Non-employment and low educational level as risk factors for inequitable treatment and mortality in heart failure: a population-based cohort study of register data.

BACKGROUND: The risk of heart failure is disproportionately high among the socioeconomically disadvantaged. Furthermore, socioeconomically deprived patients are at risk of inequitable access to heart failure treatment and poor outcomes. Non-employment as a risk factor in this respect has not previously been studied at the level of the individual. The aim of this register-based cohort study was to analyse equity in access to renin-angiotensin system blockers and mortality, by employment status and educational level. METHODS: The study population consisted of Swedish patients aged 20-64 years hospitalised for heart failure in July 2006-December 2010, without a heart failure hospitalisation within one year or more before index hospitalisation and without renin-angiotensin system blocker dispensation in the 6 months preceding index hospitalisation. Non-access to renin-angiotensin system blockers, measured as drug dispensations, was investigated by employment status and educational level through logistic regression. Cox regression models were used to obtain hazard ratios for all-cause death by educational level and employment status. Interaction analysis was used to test whether associations between access to treatment and mortality differed by employment status. RESULTS: Among the 3874 patients, 1239 (32%) were women. The median age was 57 years. Fifty-three percent were employed. The non-employed patients had more comorbidity and lower access (68%) to renin-angiotensin system blockers compared with the employed (82%). The adjusted odds ratio for non-access to renin-angiotensin system blockers among the non-employed was 1.76. Non-employment was associated with an adjusted hazard ratio of 1.76 for death. Low educational level was associated with a higher death risk. Mortality was highest among the non-employed without access to renin-angiotensin system blockers and the association between access to renin-angiotensin system blockers and survival was slightly weaker in this group. CONCLUSIONS: Non-employment and low educational level were associated with elevated mortality in heart failure. Non-employment was a risk factor for lower access to evidence-based treatment, and among the non-employed access to treatment was associated with a slightly smaller risk reduction than among the employed. The results underscore that clinicians need to be aware of the importance of socioeconomic factors in heart failure care.

Bilateral internal iliac branch device with ipsilateral deployment.

Iliac branch endograft devices offer an elegant solution to preserve perfusion to the internal iliac artery when treating aortoiliac aneurysms; however, they are difficult to perform when bilateral access is not available owing to aortoiliac anatomy or previous endovascular aortic aneurysm repair. We present a technique to perform iliac branch endograft deployment from ipsilateral access in a patient with a prior EVAR endovascular aortic aneurysm repair, obviating the need for a difficult up-and-over access.

Lower socioeconomic status predicts higher mortality and morbidity in patients with heart failure.

OBJECTIVE: It is not fully understood whether and how socioeconomic status (SES) has a prognostic impact in patients with heart failure (HF). We assessed SES and its association with patient characteristics and outcomes in a contemporary and well-characterised HF cohort. METHODS: Socioeconomic risk factors (SERF) were defined in the Swedish HF Registry based on income (low vs high according to the annual median value), education level (no degree/compulsory school vs university/secondary school) and living arrangement (living alone vs cohabitating). RESULTS: Of 44 631 patients, 21% had no, 33% one, 30% two and 16% three SERF. Patient characteristics strongly and independently associated with lower SES were female sex and no specialist referral. Additional independent associations were older age, more severe HF, heavier comorbidity burden, use of diuretics and less use of HF devices. Lower SES was associated with higher risk of HF hospitalisation/mortality, and overall cardiovascular and non-cardiovascular events. These associations persisted after extensive adjustment for patient characteristics, treatments and care. The magnitude of the association increased linearly with the increasing number of coexistent SERF: HR (95% CI) 1.09 (1.05 to 1.13) for one, 1.16 (1.12 to 1.20) for two and 1.22 (1.18 to 1.28) for three SERF (p<0.01). CONCLUSIONS: In a contemporary and well-characterised HF cohort and after comprehensive adjustment for confounders, lower SES was linked with multiple factors such as less use of HF devices and age, but most strongly with female sex and lack of specialist referral; and associated with greater risk of morbidity/mortality.

First National Genomic Epidemiological Study of Neisseria gonorrhoeae Strains Spreading Across Sweden in 2016.

The increasing transmission and antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global health concern with worrying trends of decreasing susceptibility to also the last-line extended-spectrum cephalosporin (ESC) ceftriaxone. A dramatic increase of reported gonorrhea cases has been observed in Sweden from 2016 and onward. The aim of the present study was to comprehensively investigate the genomic epidemiology of all cultured N. gonorrhoeae isolates in Sweden during 2016, in conjunction with phenotypic AMR and clinical and epidemiological data of patients. In total, 1279 isolates were examined. Etest and whole-genome sequencing (WGS) were performed, and epidemiological data obtained from the Public Health Agency of Sweden. Overall, 51.1%, 1.7%, and 1.3% resistance to ciprofloxacin, cefixime, and azithromycin, respectively, was found. No isolates were resistant to ceftriaxone, however, 9.3% of isolates showed a decreased susceptibility to ceftriaxone and 10.5% to cefixime. In total, 44 penA alleles were found of which six were mosaic (n = 92). Using the typing schemes of MLST, NG-MAST, and NG-STAR; 133, 422, and 280 sequence types, respectively, and 93 NG-STAR clonal complexes were found. The phylogenomic analysis revealed two main lineages (A and B) with lineage A divided into two main sublineages (A1 and A2). Resistance and decreased susceptibility to ESCs and azithromycin and associated AMR determinants, such as mosaic penA and mosaic mtrD, were predominantly found in sublineage A2. Resistance to cefixime and azithromycin was more prevalent among heterosexuals and MSM, respectively, and both were predominantly spread through domestic transmission. Continuous surveillance of the spread and evolution of N. gonorrhoeae, including phenotypic AMR testing and WGS, is essential for enhanced knowledge regarding the dynamic evolution of N. gonorrhoeae and gonorrhea epidemiology.

Effectiveness by gender and age of renin-angiotensin system blockade in heart failure-A national register-based cohort study.

PURPOSE: Investigate effectiveness by gender and age and equity implications of treatment with renin-angiotensin system blockade (RASb) in heart failure (HF) patients. METHODS: In this population-based register study, we used inpatient data from 2006 to 2010 for patients age 20 years or older with no HF hospitalisation for minimum of 1 year before an index hospitalisation. A wash-out period for RASb of 6 months preceding admission was used. Hospital data were linked with drug dispensation data and cause of death data. The associations between time-dependent RASb exposure and all-cause death and HF death, respectively, were examined by Cox regression models. Interactions by gender and age were also investigated on the multiplicative and additive scales. RESULTS: Thirty thousand seven hundred twenty-one patients were analysed. Fifty-one percent were women. Median age was 83. Fifty-three percent of women and 64% of men received RASb after the index hospitalisation. Younger patients were more likely to receive RASb than older ones. One-year mortality was 28%. RASb was associated with an overall hazard ratio (HR) for all-cause death of 0.72 (95% confidence interval 0.69-0.75), and an HR of 0.85 (0.77-0.93) for HF death. Interaction analyses showed HRs for all-cause death associated with RASb between 0.12 (0.10-0.13) in the youngest, and 0.80 (0.76-0.84) in the oldest patients. CONCLUSIONS: RASb appeared effective for women and men and for patients of all ages in this hospitalised HF cohort. No gender difference in effectiveness was found. RASb exposure was low overall, indicating a need for improved adherence to treatment guidelines. Treatment with RASb may be inequitable for women and older patients.

Defence priming in Arabidopsis - a Meta-Analysis.

Defence priming by organismal and non-organismal stimulants can reduce effects of biotic stress in plants. Thus, it could help efforts to enhance the sustainability of agricultural production by reducing use of agrochemicals in protection of crops from pests and diseases. We have explored effects of applying this approach to both Arabidopsis plants and seeds of various crops in meta-analyses. The results show that its effects on Arabidopsis plants depend on both the priming agent and antagonist. Fungi and vitamins can have strong priming effects, and priming is usually more effective against bacterial pathogens than against herbivores. Moreover, application of bio-stimulants (particularly vitamins and plant defence elicitors) to seeds can have promising defence priming effects. However, the published evidence is scattered, does not include Arabidopsis, and additional studies are required before we can draw general conclusions and understand the molecular mechanisms involved in priming of seeds' defences. In conclusion, defence priming of plants has clear potential and application of bio-stimulants to seeds may protect plants from an early age, promises to be both labour- and resource-efficient, poses very little environmental risk, and is thus both economically and ecologically promising.

Nicotinamide; antioxidative and DNA hypomethylation effects in plant cells.

The effects of nicotinamide (NIC) and its natural plant metabolites nicotinic acid (NIA) and trigonelline (TRIG) were studied with respect to defense in plant cell cultures. NIC and NIA could protect against oxidative stress damage caused by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), which generates free radicals. Damage was analyzed as DNA strand breaks in cell cultures of Pisum sativum (garden pea), Daucus carota (carrot), Populus tremula L. × P. tremuloides (hybrid aspen) and Catharanthus roseus (Madagascar periwinkle), monitored by single cell gel electrophoresis (comet assay), and assays of cell leakage in C. roseus. The activities of aconitase and fumarase enzymes, which have key roles in energy metabolism, were analyzed in P. sativum cultures after treatment with NIC or NIA. Aconitase activity was increased by NIA, and fumarase activity was increased by both compounds. These compounds were shown to promote glutathione metabolism in P. sativum cultures, and NIC was shown to have a global DNA hypomethylating effect. Neither TRIG nor poly(ADP-ribose) polymerase (PARP) inhibitor 3-aminobenzamide offered any protection against DNA damage or cell leakage, nor did they promote aconitase or fumarase activities, or glutathione metabolism. By this broad approach addressing multiple biochemical factors and different plant species, we demonstrate that NIC and NIA protect plant cells from oxidative stress, and that NIC clearly exerts an epigenetic effect; decreased DNA methylation. This indicates that these compounds have important roles in the regulation of metabolism in plant cells, especially in connection to stress.

Inequity of access to ACE inhibitors in Swedish heart failure patients: a register-based study.

BACKGROUND: Several international studies suggest inequity in access to evidence-based heart failure (HF) care. Specifically, studies of ACE inhibitors (ACEIs) point to reduced ACEI access related to female sex, old age and socioeconomic position. Thus far, most studies have either been rather small, lacking diagnostic data, or lacking the possibility to account for several individual-based sociodemographic factors. Our aim was to investigate differences, which could reflect inequity in access to ACEIs based on sex, age, socioeconomic status or immigration status in Swedish patients with HF. METHODS: Individually linked register data for all Swedish adults hospitalised for HF in 2005-2010 (n=93,258) were analysed by multivariate regression models to assess the independent risk of female sex, high age, low employment status, low income level, low educational level or foreign country of birth, associated with lack of an ACEI dispensation within 1 year of hospitalisation. Adjustment for possible confounding was made for age, comorbidity, Angiotensin receptor blocker therapy, period and follow-up time. RESULTS: Analysis revealed an adjusted OR for no ACEI dispensation for women of 1.31 (95% CI 1.27 to 1.35); for the oldest patients of 2.71 (95% CI 2.53 to 2.91); and for unemployed patients of 1.59 (95% CI 1.46 to 1.73). CONCLUSIONS: Access to ACEI treatment was reduced in women, older patients and unemployed patients. We conclude that access to ACEIs is inequitable among Swedish patients with HF. Future studies should include clinical data, as well as mortality outcomes in different groups.

The influence of gender on ICU admittance.

BACKGROUND: We assume that critically ill patients are admitted to an intensive care unit (ICU) based on their illness severity coupled with their co-morbidities. Patient attributes such as religion, nationality, socioeconomic class or gender are not relevant in this setting. We aimed to explore the association of patient gender with admission to the ICU amongst hospital physicians working in Sweden. METHODS: Primary outcome assessed was gender bias among respondents. Two different versions of an online survey, with eight patient cases, were sent to physicians in Sweden who within their field of specialty meet patients that could be eligible for intensive care. The versions of the survey were identical except that the patient gender in each case was exchanged between the two surveys. Depending on the respondent's birthday (odd or even number) they were directed to one of the two surveys. At the end of each case the respondent was asked to answer if they thought that the patient needed ICU care, yes or no. The respondents were not told in advance about the design of the survey. The respondents were also asked to state their age, sex, field of specialty, size of hospital and title. RESULTS: Of 1426 respondents, 679 and 747 answered survey 1 and 2, respectively. Overall, there were no significant differences in willingness to admit in between cases describing a man or woman in the physician responses. DISCUSSION: Anesthesiology/intensive care physicians more often choose to admit patients to the ICU compared to all other specialties. Female physicians tended to be more willing to admit patients, regardless of patient gender, than their male counterparts. CONCLUSIONS: Using a survey, with eight cases differing only with regards to the gender of the patient, we demonstrate an absence of a gender bias among Swedish hospital physicians.

UV-B exposure of indoor-grown Picea abies seedlings causes an epigenetic effect and selective emission of terpenes.

Terpenoids are involved in various defensive functions in plants, especially conifers. Epigenetic mechanisms, for example DNA methylation, can influence plant defence systems. The purpose of the present study was to investigate the influence of UV-B exposure on the release of terpenoids from spruce seedlings and on needle DNA methylation. Ten-week-old seedlings grown indoors were exposed to UV-B radiation during 4 h, and the volatile compounds emitted from the seedlings were analysed. Analysis of the volatiles 1, 3, and 22 d after this UV-B exposure showed that bornyl acetate, borneol, myrcene, and limonene contents increased during the first 3 days, while at day 22 the level of emission had returned to the control level. UV-B exposure decreased the level of DNA methylation in needles of young seedlings, reflected in methylation changes in CCGG sequences. Exposure of young seedlings to UV-B radiation might be a way to potentiate the general defensive capacity, improving their ability to survive in outdoor conditions. UV-B-induced defence is discussed in the light of epigenetic mechanisms.

Increased metal tolerance in Salix by nicotinamide and nicotinic acid.

We have earlier shown that nicotinamide (NIC) and nicotinic acid (NiA) can induce defence-related metabolism in plant cells; e.g. increase the level of glutathione. Here we investigated if NIC and NiA could increase the metal tolerance in metal sensitive clones of Salix viminalis and whether this would be mediated via increased glutathione level. Salix clones, sensitive or tolerant to zinc (Zn), copper (Cu) and cadmium (Cd) were grown in the presence of heavy metals (Cd, Cu or Zn) or NIC and NiA as well as in combination. In addition, the influence of N-acetyl-cystein (NAC) and l-2-oxothiazolidine 4-carboxylate (OTC), stimulators of reduced glutathione (GSH) biosynthesis, and the glutathione biosynthesis inhibitor buthionine sulfoximine (BSO) was analysed. Tolerance was measured as effects on root and shoot dry weight, and the glutathione and metal concentrations in the tissues were analysed. Results showed that NIC and NiA decreased the toxic effects of Cd, Cu and Zn on growth significantly in sensitive clones, but also to some extent in tolerant clones. However, the glutathione level and metal concentration did not change by NIC or NiA addition. Treatment with NAC, OTC or BSO did not per se influence the sensitivity to Cd, although the glutathione level increased in the presence of NAC and OTC and decreased in response to BSO. The results suggest that NIC and NiA increased the defence against heavy metals but not via glutathione formation per se.

Cell suspension cultures of Populus tremula x P. tremuloides exhibit a high level of cellulose synthase gene expression that coincides with increased in vitro cellulose synthase activity.

Compared to wood, cell suspension cultures provide convenient model systems to study many different cellular processes in plants. Here we have established cell suspension cultures of Populus tremula L. x P. tremuloides Michx. and characterized them by determining the enzymatic activities and/or mRNA expression levels of selected cell wall-specific proteins at the different stages of growth. While enzymes and proteins typically associated with primary cell wall synthesis and expansion were detected in the exponential growth phase of the cultures, the late stationary phase showed high expression of the secondary-cell-wall-associated cellulose synthase genes. Interestingly, detergent extracts of membranes from aging cell suspension cultures exhibited high levels of in vitro cellulose synthesis. The estimated ratio of cellulose to callose was as high as 50 : 50, as opposed to the ratio of 30 : 70 so far achieved with membrane preparations extracted from other systems. The increased cellulose synthase activity was also evidenced by higher levels of Calcofluor white binding in the cell material from the stationary-phase cultures. The ease of handling cell suspension cultures and the improved capacity for in vitro cellulose synthesis suggest that these cultures offer a new basis for studying the mechanism of cellulose biosynthesis.

Lignin isolated from primary walls of hybrid aspen cell cultures indicates significant differences in lignin structure between primary and secondary cell wall.

Hybrid aspen (Populus tremula x tremuloides) cell cultures were grown for 7, 14 and 21 days. The cell cultures formed primary cell walls but no secondary cell wall according to carbohydrate analysis and microscopic characterization. The primary walls were lignified, increasingly with age, according to Klason lignin analysis. Presence of lignin in the primary walls, with a higher content in 21-day old cells than in 7-day old cells, was further supported by phloroglucinol/HCl reagent test and confocal microscopy after both immunolocalization and staining with acriflavin. Both laccase and peroxidase activity were found in the cultures and the activity increased during lignin formation. The lignin from the cell culture material was compared to lignin from mature aspen wood, where most of the lignin originates in the secondary cell wall, and which served as our secondary cell wall control. Lignin from the cell walls was isolated and characterized by thioacidolysis followed by gas chromatography and mass spectrometry. The lignin in the cell cultures differed from lignin of mature aspen wood in that it consisted exclusively of guaiacyl units, and had a more condensed structure. Five lignin structures were identified by mass spectrometry in the cell suspension cultures. The results indicate that the hybrid aspen cell culture used in this investigation may be a convenient experimental system for studies of primary cell wall lignin.