The Use of a Variable Representing Compliance Improves Accuracy of Estimation of the Effect of Treatment Allocation Regardless of Discontinuation in Trials with Incomplete Follow-up

Abstract–In Clinical Trials, not all randomized patients follow the course of treatment they are allocated to. The potential impact of such deviations is increasingly recognized, and it has been one of the reasons for a redefinition of the targets of estimation (“Estimands”) in the ICH E9 draft Addendum. Among others, the effect of treatment assignment, regardless of the adherence, appears an Estimand of practical interest, in line with the intention-to-treat principle. This study aims at evaluating the performance of different estimation techniques in trials with incomplete post-discontinuation follow-up when a “treatment-policy” strategy is implemented. To achieve that, we have (i) modeled and visualized as directed acyclic diagram a reasonable data-generating model; (ii) investigated which set of variables allows identification and estimation of such effect; (iii) simulated 10,000 trials in Major Depressive Disorder, with varying real treatment effects, proportions of patients discontinuing the treatment, and incomplete follow-up. Our results suggest that, at least in a “Missing at Random” setting, all studied estimation methods increase their performance when a variable representing compliance is used. This effect is more pronounced the higher the proportion of post-discontinuation follow-up is

Nasal IL-13 production identifies patients with late phase allergic responses

BACKGROUND: There is limited knowledge on how local cytokine secretion patterns after nasal allergen challenge correlate with clinical symptoms especially with regards to the "late allergic response" (LAR) which occurs in approximately 40-50% of allergic patients. OBJECTIVE: In this study we aimed to characterise the immunological and clinical nasal responses to birch pollen allergen challenge with a special focus on the LAR. METHODS: In this randomised double-blinded placebo-control trial, birch pollen allergic participants were challenged with pollen extract (n=20) or placebo (n=10) on three consecutive days. On days one and three nasal secretions were collected at selected time points over a 24h time course for the measurement of 33 inflammatory mediators. Clinical responses were determined through subjective symptom scores and objective nasal airflow measurements. RESULTS: Provoked participants had significantly greater clinical responses and showed significant increases in tryptase and sST2 within minutes compared to placebo. Eight out of 20 provoked participants displayed high IL-13 levels 2-8 hours after allergen provocation. This group also showed significant changes in clinical parameters, with a secondary drop in nasal airflow measured by peak nasal inspiratory flow and increased symptoms of nasal obstruction which significantly differed from IL-13 non responders at 6 hours. CONCLUSION: IL-13 response status correlates with cytokine and clinical responses in the late phase after allergen provocation

Biogenesis and functions of bacterial S-layers.

The outer surface of many archaea and bacteria is coated with a proteinaceous surface layer (known as an S-layer), which is formed by the self-assembly of monomeric proteins into a regularly spaced, two-dimensional array. Bacteria possess dedicated pathways for the secretion and anchoring of the S-layer to the cell wall, and some Gram-positive species have large S-layer-associated gene families. S-layers have important roles in growth and survival, and their many functions include the maintenance of cell integrity, enzyme display and, in pathogens and commensals, interaction with the host and its immune system. In this Review, we discuss our current knowledge of S-layer and related proteins, including their structures, mechanisms of secretion and anchoring and their diverse functions

Depression and anxiety among migrants in Austria: A population based study of prevalence and utilization of health care services

BACKGROUND: Although migrants form a large part of the Austrian population, information about mental health of migrants in Austria is scarce. Therefore, we compared the prevalence of dysphoric disorders (depression and anxiety) and the corresponding utilization of health care services of Eastern European, western and other migrants with the non-migrant population in Austria. METHODS: We performed a telephone survey on a random sample of the general population of Austria aged 15 years and older (n=3509) between October 2010 and September 2011. Depression and anxiety were measured with the Patient Health Questionnaire-4 and utilization of health care services in the last 4 weeks was inquired. RESULTS: 15.0% of our sample had a migration background. Female migrants from Eastern Europe, first and second generation, had a higher prevalence of dysphoric disorders (29.7% and 33.4% respectively) than Austrian women (15.2%) (p<0.001). The prevalence in the other migrant groups did not differ significantly from the Austrian population. There was no gender difference in dysphoric disorders in the Austrian population. After adjustment for age and chronic diseases, having a dysphoric disorder was associated with a higher utilization of health care services among migrant and Austrian women, but not among men. LIMITATIONS: Because of the explorative nature of the study multiple testing correction was not performed. The reason for health care utilization was not assessed. CONCLUSIONS: Mental health of female migrants from Eastern Europe should be studied in more detail; men could be an underserved group, both in migrants and Austrians

Depression and anxiety among migrants in Austria: A population based study of prevalence and utilization of health care services

Item does not contain fulltextBACKGROUND: Although migrants form a large part of the Austrian population, information about mental health of migrants in Austria is scarce. Therefore, we compared the prevalence of dysphoric disorders (depression and anxiety) and the corresponding utilization of health care services of Eastern European, western and other migrants with the non-migrant population in Austria. METHODS: We performed a telephone survey on a random sample of the general population of Austria aged 15 years and older (n=3509) between October 2010 and September 2011. Depression and anxiety were measured with the Patient Health Questionnaire-4 and utilization of health care services in the last 4 weeks was inquired. RESULTS: 15.0% of our sample had a migration background. Female migrants from Eastern Europe, first and second generation, had a higher prevalence of dysphoric disorders (29.7% and 33.4% respectively) than Austrian women (15.2%) (p<0.001). The prevalence in the other migrant groups did not differ significantly from the Austrian population. There was no gender difference in dysphoric disorders in the Austrian population. After adjustment for age and chronic diseases, having a dysphoric disorder was associated with a higher utilization of health care services among migrant and Austrian women, but not among men. LIMITATIONS: Because of the explorative nature of the study multiple testing correction was not performed. The reason for health care utilization was not assessed. CONCLUSIONS: Mental health of female migrants from Eastern Europe should be studied in more detail; men could be an underserved group, both in migrants and Austrians

Production， suppression and utilization of higher harmonics in alternators

種別:卒業論文東京帝国大学工科大

Expression of programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand (PD-L1) in adenocarcinomas of the gastroesophageal junction change significantly after neoadjuvant treatment.

The effects of cytotoxic chemotherapy on the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in cancer cells and peritumoral cells are unclear. The aim of this study was to investigate the impact of neoadjuvant chemotherapy on PD-1 and PD-L1 expression in adenocarcinomas of the gastroesophageal junction. PD-1 and PD-L1 expression in cancer cells and tumor-infiltrating lymphocytes in paired diagnostic biopsies and surgical specimens from patients with pretreated and curatively resected adenocarcinomas of the gastroesophageal junction were evaluated by immunohistochemistry. Paired tumor samples were available from 40 patients. PD-1 expression in cancer cells (p &lt; 0.001; Exact Symmetry Test) and tumor-infiltrating lymphocytes (p &lt; 0.001; Exact Symmetry Test) increased significantly after neoadjuvant therapy. Furthermore, we observed a significant decrease in PD-L1 expression in cancer cells (p = 0.003) after neoadjuvant therapy was observed. In this study we could show that tumor-cell expression of PD-1 and PD-L1 was significantly altered in patients with adenocarcinomas of the gastroesophageal junction after receiving neoadjuvant chemotherapy. Based on these observations, patients might profit from the combined use of cytotoxic chemotherapy and the blockade of the PD-1 axis