79 research outputs found
A randomized double-blind placebo-controlled trial to evaluate the value of a single bolus intravenous alfentanil in CT colonography
<p>Abstract</p> <p>Background</p> <p>Although CT colonography is a less invasive alternative for colonoscopy for the detection of colorectal polyps and cancer, procedural pain is common. In several studies, CT colonography pain and burden is higher than in colonoscopy. Apart from discomfort, anxiety and its related stress-induced peri- procedural side effects, this may influence the adherence for CT colonography as a possible screening tool for colorectal cancer. We hypothesize that a single bolus intravenous alfentanil will give a clinically relevant reduction in maximum pain defined as at least 1.3 point reduction on an 11-point numeric rating scale (NRS).</p> <p>Methods/Design</p> <p>A randomized double-blind placebo-controlled trial in which patients scheduled for elective CT colonography in a single tertiary centre are eligible for inclusion. The first 90 consenting patient will be block-randomized to either the alfentanil group or the placebo group. Before bowel insufflation, the alfentanil group receives a single bolus intravenous alfentanil 7.5 μg/kg dissolved in 0.9% NaCl, while the placebo group receives an intravenous bolus injection of pure 0.9% NaCl. For both groups an equal amount of fluid per kilogram (75 μL/kg) is injected. The primary outcome is the difference in maximum pain on an 11-point NRS. Secondary outcomes include: pain and burden of different CT colonography aspects, side effects, procedural time and recovery time. For the primary outcome an independent samples t-test is performed and a P value < 0.05 is considered statistically significant.</p> <p>Discussion</p> <p>This study will provide evidence whether a single bolus intravenous alfentanil gives a clinically relevant reduction in maximum pain during CT colonography.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC= NTR2902">NTR2902</a></p> <p><it>This trial will be conducted in accordance with the protocol and in compliance with the moral, ethical, and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and Good Clinical Practice (GCP). The department of radiology of the Academic Medical Center of Amsterdam is responsible for the design and conduct of the trial</it>.</p
Measuring Political Commitment in Statistical Models for Evidence-based Agenda Setting in Nonmotorized Traffic
When investigating national and international transport policies of the last decade, an ever increasing
emphasis on promoting non-motorized transport modes such as walking or cycling can be identified, aiming
at reaching multiple political targets (eg. reducing pollution, increasing health or lowering land
consumption). However, despite substantial financial efforts being put into infrastructural or awarenessraising
activities, achieving the desired modal shift towards active mobility remains a challenge. This is
frequently due to unclear cause and effect patterns between active mode shares and their determinants, which
in turn leads to uncoordinated or highly fragmented initiatives that impede target-oriented planning.
An internationally adopted approach to overcome this problem is applying aggregated statistical models that
explain modal choice involving multiple regression techniques and hypothetical covariates. Still, general
critique against these models points out that important intangible soft factors such as attitudinal
characteristics of the local population or mind-sets and political commitment of decision makers are not duly
reflected. Also, for Austria there is currently no systematic holistic approach to explain spatial variance in
active travel shares on the scale of municipalities.
Hence the main objective of our research is to design a comprehensive macroscopic model-based approach
for the quantitative explanation of modal split shares in active travel modes in Austria. In our approach we
attach great importance to the inclusion of soft factors in order to contribute novel findings on the dynamics
behind active travel. The research outcomes will aid decision makers and planners in their question where
and more specifically, how to effectively invest into active mobility by revealing key soft factors and
intangible determinants of active travel mode shares alongside a broad range of more known, traditional
factors. Based on this evidence-based decision support approach it is possible to simulate impacts of actions
when aiming at locally promoting active travel modes
The Tinnitus Research Initiative (TRI) database: A new approach for delineation of tinnitus subtypes and generation of predictors for treatment outcome
Tinnitus, the phantom perception of sound, is a frequent disorder that causes significant morbidity and treatment is elusive. A large variety of different treatment options have been proposed and from most of them some patients benefit. However, a particular treatment that helps one patient may fail for others. This suggests that there are different forms of tinnitus which differ in their pathophysiology and their response to specific treatments. Therefore, it is a major challenge for tinnitus treatment to identify the most promising therapy for a specific patient
Preoperative anaemia and outcome after elective cardiac surgery:a Dutch national registry analysis
Background: Previous studies have shown that preoperative anaemia in patients undergoing cardiac surgery is associated with adverse outcomes. However, most of these studies were retrospective, had a relatively small sample size, and were from a single centre. The aim of this study was to analyse the relationship between the severity of preoperative anaemia and short- and long-term mortality and morbidity in a large multicentre national cohort of patients undergoing cardiac surgery. Methods: A nationwide, prospective, multicentre registry (Netherlands Heart Registration) of patients undergoing elective cardiac surgery between January 2013 and January 2019 was used for this observational study. Anaemia was defined according to the WHO criteria, and the main study endpoint was 120-day mortality. The association was investigated using multivariable logistic regression analysis. Results: In total, 35 484 patients were studied, of whom 6802 (19.2%) were anaemic. Preoperative anaemia was associated with an increased risk of 120-day mortality (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI]: 1.4–1.9; P<0.001). The risk of 120-day mortality increased with anaemia severity (mild anaemia aOR 1.6; 95% CI: 1.3–1.9; P<0.001; and moderate-to-severe anaemia aOR 1.8; 95% CI: 1.4–2.4; P<0.001). Preoperative anaemia was associated with red blood cell transfusion and postoperative morbidity, the causes of which included renal failure, pneumonia, and myocardial infarction. Conclusions: Preoperative anaemia was associated with mortality and morbidity after cardiac surgery. The risk of adverse outcomes increased with anaemia severity. Preoperative anaemia is a potential target for treatment to improve postoperative outcomes
Infants and Newborns with Atypical Teratoid Rhabdoid Tumors (ATRT) and Extracranial Malignant Rhabdoid Tumors (eMRT) in the EU-RHAB Registry: A Unique and Challenging Population
Malignant rhabdoid tumors (MRT) predominantly affect infants and young
children. Patients below six months of age represent a particularly therapeutically challenging group.
Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors,
genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and
treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were
analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations
using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH,
and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients
presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK).
Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27%
(26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation
subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based
subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were
23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4%
vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%)
were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses
confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model,
clinical factors that favorably influence the prognosis were female sex, localized stage, absence of
a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants
with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which
need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option
Infants and newborns with Atypical Teratoid Rhabdoid Tumors (ATRT) and Extracranial Malignant Rhabdoid Tumors (eMRT) in the EU-RHAB registry: a unique and challenging population
SIMPLE SUMMARY: Malignant rhabdoid tumors (MRT) are deadly tumors that predominantly affect infants and young children. Even when considering the generally young age of these patients, the treatment of infants below the age of six months represents a particular challenge due to the vulnerability of this patient population. The aim of our retrospective study was to assess the available information on prognostic factors, genetics, toxicity of treatment and long-term outcomes of MRT. We confirmed that, in a cohort of homogenously treated infants with MRT, significant predictors of outcome were female sex, localized stage, absence of a GLM and maintenance therapy, and these significantly favorably influence prognosis. Stratification-based biomarker-driven tailored trials may be a key option to improve survival rates. ABSTRACT: Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option
Expression of miRNAs miR-133b and miR-206 in the Il17a/f Locus Is Co-Regulated with IL-17 Production in αβ and γδ T Cells
Differentiation of T helper 17 cells (Th17) is a multistep process that involves the cytokines IL-6, TGF-β, and IL-23 as well as IL-1β, IL-21, and TNF-α. Thereby, robust induction of the capacity to produce IL-17 involves epigenetic modifications of the syntenic Il17a/f locus. Using inbred mouse strains, we identified co-regulation of gene transcription at the Il17a/f locus with the nearby microRNAs miR-133b and miR-206 that are clustered approximately 45 kb upstream of Il17a/f. Expression of these microRNAs was specific for Th17 as compared to other CD4+ T cell subsets and this was equally valid for in vitro polarized and ex vivo derived cells. From all factors analyzed, IL-23 was the most important cytokine for the in vitro induction of miR-133b and miR-206 in naive CD4+ T cells of wild type mice. However, analysis of IL-23R deficient mice revealed that IL-23R signaling was not essential for the induction of miR-133b and miR-206. Importantly, we found a similar co-regulation in CCR6+ and other γδ T cell subsets that are predisposed to production of IL-17. Taken together, we discovered a novel feature of T cell differentiation towards an IL-17-producing phenotype that is shared between αβ and γδ T cells. Notably, the specific co-regulation of miR-133b and miR-206 with the Il17a/f locus also extended to human Th17 cells. This qualifies expression of miR-133b and miR-206 in T cells as novel biomarkers for Th17-type immune reactions
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