Sex hormones and cortisol during experimental trauma memory consolidation: Prospective association with intrusive memories

Background: Trauma- and stress-related disorders, such as post-traumatic stress disorder (PTSD), are more common in females than in males. Sex hormones affect learning and emotional memory formation and may be associated with the development of PTSD. Most previous studies have indexed these hormones in isolation. Objectives: To investigate associations of sex hormones and cortisol during memory consolidation on the development of intrusive memories. Methods: We employed an experimental trauma film paradigm in 61 healthy women and indexed salivary testosterone, progesterone, estradiol, and cortisol on day one and day two post experimental trauma exposure and their effects on intrusion frequency, distress, and vividness. Intrusive trauma memories were indexed by means of a diary in which participants documented intrusion frequency, distress, and vividness. Results and conclusion: Participants reported an average of 5.3 intrusions over the course of seven days (SD = 4.6, range 0-26). Progesterone, and estradiol indexed on day one predicted intrusion frequency, with higher progesterone and lower estradiol predicting more intrusive memories (p-values AUC progesterone 0.01 and estradiol 0.02). There was no evidence for associations between hormone concentration indices on day two and intrusion outcomes. Further research on the roles of gonadal and adrenal hormones in trauma memory formation is needed to advance our efforts to understand their influence on PTSD development

Neurovascular disease in Switzerland: 10-year trends show non-traditional risk factors on the rise and higher exposure in women

BACKGROUND AND PURPOSE Effective risk factor modification is the prerequisite to prevent neurovascular disease such as stroke or vascular dementia. Non-traditional vascular risk factors (nt-vrfs) including stress significantly add to the risk of neurovascular disease arising from traditional vascular risk factors (t-vrfs). In order to discover sex-specific changes that may underlie previously reported inclines in the prevalence of neurovascular and cardiovascular disease in women, 10-year trends in the prevalence of vrfs in Switzerland were assessed. METHODS Anonymized data from 22,134 participants (51% women) of the governmental Swiss Health Survey, performed every 5 years (2007, 2012 and 2017), were obtained. Epidemiological parameters, t-vrfs and nt-vrfs were analyzed in a cross-sectional study design. RESULTS Over the observation period, the number of women having full-time jobs increased considerably (2007 38%, 2012 39%, 2017 44%). This was accompanied by a substantial rise in the prevalence of nt-vrfs in women and men including stress at work (2007, not available; 2012 women/men 58%/60%; 2017 women/men 66%/65%), low locus of control (women/men: 2007 21%/19%, 2012 22%/19%, 2017 25%/22%) and sleep disorders (women/men: 2007 30%/22%, 2012 28%/20%, 2017 32%/26%). Amongst t-vrfs, only the prevalence of obesity and hypercholesterolemia increased over time in both sexes, whilst other t-vrfs remained stable (hypertension [27%], diabetes [5%]) or decreased (smoking [9.4 cigarettes/day]). CONCLUSIONS A rise in women's economic participation alongside a higher affection with nt-vrfs in the female Swiss population emphasizes the need to improve vascular risk stratification and implement effective preventive measures for neurovascular and cardiovascular disease

Inter-hospital transfer of patients with ruptured abdominal aortic aneurysm in Switzerland

Objectives: To analyse the association of inter-hospital transfer on hospital mortality in patients with ruptured abdominal aortic aneurysms (rAAA) in Switzerland. Design: Secondary data analysis of case-related hospital discharge data from the Swiss Federal Statistical Office for the years 2009-2018. All cases with rAAA as primary or secondary diagnosis were included. Cases with rAAA as a secondary diagnosis without surgical treatment and cases that had been transferred to another hospital without surgical treatment at the referring hospital were excluded. Methods: Logistic regression models for hospital mortality were constructed with age, sex, type of admission, van Walraven comorbidity score, type of treatment, insurance class, hospital level, and year of treatment as independent variables. Results: From 1 January 2009 to 31 December 2018, 1798 cases with rAAA were treated either surgically (62.5%) or palliatively (37.5%) in Switzerland. 72.9% of the cases were directly treated (surgically or palliative) at the hospital of first presentation, whereas 27.1% of all cases with rAAA were transferred between hospitals. The overall crude hospital mortality was 50.3%; in the surgically treated cohort it was 23.1%, in the palliative treated cohort it was 95.7%.Inter-hospital transfer was associated with better survival compared to patients directly admitted (OR 0.52, 95%-CI: 0.36-0.75, p<.001). Treatment in major hospitals was associated with a significantly higher mortality compared to treatment in university hospitals (OR 1.98, 1.41-2.79, p<.001). There was no evidence for an association of open repair with hospital mortality, OR 1.06, 0.77-1.48, p=.722, compared to endovascular repair. Conclusions: In a healthcare system such as Switzerland with a highly specialised rescue chain, transfer of haemodynamically stable patients with rAAA is probably safe. In this setting, a centralised medical care might outweigh the potential disadvantages of a limited delay due to patient transfer. Further studies are needed to address potential confounding factors such as hemodynamic and anatomical features. Keywords: "DRG"; "aortic aneurysm; "aortic rupture"; "patient transfer"; "secondary data analysis"; abdominal"

Hospital incidence and mortality of patients treated for abdominal aortic aneurysms in Switzerland - a secondary analysis of Swiss DRG statistics data

AIM OF THE STUDY To analyse hospital incidence and in-hospital mortality of patients treated for abdominal aortic aneurysms in Switzerland. METHODS Secondary data analysis of case-related hospital discharge data of the Swiss Federal Statistical Office for the years 2009-2018. Patients who were hospitalised and surgically treated for nonruptured abdominal aortic aneurysms or hospitalised and treated for ruptured abdominal aortic aneurysms were included in the analysis. Standardised annual incidences rates were calculated using the European standard population 2013. In-hospital all-cause mortality rates were calculated as raw values and standardised for age, sex, and the van Walraven comorbidity score. RESULTS A total of 10,728 cases were included in this study, of which 87.1% were male. Overall, 22.7% of the patients presented with a ruptured abdominal aortic aneurysm; 46% of these cases were surgically treated whereas 54% received conservative therapy. The age-standardised cumulative hospital incidences for treatment of nonruptured abdominal aortic aneurysms were 2.6 (95% confidence interval 2.5-2.8) and 19.7 (19.2-20.1) per 100,000 for women and men, respectively; for ruptured aneurysms it was 0.4 (0.3-2.4) per 100,000 in women, and 2.7 (2.6-2.9) in men. The annual incidence rates were stable in the decade observed. The adjusted mortality rates for treatment of nonruptured aneurysms decreased from 5.5% (2.6-11.2%) in 2009 to 1.4% (0.5-3.6%) in 2018 in women, and from 2.4% (1.3-4.5%) in 2009 to 0.6% (0.2-1.5%) in 2018 in men. The adjusted mortality rates for treatment of ruptured abdominal aortic aneurysms remained high without relevant improvements for either sex over time: for women 32.4% (24.1-42.1%), for men 19.7% (16.8-22.8%). CONCLUSIONS The hospital incidence rates for nonruptured and ruptured abdominal aortic aneurysms remained unchanged in the decade observed. Compared with Germany, there was no evidence for a decrease in the annual incidence rates for ruptured abdominal aortic aneurysms in Switzerland. Mortality rates in the elective setting were low and decreased in the last decade but remained high in patients treated for ruptured aneurysms. Efforts to reduce the incidence of ruptured abdominal aortic aneurysms are needed to reduce aneurysm-related mortality in Switzerland

Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort

OBJECTIVES: Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database. METHODS: Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months. RESULTS: Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference -1.0, 95% CI -3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (-6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles. CONCLUSION: Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population

The incremental value of the contribution of a biostatistician to the reporting quality in health research-A retrospective, single center, observational cohort study.

BACKGROUND The reporting quality in medical research has recently been critically discussed. While reporting guidelines intend to maximize the value from funded research, and initiatives such as the EQUATOR network have been introduced to advance high quality reporting, the uptake of the guidelines by researchers could be improved. The aim of this study was to assess the contribution of a biostatistician to the reporting and methodological quality of health research, and to identify methodological knowledge gaps. METHODS In a retrospective, single center, observational cohort study, two groups of publications were compared. The group of exposed publications had an academic biostatistician on the author list, whereas the group of non-exposed publications did not include a biostatistician of the evaluated group. Rating of reporting quality was done in blinded fashion and in duplicate. The primary outcome was a sum score based on six dimensions, ranging between 0 (worst) and 11 (best). The study protocol was reviewed and approved as a registered report. RESULTS There were 131 publications in the exposed group published between 2017 and 2018. Of these, 95 were either RCTs, observational, or prediction / prognostic studies. Corresponding matches in the group of non-exposed publications were identified in a reproducible manner. Comparison of reporting quality overall revealed a 1.60 (95%CI from 0.92 to 2.28, p <0.0001) units higher reporting quality for exposed publications. A subgroup analysis within study types showed higher reporting quality across all three study types. CONCLUSION Our study is the first to report an association of a higher reporting quality and methodological strength in health research publications with a biostatistician on the author list. The higher reporting quality persisted through subgroups of study types and dimensions. Methodological knowledge gaps were identified for prediction / prognostic studies, and for reporting on statistical methods in general and missing values, specifically

Circle of Willis variants and their association with outcome in patients with middle cerebral artery-M1-occlusion stroke.

BACKGROUND An incomplete circle of Willis (CoW) has been associated with a higher risk of stroke and might affect collateral flow in large vessel occlusion (LVO) stroke. We aimed to investigate the distribution of CoW variants in a LVO stroke and transient ischemic attack (TIA) cohort and analyze their impact on 3-month functional outcome. METHODS CoW anatomy was assessed with time-of-flight magnetic resonance angiography (TOF-MRA) in 193 stroke patients with acute middle cerebral artery (MCA)-M1-occlusion receiving endovascular treatment (EVT) and 73 TIA patients without LVO. The main CoW variants were categorized into four vascular models of presumed collateral flow via the CoW. RESULTS 82.4% (n = 159) of stroke and 72.6% (n = 53) of TIA patients had an incomplete CoW. Most variants affected the posterior circulation (stroke: 77.2%, n = 149; TIA: 58.9%, n = 43; p = 0.004). Initial stroke severity defined by the National Institutes of Health Stroke Scale (NIHSS) on admission was similar for patients with and without CoW variants. CoW integrity did not differ between groups with favorable (modified Rankin Scale [mRS]): 0-2) and unfavorable (mRS: 3-6) 3-month outcome. However, we found trends towards a higher mortality in patients with any type of CoW variant (p = 0.08) and a higher frequency of incomplete CoW among patients dying within 3 months after stroke onset (p = 0.119). In a logistic regression analysis adjusted for the potential confounders age, sex and atrial fibrillation, neither the vascular models nor anterior or posterior variants were independently associated with outcome. CONCLUSION Our data provide no evidence for an association of CoW variants with clinical outcome in LVO stroke patients receiving EVT

Circle of Willis variants and their association with outcome in patients with middle cerebral artery-M1-occlusion stroke

BACKGROUND: An incomplete circle of Willis (CoW) has been associated with a higher risk of stroke and might affect collateral flow in large vessel occlusion (LVO) stroke. We aimed to investigate the distribution of CoW variants in a LVO stroke and transient ischemic attack (TIA) cohort and analyze their impact on 3-month functional outcome. METHODS: CoW anatomy was assessed with time-of-flight magnetic resonance angiography (TOF-MRA) in 193 stroke patients with acute middle cerebral artery (MCA)-M1-occlusion receiving endovascular treatment (EVT) and 73 TIA patients without LVO. The main CoW variants were categorized into four vascular models of presumed collateral flow via the CoW. RESULTS: 82.4% (n = 159) of stroke and 72.6% (n = 53) of TIA patients had an incomplete CoW. Most variants affected the posterior circulation (stroke: 77.2%, n = 149; TIA: 58.9%, n = 43; p = 0.004). Initial stroke severity defined by the National Institutes of Health Stroke Scale (NIHSS) on admission was similar for patients with and without CoW variants. CoW integrity did not differ between groups with favorable (modified Rankin Scale [mRS]): 0-2) and unfavorable (mRS: 3-6) 3-month outcome. However, we found trends towards a higher mortality in patients with any type of CoW variant (p = 0.08) and a higher frequency of incomplete CoW among patients dying within 3 months after stroke onset (p = 0.119). In a logistic regression analysis adjusted for the potential confounders age, sex and atrial fibrillation, neither the vascular models nor anterior or posterior variants were independently associated with outcome. CONCLUSION: Our data provide no evidence for an association of CoW variants with clinical outcome in LVO stroke patients receiving EVT

Effectiveness and safety of tocilizumab in patients with systemic sclerosis : a propensity score matched controlled observational study of the EUSTAR cohort

Objectives Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database. Methods Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months. Results Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference -1.0, 95% CI -3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (-6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles. Conclusion Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population

Is reporting quality in medical publications associated with biostatisticians as co-authors? A registered report protocol

BACKGROUND Quality in medical research has recently been criticized for being low, especially in observational research. Methodology is increasingly difficult, but collaboration between clinical researchers and biostatisticians may improve research and reporting quality. The aim of this study is to quantify the value of a biostatistician in the team of authors. METHODS Single-center, retrospective observational study following the STROBE reporting guidelines. We will systematically review all medical publications with biostatisticians from our center as co-authors or authors and review corresponding papers without biostatisticians from our center during the same time range. We will compare aspects of reporting quality, overall and for the three study types observational, randomized trial, and prognostic separately. DISCUSSION We anticipate that the results of the study will raise awareness of the importance of high methodological quality, as well as appropriate reporting quality in clinical research. CONCLUSION Our study will have a direct impact on our center by making each of us more aware of the reporting guidelines for various research designs. This in turn will enhance reporting quality in future research with our involvement. Our study will also raise awareness of the important role that biostatisticians play in the design and analysis of health research projects