Major Depressive Disorder (MDD) and Antidepressant Medication Are Overrepresented in High-Dose Statin Treatment

Objective: To examine the dose-dependent relationship of different types of statins with the occurrence of major depressive disorder (MDD) and prescription of antidepressant medication. Methods: This cross-sectional study used medical claims data for the general Austrian population (n = 7,481,168) to identify all statin-treated patients. We analyzed all patients with MDD undergoing statin treatment and calculated the average defined daily dose for six different types of statins. In a sub-analysis conducted independently of inpatient care, we investigated all patients on antidepressant medication (statin-treated patients: n = 98,913; non-statin-treated patients: n = 789,683). Multivariate logistic regression analyses were conducted to calculate the risk of diagnosed MDD and prescription of antidepressant medication in patients treated with different types of statins and dosages compared to non-statin-treated patients. Results: In this study, there was an overrepresentation of MDD in statin-treated patients when compared to non-statin-treated patients (OR: 1.22, 95% CI: 1.20–1.25). However, there was a dose dependent relationship between statins and diagnosis of MDD. Compared to controls, the ORs of MDD were lower for low-dose statin-treated patients (simvastatin>0– 0– 0– 40– 60–80 mg:OR: 5.27, 95% CI: 4.21–6.60; atorvastatin>40– 60– 20– < =40 mg:OR: 2.09, 95% CI: 1.31–3.34). The results were confirmed in a sex-specific analysis and in a cohort of patients taking antidepressants, prescribed independently of inpatient care. Conclusions: This study shows that it is important to carefully re-investigate the relationship between statins and MDD. High-dose statin treatment was related to an overrepresentation, low-dose statin treatment to an underrepresentation of MDD

The influence of alloying on the stacking fault energy of gold from density functional theory calculations

The generalized stacking fault (SFE) energy curves of pure gold (Au) and its binary alloys with transition metals are determined from density functional theory (DFT). Alloy elements Ag, Al, Cu, Ni, Ti, Zr, Zn, In, Ga, Sn, Mn, Cd, Sn, Ta and Cr are substituted into Au at concentrations up to 4%. A comparison of various proposed methodologies to calculate SFEs is given. The intrinsic SFE decreases for all alloying elements from its value for pure Au, but SFE energies (both stable and unstable) vary strongly with the distance of the alloying element from the stacking fault region, and with alloy concentration. The compositional dependence of the SFE on the volume change associated with alloying element is determined. This work demonstrates that the SFE is strongly influenced by misfit strain caused by the alloying elements. Moreover, the computed generalized SFE curves provide information valuable to developing an understanding of the deformation behavior of Au and Au-alloys

Systematic population-wide ecological analysis of regional variability in disease prevalence

The prevalence of diseases often varies substantially from region to region. Besides basic demographic properties, the factors that drive the variability of each prevalence are to a large extent unknown. Here we show how regional prevalence variations in 115 different diseases relate to demographic, socio-economic, environmental factors and migratory background, as well as access to different types of health services such as primary, specialized and hospital healthcare. We have collected regional data for these risk factors at different levels of resolution; from large regions of care (Versorgungsregion) down to a 250 by 250 m square grid. Using multivariate regression analysis, we quantify the explanatory power of each independent variable in relation to the regional variation of the disease prevalence. We find that for certain diseases, such as acute heart conditions, diseases of the inner ear, mental and behavioral disorders due to substance abuse, up to 80% of the variance can be explained with these risk factors. For other diagnostic blocks, such as blood related diseases, injuries and poisoning however, the explanatory power is close to zero. We find that the time needed to travel from the inhabited center to the relevant hospital ward often contributes significantly to the disease risk, in particular for diabetes mellitus. Our results show that variations in disease burden across different regions can for many diseases be related to variations in demographic and socio-economic factors. Furthermore, our results highlight the relative importance of access to health care facilities in the treatment of chronic diseases like diabetes

Quantification of diabetes comorbidity risks across life using nation-wide big claims data

Despite substantial progress in the study of diabetes, important questions remain about its comorbidities and clinical heterogeneity. To explore these issues, we develop a framework allowing for the first time to quantify nation-wide risks and their age- and sex-dependence for each diabetic comorbidity, and whether the association may be consequential or causal, in a sample of almost two million patients. This study is equivalent to nearly 40,000 single clinical measurements. We confirm the highly controversial relation of increased risk for Parkinson's disease in diabetics, using a 10 times larger cohort than previous studies on this relation. Detection of type 1 diabetes leads detection of depressions, whereas there is a strong comorbidity relation between type 2 diabetes and schizophrenia, suggesting similar pathogenic or medication-related mechanisms. We find significan sex differences in the progression of, for instance, sleep disorders and congestive heart failure in diabetic patients. Hypertension is a highly sex-sensitive comorbidity with females being at lower risk during fertile age, but at higher risk otherwise. These results may be useful to improve screening practices in the general population. Clinical management of diabetes must address age- and sex-dependence of multiple comorbid conditions

High-risk multimorbidity patterns on the road to cardiovascular mortality

Background Multimorbidity, the co-occurrence of two or more diseases in one patient, is a frequent phenomenon. Understanding how different diseases condition each other over the lifetime of a patient could significantly contribute to personalised prevention efforts. However, most of our current knowledge on the long-term development of the health of patients (their disease trajectories) is either confined to narrow time spans or specific (sets of) diseases. Here, we aim to identify decisive events that potentially determine the future disease progression of patients. Methods Health states of patients are described by algorithmically identified multimorbidity patterns (groups of included or excluded diseases) in a population-wide analysis of 9,000,000 patient histories of hospital diagnoses observed over 17 years. Over time, patients might acquire new diagnoses that change their health state; they describe a disease trajectory. We measure the age- and sex-specific risks for patients that they will acquire certain sets of diseases in the future depending on their current health state. Results In the present analysis, the population is described by a set of 132 different multimorbidity patterns. For elderly patients, we find 3 groups of multimorbidity patterns associated with low (yearly in-hospital mortality of 0.2–0.3%), medium (0.3–1%) and high in-hospital mortality (2–11%). We identify combinations of diseases that significantly increase the risk to reach the high-mortality health states in later life. For instance, in men (women) aged 50–59 diagnosed with diabetes and hypertension, the risk for moving into the high-mortality region within 1 year is increased by the factor of 1.96 ± 0.11 (2.60 ± 0.18) compared with all patients of the same age and sex, respectively, and by the factor of 2.09 ± 0.12 (3.04 ± 0.18) if additionally diagnosed with metabolic disorders. Conclusions Our approach can be used both to forecast future disease burdens, as well as to identify the critical events in the careers of patients which strongly determine their disease progression, therefore constituting targets for efficient prevention measures. We show that the risk for cardiovascular diseases increases significantly more in females than in males when diagnosed with diabetes, hypertension and metabolic disorders

Betatrophin is downregulated in pregnant women with a history of RYGB operation and a high risk of postprandial hypoglycaemia

Betatrophin is a liver and adipose tissue-derived protein which has recently been linked to glucose metabolism. So far, no data exist about the role of betatrophin in pregnant women with a history of Roux-En-Y gastric bypass (RYGB) operation with a high risk of postprandial hypoglycaemia. In this prospective clinical study, an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed between the 24th and 28th week of pregnancy and 3-6 months post-partum in a cohort of obese and normal-weight pregnant women, as well as in women with a history of RYGB operation. In the cohort of pregnant women with RYGB and exaggerated risk of postprandial hypoglycaemic events, basal and dynamic betatrophin levels during the OGTT were lower than in the obese or normal-weight pregnant women (basal levels: 13.66 ± 5.88 vs. 19.03 ± 4.15 vs. 15.68 ± 6.48, p = 0.016; OGTT 60': 13.33 ± 5.40 vs. 17.37 ± 3.16 vs. 15.84 ± 4.99, p = 0.030). During the OGTT, basal and dynamic betatrophin levels at 60' were positively associated with glucose levels at 60 min (r = 0.55, p = 0.01 and r = 0.45, p = 0.039). This positive association was followed by significant hypoglycaemic events in the RYGB group. It was only in the RYGB group that betatrophin was negatively related to the disposition index (rho = -0.53, p = 0.014). After pregnancy there was a decrease in basal and stimulated betatrophin levels during the OGTT in all three patient groups. In comparison to normal-weight and obese pregnant women, women with a history of RYGB operation and a high risk of postprandial hypoglycaemic events have lower levels of betatrophin. This indicate a mechanistic role in order to decrease the risk of postprandial hypoglycaemia in this specific cohort

Decompression of Multimorbidity Along the Disease Trajectories of Diabetes Mellitus Patients

Multimorbidity, the presence of two or more diseases in a patient, is maybe the greatest health challenge for the aging populations of many high-income countries. One of the main drivers of multimorbidity is diabetes mellitus (DM) due to its large number of risk factors and complications. Yet, we currently have very limited understanding of how to quantify multimorbidity beyond a simple counting of diseases and thereby inform prevention and intervention strategies tailored to the needs of elderly DM patients. Here, we conceptualize multimorbidity as typical temporal progression patterns of multiple diseases, so-called trajectories, and develop a framework to perform a matched and sex-specific comparison between DM and non-diabetic patients. We find that these disease trajectories can be organized into a multi-level hierarchy in which DM patients progress from relatively healthy states with low mortality to high-mortality states characterized by cardiovascular diseases, chronic lower respiratory diseases, renal failure, and different combinations thereof. The same disease trajectories can be observed in non-diabetic patients, however, we find that DM patients typically progress at much higher rates along their trajectories. Comparing male and female DM patients, we find a general tendency that females progress faster toward high multimorbidity states than males, in particular along trajectories that involve obesity. Males, on the other hand, appear to progress faster in trajectories that combine heart diseases with cerebrovascular diseases. Our results show that prevention and efficient management of DM are key to achieve a compression of morbidity into higher patient ages. Multidisciplinary efforts involving clinicians as well as experts in machine learning and data visualization are needed to better understand the identified disease trajectories and thereby contribute to solving the current multimorbidity crisis in healthcare

Reply to Klitz and Niklasson: Can viral infections explain the cross-sectional Austrian diabetes data?

The vast majority of diabetes patients suffer from type II diabetes. There are several theories for potential causes of its development, the most favored being the "exhaustion" of beta-cells by chronic excess caloric intake combined with inactivity leading to obesity, diabetes, and cardiovascular disease. Viral infection could be a potential cause, however mainly for type I diabetes. Furthermore, autoimmunity might play a role in type I patients..

Sex-related effects in major depressive disorder: Results of the European Group for the Study of Resistant Depression

Background: Sex-related effects on the evolution and phenotype of major depressive disorder (MDD) were reported previously. Methods: This European multicenter cross-sectional study compared sociodemographic, clinical, and treatment patterns between males and females in a real-world sample of 1410 in- and outpatients with current MDD. Results: Male MDD patients (33.1%) were rather inpatients, suffered from moderate to high suicidality levels, received noradrenergic&nbsp;and specific serotonergic antidepressants (ADs) as first-line AD treatment, generally higher mean AD daily doses, and showed a trend towards a more frequent administration of add-on treatments. Female MDD patients (66.9%) were rather outpatients, experienced lower suicidality levels, comorbid thyroid dysfunction, migraine, asthma, and a trend towards earlier disease onset. Conclusions: The identified divergencies may contribute to the concept of male&nbsp;and female depressive syndromes and serve as predictors of disease severity and course, as they reflect phenomena that were repeatedly related to treatment-resistant depression (TRD). Especially the greater necessity of inpatient treatment and more complex psychopharmacotherapy in men may reflect increased therapeutic efforts undertaken to treat suicidality and to avoid TRD. Hence, considering sex may guide the diagnostic and treatment processes towards targeting challenging clinical manifestations including comorbidities and suicidality, and prevention of TRD and chronicity