What is associated with painful polyneuropathy? A cross-sectional analysis of symptoms and signs in patients with painful and painless polyneuropathy.

ABSTRACT: It is still unclear how and why some patients develop painful and others painless polyneuropathy. The aim of this study was to identify multiple factors associated with painful polyneuropathies (NeuP). A total of 1181 patients of the multicenter DOLORISK database with painful (probable or definite NeuP) or painless (unlikely NeuP) probable or confirmed neuropathy were investigated clinically, with questionnaires and quantitative sensory testing. Multivariate logistic regression including all variables (demographics, medical history, psychological symptoms, personality items, pain-related worrying, life-style factors, as well as results from clinical examination and quantitative sensory testing) and machine learning was used for the identification of predictors and final risk prediction of painful neuropathy. Multivariate logistic regression demonstrated that severity and idiopathic etiology of neuropathy, presence of chronic pain in family, Patient-Reported Outcomes Measurement Information System Fatigue and Depression T-Score, as well as Pain Catastrophizing Scale total score are the most important features associated with the presence of pain in neuropathy. Machine learning (random forest) identified the same variables. Multivariate logistic regression archived an accuracy above 78%, random forest of 76%; thus, almost 4 out of 5 subjects can be classified correctly. This multicenter analysis shows that pain-related worrying, emotional well-being, and clinical phenotype are factors associated with painful (vs painless) neuropathy. Results may help in the future to identify patients at risk of developing painful neuropathy and identify consequences of pain in longitudinal studies.

Digital Examination vs. 4D Transperineal Ultrasound-Do They Compare in Labour Management? A Pilot Study.

The aim was to compare transperineal ultrasound (TPU) with parameters of the Bishop Score during the first stage of labour and evaluate how TPU can contribute towards improving labour management. Digital examination (DE) and TPU were performed on 42 women presenting at the labour ward with regular contractions. TPU measurements included the head-symphysis distance, angle of progression, diameter of the cervical wall, cervical dilation (CD) and cervical length (CL). To examine if TPU can monitor labour progress, correlations of TPU parameters were calculated. Agreement of DE and TPU was examined for CL and CD measurements and for two groups divided into latent (CD < 5 cm) and active stages of labour (CD ≥ 5 cm). TPU parameters indicated a moderate negative correlation of CD and CL (Pearson: r = -0.667; Spearman = -0.611). The other parameters showed a weak to moderate correlation. DE and TPU measurements for CD showed better agreement during the latent stage than during the active stage. The results of the present study add to the growing evidence that TPU may contribute towards an improved labour management, suggesting a combined approach of TPU and DE to monitor the latent first stage of labour and using only DE during the active stage of labour.

Reliability and Reproducibility of Analyzing 3D Transperineal Ultrasound Volumes Obtained in the First Phase of Labor - A Pilot Study.

PURPOSE: The aim of this study was to investigate the reliability and reproducibility of transperineal ultrasound (TPUS) in the initial phase of labor. As TPUS is a common method, it could supplement vaginal palpation and even replace it in certain situations. In addition, we used a 4-dimensional method for the assessment of cervical effacement. MATERIALS AND METHODS: 54 women in labor were included and underwent TPUS. The resulting images from the acquired 4D volumes were evaluated after the examination for the first time and a second time after 21 days. The measured values were cervical length, dilatation and effacement, the angle of progression (AoP), and head-perineum distance. RESULTS: 54 patients were examined. TPUS images were unable to be evaluated in 12 patients because of cervical dilatation of more than 5 cm or poor image quality. Thus, 42 measurements were included. The concordance correlation coefficients according to Lin are satisfactory overall, with one exception for cervical effacement. The accuracy component of cervical length (CCCLin: 0.93; accuracy: 1.00), dilatation (CCCLin: 0.93; accuracy: 1.00), and AoP (CCCLin: 0.87; accuracy: 1.00) is excellent and still high for the head-perineum distance (CCCLin: 0.89; accuracy: 0.96) and cervical effacement (CCCLin: 0.77; accuracy: 0.97). CONCLUSION: TPUS is a valuable noninvasive tool with good diagnostic accuracy for the AoP, cervical length, and dilatation. Our study provides support for the use of TPUS to complement a vaginal examination. It should not replace a digital examination but should serve as a suitable alternative method for monitoring labor progression in the future.

Obstetric anal sphincter injuries (OASIS): using transperineal ultrasound (TPUS) for detecting, visualizing and monitoring the healing process.

PURPOSE: The aim of this study was to examine whether OASIS, and its extent, can be confirmed or excluded using transperineal ultrasound (TPUS). A further objective of this study was to monitor the healing process over a period of 6 months and to establish a connection between the sonographic appearance of obstetric anal sphincter injury (OASIS) and anal incontinence. MATERIALS AND METHODS: In this retrospective clinical study, women with OASIS who gave birth between March 2014 and August 2019 were enrolled. All the patients underwent TPUS 3 days and 6 months after delivery. A GE E8 Voluson ultrasound system with a 3.5-5 MHz ultrasound probe was used. The ultrasound images showed a third-degree injury, with the measurement of the width of the tear and its extent (superficial, partial, complete, EAS and IAS involvement). A positive contraction effect, a sign of sufficient contraction, was documented. Six months after delivery, a sonographic assessment of the healing (healed, scar or still fully present) was performed. A Wexner score was obtained from each patient. The patients' medical histories, including age, parity, episiotomy and child's weight, were added. RESULTS: Thirty-one of the 55 recruited patients were included in the statistical evaluation. Three patients were excluded from the statistical evaluation because OASIS was excluded on TPUS 3 days after delivery. One patient underwent revision surgery for anal incontinence and an inadequately repaired anal sphincter injury, as shown sonographic assessment, 9 days after delivery. Twenty patients were excluded for other reasons. The results suggest that a tear that appears smaller (in mm) after 3 days implies better healing after 6 months. This effect was statistically significant, with a significance level of alpha = 5% (p = 0.0328). Regarding anal incontinence, women who received an episiotomy had fewer anal incontinence symptoms after 6 months. The effect of episiotomy was statistically significant, with a significance level of alpha = 5% (p = 0.0367). CONCLUSION: TPUS is an accessible, non-invasive method for detecting, quantifying, following-up and monitoring OASIS in patients with third-degree perineal tears. The width, as obtained by sonography, is important with regard to the healing of OASIS. A mediolateral episiotomy seems to prevent anal incontinence after 6 months.

Methodological Aspects in Studies Based on Clinical Routine Data.

Randomized controlled clinical trials are regarded as the gold standard for comparing different clinical interventions, but generally their conduct is operationally cumbersome, time-consuming, and expensive. Studies and investigations based on clinical routine data on the contrary utilize existing data acquired under real-life conditions and are increasingly popular among practitioners. In this paper, methodological aspects of studies based on clinical routine data are discussed. Important limitations and considerations as well as unique strengths of these types of studies are indicated and exemplarily demonstrated in a recent real-case study based on clinical routine data. In addition two simulation studies reveal the impact of bias in studies based on clinical routine data on the type I error rate and false decision rate in favor of the inferior intervention. It is concluded that correctly analyzing clinical routine data yields a valuable addition to clinical research; however, as a result of a lack of statistical foundation, internal validity, and comparability, generalizing results and inferring properties derived from clinical routine data to all patients of interest has to be considered with extreme caution. FUNDING: Grünenthal GmbH.

Anatomy meets dentistry! Linking anatomy and clinical practice in the preclinical dental curriculum.

BACKGROUND: Establishing a strong link early on between preclinical coursework and the clinical context is necessary for students to be able to recognize the practical relevance of the curriculum during their preclinical anatomical courses and to transfer knowledge more easily. Our objective was to enhance the clinical relevance of a preclinical anatomy course for second-year medical students of dentistry by implementing an interdisciplinary skills training course on "Palpation of the Head and Neck Muscles" and to measure the learning outcomes. METHODS: For the curricular development of the expanded course module, Kern's 6-step approach was applied including subjective evaluation. We used a peer-teaching format supported by an e-learning application. A randomized control study measured effects of the two components (skills training, e-module) on learning outcomes. Four learning methods were compared: (1) lecture, (2) lecture + e-module, (3) lecture + skills training, (4) lecture + skills training + e-module. An objective structured clinical examination (OSCE) was used to measure and compare learning outcomes. RESULTS: The two-way variance analysis demonstrated that participation in the skills training had a statistically significant effect on the OSCE results (p = 0.0007). Students who participated in the skills training did better (φ 107.4 ± 14.4 points) than students who only attended the lecture (φ 88.8 ± 26.2 points). Students who used the e-module but did not attend the skills training earned a slightly but not significantly higher average number of points (φ 91.8 ± 31.3 points) than those who only attended the lecture. The learning outcomes of the skills training were again significantly increased when the training was combined with the e-module (φ 121.8 ± 21.8 points), thus making it the ideal method for achieving the learning objectives defined in this study. CONCLUSIONS: The "Palpation of the Head and Neck Muscles" interdisciplinary skills training course linking basic anatomical knowledge and clinical skills led to clearly improved learning outcomes for both, anatomical knowledge and clinical skills. The additional use of an e-learning tool (e-module) improved the learning effect.

Intestinal genetic inactivation of caspase-8 diminishes migration of enterocytes.

AIM: To verify the hypothesis that caspase-8 (Casp8), which regulates cellular apoptosis and necroptosis, is critically involved in enterocyte migration. METHODS: Casp8-silenced Caco2 cells were used in migration assays. In addition, enterocyte-specific Casp8 heterozygous (Casp8(+/∆int)) or homozygous knockout mice (Casp8(∆int)) were generated by crossing genetically modified mice carrying loxP recombination sites in intron 2 and 4 of the murine Casp8 gene with transgenic animals expressing a cre-transgene under control of the villin promoter in a pure C57/BL6 genetic background. The nucleoside analog BrdU was injected i.p. in male Casp8(+/∆int) and Casp8(∆int) animals 4 h, 20 h, or 40 h before performing morphometric studies. Locations of anti-BrdU-immunostained cells (cell(max)) in at least 50 hemi-crypts of 6 histoanatomically distinct intestinal mucosal regions were numbered and extracted for statistical procedures. For the mice cohort (n = 28), the walking distance of enterocytes was evaluated from cell(max) within crypt (n = 57), plateau (n = 19), and villus (n = 172) positions, resulting in a total of 6838 observations. Data analysis was performed by fitting a three-level mixed effects model to the data. RESULTS: In cell culture experiments with Caco2 cells, Casp8 knockdown efficiency mediated by RNA interference on Casp8 transcripts was 80% controlled as determined by Western blotting. In the scratch assay, migration of Casp8-deleted Caco2 cells was significantly diminished when compared with controls (Casp8(∆scramble) and Caco2). In BrdU-labeled Casp8(∆int) mice, cell(max) locations were found along the hemi-crypts in a lower position than it was for Casp8(+/∆int) or control (cre-negative) animals. Statistical data analysis with a three-level mixed effects model revealed that in the six different intestinal locations (distinct segments of the small and large intestine), cell movement between the three mice groups differed widely. Especially in duodenal hemi-crypts, enterocyte movement was different between the groups. At 20 h, duodenal cell(max) location was significantly lower in Casp8(∆int) (25.67 ± 2.49) than in Casp8(+/∆int) (35.67 ± 4.78; P < 0.05) or control littermates (44.33 ± 0.94; P < 0.01). CONCLUSION: Casp8-dependent migration of enterocytes is likely involved in intestinal physiology and inflammation-related pathophysiology.

The impact of selection bias on test decisions in randomized clinical trials.

Selection bias affects the evaluation of clinical trials, for example, by elevating type I error rate. We investigated the effect of selection bias on type I error rate considering permuted block randomization. We also considered stratified randomization in general and for the special case of multicenter clinical trials, where we incorporated preferences of the investigator in our approach. Finally, the effect of underrunning is modeled, that is, where the randomization list exceeds the actual number of patients taking part in the trial. For all situations, we illustrate and discuss the impact of selection bias on type I error rate.