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Purpose: Hyponatremia is the most common electrolyte disorder, with potentially serious consequences. Studies validating hyponatremia used as a principal diagnosis are lacking. Studying principal diagnoses is important since it indicates the main reason for inpatient care. The aim of this study was to assess the validity of principal diagnoses of hyponatremia according to the International Classification of Diseases, tenth revision (ICD-10) in patients discharged from hospital. Methods: Three independent reviewers retrospectively analyzed medical records of 428 hospitalized patients, ≥18 years old, discharged with a principal diagnosis of either hyponatremia or syndrome of inappropriate anti-diuretic hormone secretion (SIADH) from three different hospitals during 2014–2017. The positive predictive value of hyponatremia as a principal diagnosis was calculated. Results: The median age of the studied population was 73 (IQR 64–81) years and 69% were women. The range of sodium levels was < 100 to 139 mmol/L. The mean sodium level was 119 mmol/L. Of the patients 27% were treated in an intensive care unit (ICU)/high dependency unit (HDU). Hyponatremia was deemed to be the principal cause of inpatient care in 411 out of 428 patients, corresponding to a positive predictive value for hyponatremia as a principal diagnosis of 96% (CI 95% 94–98). Conclusions: The current study showed that 19 diagnoses out of 20 were correct implying a high validity. Thus, a principal diagnosis of hyponatremia, appears to be a useful measure in clinical and epidemiological studies aiming to target a clinically relevant consequence of hyponatremia in hospitalized patients. [ABSTRACT FROM AUTHOR]

Objective: Increased prevalence of cardiovascular disease has been reported in autoimmune Addison’s disease (AAD), but pathomechanisms are poorly understood. Design: Cross-sectional study. Methods: We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at >18-h glucocorticoid withdrawal and 43 matched controls, overall and stratified for sex. Biomarker levels were correlated with the frequency of adrenal crises and quality of life (QoL) by AddiQoL-30. Finally, we investigated changes in biomarker levels following 250 µg tetracosactide injection in patients without residual adrenocortical function (RAF) to explore glucocorticoid-independent effects of high ACTH. Results: Nineteen biomarkers significantly differed between patients with AAD and controls; all but 1 (ST1A1) were higher in AAD. Eight biomarkers were significantly higher in female patients compared with controls (IL6, MCP1, GAL9, SPON2, DR4, RAGE, TNFRSF9, and PGF), but none differed between male patients and controls. Levels of RAGE correlated with the frequency of adrenal crises (r = 0.415, P = .006) and AddiQoL-30 scores (r = −0.347, P = .028) but not after correction for multiple testing. PDL2 and leptin significantly declined 60 min after injection of ACTH in AAD without RAF (−0.15 normalized protein expression [NPX], P = .0001, and −0.25 NPX, P = .0003, respectively)Conclusions: We show that cardiovascular and inflammatory biomarkers are altered in AAD compared with controls, particularly in women. RAGE might be a marker of disease severity in AAD, associated with more adrenal crises and reduced QoL. High ACTH reduced PDL2 and leptin levels in a glucocorticoid-independent manner but the overall effect on biomarker profiles was small. [ABSTRACT FROM AUTHOR]

The Gram-negative bacterium A. salmonicida is the causal agent of furunculosis and used to be one of the most loss-causing bacterial infections in the salmonid aquaculture industry with a mortality rate of about 90% until the 1990s, when an inactivated vaccine with mineral oil as adjuvant was successfully implemented to control the disease. However, the use of this vaccine is associated with inflammatory side effects in the peritoneal cavity as well as autoimmune reactions in Atlantic salmon, and incomplete protection has been reported in rainbow trout. We here aimed at developing and testing a recombinant alternative vaccine based on virus-like particles (VLPs) decorated with VapA, the key structural surface protein in the outer A-layer of A. salmonicida. The VLP carrier was based on either the capsid protein of a fish nodavirus, namely red grouper nervous necrotic virus (RGNNV) or the capsid protein of Acinetobacter phage AP205. The VapA and capsid proteins were expressed individually in E. coli and VapA was fused to auto-assembled VLPs using the SpyTag/SpyCatcher technology. Rainbow trout were vaccinated/immunized with the VapA-VLP vaccines by intraperitoneal injection and were challenged with A. salmonicida 7 weeks later. The VLP vaccines provided protection comparable to that of a bacterin-based vaccine and antibody response analysis demonstrated that vaccinated fish mounted a strong VapA-specific antibody response. To our knowledge, this is the first demonstration of the potential use of antigendecorated VLPs for vaccination against a bacterial disease in salmonids. [ABSTRACT FROM AUTHOR]

Purpose: Residual adrenocortical function, RAF, has recently been demonstrated in one-third of patients with autoimmune Addison's disease (AAD). Here, we set out to explore any influence of RAF on the levels of plasma metanephrines and any changes following stimulation with cosyntropin. Methods: We included 50 patients with verified RAF and 20 patients without RAF who served as controls upon cosyntropin stimulation testing. The patients had abstained from glucocorticoid and fludrocortisone replacement > 18 and 24 h, respectively, prior to morning blood sampling. The samples were obtained before and 30 and 60 min after cosyntropin stimulation and analyzed for serum cortisol, plasma metanephrine (MN), and normetanephrine (NMN) by liquid-chromatography tandem-mass pectrometry (LC-MS/MS). Results: Among the 70 patients with AAD, MN was detectable in 33%, 25%, and 26% at baseline, 30 min, and 60 min after cosyntropin stimulation, respectively. Patients with RAF were more likely to have detectable MN at baseline (p = 0.035) and at the time of 60 min (p = 0.048) compared to patients without RAF. There was a positive correlation between detectable MN and the level of cortisol at all time points (p = 0.02, p = 0.04, p < 0.001). No difference was noted for NMN levels, which remained within the normal reference ranges. Conclusion: Even very small amounts of endogenous cortisol production affect MN levels in patients with AAD. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to explore the time-course of hospitalization due to hyponatremia associated with omeprazole and esomeprazole. Methods: In this register-based case–control study, we compared patients hospitalized with a main diagnosis of hyponatremia (n = 11,213) to matched controls (n = 44,801). We used multiple regression to investigate time-related associations between omeprazole and esomeprazole and hospitalization because of hyponatremia. Results: The overall adjusted OR (aOR) between proton pump inhibitor (PPI) exposure, regardless of treatment duration and hospitalization with a main diagnosis of hyponatremia, was 1.23 (95% confidence interval CI 1.15–1.32). Exposure to PPIs was associated with a prompt increase in risk of hospitalization for hyponatremia from the first week (aOR 6.87; 95% CI 4.83–9.86). The risk then gradually declined, reaching an aOR of 1.64 (0.96–2.75) the fifth week. The aOR of ongoing PPI treatment was 1.10 (1.03–1.18). Conclusion: The present study shows a marked association between omeprazole and esomeprazole and hyponatremia related to recently initiated treatment. Consequently, newly initiated PPIs should be considered a potential culprit in any patient suffering from hyponatremia. However, if the patient has had this treatment for a longer time, the PPI should be considered a less likely cause. [ABSTRACT FROM AUTHOR]

Background: Prebiotics are known to have a positive impact on fish health and growth rate, and β-glucans are among the most used prebiotics on the market. In this study, rainbow trout (Oncorhynchus mykiss) were treated with a β-1,3;1,6-glucan dietary supplement (at a dose of 0 g, 1 g, 10 g, and 50 g β-glucan per kg of feed). After 6 weeks, the effect of the β-glucan was evaluated by determining the changes in the microbiota and the blood serum metabolites in the fish. The impact of β-glucan on the immune system was evaluated through a challenge experiment with the bacterial fish pathogen Yersinia ruckeri. Results: The microbiota showed a significant change in terms of composition following β-glucan treatment, notably an increase in the relative abundance of members of the genus Aurantimicrobium, associated with a decreased abundance of the genera Carnobacterium and Deefgea. Furthermore, analysis of more than 200 metabolites revealed that the relative levels of 53 metabolites, in particular compounds related to phosphatidylcholines, were up- or downregulated in response to the dietary supplementation, this included the amino acid alanine that was significantly upregulated in the fish that had received the highest dose of β-glucan. Meanwhile, no strong effect could be detected on the resistance of the fish to the bacterial infection. Conclusions: The present study illustrates the ability of β-glucans to modify the gut microbiota of fish, resulting in alteration of the metabolome and affecting fish health through the lipidome of rainbow trout. [ABSTRACT FROM AUTHOR]

Objective: Depression is common in individuals with endocrine-metabolic disorders and vice versa, and a better understanding of the underlying factors contributing to the comorbidity of these disorders is needed. This study investigated the familial coaggregation of depression and endocrine-metabolic disorders and estimated the contribution of genetic and environmental factors to their co-occurrence.Methods: This population-based cohort study included 2.2 million individuals born in Sweden between 1973 and 1996, with follow-up through 2013. Participants were linked to their biological parents, allowing identification of full siblings, maternal half siblings, and paternal half siblings. Diagnoses of depression and endocrine-metabolic conditions were investigated, with the latter grouped into autoimmune disorders (autoimmune hypothyroidism, Graves' disease, and type 1 diabetes) and non-autoimmune disorders (type 2 diabetes, obesity, and polycystic ovary syndrome). Logistic regression and Cox regression were used to estimate the associations between endocrine-metabolic disorders and depression within the same individual and across siblings. Quantitative genetic modeling was performed to investigate the relative contribution of genetic and environmental influences.Results: Individuals with endocrine-metabolic disorders had a significantly higher risk of depression, with odds ratios ranging from 1.43 (95% CI=1.30, 1.57) for Graves' disease to 3.48 (95% CI=3.25, 3.72) for type 2 diabetes. Increased risks extended to full and half siblings. These correlations were mainly explained by shared genetic influences for non-autoimmune conditions, and by nonshared environmental factors for autoimmune disorders, especially for type 1 diabetes.Conclusions: These findings provide phenotypic and etiological insights into the co-occurrence of depression and various endocrine-metabolic conditions, which could guide future research aiming at identifying pathophysiological mechanisms and intervention targets. [ABSTRACT FROM AUTHOR]

Context: A seasonal variation in hyponatremia, with higher incidence rates during hot summer days, has been demonstrated. Whether this applies to cool temperate regions is currently unknown. Objective: The aim of this study was to investigate the influence of ambient temperature on hyponatremia in the Swedish population under current and future climate scenarios. Methods: This nationwide cohort study identified all patients hospitalized with a first-ever principal diagnosis of hyponatremia between October 2005 and December 2014. Incidence rates for hyponatremia were calculated as number of hospitalizations divided by person-days at risk in the adult Swedish population at a given temperature, in increments of 1 °C. Results: The incidence of hyponatremia was stable at 0.3 per million person-days from -10 to 10 °C, but increased rapidly at 24-hour mean temperatures above 15 °C, with 2.26 hospitalizations per million days at the highest recorded temperature of 25 °C. Women and elderly carried the greatest risk, with an incidence of 35 hospitalizations per million days in individuals ≥ 80 years of age on the hottest days, corresponding to a 15-fold increase in incidence compared with cool days. A future 1 or 2 °C increase in mean temperature is expected to increase the incidence of hyponatremia by 6.3% and 13.9%, respectively. Conclusion: The risk of hospitalization due to hyponatremia increases rapidly at temperatures above 15 °C, indicating a threshold effect. Over the next decades, rising global temperatures are expected to increase the inpatient burden of hyponatremia by approximately 10%. Strategies for protecting vulnerable groups are necessary to reduce this risk. [ABSTRACT FROM AUTHOR]

Objective: Type 1 diabetes and Hashimoto’s thyroiditis frequently cluster in individuals and in families, indicating shared origins. The objective of this study was to investigate familial co-aggregation of these diseases and to quantify shared genetic and environmental factors. Design: This study is a twin cohort study. Methods: National health registers were used to identify cases among 110 814 Swedish twins. Co-aggregation was calculated as risk ratios for type 1 diabetes among co-twins of individuals with Hashimoto’s thyroiditis, and viceversa. Variance explained by genetics (i.e. heritability), and the proportions thereof shared between the diseases, was estimated by contrasting associations in monozygotic and dizygotic twins using structural equation models. Results: Individuals with one disease were at a high risk for the other disease (adjusted risk ratio: 11.4 (95% CI: 8.5– 15.3)). Co-aggregation was more common in monozygotic than in dizygotic pairs, with adjusted risk ratios of 7.0 (95% CI: 3.2–15.1) and 1.7 (95% CI: 0.7–4.1), respectively. Genetic effects shared across diseases accounted for 11% of the variance for type 1 diabetes and 9% of the variance for Hashimoto’s thyroiditis, while environmental factors unique to individual twins, but shared across diseases, accounted for 10% of the variance for type 1 diabetes and 18% of the variance for Hashimoto’s thyroiditis. Conclusions: Both genes and environment unique to individual twins contribute to considerable etiologic overlap between type 1 diabetes and Hashimoto’s thyroiditis. These findings add to the current knowledge on the mechanisms behind autoimmune disease clustering and could guide future research aimed at identifying pathophysiological mechanisms and intervention targets. [ABSTRACT FROM AUTHOR]

Objective: Diuretics are often implicated in hyponatraemia. While thiazides constitute one of the most common causes of hyponatraemia, data on loop diuretics and potassium‐sparing agents are limited and partly conflicting. The objective of this investigation was to study the association between use of different types of non‐thiazide diuretics and hospitalization due to hyponatraemia. Design, Patients and Measurements: This was a register‐based case‐control study on the adult Swedish population. By linking national registers, patients hospitalized with a principal diagnosis of hyponatraemia (n = 11,213) from 1 October 2005 through 31 December 2014 were compared with matched controls (n = 44,801). Multivariable logistic regression, adjusted for multiple confounders, was used to analyse the association between use of diuretics and hyponatraemia. In addition, newly initiated use (≤90 days) and ongoing use were examined separately. Results: Adjusted odds ratios (aORs) (95% CI) were 0.61 (0.57–0.66) for the use of furosemide, 1.69 (1.54–1.86) for the use of amiloride and 1.96 (1.78–2.18) for the use of spironolactone and hospitalization due to hyponatraemia. For newly initiated therapy, aORs ranged from 1.23 (1.04–1.47) for furosemide to 3.55 (2.75–4.61) for spironolactone. The aORs for ongoing use were 0.52 (0.47–0.57) for furosemide, 1.62 (1.47–1.79) for amiloride and 1.75 (1.56–1.98) for spironolactone. Conclusions: Ongoing use of furosemide was inversely correlated with hospitalization due to hyponatraemia, suggesting a protective effect. Consequently, if treatment with furosemide precedes the development of hyponatraemia by some time, other causes of hyponatraemia should be sought. Spironolactone and amiloride may both contribute to hyponatraemia; this effect is most prominent early in treatment. [ABSTRACT FROM AUTHOR]

Background: Selective serotonin reuptake inhibitors (SSRIs) have a wide and increasing use for the treatment of depression and anxiety. Previous studies have indicated an increased risk of hyponatremia during the first months of treatment. We aimed to investigate the detailed time-course of SSRI-associated hyponatremia with a high temporal resolution, using registry data encompassing the total Swedish population. Methods: This was a population-based case control study using several national registers. Patients hospitalized with a principal diagnosis of hyponatremia (n = 11,213) were compared with matched controls (n = 44,801). Multivariable regression was applied to explore time-dependent associations between SSRIs and hospitalization due to hyponatremia. Results: Individuals initiating treatment with SSRIs were exposed to an immediately increased risk for hospitalization at week 1, reaching an adjusted odds ratio (aOR) (95% confidence interval) of 29 (19–46). The associations then gradually declined, reaching an aOR of 2.1 (1.0–4.2) by week 13. The aOR for individuals treated for longer than 13 weeks was 0.78 (0.71–0.85). Conclusions: This study revealed a dramatically increased risk of hyponatremia exclusively related to newly initiated treatment. Consequently, even subtle symptoms consistent with hyponatremia during the first weeks of SSRI treatment should prompt analysis of sodium levels. In patients treated with SSRIs for several months or years, other causes should primarily be sought in the event of hyponatremia. [ABSTRACT FROM AUTHOR]

Purpose: Thiazide diuretics are the most common origin of drug-induced hyponatremia. However, population-based studies on clinical outcomes are lacking. We therefore explored the time course and absolute risk of thiazide-associated hospitalization due to hyponatremia in Sweden. Methods: Population-based case-control study including patients hospitalized with a principal diagnosis of hyponatremia (n = 11,213) compared with controls (n = 44,801). Linkage of registers was used to acquire data. Multivariable regression was applied to explore time-dependent associations between thiazide diuretics and hospitalization due to hyponatremia. Attributable risks were calculated assessing the disease burden attributable to thiazides. Results: Individuals initiating thiazide treatment were exposed to an immediate increase in risk for hospitalization with adjusted odds ratio (aOR) (95% CI) of 48 (28–89). The associations gradually declined reaching an aOR of 2.9 (2.7–3.1) for individuals treated for longer than 13 weeks. The attributable risk of hyponatremia-associated hospitalization due to thiazides of any treatment length was 27% (3095/11,213). Among 806 patients initiating treatment < 90 days before hospitalization, hyponatremia could be attributed to thiazides in 754. Based on nationwide data, 616,678 individuals were initiated on thiazides during the 8-year study period suggesting an absolute risk of 0.12% (754/661,678) for subsequent hospitalization with a main diagnosis of hyponatremia. Conclusions: Thiazide diuretics attributed to more than one in four individuals hospitalized due to hyponatremia. The risk increase was very pronounced during the first month of treatment and then gradually declined, without returning to normal. However, the absolute risk for the development of hyponatremia demanding hospitalization may for most individuals be modest. [ABSTRACT FROM AUTHOR]

Purpose: Drug-induced hyponatremia is common, with medications from many drug-classes implicated. Lipid-lowering agents are among the most prescribed drugs. Limited evidence suggests an inverse association between statins and hyponatremia, while data on other lipid-lowering agents is absent. The objective of this investigation was to study the association between lipid-lowering drugs and hospitalization due to hyponatremia. Methods: This was a register-based case–control study of the general Swedish population. Those hospitalized with a main diagnosis of hyponatremia (n = 11,213) were compared with matched controls (n = 44,801). Multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations, and socioeconomic factors was used to explore the association between severe hyponatremia and the use of lipid-lowering drugs. Results: Unadjusted ORs (95% CI) for hospitalization due to hyponatremia were 1.28 (1.22–1.35) for statins, 1.09 (0.79–1.47) for ezetimibe, 1.38 (0.88–2.12) for fibrates, and 2.12 (1.31–3.35) for resins. After adjustment for confounding factors the adjusted odds ratios (95% CI) compared with controls were 0.69 (0.64–0.74) for statins, 0.60 (0.41–0.86) for ezetimibe, 0.87 (0.51–1.42) for fibrates, and 1.21 (0.69–2.06) for resins. Conclusions: Use of statins and ezetimibe was inversely correlated with severe hyponatremia. Consequently, these drugs are unlikely culprits in patients with hyponatremia, and they appear safe to initiate in hyponatremic patients. A potential protective effect warrants further studies on how statins and other lipid-lowering drugs are linked to dysnatremias. [ABSTRACT FROM AUTHOR]

Context: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are known to coaggregate in families, but the magnitude and nature of a shared etiology is unknown.Objectives: To estimate the shared genetic influence on overt HT and GD and to examine if the heritability differs between men and women.Design, Setting, and Patients: We used national health registries to identify cases of HT and GD in a cohort of 110 814 Swedish twins. By comparing intra-class and cross-twin cross-trait correlations in dizygotic and monozygotic twins, we calculated heritability and the proportions thereof shared between the diseases. Univariate estimates of heritability were calculated by sex.Results: The heritability for HT and GD was 65% (95% CI, 61-70) and 63% (95% CI, 55-72), respectively. The genetic correlation was 0.35 (95% CI, 0.20-0.50) and shared genetic effects accounted for 8% of the variance for both HT and GD. Univariate heritability was significantly higher in men than in women for HT (90% vs 60%, P < 0.001) but not for GD (79% vs 63%, P = 0.085).Conclusions: From a genetic perspective, HT and GD appear to be only modestly related diseases. Hence, the term "autoimmune thyroid disease," used to cluster these disorders, may have limited validity in a genetic context. Moreover, the mechanisms contributing to HT are partly different for the sexes, with genetic components more important in men. [ABSTRACT FROM AUTHOR]

Background: Many drugs used in psychiatry have been reported to cause hyponatraemia. However, lithium may be an exception due to its potential for causing nephrogenic diabetes insipidus, but clinical data are largely absent. The objective of this investigation was to study the association between lithium therapy and hospitalization due to hyponatraemia. Methods: This study was a register-based case–control investigation of the general Swedish population. Patients hospitalized with a principal diagnosis of hyponatraemia (n =11,213) were compared with matched controls (n =44,801). Analyses using multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations and socioeconomic factors were deployed to calculate the association between severe hyponatraemia and the use of lithium. Additionally, newly initiated (⩽90 days) and ongoing lithium therapy was studied separately. Results: Compared with controls, the unadjusted odds ratio (OR) (95% confidence interval (CI)) for hospitalization due to hyponatraemia was 1.07 (0.70–1.59) for lithium. However, after adjustment for confounding factors the risk was reduced (adjusted OR: 0.53 (0.31–0.87)). Newly initiated lithium therapy was not significantly associated with hyponatraemia (adjusted OR 0.73 (0.35–5.38)). In contrast, for ongoing therapy the corresponding adjusted OR was significantly reduced (adjusted OR: 0.52 (0.30–0.87)). Conclusions: A marked inverse association was found between ongoing lithium therapy and hospitalization due to hyponatraemia. [ABSTRACT FROM AUTHOR]

Objective: Co-aggregation of autoimmune diseases is common, suggesting pa rtly shared etiologies. Genetic factors are believed to be important, but objective measures of environ mental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at esti mating heritability and genetic overlap in seven organspecific autoimmune diseases. Design: Prospective twin cohort study. Methods: We used a cohort of 110 814 twins to examine co-aggregation an d heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 dia betes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disea se as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estim ate the genetic influence on co-aggregation. Heritability for individual disorders was calculated using stru ctural equational modeling adjusting for censoring and truncation of data. Results: Co-aggregation was more pronounced in monozygotic twins (media n HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moder ate for atrophic gastritis (0.38, 95% CI: 0.23-0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49-0. 71) for Graves' disease to 0.97 (95% CI: 0.91-1.00) for Addison's disease. Conclusions: Overall, co-aggregation was more pronounced in monozygotic tha n in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co- aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our r esults validate and refine previous heritability estimates based on smaller twin cohorts. [ABSTRACT FROM AUTHOR]

Context: Glucose-lowering medications have occasionally been reported to cause hyponatremia, but the evidence is scarce. Objectives: To explore the association between glucose-lowering medications and severe hyponatremia. Design, setting, and participants: Subjects hospitalized with a principal diagnosis of hyponatremia (n = 14,359) were compared with matched controls (n = 57,383). Data were derived by linkage of national population-based registers. Multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations, and socioeconomic factors was used to explore the association between hospitalization for hyponatremia and the use of different glucose-lowering medications. Furthermore, newly initiated (≤90 days) and ongoing use was investigated separately. Main outcome measures: Hospitalization due to hyponatremia. Results: The unadjusted ORs (95% CI) for hospitalization due to hyponatremia were 1.41 (1.29–1.54) for insulins, 1.38 (1.27–1.50) for metformin, and 1.22 (1.07–1.38) for sulfonylureas. However, after adjustment for confounding factors the association was consistently reversed. Thus, for any glucose-lowering medication the adjusted OR was 0.63 (0.58–0.68). For insulins, metformin and sulfonylureas, adjusted ORs (95% CI) were 0.58 (0.52–0.65), 0.81 (0.72–0.90) and 0.81 (0.69–0.94), respectively. Odds ratios for newly initated medications were overall higher while those for ongoing treatment were further decreased. Thus, adjusted ORs (95% CI) for ongoing treatment with insulins, metformin, and sulfonylureas were 0.54 (0.48–0.61), 0.82 (0.73–0.91) and 0.78 (0.66–0.92). Conclusions: Glucose-lowering medications did not increase the risk for hospitalization due to severe hyponatremia. In fact, the association was inverse across all investigated drugs. The association may be mediated by pharmacologic mechanisms, but the uniform effects across drug-classes suggest properties of the diabetic disease are of importance. [ABSTRACT FROM AUTHOR]

Purpose In a patient with clinically significant hyponatremia without other clear causes, thiazide treatment should be replaced with another drug. Data describing to which extent this is being done are scarce. The aim of this study was to investigate sociodemographic and socioeconomic factors that may be of importance for the withdrawal of thiazide diuretics in patients hospitalized due to hyponatremia. Methods: The study population was sampled from a case‐control study investigating individuals hospitalized with a main diagnosis of hyponatremia. For every case, four matched controls were included. In the present study, cases (n = 5204) and controls (n = 7425) that had been dispensed a thiazide diuretic prior to index date were identified and followed onward regarding further dispensations. To investigate the influence of socioeconomic and sociodemographic factors, multiple logistic regression was used. Results: The crude prevalence of thiazide withdrawal for cases and controls was 71.9% and 10.8%, respectively. Thiazide diuretics were more often withdrawn in medium‐sized towns (adjusted OR, 1.52; 95% CI, 1.21‐1.90) and rural areas (aOR, 1.81; 95% CI, 1.40‐2.34) compared with metropolitan areas and less so among divorced (aOR, 0.72; 95% CI, 0.53‐0.97). However, education, employment status, income, age, country of birth, and gender did not influence withdrawal of thiazides among patients with hyponatremia. Conclusions: Thiazide diuretics were discontinued in almost three out of four patients hospitalized due to hyponatremia. Educational, income, gender, and most other sociodemographic and socioeconomic factors were not associated with withdrawal of thiazides. [ABSTRACT FROM AUTHOR]

Purpose: Several studies have reported an association between hyponatremia and lethality. However, it remains elusive whether hyponatremia independently contributes to lethality. The aim of the study was to investigate associations between hyponatremia and lethality and differences in lethality between men and women hospitalized due to hyponatremia. Methods: Four registries were utilized in this population-based retrospective study: The National Patient Registry, the Cause of Death Register, the Swedish Prescribed Drug Register and the Total Population Register (NPR) from which the controls were sampled. All hospitalized patients with a first-ever principal ICD10 diagnosis of hyponatremia or syndrome of inappropriate ADH secretion in the NPR between 1 October 2005 and 31 December 2014 were defined as cases. Cox regression with adjustment for potential confounders was used. Results: 14,359 individuals with a principal diagnosis of hyponatremia, and 57,382 matched controls were identified. Median age was 76 years and the majority were women (72%). Median age for women and men was 79 and 68 years, respectively. Adjusted hazard ratios (and 95% CI) for lethality in those with hyponatremia compared with controls were for the entire population 5.5 (4.4–7.0) and in the subgroup free from previously known underlying disease 6.7 (3.3–13.3). Lethality in women with hyponatremia was lower compared with men: HR: 0.56 (0.49–0.64). In the healthier group the lethality remained lower for women: HR: 0.49 (0.34–0.71). Conclusions: Patients hospitalized due to hyponatremia faced an increased subsequent lethality that was independent of concomitant disease. This increase was nearly twice as large among men compared with women. [ABSTRACT FROM AUTHOR]

Purpose: The pathophysiology behind autoimmune Addison's disease (AAD) is poorly understood, and the relative influence of genetic and environmental factors remains unclear. In this study, we examined the heritability of AAD and explored disease-associated autoimmune comorbidity among Swedish twins. Methods: A population-based longitudinal cohort of 112,100 Swedish twins was used to calculate the heritability of AAD, and to explore co-occurrence of 10 organ-specific autoimmune disorders in twin pairs with AAD. Diagnoses were collected 1964-2012 through linkage to the Swedish National Patient Register. The Swedish Prescribed Drug Register was used for additional diagnostic precision. When available, biobank serum samples were used to ascertain the AAD diagnosis through identification of 21-hydroxylase autoantibodies. Results: We identified 29 twins with AAD. Five out of nine (5/9) monozygotic pairs and zero out of fifteen (0/15) dizygotic pairs were concordant for AAD. The probandwise concordance for monozygotic twins was 0.71 (95% CI 0.40-0.90) and the heritability 0.97 (95% CI 0.88-99). Autoimmune disease patterns of monozygotic twin pairs affected by AAD displayed a higher degree of similarity than those of dizygotic twins, with an incidence rate ratio of 15 (95% CI 1.8-116) on the number of shared autoimmune diagnoses within pairs. Conclusions: The heritability of AAD appears to be very high, emphasizing the need for further research on the genetic etiology of the disease. Monozygotic twin concordance for multiple autoimmune manifestations suggests strong genetic influence on disease specificity in organ-specific autoimmunity. [ABSTRACT FROM AUTHOR]

Aeromonas salmonicida subsp. salmonicida is the etiological agent of furunculosis and a major fish health problem in salmonid aquaculture worldwide. Injection vaccination with commercial mineral oil-adjuvanted bacterin vaccines has been partly successful in preventing the disease but in Danish rainbow trout (Oncorhynchus mykiss, Walbaum) aquaculture furunculosis outbreaks still occur. In this study we tested the efficacy of experimental subunit vaccines against A. salmonicida infection in rainbow trout. We utilized in silico screening of the proteome of A. salmonicida subsp. salmonicida strain A449 and identified potential protective protein antigens that were tested by in vivo challenge trial. A total of 14 proteins were recombinantly expressed in Escherichia coli and prepared in 3 different subunit vaccine combinations to immunize 3 groups of rainbow trout by intraperitoneal (i.p.) injection. The fish were exposed to virulent A. salmonicida 7 weeks after immunization. To assess the efficacy of the subunit vaccines we evaluated the immune response in fish after immunization and challenge infection by measuring the antibody levels and monitoring the survival of fish in different groups. The survival of fish at 3 weeks after challenge infection showed that all 3 groups of fish immunized with 3 different protein combinations exhibited significantly lower mortalities (17–30%) compared to the control groups (48% and 56%). The ELISA results revealed significantly elevated antibody levels in fish against several protein antigens, which in some cases were positively correlated to the survival. [ABSTRACT FROM AUTHOR]

Background: Tolvaptan is the only vasopressin V2 receptor antagonist licensed by the European Medicines Agency for the treatment of hyponatraemia (HN) secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We have investigated the cost-effectiveness of tolvaptan versus no active treatment (NAT) in adult patients within the licensed indication who have either failed to respond to fluid restriction or for whom the use of fluid restriction is not suitable, from the societal perspective in Sweden. Methods: A cost-utility analysis, considering a 'general SIADH' population and two subpopulations of patients (small-cell lung cancer [SCLC] and pneumonia) to broadly represent the complex clinical pathway of SIADH, was performed. A discrete event simulation was developed to model the progression of individuals through inpatient admissions over a 30-day time horizon (180 days for the SCLC cohort). Clinical data were derived from tolvaptan trials and observational data sources. All costs are given in Swedish kronor (SEK). Results: In the 'general SIADH' population, tolvaptan was associated with reduced costs (SEK 5,779 per patient [€624]) and increased quality-adjusted life-years (QALYs) (0.0019) compared with NAT and was therefore the dominant treatment strategy. Tolvaptan was also associated with reduced costs and increased QALYs in the SCLC and pneumonia subpopulations. The most influential variables in our analysis were reduction in hospital length of stay, duration of treatment and long term treatment with tolvaptan in SCLC patients. Conclusions: Tolvaptan represents a cost-effective treatment option in Sweden for hospitalised patients with HN secondary to SIADH who have either failed to respond to or are unsuitable for fluid restriction. [ABSTRACT FROM AUTHOR]

Eye flukes of the genus Diplostomum were recorded with a prevalence of 7.4% and a mean intensity of 11.9 (range 1-75) parasites per fish in eye lenses of a total of 188 Atlantic cod, Gadus morhua, sampled in the Southeastern Baltic Sea from March 2013 to February 2014. A slight decrease of infection level, among the fish with body length ranging from 30 to 89.5 cm, was found when data were compared to a corresponding survey in the 1980s. Due to imprecise species identification of eye flukes based on morphometric analyses we present, as a baseline for further studies, rDNA sequences from a subsample of 19 eye flukes based on sequencing of a part of 18S, ITS-1, 5.8S, ITS-2 and part of 28S. We discuss the use of eye fluke recordings in Baltic cod as an environmental indicator due to the dependence of the parasite´s life cycle on biotic (occurrence of snail and bird hosts) and abiotic (temperature and salinity) parameters. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]