The Effect of Albumin Administration in Critically Ill Patients: A Retrospective Single-Center Analysis.

OBJECTIVES: The aim of this study was to analyze the development of albumin administration in patients admitted to the adult ICU. In addition, we assessed the impact of albumin administration on serum hemoglobin concentration. DESIGN: We conducted a retrospective single-center study including all patients who were admitted to the ICU from January 2013 to December 2021 and stayed at least 24 hours. SETTING: The study was conducted in an academic hospital (University Hospital Basel, Switzerland). PATIENTS: A total of 20,927 admissions were included, of which 3748 received albumin at least once during their ICU stay. To analyze volume expansion, 2006 admissions met the inclusion criteria, namely at least two hemoglobin measurements within 12 hours, one albumin delivery, and experienced no bleeding, dialysis, or transfusions during this period. INTERVENTIONS: None. MEASUREMENTS: We examined the hemoglobin levels before and after albumin administration and compared them with a matched control group to assess the amount and duration of volume expansion. MAIN RESULTS: From 2013 to 2021 the proportion of critically ill patients treated with albumin rose from 5.0% to 32.5%. An overproportioned increase in albumin use could be seen in surgical patients (4.7-47.2%) and in those receiving RBC transfusion (13.7-72.6%). In those patients receiving albumin, a significant drop in hemoglobin of around 5 g/L on average could be observed following treatment with albumin. CONCLUSION: Hemodilution was observable for at least 12 hours after albumin administration and may have caused a decrease in hemoglobin concentration of greater than 8 g/L when isooncotic albumin solution (5%, 25 g in 500 mL) was administered. This makes albumin, especially in its isooncotic form, an ideal colloid to achieve long-lasting volume expansion. However, RBC transfusions may increase under albumin therapy, as transfusion thresholds may be undershot after albumin administration.

Does the age of packed red blood cells, donor sex or sex mismatch affect the sublingual microcirculation in critically ill intensive care unit patients? A secondary interpretation of a retrospective analysis.

In vitro studies have thoroughly documented age-dependent impact of storage lesions in packed red blood cells (pRBC) on erythrocyte oxygen carrying capacity. While studies have examined the effect of pRBC age on patient outcome only few data exist on the microcirculation as their primary site of action. In this secondary analysis we examined the relationship between age of pRBC and changes of microcirculatory flow (MCF) in 54 patients based on data from the Basel Bedside assessment Microcirculation Transfusion Limit study (Ba2MiTraL) on effects of pRBC on sublingual MCF. Mean change from pre- to post-transfusion proportion of perfused vessels (∆PPV) was + 8.8% (IQR - 0.5 to 22.5), 5.5% (IQR 0.1 to 10.1), and + 4.7% (IQR - 2.1 to 6.5) after transfusion of fresh (≤ 14 days old), medium (15 to 34 days old), and old (≥ 35 days old) pRBC, respectively. Values for the microcirculatory flow index (MFI) were + 0.22 (IQR - 0.1 to 0.6), + 0.22 (IQR 0.0 to 0.3), and + 0.06 (IQR - 0.1 to 0.3) for the fresh, medium, and old pRBC age groups, respectively. Lower ∆PPV and transfusion of older blood correlated with a higher Sequential Organ Failure Assessment (SOFA) score of patients upon admission to the intensive care unit (ICU) (p = 0.01). However, regression models showed no overall significant correlation between pRBC age and ∆PPV (p = 0.2). Donor or recipient sex had no influence. We detected no significant effect of pRBC on microcirculation. Patients with a higher SOFA score upon ICU admission might experience a negative effect on the ∆PPV after transfusion of older blood.

Atri-U: assisted image analysis in routine cardiovascular magnetic resonance volumetry of the left atrium.

BACKGROUND: Artificial intelligence can assist in cardiac image interpretation. Here, we achieved a substantial reduction in time required to read a cardiovascular magnetic resonance (CMR) study to estimate left atrial volume without compromising accuracy or reliability. Rather than deploying a fully automatic black-box, we propose to incorporate the automated LA volumetry into a human-centric interactive image-analysis process. METHODS AND RESULTS: Atri-U, an automated data analysis pipeline for long-axis cardiac cine images, computes the atrial volume by: (i) detecting the end-systolic frame, (ii) outlining the endocardial borders of the LA, (iii) localizing the mitral annular hinge points and constructing the longitudinal atrial diameters, equivalent to the usual workup done by clinicians. In every step human interaction is possible, such that the results provided by the algorithm can be accepted, corrected, or re-done from scratch. Atri-U was trained and evaluated retrospectively on a sample of 300 patients and then applied to a consecutive clinical sample of 150 patients with various heart conditions. The agreement of the indexed LA volume between Atri-U and two experts was similar to the inter-rater agreement between clinicians (average overestimation of 0.8 mL/m2 with upper and lower limits of agreement of - 7.5 and 5.8 mL/m2, respectively). An expert cardiologist blinded to the origin of the annotations rated the outputs produced by Atri-U as acceptable in 97% of cases for step (i), 94% for step (ii) and 95% for step (iii), which was slightly lower than the acceptance rate of the outputs produced by a human expert radiologist in the same cases (92%, 100% and 100%, respectively). The assistance of Atri-U lead to an expected reduction in reading time of 66%-from 105 to 34 s, in our in-house clinical setting. CONCLUSIONS: Our proposal enables automated calculation of the maximum LA volume approaching human accuracy and precision. The optional user interaction is possible at each processing step. As such, the assisted process sped up the routine CMR workflow by providing accurate, precise, and validated measurement results.

Dialysis after graft loss: a Swiss experience.

BACKGROUND: Patients returning to dialysis after graft loss have high early morbidity and mortality. METHODS: We used data from the Swiss Transplant Cohort Study to describe the current practice and outcomes in Switzerland. All patients who received a renal allograft between May 2008 and December 2014 were included. The patients with graft loss were divided into two groups depending on whether the graft loss occurred within 1 year after transplantation (early graft loss group) or later (late graft loss group). Patients with primary non-function who never gained graft function were excluded. RESULTS: Seventy-seven out of 1502 patients lost their graft during follow-up, 40 within 1 year after transplantation. Eleven patients died within 30 days after allograft loss. Patient survival was 86, 81 and 74% at 30, 90 and 365 days after graft loss, respectively. About 92% started haemodialysis, 62% with definitive vascular access, which was associated with decreased mortality (hazard ratio = 0.28). At the time of graft loss, most patients were on triple immunosuppressive therapy with significant reduction after nephrectomy. One year after graft loss, 77.5% (31 of 40) of patients in the early and 43.2% (16 out of 37) in the late-loss group had undergone nephrectomy. Three years after graft loss, 36% of the patients with early and 12% with late graft loss received another allograft. CONCLUSION: In summary, our data illustrate high mortality, and a high number of allograft nephrectomies and re-transplantations. Patients commencing haemodialysis with a catheter had significantly higher mortality than patients with definitive access. The role of immunosuppression reduction and allograft nephrectomy as interdependent factors for mortality and re-transplantation needs further evaluation.

Factors associated with clinical and radiological status on admission in patients with aneurysmal subarachnoid hemorrhage.

Grading scales yield objective measure of the severity of aneurysmal subarachnoid hemorrhage and serve as to guide treatment decisions and for prognostication. The purpose of this cohort study was to determine what factors govern a patient's disease-specific admission scores in a representative Central European cohort. The Swiss Study of Subarachnoid Hemorrhage includes anonymized data from all tertiary referral centers serving subarachnoid hemorrhage patients in Switzerland. The 2009-2014 dataset was used to evaluate the impact of patient and aneurysm characteristics on the patients' status at admission using descriptive and multivariate regression analysis. The primary/co-primary endpoints were the GCS and the WFNS grade. The secondary endpoints were the Fisher grade, the presence of a thick cisternal or ventricular clot, the presence of a new focal neurological deficit or cranial nerve palsy, and the patient's intubation status. In our cohort of 1787 consecutive patients, increasing patient age by 10 years and low pre-ictal functional status (mRS 3-5) were inversely correlated with "high" GCS score (GCS ≥ 13) (OR 0.91, 95% CI 0.84-0.97 and OR 0.67, 95% CI 0.31-1.46), "low" WFNS grade (grade VI-V) (OR 1.21, 95% CI 1.04-1.20 and OR 1.47, 95% CI 0.66-3.27), and high Fisher grade (grade III-IV) (OR 1.08, 95% CI 1.00-1.17 and OR 1.54, 95% CI 0.55-4.32). Other independent predictors for the patients' clinical and radiological condition at admission were the ruptured aneurysms' location and its size. In sum, chronological age and pre-ictal functional status, as well as the ruptured aneurysm's location and size, determine the patients' clinical and radiological condition at admission to the tertiary referral hospital.

GABA metabolism and its role in gamma-band oscillatory activity during auditory processing: An MRS and EEG study.

Gamma-aminobutyric acid (GABA) and glutamate are believed to have inhibitory and exhibitory neuromodulatory effects that regulate the brain's response to sensory perception. Furthermore, frequency-specific synchronization of neuronal excitability within the gamma band (30-80 Hz) is attributable to a homeostatic balance between excitation and inhibition. However, our understanding of the physiological mechanism underlying gamma rhythms is based on animal models. Investigations of the relationship between GABA concentrations, glutamate concentrations, and gamma band activity in humans were mostly restricted to the visual cortex and are conflicting. Here, we performed a multimodal imaging study combining magnetic resonance spectroscopy (MRS) with electroencephalography (EEG) in the auditory cortex. In 14 healthy subjects, we investigated the impact of individual differences in GABA and glutamate concentration on gamma band response (GBR) following auditory stimulus presentation. We explored the effects of bulk GABA on the GBR across frequency (30-200 Hz) and time (-200 to 600 ms) and found no significant relationship. Furthermore, no correlations were found between gamma peak frequency or power measures and metabolite concentrations (GABA, glutamate, and GABA/glutamate ratio). These findings suggest that, according to MRS measurements, and given the auditory stimuli used in this study, GABA and glutamate concentrations are unlikely to play a significant role in the inhibitory and excitatory drive in the generation of gamma band activity in the auditory cortex. Hum Brain Mapp 38:3975-3987, 2017. © 2017 Wiley Periodicals, Inc.

Cancer-related therapies at the end of life in hospitalized cancer patients from four Swiss cantons: SAKK 89/09.

The use of cancer-related therapies in cancer patients hospitalized at the end of life has increased in many countries over time. Given the scarcity of published Swiss data, the objective of this study was to evaluate the influence of hospital type and other factors on the delivery of health care during the last month before death. Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating Swiss cantons) who deceased between 2006 and 2008. Primary endpoints were delivery of cancer-related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of hospital type, patient and geographic characteristics. Of 3,809 identified cancer patients in the claims database, 2,086 patients dying from cancer were hospitalized during the last 30 days before death, generating 2,262 inpatient episodes. Anticancer drug therapy was given in 22.2% and radiotherapy in 11.7% of episodes. Besides age and cancer type, the canton of residence and hospital type showed independent, statistically significant associations with intensity of care, which was highest in university hospitals. These results should initiate a discussion among oncologists in Switzerland and may question the compliance with standard of care guidelines for terminal cancer patients.

Delivery of health care at the end of life in cancer patients of four swiss cantons: a retrospective database study (SAKK 89/09).

BACKGROUND: The use of cancer related therapy in cancer patients at the end-of-life has increased over time in many countries. Given a lack of published Swiss data, the objective of this study was to describe delivery of health care during the last month before death of cancer patients. METHODS: Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating cantons), deceased between 2006-2008. Primary endpoints were hospitalization rate and delivery of cancer related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of patient and geographic characteristics. RESULTS: 3809 identified cancer patients were included. Hospitalization rate (mean 68.5%, 95% CI 67.0-69.9) and percentage of patients receiving anti-cancer drug therapies (ACDT, mean 14.5%, 95% CI 13.4-15.6) and radiotherapy (mean 7.7%, 95% CI 6.7-8.4) decreased with age. Canton of residence and insurance type status most significantly influenced the odds for hospitalization or receiving ACDT. CONCLUSIONS: The intensity of cancer specific care showed substantial variation by age, cancer type, place of residence and insurance type status. This may be partially driven by cultural differences within Switzerland and the cantonal organization of the Swiss health care system.

Enhancement of the haemostatic effect of platelets in the presence of high normal concentrations of von Willebrand factor for critically ill patients needing platelet transfusion-a protocol for the will-plate randomised controlled trial.

INTRODUCTION: von Willebrand Factor (vWF) is a key protein mediating platelet adhesion on the surface of damaged endothelia. To the best of our knowledge, no trial exists that investigated the effect of platelet transfusion in combination with the administration of balanced vWF in severe blood loss, despite being widely used in clinical practice. The Basel Will-Plate study will investigate the impact of the timely administration of balanced vWF (1:1 vWF and FVIII) in addition to platelet transfusion on the need for blood and coagulation factor transfusion in patients admitted to the intensive care unit (ICU) who suffer from severe bleeding. The study hypothesis is based on the assumption that adding balanced vWF to platelets will reduce the overall need for transfusion of blood products compared to the transfusion of platelets alone. METHODS AND ANALYSIS: The Will-Plate study is an investigator-initiated, single-centre, double-blinded randomised controlled clinical trial in 120 critically ill patients needing platelet transfusion. The primary outcome measure will be the number of fresh frozen plasma (FFP) and red blood cell (RBC) transfusions according to groups. Secondary outcome measures include the number of platelet concentrates transfused within the first 48 h after treatment of study medication, quantity of blood loss in the first 48 h after treatment with the study medication, length of stay in ICU and hospital, number of revision surgeries for haemorrhage control, ICU mortality, hospital mortality, 30-day mortality and 1-year mortality. Patients will be followed after 30 days and 1 year for activities of daily living and mortality assessment. The sample size was calculated to detect a 50% reduction in the number of blood products subsequently transfused within 2 days in patients with Wilate® compared to placebo. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the ICH-GCP or ISO EN 14155 (as far as applicable) and all national legal and regulatory requirements. The study results will be presented at international conferences and published in a peer-reviewed journal. TRIALS REGISTRATION: ClinicalTrials.gov NCT04555785. PROTOCOL VERSION: Clinical Study Protocol Version 2, 01.11.2020. Registered on Sept. 21, 2020.

Multilingual RECIST classification of radiology reports using supervised learning.

Objectives: The objective of this study is the exploration of Artificial Intelligence and Natural Language Processing techniques to support the automatic assignment of the four Response Evaluation Criteria in Solid Tumors (RECIST) scales based on radiology reports. We also aim at evaluating how languages and institutional specificities of Swiss teaching hospitals are likely to affect the quality of the classification in French and German languages. Methods: In our approach, 7 machine learning methods were evaluated to establish a strong baseline. Then, robust models were built, fine-tuned according to the language (French and German), and compared with the expert annotation. Results: The best strategies yield average F1-scores of 90% and 86% respectively for the 2-classes (Progressive/Non-progressive) and the 4-classes (Progressive Disease, Stable Disease, Partial Response, Complete Response) RECIST classification tasks. Conclusions: These results are competitive with the manual labeling as measured by Matthew's correlation coefficient and Cohen's Kappa (79% and 76%). On this basis, we confirm the capacity of specific models to generalize on new unseen data and we assess the impact of using Pre-trained Language Models (PLMs) on the accuracy of the classifiers.

Structure-based prediction of BRAF mutation classes using machine-learning approaches.

The BRAF kinase is attracting a lot of attention in oncology as alterations of its amino acid sequence can constitutively activate the MAP kinase signaling pathway, potentially contributing to the malignant transformation of the cell but at the same time rendering it sensitive to targeted therapy. Several pathologic BRAF variants were grouped in three different classes (I, II and III) based on their effects on the protein activity and pathway. Discerning the class of a BRAF mutation permits to adapt the treatment proposed to the patient. However, this information is lacking new and experimentally uncharacterized BRAF mutations detected in a patient biopsy. To overcome this issue, we developed a new in silico tool based on machine learning approaches to predict the potential class of a BRAF missense variant. As class I only involves missense mutations of Val600, we focused on the mutations of classes II and III, which are more diverse and challenging to predict. Using a logistic regression model and features including structural information, we were able to predict the classes of known mutations with an accuracy of 90%. This new and fast predictive tool will help oncologists to tackle potential pathogenic BRAF mutations and to propose the most appropriate treatment for their patients.

Performance of a deep learning tool to detect missed aortic dilatation in a large chest CT cohort.

Purpose: Thoracic aortic (TA) dilatation (TAD) is a risk factor for acute aortic syndrome and must therefore be reported in every CT report. However, the complex anatomy of the thoracic aorta impedes TAD detection. We investigated the performance of a deep learning (DL) prototype as a secondary reading tool built to measure TA diameters in a large-scale cohort. Material and methods: Consecutive contrast-enhanced (CE) and non-CE chest CT exams with "normal" TA diameters according to their radiology reports were included. The DL-prototype (AIRad, Siemens Healthineers, Germany) measured the TA at nine locations according to AHA guidelines. Dilatation was defined as >45 mm at aortic sinus, sinotubular junction (STJ), ascending aorta (AA) and proximal arch and >40 mm from mid arch to abdominal aorta. A cardiovascular radiologist reviewed all cases with TAD according to AIRad. Multivariable logistic regression (MLR) was used to identify factors (demographics and scan parameters) associated with TAD classification by AIRad. Results: 18,243 CT scans (45.7% female) were successfully analyzed by AIRad. Mean age was 62.3 ± 15.9 years and 12,092 (66.3%) were CE scans. AIRad confirmed normal diameters in 17,239 exams (94.5%) and reported TAD in 1,004/18,243 exams (5.5%). Review confirmed TAD classification in 452/1,004 exams (45.0%, 2.5% total), 552 cases were false-positive but identification was easily possible using visual outputs by AIRad. MLR revealed that the following factors were significantly associated with correct TAD classification by AIRad: TAD reported at AA [odds ratio (OR): 1.12, p < 0.001] and STJ (OR: 1.09, p = 0.002), TAD found at >1 location (OR: 1.42, p = 0.008), in CE exams (OR: 2.1-3.1, p < 0.05), men (OR: 2.4, p = 0.003) and patients presenting with higher BMI (OR: 1.05, p = 0.01). Overall, 17,691/18,243 (97.0%) exams were correctly classified. Conclusions: AIRad correctly assessed the presence or absence of TAD in 17,691 exams (97%), including 452 cases with previously missed TAD independent from contrast protocol. These findings suggest its usefulness as a secondary reading tool by improving report quality and efficiency.

Demographic, psychosocial and health disparities between living and deceased renal allograft recipients in Switzerland.

BACKGROUND: Living donor renal transplantation is widely performed in Switzerland with a superior long-term outcome and lower waiting time compared with deceased renal transplantation. However the chances of receiving a living donor kidney transplant are not the same for all transplant candidates. The current study aimed to identify psychosocial and demographic characteristics that predict lower access to living kidney donation in Switzerland. METHODS: The study was a nationwide multicentre study nested within the Swiss Transplant Cohort Study. Pre-transplant demographic, psychosocial and health characteristics of 1126 deceased and 859 living renal transplant recipients were compared using logistic regression analysis. RESULTS: Transplant candidates with higher age (odds ratio [OR] per 10 years 0.67, 95% confidence interval [CI] 0.60–0.74), lower education (OR 0.46, 95% CI 0.36–0.59), a work capacity of less than 50% (OR 0.48, 95% CI 0.35–0.66), single or formerly married (OR 0.38, 95% CI 0.26–0.53 / OR 0.37, 95% CI 0.26–0.53) or with a higher hospital depression score (OR per 5 points 0.61, 95% CI 0.50–0.74) were less likely to receive an allograft from a living donor. In some regions of Switzerland candidates were more likely to undergo living transplantation than in other regions. No association was found with gender or income. CONCLUSIONS: Interventions to increase access to kidney transplantation from living donors should target transplant candidates of older age, lower education, lower working capacity and not living in a committed relationship. The observed regional differences suggest that additional determinants of living donation may play a role such as population and health professional attitudes toward living donation.

Impact of Hyponatremia after Renal Transplantation on Decline of Renal Function, Graft Loss and Patient Survival: A Prospective Cohort Study.

BACKGROUND: Hyponatremia is one of the most common electrolyte disorders observed in hospitalized and ambulatory patients. Hyponatremia is associated with increased falls, fractures, prolonged hospitalisation and mortality. The clinical importance of hyponatremia in the renal transplant field is not well established, so the aim of this study was to determine the relationships between hyponatremia and mortality as main outcome and renal function decline and graft loss as secondary outcome among a prospective cohort of renal transplant recipients. METHODS: This prospective cohort study included 1315 patients between 1 May 2008 and 31 December 2014. Hyponatremia was defined as sodium concentration below 136 mmol/L at 6 months after transplantation. The main endpoint was mortality. A secondary composite endpoint was also defined as: rapid decline in renal function (≥5 mL/min/1.73 m2 drop of the eGFR/year), graft loss or mortality. RESULTS: Mean sodium was 140 ± 3.08 mmol/L. 97 patients displayed hyponatremia with a mean of 132.9 ± 3.05 mmol/L. Hyponatremia at 6 months after transplantation was associated neither with mortality (HR: 1.02; p = 0.97, 95% CI: 0.47-2.19), nor with the composite outcome defined as rapid decline in renal function, graft loss or mortality (logrank test p = 0.9). CONCLUSIONS: Hyponatremia 6 months after transplantation is not associated with mortality in kidney allograft patients.

Fully automated guideline-compliant diameter measurements of the thoracic aorta on ECG-gated CT angiography using deep learning.

BACKGROUND: Manually performed diameter measurements on ECG-gated CT-angiography (CTA) represent the gold standard for diagnosis of thoracic aortic dilatation. However, they are time-consuming and show high inter-reader variability. Therefore, we aimed to evaluate the accuracy of measurements of a deep learning-(DL)-algorithm in comparison to those of radiologists and evaluated measurement times (MT). METHODS: We retrospectively analyzed 405 ECG-gated CTA exams of 371 consecutive patients with suspected aortic dilatation between May 2010 and June 2019. The DL-algorithm prototype detected aortic landmarks (deep reinforcement learning) and segmented the lumen of the thoracic aorta (multi-layer convolutional neural network). It performed measurements according to AHA-guidelines and created visual outputs. Manual measurements were performed by radiologists using centerline technique. Human performance variability (HPV), MT and DL-performance were analyzed in a research setting using a linear mixed model based on 21 randomly selected, repeatedly measured cases. DL-algorithm results were then evaluated in a clinical setting using matched differences. If the differences were within 5 mm for all locations, the cases was regarded as coherent; if there was a discrepancy >5 mm at least at one location (incl. missing values), the case was completely reviewed. RESULTS: HPV ranged up to ±3.4 mm in repeated measurements under research conditions. In the clinical setting, 2,778/3,192 (87.0%) of DL-algorithm's measurements were coherent. Mean differences of paired measurements between DL-algorithm and radiologists at aortic sinus and ascending aorta were -0.45±5.52 and -0.02±3.36 mm. Detailed analysis revealed that measurements at the aortic root were over-/underestimated due to a tilted measurement plane. In total, calculated time saved by DL-algorithm was 3:10 minutes/case. CONCLUSIONS: The DL-algorithm provided coherent results to radiologists at almost 90% of measurement locations, while the majority of discrepent cases were located at the aortic root. In summary, the DL-algorithm assisted radiologists in performing AHA-compliant measurements by saving 50% of time per case.

Impact of Aneurysm Multiplicity on Treatment and Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: One-third of patients with aneurysmal subarachnoid hemorrhage (aSAH) have multiple intracranial aneurysms (MIA). OBJECTIVE: To determine the predictors of outcome in aSAH patients with MIA compared to aSAH patients with a single intracranial aneurysm (SIA). METHODS: The Swiss Study of Subarachnoid Hemorrhage dataset 2009-2014 was used to evaluate outcome in aSAH patients with MIA compared to patients with SIA with the aid of descriptive and multivariate regression analysis. The primary endpoints of this cohort study were presence of new stroke on computed tomography (CT) after aneurysm treatment, and presence of stroke on CT prior to discharge. The secondary endpoints were the clinical and the functional status, and the overall mortality at discharge and at 1 yr. RESULTS: Among 1689 consecutive patients, 467 had MIA (prevalence: 26.4%). The incidence of stroke was higher in the MIA than in the SIA group, both after aneurysm treatment (19.3% vs 15.1%) and at discharge (24% vs 21.4%). However, the 95% confidence interval (CI) for the corresponding odds ratio (OR) in our multivariate model included 1, indicating that the detected trends did not reach statistical significance. As for the secondary endpoints, aneurysm multiplicity was found to be an independent, statistically significant predictor for occurrence of a new focal neurological deficit between admission and discharge (OR 1.40, 95% CI 1.08-1.81). Yet, the MIA and SIA groups did not differ in terms of either functional outcome or overall survival. CONCLUSION: aSAH patients with MIA have a higher short-term morbidity than patients with SIA. This excess morbidity does not worsen the functional outcome or lower overall survival.

Low 5-year cumulative incidence of post-transplant lymphoproliferative disorders after solid organ transplantation in Switzerland.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of transplantation occurring in the setting of immunosuppression and oncogenic viral infections. However, little is known about the cumulative incidence, histological subtypes, risk determinants and outcome of PTLD in solid organ transplant (SOT) recipients in Switzerland. METHODS: This retrospective observational study investigated adult SOT recipients from two sequential cohorts, the pre-SCTS (Swiss Transplant Cohort Study) series, with data collected from January 1986 to April 2008, and the STCS series, with data collected from May 2008 to December 2014 in Switzerland. SOT recipients were cross-referenced with the data of all the patients with a lymphoma diagnosis in each transplant centre and with the data of the Swiss Transplant Cohort Study (STCS) to determine the cumulative incidence of PTLD, pre-therapeutic clinical features, clinical course and outcome. Kaplan-Meier analysis was performed for overall survival after PTLD. RESULTS: We identified 79 cases of PTLD during the study period in the two cohorts: pre-STCS from 1986 to 2008 (n = 62) and STCS from 2008 to 2014 (n = 17). Histological subgroups included: early lesions (pre-STCS n = 2, STCS n = 0); polymorphic PTLD (pre-STCS n = 8, STCS n = 7); monomorphic PTLD (pre-STCS n = 47, STCS n = 10), and Hodgkin's lymphoma (pre-STCS n = 5, STCS n = 0). Median time to PTLD diagnosis was 90 months (range 3-281 months) and 14 months (range 2-59 months) in the pre-STCS and STCS cohorts, respectively. Median follow-up after transplantation was 141 months for the pre-STCS patients and 33 months for the STCS patients. Cumulative incidences of PTLD during the STCS period at 0.5, 1 and 5 years were 0.17% (95% confidence interval 0.07-0.46%), 0.22% (0.09-0.53%) and 0.96% (0.52-1.80%), respectively. For the pre-STCS case series, it was not possible to estimate the incidence rate of PTLD. Survival after PTLD diagnosis was 80% (68-87%) at 1 year and 56% (42-68%) at 5 years for the pre-STCS and STCS cohorts combined. CONCLUSIONS: At 5 years, the cumulative incidence of PTLD, regardless of the organ transplanted, was only 0.96% in the STCS cohort, which is lower than that reported in the literature.

Predictors of Occurrence and Anatomic Distribution of Multiple Aneurysms in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The literature on multiple intracranial aneurysms (MIA) in patients with aneurysmal subarachnoid hemorrhage (aSAH) focuses largely on risk factor analysis and consists essentially of retrospective cohort studies of limited sample size, or studies in populations outside Europe and North America. The purpose of this cohort study was to identify predictors for aneurysm multiplicity and to investigate the anatomic distribution of MIA in a representative Western cohort of patients with aSAH. METHODS: The Swiss Study of Subarachnoid Hemorrhage (SOS) database includes anonymized data from all tertiary neurovascular facilities in Switzerland. The dataset for 2009-2014 was used to compare characteristics of patients with aSAH and MIA and those with a single intracranial aneurysm (SIA) by means of descriptive and multivariate regression analysis. RESULTS: Among 1689 unselected patients with aSAH, 467 had MIA (prevalence, 27.6%). The location of the ruptured index aneurysm was correlated with the probability of finding bystander aneurysms and predicted their likely anatomic distribution. Patients with a ruptured basilar artery aneurysm (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.30-3.44) or a ruptured middle cerebral artery aneurysm (OR, 1.86; 95% CI, 1.35-2.55) were at the greatest risk for having MIA. Larger size of the index aneurysm (OR per 1 mm, 1.03; 95% CI, 1.01-1.06) was also positively correlated with aneurysm multiplicity. Males were less likely than females to have MIA (OR, 0.79; 95% CI, 0.61-1.01). CONCLUSIONS: In patients with aSAH, the location of the ruptured index aneurysm is correlated with the probability of finding bystander aneurysms, and is predictive of the sites at which bystander aneurysms are most likely to be found.

Surveillance of Physicians Causing Potential Drug-Drug Interactions in Ambulatory Care: A Pilot Study in Switzerland.

OBJECTIVES: We analysed potential drug-drug interactions (DDI) in ambulatory care in Switzerland based on claims data from three large health insurers in 2010 to identify physicians with peculiar prescription behaviour differing from peers of the same specialty. METHODS: We analysed contraindicated or potentially contraindicated DDI from the national drug formulary and calculated for each physician the ratios of the number of patients with a potential DDI divided by the number of patients at risk and used a zero inflated binomial distribution to correct for the inflated number of observations with no DDI. We then calculated the probability that the number of caused potential DDI of physicians was unlikely (p-value < 0.05 and ≥ 0.01) and very unlikely (p-value <0.01) to be due to chance. RESULTS: Of 1'607'233 females and 1'525'307 males 1.3% and 1.2% were exposed to at least one potential DDI during 12 months. When analysing the 40 most common DDI, 598 and 416 of 18,297 physicians (3.3% and 2.3%) were causing potential DDI in a frequency unlikely (p<0.05 and p ≥ 0.01) and very unlikely (p<0.01) to be explained by chance. Patients cared by general practitioners and cardiologists had the lowest probability (0.20 and 0.26) for not being exposed to DDI. CONCLUSIONS: Contraindicated or potentially contraindicated DDI are frequent in ambulatory care in Switzerland, with a small proportion of physicians causing potential DDI in a frequency that is very unlikely to be explained by chance when compared to peers of the same specialty.

[Iron substitution in outpatients in Switzerland: Increase of costs associated with intravenous administration]. / Ambulante Eisensubstitution in der Schweiz - Kostensteigerung infolge venöser Applikation.

Iron anaemia and iron-deficient erythropoiesis are treated with oral iron supplements. For chronic haemodialysis or in the case of therapy failure or intolerance to oral iron therapy, intravenous supplements are administered. The costs of iron supplements borne by statutory health care insurance had strongly increased during the observation period from 2006 to 2010. Based on the invoice data of a large health insurance company with a market share of around 18 %, prescription data of iron preparations and laboratory tests were analysed and extrapolated to the Swiss population. During the 5-year observation period, costs of intravenous iron substitution increased by 16.5 m EUR (340.3 %) and the number of individuals treated by 243.5 %. A sharp rise was observed in women of menstruating age, which was mainly due to prescriptions issued by primary care physicians. More than 8 % of intravenous iron substitutions were administered without prior laboratory analysis,and must therefore be regarded as off-label use. A cost-benefit analysis is needed to demonstrate the additional value of intravenous over oral iron supplementation, and intravenous iron supplementation should be administered only to patients with proven iron deficiency.