Two distinct aetiologies of cardia cancer, evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status

Background: Non-cardia gastric adenocarcinoma is positively associated with Helicobacter pylori infection and atrophic gastritis. The role of H pylori infection and atrophic gastritis in cardia cancer is unclear. Aim: To compare cardia versus non-cardia cancer with respect to the premorbid state of the stomach. Methods: Nested case–control study. To each of 129 non-cardia and 44 cardia cancers, three controls were matched. Serum collected a median of 11.9 years before the diagnosis of cancer was tested for anti-H pylori antibodies, pepsinogen I:II and gastrin. Results: Non-cardia cancer was positively associated with H pylori (OR 4.75, 95% CI 2.56 to 8.81) and gastric atrophy (pepsinogen I:II ,2.5; OR 4.47, 95% CI 2.71 to 7.37). The diffuse and intestinal histological subtypes of non-cardia cancer were of similar proportions and both showed a positive association with H pylori and atrophy. Cardia cancer was negatively associated with H pylori (OR 0.27, 95% CI 0.12 to 0.59), but H pylori-positive cardia cancer showed an association with gastric atrophy (OR 3.33, 95% CI 1.06 to 10.5). The predominant histological subtype of cardia cancer was intestinal and was not associated with gastric atrophy compared with the diffuse subtype ((OR 0.72, 95% CI 0.19 to 2.79) vs (OR 3.46, 95% CI 0.32 to 37.5)). Cardia cancer in patients with atrophy had an intestinal: diffuse ratio (1:1) similar to non-cardia cancer (1.9:1), whereas cardia cancers in patients without atrophy were predominantly intestinal (7:1). Conclusion: These findings indicate two aetiologies of cardia cancer, one associated with H pylori atrophic gastritis, resembling non-cardia cancer, and the other associated with non-atrophic gastric mucosa, resembling oesophageal adenocarcinoma. Serological markers of gastric atrophy may provide the key to determining gastric versus oesophageal origin of cardia cancer

Heart failure in Norway, 2000-2014: analyzing incident, total and readmission rates using data from the Cardiovascular Disease in Norway (CVDNOR) Project

Postponed access until 23rd October 2020.Aims To examine trends in heart failure (HF) hospitalization rates and risk of readmissions following an incident HF hospitalization. Methods and results During 2000–2014, we identified in the Cardiovascular Disease in Norway Project 142 109 hospitalizations with HF as primary diagnosis. Trends of incident and total (incident and recurrent) HF hospitalization rates were analysed using negative binomial regression models. Changes over time in 30-day and 3-year risk of HF recurrences or cardiovascular disease (CVD)-related readmissions were analysed using Fine and Grey competing risk regression, with death as competing events. Age-standardized rates declined on average 1.9% per year in men and 1.8% per year in women for incident HF hospitalizations (both Ptrend < 0.001) but did not change significantly in either men or women for total HF hospitalizations. In men surviving the incident HF hospitalization, 30-day and 3-year risk of a HF recurrent event increased 1.7% and 1.2% per year, respectively. Similarly, 30-day and 3-year risk of a CVD-related hospitalization increased 1.5% and 1.0% per year, respectively (all Ptrend < 0.001). No statistically significant changes in the risk of HF recurrences or CVD-related readmissions were observed among women. In-hospital mortality for a first and recurrent HF episode declined over time in both men and women. Conclusions Incident HF hospitalization rates declined in Norway during 2000–2014. An increase in the risk of recurrences in the context of reduced in-hospital mortality following an incident and recurrent HF hospitalization led to flat trends of total HF hospitalization rates.acceptedVersio

Mortality following first-time hospitalization with acute myocardial infarction in Norway, 2001-2014: Time trends, underlying causes and place of death

Background Trends on cause-specific mortality following acute myocardial infarction (AMI) are poorly described and no studies have analyzed where do AMI patients die. We analyzed trends in 28-day and one-year mortality following an incident AMI with focus on changes over time in the underlying cause and place of death. Methods We identified in the ‘Cardiovascular Disease in Norway’ Project all patients 25+ years, hospitalized with an incident AMI in Norway, 2001–2014. Information on date, underlying cause and place of death was obtained from the Cause of Death Registry. Results Of 144,473 patients included in the study, 11.4% died within first 28 days. The adjusted 28-day mortality declined by 5.2% per year (ptrend < 0.001). Of 118,881 patients surviving first 28 days, 10.1% died within one year. The adjusted one-year CVD mortality declined by 6.2% per year (ptrend < 0.001) while non-CVD mortality increased by 1.4% per year (ptrend < 0.001), mainly influenced by increased risk of dying from neoplasms. We observed a shift over time in the underlying cause of death toward more non-CVD deaths, and in the place of death toward more deaths occurring in nursing homes. Conclusions We observed a decline in 28-day mortality following an incident AMI hospitalization. One-year CVD mortality declined while one-year risk of dying from non-CVD conditions increased. The resulting shift toward more non-CVD deaths and deaths occurring outside a hospital need to be considered when formulating priorities in treating and preventing adverse events among AMI survivors.acceptedVersio

Smoking, plasma cotinine and risk of atrial fibrillation: the Hordaland Health Study

Background: Cigarette smoking has been identified as a major modifiable risk factor for coronary heart disease and mortality. However, findings on the relationship between smoking and atrial fibrillation (AF) have been inconsistent. Furthermore, findings from previous studies were based on self‐reported smoking. Objective: To examine the associations of smoking status and plasma cotinine levels, a marker of nicotine exposure, with risk of incident AF in the Hordaland Health Study. Methods: We conducted a prospective analysis of 6682 adults aged 46‐74 years without known AF at baseline. Participants were followed via linkage to the Cardiovascular Disease in Norway (CVDNOR) project and the Cause of Death Registry. Smoking status was assessed by both questionnaire and plasma cotinine levels. Results: A total of 538 participants developed AF over a median follow‐up period of 11 years. Using questionnaire data, current smoking (HR: 1.41, 95% CI: 1.09–1.83), but not former smoking (HR: 1.03, 95% CI: 0.83–1.28), was associated with an increased risk of AF after adjustment for gender, age, body mass index, hypertension, physical activity and education. Using plasma cotinine only, the adjusted HR (95% CI) was 1.40 (1.12–1.75) for participants with cotinine ≥85 nmol L−1 compared to those with cotinine <85 nmol L−1. However, the risk increased with elevated plasma cotinine levels until 1199 nmol L−1 (HR: 1.55, 95% CI: 1.16–2.05 at the third group vs. the reference group) and plateaued at higher levels. Conclusions: Current, but not former smokers, had a higher risk of developing AF. Use of plasma cotinine measurement corroborated this finding.publishedVersio

Syn‐rift sediment gravity flow deposition on a Late Jurassic fault‐terraced slope, northern North Sea

Structurally controlled bathymetry in rifts has a significant influence on sediment routing pathways and depositional architecture of sediment gravity flow deposits. In contrast to rift segments characterized by crustal-scale half-grabens, the tectono-stratigraphic evolution of deep-water rift domains characterised by distributed faulting on narrow fault terraces has received little attention. We use 3D broadband seismic data, calibrated by boreholes, from the Lomre and Uer terraces in the northern North Sea rift to investigate Late Jurassic syn-rift sediment gravity flow systems on fault-terraced slopes. The sediment gravity flow fairways were sourced from hinterland drainages via basin margin deltaic systems on the Horda Platform to the southeast. The deep-water sedimentary systems evolve from initial, widespread submarine channelized lobe complexes, through submarine channels, to incised submarine canyons. This progressive confinement of the sediment gravity flow system was concomitant with progressive localization of strain onto the main terrace-bounding faults. Although the normal fault network on the terraces has local impact on deep-water sediment transport and the architecture of gravity flow deposits, it is the regional basin margin to rift axis gradient that dominantly controls deep-water sediment routing. Furthermore, the gravity flow deposits on the Lomre and Uer terraces were predominantly sourced by rift margin deltaic systems, not from erosion of local uplifted footwall crests, emphasising the significance of hinterland catchments in the development of volumetrically significant deep-water syn-rift depositional systems

Plasma free choline, betaine and cognitive performance: the Hordaland Health Study

Choline and betaine are nutrients involved in one-carbon metabolism. Choline is essential for neurodevelopment and brain function. We studied the associations between cognitive function and plasma concentrations of free choline and betaine. In a cross-sectional study, 2195 subjects (55 % women), aged 70–74 years, underwent extensive cognitive testing including the Kendrick Object Learning Test (KOLT), Trail Making Test (part A, TMT-A), modified versions of the Digit Symbol Test (m-DST), Block Design (m-BD), Mini-Mental State Examination (m-MMSE) and Controlled Oral Word Association Test (COWAT). Compared with low concentrations, high choline (>8·4 μmol/l) was associated with better test scores in the TMT-A (56·0 v. 61·5, P= 0·004), m-DST (10·5 v. 9·8, P= 0·005) and m-MMSE (11·5 v. 11·4, P= 0·01). A generalised additive regression model showed a positive dose–response relationship between the m-MMSE and choline (P= 0·012 from a corresponding linear regression model). Betaine was associated with the KOLT, TMT-A and COWAT, but after adjustments for potential confounders, the associations lost significance. Risk ratios (RR) for poor test performance roughly tripled when low choline was combined with either low plasma vitamin B12 ( ≤ 257 pmol/l) concentrations (RRKOLT= 2·6, 95 % CI 1·1, 6·1; RRm-MMSE= 2·7, 95 % CI 1·1, 6·6; RRCOWAT= 3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) ( ≥ 3·95 μmol/l) concentrations (RRm-BD= 2·8, 95 % CI 1·3, 6·1). Low betaine ( ≤ 31·1 μmol/l) combined with high MMA was associated with elevated RR on KOLT (RRKOLT= 2·5, 95 % CI 1·0, 6·2). Low plasma free choline concentrations are associated with poor cognitive performance. There were significant interactions between low choline or betaine and low vitamin B12 or high MMA on cognitive performance.publishedVersio

Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts

BACKGROUND: The magnitude of the association between Helicobacter pylori and incidence of gastric cancer is unclear. H pylori infection and the circulating antibody response can be lost with development of cancer; thus retrospective studies are subject to bias resulting from classifi- cation of cases as H pylori negative when they were infected in the past. AIMS: To combine data from all case control studies nested within prospective cohorts to assess more reliably the relative risk of gastric cancer associated with H pylori infection.To investigate variation in relative risk by age, sex, cancer type and subsite, and interval between blood sampling and cancer diagnosis. METHODS: Studies were eligible if blood samples for H pylori serology were collected before diagnosis of gastric cancer in cases. Identified published studies and two unpublished studies were included. Individual subject data were obtained for each. Matched odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between H pylori and gastric cancer. RESULTS: Twelve studies with 1228 gastric cancer cases were considered. The association with H pylori was restricted to noncardia cancers (OR 3.0; 95% CI 2.3–3.8) and was stronger when blood samples for H pylori serology were collected 10+ years before cancer diagnosis (5.9; 3.4–10.3). H pylori infection was not associated with an altered overall risk of cardia cancer (1.0; 0.7–1.4). CONCLUSIONS: These results suggest that 5.9 is the best estimate of the relative risk of non-cardia cancer associated with H pylori infection and that H pylori does not increase the risk of cardia cancer. They also support the idea that when H pylori status is assessed close to cancer diagnosis, the magnitude of the non-cardia association may be underestimated

Association Between Maternal Folic Acid Supplementation and Congenital Heart Defects in Offspring in Birth Cohorts From Denmark and Norway

Background: Evidence linking individual‐level maternal folic acid supplementation to offspring risk of congenital heart defects is lacking. We investigated whether folic acid supplementation in early pregnancy reduces offspring risk of heart defects in 2 large birth cohort studies. Methods and Results: Women recruited in early pregnancy within the DNBC (Danish National Birth Cohort), 1996–2003, and MoBa (Norwegian Mother and Child Cohort Study), 2000–2009, were followed until delivery. Information on periconceptional intake of folic acid and other supplements was linked with information on heart defects from national registers. Among 197 123 births, we identified 2247 individuals with heart defects (114/10 000). Periconceptional (4 weeks before through 8 weeks after conception) use of folic acid plus other supplements (54.8%), folic acid only (12.2%), and non–folic acid supplements (5.0%) were compared with no supplement use (28.0%); the adjusted relative risks of heart defects were 0.99 (95% CI, 0.80–1.22), 1.08 (95% CI, 0.93–1.25), and 1.07 (95% CI, 0.97–1.19), respectively. For initiation of folic acid in the preconception period weeks −4 to −1 (33.7%) and the postconception periods 0 to 4 weeks (15.5%), 5 to 8 weeks (17.8%), and 9 to 12 weeks (4.6%), compared with no or late folic acid intake (29.1%), relative risks of heart defect were 1.11 (95% CI, 1.00–1.25), 1.09 (95% CI, 0.95–1.25), 0.98 (95% CI, 0.86–1.12), and 0.97 (95% CI, 0.78–1.20), respectively. Relative risks of severe defects, conotruncal defects, and septal defects showed similar results. Conclusions: Folic acid was not associated with offspring risk of heart defects, including severe defects, conotruncal defects, or septal defects.publishedVersio

Prevention of Neural Tube Defects: A Cross-Sectional Study of the Uptake of Folic Acid Supplementation in Nearly Half a Million Women

BACKGROUND: Taking folic acid supplements before pregnancy to reduce the risk of a neural tube defect (NTD) is especially important in countries without universal folic acid fortification. The extent of folic acid supplementation among women who had antenatal screening for Down's syndrome and NTDs at the Wolfson Institute of Preventive Medicine, London between 1999 and 2012 was assessed. METHODS AND FINDINGS: 466,860 women screened provided details on folic acid supplementation. The proportion of women who took folic acid supplements before pregnancy was determined according to year and characteristics of the women. The proportion of women taking folic acid supplements before pregnancy declined from 35% (95% CI 34%-35%) in 1999-2001 to 31% (30%-31%) in 2011-2012. 6% (5%-6%) of women aged under 20 took folic acid supplements before pregnancy compared with 40% of women aged between 35 and 39. Non-Caucasian women were less likely to take folic acid supplements before pregnancy than Caucasian women; Afro-Caribbean 17% (16%-17%), Oriental 25% (24%-25%) and South Asian 20% (20%-21%) compared with 35% (35%-35%) for Caucasian women. 51% (48%-55%) of women who previously had an NTD pregnancy took folic acid supplements before the current pregnancy. CONCLUSIONS: The policy of folic acid supplementation is failing and has led to health inequalities. This study demonstrates the need to fortify flour and other cereal grain with folic acid in all countries of the world