Regional variation and temporal trends in transcatheter and surgical aortic valve replacement in Switzerland: A population-based small area analysis.

BACKGROUND: Aortic valve stenosis (AS) is the most common valvular heart disease and if severe, is treated with either transcatheter (TAVR) or surgical aortic valve replacement (SAVR). We assessed temporal trends and regional variation of these interventions in Switzerland and examined potential determinants of geographic variation. METHODS: We conducted a population-based analysis using patient discharge data from all Swiss public and private acute care hospitals from 2013 to 2018. We generated hospital service areas (HSAs) based on patient flows for TAVR. We calculated age-standardized mean procedure rates and variation indices (extremal quotient [EQ] and systematic component of variation [SCV]). Using multilevel regression, we calculated the influence of calendar year and regional demographics, socioeconomic factors (language, insurance status), burden of disease, and number of cardiologists/cardiovascular surgeons on geographic variation. RESULTS: Overall, 8074 TAVR and 11,825 SAVR procedures were performed in 8 HSAs from 2013 to 2018. Whereas the age-/sex-standardized rate of TAVR increased from 12 to 22 procedures/100,000 persons, the SAVR rate decreased from 33 to 24 procedures during this period. After full adjustment, the predicted TAVR and SAVR rates varied from 12 to 22 and 20 to 35 per 100,000 persons across HSAs, respectively. The regional procedure variation was low to moderate over time, with a low overall variation in TAVR (EQ 1.9, SCV 3.9) and SAVR (EQ 1.6, SCV 2.2). In multilevel regression, TAVR rates increased annually by 10% and SAVR rates decreased by 5%. Determinants of higher TAVR rates were older age, male sex, living in a German speaking area, and higher burden of disease. A higher proportion of (semi)private insurance was also associated with higher TAVR and lower SAVR rates. After full adjustment, 10.6% of the variance in TAVR and 18.4% of the variance in SAVR remained unexplained. Most variance in TAVR and SAVR rates was explained by language region and insurance status. CONCLUSION: The geographic variation in TAVR and SAVR rates was low to moderate across Swiss regions and largely explained by differences in regional demographics and socioeconomic factors. The use of TAVR increased at the expense of SAVR over time.

Bleeding Risk in Elderly Patients with Venous Thromboembolism Who Would Have Been Excluded from Anticoagulation Trials.

Older patients with venous thromboembolism (VTE) are underrepresented in clinical anticoagulation trials. We examined to which extent elderly patients with VTE would be excluded from such trials and compared the bleeding risk between hypothetically excluded and enrolled patients. We studied 991 patients aged ≥65 years with acute VTE in a prospective multicenter cohort. We identified 12 landmark VTE oral anticoagulation trials from the eighth and updated ninth American College of Chest Physician Guidelines. For each trial, we abstracted the exclusion criteria and calculated the proportion of our study patients who would have been excluded from trial participation. We examined the association between five common exclusion criteria (hemodynamic instability, high bleeding risk, comorbidity, co-medication, and invasive treatments) and major bleeding (MB) within 36 months using competing risk regression, adjusting for age, sex, and periods of anticoagulation. A median of 31% (range: 20-52%) of our patients would have been excluded from participation in the landmark trials. Hemodynamic instability (sub-hazard ratio [SHR]: 2.2, 95% CI: 1.1-4.7), comorbidity (SHR: 1.5, 95% CI: 1.1-2.2), and co-medication (SHR: 1.5, 95% CI: 1.0-2.3) were associated with MB. Compared to eligible patients, those with ≥2 exclusion criteria had a twofold (SHR: 2.16, 95% CI: 1.38-3.39) increased risk of MB. Overall, about one-third of older patients would not be eligible for participation in guideline-defining VTE anticoagulation trials. The bleeding risk increases significantly with the number of exclusion criteria present. Thus, results from such trials may not be generalizable to older, multimorbid, and co-medicated patients.

Definitions of fatal bleeding in clinical studies evaluating anticoagulant treatment for venous thromboembolism: A scoping review.

BACKGROUND: Fatal bleeding is a component of the primary safety outcome in most studies evaluating anticoagulation for venous thromboembolism (VTE), but a standardized definition for fatal bleeding is lacking. OBJECTIVES: To summarize definitions of fatal bleeding and describe the range of case-fatality rates of major bleeding in VTE studies. METHODS: MEDLINE, Embase, and CENTRAL databases were searched from January 2008 to July 2021 for prospective studies that enrolled patients with VTE and evaluated the efficacy/safety of anticoagulation for VTE treatment or included fatal or major bleeding as primary outcome. Two authors independently performed study selection and data extraction. The primary outcome was the definition of fatal bleeding. The secondary outcome was the case-fatality rate of major bleeding. Data were analyzed using descriptive statistics. RESULTS: Of 4911 records identified, we included 132 articles representing 89 distinct studies. Twenty-seven (20%) articles and 7 of 89 (8%) studies reported a definition of fatal bleeding. Overall, we identified 3 different types of definitions that were either on the basis of a specific time interval between bleeding and death, bleeding location (intracranial) or clinical presentation (hemodynamic deterioration), or mainly relied on the judgment of the adjudication committee to determine the cause of death. The case-fatality rate of major bleeding ranged from 0 to 60% (median, 9.1%; interquartile range, 2.8%-18%). CONCLUSION: Less than 10% of studies assessing anticoagulant treatment for VTE reported a definition for fatal bleeding. The lack of a (standardized) definition for fatal bleeding may lead to inaccurate estimates of the risk of fatal bleeding, particularly when compared across studies.

Accuracy and interrater agreement of death event adjudications by physician trainees: validation of the ISTH definition of pulmonary embolism-related death in an autopsy cohort.

BACKGROUND: We previously determined good agreement and high specificity of the International Society on Thrombosis and Haemostasis (ISTH) definition of pulmonary embolism (PE)-related death among an expert central adjudication committee (CAC). CACs are often composed of experts in the corresponding research field. Involving physician trainees in CACs would allow investigators to divide the workload and foster trainees' research experience. OBJECTIVE: To evaluate the accuracy of the ISTH definition of PE-related death for PE- versus non-PE-related deaths as confirmed by autopsy and its interrater agreement among physician trainees. METHODS: This retrospective autopsy cohort included all patients with PE-related deaths between January 2010 and July 2019 as well as patients who died in 2018 from a cause other than PE at the New York-Presbyterian Hospital. Based on premortem clinical summaries, two physician trainees independently determined the cause of death using the ISTH definition of PE-related death. We calculated the sensitivity and specificity of the ISTH definition to identify autopsy-confirmed PE-related death and its interrater agreement. RESULTS: Overall, 126 death events were adjudicated (median age, 68 years; 60 [48%] women), of which 29 (23%) were due to PE, as confirmed by autopsy. Sensitivity and specificity of the ISTH definition for autopsy-confirmed PE-related death was 48% (95% CI, 29-67) and 100% (95% CI, 96-100), respectively. Interrater reliability for PE-related death was good (percentage agreement, 93%; 95% CI, 87-96, Cohen's Kappa, 0.67; 95% CI, 44-85). CONCLUSION: Our findings are consistent with our previous validation study. They further support the use of the ISTH definition of PE-related death and revealed high agreement between adjudicators with varied experience.

Water-pipe Smoking as a Risk Factor for Transmitting Mycobacterium tuberculosis.

A 20-year-old Swiss male presented at the emergency department with acute onset of febrile temperatures and hemoptysis and a 3-month history of productive cough. An X-ray and CT scan of the chest, sputum samples for acid-fast bacilli, polymerase chain reaction(PCR), and cultures for Mycobacteria revealed pulmonary infection with Mycobacterium tuberculosis. None of the classical risk factors for tuberculosis were present, but the patient reported regularly smoking a water pipe. Water-pipe smoking poses a serious risk of M. tuberculosis transmission. LEARNING POINTS: This case report illustrates an unusual risk factor for tuberculosis: water-pipe smoking.With the higher social acceptance of water-pipe smoking, physicians must be aware of the associated complications.

Unraveling Diagnostic Biomarkers of Schizophrenia Through Structure-Revealing Fusion of Multi-Modal Neuroimaging Data.

Fusing complementary information from different modalities can lead to the discovery of more accurate diagnostic biomarkers for psychiatric disorders. However, biomarker discovery through data fusion is challenging since it requires extracting interpretable and reproducible patterns from data sets, consisting of shared/unshared patterns and of different orders. For example, multi-channel electroencephalography (EEG) signals from multiple subjects can be represented as a third-order tensor with modes: subject, time, and channel, while functional magnetic resonance imaging (fMRI) data may be in the form of subject by voxel matrices. Traditional data fusion methods rearrange higher-order tensors, such as EEG, as matrices to use matrix factorization-based approaches. In contrast, fusion methods based on coupled matrix and tensor factorizations (CMTF) exploit the potential multi-way structure of higher-order tensors. The CMTF approach has been shown to capture underlying patterns more accurately without imposing strong constraints on the latent neural patterns, i.e., biomarkers. In this paper, EEG, fMRI, and structural MRI (sMRI) data collected during an auditory oddball task (AOD) from a group of subjects consisting of patients with schizophrenia and healthy controls, are arranged as matrices and higher-order tensors coupled along the subject mode, and jointly analyzed using structure-revealing CMTF methods [also known as advanced CMTF (ACMTF)] focusing on unique identification of underlying patterns in the presence of shared/unshared patterns. We demonstrate that joint analysis of the EEG tensor and fMRI matrix using ACMTF reveals significant and biologically meaningful components in terms of differentiating between patients with schizophrenia and healthy controls while also providing spatial patterns with high resolution and improving the clustering performance compared to the analysis of only the EEG tensor. We also show that these patterns are reproducible, and study reproducibility for different model parameters. In comparison to the joint independent component analysis (jICA) data fusion approach, ACMTF provides easier interpretation of EEG data by revealing a single summary map of the topography for each component. Furthermore, fusion of sMRI data with EEG and fMRI through an ACMTF model provides structural patterns; however, we also show that when fusing data sets from multiple modalities, hence of very different nature, preprocessing plays a crucial role.

Evaluation of Tumor Budding in Primary Colorectal Cancer and Corresponding Liver Metastases Based on H&E and Pancytokeratin Staining.

In colorectal cancer, tumor budding is associated with tumor progression and represents an additional prognostic factor in the TNM classification. Tumor buds can be found at the invasive front (peritumoral budding; PTB) and in the tumor center (intratumoral budding; ITB) of primary tumors. Previous studies have shown that tumor buds are also present in colorectal liver metastases (CRLM). Data on the prognostic and predictive role in this clinical context are still sparse and no standardized approach to evaluate budding in CRLM has been published so far. This study aimed to analyze and correlate perimetastatic (PMB) and intrametastatic budding (IMB) on H&E and pancytokeratin staining, compare it to budding results in corresponding primary tumors and to propose a standardized scoring system in CRLM as the basis for future studies. Tumor tissue of 81 primary tumors and 139 corresponding CRLM was used for ngTMA construction. For each primary tumor and metastasis, two punches from the center and two punches from the periphery from areas with highest tumor budding density were included. TMA slides were stained for H&E and pancytokeratin (Pan-CK). PTB, ITB, PMB, and IMB were analyzed and classified as bd1, bd2, and bd3 according to ITBCC guidelines. ITB and PTB as well as IMB and PMB showed significant correlation on H&E and Pan-CK staining. No correlation was found for tumor bud counts in primary tumors and corresponding metastases. The agreement for categorized tumor bud counts showed fair to good agreement for metastases and poor agreement for primary tumors between different classes on H&E and Pan-CK staining. Based on our results, tumor budding in primary tumors and CRLM seems to be different processes which might be the results of differing surrounding microenvironments. The evaluation of tumor budding in CRLM is challenging in cases without desmoplastic stroma reaction or intense perimetastatic ductular reaction. We therefore propose to evaluate tumor budding only in metastases with desmoplastic stroma reaction based on H&E staining since important morphological features are obscured on Pan-CK staining.