Austrian Cohort Research Articles

Postoperative Opioid Administration and Prescription Practices Following Hysterectomy in Two Tertiary Care Centres: A Comparative Cohort Study between Canada and Austria.

Background: In light of the opioid epidemic, opioid-prescribing modalities for postoperative pain management have been discussed controversially and show a wide variation across geographic regions. The aim of this study was to compare postoperative pain treatment regimes. Methods: We performed a matched cohort study of women undergoing hysterectomy in Austria (n = 200) and Canada (n = 200). We aimed to compare perioperative opioid medications, converted to morphine equivalent dose (MED) and doses of non-opioid analgesic (NOA) within the first 24 h after hysterectomy, and opioid prescriptions at discharge between the two cohorts. Results: The total MED received intraoperatively, in the post-anaesthesia care unit (PACU) and during the first 24 h after surgery, was similar in both cohorts (145.59 vs. 137.87; p = 0.17). Women in the Austrian cohort received a higher MED intraoperatively compared to the Canadian cohort (117.24 vs. 79.62; p < 0.001) but a lower MED in the PACU (25.96 vs. 30.42; p = 0.04). The primary outcome, MED within 24 h in the postoperative ward, was markedly lower in the Austrian compared to the Canadian cohort (2.36 vs. 27.98; p < 0.001). In a regression analysis, only the variables "Country" and "mode of hysterectomy" affected this outcome. A total of 98.5% in the Canadian cohort were given an opioid prescription at discharge vs. 0% in the Austrian cohort. Conclusions: Our analysis reveals marked differences between Austria and Canada regarding pain management practices following elective hysterectomy; the significantly higher intraoperative and significantly lower postoperative MED administration in the Austrian cohort compared to the Canadian cohort seems to be significantly affected by each country's cultural attitudes towards pain management; this may have significant public health consequences and warrants further research.

Prevalence of osteoporosis in the adult population and its association with body composition: Results from the austrian lead cohort

Prevalence of osteoporosis in the adult population and its association with body composition: Results from the austrian lead cohort

Oscillometry Reference Values for Children and Adolescents

BackgroundOscillometry devices allow quantification of respiratory function at tidal breathing but device-specific reference equations are scarce: the present study aims to create sex-specific oscillometric reference values for children and adolescents using the Resmon PRO FULL device.MethodsHealthy participants (N=981) aged 6 to 17 years of the Austrian LEAD general population cohort were included. Subjects had normal weight (BMI≤99th percentile) and normal lung volumes (total lung capacity (TLC)≥lower limit of normal). Oscillometry data were collected using a single frequency mode of 8 Hz. Sex-specific prediction equations were developed for total (tot), inspiratory (insp) and expiratory (exp) resistance (R) and reactance (X) as well as for the modulus of impedance (Z) value using the LMS (lambda, mu, sigma) method. Height was used as a single covariate.ResultsReference equations for all oscillometry parameters were created for Caucasian children aged 6 to 17 years with a height span from 101 to 183 cm and a lung volume span from 1.7 L to 8.8 L TLC. R and Z values progressively decrease and X values increase with increasing height. Oscillometry parametersversuslung volume curves differ from thoseversusheight curves. Stratified for lung size, no sex differences are found for oscillometry parameters.ConclusionOur study provides reference values for oscillometry parameters in children and adolescents using strictly defined criteria for weight and lung volumes. No sex related differences in oscillometry parameters corrected for height or lung size are found.

Denial of reproductive potential: a predictor of unperceived pregnancy in an Austrian neonaticide sample.

This study aims to describe the phenomenon of unperceived pregnancy followed by neonaticide with a focus on the lack of awareness of reproductive potential in an Austrian sample. An explorative comparative study of neonaticide cases with single and repeat perpetrators was conducted using nationwide register-based data from 1995 to 2017. A total number of 55 cases out of 66 were included in the analysis. A standardized coding sheet was used and calculations were performed. 48 women gave birth to 101 children, of which 55 were killed, 23 children lived out of home care and 23 lived with the perpetrator We found a higher fertility rate in both neonaticide perpetrators in the single (1,9) and the repeat group (4,25) in comparison to the general population (1,4). The use of contraception was only 31% among neonaticide perpetrators, deviating substantially from the general Austrian population age group (16-29yrs) which used contraception in 91%. The neonaticide perpetrators used an effective contraception method (pearl-index < 4) in only 2%, whereas 20% of the general population did so. The number of unperceived pregnancies was high in both groups (50/55) 91%. Future case reports and forensic evaluations should take reproductive behavior into account, as it may offer valuable insights into the events leading up to neonaticide. Our findings suggest that denial of reproductive potential often precedes unperceived pregnancies. In the Austrian cohort, women who experienced unperceived pregnancies resulting in unassisted births and subsequent neonaticide showed a low prevalence of contraceptive use. This is particularly noteworthy given that the primary motive for neonaticide is unwanted pregnancy.

Safety First or Saving Lives? How Medical Responders Would Decide when Facing an Active Violent Incident. Results from an Explorative Cross-National Survey

Abstract In recent years, public authorities and rescue services have been discussing how Medical First Responders (MFRs) should behave in an Active Violent Incident (AVI) where it is necessary to weigh up self-protection and the rescuing of others. The aim of this exploratory study is to generate a preliminary picture of how European MFRs position themselves on this and related questions. With the help of a network of experts, an AVI scenario and accompanying questionnaire were developed and pretested. A refined version was then distributed among MFRs in eight European countries and Israel. We performed descriptive statistics and tested for significant differences among the participating countries. 1164 MFRs completed the survey. In the absence of police protection, a majority of respondents opted against providing immediate casualty care (56.6 %). Under certain circumstances, however, the rest decided in favour. More than 65.5 % did not fear disciplinary or legal consequences for not providing assistance immediately. Even with police protection, one in ten respondents would still not enter a “yellow zone”, one in four would leave this to Emergency Medical Services (EMS) units specifically trained for such operations. While there are very few strong contrasts between MFRs with different work experience, roles (supervisor/instructor) or additional qualifications (e.g., firefighting, military service), there are significant differences between MFRs from participating countries. Most notably, (1) only Norwegian participants identified, on average, a clear paradigm shift from “safety first” to “controlled risk taking”; (2) while 69.8 % of the Austrian cohort were unwilling to enter without being escorted by the police, among Norwegians MFRs the figure was 42.7 %; (3) the question whether “weapons” are “useful” equipment in such a scenario is particularly divisive (ranging from 14.3 % of German to 58.9 % of Israeli respondents). Although most of the questions were answered in the same way by a large majority, significant differences can be observed, especially between countries. We offer various explanations for these and discuss whether MFRs can actually remain passive given the situational normative forces inherent to an AVI.

#506 Long-term exposure to air pollution and CKD-associated mortality: results from the pooled cohort of the European multicentre ELAPSE-study

Abstract Background and Aims Air pollution has been shown to be associated with cause-specific mortality. However, mortality due to chronic kidney disease (CKD) is understudied in this context, with no European data available so far. We investigated the relation between long-term exposure to air pollution and CKD-associated mortality in the Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE). Method Data of five population-based cohorts from four European countries from the pooled ELAPSE cohort were linked to data from local mortality registries. CKD-associated mortality was defined using ICD10 codes N18-N19 or corresponding ICD9 codes. Mean annual exposure at home address was determined with Europe-wide hybrid land use regression models for nitrogen dioxide (NO2), black carbon (BC), ozone (O3), particulate matter ≤2.5 µm (PM2.5) and several elemental constituents of PM2.5 with a spatial resolution of 100 m x 100 m. Cox regression models were adjusted for age (time-axis), cohort and sex (both as strata), calendar year of recruitment, smoking status, marital status, employment status and neighborhood mean income. Results Over a mean follow-up time of 20.4 years, 313 of 289,564 persons died from CKD. Associations were observed for all pollutants, positive for PM2.5 (hazard ratio (HR) with 95% confidence interval (CI) of 1.31 (1.03-1.66) per 5 µg/m3 increase), BC (1.26 (1.03-1.53) per 0.5 × 10− 5/m), NO2 (1.13 (0.93-1.38) per 10 µg/m3) and negative for O3 (0.71 (0.54-0.93) per 10 µg/m3). Results were robust when additionally adjusting for smoking intensity and duration, BMI, education or residential greenness, but susceptible to cohort selection. Findings are mainly based on the large Austrian cohort, that contributed 226 cases. Among the elemental constituents, Cu, Fe, K, Ni, S and Zn, representing different PM2.5 sources including traffic, industry, biomass and oil burning and long-range transport, were associated with CKD-related mortality. Conclusion In conclusion, our results suggest a possible association between air pollution from different sources with CKD-related mortality. Our results indicate that measures to improve air quality and decrease air pollution might also be beneficial from a renal perspective.

Associations between change in BMI and the risk of hypertension and dyslipidaemia in people receiving integrase strand-transfer inhibitors, tenofovir alafenamide, or both compared with other contemporary antiretroviral regimens: a multicentre, prospective observational study from the RESPOND consortium cohorts

Integrase strand-transfer inhibitors (INSTIs) and tenofovir alafenamide have been associated with weight gain in several clinical trials and observational cohorts. However, whether weight gain associated with INSTIs and tenofovir alafenamide confers a higher risk of weight-related clinical events is unclear. We aimed to assess whether changes in BMI differentially increase hypertension or dyslipidaemia risk in people with HIV receiving INSTIs, tenofovir alafenamide, or both versus other contemporary regimens. This multicentre, prospective observational study analysed prospective data from RESPOND, an international consortium of HIV cohorts for which recruitment began in 2017 and is still ongoing from HIV clinics and hospitals in 37 European countries and Australia. Participants were eligible if they were aged 18 years or older, receiving INSTI-containing antiretroviral therapy (ART) regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. We excluded participants without baseline CD4 or HIV RNA results and those receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues. They were followed up from baseline until the earliest hypertension or dyslipidaemia event, their last visit, or Dec 31, 2021, whichever was earlier. The primary outcomes were incidence of hypertension and dyslipidaemia, for which we used multivariable Poisson regression adjusted for time-updated BMI to determine unadjusted and adjusted incidence rate ratios (IRRs) of hypertension and dyslipidaemia in people receiving INSTIs, tenofovir alafenamide, or both, and tested for interaction between time-updated ART regimen and BMI. Of the 35 941 RESPOND participants, 9704 (7327 [75·5 %] male and 2377 [24·5%] female) were included in the hypertension analysis and 5231 (3796 [72·6%] male and 1435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54-1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30-1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31-1·68) or without (1·25, 1·13-1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10-1·40) and tenofovir alafenamide alone (1·22, 1·03-1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07-1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96-1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (pinteraction=0·46 for hypertension; pinteraction=0·31 for dyslipidaemia). Although residual confounding cannot be entirely excluded, the use of INSTIs was associated with incident hypertension, and the use of tenofovir alafenamide was associated with dyslipidaemia, with the latter association partly mediated by weight gain. These results reiterate the need for hypertension and dyslipidaemia screening in people with HIV. The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.

Diagnosis and prognosis of abnormal cardiac scintigraphy uptake suggestive of cardiac amyloidosis using artificial intelligence: a retrospective, international, multicentre, cross-tracer development and validation study

The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners. In this retrospective, international, multicentre, cross-tracer development and validation study, 16 241 patients with 19 401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts. The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001). AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways. Pfizer.

Outcome in very preterm infants: a population-based study from a regional center in Austria.

To determine short-term morbidity and mortality rates in the first state-wide Austrian neonatal cohort and comparison to (inter)national data. Observational, population-based cohort study, analyzing data of preterm infants (<32 + 0 weeks of gestation) born between 2007 and 2020 (n = 501) in an Austrian state who were admitted to the neonatal intensive care unit. Outcome criteria were mortality, neonatal morbidities: bronchopulmonary dysplasia (BPD), severe necrotizing enterocolitis (NEC), severe intraventricular hemorrhage (IVH grades III-IV), severe retinopathy of prematurity (ROP grades III-V) and survival-free of major complications. Overall survival rate was 95%, survival free of major complications was 79%. Prevalence for BPD was 11.2%, surgical NEC 4.0%, severe IVH 4.6%, and for severe ROP 2.6%, respectively. In the extremely low gestational age neonates (ELGAN) born <28 weeks of gestation (n = 158), survival was 88% and survival free of major complications 58.8%. Over time, mortality decreased significantly, predominantly driven by the improvement of infants born <28 week of gestation and survival free of major complications improved. This study demonstrates a very low mortality rate that decreases over time. Short-term morbidities and survival free of major complications do not differ from (inter)national data in a similar group of very preterm infants. Standard operating procedures, simulation trainings and accordance to international trials may improve patient care and surpass center case loads.

The Impact of Educational Status on the Occurrence of Colonic Diverticula: Insights from an Austrian Cohort Study

Objective: Education often reflects socioeconomic status. Research indicates that lower socioeconomic status may increase the risk of diverticulosis, and according to data from the USA, diverticular disease is a significant and costly health problem. Our study explores the link between educational level and colonic diverticula occurrence. Subject and Methods: We conducted a cohort study on 5,532 asymptomatic Austrian patients who underwent colonoscopy, categorizing them by education level using the updated Generalized International Standard Classification of Education (GISCED). Logistic regression models, adjusting for age, gender, metabolic syndrome, diet, and activity, were used to determine the association between education and diverticulosis. Results: Overall, 39% of the patients had low educational status, while 53% had medium, and 8% had high educational status. Colon diverticula were less frequent in patients with medium (OR 0.73) and high (aOR 0.62) educational status. Medium educational level remained associated with lower rates of diverticulosis after adjustment for age and sex (aOR 0.85) and further metabolic syndrome, dietary habits, and physical activity (aOR 0.84). In higher education status, this phenomenon was only seen by trend. Conclusion: Low education correlated with higher colon diverticula risk, while medium education showed lower rates even after adjustments. This trend persisted at higher education levels, highlighting the potential for strategies for cost reduction tailored to socioeconomic conditions.

Real world evidence reveals improved survival outcomes in biliary tract cancer through molecular matched targeted treatment

Biliary tract cancers are rare cancers with poor prognosis due to a lack of therapeutic options, especially after the failure of first-line systemic treatment. Targeted treatments for this clinical situation are promising and have entered clinical practice. We aimed to describe the overall survival of matched targeted treatment after first-line treatment in patients with biliary tract cancers in an Austrian real-world multicenter cohort. We performed a multicenter retrospective chart review of patients with biliary tract cancer between September 2015 and January 2022. Data, including comprehensive molecular characteristics—next generation sequencing (NGS) and immunohistochemistry (IHC), clinical history, surgical procedures, ablative treatments, patient history, and systemic chemotherapy, were extracted from the records of the participating institutions. Targeted treatment was matched according to the ESMO scale for the clinical actionability of molecular targets (ESCAT). We identified 159 patients with the available molecular characteristics. A total of 79 patients underwent second-line treatment. Of these, 36 patients received matched targeted treatment beyond the first-line and were compared with 43 patients treated with cytotoxic chemotherapy in terms of efficacy outcomes. For Tier I/II alterations, we observed a progression free survival ratio (PFStargeted/PFSpre-chemotherapy) of 1.86, p = 0.059. The overall survival for patients receiving at least two lines of systemic treatment significantly favored the targeted approach, with an overall survival of 22.3 months (95% CI 14.7–29.3) vs. 17.5 months (95% CI 1.7–19.8; p = 0.048). Our results underscore the value of targeted treatment approaches based on extended molecular characterization of biliary tract cancer to improve clinical outcomes.

Associations between long-term exposure to air pollution, noise, and body composition in the Austrian LEAD cohort

Associations between long-term exposure to air pollution, noise, and body composition in the Austrian LEAD cohort

Prevention of Early Sudden Cardiac Death after Myocardial Infarction Using the Wearable Cardioverter Defibrillator-Results from a Real-World Cohort.

After acute myocardial infarction (AMI), patients are at risk of sudden cardiac death. The VEST trial failed to show a reduction in arrhythmic mortality in AMI patients with an LVEF ≤ 35% prescribed with a WCD, having a lower-than-expected WCD wearing compliance. The aim was to investigate on outcomes of patients in a real-world Austrian cohort with good compliance. A retrospective analysis of all eligible Austrian WCD patients according to the VEST trial inclusion and exclusion criteria between 2010 and 2020 was performed. In total, 105 Austrian patients (64 ± 11 years, 12% female; LVEF 28 ± 6%) received a WCD for a median of 69 (1; 277) days after AMI (wearing duration 23.5 (0; 24) hours/day). Within the first 90 days, 4/105 (3.8%) patients received 9 appropriate shocks (2 (1; 5) shocks). No inappropriate shocks were delivered, and 3/105 (2.9%) patients died during follow-up. Arrhythmic mortality (1.9% Austria vs. 1.6% VEST, p = 0.52), as well as all-cause mortality (2.9% vs. 3.1%, p = 0.42) was comparable in both cohorts. The WCD is a safe treatment option in a highly selected cohort of patients with LVEF ≤ 35% after AMI. However, despite excellent WCD wearing duration in our cohort, the arrhythmic mortality rate was not significantly different.

Simulation of bempedoic acid and ezetimibe in the lipid-lowering treatment pathway in Austria using the contemporary SANTORINI cohort of high and very high risk patients.

The low-density lipoprotein cholesterol goals in the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guidelines necessitate greater use of combination therapies. We describe areal-world cohort of patients in Austria and simulate the addition of oral bempedoic acid and ezetimibe to estimate the proportion of patients reaching goals. Patients at high or very high cardiovascular risk on lipid-lowering treatments (excluding proprotein convertase subtilisin/kexin type9 inhibitors) from the Austrian cohort of the observational SANTORINI study were included using specific criteria. For patients not at their risk-based goals at baseline, addition of ezetimibe (if not already received) and subsequently bempedoic acid was simulated using aMonte Carlo simulation. Acohort of patients (N = 144) with amean low-density lipoprotein cholesterol of 76.4 mg/dL, with 94% (n = 135) on statins and 24% (n = 35) on ezetimibe monotherapy or in combination, were used in the simulation. Only 36% of patients were at goal (n = 52). Sequential simulation of ezetimibe (where applicable) and bempedoic acid increased the proportion of patients at goal to 69% (n = 100), with adecrease in the mean low-density lipoprotein cholesterol from 76.4 mg/dL at baseline to 57.7 mg/dL overall. The SANTORINI real-world data in Austria suggest that aproportion of high and very high-risk patients remain below the guideline-recommended low-density lipoprotein cholesterol goals. Optimising use of oral ezetimibe and bempedoic acid after statins in the lipid-lowering pathway could result in substantially more patients attaining low-density lipoprotein cholesterol goals, likely with additional health benefits.

Differences and Similarities in Perceptions of Recruits, Soldiers, and Veterans in an Austrian Cohort

Differences and Similarities in Perceptions of Recruits, Soldiers, and Veterans in an Austrian Cohort

Exposure to ambient air pollution and elevated blood levels of gamma-glutamyl transferase in a large Austrian cohort

Gamma glutamyl transferase (GGT) is related to oxidative stress and an indicator for liver damage. We investigated the association between air pollution and GGT in a large Austrian cohort (N = 116,109) to better understand how air pollution affects human health.Data come from voluntary prevention visits that were routinely collected within the Vorarlberg Health Monitoring and Prevention Program (VHM&PP). Recruitment was ongoing from 1985 to 2005. Blood was drawn and GGT measured centralized in two laboratories. Land use regression models were applied to estimate individuals' exposure at their home address for particulate matter (PM) with a diameter of <2.5 μm (PM2.5), <10 μm (PM10), fraction between 10 μm and 2.5 μm (PMcoarse), as well as PM2.5 absorbance (PM2.5abs), NO2, NOx and eight components of PM. Linear regression models, adjusting for relevant individual and community-level confounders were calculated.The study population was 56 % female with a mean age of 42 years and mean GGT was 19.0 units. Individual PM2.5 and NO2 exposures were essentially below European limit values of 25 and 40 μg/m3, respectively, with means of 13.58 μg/m3 for PM2.5 and 19.93 μg/m3 for NO2. Positive associations were observed for PM2.5, PM10, PM2.5abs, NO2, NOx, and Cu, K, S in PM2.5 and PM10 fractions and Zn mainly in PM2.5 fraction. The strongest association per interquartile range observed was an increase of serum GGT concentration by 1.40 % (95 %-CI: 0.85 %; 1.95 %) per 45.7 ng/m3 S in PM2.5. Associations were robust to adjustments for other biomarkers, in two-pollutant models and the subset with a stable residential history.We found that long-term exposure to air pollution (PM2.5, PM10, PM2.5abs, NO2, NOx) as well as certain elements, were positively associated with baseline GGT levels. The elements associated suggest a role of traffic emissions, long range transport and wood burning.

Evidence of polygenic regulation of the physiological presence of neurofilament light chain in human serum.

The measurement of neurofilament light chain (NfL) in blood is a promising biomarker of neurological injury and disease. We investigated the genetic factors that underlie serum NfL levels (sNfL) of individuals without neurological conditions. We performed a discovery genome-wide association study (GWAS) of sNfL in participants of the German BiDirect Study (N = 1,899). A secondary GWAS for meta-analysis was performed in a small Austrian cohort (N = 287). Results from the meta-analysis were investigated in relation with several clinical variables in BiDirect. Our discovery GWAS identified 12 genomic loci at the suggestive threshold ((p < 1 × 10-5). After meta-analysis, 7 loci were suggestive of an association with sNfL. Genotype-specific differences in sNfL were observed for the lead variants of meta-analysis loci (rs34523114, rs114956339, rs529938, rs73198093, rs34372929, rs10982883, and rs1842909) in BiDirect participants. We identified potential associations in meta-analysis loci with markers of inflammation and renal function. At least 6 protein-coding genes (ACTG2, TPRKB, DMXL1, COL23A1, NAT1, and RIMS2) were suggested as genetic factors contributing to baseline sNfL levels. Our findings suggest that polygenic regulation of neuronal processes, inflammation, metabolism and clearance modulate the variability of NfL in the circulation. These could aid in the interpretation of sNfL measurements in a personalized manner.

The impact of obesity and metabolic syndrome on clinical and cognitive parameters in bipolar disorder: Results from the BIPFAT/BIPLONG study

IntroductionPatients with bipolar disorder have a hig risk of becoming overweight and obese, associated with an increased risk of somatic diseases and premature mortality. The Austrian BIPFAT/BIPLONG study aims at investigating lipid metabolism, psychosocial functioning, and cognitive parameters in bipolar disorder (BD).ObjectivesThe aim was to investigate to what extent overweight, obesity and metabolic syndrome (MetS) are associated with clinical symptoms (e.g. suicidality, depressive symptoms) and cognitive factors (attention, memory, executive function) in BD.MethodsIn addition to anamnestic interview and psychological tests, all participants were tested with a neuropsychological test battery including the Trail Making Test A/B, the Stroop Color and Word Interference Test, the d2 Test of Attention Revised, Digit Span, Digit-Symbol-Test, and the California Verbal Learning Test. Additionally, body mass index (BMI) and variables defining MetS including waist circumference, serum triglycerides, high-density lipoprotein, blood pressure, and fasting glucose levels have been collected in DSM-5 diagnosed patients with BD and healthy controls.ResultsIn our Austrian bipolar cohort (n=290), the median BMI was 27.9 (SD=5.9), 30.5 % of the patients were overweight (BMI = 25.5-29.9) and 24.6% of the patients were obese (BMI ≥ 30.0). In the control group (n=183), the median BMI was 24.5 (SD=4.8), 15.2% were overweight and 8.0% were obese. A sub-analysis in 215 patients showed that compared to overweight patients, normal weight patients showed more suicidal ideation in psychiatric history (χ2(2)=7.97, p=.019). In addition, there was a significant association between suicidal ideation and glucose (r=.15, p=.043) and cholesterol (r=−.17, p=.028). In another sub-analysis with 148 euthymic bipolar patients, we found a high prevalence of MetS in patients with BD (30.4% versus 15.4% in healthy controls) associated with impaired executive function compared to patients without MetS or healthy controls with and without MetS (p=.020). Clinical variables (illness duration, suicidality, number of affective episodes, medication, age of onset, and history of psychosis) did not relate to MetS in BD (p &gt; .05). A longitudinal analysis in 52 patients (35 without MetS and 17 with MetS) did not find an association of MetS on the one-year trajectory of cognitive decline in BD. In contrast, high baseline BMI predicted a decrease in the patient’s performance in working memory in the 12-months observation period.ConclusionsThe BIPFAT/BIPLONG study demonstrated a high prevalence of overweight, obesity and MetS in bipolar patients with adverse effects on cognitive function. Clinical variables such as suicidality were not related to the presence of obesity or MetS. Clinical impact and further (unpublished) results will be presented.Disclosure of InterestNone Declared

Toward the Definition of Patient-Reported Outcome Measurements in Hereditary Spastic Paraplegia.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of rare neurodegenerative diseases, characterized by a progressive spastic paraparesis. Currently, there is a HSP-specific clinician-reported outcome measure (CROM) called Spastic Paraplegia Rating Scale (SPRS). There are, however, no specific patient-reported outcome measures (PROMs) for HSP. In the present cohort study, we prospectively follow up a well-examined Austrian HSP cohort using validated rating scales and compared PROM with disease-specific and non-disease-specific CROM. Patients were recruited and followed up at the Center for Rare Movement Disorders, Innsbruck, Austria. CROM included the SPRS, Scale for the Assessment and Rating of Ataxia (SARA), Barthel Index (BI), and Mini-Mental State Examination (MMSE). PROM included the EQ-5D questionnaire and the Patient Health Questionnaire 9 (PHQ-9). Standardized response means (SRMs) were calculated for all scales at follow-up (FU) after 1 year. A total of 55 patients (36 males) with HSP were included in the study. FU was performed for 30 patients (21 males). Apart from females reporting more problems in the EQ-5D domain of anxiety and depression (p = 0.008), other clinician-reported outcomes (CROs) or patient-reported outcomes (PROs) did not differ significantly across sex. SPRS showed significant correlations with SARA (p < 0.001), mainly driven by the gait item, as well as the BI. Although SPRS did not correlate with EQ-5D visual analogue scale and PHQ-9 scores, several EQ-5D domains correlated significantly with SPRS. At FU, SPRS showed the highest responsiveness (SRM 1.11), followed by SARA (SRM 0.47). Neither MMSE nor PRO significantly increased at FU. In this study, we present an Austrian cohort of patients with HSP and a prospective study evaluating correlations of CRO and PRO as well as their progression. Demographics from our cohort are comparable with several other European cohort studies. Our data highlight the capabilities of the SPRS to show clinical progression and warrant consideration of ataxia rating scales such as SARA in HSP cohorts. We also show that the generic PROMs are not suitable to detect change in HSP, and thus, we propose to create a disease-specific PROM fully depicting the effect of HSP on the patients' lives.

Characteristics and outcomes of patients with psoriasis treated with apremilast in the real-world in Austria - results the APPRECIATE study.

Apremilast, an oral phosphodiesterase 4 inhibitor, is approved in the European Union for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients refractory or contraindicated to or intolerant of other systemic therapies. The APPRECIATE study assessed apremilast use in real-world practice and its clinical value to physicians and patients. APPRECIATE was a multinational, observational, retrospective, cross-sectional study. Apremilast effectiveness at 6 (±1) months was assessed on the basis of psoriasis severity and health-related quality-of-life scores and treatment satisfaction using physician/patient-reported outcomes, respectively. We report the Austrian cohort of 72 patients. At 6 (±1) months, three-quarters of patients remained on apremilast, while physicians and patients reported treatment benefits across all psoriasis symptoms and manifestations. Of patients, the majority were satisfied with their treatment and achieved treatment goals considered most relevant. Patients' and physicians' perceptions of treatment effectiveness were aligned, and health-related quality-of-life scores indicated an improvement in the majority of patients. Apremilast tolerability was consistent with the known safety profile. Among psoriasis patients receiving apremilast in Austria, improvement in clinical outcomes were observed and satisfaction with apremilast treatment among patients and physicians was high. ClinicalTrials.gov NCT02740218.