Mendelian randomization study.

There has been a consistent and notable increase in the global prevalence of skin cutaneous melanoma (SKCM). Although genetic factors are closely associated with the occurrence and development of melanoma, the potential influence of environmental factors cannot be overlooked. The existing literature lacks a definitive consensus on the correlation between air pollution and the incidence rate of SKCM. This study seeks to investigate the causal relationship between air pollution, specifically focusing on particulate matter (PM) 2.5, PM2.5-10, PM10, and nitrogen oxides, and the risk of SKCM. A 2-sample Mendelian randomization (MR) method was applied, utilizing extensive publicly accessible genome-wide association studies summary datasets within European populations. The primary analytical method employed was the inverse variance weighted method. Supplementary methods, including the weighted median model, MR-Egger, simple model, and weighted model, were chosen to ensure robust analysis. Heterogeneity assessment was conducted using Cochran's Q test. To identify potential pleiotropy, both MR-Egger regression and the MR-PRESSO global test were employed. Additionally, a sensitivity analysis was performed using the leave-one-out method. The analysis revealed no statistically significant association between air pollution and SKCM risk, with specific findings as follows: PM2.5 (P = .485), PM2.5-10 (P = .535), PM10 (P = .136), and nitrogen oxides (P = .745). While some results exhibited heterogeneity, all findings demonstrated an absence of pleiotropy. This study did not find substantive evidence supporting a causal relationship between air pollution and the risk of SKCM within European populations. The comprehensive MR analysis, encompassing various pollutants, suggests that environmental factors such as air pollution may not be significant contributors to the development of SKCM.

Public health and economic benefits of seasonal influenza vaccination in risk groups in France, Italy, Spain and the UK: state of play and perspectives.

BACKGROUND: Seasonal influenza epidemics have a substantial public health and economic burden, which can be alleviated through vaccination. The World Health Organization (WHO) recommends a 75% vaccination coverage rate (VCR) in: older adults (aged ≥ 65 years), individuals with chronic conditions, pregnant women, children aged 6-24 months and healthcare workers. However, no European country achieves this target in all risk groups. In this study, potential public health and economic benefits achieved by reaching 75% influenza VCR was estimated in risk groups across four European countries: France, Italy, Spain, and the UK. METHODS: A static epidemiological model was used to estimate the averted public health and economic burden of increasing the 2021/2022 season VCR to 75%, using the efficacy data of standard-dose quadrivalent influenza vaccine. For each country and risk group, the most recent data on population size, VCR, pre-pandemic influenza epidemiology, direct medical costs and absenteeism were identified through a systematic literature review, supplemented by manual searching. Outcomes were: averted influenza cases, general practitioner (GP) visits, hospitalisations, case fatalities, number of days of work lost, direct medical costs and absenteeism-related costs. RESULTS: As of the 2021/2022 season, the UK achieved the highest weighted VCR across risk groups (65%), followed by Spain (47%), France (44%) and Italy (44%). Based on modelling, the 2021/2022 VCR prevented an estimated 1.9 million influenza cases, avoiding 375,200 GP visits, 73,200 hospitalisations and 38,400 deaths. To achieve the WHO 75% VCR target, an additional 24 million at-risk individuals would need to be vaccinated, most of which being older adults and patients with chronic conditions. It was estimated that this could avoid a further 918,200 influenza cases, 332,000 GP visits, 16,300 hospitalisations and 6,300 deaths across the four countries, with older adults accounting for 52% of hospitalisations and 80% of deaths. An additional €84 million in direct medical costs and €79 million in absenteeism costs would be saved in total, with most economic benefits delivered in France. CONCLUSIONS: Older adults represent most vaccine-preventable influenza cases and deaths, followed by individuals with chronic conditions. Health authorities should prioritise vaccinating these populations for maximum public health and economic benefits.

Operative management of primary hyperparathyroidism in Europe.

BACKGROUND: Multicentre studies have previously reported on national outcomes of surgery for primary hyperparathyroidism, but not investigated whether management and outcome are uniform among countries. This study investigated whether there are differences among European countries in operative management and outcome of surgery for primary hyperparathyroidism. METHODS: Using data from Eurocrine®, a pan-European registry for endocrine surgeries, a retrospective observational cross-sectional multicentre study with 99 participating centres in 14 European countries was performed. Data on age, sex, calcium levels, operative strategy, conversion rate and rate of failed exploration were analysed for patients who underwent initial surgery for sporadic primary hyperparathyroidism. Primary outcome measures were intention to perform limited parathyroidectomy and the rate of hypercalcaemia at first follow-up. RESULTS: A total of 9548 patients were registered between 2015 and 2020. There were 7642 (80%, range 74.5-93.2%) females. There was intention to perform limited parathyroidectomy in 7320 of 9548 (76.7%) operations, ranging from 498 of 1007 (49.5%) to 40 of 41 (97.6%) among countries. Hypercalcaemia at first follow-up (median time to follow-up 15 days) was found in 416 of 9548 (4.4%) operations, ranging from 0 of 119 (0%) to 3 of 38 (7.9%) among countries. CONCLUSION: This study demonstrated large differences in the intention to perform limited parathyroidectomy for primary hyperparathyroidism among European countries, as well as differences in the rate of postoperative hypercalcaemia. Future studies are needed to evaluate the impact of these different healthcare practices on patient outcomes.

Alpine salamanders at risk? The current status of an emerging fungal pathogen.

Amphibians globally suffer from emerging infectious diseases like chytridiomycosis caused by the continuously spreading chytrid fungi. One is Batrachochytrium salamandrivorans (Bsal) and its disease ‒ the 'salamander plague' ‒ which is lethal to several caudate taxa. Recently introduced into Western Europe, long distance dispersal of Bsal, likely through human mediation, has been reported. Herein we study if Alpine salamanders (Salamandra atra and S. lanzai) are yet affected by the salamander plague in the wild. Members of the genus Salamandra are highly susceptible to Bsal leading to the lethal disease. Moreover, ecological modelling has shown that the Alps and Dinarides, where Alpine salamanders occur, are generally suitable for Bsal. We analysed skin swabs of 818 individuals of Alpine salamanders and syntopic amphibians at 40 sites between 2017 to 2022. Further, we compiled those with published data from 319 individuals from 13 sites concluding that Bsal infections were not detected. Our results suggest that the salamander plague so far is absent from the geographic ranges of Alpine salamanders. That means that there is still a chance to timely implement surveillance strategies. Among others, we recommend prevention measures, citizen science approaches, and ex situ conservation breeding of endemic salamandrid lineages.

Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation.

BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

Aortic arch surgery for DeBakey type 1 aortic dissection in patients aged 60 years or younger.

BACKGROUND: Extended aortic repair is considered a key issue for the long-term durability of surgery for DeBakey type 1 aortic dissection. The risk of aortic degeneration may be higher in young patients due to their long life expectancy. The early outcome and durability of aortic surgery in these patients were investigated in the present study. METHODS: The subjects of the present analysis were patients under 60 years old who underwent surgical repair for acute DeBakey type 1 aortic dissection at 18 cardiac surgery centres across Europe between 2005 and 2021. Patients underwent ascending aortic repair or total aortic arch repair using the conventional technique or the frozen elephant trunk technique. The primary outcome was 5-year cumulative incidence of reoperation on the distal aorta. RESULTS: Overall, 915 patients underwent surgical ascending aortic repair and 284 patients underwent surgical total aortic arch repair. The frozen elephant trunk procedure was performed in 128 patients. Among 245 propensity score-matched pairs, total aortic arch repair did not decrease the rate of distal aortic reoperation compared to ascending aortic repair (5-year cumulative incidence, 6.7% versus 6.7%, subdistributional hazard ratio 1.127, 95% c.i. 0.523 to 2.427). Total aortic arch repair increased the incidence of postoperative stroke/global brain ischaemia (25.7% versus 18.4%, P = 0.050) and dialysis (19.6% versus 12.7%, P = 0.003). Five-year mortality was comparable after ascending aortic repair and total aortic arch repair (22.8% versus 27.3%, P = 0.172). CONCLUSIONS: In patients under 60 years old with DeBakey type 1 aortic dissection, total aortic arch replacement compared with ascending aortic repair did not reduce the incidence of distal aortic operations at 5 years. When feasible, ascending aortic repair for DeBakey type 1 aortic dissection is associated with satisfactory early and mid-term outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04831073.

Helicobacter pylori infection found during upper endoscopy performed for the diagnosis of celiac, inflammatory bowel diseases, and eosinophilic esophagitis: A multicenter pediatric European study.

BACKGROUND: Helicobacter pylori may be found during upper gastrointestinal endoscopy (UGE) performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD), and eosinophilic esophagitis (EoE). We aimed to describe the frequency of H. pylori in children undergoing UGE for CeD, IBD, and EoE and the number of children receiving eradication treatment. MATERIALS AND METHODS: A retrospective multicenter study from 14 countries included pediatric patients diagnosed with CeD, IBD, and EoE between January 2019 and December 2021. DATA COLLECTED: age, gender, hematologic parameters, endoscopic, histologic, and H. pylori culture results, and information on eradication treatment. RESULTS: H. pylori was identified in 349/3890 (9%) children [167 (48%) male, median 12 years (interquartile range 8.1-14.6)]. H. pylori was present in 10% (173/1733) CeD, 8.5% (110/1292) IBD and 7.6% (66/865) EoE patients (p = NS). The prevalence differed significantly between Europe (Eastern 5.2% (28/536), Southern 3.8% (78/2032), Western 5.6% (28/513)) and the Middle East 26.6% (215/809) [odds ratio (OR) 7.96 95% confidence interval (CI) (6.31-10.1) p < 0.0001]. Eradication treatment was prescribed in 131/349 (37.5%) patients, 34.6% CeD, 35.8% IBD, and 56.1% EoE. Predictors for recommending treatment included erosions/ulcers [OR 6.45 95% CI 3.62-11.47, p < 0.0001] and nodular gastritis [OR 2.25 95% CI 1.33-3.81, p 0.003]. Treatment rates were higher in centers with a low H. pylori prevalence (<20%) [OR 3.36 95% CI 1.47-7.66 p 0.004]. CONCLUSIONS: Identifying H. pylori incidentally during UGE performed for the most common gastrointestinal diseases varies significantly among regions but not among diseases. The indications for recommending treatment are not well defined, and less than 40% of children received treatment.

Long-term survival for lymphoid neoplasms and national health expenditure (EUROCARE-6): a retrospective, population-based study.

BACKGROUND: Management of lymphoid malignancies requires substantial health system resources. Total national health expenditure might influence population-based lymphoid malignancy survival. We studied the long-term survival of patients with 12 lymphoid malignancy types and examined whether different levels of national health expenditure might explain differences in lymphoid malignancy prognosis between European countries and regions. METHODS: For this observational, retrospective, population-based study, we analysed the EUROCARE-6 dataset of patients aged 15 or older diagnosed between 2001 and 2013 with one of 12 lymphoid malignancies defined according to International Classification of Disease for Oncology (third edition) and WHO classification, and followed up to 2014 (Jan 1, 2001-Dec 31, 2014). Countries were classified according to their mean total national health expenditure quartile in 2001-13. For each lymphoid malignancy, 5-year and 10-year age-standardised relative survival (ASRS) was calculated using the period approach. Generalised linear models indicated the effects of age at diagnosis, gender, and total national health expenditure on the relative excess risk of death (RER). FINDINGS: 82 cancer registries (61 regional and 21 national) from 27 European countries provided data eligible for 10-year survival estimates comprising 890 730 lymphoid malignancy cases diagnosed in 2001-13. Median follow-up time was 13 years (IQR 13-14). Of the 12 lymphoid malignancies, the 10-year ASRS in Europe was highest for hairy cell leukaemia (82·6% [95% CI 78·9-86·5) and Hodgkin lymphoma (79·3% [78·6-79·9]) and lowest for plasma cell neoplasms (29·5% [28·9-30·0]). RER increased with age at diagnosis, particularly from 55-64 years to 75 years or older, for all lymphoid malignancies. Women had higher ASRS than men for all lymphoid malignancies, except for precursor B, T, or natural killer cell, or not-otherwise specified lymphoblastic lymphoma or leukaemia. 10-year ASRS for each lymphoid malignancy was higher (and the RER lower) in countries in the highest national health expenditure quartile than in countries in the lowest quartile, with a decreasing pattern through quartiles for many lymphoid malignancies. 10-year ASRS for non-Hodgkin lymphoma, the most representative class for lymphoid malignancies based on the number of incident cases, was 59·3% (95% CI 58·7-60·0) in the first quartile, 57·6% (55·2-58·7) in the second quartile, 55·4% (54·3-56·5) in the third quartile, and 44·7% (43·6-45·8) in the fourth quartile; with reference to the European mean, the RER was 0·80 (95% CI 0·79-0·82) in the first, 0·91 (0·90-0·93) in the second, 0·94 (0·92-0·96) in the third, and 1·45 (1·42-1·48) in the fourth quartiles. INTERPRETATION: Total national health expenditure is associated with geographical inequalities in lymphoid malignancy prognosis. Policy decisions on allocating economic resources and implementing evidence-based models of care are needed to reduce these differences. FUNDING: Italian Ministry of Health, European Commission, Estonian Research Council.

The early educational environment at five years of age in a European cohort of children born very preterm: challenges and opportunities for research.

BACKGROUND: Early childhood education offers opportunities for stimulation in multiple developmental domains and its positive impact on long-term outcomes and wellbeing for children is well documented. Few studies have explored early education in children born very preterm (VPT; <32 weeks of gestation) who are at higher risk of neurodevelopmental disorders and poor educational outcomes than their term-born peers. The purpose of the study is to describe and compare the educational environment of children born VPT in European countries at 5 years of age according to the degree of perinatal risk. METHODS: Data originated from the population-based Screening to Improve Health In very Preterm infants (SHIPS) cohort of children born VPT in 2011/2012 in 19 regions from 11 European countries. Perinatal data were collected from medical records and the 5-year follow-up was conducted using parental questionnaires. Outcomes at 5 years were participation in early education (any, type, intensity of participation) and receipt of special educational support, which were harmonized across countries. RESULTS: Out of 6,759 eligible children, 3,687 (54.6%) were followed up at 5 years (mean gestational age 29.3 weeks). At 5 years, almost all children (98.6%) were in an educational program, but type (preschool/primary), attendance (full-time/part-time) and use and type of school support/services differed by country. In some countries, children with high perinatal risk were more likely to be in full-time education than those with low risk (e.g. Estonia: 97.9% vs. 87.1%), while the inverse pattern was observed elsewhere (e.g. Poland: 78.5% vs. 92.8%). Overall, 22.8% of children received special educational support (country range: 12.4-34.4%) with more support received by children with higher perinatal risk. Large variations between countries remained after adjustment for socio-demographic characteristics. CONCLUSIONS: There are marked variations in approaches to early education for children born VPT in Europe, raising opportunities to explore its impact on their neurodevelopment and well-being.

Healthy lifestyle change and all-cause and cancer mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35-70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years). RESULTS: After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI. CONCLUSIONS: Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.

Centralized industrialization of pork in Europe and America contributes to the global spread of Salmonella enterica.

Salmonella enterica causes severe food-borne infections through contamination of the food supply chain. Its evolution has been associated with human activities, especially animal husbandry. Advances in intensive farming and global transportation have substantially reshaped the pig industry, but their impact on the evolution of associated zoonotic pathogens such as S. enterica remains unresolved. Here we investigated the population fluctuation, accumulation of antimicrobial resistance genes and international serovar Choleraesuis transmission of nine pig-enriched S. enterica populations comprising more than 9,000 genomes. Most changes were found to be attributable to the developments of the modern pig industry. All pig-enriched salmonellae experienced host transfers in pigs and/or population expansions over the past century, with pigs and pork having become the main sources of S. enterica transmissions to other hosts. Overall, our analysis revealed strong associations between the transmission of pig-enriched salmonellae and the global pork trade.

Long-term effectiveness and safety of edoxaban in patients with atrial fibrillation: 4-year data from the ETNA-AF-Europe study.

BACKGROUND: To assess long-term effectiveness and safety of edoxaban in Europe. METHODS AND RESULTS: ETNA-AF-Europe, a prospective, multinational, multi-centre, post-authorisation, observational study was conducted in agreement with the European Medicines Agency. The primary and secondary objectives assessed real-world safety (including bleeding and deaths) and effectiveness (including stroke, systemic embolic events and clinical edoxaban use), respectively. Median (interquartile range) age of the 13,164 patients was 75.0 (68.0-80.0) years; CHA2DS2-VASc and HAS-BLED scores were 3.0 (2.0-4.0) and 2.0 (1.0-2.0), respectively. Follow-up duration was 3.98 (3.21-4.05) years. Patients on edoxaban 30 mg (n = 3042) at baseline were older (80.0 vs 73.0 years), more likely assessed as frail by investigators (27.0% vs 6.6%) and had more comorbidities than those on edoxaban 60 mg (n = 9617; missing dosing information for n = 505). Annualised event rates of all-cause and cardiovascular death in the overall population, edoxaban 60 mg and edoxaban 30 mg groups were 4.1%, 2.8% and 8.4%, and 1.0%, 0.7% and 2.0%, respectively. Annualised rates of stroke were relatively constant throughout the follow-up, transient ischaemic attack and systemic embolism were < 1% in the overall population. Rates of any major and major gastrointestinal bleeding were low, with slightly higher rates for edoxaban 30 vs 60 mg group. Intracranial haemorrhage was uncommon (0.2%). CONCLUSIONS: In European patients with AF, long-term therapy with edoxaban is associated with low and relatively constant annualised rates of stroke and major bleeding. Differences in outcomes between the two approved doses are attributable to differences in clinical characteristics.