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Bij besluitvorming over maatregelen op het gebied van emissie-reductie zijn niet alleen gegevens over emissies nodig maar ook over de onzekerheid daarvan. Dit rapport beschrijft een studie naar het gebruik van gestructureerde expertbevraging bij onzekerheidsanalyse van de NOx-emissies uit personenauto's. Experts van verschillende Nederlandse onderzoeksinstituten zijn bevraagd over prestatiegegevens (emissie-factoren) en volumegegevens (kilometrages). De totale populatie onzekerheid is berekend door het opschalen van de onzekerheid van individuele auto's door Monte Carlo simulaties. In de berekening is expliciet onderscheid gemaakt tussen variabelen die inherent variabel zijn (aleatorische onzekerheid) en variabelen die onzeker zijn vanwege een gebrek aan kennis (epistemische onzekerheid). Het kleinste 95% betrouwbaarheidsinterval werd verkregen voor de TNO-CBS expert (-12% tot +15%), en het grootste interval voor de RIVM expert (-35% tot +51%). De combinatie van experts (decision-makers [DM] genoemd in deze methode) kreeg intervallen van -30% tot +41% (DM voor propagatie) en van -46% tot +81% (DM na aggregatie). Het gebruik van expert bevraging bleek arbeidsintensief en er is veel discussie over het wel of niet combineren van expert antwoorden. Het gebruik van deze methode moet daarom goed onderbouwd worden, en moet zich richten op de meest gevoelige en controversiele parameters.

Aims Treatment delay is a powerful predictor of survival in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We investigated effectiveness of pre-hospital diagnosis of STEMI with direct referral to PCI, alongside more conventional referral strategies. Methods and results From January 2003 to December 2004, 658 STEMI patients were referred for primary PCI at our intervention laboratory. Three predefined referral routes were compared: (1) for patients within 90 min drive of the PCI centre, pre-hospital diagnosis and direct transportation ( n =166), (2) diagnosis at the interventional hospital emergency department ( n =316), (3) diagnosis at local hospitals before transportation ( n =176). Pre-hospital diagnosis was associated with more than 45 min reduction in treatment delay ( P =0.001). No significant difference in in-hospital mortality was apparent in the overall study population. In the cardiogenic shock subgroup ( n =80), pre-hospital diagnosis was associated with a two-thirds reduction in in-hospital mortality ( P =0.019); mortality was only 6.2% in shock patients who underwent PCI in

We investigated the diagnostic accuracy of (99m)Tc-3,3- diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy for differentiation of monoclonal immunoglobulin light-chain (AL) and transthyretin (TTR)-related cardiac amyloidosis. BACKGROUND: Differential diagnosis between TTR-related and AL amyloidosis is often complex and time-consuming. METHODS: Patients under routine observation with TTR-related/AL systemic amyloidosis and echocardiographic evidence of cardiac involvement were studied with (99m)Tc-DPD scintigraphy. RESULTS: Patients with cardiac involvement of TTR-related (group A; n = 15) and AL (group B; n = 10) etiology were comparable for left ventricular mass and renal function. Heart and heart/whole-body tracer retention were significantly higher (p < 0.05) in group A as compared with group B and with 10 unaffected controls. At visual scoring, cardiac (99m)Tc-DPD uptake was present in all group A patients and absent in all group B patients; thus, using genotyping/immunohistochemistry as the reference technique, the accuracy of (99m)Tc-DPD scintigraphy for distinction of TTR-related and AL etiology was 100%. Cardiac (99m)Tc-DPD uptake was also absent among unaffected controls. Using echocardiography as the reference standard for recognition of cardiac involvement, sensitivity and specificity of scintigraphy were both 100% for group A patients; in group B, sensitivity was 0% and specificity was 100% (accu racy, 50%). Eleven patients with myocardial (99m)Tc-DPD uptake underwent (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) scintigraphy; all patients showed a (99m)Tc-MDP myocardial visual score of 0. CONCLUSIONS: Etiology is a third major cause-in addition to type of organ-involved (soft-tissue/heart) and tracer type-of scintigraphic variability in cardiac amyloidosis. This is a highly relevant consideration for future studies. We conclude that (99m)Tc-DPD scintigraphy is a useful step in the workup of the differential diagnosis of TTR versus AL etiology in patients with documented cardiac amyloidosis.

BACKGROUND: Many ICD carriers experience inappropriate shocks, but the relative merits of dual- /single-chamber devices for arrhythmia discrimination still remain unclear. We explored possible advantages of the atrial data provided by dual-chamber implantable defibrillators (ICD) for discrimination of real-life supraventricular/ventricular tachyarrhythmias (SVT/VT). METHODS: 100 dual-chamber traces from 24 ICD were blindly reviewed in dual-chamber and simulated single-chamber (with/without discriminator data) reading modes by five electrophysiologists who determined chamber of origin and provided Likert-scale "confidence" ratings. We assessed 1) intra/interobserver concordance; 2) diagnostic accuracy, using expert diagnoses as a reference standard; 3) ROC curves of sensitivity/specificity of "likelihood perception" scores, generated by combining chamber-of-origin diagnostic judgments with Likert-scale "confidence" ratings. We also assessed diagnostic accuracy of automated discrimination by all possible dual-/single-chamber algorithm configurations. RESULTS: Interobserver concordance was "substantial" (modified Cohen kappa-test values for dual-/single-chamber, 0.79/0.68); intraobserver concordance "almost complete" (kappa ≥ 0.89). Dual-chamber mode provided best diagnostic sensitivity/specificity (99%/92%) and highest reader confidence (p

Objective: To identify efficient PubMed search strategies to retrieve articles regarding putative occupational determinants of conditions not generally considered to be work related. Methods: Based on MeSH definitions and expert knowledge, we selected as candidate search terms the four MeSH terms describing 'occupational disease', 'occupational exposure', 'occupational health' and 'occupational medicine' (DEHM) alongside 22 other promising terms. We first explored overlaps between the candidate terms in PubMed. Using random samples of abstracts retrieved by each term, we estimated the proportions of articles containing potentially pertinent information regarding occupational aetiology in order to formulate two search strategies (one more 'specific', one more 'sensitive'). We applied these strategies to retrieve information on the possible occupational aetiology of meningioma, pancreatitis and atrial fibrillation. Results: Only 20.3% of abstracts were retrieved by more than one DEHM term. The more 'specific' search string was based on the combination of terms that yielded the highest proportion (40%) of potentially pertinent abstracts. The more 'sensitive' string was based on the use of broader search fields and additional coverage provided by other search terms under study. Using the specific string, the numbers of abstracts needed to read to find one potentially pertinent article were 1.2 for meningioma, 1.9 for pancreatitis and 1.8 for atrial fibrillation. Using the sensitive strategy, the numbers needed to read were 4.4 for meningioma, 8.9 for pancreatitis and 10.5 for atrial fibrillation. Conclusions: The proposed strings could help health care professionals explore putative occupational aetiology for diseases that are not generally thought to be work related.

Background Carpal tunnel syndrome (CTS) is a socially and economically relevant disease caused by compression or entrapment of the median nerve within the carpal tunnel. This population-based case-control study aims to investigate occupational/non-occupational risk factors for surgically treated CTS. Methods Cases (n = 220) aged 18-65 years were randomly drawn from 13 administrative databases of citizens who were surgically treated with carpal tunnel release during 2001. Controls (n = 356) were randomly sampled from National Health Service registry records and were frequency matched by age-gender-specific CTS hospitalization rates. Results At multivariate analysis, risk factors were blue-collar/housewife status, BMI ≥ 30 kg/m2, sibling history of CTS and coexistence of trigger finger. Being relatively tall (cut-offs based on tertiles: women ≥165 cm; men ≥175 cm) was associated with lower risk. Blue-collar work was a moderate/strong risk factor in both sexes. Raised risks were apparent for combinations of biomechanical risk factors that included frequent repetitivity and sustained force. Conclusion This study strongly underlines the relevance of biomechanical exposures in both non-industrial and industrial work as risk factors for surgically treated CTS.

OBJECTIVES To evaluate implementation of low-density lipoprotein cholesterol (LDL-C) control recommendations in secondary care and explore key points in the decisional workup. METHODS AND RESULTS In a nationwide survey of secondary-care outpatients (n=11,124), we studied prevalence/predictors of (1) LDL-C value availability; (2) ongoing treatment with statins; (3) achievement of US National Cholesterol Education Program III target LDL-C values. Agreement between US National Cholesterol Education Program III risk category and physicians' personal risk assessments was also studied. LDL-C values were available for 78% evaluable patients; 71% of the patients with dyslipidema were undergoing treatment with statins; 34% patients undergoing treatment had target LDL-C values. At regression analysis, non-availability of LDL-C values was predicted by absence of diabetes, presence of normotension, and advancing age; lack of statins treatment by female sex, diabetes, overweight and northern location (southern location predicted treatment); non-achievement of target LDL-C values by age, diabetes, attending a diabetic clinic, cigarette smoking, history of cardiovascular disease, and taking less than six pills per day. Physicians provided underestimates of patients' risk (39% high-risk patients were rated as intermediate-risk patients and a further 10% as low-risk patients). CONCLUSION Suboptimal prevention practice seems to be associated with various factors acting at different levels within the complex process running from individual risk-level ascertainment to LDL-C target achievement. Multicomponent interventions that target the different key steps need to be considered.

To investigate associations between gender and myocardial involvement in systemic amyloidosis, we reviewed all patients presenting between 1994 and September 2006 in our institutional network (100 AL and 98 familial transthyretin-related amyloidosis (ATTR) patients, plus 12 elderly men with senile systemic amyloidosis). We focused on echocardiographic descriptors of myocardial involvement (height-indexed mean left ventricular (LV) wall thickness, LV mass index), and baseline LV function. Among familial ATTR patients, female prevalence was lower within the highest tertile of either echocardiographic indicator of myocardial involvement. Gender was independently associated with height-indexed mean LV wall thickness (as were gene mutations). Female prevalence appeared rather similar across the different neurological stages. Within the subgroup of familial ATTR patients with amyloidotic cardiomyopathy, women tended to display a considerably less severe morphological and functional echocardiographic profile. We explored the possible role of female sex hormones by considering menopausal status: women in the highest tertile of mean LV wall thickness index were more often postmenopausal than those in the other two tertiles and had a much higher ( approximately 15 years) mean age; analogous age-related associations were not observable for men. In conclusion, these findings raise the hypothesis that some biological characteristic associated with female gender protects against myocardial involvement in familial ATTR.

OBJECTIVES: To see whether use of a sirolimus-eluting stent (SES) is superior to a third-generation thin-strut, cobalt-chromium stent (CCS) in terms of in-segment late loss at 9 months in patients with symptomatic coronary artery disease. BACKGROUND: Stent-strut thickness has been shown to be strictly related with risk of in-stent restenosis, but available demonstrations of the angiographic efficacy of SES have been based on comparisons with thick-strut bare metal control stents. METHODS: The primary outcome measure of this single-center, single-blind randomized comparative trial was 9-month in-segment late loss. Eligibility criteria were symptomatic coronary artery disease and target vessel diameter appropriate for implantation a 3-mm stent. Based on a power calculation, 104 patients were randomly assigned to receive a SES (Cypher™) or a CCS (Vision™). RESULTS: In-segment late loss was significantly lower in the SES group (0.18 ± 0.40 mm vs 0.58 ± 0.51 mm, P < 0.001). Regarding subsidiary outcome measures, in-segment restenosis (at 9 months) was recorded in 10% (5/50) patients treated with SES and 23% (11/48) receiving CCS (P = 0.14). No clinical difference between the two groups was apparent at 12 months. Freedom from target vessel failure at 12 months was 72% for SES patients and 68% for CCS patients (P = 0.65). CONCLUSIONS: In patients with de-novo coronary lesions at medium risk of restenosis the anti-proliferative effect of SES is greater than that of a thin-strut CCS. Nevertheless, the angiographic results of the CCS were rather good. It remains to be seen whether the angiographic superiority of SES can translate into clinical superiority. © 2007 Wiley-Liss, Inc.

Transthyretin-related hereditary amyloidosis (ATTR) is genotypically/phenotypically heterogeneous. We investigated myocardial involvement in ATTR in a cohort of patients with a wide range of mutations. Clinical/echocardiographic follow-up of 41 consecutive symptomatic ATTR patients from a single referral center was analyzed according to TTR mutation. Diagnosis was based on histology, immunohistochemistry and genotyping. Median follow up was 40 months (range 8-120). Among the 12 different mutations identified, Val30Met was found in 10 patients and Glu89Gln in seven. Compared with Val30Met, Glu89Gln was associated with higher LV mass index, lower left ventricular ejection fraction and shorter E-wave deceleration time. All Glu89Gln carriers had cardiomyopathy, which was more severe (for left ventricular thickness, left ventricular mass and restrictive pathophysiology) than in the six affected Val30Met patients. Glu89Gln was independently associated with higher risk of major cardiovascular events among cardiomyopathy patients. This follow-up study of ATTR patients carrying a wide range of mutations indicates that (1) cardiac involvement is a very important component of phenotypic expression; and (2) genotype is an important source of heterogeneity in myocardial involvement, with Glu89Gln being associated with a severe, heart-driven prognosis. We think that combined heart-liver transplantation could be considered for Glu89Gln carriers with established, morphologically severe cardiomyopathy.

We recently reported a case-control study1 testing the hypothesis that heavy occupational lifting or manual handling (requiring the Valsalva maneuver) may be a risk factor for retinal detachment among people who are myopic (nearsighted). This study also suggested a possible role for obesity. To evaluate the study hypothesis, we had restricted our analysis to myopic subjects, adjusting for degree of myopia. Other etiologic studies of retinal detachment,2,3 although not restricted to myopic subjects, have provided little information on risk factors among nonmyopic people. We therefore did a supplementary analysis of our data to explore how risk factors for retinal detachment vary in nonmyopic subjects compared with near-sighted people. In the absence of data for suitable nonmyopic control subjects, we conducted a case-case analysis of all the myopic cases of retinal detachment included in the parent study1 (26 women, 35 men), alongside the previously excluded nonmyopic cases (29 women, 30 men). We analyzed risk factors such as heavy lifting/manual handling, body mass index (BMI), and alcohol consumption, along with age, head/eye trauma, and eye surgery. Occupational lifting of at least 10 kg (commonly requiring the Valsalva maneuver) was again evaluated by a cumulative lifting index, calculated as the product of load (kg), frequency (number of lifting maneuvers/ wk), and number of years of lifting (using the same cut-offs: heavy lifting, 8000 kg frequency year; reference category, no lifting).1 For multivariate analysis, we used ordered logistic regression analysis to take into account severity of myopia (mild/moderate/ severe), additionally adjusting for sex. Perhaps unsurprisingly, there was no sign of any association for either eye surgery or head trauma retinal detachment (Table). The point estimates close to unity suggest that the effects of these 2 major predisposing factors on retinal detachment4 are similar in nonmyopic and myopic people. The more pronounced age-related risk in nonmyopic cases (4-fold after 65 years) can be attributed to the impact of near-sightedness as a predisposing factor for retinal detachment across the age spectrum. Regarding heavy lifting/manual handling, the absence of any clear association (between nonmyopic and myopic cases) with retinal detachment leads us to hypothesize that this factor may increase the risk of retinal detachment regardless of myopia. As for BMI, there were signs of a possible dose-response relation, suggesting that obesity might conceivably be an even more prominent risk factor for retinal detachment among nonmyopic people. Perhaps the most intriguing finding relates to alcohol consumption: heavy drinking appeared to be associated with a roughly 4-fold higher risk of retinal detachment in nonmyopic cases compared with myopic cases. Notably, there were signs of a dose-response relation through light to moderate to heavy drinking (and, considering the nondrinkers, perhaps also of the J-shaped curve often observed in etiologic studies of cardiovascular diseases 5). Available data regarding the possible role of heavy drinking as a risk factor for eye diseases are contradictory. 6 Our observations suggest that the plausible etiologic role of heavy drinking in retinal detachment might be more relevant (or more evident) in nonmyopic people, and underline the need6 for clarification of the effect of heavy drinking on this and other eye conditions. These results may provide useful hints for future hypothesis-driven research into plausible risk factors for retinal detachment, including high alcohol intake, heavy lifting, and obesity. They also highlight the need for analytic studies to evaluate risk factors separately for nonmyopic people— especially because retinal detachment often occurs in the absence of myopia.