Long-term prospective outcome data using EndoPredict as risk stratification and chemotherapy decision biomarker in hormone receptor-positive, HER2-negative early breast cancer.

PURPOSE: To report the prospective long-term outcome data of patients whose chemotherapy decision was guided by the EndoPredict test. METHODS: Patients with hormone receptor-positive HER2-negative early breast cancer with 0-3 positive lymph nodes were enrolled. The EndoPredict test was carried out on all tumor samples. Treatment compliance, local recurrence, distant metastases, and survival were evaluated. Associations of EPclin risk stratification with 5-year disease-free survival and distant metastasis-free survival were evaluated by time-to-event analysis. RESULTS: 368 consecutive patients were included in the analysis. Median follow-up was 8.2 years. EndoPredict allocated 238 (65%) in the low-risk and 130 (35%) patients in the high-risk group. Risk for disease recurrence or death in EPclin high-risk patients was twofold higher than in EPclin low-risk patients (hazard ratio [HR] 2.08; 95% CI 1.26-3.44; p = 0.004). EPclin low-risk patients had a 5-year disease-free survival of 95.3% (95% CI 92.6-98.0%). EPclin high-risk patients were at higher risk of developing distant metastases or death (HR 2.21; 95% CI 1.27-3.88; p = 0.005). EPclin high-risk patients who underwent chemotherapy had a 5-year DFS of 89.1% (95% CI 82.7-96.1%) in contrast to high-risk patients without chemotherapy (68.9%; 95% CI 56.2-84.5%; HR 0.46; 95% CI 0.23-0.95; p = 0.036). EPclin high-risk patients were at higher risk of experiencing distant metastases or death than EPclin low-risk patients regardless of menopausal status (premenopausal: HR 3.55; 95% CI 1.17-12.32; p = 0.025; postmenopausal: HR 1.92; 95% CI 0.99-3.7; p = 0.054). CONCLUSION: EndoPredict can guide decisions on adjuvant chemotherapy in early luminal breast cancer. EndoPredict risk stratification is also applicable in premenopausal women.

LINAS-Score: prognostic model for mortality assessment in patients with cirrhotic liver and infected ascites.

BACKGROUND AND AIM: Patients with liver cirrhosis often face a grave threat from infected ascites (IA). However, a well-established prognostic model for this complication has not been established in routine clinical practice. Therefore, we aimed to assess mortality risk in patients with liver cirrhosis and IA. METHODS: We conducted a retrospective study across three tertiary hospitals, enrolling 534 adult patients with cirrhotic liver and IA, comprising 465 with spontaneous bacterial peritonitis (SBP), 34 with bacterascites (BA), and 35 with secondary peritonitis (SP). To determine the attributable mortality risk linked to IA, these patients were matched with 122 patients with hydropic decompensated liver cirrhosis but without IA. Clinical, laboratory, and microbiological parameters were assessed for their relation to mortality using univariable analyses and a multivariable random forest model (RFM). Least absolute shrinkage and selection operator (Lasso) regression model was used to establish an easy-to-use mortality prediction score. RESULTS: The in-hospital mortality risk was highest for SP (39.0%), followed by SBP (26.0%) and BA (25.0%). Besides illness severity markers, microbiological parameters, such as Candida spp., were identified as the most significant indicators for mortality. The Lasso model determined 15 parameters with corresponding scores, yielding good discriminatory power (area under the receiver operating characteristics curve = 0.89). Counting from 0 to 83, scores of 20, 40, 60, and 80 corresponded to in-hospital mortalities of 3.3%, 30.8%, 85.2%, and 98.7%, respectively. CONCLUSION: We developed a promising mortality prediction score for IA, highlighting the importance of microbiological parameters in conjunction with illness severity for assessing patient outcomes.

Structure and quality of bedside teaching: A videographic analysis.

Bedside teaching (BST) is a core element of medical education. In light of a reported decrease in BST, evidence on how to use BST time most efficiently should be developed. Given that little research into the tangible quality characteristics of good BST has been reported, we investigated the influence of various teacher and structural characteristics on the perceived quality of BST. We filmed and coded 36 BSTs involving 24 lecturers and 259 students. Structural characteristics of interest were: number of students and patients, overall duration, and the proportion of clinical examination. Lecturer questionnaires provided insight into teaching experience and intrinsic motivation, and student evaluations assessed the quality of BSTs in three dimensions. Correlations are reported using the Pearson r and a linear mixed model (LMM). The intrinsic motivation of lecturers was significantly positively correlated with perceived quality, but their experience was only weakly so correlated. In the LMM, a significant association was observed for the quality dimension of clinical teaching with the number of patients and the proportion of time spent on clinical examination. Based on our findings, we recommend including multiple patients in BSTs, and providing substantial opportunities for clinical examination. Regarding lecturers, motivation matters more than experience.

Too much time or not enough? An observational study of teacher wait time after questions in case-based seminars.

BACKGROUND: We define teacher wait time (TWT) as a pause between a teacher question and the following response given by a student. TWT is valuable because it gives students time to activate prior knowledge and reflect on possible answers to teacher questions. We seek to gain initial insights into the phenomenon of TWT in medical education and give commensurate recommendations to clinical teachers. METHODS: We observed n = 719 teacher questions followed by wait time. These were video-recorded in 29 case-based seminars in undergraduate medical education in the areas of surgery and internal medicine. The seminars were taught by 19 different clinical teachers. The videos were coded with satisfactory reliability. Time-to-event data analysis was used to explore TWT overall and independently of question types. RESULTS: In our sample of case-based seminars, about 10% of all teacher questions were followed by TWT. While the median duration of TWT was 4.41 s, we observed large variation between different teachers (median between 2.88 and 10.96 s). Based on our results, we recommend that clinical teachers wait for at least five, but not longer than 10-12 s after initial questions. For follow-up and reproduction questions, we recommend shorter wait times of 5-8 s. CONCLUSIONS: The present study provides insights into the frequency and duration of TWT and its dependence on prior questions in case-based seminars. Our results provide clinical teachers with guidance on how to use TWT as an easily accessible tool that gives students time to reflect on and respond to teacher questions.

Vaccination frequency in people newly diagnosed with multiple sclerosis.

BACKGROUND: Infections are discussed as risk factor for multiple sclerosis (MS) development and relapses. This may lead to decreased vaccination frequency in newly diagnosed patients. OBJECTIVE: The aim of this study was to evaluate the relation of MS diagnosis to subsequent vaccination frequency. METHODS: Based on German ambulatory claims data from 2005 to 2019, regression models were used to assess the relation of MS diagnosis (n = 12,270) to vaccination. A cohort of patients with MS was compared to control cohorts with Crohn's disease, psoriasis, and without these autoimmune diseases (total n = 198,126) in the 5 years after and before diagnosis. RESULTS: Patients with MS were less likely to be vaccinated compared to persons without the autoimmune diseases 5 years after diagnosis (odds ratio = 0.91, p < 0.001). Exceptions were vaccinations against influenza (1.29, p < 0.001) and pneumococci (1.41, p < 0.001). Differences were strong but less pronounced after than before diagnosis (p < 0.001). The likelihood of vaccination was also lower compared to patients with Crohn's disease or psoriasis. CONCLUSIONS: Patients with MS were not adequately vaccinated despite guideline recommendations. Increasing awareness about the importance of vaccination is warranted to reduce the risk of infection, in particular, in patients with MS receiving immunotherapies.

Does the presence of a specialist doctor reduce the burden of disease in people with epilepsy in low-resource settings? A comparison of two epilepsy clinics in rural Tanzania.

BACKGROUND: With an estimated lifetime prevalence of epilepsy of 7.6 per 1,000 people, epilepsy represents one of the most common neurological disorders worldwide, with the majority of people with epilepsy (PWE) living in low-income and middle-income countries (LMICs). Adequately treated, up to 70 % of PWE will become seizure-free, however, as many as 85% of PWE worldwide, mostly from LMICs, do not receive adequate treatment. OBJECTIVE: To assess the impact of the presence of a neurologist on the management of PWE in Tanzania. METHODS: Two epilepsy clinics in rural Tanzania, one continuously attended by a neurologist, and one mainly attended by nurses with training in epilepsy and supervised intermittently by specialist doctors (neurologists/psychiatrists) were comparatively analyzed by multivariable linear and logistic regression models with regard to the outcome parameters seizure frequency, the occurrence of side effects of antiepileptic medication and days lost after a seizure. RESULTS: The presence of a neurologist significantly reduced the mean number of seizures patients experienced per month by 4.49 seizures (p < 0.01) while leading to an increase in the occurrence of reported side effects (OR: 2.15, p = 0.02). CONCLUSION: The presence of a neurologist may play a substantial role in reducing the burden of the disease of PWE in LMICs. Hence, specialist training should be encouraged, and relevant context-specific infrastructure established.

Implementation of an internet-based asthma patient education program in primary care: results of a single-arm trial.

Asthma education programs (AEPs) for patients are known to be important to provide skills to effectively manage the disease. We developed an electronic AEP (eAEP) and assessed the extent to which patients with asthma in primary care are capable to use the eAEP and whether asthma knowledge improved after eAEP.A single-arm pilot study was performed between November 2019 and December 2020 in 12 general practices in Upper Bavaria, Germany. Asthma knowledge was assessed by the Asthma Knowledge Test (AKT) at baseline, 2 weeks after completion of the eAEP, as well as after 3 and 6 months. AKT sum scores at baseline and follow-up were compared with each other using the Wilcoxon test.In total, 72 patients with asthma were included, of whom all participated in the 2-week follow-up, while data on the 3- and 6-month follow-up was available in 62 and 51 patients, respectively. The eAEP was well accepted and positively evaluated by participants. The mean AKT score significantly (p < .001) increased from 22.8 ± 11.0 at baseline to 44.6 ± 8.3 two weeks after completion of the eAEP. After 3 months, the mean score was still 41.8 ± 7.6, and after 6 months it was 40.2 ± 9.3 (p < .001 each compared to baseline).The internet-based asthma education program was well accepted by primary care patients and resulted in a major increase of asthma knowledge. Thus, it has the potential to be an important adjunct in the treatment of patients with asthma in general practice.

Effects of Early Clozapine Treatment on Remission Rates in Acute Schizophrenia (The EARLY Trial): Protocol of a Randomized-Controlled Multicentric Trial.

BACKGROUND: Quick symptomatic remission after the onset of psychotic symptoms is critical in schizophrenia treatment, determining the subsequent disease course and recovery. In this context, only every second patient with acute schizophrenia achieves symptomatic remission within three months of initiating antipsychotic treatment. The potential indication extension of clozapine-the most effective antipsychotic-to be introduced at an earlier stage (before treatment-resistance) is supported by several lines of evidence, but respective clinical trials are lacking. METHODS: Two hundred-twenty patients with acute non-treatment-resistant schizophrenia will be randomized in this double-blind, 8-week parallel-group multicentric trial to either clozapine or olanzapine. The primary endpoint is the number of patients in symptomatic remission at the end of week 8 according to international consensus criteria ('Andreasen criteria'). Secondary endpoints and other assessments comprise a comprehensive safety assessment (i. e., myocarditis screening), changes in psychopathology, global functioning, cognition, affective symptoms and quality of life, and patients' and relatives' views on treatment. DISCUSSION: This multicentre trial aims to examine whether clozapine is more effective than a highly effective second-generation antipsychotics (SGAs), olanzapine, in acute schizophrenia patients who do not meet the criteria for treatment-naïve or treatment-resistant schizophrenia. Increasing the likelihood to achieve symptomatic remission in acute schizophrenia can improve the overall outcome, reduce disease-associated burden and potentially prevent mid- and long-term disease chronicity.

Agreement between cardiac output measurements by pulse wave analysis using the Pressure Recording Analytical Method and transthoracic echocardiography in patients with veno-venous extracorporeal membrane oxygenation therapy: An observational method comparison.

BACKGROUND: Measuring cardiac output (CO) is important in patients treated with veno-venous extracorporeal membrane oxygenation (vvECMO) because vvECMO flow and CO need to be balanced. Uncalibrated pulse wave analysis with the Pressure Recording Analytical Method (PRAM) may be suitable to measure CO in patients with vvECMO therapy. OBJECTIVE: To assess the agreement between CO measured by PRAM (PRAM-CO; test method) and CO measured by transthoracic echocardiography (TTE-CO; reference method). DESIGN: A prospective observational method comparison study. SETTING: The ICU of a German university hospital between March and December 2021. PATIENTS: Thirty one adult patients with respiratory failure requiring vvECMO therapy: 29 of the 31 patients (94%) were treated for COVID-19 related respiratory failure. MAIN OUTCOME MEASURES: PRAM-CO and TTE-CO were measured simultaneously at two time points in each patient with at least 20 min between measurements. A radial or femoral arterial catheter-derived blood pressure waveform was used for PRAM-CO measurements. TTE-CO measurements were conducted using the pulsed wave Doppler-derived velocity time integral of the left ventricular outflow tract (LVOT) and the corresponding LVOT diameter. PRAM-CO and TTE-CO were compared using Bland-Altman analysis and the percentage error (PE). We defined a PE of <30% as clinically acceptable. RESULTS: Mean ±â€ŠSD PRAM-CO was 6.86 ±â€Š1.49 l min -1 and mean TTE-CO was 6.94 ±â€Š1.58 l min -1 . The mean of the differences between PRAM-CO and TTE-CO was 0.09 ±â€Š0.73 l min -1 with a lower 95% limit of agreement of -1.34 l min -1 and an upper 95% limit of agreement of 1.51 l min -1 . The PE was 21%. CONCLUSIONS: The agreement between PRAM-CO and TTE-CO is clinically acceptable in adult patients with vvECMO therapy.

Evaluation of a questionnaire to assess the indication for screening colonoscopy for asymptomatic patients.

INTRODUCTION: Colorectal cancer is the second most common cause of cancer death worldwide. Screening colonoscopy is a very effective measure to prevent colorectal cancer and can reduce mortality at the population level. However, the participation rates of screening programs are low.To provide easily accessible information on screening colonoscopy and to increase the participation rates of screening programs, we developed a questionnaire for asymptomatic patients based on the German guidelines to assess the indication for screening colonoscopy. We evaluated the questionnaire with reference to the indications given by specialists in gastroenterology. METHODS: Patients who visited a specialist in gastroenterology in an outpatient clinic of a tertiary hospital for other reasons than a colonoscopy were eligible for the study. A maximum of seven questions to assess the indication for screening colonoscopy were answered by the patients. Afterward, the indication for screening colonoscopy was given or not by a specialist in gastroenterology. The accuracy of the questionnaire was measured in terms of sensitivity, specificity, and predictive values. RESULTS: In total, 335 patients were included in the analyses, of whom 50 and 285 patients were given and were not given an indication for screening colonoscopy by the specialists, respectively. In 0/50 patients, the questionnaire was false negative and in 8/285 patients false positive. Thus, the questionnaire had a sensitivity of 100% (95% confidence interval: 93-100%), a specificity of 97% (95-99%), a negative predictive value of 100% (99-100%), and a positive predictive value of 86% (75-94%).A subgroup analysis including patients who had never had a colonoscopy (n=109) showed comparable results: sensitivity of 100% (92-100%), specificity of 92% (83-97%), negative predictive value of 100% (94-100%), and positive predictive value of 90% (87-97%). CONCLUSION: The self-assessment questionnaire for asymptomatic individuals to assess the recommendation for screening colonoscopy is very sensitive and specific compared to a specialist in gastroenterology.The questionnaire can be found at: https://www.interdisziplinaere-endoskopie.mri.tum.de/de/infos-patienten/index.php.

Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes.

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

Association of pregnancies with risk of multiple sclerosis.

BACKGROUND: Pregnancies have an impact on the disease course of multiple sclerosis (MS), but their relationship with MS risk is yet unclear. OBJECTIVE: To determine the relationships of pregnancies and gynecological diagnoses with MS risk. METHODS: In this retrospective case-control study, we assessed differences in gynecological International Classification of Diseases, 10th Revision (ICD-10) code recording rates between women with MS (n = 5720), Crohn's disease (n = 6280), or psoriasis (n = 40,555) and women without these autoimmune diseases (n = 26,729) in the 5 years before diagnosis. RESULTS: Twenty-eight ICD-10 codes were recorded less frequently for women with MS as compared to women without autoimmune disease, 18 of which are pregnancy-related. After adjustment for pregnancies, all codes unrelated to pregnancies were still negatively associated with MS. In a sensitivity analysis excluding women with evidence for possible demyelinating events before diagnosis, all associations were more pronounced. In comparison to women with psoriasis, most associations could be confirmed; that was not true in comparison to women with Crohn's disease. CONCLUSION: Our findings provide evidence for a possible protective effect of pregnancies on MS risk likely independent of or in addition to a previously suggested reversed causality. The negative associations of gynecological disorders with disease risk need further investigation. The associations might be shared by different autoimmune diseases.

Pulse Wave Analysis Using the Pressure Recording Analytical Method to Measure Cardiac Output in Pediatric Cardiac Surgery Patients: A Method Comparison Study Using Transesophageal Doppler Echocardiography as Reference Method.

BACKGROUND: Cardiac output (CO) is a key determinant of oxygen delivery, but choosing the optimal method to obtain CO in pediatric patients remains challenging. The pressure recording analytical method (PRAM), implemented in the MostCareUp system (Vygon), is an invasive uncalibrated pulse wave analysis (PWA) method to measure CO. The objective of this study is to compare CO measured by PRAM (PRAM-CO; test method) with CO simultaneously measured by transesophageal Doppler echocardiography (TEE-CO; reference method) in pediatric patients. METHODS: In this prospective observational method comparison study, PRAM-CO and TEE-CO were assessed in pediatric elective cardiac surgery patients at 2 time points: after anesthesia induction and after surgery. The study was performed in a German university medical center from March 2019 to March 2020. We included pediatric patients scheduled for elective cardiac surgery with arterial catheter and TEE monitoring. PRAM-CO and TEE-CO were compared using Bland-Altman analysis accounting for repeated measurements per subject, and the percentage error (PE). RESULTS: We included 52 PRAM-CO and TEE-CO measurement pairs of 30 patients in the final analysis. Mean ± SD TEE-CO was 2.15 ± 1.31 L/min (range 0.55-6.07 L/min), and mean PRAM-CO was 2.21 ± 1.38 L/min (range 0.55-5.90 L/min). The mean of the differences between TEE-CO and PRAM-CO was -0.06 ±0.38 L/min with 95% limits of agreement (LOA) of 0.69 (95% confidence interval [CI], 0.53-0.82 L/min) to -0.80 L/min (95% CI, -1.00 to -0.57 L/min). The resulting PE was 34% (95% CI, 27%-41%). CONCLUSIONS: With a PE of <45%, PRAM-CO shows clinically acceptable agreement with TEE-CO in hemodynamically stable pediatric patients before and after cardiac surgery.

Effectiveness of an online education program for asthma patients in general practice: study protocol for a cluster randomized controlled trial.

BACKGROUND: Asthma education programs (AEPs) have been shown to increase quality of life and reduce emergency treatments and hospital admissions. Despite the proven benefits, only a minority of asthma patients attend such programs. To increase the number of educated patients, an online education program (electronic AEP, eAEP) for asthma patients has been developed. The present study aims to investigate the effectiveness of the eAEP in terms of asthma knowledge, asthma control and emergency treatments in general practice settings. METHODS: This is a cluster randomized controlled trial including 100 patients with bronchial asthma from 20 general practices in Bavaria, Germany. General practices will be randomly assigned to either the intervention or control group. Patients in the intervention group will receive access to the eAEP and instructions to complete this program within two weeks. Patients in the control group will receive usual care including a referral to face-to-face AEP (fAEP) by a certified primary care physician or a pulmonologist according to guideline recommendations. Furthermore, patients of both the intervention and control groups will be invited to a follow-up consultation in their general practice after completion of the eAEP and fAEP (three weeks and twelve weeks after study inclusion, respectively) to discuss any open issues. Outcomes for both groups will be assessed at baseline (t0), after two weeks (t1), three months (t2) and six months (t3). The primary outcome is the comparison of asthma knowledge gain between intervention and control groups after completion of the eAEP (two weeks after study inclusion) and fAEP (twelve weeks after study inclusion), respectively. Secondary outcomes include asthma control, frequency of emergency treatments, patient autonomy as well as attitudes towards asthma medication. DISCUSSION: The results of the present trial will provide knowledge about the effectiveness of an online education program for asthma patients compared to usual care in primary care. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00028805 . Registered 22 April 2022.

Is there an increase over time in the complexity of teacher questions and student responses in case-based clinical seminars? A cross-sectional video study.

BACKGROUND: Case-based group discussions (CBGD) are a specific, interaction-focused format dedicated to fostering medical students' skills in applying basic biomedical knowledge to patient cases. Existing conceptions of CBGD suggest that a gradient towards increased opportunities for students to make elaborative verbal contributions is an important element of such seminars. To verify this assumption, we investigate empirically if clinical teachers progress from more basic, knowledge-oriented questions towards more advanced, elaboration-oriented questions in such seminars. METHODS: We videotaped 21 different clinical teachers and 398 medical students in 32 CBGD-seminars on surgery and internal medicine. We coded closed-reproductive and open-elaborative teacher questions as well as reproductive and elaborative student responses to these questions. Inter-rater reliability was satisfactory. To determine trends regarding the teacher questions / student responses, we compared eight time-segments of equal duration per seminar. RESULTS: Overall, clinical teachers asked more closed-reproductive than open-elaborative questions. Students gave more reproductive than elaborative responses. Regarding the frequencies of these forms of teacher questions / student responses, we found no significant differences over time. CONCLUSIONS: Clinical teachers did not deliberately modify the types of questions over time to push students towards more elaborative responses. We conclude that the critical question to which degree promising teaching approaches are actually put into clinical teaching practice should be raised more purposefully in medical education research.

Ticagrelor or Prasugrel in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: In this prespecified subgroup analysis, we included 1653 patients with ST-segment-elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization. RESULTS: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95-1.82]; P=0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P=0.83), stroke (1.3% versus 1.0%; P=0.46), and definite stent thrombosis (1.8% versus 1.0%; P=0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18-3.23]; P=0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80-1.87]; P=0.36). CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Diverse 'just-right' levels of chromosomal instability and their clinical implications in neoadjuvant treated gastric cancer.

BACKGROUND: The Cancer Genome Atlas (TCGA) consortium described EBV positivity(+), high microsatellite instability (MSI-H), genomic stability (GS) and chromosomal instability (CIN) as molecular subtypes in gastric carcinomas (GC). We investigated the predictive and prognostic value of these subtypes with emphasis on CIN in the context of neoadjuvant chemotherapy (CTx) in GC. METHODS: TCGA subgroups were determined for 612 resected adenocarcinomas of the stomach and gastro-oesophageal junction (291 without, 321 with CTx) and 143 biopsies before CTx. EBV and MSI-H were analysed by standard assays. CIN was detected by multiplex PCRs analysing 22 microsatellite markers. Besides the TCGA classification, CIN was divided into four CIN-subgroups: low, moderate, substantial, high. Mutation profiling was performed for 52 tumours by next-generation sequencing. RESULTS: EBV(+) (HR, 0.48; 95% CI, 0.23-1.02), MSI-H (HR, 0.56; 95% CI, 0.35-0.89) and GS (HR, 0.72; 95% CI, 0.45-1.13) were associated with increased survival compared to CIN in the resected tumours. Considering the extended CIN-classification, CIN-substantial was a negative prognostic factor in uni- and multivariable analysis in resected tumours with CTx (each p < 0.05). In biopsies before CTx, CIN-high predicted tumour regression (p = 0.026), but was not prognostically relevant. CONCLUSION: A refined CIN classification reveals tumours with different biological characteristics and potential clinical implications.

Prediction of lung emphysema in COPD by spirometry and clinical symptoms: results from COSYCONET.

BACKGROUND: Lung emphysema is an important phenotype of chronic obstructive pulmonary disease (COPD), and CT scanning is strongly recommended to establish the diagnosis. This study aimed to identify criteria by which physicians with limited technical resources can improve the diagnosis of emphysema. METHODS: We studied 436 COPD patients with prospective CT scans from the COSYCONET cohort. All items of the COPD Assessment Test (CAT) and the St George's Respiratory Questionnaire (SGRQ), the modified Medical Research Council (mMRC) scale, as well as data from spirometry and CO diffusing capacity, were used to construct binary decision trees. The importance of parameters was checked by the Random Forest and AdaBoost machine learning algorithms. RESULTS: When relying on questionnaires only, items CAT 1 & 7 and SGRQ 8 & 12 sub-item 3 were most important for the emphysema- versus airway-dominated phenotype, and among the spirometric measures FEV1/FVC. The combination of CAT item 1 (≤ 2) with mMRC (> 1) and FEV1/FVC, could raise the odds for emphysema by factor 7.7. About 50% of patients showed combinations of values that did not markedly alter the likelihood for the phenotypes, and these could be easily identified in the trees. Inclusion of CO diffusing capacity revealed the transfer coefficient as dominant measure. The results of machine learning were consistent with those of the single trees. CONCLUSIONS: Selected items (cough, sleep, breathlessness, chest condition, slow walking) from comprehensive COPD questionnaires in combination with FEV1/FVC could raise or lower the likelihood for lung emphysema in patients with COPD. The simple, parsimonious approach proposed by us might help if diagnostic resources regarding respiratory diseases are limited. Trial registration ClinicalTrials.gov, Identifier: NCT01245933, registered 18 November 2010, https://clinicaltrials.gov/ct2/show/record/NCT01245933 .

Polyscore of autonomic parameters for risk stratification of the elderly general population: the Polyscore study.

AIMS: Present society is constantly ageing and elderly frequently suffer from conditions that are difficult and/or costly to treat if detected late. Effective screening of the elderly is therefore needed so that those requiring detailed clinical work-up are identified early. We present a prospective validation of a screening strategy based on a Polyscore of seven predominantly autonomic, non-invasive risk markers. METHODS AND RESULTS: Within a population-based survey in Germany (INVADE study), participants aged ≥60 years were enrolled between August 2013 and February 2015. Seven prospectively defined Polyscore components were obtained during 30-min continuous recordings of electrocardiogram, blood pressure, and respiration. Out of 1956 subjects, 168 were excluded due to atrial fibrillation, implanted pacemaker, or unsuitable recordings. All-cause mortality over a median 4-year follow-up was prospectively defined as the primary endpoint. The Polyscore divided the investigated population (n = 1788, median age: 72 years, females: 58%) into three predefined groups with low (n = 1405, 78.6%), intermediate (n = 326, 18.2%), and high risk (n = 57, 3.2%). During the follow-up, 82 (4.6%) participants died. Mortality in the Polyscore-defined risk groups was 3.4%, 7.4%, and 17.5%, respectively (P < 0.0001). The Polyscore-based mortality prediction was independent of Framingham score, diabetes, chronic kidney disease, and major stroke and/or myocardial infarction history. It was particularly effective in those aged <75 years (n = 1145). CONCLUSION: The Polyscore-based mortality risk assessment from short-term non-invasive recordings is effective in the elderly general population, especially those aged 60-74 years. Implementation of a comprehensive Polyscore screening of this age group is proposed to advance preventive medical care.

COVID-19 vaccine hesitancy in people with migratory backgrounds: a cross-sectional study among Turkish- and German-speaking citizens in Munich.

BACKGROUND: This study aimed to investigate the knowledge, attitudes, behaviors, and COVID-19 vaccine hesitancy of people with migratory backgrounds among Turkish- and German-speaking patients in Munich. METHODS: Primary outcomes were the intention to get vaccinated for COVID-19 and COVID-19 knowledge levels (25 true/false items). Other variables included demographics, attitudes to COVID-19 and vaccination (7 items), and behaviors regarding COVID-19 (7 items). The attitude and behavior questions had 5-point Likert scales. Of the 10 Turkish-speaking family physicians in Munich, six agreed to administer Turkish or German questionnaires to consecutive patients in February 2021. Furthermore, participants with either citizenship, country of origin, native language, or place of birth being non-German were categorized as "Having a migratory background." Data from 420 respondents were analyzed. RESULTS: Women constituted 41.4% (n = 174), the mean age was 42.2 ± 15.5 years, 245 (58.3%) preferred the Turkish questionnaire, 348 (82.9%) had a migratory background, and 197 (47.9%) intended to be vaccinated. The mean knowledge, attitude, and behavioral scores were 21.5 ± 3.2 (max = 25), 3.7 ± 0.8 (max = 5), and 4.0 ± 0.5 (max = 5). While 42.3% (n = 145) of the participants with a migratory background considered getting vaccinated, this proportion was 76.5% (n = 52) for non-immigrant Germans (Chi-square = 26.818, p < 0.001). Non-migratory background (odds ratio (OR): 3.082), high attitude scores (OR: 2.877), male sex (OR: 2.185), years of schooling (OR: 1.064), and age (OR: 1.022) were positively associated with vaccination intention. CONCLUSIONS: We suggest initiating or supporting projects run by persons or groups with immigrant backgrounds to attempt to elaborate and change their vaccination attitudes.