Effect of mechanical insufflation-exsufflation for ineffective cough on weaning duration in diseases of the peripheral or central nervous system (MEDINE): study protocol for a randomised controlled trial in a neurological weaning centre.

INTRODUCTION: Patients with neurological or neurosurgical disease can suffer from impaired cough, which may result in life-threatening retention of tracheobronchial secretions, atelectasis, pneumonia and finally death. Due to a lack of alternatives and pathophysiological plausibility, the application of mechanical insufflation-exsufflation (MI-E) has already become international standard care in neuromuscular disease and spinal cord injury although a lack of evidence for efficacy. High-quality studies to support the use of MI-E in neurological and neurosurgical patients during weaning from mechanical ventilation are missing. The goal of this exploratory study is to display the effect size of MI-E intervention on the duration of mechanical ventilation and additional outcomes. METHODS AND ANALYSIS: One hundred adult patients with a cough deficiency or retention of secretion admitted to a neurological intensive care unit (ICU) are planned to be recruited for this randomised controlled trial. Patients are randomised 1:1 to receive either MI-E or best standard care. Observation will take place until discharge from the hospital, death or end of the study period. The primary endpoint of this trial is the duration of mechanical ventilation from randomisation until successful weaning. The outcome will be analysed with Kaplan-Meier estimation and competing risks analyses. Secondary endpoint is the proportion of patients with successful weaning. Further outcomes will include the incidence of hospital-acquired pneumonia, mortality, decannulation rate, length of stay on the ICU and the total score of the Glasgow Coma Scale. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee of the University of Oldenburg. The findings of this study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: DRKS00020981.

The impact of pandemic-related social distancing regulations on exercise performance-Objective data and training recommendations to mitigate losses in physical fitness.

Introduction: In the context of the COVID-19 pandemic in Germany, governmental restrictions led to the closure of sports facilities for several months. To date, only subjective and fitness-tracking related data on physical activity during the pandemic are available. Using data of a chip-controlled fitness circuit, training data as a measure of physical performance before and after the lockdown during the first wave of the COVID-19 pandemic will show the impact of the training interruption on exercise performance in middle-aged and older adults. The re-training data are analyzed, to extract practical recommendations. Methods: Objective training data of 17,450 participants [11,097 middle-aged (45-64 yrs), 6,353 older (≥65 yrs)] were exported from chip-controlled milon® fitness circuit systems before and after the first COVID-19 related lockdown in Germany. The change in the product of training weight (sum of lifting and lowering the training weight) and repetitions on the leg extension resistance exercise device (leg score) between the last three training sessions before the lockdown and the first ten training sessions after individual training resumption as well as the last training session before the second lockdown in October 2020 was analyzed. Results: Participants who trained with high intensity before the lockdown, experienced deleterious effects of the training interruption (middle-aged group: -218 kg, older group: ~-230.8 kg; p < 0.001 for change in leg score from to post-lockdown) with no age effect. Participants training with a leg score of more than 3,000 kg did not resume their leg score until the second lockdown. Conclusion: The interruption of training in a fitness circuit with combined resistance and endurance training due to the lockdown affected mainly those participants who trained at high intensity. Apparently, high-intensity training could not be compensated by home-based training or outdoor activities. Concepts for high-intensity resistance training during closure of sports facilities are needed to be prepared for future periods of high incidence rates of infectious diseases, while especially vulnerable people feel uncomfortable to visit sports facilities. Trial registration: Identifier, DRKS00022433.

Flexible semiparametric mode regression for time-to-event data.

The distribution of time-to-event outcomes is usually right-skewed. While for symmetric and moderately skewed data the mean and median are appropriate location measures, the mode is preferable for heavily skewed data as it better represents the center of the distribution. Mode regression has been introduced for uncensored data to model the relationship between covariates and the mode of the outcome. Starting from nonparametric kernel density based mode regression, we examine the use of inverse probability of censoring weights to extend mode regression to handle right-censored data. We add a semiparametric predictor to add further flexibility to the model and we construct a pseudo Akaike's information criterion to select the bandwidth and smoothing parameters. We use simulations to evaluate the performance of our proposed approach. We demonstrate the benefit of adding mode regression to one's toolbox for analyzing survival data on a pancreatic cancer data set from a prospectively maintained cancer registry.

Validity of hospital ICD-10-GM codes to identify anaphylaxis.

PURPOSE: Anaphylaxis (ANA) is an important adverse drug reaction. We examined positive predictive values (PPV) and other test characteristics of ICD-10-GM code algorithms for detecting ANA as used in a multinational safety study (PASS). METHODS: We performed a cross-sectional study on routine data from a German academic hospital (2004-2019, age ≥ 18). Chart review was used for case verification. Potential cases were identified from the hospital administration system. The main outcome required at least one of the following: any type of specific in-hospital code (T78.2, T88.6, and T80.5) OR specific outpatient code in combination with a symptom code OR in-hospital non-specific code (T78.4, T88.7, and Y57.9) in combination with two symptom codes. PPV were calculated with 95% confidence interval. Sensitivity analyses modified type of codes, unit of analysis, verification criteria and time period. The most specific algorithm used only primary codes for ANA (numbers added in brackets). RESULTS: Four hundred and sixteen eligible cases were evaluated, and 78 (37) potential ANA cases were identified. PPV were 62.8% (95% CI 51.1-73.5) (main) and 77.4% (58.9-90.4) (most specific). PPV from all modifications ranged from 12.9% to 80.6%. The sensitivity of the main algorithm was 66.2%, specificity 91.5%, and negative predictive value 92.6%. Corresponding figures for the most specific algorithm were 32.4%, 98.0%, and 87.0%. CONCLUSIONS: The PPV of the main algorithm seems of acceptable validity for use in comparative safety research but will underestimate absolute risks by about a third. Restriction to primary discharge codes markedly improves PPV to the expense of reducing sensitivity.

Weighted expectile regression for right-censored data.

Expectile regression can be used to analyze the entire conditional distribution of a response, omitting all distributional assumptions. Among its benefits are computational simplicity, efficiency, and the possibility to incorporate a semiparametric predictor. Due to its advantages in full data settings, we propose an extension to right-censored data situations, where conventional methods typically focus only on mean effects. We propose to extend expectile regression with inverse probability weights. Estimates are easy to implement and computationally simple. Expectiles can be converted to more easily interpreted tail expectations, that is, the expected residual life. It provides a meaningful effect measure, similar to the hazard rate. The results from an extensive simulation study are presented, evaluating consistency and sensitivity to violations of assumptions. We use the proposed method to analyze survival times of colorectal cancer patients from a regional certified high volume cancer center.

Generalized expectile regression with flexible response function.

Expectile regression, in contrast to classical linear regression, allows for heteroscedasticity and omits a parametric specification of the underlying distribution. This model class can be seen as a quantile-like generalization of least squares regression. Similarly as in quantile regression, the whole distribution can be modeled with expectiles, while still offering the same flexibility in the use of semiparametric predictors as modern mean regression. However, even with no parametric assumption for the distribution of the response in expectile regression, the model is still constructed with a linear relationship between the fitted value and the predictor. If the true underlying relationship is nonlinear then severe biases can be observed in the parameter estimates as well as in quantities derived from them such as model predictions. We observed this problem during the analysis of the distribution of a self-reported hearing score with limited range. Classical expectile regression should in theory adhere to these constraints, however, we observed predictions that exceeded the maximum score. We propose to include a response function between the fitted value and the predictor similarly as in generalized linear models. However, including a fixed response function would imply an assumption on the shape of the underlying distribution function. Such assumptions would be counterintuitive in expectile regression. Therefore, we propose to estimate the response function jointly with the covariate effects. We design the response function as a monotonically increasing P-spline, which may also contain constraints on the target set. This results in valid estimates for a self-reported listening effort score through nonlinear estimates of the response function. We observed strong associations with the speech reception threshold.

TP53 co-mutations in EGFR mutated patients in NSCLC stage IV: A strong predictive factor of ORR, PFS and OS in EGFR mt+ NSCLC.

INTRODUCTION: The impact of TP53 co-mutations in EGFR mutated patients on PFS and OS is controversial. Different classifications of TP53 mutations with respect to functional and potential clinical impact have been published. Therefore, we retrospectively analyzed the impact of TP53 co-mutations on ORR, PFS and OS in a cohort of EGFR mutated NSCLC IV patients (UICC 7) using different classifications of TP53 mutations. METHODS: 75 EGFR mutated NSCLC IV patients homogeneously treated with 1st line EGFR TKI were analyzed for TP53 co-mutations. TP53 mutations were classified according to three different types of classifications. The endpoints ORR, PFS and OS were investigated. RESULTS: TP53 co-mutations were found in 29/59 patients (49.2%). TP53 co-mutations were a statistically significant independent negative predictive factor for ORR, PFS and OS. TP53 co-mutations were associated with inferior mPFS and mOS: mPFS/mOS 12 vs. 18/24 vs. 42 months for non-disruptive/disruptive mutations vs. WT (p < 0.004)/(p < 0.009), 11 vs. 17/23 vs. 42 months for pathogenic vs. non-pathogenic/WT (p < 0.001)/(p < 0.001), and 7 vs. 12 vs. 18/12 vs. 28 vs. 42 months for exon 8 vs. non-exon 8 vs. WT (p < 0.001)/(p < 0.002). CONCLUSIONS: TP53 co-mutations are frequent in EGFR mt+ NSCLC and have a strong negative impact on all clinical endpoints of TKI therapy.

Modeling physical activity data using L0 -penalized expectile regression.

In recent years accelerometers have become widely used to objectively assess physical activity. Usually intensity ranges are assigned to the measured accelerometer counts by simple cut points, disregarding the underlying activity pattern. Under the assumption that physical activity can be seen as distinct sequence of distinguishable activities, the use of hidden Markov models (HMM) has been proposed to improve the modeling of accelerometer data. As further improvement we propose to use expectile regression utilizing a Whittaker smoother with an L0 -penalty to better capture the intensity levels underlying the observed counts. Different expectile asymmetries beyond the mean allow the distinction of monotonous and more variable activities as expectiles effectively model the complete distribution of the counts. This new approach is investigated in a simulation study, where we simulated 1,000 days of accelerometer data with 1 and 5 s epochs, based on collected labeled data to resemble real-life data as closely as possible. The expectile regression is compared to HMMs and the commonly used cut point method with regard to misclassification rate, number of identified bouts and identified levels as well as the proportion of the estimate being in the range of ±10% of the true activity level. In summary, expectile regression utilizing a Whittaker smoother with an L0 -penalty outperforms HMMs and the cut point method and is hence a promising approach to model accelerometer data.

Modeling determinants of satisfaction with health care in youth with inflammatory bowel disease part 2: semiparametric distributional regression.

Background: Methodological challenges arise with the analysis of patient satisfaction as a measure of health care quality. One of them is the necessity to adjust for differences in patient characteristics or other variables. A combination of several helpful extensions to regression analysis is shown based on patients with inflammatory bowel disease (IBD) to help identify important covariates associated with the distribution of satisfaction. Patients and methods: Analyses were based on cross-sectional data from a postal survey on the health care of patients with IBD aged 15-25, with satisfaction assessed using a 32-item validated questionnaire weighing experience by perceived relevance. The weighted summary score was modeled using a Beta distribution in a generalized additive model for location, scale and shape. Covariates were distinguished in 3 groups and the model was entered in separate, consecutive analyses. First, demographic and disease-related variables were included. Next, information about the IBD specialist was added. The third step added care quality indicators. Results are presented as OR with 95% CI. Results: In the survey, 619 questionnaires were returned and the data set had 453 complete cases for analysis. Satisfaction appeared increased for patients working (OR 1.59, 95% CI: 1.19-2.11) or studying (1.25, 1.00-1.56) as compared to those still at school or in non-academic job training. High anxiety scores and an older age of onset were associated with lower satisfaction. The variation of satisfaction is higher for patients with Crohn's disease or who have statutory insurance (1.19, 1.01-1.40 and 1.22, 1.06-1.40). Conclusion: Modeling the entire distribution of the response uncovered additional influences on the variance of patient satisfaction not previously identified by classical regression. It also resulted in a richer model for the mean. The construction of a combined model for different features of the distribution also helped to improve the control of confounding.

Evaluation of Electronic and Paper-Pen Data Capturing Tools for Data Quality in a Public Health Survey in a Health and Demographic Surveillance Site, Ethiopia: Randomized Controlled Crossover Health Care Information Technology Evaluation.

BACKGROUND: Periodic demographic health surveillance and surveys are the main sources of health information in developing countries. Conducting a survey requires extensive use of paper-pen and manual work and lengthy processes to generate the required information. Despite the rise of popularity in using electronic data collection systems to alleviate the problems, sufficient evidence is not available to support the use of electronic data capture (EDC) tools in interviewer-administered data collection processes. OBJECTIVE: This study aimed to compare data quality parameters in the data collected using mobile electronic and standard paper-based data capture tools in one of the health and demographic surveillance sites in northwest Ethiopia. METHODS: A randomized controlled crossover health care information technology evaluation was conducted from May 10, 2016, to June 3, 2016, in a demographic and surveillance site. A total of 12 interviewers, as 2 individuals (one of them with a tablet computer and the other with a paper-based questionnaire) in 6 groups were assigned in the 6 towns of the surveillance premises. Data collectors switched the data collection method based on computer-generated random order. Data were cleaned using a MySQL program and transferred to SPSS (IBM SPSS Statistics for Windows, Version 24.0) and R statistical software (R version 3.4.3, the R Foundation for Statistical Computing Platform) for analysis. Descriptive and mixed ordinal logistic analyses were employed. The qualitative interview audio record from the system users was transcribed, coded, categorized, and linked to the International Organization for Standardization 9241-part 10 dialogue principles for system usability. The usability of this open data kit-based system was assessed using quantitative System Usability Scale (SUS) and matching of qualitative data with the isometric dialogue principles. RESULTS: From the submitted 1246 complete records of questionnaires in each tool, 41.89% (522/1246) of the paper and pen data capture (PPDC) and 30.89% (385/1246) of the EDC tool questionnaires had one or more types of data quality errors. The overall error rates were 1.67% and 0.60% for PPDC and EDC, respectively. The chances of more errors on the PPDC tool were multiplied by 1.015 for each additional question in the interview compared with EDC. The SUS score of the data collectors was 85.6. In the qualitative data response mapping, EDC had more positive suitability of task responses with few error tolerance characteristics. CONCLUSIONS: EDC possessed significantly better data quality and efficiency compared with PPDC, explained with fewer errors, instant data submission, and easy handling. The EDC proved to be a usable data collection tool in the rural study setting. Implementation organization needs to consider consistent power source, decent internet connection, standby technical support, and security assurance for the mobile device users for planning full-fledged implementation and integration of the system in the surveillance site.

Modeling determinants of satisfaction with health care in youth with inflammatory bowel disease: a cross-sectional survey.

PURPOSE: Patient satisfaction is frequently used as a health care quality measure despite methodological challenges. By the example of pediatric inflammatory bowel disease (IBD), we assessed factors associated with low satisfaction and examined differences by type of provider. PATIENTS AND METHODS: In a cross-sectional design, a 32-item questionnaire and global questioning were used to assess satisfaction in patients aged 15-25 years. Determinants of low satisfaction were identified by logistic regression (OR with 95% CI). Separate models were calculated for patient-related variables such as age, socioeconomic status (SES), health status (emotional, somatic, quality of life) or region of residence (step 1), and impact of provider (pediatric specialist, adult specialist, no specialist) (step 2). As secondary analysis, we studied the effect of additional indicators such as waiting time, consultation time, and an IBD Management Quality Index (IMQI) on effect estimates (step 3). RESULTS: A total of 567 cases were available for analysis (response 48.2%). The strongest predictors of low satisfaction were anxiety symptoms (OR 2.49, CI 1.14 to 5.45). In step 2, not being seen by a specialist (1.89, 1.16 to 3.10) and having been with the new provider for less than 12 months (1.71, 1.03 to 2.83) were associated with low satisfaction. Satisfaction with adult care provider was similar to pediatric care if adjusted for anxiety, health status, and time with provider (0.95, 0.59 to 1.51). Presence of other quality indicators (step 3), waiting time >30 minutes, consultation time <15 minutes, and low IMQI were all associated with low satisfaction. Age, SES, and region of residence were not found to affect satisfaction in any of the models. CONCLUSION: Anxiety symptoms were most strongly associated with low patient satisfaction. The relevance of recent provider change and not being seen by a specialist underlines the importance of well-planned transition in this age group.

Counteracting the Slowdown of Reaction Times in a Vigilance Experiment With 40-Hz Transcranial Alternating Current Stimulation.

Indicators for a decrement in vigilance are a slowdown in reaction times and an increase in alpha power in the electroencephalogram in posterior regions of the brain. Transcranial alternating current stimulation (tACS) is a neuropsychological technique that has been found to interact with intrinsic brain oscillations and is able to enhance cognitive and behavioral performance. Recent studies show that tACS in the gamma frequency range (30-80 Hz) is able to downregulate amplitudes in the alpha frequency range (8-12 Hz), in accordance to the effect referred to as cross-frequency coupling, where intrinsic alpha and gamma waves modulate each other. We applied 40 Hz gamma-tACS to the visual cortex during a vigilance experiment and investigated if stimulation improves reaction times and error rates with time-on-task. In our sham controlled experiment, participants completed two blocks of 30 minutes duration while performing the same visual two-choice task. The first block was used as BASELINE. A statistical analysis with a linear mixed model revealed a significantly lower increase of modeled reaction times over time in the INTERVENTION-block of the tACS-group as compared with their BASELINE-block whereas there was no significant change between the BASELINE- and INTERVENTION-block for the SHAM-group. Error rates did not differ between groups. This paper indicates that gamma-tACS can enhance performance in vigilance tasks as it significantly decreased the slowdown of reaction times in our study.

Adjusting Expectations: Hearing Abilities in a Population-Based Sample Using an SSQ Short Form.

The German short form of the Speech, Spatial, and Qualities of Hearing Scale (SSQ) was administered in a cross-sectional study based on stratified random samples complemented by audiometric tests and a general interview. Data from 1,711 unaided adults aged 18 to 97 years were analyzed in order to determine a distribution of hearing abilities considered as normal and the main factors that impact self-assessments. An innovative mathematical approach was used to overcome the constraints of statistics based on the mean. Quantile regression analysis yielded a benchmark distribution of SSQ scores that might support audiologists in setting realistic SSQ score targets and estimated how the effect of auditory and nonauditory factors changes across the distribution of SSQ scores. Regression models showed significant effects for nonauditory factors on SSQ ratings when controlled for pure-tone hearing and interaural asymmetry. Self-reporting of hearing difficulties, when asked in general terms, was substantially related to SSQ ratings. This effect was observed in both high and low scoring participants and led to a considerable score decrease in all SSQ subscales. Gender, educational level, and self-reporting of health issues also were significantly related to SSQ ratings, but the corresponding effects were regularly unbalanced across the score distribution and particularly large at lower quantiles. The estimated effects of age, however, were mostly small in size, inconsistent regarding the direction, and failed significance for all SSQ items. Overall, the results suggest that nonauditory factors and cumulative effects must be considered when evaluating rehabilitative interventions against an ideal outcome.