Clinical profile and outcome of isolated pulmonary embolism: a systematic review and meta-analysis.

Background: Isolated pulmonary embolism (PE) appears to be associated with a specific clinical profile and sequelae compared to deep vein thrombosis (DVT)-associated PE. The objective of this study was to identify clinical characteristics that discriminate both phenotypes, and to characterize their differences in clinical outcome. Methods: We performed a systematic review and meta-analysis of studies comparing PE phenotypes. A systematic search of the electronic databases PubMed and CENTRAL was conducted, from inception until January 27, 2023. Exclusion criteria were irrelevant content, inability to retrieve the article, language other than English or German, the article comprising a review or case study/series, and inappropriate study design. Data on risk factors, clinical characteristics and clinical endpoints were pooled using random-effects meta-analyses. Findings: Fifty studies with 435,768 PE patients were included. In low risk of bias studies, 30% [95% CI 19-42%, I 2 = 97%] of PE were isolated. The Factor V Leiden [OR: 0.47, 95% CI 0.37-0.58, I 2 = 0%] and prothrombin G20210A mutations [OR: 0.55, 95% CI 0.41-0.75, I 2 = 0%] were significantly less prevalent among patients with isolated PE. Female sex [OR: 1.30, 95% CI 1.17-1.45, I 2 = 79%], recent invasive surgery [OR: 1.31, 95% CI 1.23-1.41, I 2 = 65%], a history of myocardial infarction [OR: 2.07, 95% CI 1.85-2.32, I 2 = 0%], left-sided heart failure [OR: 1.70, 95% CI 1.37-2.10, I 2 = 76%], peripheral artery disease [OR: 1.36, 95% CI 1.31-1.42, I 2 = 0%] and diabetes mellitus [OR: 1.23, 95% CI 1.21-1.25, I 2 = 0%] were significantly more frequently represented among isolated PE patients. In a synthesis of clinical outcome data, the risk of recurrent VTE in isolated PE was half that of DVT-associated PE [RR: 0.55, 95% CI 0.44-0.69, I 2 = 0%], while the risk of arterial thrombosis was nearly 3-fold higher [RR: 2.93, 95% CI 1.43-6.02, I 2 = 0%]. Interpretation: Our findings suggest that isolated PE appears to be a specific entity that may signal a long-term risk of arterial thrombosis. Randomised controlled trials are necessary to establish whether alternative treatment regimens are beneficial for this patient subgroup. Funding: None.

Association of birth weight with corneal aberrations in adulthood – Results from a population-based study

Purpose: Low birth weight (BW) is associated with increased corneal aberrations in childhood and alterations of corneal geometry in adulthood. Increased corneal aberrations may be a factor contributing to decreased visual function in former low BW newborns in later life. Hence, the aim of this study was to analyze the long-term effect of low BW on corneal aberrations in adulthood.MethodsIn the German population-based Gutenberg Health Study (GHS) participants (age: 40–80 years) were examined with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). The relationship between self-reported BW and the different types of corneal aberrations was analyzed using linear regression analysis as uni- and multivariable analysis with adjustment for potential confounders. The main outcome measures were corneal aberrations defined as astigmatism (Z2−2; Z22), coma (Z3−1; Z31), trefoil (Z3−3; Z33), spherical aberration (Z40) and root-mean square of higher order aberrations (HOA; 3rd up to 8th order; aperture size: 6 mm).ResultsOverall, 5,628 participants were included in this analysis (3,004 women, aged 56.0 +/- 10.3 years). In a multivariable analysis lower BW was associated with decreased horizontal trefoil (B = 0.004 [0.001; 0.006] µm/500 g; p=.008); higher spherical aberrations (B=-0.006 [-0.008;-0.003] µm/500 g; p<.001), higher RMS (B=-0.028 [-0.042;-0.014] µm/500 g; p<.001), increased HOA (B=-0.007 [-0.010;-0.003] µm/500 g; p<.001) and increased LOA (B=-0.027 [-0.041;-0.013] µm/500 g; p<.001). No association was observed between birth weight and the other types of corneal aberrations in multivariable model.ConclusionOur results indicate an association between BW and spherical aberration in adults aged 40 to 80 years. This indicates that low BW may have an association with an altered corneal shape development which may affect optical image quality and, hence, visual function. (AU)

Depressive symptoms predict the incidence of common chronic diseases in women and men in a representative community sample.

BACKGROUND: Depression, the most frequent and harmful mental disorder, has been associated with specific somatic diseases as the leading cause of death. The purposes of this prospective study were to predict incident chronic diseases based on baseline depressive symptoms and to test sex-dependent effects. METHODS: In a representative German community sample of over 12 000 participants, baseline depressive symptoms (assessed using the Patient Health Questionnaire-9) were tested as a predictor of new onset of cardiovascular disease (CVD), chronic obstructive lung disease, diabetes, cancer, and migraine at 5-year follow-up. To study disease incidence, we created subsamples for each chronic disease by excluding participants who already had the respective disease at baseline. Potential confounders were included in logistic regression models and sex-specific analyses were performed. RESULTS: Controlling for demographic characteristics and loneliness, in men and women, baseline depressive symptoms were predictive of CVD, chronic obstructive lung disease, diabetes, and migraine, but not of cancer. When we additionally adjusted for metabolic and lifestyle risk factors, there was an 8% increase of chronic obstructive lung disease and migraine per point of depressive symptoms. There was a trend for CVD (4%; p = 0.053). Sex-sensitive analyses revealed trends for the relevance of depressive symptoms for CVD in men (p = 0.065), and for diabetes in women (p = 0.077). CONCLUSIONS: These findings underscore the need to implement screening for depression in the treatment of major somatic illnesses. At the same time, depressed patients should be screened for metabolic and lifestyle risk factors and for somatic diseases and offered lifestyle interventions.

Association of birth weight with corneal aberrations in adulthood - Results from a population-based study.

PURPOSE: Low birth weight (BW) is associated with increased corneal aberrations in childhood and alterations of corneal geometry in adulthood. Increased corneal aberrations may be a factor contributing to decreased visual function in former low BW newborns in later life. Hence, the aim of this study was to analyze the long-term effect of low BW on corneal aberrations in adulthood. METHODS: In the German population-based Gutenberg Health Study (GHS) participants (age: 40-80 years) were examined with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). The relationship between self-reported BW and the different types of corneal aberrations was analyzed using linear regression analysis as uni- and multivariable analysis with adjustment for potential confounders. The main outcome measures were corneal aberrations defined as astigmatism (Z2-2; Z22), coma (Z3-1; Z31), trefoil (Z3-3; Z33), spherical aberration (Z40) and root-mean square of higher order aberrations (HOA; 3rd up to 8th order; aperture size: 6 mm). RESULTS: Overall, 5,628 participants were included in this analysis (3,004 women, aged 56.0 +/- 10.3 years). In a multivariable analysis lower BW was associated with decreased horizontal trefoil (B = 0.004 [0.001; 0.006] µm/500 g; p=.008); higher spherical aberrations (B=-0.006 [-0.008;-0.003] µm/500 g; p<.001), higher RMS (B=-0.028 [-0.042;-0.014] µm/500 g; p<.001), increased HOA (B=-0.007 [-0.010;-0.003] µm/500 g; p<.001) and increased LOA (B=-0.027 [-0.041;-0.013] µm/500 g; p<.001). No association was observed between birth weight and the other types of corneal aberrations in multivariable model. CONCLUSION: Our results indicate an association between BW and spherical aberration in adults aged 40 to 80 years. This indicates that low BW may have an association with an altered corneal shape development which may affect optical image quality and, hence, visual function.

Five-year change in refractive error and its risk factors: results from the Gutenberg Health Study.

BACKGROUND/AIMS: To examine the 5-year change in refractive error in phakic eyes and its risk factors in the general population. METHODS: The Gutenberg Health Study (GHS) is a population-based cohort study including 15 010 participants from Germany aged 35-74 years at baseline examination (2007-2012). After 5 years, a follow-up examination was carried out (83% participation). 5-year change of spherical equivalent (SE) was computed as difference between follow-up and baseline objective refraction. Linear and logistic regression analysis were conducted analysing potential risk factors. Only phakic eyes at follow-up examination were included. RESULTS: Right eyes of 10 175 subjects were included. An age-related shift of refractive error was identified, namely -0.12 D for age 35-44 years, 0.25 D for age 45-54 years, 0.25 D for age 55-64 years and 0.12 D for age 65-74 years during the 5-year follow-up. Smokers had a hyperopic shift (OR=1.31; p<0.001), while baseline SE (OR=0.89 per dioptre; p<0.001) and female sex (OR=1.49; p<0.001) were linked with a myopic shift. Education, occupation and other cardiovascular parameters were not associated with change in refractive error. CONCLUSIONS: The GHS demonstrates a parabolic shift in refractive error with a myopic shift at age 35-44 years, followed by a hyperopic shift at age 45-64 years which decreases at higher age. Smoking is associated with a hyperopic shift whereas female sex and myopic baseline SE is associated with a myopic shift. Educational level and occupation were not linked to a change in refractive error at age 35-74 years.

The Prevalence of Hearing Loss and Provision With Hearing Aids in the Gutenberg Health Study.

BACKGROUND: Hearing is a basic ability that is needed for participation in daily life. Hearing loss often greatly reduces a person's quality of life. Nevertheless, epidemiological data on the prevalence of hearing disorders in Germany are sparse. This study investigated the prevalence of hearing disorders and the actual provision with hearing aids. METHODS: The Gutenberg Health Study (GHS) is a representative cohort study carried out at the Department of Medicine of Mainz University to investigate the health of the population of the city of Mainz and the neighboring Mainz‒Bingen district. The GHS participants underwent pure-tone audiometry of each ear independently. RESULTS: Tone audiometry data from a total of 5024 participants were evaluated. The prevalence of hearing loss-regardless of severity-in at least one ear was 40.6% in this study population. The hearing loss was mild in 22.5% of the participants, moderate in 8.3%. Some 2.8% had severe hearing loss. In this group, the women had better hearing than the men (by a mean 4.3 dB). The prevalence of hearing disorders rose with increasing age. The minimum tone audiometry conditions for bilateral hearing aid provision-as defined in the relevant German guideline-were met in 47.7% of the participants. Only 7.7% of the participants already had hearing aids for both ears. The discrepancy between the prevalence of hearing loss and the indication for provision with hearing aids arises from differences in how hearing loss was ascertained and the indications set. CONCLUSION: The prevalence of hearing loss was high, at 40.6%. Regular hearing tests should be recommended for the general German population, starting at no later than 60 years of age.

Subtype-specific plasma signatures of platelet-related protein releasate in acute pulmonary embolism.

INTRODUCTION: There is evidence that plasma protein profiles differ in the two subtypes of pulmonary embolism (PE), isolated PE (iPE) and deep vein thrombosis (DVT)-associated PE (DVT-PE), in the acute phase. The aim of this study was to determine specific plasma signatures for proteins related to platelets in acute iPE and DVT-PE compared to isolated DVT (iDVT). METHODS: Within the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism (GMP-VTE) Project, a multicenter prospective cohort study of 693 confirmed VTE cases, a highly sensitive targeted proteomics approach based on dual-antibody proximity extension assay was applied. LASSO-regularized logistic regression analysis selected 33 and 30 of 135 platelet-related candidate proteins in iPE and DVT-PE vs. iDVT, respectively. RESULTS: All regulated proteins were well associated with six prominently released platelet proteins and the majority showed specificity for iPE and DVT-PE compared to iDVT. While iPE-specific proteins were assigned to be predominantly released via shedding mechanisms and extracellular vesicles, granule secretion was identified as a major release mechanism assigned to DVT-associated PE-specific proteins. Network analysis demonstrated three interconnected clusters of specifically regulated proteins in iPE linked to immunoreceptor signaling, pathogen clearance and chemotaxis, whereas for DVT-associated PE one cluster linked to tissue remodeling and leukocyte trafficking. Machine learning-based analysis reveals specific plasma signatures and differential release mechanisms of proteins related to platelets in acute iPE and DVT-associated PE. CONCLUSION: These data suggest that the platelet protein releasate contributes to the differential regulation of plasma proteins in acute PE compared to iDVT, which may be associated with different platelet activation patterns.

Can peer mentoring improve online teaching effectiveness? An RCT during the COVID-19 pandemic.

Online delivery of higher education has taken center stage but is fraught with issues of student self-organization. We conducted an RCT to study the effects of remote peer mentoring at a German university that switched to online teaching due to the COVID-19 pandemic. Mentors and mentees met one-on-one online and discussed topics like self-organization and study techniques. We find positive impacts on motivation, studying behavior, and exam registrations. The intervention did not shift earned credits on average, but there is evidence for positive effects on the most able students.

Atherosclerosis and Its Impact on the Outcomes of Patients with Deep Venous Thrombosis.

Introduction: Atherosclerosis and pulmonary embolism (PE) affect cardiovascular mortality substantially. We aimed to investigate the impact of atherosclerosis on the outcomes of patients with deep venous thrombosis (DVT) and to identify the differences in DVT patients with and without PE. Methods: Patients with DVT with and without symptomatic atherosclerosis (defined as coronary artery disease, myocardial infarction and/or peripheral artery disease) as well as with and without PE under oral anticoagulation were enrolled during January 2011−April 2013 and compared. The impact of symptomatic atherosclerosis on several outcomes was analyzed. Results: Overall, 509 DVT patients (70.0 [56.0−77.0] years, 51.9% females) were included in this study. Among them, 179 (36.3%) had symptomatic atherosclerosis and 204 (40.1%) a concomitant PE. DVT patients with symptomatic atherosclerosis were older (74.0 [IQR 65.0−80.0] vs. 63.0 [48.0−75.0] years, p < 0.0001), more often male (56.4% vs. 43.9%, p = 0.0087) and had a higher prevalence of classical CVRF and a higher Charlson comorbidity index (7.00 [5.00−8.00] vs. 4.00 [2.00−6.00], p < 0.001). Symptomatic atherosclerosis was associated with increased mortality (HR 1.98 [95%CI 1.12−3.49], p = 0.018) and hospitalizations (HR 1.64 [95%CI 1.21−2.21], p = 0.0012) and primary long-term outcome (HR 1.99 [95%CI 1.31−3.04], p = 0.0013) during the 2 years follow-up-period in DVT patients. DVT patients without PE had diabetes mellitus (28.2% vs. 16.3%, p < 0.01) and symptomatic atherosclerosis (42.9% vs. 26.4%, p < 0.001) more often compared to DVT patients with PE, and symptomatic atherosclerosis was associated with isolated DVT (without PE) (OR 2.01 [95%CI 1.28−3.16], p < 0.01). Conclusions: Atherosclerosis was associated with isolated DVT (without PE) and increased mortality in DVT patients under oral anticoagulation. The profile of CVRF and comorbidities differed between DVT patients with and without a concomitant PE. In the case of DVT or PE, patients should be screened for concomitant atherosclerotic disease. Clinical Trial Registration: at clinicaltrials with Unique identifier NCT01809015.

Intraocular Pressure and Its Relation to Ocular Geometry: Results From the Gutenberg Health Study.

Purpose: The purpose of this study was to investigate the association between intraocular pressure (IOP) and ocular geometry. Methods: The Gutenberg Health Study is a population-based cohort study in Mainz, Germany. Study participants underwent a comprehensive ophthalmologic examination including noncontact tonometry, objective refraction, optical biometry, and Scheimpflug imaging of the anterior segment at the first 5-year follow-up examination (in 2012-2017). Multivariable linear regression analysis was carried out to determine associations of IOP and geometric parameter of the human phakic eye, namely central corneal thickness (CCT), corneal curvature, anterior chamber depth (ACD), lens thickness, and axial length. In addition, the relationship of IOP and the anterior chamber angle (ACA) width was analyzed. Results: There were 6640 participants with phakia (age 57.3 ± 10.2 years, 49.1% women) that were included in this cross-sectional analysis. Mean IOP was 14.8 ± 2.9 mm Hg in the right eyes and 14.9 ± 2.9 mm Hg in the left eyes. IOP increased with higher CCT, greater posterior segment length, higher age (all P < 0.001), thicker lens (P = 0.003), and female sex (P = 0.05), whereas the ACD was not associated with higher IOP. The IOP increased with a narrower ACA in univariable analysis (P < 0.001), but not in adjusted analysis in subjects with an open angle. Conclusions: IOP values are related to ocular geometry, as shown in this population-based study on Caucasian subjects. Thus, knowledge of the architecture of the eye is an important factor when measuring IOP. Longitudinal evaluation will analyze whether some of these parameters are also risk factors for the development of glaucoma.

Peripheral corneal thickness and associated factors - results from the population-based German Gutenberg Health Study.

PURPOSE: Changes in peripheral corneal thickness are described in various corneal diseases such as corneal ectasia. However, few data exist describing the increase in corneal thickness from central to peripheral and reporting the normal distribution of corneal thickness in rings around the corneal centre. The aim of this study was to report these cornea characteristics and investigate associated factors in a population-based setting. METHODS: The Gutenberg Health Study is a prospective, population-based study examining participants in a 5-year follow-up (age range 40-80 years) using Scheimpflug imaging. Corneal thickness was assessed in each participant at the apex, as well as in the corneal centre (thinnest corneal thickness) and in rings with 2, 4, 6, 8 and 10 mm diameter around the corneal centre, and the increase in corneal thickness towards the periphery. The relationship between corneal thickness at these locations and possible associated factors was determined using linear regression models. For this purpose, general and ocular parameters were included. RESULTS: A total of 9729 participants were included in the present analysis (4874 women, age 59.2 ± 10.8 years). Multivariable analysis showed a correlation between the increase in corneal thickness in the circles from 0 to 10 mm (diameter) and the following parameters: age (B = -0.24 µm per year, p < 0.001); body height (B = -0.04 µm, p = 0.005); smoking (B = -0.72 µm, p < 0.001); spherical equivalent (B = -0.70 µm per dioptre, p < 0.001); white-to-white distance (B = -0.75 µm/mm, p < 0.001); mean corneal radius (B = -3.61 µm/mm, p < 0.001); intraocular pressure (B = -0.12 µm/mmHg, p < 0.001); glaucoma (B = -1.94 µm, p < 0.001); and pseudophakia (B = 0.89 µm, p < 0.001). CONCLUSION: The results of the present study suggest that several general and ocular parameters are associated with peripheral corneal thickness. In the context of diagnosing glaucoma, a smaller increase in corneal thickness towards the periphery might be a new additional marker.

Variation of platelet function in clinical phenotypes of acute venous thromboembolism - Results from the GMP-VTE project.

BACKGROUND: The role of platelets in the pathogenesis of venous thromboembolism (VTE) is receiving increasing attention; however, limited information is available on platelet function in the acute phase of the disease. OBJECTIVE: To characterize platelet function according to VTE phenotypes. PATIENTS/METHODS: In total, 154 subjects (isolated pulmonary embolism [iPE], n = 28; isolated deep vein thrombosis [iDVT], n = 35; DVT+PE, n = 91) were included. In this study platelet function analyzer (PFA)-200, light transmission aggregometry (LTA), thrombin generation (TG) in presence (PRP) and absence (PFP) of platelets and platelet flow cytometry were investigated. LASSO regression was used to select clinical and platelet biomarkers that distinguish between VTE phenotypes. RESULTS: PFA-200 results did not differ between VTE phenotypes. LTA from DVT+PE subjects showed lowest maximum aggregation after epinephrine and adenosine diphosphate compared to iPE and iDVT. Lower % of PAC-1-positive platelets after in-vitro trigger were present in DVT+PE and iPE compared to iDVT. TG in PRP had lower peak height and velocity in DVT+PE and iPE against iDVT. The results of LASSO regression for the distinction between DVT+PE vs iDVT identified 18 variables (AUC =0.93) of which 72% were platelet biomarkers. For distinction between iPE and iDVT, 10 variables were selected (AUC = 0.96) of which 50% were platelet-related. Obesity was the only variable weakly discriminating between DVT+PE vs iPE (AUC = 0.66). CONCLUSION: This explorative study suggests an important distinction between PE-related phenotypes and iDVT when considering clinical and platelet function data. Lower platelet-dependent TG along with reduced platelet reactivity suggest higher platelet degranulation in PE-dependent phenotypes compared to iDVT.

Hearing Loss and Its Burden of Disease in a Large German Cohort-Hearing Loss in Germany.

OBJECTIVES/HYPOTHESIS: Hearing loss is the most common sensory impairment worldwide. It restricts patients in many aspects of their daily lives and can lead to social exclusion. Understanding this burden is a mandatory requirement for the care of those affected. Therefore, the aim of this study was to estimate the burden of hearing loss in a large German cohort. STUDY DESIGN: Cohort study. METHODS: The Gutenberg Health Study is designed as a single-center, prospective, and observational cohort study and representative for the city of Mainz, Germany, with its district. Participants were interviewed concerning common otologic symptoms and tested by pure-tone audiometry. The primary outcome was hearing impairment stratified by age and sex. The prevalence of tinnitus was estimated for a subcohort to calculate disability-adjusted life years (DALYs). All results were weighted by the European Standard Population (ESP) 2013. RESULTS: A total of 5,024 participants (mean age: 61.2 years, 2,591 men and 2,433 women) were included in the study. Hearing impairment showed the following prevalence: 28.2% (95% confidence interval [CI], 26.9%-29.4%) mild impairment, 10.1% (95% CI, 9.3%-11.0%) moderate impairment, 2.3% (95% CI, 1.9%-2.7%) moderately severe impairment, 0.2% (95% CI, 0.1%-0.4%) severe impairment, 0% (95% CI, 0.0%-0.1%) profound impairment, and 0.1% (95% CI, 0.0%-0.2%) complete impairment. Weighted for the ESP 2013 (all ages), hearing impairment across all levels (with/without tinnitus) causes a total of 2,118.97 DALYs per 100,000. CONCLUSION: With 40.9% affected, the hearing loss represents a relevant burden of the German population. Understanding this will provide the basis for future guidelines on how to care for these patients. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:1843-1849, 2022.

Association of Birth Weight With Foveolar Thickness in Adulthood: Results From a Population-Based Study.

Purpose: Low birth weight (BW) is associated with alterations of foveal shape development in childhood-leading to an increased retinal thickness of the fovea. The aim of the present study was to assess whether BW has a long-term effect on foveal retinal thickness (RT) and is still present in adulthood. Methods: In the German population-based Gutenberg Health Study (GHS), participants were examined with spectral-domain optical coherence tomography. The association between self-reported BW and RT in the foveolar and perifoveal locations was assessed. Multivariable linear regression analyses with adjustment for potential confounders and grading of foveal hypoplasia were performed. Results: Overall, RT measurements and self-reported BW were available for 2,539 participants (1300 female, mean age 54.5 ± 9.7 years). The absolute foveolar RT was 239.6 ± 25.8 µm, 232.2 ± 20.1 µm and 234.8 ± 21.0 µm, respectively, in the low (<2500 g), normal (2500-4000 g) and high (>4000 g) BW groups (P < 0.001). After adjustment for confounders, an association was observed between lower BW and increased foveolar thickness (B = -0.35 [95% confidence interval {CI}: -0.49; -0.20] µm/100 g; P < 0.001), whereas only a weak association with RT was observed with the nasal (P = 0.010), temporal (P = 0.011), and inferior (P = 0.021) quadrants in the 1 mm distance, with no association in the 2 mm distance to the fovea. Foveal hypoplasia grade 1 was more frequent in the low BW group (6.8%) compared to the normal (0.9%) and high BW group (1.2%). Conclusions: This study provides evidence of an association between lower BW and increased foveolar thickness and foveal hypoplasia, indicating that prenatal growth may affect macular morphology, which in turn may persist until adulthood and predispose to retinal disease later in life.

Association of Birth Weight with Central and Peripheral Corneal Thickness in Adulthood-Results from the Population-Based German Gutenberg Health Study.

Purpose: Low birth weight (BW) is associated with altered ocular geometry such as a steeper corneal shape in adulthood. However, it is unclear whether low birth weight affects corneal thickness development in the center or periphery in adulthood which may contribute to ocular disease. The purpose of this study was to investigate corneal thickness in former low birth weight individuals in adulthood. Methods: The German Gutenberg Health Study is a prospective, population-based study in which every participant (age range 40-80 years) was measured with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). BW was collected by self-reports. The relationship between birth weight and corneal thickness at different locations were assessed. Linear regression models were carried out including uni- and multivariable analyses with adjustment for age, sex, mean corneal radius, and white-to-white distance. Main outcome measures were corneal thickness at the apex, at the pupil center, and at the corneal periphery. Results: Overall, 5657 participants were successfully measured (3019 females, aged 56.0 ± 10.3 years). In multivariable analyses a lower BW was associated with a thinner corneal thickness at the apex (B = 1.71 µm/500 g, p < 0.001) and at the pupil (B = 1.69 µm/500 g, p < 0.001). These effects diminished towards the corneal periphery resulting in no differences in the perilimbal regions. Conclusion: The present study provides evidence that lower birth weight goes along with corneal thickness alterations even into adult ages of 40 to 80 years. Thinner measurements of the cornea were particularly found in the corneal center and diminished in the periphery. This indicates that there may be fetal origins affecting corneal thickness development particularly in the corneal center.

Homoarginine and methylarginines independently predict long-term outcome in patients presenting with suspicion of venous thromboembolism.

Endogenous arginine derivatives homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethyarginine (SDMA) are independent mortality predictors in atherosclerotic cardiovascular disease (CVD). Our study reports the first analysis, whether homoarginine, ADMA and SDMA predict venous thromboembolism (VTE) recurrence and overall mortality in patients with suspected acute VTE. We assessed serum levels of homoarginine, ADMA and SDMA by LC-MS/MS in 865 individuals from a prospective consecutive cohort of patients with clinical suspicion of VTE. The median follow-up time for mortality was 1196 days. VTE was confirmed by imaging in 418 patients and excluded in 447 patients. Low levels of homoarginine and high levels of ADMA or SDMA independently predicted all-cause mortality after adjustment for sex, age, oral anticoagulants, body mass index, arterial hypertension, diabetes mellitus, smoking, dyslipidemia, chronic heart failure, history of stroke, creatinine and cancer both in patients with VTE and without VTE. Interestingly, none of those parameters was predictive for VTE recurrence. We provide the first report that low circulating levels of homoarginine and high circulating levels of ADMA and SDMA independently predict all-cause mortality in patients with suspected VTE. These parameters might serve as markers of "frailty" and should be considered for future risk stratification approaches in this clinical population. Taking into account that homoarginine supplementation is protective in animal models of CVD and safe in healthy human volunteers, our study provides the basis for future homoarginine supplementation studies in patients with suspected VTE to investigate possible direct protective effects of homoarginine in this population.

Inflammation predicts new onset of depression in men, but not in women within a prospective, representative community cohort.

Depression has been associated with increased inflammation. However, only few large-scale, prospective studies have evaluated whether inflammation leads to new cases of depression and whether this association can be found in men and women. Longitudinal data of N = 10,357 adult participants with no evidence of depression at baseline (based on Patient Health Questionnaire (PHQ-9), lifetime diagnoses, and current antidepressant medication) were evaluated for depression 5 years later. Multivariate logistic regression models were used to predict the onset of depression based on C-reactive protein (CRP) and white blood cell count (WBC). We used interaction terms and separate analyses in men and women to investigate gender-dependent associations. Based on both markers, inflammation was predictive of new cases of depression 5 years later, even when adjusting for sociodemographic, physical health, health behavior variables, and baseline depression symptoms. As established by interaction terms and separate analyses, inflammatory markers were predictive of depression in men, but not in women. Additional predictors of new onset of depression were younger age, loneliness, smoking (only in men), cancer and less alcohol consumption (only in women). The study indicates gender differences in the etiology of depressive disorders within the community, with a greater role of physical factors in men.

Cost saving analysis of specialized, eHealth-based management of patients receiving oral anticoagulation therapy: Results from the thrombEVAL study.

To evaluate the cost-saving of a specialized, eHealth-based management service (CS) in comparison to regular medical care (RMC) for the management of patients receiving oral anticoagulation (OAC) therapy. Costs of hospitalization were derived via diagnosis-related groups which comprise diagnoses (ICD-10) and operation and procedure classification system (OPS), which resulted in OAC-related (i.e. bleeding/ thromboembolic events) and non-OAC-related costs for both cohorts. Cost for anticoagulation management comprised INR-testing, personnel, and technical support. In total, 705 patients were managed by CS and 1490 patients received RMC. The number of hospital stays was significantly lower in the CS cohort compared to RMC (CS: 23.4/100 py; RMC: 68.7/100 py); with the most pronounced difference in OAC-related admissions (CS: 2.8/100 py; RMC: 13.3/100 py). Total costs for anticoagulation management amounted to 101 EUR/py in RMC and 311 EUR/py in CS, whereas hospitalization costs were 3261 [IQR 2857-3689] EUR/py in RMC and 683 [504-874] EUR/py in CS. This resulted in an overall cost saving 2368 EUR/py favoring the CS. The lower frequency of adverse events in anticoagulated patients managed by the telemedicine-based CS compared to RMC translated into a substantial cost-saving, despite higher costs for the specialized management of patients.Trial registration: ClinicalTrials.gov, unique identifier NCT01809015, March 8, 2013.

The relevance of depressive symptoms for the outcome of patients receiving vitamin K antagonists: results from the thrombEVAL cohort study.

AIMS: Although depressive symptoms are highly prevalent in patients receiving oral anticoagulation (OAC), the relevance of depression for the outcome of anticoagulated individuals is unknown. METHODS AND RESULTS: We analysed data from the multicentre cohort study thrombEVAL (NCT01809015) investigating the efficacy of OAC with vitamin K antagonists. There was an independent study monitoring, and an independent review panel assessed the endpoints. Out of n = 1558 participants, information about depressive symptoms, as measured by the two-item screener of the patient health questionnaire (PHQ-2), was available in n = 1405 individuals. The mean follow-up period was 28.04 months, with a standard deviation of 11.52 months. In multivariable Cox regression analysis, baseline PHQ-2 sum score was a strong and robust predictor of clinically relevant bleeding [hazard ratio (HR) 1.13, 95% confidence interval 1.03-1.24; P = 0.011] and all-cause mortality (HR 1.18, 1.08-1.28; P = 0.001) independent of age, sex, high school graduation, partnership, clinical profile, intake of serotonin reuptake inhibitors, and quality of OAC therapy. Individuals with clinically significant depressive symptoms (PHQ-2 ≥ 3) had a 57% increased risk for clinically relevant bleeding (fully adjusted HR 1.57, 1.08-2.28) and 54% greater risk for death (fully adjusted HR 1.54, 1.09-2.17). There was no association of depressive symptoms with thromboembolic events. For hospitalization, individuals with depressive symptoms (PHQ-2 ≥ 3) did not experience an elevated risk in the fully adjusted model (HR 1.08, 0.86-1.35; P = 0.52). CONCLUSION: Assessment of depression by the PHQ-2 provided independent long-term prognostic information beyond common biomedical risk factors. These findings highlight the need for targeting depressive symptoms in the management of patients receiving OAC therapy.