Beta-blocker therapy is not associated with mortality after intracerebral hemorrhage

BackgroundBeta-blocker therapy has been suggested to have neuroprotective properties in the setting of acute stroke; however, the evidence is weak and contradictory. We aimed to examine the effects of pre-admission therapy with beta-blockers (BB) on the mortality following spontaneous intracerebral hemorrhage (ICH). MethodsRetrospective analysis of the Helsinki ICH Study database. ResultsA total of 1013 patients with ICH were included in the analysis. Patients taking BB were significantly older, had a higher premorbid mRS score, had more DNR orders, and more comorbidities as atrial fibrillation, hypertension, diabetes mellitus, ischemic heart disease, and heart failure. After adjustment for age, pre-existing comorbidities, and prior use of antithrombotic and antihypertensive medications, no differences in in-hospital mortality (OR 1.1, 95% CI 0.8-1.7), 12-month mortality (OR 1.3, 95% CI 0.9-1.9), and 3-month mortality (OR 1.2, 95% CI 0.8-1.7) emerged. ConclusionPre-admission use of BB was not associated with mortality after ICH.Peer reviewe

Chemisorption of alkyl thiols and S-alkyl thiosulfates on Pt(111) and polycrystalline platinum surfaces

The self-assembled monolayers prepared from 1-dodecanethiol (C12SH) or S-dodecylthio sulfate (Bunte salt, C12SSO3Na) have been characterised on polycrystalline gold and platinum surfaces and on Pt(111). Contact angle and impedance measurements show that the film quality decreases in the order Au/C12SH > Pt/C12SH similar to Au/C12SSO3-Na > Pt/C12S SO3Na. XPS measurements show that the S-SO3 bond of organic thiosulfates is broken on platinum surfaces and the state of the surface-bound sulfur is indistinguishable from that of thiolate. On platinum three sulfur species are formed upon SAM formation and we suggest that the catalytic activity of platinum is responsible for their existence in pristine monolayers. (c) 2005 Elsevier B.V. All rights reserved

Feasibility of Day Surgery in Patients With Breast Conservation and Sentinel Node Biopsy : A Randomized Controlled Trial

Background and Aims: The aim of this study was to analyze feasibility of day surgery in breast cancer patients with breast conserving surgery and sentinel node biopsy. Material and Methods: The study was a randomized controlled trial comparing day surgery with one night hospital stay in breast cancer patients with breast conserving surgery and sentinel node biopsy. A total of 40 patients with 3-cm tumor and clinically N0 were randomized to one night stay group and 38 patients to day surgery group. Within discharge, patients and their relatives were given questionnaires in order to evaluate their experience regarding the duration of hospital stay. Results: Randomized groups were similar regarding patient age and tumor stage. A total of 18 (47%) day surgery group patients were discharged the same day. The most common reason for overnight hospital stay was axillary clearance, 9 (24%). None of the patients in the day surgery group, but 2 patients in the overnight hospital stay group had re-operation due to complications. Perception and preference results were analyzed both according to randomization and actual treatment groups. Patients in both groups had rather similar experiences on the first postoperative day. Also, spouse's or relative's perception after discharge was similar in both groups. Conclusion: Day surgery was well received by the patients and their relatives. Day surgery appears as feasible in patients with breast conservation and sentinel node biopsy.Peer reviewe

Common origin of the gelsolin gene variant in 62 Finnish AGel amyloidosis families

Finnish gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominantly inherited systemic disorder with ophthalmologic, neurologic and dermatologic symptoms. Only the gelsolin (GSN) c.640G>A variant has been found in the Finnish patients thus far. The purpose of this study was to examine whether the Finnish patients have a common ancestor or whether multiple mutation events have occurred at c.640G, which is a known mutational hot spot. A total of 79 Finnish AGel amyloidosis families including 707 patients were first discovered by means of patient interviews, genealogic studies and civil and parish registers. From each family 1-2 index patients were chosen. Blood samples were available from 71 index patients representing 64 families. After quality control, SNP array genotype data were available from 68 patients from 62 nuclear families. All the index patients had the same c.640G>A variant (rs121909715). Genotyping was performed using the Illumina CoreExome SNP array. The homozygosity haplotype method was used to analyse shared haplotypes. Haplotype analysis identified a shared haplotype, common to all studied patients. This shared haplotype included 17 markers and was 361 kb in length (GRCh37 coordinates 9:124003326–124364349) and this level of haplotype sharing was found to occur highly unlikely by chance. This GSN haplotype ranked as the largest shared haplotype in the 68 patients in a genome-wide analysis of haplotype block lengths. These results provide strong evidence that although there is a known mutational hot spot at GSN c.640G, all of the studied 62 Finnish AGel amyloidosis families are genetically linked to a common ancestor.Peer reviewe

The role of polygenic risk and susceptibility genes in breast cancer over the course of life

Polygenic risk scores (PRS) for breast cancer have potential to improve risk prediction, but there is limited information on their utility in various clinical situations. Here we show that among 122,978 women in the FinnGen study with 8401 breast cancer cases, the PRS modifies the breast cancer risk of two high-impact frameshift risk variants. Similarly, we show that after the breast cancer diagnosis, individuals with elevated PRS have an elevated risk of developing contralateral breast cancer, and that the PRS can considerably improve risk assessment among their female first-degree relatives. In more detail, women with the c.1592delT variant in PALB2 (242-fold enrichment in Finland, 336 carriers) and an average PRS (10-90(th) percentile) have a lifetime risk of breast cancer at 55% (95% CI 49-61%), which increases to 84% (71-97%) with a high PRS (>90(th) percentile), and decreases to 49% (30-68%) with a low PRS (<10(th) percentile). Similarly, for c.1100delC in CHEK2 (3.7-fold enrichment; 1648 carriers), the respective lifetime risks are 29% (27-32%), 59% (52-66%), and 9% (5-14%). The PRS also refines the risk assessment of women with first-degree relatives diagnosed with breast cancer, particularly among women with positive family history of early-onset breast cancer. Here we demonstrate the opportunities for a comprehensive way of assessing genetic risk in the general population, in breast cancer patients, and in unaffected family members. Identifying women at high risk of breast cancer has important implications for screening. Here, the authors demonstrate that polygenic risk scores improve breast cancer risk prediction in the population, in women with mutations in high-risk genes and in women with close relatives with the disease

Life expectancy and disease burden in the Nordic countries : results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background The Nordic countries have commonalities in gender equality, economy, welfare, and health care, but differ in culture and lifestyle, which might create country-wise health differences. This study compared life expectancy, disease burden, and risk factors in the Nordic region. Methods Life expectancy in years and age-standardised rates of overall, cause-specific, and risk factor-specific estimates of disability-adjusted life-years (DALYs) were analysed in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Data were extracted for Denmark, Finland, Iceland, Norway, and Sweden (ie, the Nordic countries), and Greenland, an autonomous area of Denmark. Estimates were compared with global, high-income region, and Nordic regional estimates, including Greenland. Findings All Nordic countries exceeded the global life expectancy; in 2017, the highest life expectancy was in Iceland among females (85.9 years [95% uncertainty interval [UI] 85.5-86.4] vs 75.6 years [75.3-75.9] globally) and Sweden among males (80.8 years [80.2-81.4] vs 70.5 years [70.1-70.8] globally). Females (82.7 years [81.9-83.4]) and males (78.8 years [78.1-79.5]) in Denmark and males in Finland (78.6 years [77.8-79.2]) had lower life expectancy than in the other Nordic countries. The lowest life expectancy in the Nordic region was in Greenland (females 77.2 years [76.2-78.0], males 70.8 years [70.3-71.4]). Overall disease burden was lower in the Nordic countries than globally, with the lowest age-standardised DALY rates among Swedish males (18 555.7 DALYs [95% UI 15 968.6-21 426.8] per 100 000 population vs 35 834.3 DALYs [33 218.2-38 740.7] globally) and Icelandic females (16 074.1 DALYs [13 216.4-19 240.8] vs 29 934.6 DALYs [26 981.9-33 211.2] globally). Greenland had substantially higher DALY rates (26 666.6 DALYs [23 478.4-30 218.8] among females, 33 101.3 DALYs [30 182.3-36 218.6] among males) than the Nordic countries. Country variation was primarily due to differences in causes that largely contributed to DALYs through mortality, such as ischaemic heart disease. These causes dominated male disease burden, whereas non-fatal causes such as low back pain were important for female disease burden. Smoking and metabolic risk factors were high-ranking risk factors across all countries. DALYs attributable to alcohol use and smoking were particularly high among the Danes, as was alcohol use among Finnish males. Interpretation Risk factor differences might drive differences in life expectancy and disease burden that merit attention also in high-income settings such as the Nordic countries. Special attention should be given to the high disease burden in Greenland. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation