The risk linked to ionizing radiation: an alternative epidemiologic approach.

Radioprotection norms have been based on risk models that have evolved over time. These models show relationships between exposure and observed effects. There is a high level of uncertainty regarding lower doses. Recommendations have been based on the conservative hypothesis of a linear relationship without threshold value. This relationship is still debated, and the diverse observations do not allow any definitive conclusion. Available data are contradictory, and various interpretations can be made. Here we review an alternative approach for defining causation and reconciling apparently contradictory conclusions. This alternative epidemiologic approach is based on causal groups: Each component of a causal group is necessary but not sufficient for causality. Many groups may be involved in causality. Thus, ionizing radiation may be a component of one or several causal groups. This formalization reconciles heterogeneous observations but implies searching for the interactions between components, mostly between critical components of a causal profile, and, for instance, the reasons why specific human groups would not show any effect despite exposure, when an effect would be expected

Epilepsy Is a Risk Factor for Sudden Cardiac Arrest in the General Population

Background People with epilepsy are at increased risk for sudden death. The most prevalent cause of sudden death in the general population is sudden cardiac arrest (SCA) due to ventricular fibrillation (VF). SCA may contribute to the increased incidence of sudden death in people with epilepsy. We assessed whether the risk for SCA is increased in epilepsy by determining the risk for SCA among people with active epilepsy in a community-based study. Methods and Results This investigation was part of the Amsterdam Resuscitation Studies (ARREST) in the Netherlands. It was designed to assess SCA risk in the general population. All SCA cases in the study area were identified and matched to controls (by age, sex, and SCA date). A diagnosis of active epilepsy was ascertained in all cases and controls. Relative risk for SCA was estimated by calculating the adjusted odds ratios using conditional logistic regression (adjustment was made for known risk factors for SCA). We identified 1019 cases of SCA with ECG-documented VF, and matched them to 2834 controls. There were 12 people with active epilepsy among cases and 12 among controls. Epilepsy was associated with a three-fold increased risk for SCA (adjusted OR 2.9 [95%CI 1.1–8.0.], p = 0.034). The risk for SCA in epilepsy was particularly increased in young and females. Conclusion Epilepsy in the general population seems to be associated with an increased risk for SCA

The use of 4D-CTA in the diagnostic work-up of brain arteriovenous malformations

Neuro Imaging Researc

Epidemiology of frequent attenders: a 3-year historic cohort study comparing attendance, morbidity and prescriptions of one-year and persistent frequent attenders

BACKGROUND: General Practitioners spend a disproportionate amount of time on frequent attenders. So far, trials on the effect of interventions on frequent attenders have shown negative results. However, these trials were conducted in short-term frequent attenders. It would be more reasonable to target intervention at persistent frequent attenders. Typical characteristics of persistent frequent attenders, as opposed to 1-year frequent attenders and non-frequent attenders, may generate hypotheses regarding modifiable factors on which new randomized trials may be designed. METHODS: We used the data of all 28,860 adult patients from 5 primary healthcare centers. Frequent attenders were patients whose attendance rate ranked in the (age and sex adjusted) top 10 percent during 1 year (1-year frequent attenders) or 3 years (persistent frequent attenders). All other patients on the register over the 3-year period were referred to as non-frequent attenders. The lists of medical problems coded by the GP using the International Classification of Primary Care (ICPC) were used to assess morbidity.First, we determined which proportion of 1-year frequent attenders was still a frequent attender during the next two consecutive years and calculated the GPs' workload for these patients. Second, we compared morbidity and number of prescriptions for non-frequent attenders, 1-year frequent attenders and persistent frequent attenders. RESULTS: Of all 1-year frequent attenders, 15.4% became a persistent frequent attender equal to 1.6% of all patients. The 1-year frequent attenders (3,045; 10.6%) were responsible for 39% of the face-to-face consultations; the 470 patients who would become persistent frequent attenders (1.6%) were responsible for 8% of all consultations in 2003. Persistent frequent attenders presented more social problems, more psychiatric problems and medically unexplained physical symptoms, but also more chronic somatic diseases (especially diabetes). They received more prescriptions for psychotropic medication. CONCLUSION: One out of every seven 1-year-frequent attenders (15.4%) becomes a persistent frequent attender. Compared with non-frequent attenders, and 1-year frequent attenders, persistent frequent attenders consume more health care and are diagnosed not only with more somatic diseases but especially more social problems, psychiatric problems and medically unexplained physical symptoms

Patients' experiences with quality of hospital care: the Consumer Quality Index Cataract Questionnaire

Background. Patients' feedback is of great importance in health care policy decisions. The Consumer Quality Index Cataract Questionnaire (CQI Cataract) was used to measure patients' experiences with quality of care after a cataract operation. This study aims to evaluate the reliability and the dimensional structure of this questionnaire and assesses its ability to measure differences between hospitals in patients' experiences with quality of care. Methods. Survey data of 4,635 respondents were available. An exploratory factor analysis was performed to evaluate the construct validity of the questionnaire and item-correlations and inter-factor correlations were calculated. Secondly, Cronbach's alpha coefficients were calculated to assess the internal consistency of the scales. Thirdly, to evaluate the ability of the questionnaire to discriminate between hospitals, multilevel analyses were performed with patients hierarchically nested within hospitals. Results. Exploratory factor analysis resulted in 14 quality of care items subdivided over three factors (i.e. communication with ophthalmologist, communication with nurses, and communication about medication). Cronbach's alpha coefficients of 0.89, 0.76 and 0.79 indicated good internal consistency. Multilevel analyses showed that the questionnaire was able to measure differences in patients' experiences with hospital care regarding communication with ophthalmologist and communication about medication. In addition, there was variation between hospitals regarding ophthalmologist ratings, hospital ratings and one dichotomous information item. Conclusion. These findings suggest that the CQI Cataract is a reliable and valid instrument. This instrument can be used to measure patients' experiences with three domains of hospital care after a cataract operation and is able to assess differences in evaluated care between hospitals

Readiness of the Belgian network of sentinel general practitioners to deliver electronic health record data for surveillance purposes: results of survey study

<p>Abstract</p> <p>Background</p> <p>In order to proceed from a paper based registration to a surveillance system that is based on extraction of electronic health records (EHR), knowledge is needed on the number and representativeness of sentinel GPs using a government-certified EHR system and the quality of EHR data for research, expressed in the compliance rate with three criteria: recording of home visits, use of prescription module and diagnostic subject headings.</p> <p>Methods</p> <p>Data were collected by annual postal surveys between 2005 and 2009 among all sentinel GPs. We tested relations between four key GP characteristics (age, gender, language community, practice organisation) and use of a certified EHR system by multivariable logistic regression. The relation between EHR software package, GP characteristics and compliance with three quality criteria was equally measured by multivariable logistic regression.</p> <p>Results</p> <p>A response rate of 99% was obtained. Of 221 sentinel GPs, 55% participated in the surveillance without interruption from 2005 onwards, i.e. all five years, and 78% were participants in 2009. Sixteen certified EHR systems were used among 91% of the Dutch and 63% of the French speaking sentinel GPs. The EHR software package was strongly related to the community and only one EHR system was used by a comparable number of sentinel GPs in both communities. Overall, the prescription module was always used and home visits were usually recorded. Uniform subject headings were only sometimes used and the compliance with this quality criterion was almost exclusively related to the EHR software package in use.</p> <p>Conclusions</p> <p>The challenge is to progress towards a sentinel network of GPs delivering care-based data that are (partly) extracted from well performing EHR systems and still representative for Belgian general practice.</p

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P &lt; 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes

New hydroxylated metabolites of 4-monochlorobiphenyl in whole poplar plants

Two new monohydroxy metabolites of 4-monochlorobiphenyl (CB3) were positively identified using three newly synthesized monohydroxy compounds of CB3: 2-hydroxy-4-chlorobiphenyl (2OH-CB3), 3-hydroxy-4-chlorobiphenyl (3OH-CB3) and 4-hydroxy-3-chlorobiphenyl (4OH-CB2). New metabolites of CB3, including 2OH-CB3 and 3OH-CB3, were confirmed in whole poplars (Populus deltoides × nigra, DN34), a model plant in the application of phytoremediation. Furthermore, the concentrations and masses of 2OH-CB3 and 3OH-CB3 formed in various tissues of whole poplar plants and controls were measured. Results showed that 2OH-CB3 was the major product in these two OH-CB3s with chlorine and hydroxyl moieties in the same phenyl ring of CB3. Masses of 2OH-CB3 and 3OH-CB3 in tissues of whole poplar plants were much higher than those in the hydroponic solution, strongly indicating that the poplar plant itself metabolizes CB3 to both 2OH-CB3 and 3OH-CB3. The total yield of 2OH-CB3 and 3OH-CB3, with chlorine and hydroxyl in the same phenyl ring of CB3, was less than that of three previously found OH-CB3s with chlorine and hydroxyl in the opposite phenyl rings of CB3 (2'OH-CB3, 3'OH-CB3, and 4'OH-CB3). Finally, these two newly detected OH-CB3s from CB3 in this work also suggests that the metabolic pathway was via epoxide intermediates. These five OH-CB3s clearly showed the complete metabolism profile from CB3 to monohydroxylated CB3. More importantly, it's the first report and confirmation of 2OH-CB3 and 3OH-CB3 (new metabolites of CB3) in a living organism

The way that you do it? An elaborate test of procedural invariance of TTO, using a choice-based design

The time tradeoff (TTO) method is often used to derive Quality-Adjusted Life Year health state valuations. An important problem with this method is that results have been found to be responsive to the procedure used to elicit preferences. In particular, fixing the duration in the health state to be valued and inferring the duration in full health that renders an individual indifferent, causes valuations to be higher than when the duration in full health is fixed and the duration in the health state to be valued is elicited. This paper presents a new test of procedural invariance for a broad range of time horizons, while using a choice-based design and adjusting for discounting. As one of the known problems with the conventional procedure is the violation of constant proportional tradeoffs (CPTO), we also investigate CPTO for the alternative TTO procedure. Our findings concerning procedural invariance are rather supportive for the TTO procedure. We find no violations of procedural invariance except for the shortest gauge duration. The results for CPTO are more troublesome: TTO scores depend on gauge duration, reinforcing the evidence reported when using the conventional procedure

Regulation of MYCN expression in human neuroblastoma cells

Contains fulltext : 81722.pdf (publisher's version ) (Open Access)BACKGROUND: Amplification of the MYCN gene in neuroblastoma (NB) is associated with a poor prognosis. However, MYCN-amplification does not automatically result in higher expression of MYCN in children with NB. We hypothesized that the discrepancy between MYCN gene expression and prognosis in these children might be explained by the expression of either MYCN-opposite strand (MYCNOS) or the shortened MYCN-isoform (DeltaMYCN) that was recently identified in fetal tissues. Both MYCNOS and DeltaMYCN are potential inhibitors of MYCN either at the mRNA or at the protein level. METHODS: Expression of MYCN, MYCNOS and DeltaMYCN was measured in human NB tissues of different stages. Transcript levels were quantified using a real-time reverse transcriptase polymerase chain reaction assay (QPCR). In addition, relative expression of these three transcripts was compared to the number of MYCN copies, which was determined by genomic real-time PCR (gQPCR). RESULTS: Both DeltaMYCN and MYCNOS are expressed in all NBs examined. In NBs with MYCN-amplification, these transcripts are significantly higher expressed. The ratio of MYCN:DeltaMYCN expression was identical in all tested NBs. This indicates that DeltaMYCN and MYCN are co-regulated, which suggests that DeltaMYCN is not a regulator of MYCN in NB. However, the ratio of MYCNOS:MYCN expression is directly correlated with NB disease stage (p = 0.007). In the more advanced NB stages and NBs with MYCN-amplification, relatively more MYCNOS is present as compared to MYCN. Expression of the antisense gene MYCNOS might be relevant to the progression of NB, potentially by directly inhibiting MYCN transcription by transcriptional interference at the DNA level. CONCLUSION: The MYCNOS:MYCN-ratio in NBs is significantly correlated with both MYCN-amplification and NB-stage. Our data indicate that in NB, MYCN expression levels might be influenced by MYCNOS but not by DeltaMYCN