Contributions of early detection and cancer prevention to colorectal cancer mortality reduction by screening colonoscopy: a validated modelling study.

BACKGROUND AND AIMS: Screening colonoscopy, recommended every ten years, reduces mortality from colorectal cancer (CRC) by early detection of prevalent but undiagnosed CRC, as well as by prevention of CRC by removal of precursor lesions. The aim of this study was to assess the relative contribution of both components to total CRC mortality reduction over time. METHODS: Using a validated multistate Markov model, we simulated hypothetical cohorts of 100,000 individuals aged 55-64 with and without use of screening at baseline. Main outcomes included proportions of prevented CRC deaths arising from (asymptomatic) CRC already prevalent at baseline and from newly developed CRC during 15-years of follow-up, and mortality rate ratios of screened versus unscreened groups over time. RESULTS: Early detection of prevalent cases accounted for 52%, 30% and 18% of deaths prevented by screening colonoscopy within 5, 10 and 15 years, respectively. Relative reduction of mortality was estimated to be much larger for mortality from incident cancers than for mortality from cancers that were already present and early detected at screening endoscopy and for total CRC mortality (i.e., 88% versus 67% and 79% within 10 years from screening). CONCLUSIONS: Reduction of CRC mortality mainly arises from early detection of prevalent cancers during the early years after screening colonoscopy, but prevention of incident cases accounts for the majority of prevented deaths in the longer run. Prevention of incident cases leads to sustained strong reduction of colorectal cancer mortality, possibly warranting an extension of screening intervals.

Associations of Migration, Socioeconomic Position and Social Relations With Depressive Symptoms - Analyses of the German National Cohort Baseline Data.

Objectives: We analyze whether the prevalence of depressive symptoms differs among various migrant and non-migrant populations in Germany and to what extent these differences can be attributed to socioeconomic position (SEP) and social relations. Methods: The German National Cohort health study (NAKO) is a prospective multicenter cohort study (N = 204,878). Migration background (assessed based on citizenship and country of birth of both participant and parents) was used as independent variable, age, sex, Social Network Index, the availability of emotional support, SEP (relative income position and educational status) and employment status were introduced as covariates and depressive symptoms (PHQ-9) as dependent variable in logistic regression models. Results: Increased odds ratios of depressive symptoms were found in all migrant subgroups compared to non-migrants and varied regarding regions of origins. Elevated odds ratios decreased when SEP and social relations were included. Attenuations varied across migrant subgroups. Conclusion: The gap in depressive symptoms can partly be attributed to SEP and social relations, with variations between migrant subgroups. The integration paradox is likely to contribute to the explanation of the results. Future studies need to consider heterogeneity among migrant subgroups whenever possible.

NIRS-Based Study of Local Cerebral Oxygenation During Transcranial Direct Current Stimulation in Patients with Mild Traumatic Brain Injury.

The purpose of our study was to assess the dynamics of local cerebral oxygenation (LCO) by near-infrared spectroscopy (NIRS) during transcranial direct current stimulation (tDCS) in the acute stage of mild traumatic brain injury (mTBI). Fifty-seven mTBI patients (18 women and 39 men, 35 ± 11.7 years old, GCS 13.7 ± 0.7) were treated by tDCS at 3-5 days after head injury. Stimulation parameters were: 1 mA, 9 V, duration-20 min. A cerebral oximeter was used to assess LCO-values in the frontotemporal lobes. Anodal and cathodal LCO values were compared before tDCS and every 2 min until the tDCS end. Significance was preset to p < 0.05. Results: A significant decrease in LCO values on the anodal side was observed at the 8th to 12th minutes of stimulation, compared to the cathodal side (at 8th minute - p = 0.011; at 12th minute - p < 0.00000001) and compared to LCO values before tDCS (p < 0.00001). The LCO on the cathodal side was not significantly different during the whole tDCS. At the end of the procedure, the interhemispheric LCO differences were not statistically significant (p = 0.757). Conclusions: Transcranial DCS in 3-5 days of mTBI leads to a significant decrease in the LCO value on the anodal side between 8 and 12 min and subsequent recovery to baseline values by the end of the procedure.

Microstructure and Thermal Analysis of Metastable Intermetallic Phases in High-Entropy Alloy CoCrFeMo0.85Ni.

CoCrFeMoNi high entropy alloys (HEAs) exhibit several promising characteristics for potential applications of high temperature coating. In this study, metastable intermetallic phases and their thermal stability of high-entropy alloy CoCrFeMo0.85Ni were investigated via thermal and microstructural analyses. Solidus and liquidus temperatures of CoCrFeMo0.85Ni were determined by differential thermal analysis as 1323 °C and 1331 °C, respectively. Phase transitions also occur at 800 °C and 1212 °C during heating. Microstructure of alloy exhibits a single-phase face-centred cubic (FCC) matrix embedded with the mixture of (Co, Cr, Fe)-rich tetragonal phase and Mo-rich rhombohedron-like phase. The morphologies of two intermetallics show matrix-based tetragonal phases bordered by Mo-rich rhombohedral precipitates around their perimeter. The experimental results presented in our paper provide key information on the microstructure and thermal stability of our alloy, which will assist in the development of similar thermal spray HEA coatings.

Detecting the Potential for Consciousness in Unresponsive Patients Using the Perturbational Complexity Index.

The difficulties of behavioral evaluation of prolonged disorders of consciousness (DOC) motivate the development of brain-based diagnostic approaches. The perturbational complexity index (PCI), which measures the complexity of electroencephalographic (EEG) responses to transcranial magnetic stimulation (TMS), showed a remarkable sensitivity in detecting minimal signs of consciousness in previous studies. Here, we tested the reliability of PCI in an independently collected sample of 24 severely brain-injured patients, including 11 unresponsive wakefulness syndrome (UWS), 12 minimally conscious state (MCS) patients, and 1 emergence from MCS patient. We found that the individual maximum PCI value across stimulation sites fell within the consciousness range (i.e., was higher than PCI*, which is an empirical cutoff previously validated on a benchmark population) in 11 MCS patients, yielding a sensitivity of 92% that surpassed qualitative evaluation of resting EEG. Most UWS patients (n = 7, 64%) showed a slow and stereotypical TMS-EEG response, associated with low-complexity PCI values (i.e., ≤PCI*). Four UWS patients (36%) provided high-complexity PCI values, which might suggest a covert capacity for consciousness. In conclusion, this study successfully replicated the performance of PCI in discriminating between UWS and MCS patients, further motivating the application of TMS-EEG in the workflow of DOC evaluation.

Stimulation of the Angular Gyrus Improves the Level of Consciousness.

BACKGROUND: Navigated repetitive transcranial magnetic stimulation (rTMS) is a promising tool for neuromodulation. In previous studies it has been shown that the activity of the default mode network (DMN) areas, particularly of its key region-the angular gyrus-is positively correlated with the level of consciousness. Our study aimed to explore the effect of rTMS of the angular gyrus as a new approach for disorders of consciousness (DOC) treatment; Methods: A 10-session 2-week high-frequency rTMS protocol was delivered over the left angular gyrus in 38 DOC patients with repeated neurobehavioral assessments obtained at baseline and in 2 days after the stimulation course was complete; Results: 20 Hz-rTMS over left angular gyrus improved the coma recovery scale revised (CRS-R) total score in minimally conscious state (MCS) patients. We observed no effects in vegetative state (VS) patients; and Conclusions: The left angular gyrus is likely to be effective target for rTMS in patients with present signs of consciousness.

Feasibility of Non-Gaussian Diffusion Metrics in Chronic Disorders of Consciousness.

Diagnostic accuracy of different chronic disorders of consciousness (DOC) can be affected by the false negative errors in up to 40% cases. In the present study, we aimed to investigate the feasibility of a non-Gaussian diffusion approach in chronic DOC and to estimate a sensitivity of diffusion kurtosis imaging (DKI) metrics for the differentiation of vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS) from a healthy brain state. We acquired diffusion MRI data from 18 patients in chronic DOC (11 VS/UWS, 7 MCS) and 14 healthy controls. A quantitative comparison of the diffusion metrics for grey (GM) and white (WM) matter between the controls and patient group showed a significant (p < 0.05) difference in supratentorial WM and GM for all evaluated diffusion metrics, as well as for brainstem, corpus callosum, and thalamus. An intra-subject VS/UWS and MCS group comparison showed only kurtosis metrics and fractional anisotropy differences using tract-based spatial statistics, owing mainly to macrostructural differences on most severely lesioned hemispheres. As a result, we demonstrated an ability of DKI metrics to localise and detect changes in both WM and GM and showed their capability in order to distinguish patients with a different level of consciousness.

A Russian validation study of the Coma Recovery Scale-Revised (CRS-R).

INTRODUCTION: The aim of the study was to develop and validate a Russian adaptation of the Coma Recovery Scale-Revised (CRS-R). SUBJECTS AND METHODS: We evaluated 58 patients with chronic disorders of consciousness (> 4 weeks post-injury, DOC) of various etiology and two patients in a locked-in state at different stages after coma. We tested sensitivity for changes over 1 week, reliability, criterion validity and diagnostic sensitivity of the Russian adaptation of the CRS-R in comparison with the Russian adaptations of Full Outline of UnResponsiveness Score (FOUR), and Glasgow Coma Scale (GCS). RESULTS: We obtained good sensitivity for changes in neurological status over week (p < 0.0001) and good test-retest reliability (r = 0.997, p < 0.0001) of the CRS-R. Inter-rater reliability was good (κ = 0.99, p < 0.001). We showed high internal consistency (α = 0.87) of the scale and good criterion validity between other scales (r = 0.597 for GCS, and r = 0.900 for FOUR). CRS-R also demonstrated a higher sensitivity in differential diagnosis of DOC, as compared to GCS, and FOUR Score (p < 0.001). CONCLUSION: The results show that the Russian version of the CRS-R is a valid and sensitive tool for the evaluation of patients with chronic DOC, which can be used for differential diagnosis and for recovery assessment.

Conventional Structural Magnetic Resonance Imaging in Differentiating Chronic Disorders of Consciousness.

Differential diagnosis of unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) is one of the most challenging problems for specialists who deal with chronic disorders of consciousness (DOC). The aim of the current study was to develop a conventional MRI-based scale and to evaluate its role in distinguishing chronic disorders of consciousness (Disorders of Consciousness MRI-based Distinguishing Scale, DOC-MRIDS). Data were acquired from 30 patients with clinically diagnosed chronic disorders of consciousness. All patients underwent conventional MRI using a Siemens Verio 3.0 T scanner, which included T2 and T1 sequences for patient assessment. Diffuse cortical atrophy, ventricular enlargement, sulcal widening, leukoaraiosis, brainstem and/or thalamus degeneration, corpus callosum degeneration, and corpus callosum lesions were assessed according to DOC-MRIDS criteria, with a total score calculation. The ROC-analysis showed that a reasonable threshold DOC-MRIDS total score was 5.5, that is, patients with DOC-MRIDS total score of 6 and above were classified as UWS and 5 and below as MCS, with sensitivity of 82.4% and specificity of 92.3%. The novel structural MRI-based scale for the assessment of typical brain lesions in patients with chronic DOC is relatively easy to apply, and provides good specificity and sensitivity values for discrimination between UWS and MCS.

Birch bark extract as therapy for chronic hepatitis C--a pilot study.

The hepatoprotective effect of birch bark extract (BBE) in patients with chronic hepatitis C (CHC) was studied. Forty-two patients with serologically confirmed chronic hepatitis C were treated for 12 weeks with 160 mg standardized BBE per day. The primary outcome parameter measured was the rate of alanine aminotransferase (ALT) normalization after 12 weeks. Secondary parameters included the course of ALT, aspartate aminotransferase (AST) levels, quantitative HCV RNA levels, subjective symptoms associated with CHC (fatigue, abdominal discomfort, depression, and dyspepsia), safety and compliance. The qualitative-quantitative analysis of BBE was made using high performance liquid chromatography to confirm the presence of 75% betulin and 3.5% betulinic acid. Significant differences in the mean ALT and HCV RNA levels were observed after 12 weeks of treatment. The level of ALT was decreased in 54.0% and normalized (p=0.046). HCV RNA was reduced in 43.2% (p=0.016). After 12 weeks of treatment, reports of fatigue and abdominal discomfort were reduced by 6-fold (p=0.028) and 3-fold (p=0.05), respectively. Dyspepsia was no longer reported (p=0.042) and the effect was significantly different from baseline. Because this study lacks a control group clinical relevance of the data can only be estimated in future by following controlled clinical trials.