EEG reactivity to pain in comatose patients: Importance of the stimulus type.

INTRODUCTION: Electroencephalogram (EEG) background reactivity is a potentially interesting outcome predictor in comatose patients, especially after cardiac arrest, but recent studies report only fair interrater reliability. Furthermore, there are no definite guidelines for its testing. We therefore investigated the EEG effect of standardized noxious stimuli in comatose patients not reactive to auditory stimuli. METHODS: In this prospective study we applied a protocol using three different painful stimuli (bilateral nipple pinching, pinprick at the nose base, finger-nail compression on each side), grouped in three distinct clusters with an alternated sequence, during EEG recordings in comatose patients. We only analyzed recordings showing any reactivity to pain. Fisher and χ2 tests were used as needed to assess contingency tables. RESULTS: Of 42 studies, 12 did not show any background reactivity, 2 presented SIRPIDs, and 2 had massive artefacts; we thus analyzed 26 EEGs recorded in 17 patients (4 women, 24%). Nipple pinching more frequently induced a change in EEG background activity (p<0.001), with a sensitivity of 97.4% for reactivity. Neither the order of the stimuli in the cluster (p=0.723), nor the cluster order (p=0.901) influenced the results. CONCLUSION: In this pilot study, bilateral, synchronous nipple pinching seems to be the most efficient method to test nociceptive EEG reactivity in comatose patients. This approach may enhance interrater reliability, but deserves confirmation in larger cohorts.

Visualizing the spatiotemporal dynamics of DNA damage in budding yeast.

Fluorescence microscopy has enabled the analysis of both the spatial distribution of DNA damage and its dynamics during the DNA damage response (DDR). Three microscopic techniques can be used to study the spatiotemporal dynamics of DNA damage. In the first part we describe how we determine the position of DNA double-strand breaks (DSBs) relative to the nuclear envelope. The second part describes how to quantify the co-localization of DNA DSBs with nuclear pore clusters, or other nuclear subcompartments. The final protocols describe methods for the quantification of locus mobility over time.

Decreasing educational differences in mortality over 40 years: evidence from the Turin Longitudinal Study (Italy)

BACKGROUND: Recent studies suggest that inequalities in premature mortality have continued to rise over the last decade in most European countries, but not in southern European countries. METHODS: In this study, we assess long-term trends (1971-2011) in absolute and relative educational inequalities in all-cause and cause-specific mortality in the Turin Longitudinal Study (Turin, Italy), a record-linkage study including all individuals resident in Turin in the 1971, 1981, 1991 and 2001 censuses, and aged 30-99 years (more than 2 million people). We examined mortality for all causes, cardiovascular disease (CVD), all cancers and specific cancers (lung, breast), as well as smoking and alcohol-related mortality. RESULTS: Overall mortality substantially decreased in all educational groups over the study period, although cancer rates only slightly declined. Absolute inequalities decreased for both genders (SII=962/694 in men/women in 1972-1976 and SII=531/259 in 2007-2011, p<0.01). Among men, absolute inequalities for CVD and alcohol-related causes declined (p<0.05), while remaining stable for other causes of death. Among women, declines in absolute inequalities were observed for CVD, smoking and alcohol-related causes and lung cancer (p<0.05). Relative inequalities in all-cause mortality remained stable for men and decreased for women (RII=1.92/2.03 in men/women in 1972-1976 and RII=2.15/1.32 in 2007-2011). Among men, relative inequalities increased for smoking-related causes, while among women they decreased for all cancers, CVD, smoking-related causes and lung cancer (p<0.05). CONCLUSIONS: Absolute inequalities in mortality strongly declined over the study period in both genders. Relative educational inequalities in mortality were generally stable among men; while they tended to narrow among women. In general, this study supports the hypothesis that educational inequalities in mortality have decreased in southern European countries.

Improving anterior deltoid activity in a musculoskeletal shoulder model - an analysis of the torque-feasible space at the sternoclavicular joint.

Modelling the shoulder's musculature is challenging given its mechanical and geometric complexity. The use of the ideal fibre model to represent a muscle's line of action cannot always faithfully represent the mechanical effect of each muscle, leading to considerable differences between model-estimated and in vivo measured muscle activity. While the musculo-tendon force coordination problem has been extensively analysed in terms of the cost function, only few works have investigated the existence and sensitivity of solutions to fibre topology. The goal of this paper is to present an analysis of the solution set using the concepts of torque-feasible space (TFS) and wrench-feasible space (WFS) from cable-driven robotics. A shoulder model is presented and a simple musculo-tendon force coordination problem is defined. The ideal fibre model for representing muscles is reviewed and the TFS and WFS are defined, leading to the necessary and sufficient conditions for the existence of a solution. The shoulder model's TFS is analysed to explain the lack of anterior deltoid (DLTa) activity. Based on the analysis, a modification of the model's muscle fibre geometry is proposed. The performance with and without the modification is assessed by solving the musculo-tendon force coordination problem for quasi-static abduction in the scapular plane. After the proposed modification, the DLTa reaches 20% of activation.

Imaging findings in fetal diaphragmatic abnormalities.

Imaging plays a key role in the detection of a diaphragmatic pathology in utero. US is the screening method, but MRI is increasingly performed. Congenital diaphragmatic hernia is by far the most often diagnosed diaphragmatic pathology, but unilateral or bilateral eventration or paralysis can also be identified. Extralobar pulmonary sequestration can be located in the diaphragm and, exceptionally, diaphragmatic tumors or secondary infiltration of the diaphragm from tumors originating from an adjacent organ have been observed in utero. Congenital abnormalities of the diaphragm impair normal lung development. Prenatal imaging provides a detailed anatomical evaluation of the fetus and allows volumetric lung measurements. The comparison of these data with those from normal fetuses at the same gestational age provides information about the severity of pulmonary hypoplasia and improves predictions about the fetus's outcome. This information can help doctors and families to make decisions about management during pregnancy and after birth. We describe a wide spectrum of congenital pathologies of the diaphragm and analyze their embryological basis. Moreover, we describe their prenatal imaging findings with emphasis on MR studies, discuss their differential diagnosis and evaluate the limits of imaging methods in predicting postnatal outcome.

Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

BACKGROUND: Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. METHODS: In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. RESULTS: We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). CONCLUSIONS: After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders.

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study.

BACKGROUND: Antiretroviral regimens containing tenofovir disoproxil fumarate have been associated with renal toxicity and reduced bone mineral density. Tenofovir alafenamide is a novel tenofovir prodrug that reduces tenofovir plasma concentrations by 90%, thereby decreasing off-target side-effects. We aimed to assess whether efficacy, safety, and tolerability were non-inferior in patients switched to a regimen containing tenofovir alafenamide versus in those remaining on one containing tenofovir disoproxil fumarate. METHODS: In this randomised, actively controlled, multicentre, open-label, non-inferiority trial, we recruited HIV-1-infected adults from Gilead clinical studies at 168 sites in 19 countries. Patients were virologically suppressed (HIV-1 RNA <50 copies per mL) with an estimated glomerular filtration rate of 50 mL per min or greater, and were taking one of four tenofovir disoproxil fumarate-containing regimens for at least 96 weeks before enrolment. With use of a third-party computer-generated sequence, patients were randomly assigned (2:1) to receive a once-a-day single-tablet containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg (tenofovir alafenamide group) or to carry on taking one of four previous tenofovir disoproxil fumarate-containing regimens (tenofovir disoproxil fumarate group) for 96 weeks. Randomisation was stratified by previous treatment regimen in blocks of six. Patients and treating physicians were not masked to the assigned study regimen; outcome assessors were masked until database lock. The primary endpoint was the proportion of patients who received at least one dose of study drug who had undetectable viral load (HIV-1 RNA <50 copies per mL) at week 48. The non-inferiority margin was 12%. This study was registered with ClinicalTrials.gov, number NCT01815736. FINDINGS: Between April 12, 2013 and April 3, 2014, we enrolled 1443 patients. 959 patients were randomly assigned to the tenofovir alafenamide group and 477 to the tenofovir disoproxil fumarate group. Viral suppression at week 48 was noted in 932 (97%) patients assigned to the tenofovir alafenamide group and in 444 (93%) assigned to the tenofovir disoproxil fumarate group (adjusted difference 4·1%, 95% CI 1·6-6·7), with virological failure noted in ten and six patients, respectively. The number of adverse events was similar between the two groups, but study drug-related adverse events were more common in the tenofovir alafenamide group (204 patients [21%] vs 76 [16%]). Hip and spine bone mineral density and glomerular filtration were each significantly improved in patients in the tenofovir alafenamide group compared with those in the tenofovir disoproxil fumarate group. INTERPRETATION: Switching to a tenofovir alafenamide-containing regimen from one containing tenofovir disoproxil fumarate was non-inferior for maintenance of viral suppression and led to improved bone mineral density and renal function. Longer term follow-up is needed to better understand the clinical impact of these changes. FUNDING: Gilead Sciences.

Vestibular Schwannoma: The Evolution of Hearing and Tumor Size in Natural Course and after Treatment by LINAC Stereotactic Radiosurgery.

OBJECTIVE: To review the natural course of tumor size and hearing during conservative management of 151 patients with unilateral vestibular schwannoma (VS), and to evaluate the same parameters for the part of the group (n = 84) who were treated by LINAC stereotactic radiosurgery (SRS). METHODS: In prospectively collected data, patients underwent MRI and complete audiovestibular tests at inclusion, during the conservative management period and after SRS. Hearing was graded according to the Gardner-Robertson (GR) scale and tumor size according to Koos. Statistics were performed using Kaplan-Meier survival analysis and multivariate analyses including linear and logistic regression. Specific insight was given to patients with serviceable hearing. RESULTS: During the conservative management period (mean follow-up time: 24 months, range: 6-96), the annual risk of GR class degradation was 6% for GRI and 15% for GR II patients. Hearing loss as an initial symptom was highly predictive of further hearing loss (p = 0.003). Tumor growth reached 25%. For SRS patients, functional hearing preservation was 51% at 1 year and 36% at 3 years. Tumor control was 94 and 91%, respectively. CONCLUSION: In VS patients, hearing loss at the time of diagnosis is a predictor of poorer hearing outcome. LINAC SRS is efficient for tumor control. Patients who preserved their pretreatment hearing presented less hearing loss per year after SRS than before treatment, suggesting a protective effect of SRS when cochlear function can be preserved.

Prevalence of ragweed allergy in rural Geneva - a pilot study.

OBJECTIVE: The prevalence of ragweed allergy is increasing worldwide. Ragweed distribution and abundance is spreading in Europe in a wide area ranging from the Rhone valley in France to Hungary and Ukraine, where the rate of the prevalence can peak at as high as 12%. Low-grade ragweed colonisation was seen in Geneva and Ticino, less than two decades ago. There were fears that allergies to ragweed would increase Switzerland. The intent of this study was to assess the rate of prevalence of sensitisation and allergy to ragweed in the population living in the first rural Swiss setting where ragweed had been identified in 1996, and to evaluate indirectly the efficacy of elimination and containment strategies. MATERIAL AND METHODS: In 2009, 35 adults in a rural village in the Canton of Geneva were recruited. Data were collected by means of questionnaires and skin-prick tests were done on each participant. The study was approved by the local Ethics Committee. RESULTS: Based on questionnaires, 48.6% had rhinitis (95% confidence interval [CI] 32.9-64.4; n = 17/35) and 17.1% asthma (95% CI 8.1-32.6; n = 6/35). Atopy was diagnosed in 26.4% (95% CI 12.9-44.4) of the sample (n = 9/34). Ragweed sensitisation was found in 2.9% (95% CI 0.7-19.7; n = 1/34), mugwort sensitisation in 2.9% (95% CI 0.1-14.9; n = 1/35), alder sensitisation in 17.1% (95% CI 6.6-33.6; n = 6/35), ash sensitisation in 12.5% (95% CI 3.5-29.0; n = 4/32) and grass sensitisation in 22.9% (95% CI 10.4-40.1; n = 8/35). Ragweed (95% CI 0.1-14.9; n = 1/34) and mugwort allergies (95% CI 0.1-14.9; n = 1/35) were both found in 2.9% of the population. CONCLUSION: This study showed a surprisingly low incidence of ragweed sensitisation and allergy, of 2.9% and 2.9%, respectively, 20 years after the first ragweed detection in Geneva. The feared rise in ragweed allergy seems not to have happened in Switzerland, compared with other ragweed colonised countries. These results strongly support early field strategies against ragweed.

¿Pueden contribuir los métodos visuales a avanzar hacia una investigación inclusiva? Un estudio sobre inclusión sociolaboral con personas con Trastorno Mental Grave (TMG) = Can visual methods help to go forward inclusive research? A study about social and labor inclusion with people with Severe Mental Illness (SMI)

En este artículo se pretende mostrar cómo la utilización de métodos visuales en la investigación contribuye a potenciar la participación activa de las personas con TMG. Se utiliza como ejemplo un estudio de caso de corte cualitativo que incorpora tres actividades de componente visual (el dibujo “el río de la vida”, las fotografías y el dibujo de proyección de futuro) para favorecer la reflexión narrada que, sobre sus experiencias y vivencias, desarrollan cinco personas con TMG. El uso de las fotografías y dibujos en este estudio permite afirmar que estas estrategias se han mostrado válidas para acceder, en la medida que los participantes han querido, a esferas de vida personales en trayectorias vitales determinadas por la enfermedad mental

The role of ultrasonography in the measurement of subcutaneous and visceral fat and its correlation with hepatic steatosis

Objective To evaluate the sonographic measurement of subcutaneous and visceral fat in correlation with the grade of hepatic steatosis. Materials and Methods In the period from October 2012 to January 2013, 365 patients were evaluated. The subcutaneous and visceral fat thicknesses were measured with a convex, 3–4 MHz transducer transversely placed 1 cm above the umbilical scar. The distance between the internal aspect of the abdominal rectus muscle and the posterior aortic wall in the abdominal midline was considered for measurement of the visceral fat. Increased liver echogenicity, blurring of vascular margins and increased acoustic attenuation were the parameters considered in the quantification of hepatic steatosis. Results Steatosis was found in 38% of the study sample. In the detection of moderate to severe steatosis, the area under the ROC curve was 0.96 for women and 0.99 for men, indicating cut-off values for visceral fat thickness of 9 cm and 10 cm, respectively. Conclusion The present study evidenced the correlation between steatosis and visceral fat thickness and suggested values for visceral fat thickness to allow the differentiation of normality from risk for steatohepatitis.

Chronic kidney disease in type 2 diabetic patients followed-up by primary care physicians in Switzerland: prevalence and prescription of antidiabetic drugs.

QUESTION UNDER STUDY: The aim of this study was to assess the prevalence of chronic kidney disease (CKD) among type 2 diabetic patients in primary care settings in Switzerland, and to analyse the prescription of antidiabetic drugs in CKD according to the prevailing recommendations. METHODS: In this cross-sectional study, each participating physician was asked to introduce anonymously in a web database the data from up to 15 consecutive diabetic patients attending her/his office between December 2013 and June 2014. Demographic, clinical and biochemical data were analysed. CKD was classified with the KDIGO nomenclature based on estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio. RESULTS: A total of 1 359 patients (mean age 66.5 ± 12.4 years) were included by 109 primary care physicians. CKD stages 3a, 3b and 4 were present in 13.9%, 6.1%, and 2.4% of patients, respectively. Only 30.6% of patients had an entry for urinary albumin/creatinine ratio. Among them, 35.6% were in CKD stage A2, and 4.1% in stage A3. Despite prevailing limitations, metformin and sulfonylureas were prescribed in 53.9% and 16.5%, respectively, of patients with advanced CKD (eGFR <30 ml/min). More than a third of patients were on a dipeptidyl-peptidase-4 inhibitor across all CKD stages. Insulin use increased progressively from 26.8% in CKD stage 1-2 to 50% in stage 4. CONCLUSIONS: CKD is frequent in patients with type 2 diabetes attending Swiss primary care practices, with CKD stage 3 and 4 affecting 22.4% of cases. This emphasizes the importance of routine screening of diabetic nephropathy based on both eGFR and urinary albumin/creatinine ratio, the latter being largely underused by primary care physicians. A careful individual drug risk/benefit balance assessment is mandatory to avoid the frequently observed inappropriate prescription of antidiabetic drugs in CKD patients.

CYP17A1 Enzyme activity is linked to ambulatory blood pressure in a family-based population study.

BACKGROUND: Genome-wide association studies have linked CYP17A1 coding for the steroid hormone synthesizing enzyme 17α-hydroxylase (CYP17A1) to blood pressure (BP). We hypothesized that the genetic signal may translate into a correlation of ambulatory BP (ABP) with apparent CYP17A1 activity in a family-based population study and estimated the heritability of CYP17A1 activity. METHODS: In the Swiss Kidney Project on Genes in Hypertension, day and night urinary excretions of steroid hormone metabolites were measured in 518 participants (220 men, 298 women), randomly selected from the general population. CYP17A1 activity was assessed by 2 ratios of urinary steroid metabolites: one estimating the combined 17α-hydroxylase/17,20-lyase activity (ratio 1) and the other predominantly 17α-hydroxylase activity (ratio 2). A mixed linear model was used to investigate the association of ABP with log-transformed CYP17A1 activities exploring effect modification by urinary sodium excretion. RESULTS: Daytime ABP was positively associated with ratio 1 under conditions of high, but not low urinary sodium excretion (P interaction <0.05). Ratio 2 was not associated with ABP. Heritability estimates (SE) for day and night CYP17A1 activities were 0.39 (0.10) and 0.40 (0.09) for ratio 1, and 0.71 (0.09) and 0.55 (0.09) for ratio 2 (P values <0.001). CYP17A1 activities, assessed with ratio 1, were lower in older participants. CONCLUSIONS: Low apparent CYP17A1 activity (assessed with ratio 1) is associated with elevated daytime ABP when salt intake is high. CYP17A1 activity is heritable and diminished in the elderly. These observations highlight the modifying effect of salt intake on the association of CYP17A1 with BP.

The knowledge about diagnostic imaging methods among primary care and medical emergency physicians

Objective To evaluate the knowledge about diagnostic imaging methods among primary care and medical emergency physicians. Materials and Methods Study developed with 119 primary care and medical emergency physicians in Montes Claros, MG, Brazil, by means of a structured questionnaire about general knowledge and indications of imaging methods in common clinical settings. A rate of correct responses corresponding to ≥ 80% was considered as satisfactory. The Poisson regression (PR) model was utilized in the data analysis. Results Among the 81 individuals who responded the questionnaire, 65% (n = 53) demonstrated to have satisfactory general knowledge and 44% (n = 36) gave correct responses regarding indications of imaging methods. Respectively, 65% (n = 53) and 51% (n = 41) of the respondents consider that radiography and computed tomography do not use ionizing radiation. The prevalence of a satisfactory general knowledge about imaging methods was associated with medical residency in the respondents' work field (PR = 4.55; IC 95%: 1.18-16.67; p-value: 0.03), while the prevalence of correct responses regarding indication of imaging methods was associated with the professional practice in primary health care (PR = 1.79; IC 95%: 1.16-2.70; p-value: 0.01). Conclusion Major deficiencies were observed as regards the knowledge about imaging methods among physicians, with better results obtained by those involved in primary health care and by residents.

Relationship between two year PSA nadir and biochemical recurrence in prostate cancer patients treated with iodine-125 brachytherapy

Objective To evaluate the relationship between two year PSA nadir (PSAn) after brachytherapy and biochemical recurrence rates in prostate cancer patients. Materials and Methods In the period from January 1998 to August 2007, 120 patients were treated with iodine-125 brachytherapy alone. The results analysis was based on the definition of biochemical recurrence according to the Phoenix Consensus. Results Biochemical control was observed in 86 patients (71.7%), and biochemical recurrence, in 34 (28.3%). Mean PSAn was 0.53 ng/ml. The mean follow-up was 98 months. The patients were divided into two groups: group 1, with two year PSAn < 0.5 ng/ml after brachytherapy (74 patients; 61.7%), and group 2, with two year PSAn ≥ 0.5 ng/ml after brachytherapy (46 patients; 38.3%). Group 1 presented biochemical recurrence in 15 patients (20.3%), and group 2, in 19 patients (43.2%) (p < 0.02). The analysis of biochemical disease-free survival at seven years, stratified by the two groups, showed values of 80% and 64% (p < 0.02), respectively. Conclusion Levels of two year PSAn ≥ 0.5 ng/ml after brachytherapy are strongly correlated with a poor prognosis. This fact may help to identify patients at risk for disease recurrence.