BITES: balanced individual treatment effect for survival data.

MOTIVATION: Estimating the effects of interventions on patient outcome is one of the key aspects of personalized medicine. Their inference is often challenged by the fact that the training data comprises only the outcome for the administered treatment, and not for alternative treatments (the so-called counterfactual outcomes). Several methods were suggested for this scenario based on observational data, i.e. data where the intervention was not applied randomly, for both continuous and binary outcome variables. However, patient outcome is often recorded in terms of time-to-event data, comprising right-censored event times if an event does not occur within the observation period. Albeit their enormous importance, time-to-event data are rarely used for treatment optimization. We suggest an approach named BITES (Balanced Individual Treatment Effect for Survival data), which combines a treatment-specific semi-parametric Cox loss with a treatment-balanced deep neural network; i.e. we regularize differences between treated and non-treated patients using Integral Probability Metrics (IPM). RESULTS: We show in simulation studies that this approach outperforms the state of the art. Furthermore, we demonstrate in an application to a cohort of breast cancer patients that hormone treatment can be optimized based on six routine parameters. We successfully validated this finding in an independent cohort. AVAILABILITY AND IMPLEMENTATION: We provide BITES as an easy-to-use python implementation including scheduled hyper-parameter optimization (https://github.com/sschrod/BITES). The data underlying this article are available in the CRAN repository at https://rdrr.io/cran/survival/man/gbsg.html and https://rdrr.io/cran/survival/man/rotterdam.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Analysis of Snoring in Patients with Obstructive Sleep Apnea (OSA) by Polysomnography and LEOSound]. / Die Analyse von Schnarchen bei Patienten mit obstruktiver Schlafapnoe (OSA) anhand von Polysomnographie und LEOSound.

INTRODUCTION: Snoring was monitored in patients with obstructive sleep apnea (OSA) using the LEOSound-Monitor and simultaneously polysomnographic (PSG) recording. In obstructive apneas snoring is normally apparent after apnea termination and the beginning of ventilation. We wanted to know how often obstructive apneas are terminated by ventilation in combination with snoring. METHODS AND INTENTION: In 40 patients with OSA (AHI > 15/h) simultaneous polysomnographic recordings were performed amongst long-term respiratory sound monitoring using the LEOSound monitor. Patients' average age was 57±11 years. Average weight was 100±19 kg by a mean body mass index (BMI) of 33±7 kg/m2. 12 out of 40 recordings had to be rejected for further analysis because of artifacts. Snoring recorded by polysomnography was compared with snoring monitored by LEOSound. RESULTS: 3778 obstructive apnea episodes were monitored. LEOSound identified snoring in 1921 (51,0%), polysomnography in 2229 (58,8%) obstructive apneas. Only in one patient there was a higher difference in snoring episodes between PSG and LEOSound. DISCUSSION: In nearly 60% of obstructive apnea events we found snoring during apnea-terminating hyperpnoea. LEOSound is a good diagnostic tool to monitor snoring. It is necessary to clarify why only 60% of all obstructive events/hyperpnoea develop snoring. From a pathophysiological point of view opening of collapsed upper airway should lead in a very high percentage to turbulences in airstream and committed snoring.

What factors explain the increase in obesity in Brazil? An ecological analysis of contextual and behavioural components.

OBJECTIVES: It has been suggested that contextual factors may be related to obesity; however, they have not yet been widely investigated. The main objective of this ecological time-series study was to analyse factors associated with the increase in obesity in the adult and elderly population in Brazil from 2006 to 2020. STUDY DESIGN: This is an ecological time-series study. Data were collected by the Surveillance System for Risk and Protection Factors for Chronic Diseases by Telephone Survey (VIGITEL), the main health survey in Brazil. METHODS: The outcome was the annual obesity growth rate (in percentage points). Independent variables were behavioural and contextual factors. Data analysis was performed using Prais-Winsten regression for temporal analyses, and Spearman correlation and crude and adjusted linear regression (beta and 95% confidence intervals [CIs]). RESULTS: The annual obesity growth rate was 0.58 percentage points (p.p.) (95% CI: 0.54; 0.63) per year. Demographic density and the percentage of the population employed showed an inverse association with the growth of obesity. Variables such as Gross Domestic Product (GDP) per capita, Gini coefficient, urbanisation rate, percentage of the population with low level of education and percentage of the population without an income were directly associated with the increase in obesity rates. The variables maintained in the final model explained 81% of the growth in obesity in Brazil over the last 15 years (2006-2020). CONCLUSIONS: The growth of obesity in Brazil was mostly explained by contextual factors, especially those of a socio-economic nature. Therefore, interventions to mitigate the increase in obesity must go beyond behavioural factors.

[Analysis of Snoring in Patients with Obstructive Sleep Apnea (OSA) by Polysomnography and LEOSound]. / Die Analyse von Schnarchen bei Patienten mit obstruktiver Schlafapnoe (OSA) anhand von Polysomnografie und LEOSound.

INTRODUCTION: Snoring was monitored in patients with obstructive sleep apnea (OSA) using the LEOSound-Monitor and simultaneously polysomnographic (PSG) recording. In obstructive apneas snoring is normally apparent after apnea termination and the beginning of ventilation. We wanted to know how often obstructive apneas are terminated by ventilation in combination with snoring. METHODS AND INTENTION: In 40 patients with OSA (AHI > 15/h) simultaneous polysomnographic recordings were performed amongst long-term respiratory sound monitoring using the LEOSound monitor. Patients' average age was 57 ±â€Š11 years. Average weight was 100 ±â€Š19 kg by a mean body  mass  index (BMI) of 33 ±â€Š7 kg/m2. 12 out of 40 recordings had to be rejected for further analysis because of artifacts. Snoring recorded by polysomnography was compared with snoring monitored by LEOSound. RESULTS: 3778 obstructive apnea episodes were monitored. LEOSound identified snoring in 1921 (51,0 %), polysomnography in 2229 (58,8 %) obstructive apneas. Only in one patient there was a higher difference in snoring episodes between PSG and LEOSound. DISCUSSION: In nearly 60 % of obstructive apnea events we found snoring during apnea-terminating hyperpnoea. LEOSound is a good diagnostic tool to monitor snoring. It is necessary to clarify why only 60 % of all obstructive events/hyperpnoea develop snoring. From a pathophysiological point of view opening of collapsed upper airway should lead in a very high percentage to turbulences in airstream and committed snoring.

[Oral anticoagulation and antiplatelet therapy in patients with atrial fibrillation after coronary interventions]. / Orale Antikoagulation und antithrombozytäre Therapie bei Patienten mit Vorhofflimmern nach Koronarintervention.

Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following elective percutaneous coronary intervention and also after acute coronary syndrome (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, unstable angina pectoris); however, DAPT is not sufficient for stroke prevention in atrial fibrillation (SPAF). For SPAF, oral anticoagulation (OAC) with vitamin K antagonists (VKA) or non-vitamin K-dependent anticoagulants (NOAC) is required. If a patient who is receiving anticoagulants for SPAF, requires a coronary intervention, triple therapy consisting of OAC plus DAPT is given, at least for a limited time following the procedure. This article reviews the current data from studies testing strategies with NOACs plus one or two antiplatelet substances in comparison to triple therapy with VKA.

[Platelet inhibition in elderly patients]. / Thrombozytenhemmung beim alten Menschen.

Single antiplatelet therapy (SAPT) using predominantly acetylsalicylic acid (ASA) is the baseline anti-thrombotic therapy in primary as well as secondary prevention of atherosclerotic disease. Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following elective percutaneous coronary interventions or acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction and unstable angina pectoris). In the past the duration of DAPT in particular has been frequently discussed. Current recommendations, such as the "Focused Update DAPT 2017" of the European Society of Cardiology (ESC) emphasize the importance of strategies aiming to reduce an increased risk of bleeding based on clinical predictors. In this case older age is an important factor relevant for bleeding. In this article, the evidence for SAPT or DAPT is summarized with a special focus on patients aged ≥75 years.

[Perianal inflammatory diseases : Classification and imaging]. / Perianale entzündliche Erkrankungen : Klassifikation und Bildgebung.

During the past 30 years, classifications and scoring systems have been developed in order to evaluate and objectify the degree and activity of anorectal fistulas. Only a few of these disease-specific instruments have been adopted into daily clinical routine. Generally, clinicians tend to use global medical judgement rather than numeric activity indices, which often seem complex and time consuming. Activity scores in Crohn disease, however, appeared to be very useful in clinical trials regarding evaluation of therapy response. Thus, activity indices must be simple and reproducible. The years 1976 and 1995, in which the Parks Classification and Perianal Disease Activity Index (PDAI) were established, can be considered milestone years for classifying patients with anorectal fistulizing disease. These instruments should be recognized at present as the gold standard for evaluating the complexity as well as the severity of anorectal fistulas and perianal Crohn disease.

Targeted spine strengthening exercise and posture training program to reduce hyperkyphosis in older adults: results from the study of hyperkyphosis, exercise, and function (SHEAF) randomized controlled trial.

A 6-month randomized controlled trial of spine-strengthening exercise and posture training reduced both radiographic and clinical measures of kyphosis. Participants receiving the intervention improved self-image and satisfaction with their appearance. Results suggest that spine-strengthening exercise and postural training may be an effective treatment option for older adults with hyperkyphosis. INTRODUCTION: The purpose of the present study is to determine in a randomized controlled trial whether spine-strengthening exercises improve Cobb angle of kyphosis in community-dwelling older adults. METHODS: We recruited adults ≥60 years with kyphosis ≥40° and enrolled 99 participants (71 women, 28 men), mean age 70.6 ± 0.6 years, range 60-88, with baseline Cobb angle 57.4 ± 12.5°. The intervention included group spine-strengthening exercise and postural training, delivered by a physical therapist, 1-h, three times weekly for 6 months. Controls received four group health education meetings. The primary outcome was change in the gold standard Cobb angle of kyphosis measured from standing lateral spine radiographs. Secondary outcomes included change in kyphometer-measured kyphosis, physical function (modified Physical Performance Test, gait speed, Timed Up and Go, Timed Loaded Standing, 6-Min Walk), and health-related quality of life (HRQoL) (PROMIS global health and physical function indexes, SRS-30 self-image domain). ANCOVA was used to assess treatment effects on change from baseline to 6 months in all outcomes. RESULTS: There was a -3.0° (95% CI -5.2, -0.8) between-group difference in change in Cobb angle, p = 0.009, favoring the intervention and approximating the magnitude of change from an incident vertebral fracture. Kyphometer-measured kyphosis (p = 0.03) and SRS-30 self-esteem (p < 0.001) showed favorable between-group differences in change, with no group differences in physical function or additional HRQoL outcomes, p > 0.05. CONCLUSIONS: Spine-strengthening exercise and posture training over 6 months reduced kyphosis compared to control. Our randomized controlled trial results suggest that a targeted kyphosis-specific exercise program may be an effective treatment option for older adults with hyperkyphosis. TRIAL REGISTRATION NUMBER AND NAME OF TRIAL REGISTER: ClinicalTrials.gov; identifier NCT01751685.

[Focused update on dual antiplatelet treatment : ESC guidelines 2017]. / Fokussiertes Update zur dualen Plättchenhemmung : ESC-Leitlinie 2017.

Dual antiplatelet treatment (DAPT) is a cornerstone of maintenance medication of patients following elective percutaneous coronary interventions or an acute coronary syndrome (ACS), e. g. ST elevation myocardial infarction, non-ST elevation myocardial infarction and unstable angina. In recent years the inclusion of P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. Following the introduction of the modern generation of drug-eluting stents for elective coronary interventions, the duration of the necessary DAPT has been clearly reduced. In patients with ACS the question arises when treatment with one of the more potent P2Y12 inhibitors, such as prasugrel and ticagrelor should be used instead of clopidogrel. A potential extension of DAPT beyond 12 months can be considered in high-risk patients after implantation of bioresorbable vascular scaffolds and following myocardial infarction. A special focus is on those patients who have already been treated with oral anticoagulants for stroke prevention in atrial fibrillation and require additional platelet inhibition following coronary stenting. This article summarizes and assesses the major recommendations given in the Focused Update DAPT 2017 of the European Society of Cardiology (ESC). In particular the recommendations address strategies to reduce an increased risk of bleeding based on clinical predictors.

[Left ventricular unloading in cardiogenic shock]. / Linksventrikuläres Unloading im kardiogenen Schock.

Cardiogenic shock is an acute life-threatening condition, which results in impaired end-organ perfusion and oxygenation. Invasive ventilation and medicinal treatment with inotropes or vasopressors are necessary in most cases; however, they are also associated with reduced long-term prognosis. Frequently, medical treatment is not even sufficient to stabilize the patient; therefore, dedicated mechanical circulatory support devices that actively reduce the load on the left ventricle were developed to allow myocardial recovery or to gain time until definitive treatment. These systems are now available for implementation at large centers.

[Apnea Detection by Means of Respiratory Sound Recordings and Polysomnography - A Comparative Study]. / Ein Vergleich der Apnoeerkennung bei Patienten mit obstruktiver Schlafapnoe (OSA) anhand von Atemgeräuschaufzeichnungen und Polysomnografie.

Introduction In this study, recognition of apnoeas by means of polysomnography (PSG) and nocturnal respiratory sound recordings in patients with obstructive sleep apnoea (OSA) was analyzed and compared. Methods In 45 patients with OSA requiring treatment (AHI > 15/h), concomitant polysomnographic recordings and long term respiratory sound recordings by means of LEOSound were performed. Patients' average age was 58 ±â€Š12 years (mean ± standard deviation), average BMI was 33 ±â€Š7 kg/m2. Audio-visual apnoea detection by LEOSound was compared to polysomnographic apnoea detection. Increased artifact rate due to dislocation of microphones led to rejection of 11 out of 45 recordings for detailed analysis. Results Comparison of apnea detection by audio-visual analysis and polysomnography yielded a median of 164 apneas for LEOSound recordings and 158 apneas for PSG. Median apnoea index (AI) was calculated to be 20/h for respiratory sounds recording and 21/h for PSG. The correlation of apnea indices from acoustic long term registration and PSG was 0.939 (p < 0.001). Discussion Acoustic long term registration of primary and secondary respiratory sounds is also capable to recognize apnoeas. Exact differentiation between apnoeas and hypopnoeas is only possible in a limited fashion.

[Validation of the German version of the Oxford Elbow Score : A cross-sectional study]. / Validierung der deutschen Version des Oxford Elbow Score : Eine Querschnittsstudie.

BACKGROUND: Elbow complaints are complex problems leading to severe consequences for affected people and the healthcare system. The German version of the Oxford Elbow Score (OES) is the first German-speaking instrument that specifically measures elbow complaints from the patient's perspective and changes of their health status. OBJECTIVE: The aim of this study is the validation of the German version of the OES. In this context the internal consistency and the construct validity were investigated. MATERIALS AND METHODS: 59 patients with elbow complaints completed the German version of the OES, the DASH and the SF-36 in a cross-sectional study. The internal consistency was calculated with Cronbach's alpha coefficients. Spearman's correlation coefficients were used to confirm construct validity. RESULTS: Cronbach's alpha for pain, function and psychological subscales was 0.88, 0.81 and 0.90, respectively. The whole questionnaire presents a Cronbach's alpha value of 0.93. Convergent construct validity was confirmed with correlation coefficients containing values of -0.84, -0.77 and -0.82 compared to DASH and values ranging from 0.41 to 0.80 compared with the physical domains of the SF-36. The divergent construct validity presented values ranging from 0.07 to 0.20 with the SF-36 domains of "general health perception" and "mental health". CONCLUSION: The German OES is an internal consistent instrument with good convergent and divergent construct validity. Other aspects of the validity, the reliability and the responsiveness should be confirmed through further studies.

A cytoarchitecture-driven myelin model reveals area-specific signatures in human primary and secondary areas using ultra-high resolution in-vivo brain MRI.

This work presents a novel approach for modelling laminar myelin patterns in the human cortex in brain MR images on the basis of known cytoarchitecture. For the first time, it is possible to estimate intracortical contrast visible in quantitative ultra-high resolution MR images in specific primary and secondary cytoarchitectonic areas. The presented technique reveals different area-specific signatures which may help to study the spatial distribution of cortical T1 values and the distribution of cortical myelin in general. It may lead to a new discussion on the concordance of cyto- and myeloarchitectonic boundaries, given the absence of such concordance atlases. The modelled myelin patterns are quantitatively compared with data from human ultra-high resolution in-vivo 7T brain MR images (9 subjects). In the validation, the results are compared to one post-mortem brain sample and its ex-vivo MRI and histological data. Details of the analysis pipeline are provided. In the context of the increasing interest in advanced methods in brain segmentation and cortical architectural studies, the presented model helps to bridge the gap between the microanatomy revealed by classical histology and the macroanatomy visible in MRI.

The influence of birth order and number of siblings on adolescent body composition: evidence from a Brazilian birth cohort study.

The aim of this study was to estimate the association between birth order and number of siblings with body composition in adolescents. Data are from a birth cohort study conducted in Pelotas, Brazil. At the age of 18 years, 4563 adolescents were located, of whom 4106 were interviewed (follow-up rate 81.3 %). Of these, 3974 had complete data and were thus included in our analysis. The variables used in the analysis were measured during the perinatal period, or at 11, 15 and/or 18 years of age. Body composition at 18 years was collected by air displacement plethysmography (BOD POD®). Crude and adjusted analyses of the association between birth order and number of siblings with body composition were performed using linear regression. All analyses were stratified by the adolescent sex. The means of BMI, fat mass index and fat-free mass index among adolescents were 23.4 (sd 4.5) kg/m², 6.1 (sd 3.9) kg/m² and 17.3 (sd 2.5) kg/m², respectively. In adjusted models, the total siblings remained inversely associated with fat mass index (ß = - 0.37 z-scores, 95 % CI - 0.52, - 0.23) and BMI in boys (ß = - 0.39 z-scores, 95 % CI - 0.55, - 0.22). Fat-free mass index was related to the total siblings in girls (ß = 0.06 z-scores, 95 % CI - 0.04, 0.17). This research has found that number of total siblings, and not birth order, is related to the fat mass index, fat-free mass index and BMI in adolescents. It suggests the need for early prevention of obesity or fat mass accumulation in only children.

A novel mutation in the XPA gene results in two truncated protein variants and leads to a severe XP/neurological symptoms phenotype.

BACKGROUND: The nucleotide excision repair (NER) pathway repairs UV-induced DNA lesions in an accurate fashion and prevents UV-irradiated areas of the skin from tumour formation. The XPA protein plays a major role in DNA damage demarcation as well as stabilization of other NER factors and was found to be defective in xeroderma pigmentosum (XP) complementation group A patients. OBJECTIVE: Characterization of four new XP-A patients. METHODS: Genomic and cDNA sequencing, post-UV cell survival of living cells, host-cell reactivation of patients' fibroblasts and Western blotting. RESULTS: One of the four investigated patients shows a novel mutation leading to two different truncated protein variants. Three patients contain the already described p.R228X mutation. All patient cell lines exhibit a strong UVC sensitivity and reduced NER capability. In most of the cases stable protein expression was detected. CONCLUSION: We discovered four new XP-A patients and a novel XPA mutation resulting in two diverse patient alleles.

[Local imaging of rectal cancer--update 2015: MRI as imaging biomarker]. / Lokale Bildgebung beim Rektumkarzinom--Update 2015: MRT als "Imaging"-Biomarker.

The significance of state of the art magnetic resonance imaging (MRI) for rectal cancer goes far beyond the detection and diagnostics of local dispersion and is increasingly focusing on patient prognosis. The identification of prognostic factors, such as tumor (T) and nodal (N) status, involvement of the circumferential resection margin, presence of extramural vascular invasion, tumor response prediction following neoadjuvant therapy, therapy-related changes in microcirculation, permeability and tissue cellularity and structured reporting are important elements of advanced rectal cancer imaging. In this context, multiparametric MRI is progressively evolving into a powerful imaging biomarker.

[Fusion of Continuously Moving Table MRI and PET Improves Lesion Detection in Recurrent Rectal Cancer]. / Kombination von MRT und PET erlaubt genauere Rezidivdiagnostik des Rektumkarzinoms durch Bildfusion.

PURPOSE: It was the aim of this study to investigate the complementary diagnostic performance of a combined pelvic and thoracoabdominal magnetic resonance imaging (MRI) examination and positron emission tomography (PET) enhanced by image fusion in patients with suspected rectal cancer recurrence. PATIENTS AND METHODS: Thirty-one patients with clinically suspected recurrence from rectal cancer were retrospectively included, who had received MRI (high resolution pelvic MRI combined with thoracoabdominal MRI performed during continuous table translation) and (18)F-FDG-PET within 30 days. MRI alone, PET alone, and MRI and PET combined including fusion images were analysed by two observers in consensus. The likelihood of malignancy of all detectable lesions was rated on a 5-point Likert scale. The standard of reference consisted of histopathology and follow-up imaging. Confidence ratings were analysed with a jackknife free response receiver-operator characteristic paradigm (JAFROC). Further test characteristics were derived by considering "probably malignant" and "definitely malignant" lesions as positive test results. RESULTS: The reference standard comprised 150 malignant lesions (48 local, 102 distant). JAFROC analysis revealed overall figures-of-merit of 0.73 for MRI, 0.63 for PET, and 0.83 for the combined approach (differences significant). The sensitivities of MRI, PET and the combined approach were 85.4, 52.1, and 95.8 % for local recurrence and 61.8, 47.1, and 81.4 % for distant recurrence, respectively. CONCLUSION: The combination of local high-resolution MRI, thoracoabdominal continuously moving table MRI and FDG-PET supported by image fusion improves lesion detection in recurrent rectal cancer.

Quantifying inter-individual anatomical variability in the subcortex using 7 T structural MRI.

Functional magnetic resonance imaging (MRI) data are usually registered into standard anatomical space. However, standard atlases, such as LPBA40, the Harvard-Oxford atlas, FreeSurfer, and the Jülich cytoarchitectonic maps all lack important detailed information about small subcortical structures like the substantia nigra and subthalamic nucleus. Here we introduce a new subcortical probabilistic atlas based on ultra-high resolution in-vivo anatomical imaging from 7 T MRI. The atlas includes six important but elusive subcortical nuclei: the striatum, the globus pallidus internal and external segment (GPi/e), the subthalamic nucleus, the substantia nigra, and the red nucleus. With a sample of 30 young subjects and carefully cross-validated delineation protocols, our atlas is able to capture the anatomical variability within healthy populations for each of the included structures at an unprecedented level of detail. All the generated probabilistic atlases are registered to MNI standard space and are publicly available.

Paramagnetic squeezing of QCD matter.

We determine the magnetization of quantum chromodynamics for several temperatures around and above the transition between the hadronic and the quark-gluon phases of strongly interacting matter. We obtain a paramagnetic response that increases in strength with the temperature. We argue that due to this paramagnetism, chunks of quark-gluon plasma produced in noncentral heavy ion collisions should become squeezed perpendicular to the magnetic field. This anisotropy will then contribute to the elliptic flow v2 observed in such collisions, in addition to the pressure gradient that is usually taken into account. We present a simple estimate for the magnitude of this new effect and a rough comparison to the effect due to the initial collision geometry. We conclude that the paramagnetic effect might have a significant impact on the value of v2.