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Het RIVM brengt elk jaar in kaart hoeveel mensen in Nederland griep en andere luchtweginfecties hebben. Dit keer staat het overzicht in het teken van de uitbraak van het coronavirus SARS-CoV-2. Dit virus overheerste in 2020 en 2021. In combinatie met de maatregelen om de verspreiding van het virus tegen te gaan, hadden hierdoor veel minder mensen andere luchtweginfecties. COVID-19 Tijdens de zomer van 2020, van mei tot en met september, hadden heel weinig mensen COVID-19, de ziekte die het coronavirus veroorzaakt. Na de zomer begon de tweede golf, die twee pieken had: in oktober en eind december. Deze golf begon onder de jongere leeftijdsgroepen (10 tot 29 jaar). Daarna kregen steeds meer mensen tussen 40 en 50 jaar COVID-19, gevolgd door mensen van 70 jaar of ouder. De derde golf begon in februari 2021. Het aantal besmettingen nam toen vooral toe door de opkomst van de Alfavariant (de Britse variant). Deze variant was tussen begin februari en eind mei 2021 de meest gemelde variant van het coronavirus. Tussen 18 mei 2020 en 23 mei 2021 zijn 1.584.237 mensen positief getest op corona. Van hen zijn 53.175 mensen opgenomen in het ziekenhuis, en 9.649 op de intensive care. Van 11.640 mensen is bekend dat ze zijn overleden. Tijdens de tweede en derde golf stierven er 14.739 mensen meer dan de afgelopen 5 jaren in dezelfde periode. Deze ‘oversterfte’ hangt naar verwachting samen met de uitbraak van dit virus. Griepepidemie Tijdens het griepseizoen zijn er nauwelijks mensen geregistreerd met de griep (2). Er was daarom deze winter geen griepepidemie. Dit komt waarschijnlijk door de coronamaatregelen, die ook helpen om de verspreiding van andere virussen te voorkomen, zoals de griep. Meldingsplichtige luchtweginfecties Sommige luchtweginfecties moeten bij de GGD worden gemeld. De GGD kan besmettingen dan intensief volgen en zo nodig snel actie nemen om te voorkomen dat ze zich verder verspreiden. Het aantal meldingen van psittacose (papegaaienziekte) is in 2020 licht gestegen naar 94, het hoogste aantal sinds 2010. Het aantal meldingen in 2020 van legionella (461), tuberculose (623) en Q-koorts (7) nam juist sterk af. Legionella kwam waarschijnlijk minder vaak voor, omdat er minder internationale reizen zijn gemaakt in 2020. Q-koorts, psittacose en legionella uiten zich meestal in de vorm van longontstekingen, maar de oorzaak daarvan wordt vaak niet onderzocht. De werkelijke aantallen liggen daardoor hoger dan de gemelde aantallen.

Griepepidemie De griepepidemie in de winter van 2019/2020 was mild en duurde 5 weken. Dat is korter dan het gemiddelde van tien weken in de afgelopen 25 jaar. De laatste twee weken van de griepepidemie, de eerste helft van maart 2020, vielen samen met het begin van de COVID-19-epidemie in Nederland. Naar schatting hebben tussen oktober 2019 en mei 2020 400.000 mensen de griep gehad. Ongeveer 74.000 mensen gingen naar de huisarts met griepachtige klachten. Mensen zijn vooral ziek geworden van het type A-griepvirus. Tijdens de epidemie stierven er 600 mensen meer dan verwacht in deze periode. Deze 'oversterfte' hangt waarschijnlijk samen met de griep. Mensen die een griepprik hebben gekregen, hadden in het griepseizoen 48 procent minder kans om griep te krijgen. De effectiviteit van het vaccin is ongeveer hetzelfde als in vorige griepseizoenen. COVID-19 epidemie in Nederland In deze rapportage zijn de gegevens over COVID-19 meegenomen voor de duur van het griepseizoen, tot en met 17 mei. Op 27 februari 2020 is de eerste COVID-19-patiënt in Nederland bevestigd. Sindsdien zijn veel mensen besmet met het nieuwe coronavirus (SARSCoV-2) dat de ziekte COVID-19 veroorzaakt. Tussen 27 februari en 17 mei 2020 heeft de GGD 43.993 mensen met COVID-19 gemeld, met een piek van 7794 meldingen in de week van 6 april. In deze eerste golf zijn 11.095 patiënten opgenomen in het ziekenhuis en zijn er 9600 mensen meer overleden dan normaal. Meldingsplichtige luchtweginfecties Sommige luchtweginfecties moeten bij de GGD worden gemeld. De GGD kan ze dan intensief volgen en als het nodig is op tijd actie nemen om te voorkomen dat ze zich verder verspreiden. Het aantal meldingen van psittacose is in 2019 sterk gestegen naar 91, het hoogste aantal sinds 2010. Het aantal gemelde gevallen van legionella (566) tuberculose (759) en Q-koorts (18) bleef stabiel. Q-koorts, psittacose en legionella uiten zich meestal in de vorm van longontstekingen. De werkelijke aantallen liggen hoger dan de gemelde. Mensen met een longontsteking worden vaak niet getest, waardoor de ziekteverwekker niet bekend is.

During the 2016/2017 winter season, the influenza epidemic in the Netherlands lasted for 15 weeks. This was longer than the nine-week average duration of epidemics in the twenty previous seasons. Influenza subtype A(H3N2) was the dominant influenza virus throughout the season. In general, baseline natural immunity against A(H3N2) is relatively low among the elderly. Indeed, the number of patients older than 65 years, who visited a general practitioner (GP) for influenza-like symptoms, was higher than last year when influenza A(H1N1)pdm09 predominated. In nursing homes, the number of patients with influenza-like symptoms was also high. In total, an estimated 500,000 patients had symptomatic influenza in the period between the beginning of October 2016 and the end of May 2017 and 6,500 patients were admitted to hospital for influenza-related symptoms. During the epidemic, there were 7,500 more deaths than expected in this 15-week period. The effectiveness of the influenza vaccine against the A(H3N2) virus was 47 per cent. The circulating Dutch A(H3N2) viruses displayed a good to moderate match with the strain that was used in the 2016 vaccine. The WHO has recommended that the same strain be used for the trivalent vaccine for the 2017/2018 season in the northern hemisphere. The B component in the 2017 trivalent vaccine also remains the same as it was in 2016, but the A(H1N1)pdm09 component will be replaced with a more recent virus. The effectiveness of the vaccine varies every season because it is never known which influenza virus(es) will dominate in the next influenza season. Also, the circulating influenza viruses can evolve over time and deviate from the chosen vaccine viruses. There were more reports of the notifiable respiratory infectious diseases made in the 2016 calendar year than in previous years: tuberculosis (889 notifications), psittacosis (60 notifications) and legionellosis (454 notifications). The increase in legionellosis notifications may be associated with the warm, wet weather conditions in 2016. However, several geographic clusters were observed whose existence could not be explained by heavy rainfall or other weather conditions and for none of these clusters could the source of infection be found. The number of notifications for Q fever (14 notifications) is still decreasing. However, the notifiable infectious diseases that present as pneumonia are notoriously underreported because most cases of community-acquired pneumonia are managed in primary care without specific diagnostic laboratory tests being made.

Griepepidemie De griepepidemie in de winter van 2018/2019 was mild en duurde 14 weken. Dat is langer dan het gemiddelde van negen weken in de afgelopen 20 jaar, maar korter dan de lange griepepidemie van 2017/2018 (18 weken). In totaal zijn tussen oktober 2018 en mei 2019 ongeveer 400.000 mensen ziek geworden door het griepvirus. Ongeveer 165.000 mensen gingen naar de huisarts met griepachtige klachten. Minder mensen moesten vanwege complicaties van griep (meestal longontsteking) in het ziekenhuis worden opgenomen. Naar schatting waren dit er ruim 11.000, tegenover 16.000 in het griepseizoen 2017/2018. Mensen zijn vooral ziek geworden van het type A griepvirus. Tijdens de griepepidemie zijn er 2900 mensen meer overleden dan normaal is in deze periode. Effectiviteit griepvaccin In het griepseizoen 2018/2019 hadden gevaccineerden in Nederland 57 procent minder kans op griep. Dat is ongeveer hetzelfde als in vorige griepseizoenen. In Europa werkte het vaccin minder goed tegen een van de meest voorkomende griepvirussen. Internationaal wordt uitgezocht wat de reden daarvan is. De effectiviteit van het griepvaccin kan per seizoen sterk verschillen. Dat komt omdat een half jaar van tevoren wordt bepaald welke virussen in het griepvaccin komen. Dat gebeurt op basis van de virussen die het griepseizoen ervoor in de wereld het meest voorkwamen. Maar griepvirussen kunnen veranderen, of andere griepvirussen kunnen overheersen tegen de tijd dat het griepseizoen in Nederland begint. Daardoor kan van tevoren nooit precies worden voorspeld welke griepvirussen hierin omloop zullen zijn. Meldingsplichtige luchtweginfecties Sommige luchtweginfecties moeten bij de GGD worden gemeld. De GGD kan ze dan intensief volgen en als het nodig is op tijd actie ondernemen om te voorkomen dat ze zich verder verspreiden. Het aantal meldingen van legionella is in 2018 nog verder gestegen naar 584, het hoogste aantal ooit gerapporteerd. Het aantal gemelde gevallen van tuberculose (806), Q-koorts (18) en psittacose (64) bleef stabiel. Q-koorts, psittacose en legionella uiten zich meestal in de vorm van longontstekingen. Het aantal gemelde gevallen is lager dan het werkelijke aantal. Dat komt doordat vaak niet op deze ziekten wordt getest als mensen een longontsteking hebben.

Influenza In the winter of 2017/2018 the influenza epidemic lasted 18 weeks. This is longer than the average over the last 20 years (nine weeks). Between October 2017 and May 2018, an estimated 900,000 people had symptomatic influenza and 340,000 people consulted their general practitioner with influenza-like symptoms. Hospitals were also temporarily overstretched as many patients had to be admitted due to complications of flu (usually pneumonia); this number is estimated to have been over 16,000. Also, during the epidemic, 9,500 more people died than would normally be the case in the influenza season (October to May). Throughout the entire epidemic, people mostly became ill due to an influenza type B virus of the Yamagata lineage. This is the first time that an influenza type B virus has been dominant right from the start of the epidemic. Influenza vaccine effectiveness In the current season, vaccination prevented 44% of the vaccinated people from getting the influenza B virus. This is despite the fact that the Yamagata lineage of influenza virus type B was not included in the vaccine. Apparently, the other B virus in the vaccine provided a reasonable level of cross-protection. The long duration of the flu epidemic can therefore not be explained by a low effectiveness of the vaccine. The effectiveness of the vaccine can differ greatly from season to season. This is because the composition of the vaccine is decided upon six months in advance and is determined based on the viruses that dominated in the previous season all over the world. However, influenza viruses can change and when the influenza season breaks out in the Netherlands other viruses may dominate. This is why it is not possible to predict exactly which viruses will be dominant. Notifiable respiratory infections Some respiratory infections have to be notified to the Public Health Services in order to prevent any further spread. In 2017, there was a striking increase in the number of notifications of legionella; at 561 this was the highest number ever reported. The number of reports of tuberculosis dropped to 787. The number of reports of Q fever (23) and psittacosis (52) remained stable. Q fever, psittacosis and legionella generally manifest themselves in the form of pneumonia. The number of reported cases is an underestimation of the real number as these diseases are normally not tested for when people have pneumonia.

De griepepidemie van 2014/2015 duurde 21 weken en was daarmee de langstdurende in meer dan 40 jaar. Waarschijnlijk heeft het hoge aantal griepgevallen tot meer longontstekingen, een bekende complicatie van de griep, en meer sterfgevallen geleid. Tijdens de griepepidemie stierven ruim 65.000 mensen, dat is ruim 8.600 meer dan in deze 21 weken was verwacht. De griepprik bleek dit seizoen minder effectief dan verwacht. Het is niet duidelijk of dit de oorzaak van de lange duur van de epidemie is geweest. Dit blijkt uit het jaarverslag influenza en andere luchtweginfecties van het RIVM. Het RIVM voert met partners continue surveillance uit om ontwikkelingen in luchtweginfecties tijdig te signaleren. Zestigplussers en mensen die tot de medische risicogroep behoren, zoals astmapatiënten, worden elk najaar door de huisarts uitgenodigd om een griepprik te halen. Tussen begin december 2014 en eind april 2015 meldden zich wekelijks meer dan 51 patiënten per 100.000 inwoners met griepverschijnselen bij de huisarts. Er is sprake van een epidemie als dit aantal in twee opeenvolgende weken wordt overschreden. Het werkelijke aantal griepgevallen is veel hoger omdat lang niet iedereen met griepverschijnselen naar de huisarts gaat. Van de twee typen van het influenzavirus die voor de mens van belang zijn (A en B), is in het begin van het seizoen vooral het influenzavirus A (H3N2) aangetroffen. Later was dat vooral het influenzavirus B. Een deel van het circulerende influenza A-virus bleek af te wijken van het A-virus dat in het griepvaccin was opgenomen. Tot dusver kan nog niet worden geregistreerd hoeveel mensen in ziekenhuizen worden opgenomen vanwege complicaties van de griep. Het RIVM is daarom in 2015 in samenwerking met twee ziekenhuizen een onderzoek gestart om dit in kaart te brengen en de schattingen hiervan beter cijfermatig te onderbouwen. Andere luchtweginfecties In 2014 zijn in Nederland twee patiënten gediagnostiseerd met het MERS-Coronavirus. De patiënten hadden deze infectie opgelopen tijdens een reis naar het Midden Oosten. Wat betreft de meldingsplichtige luchtweginfectieziekten tuberculose, legionellose, papegaaienziekte (psittacose) en Q-koorts zijn er in het kalenderjaar 2014 geen zorgwekkende uitbraken of veranderingen in het aantal zieken waargenomen. Van deze infecties kwamen respectievelijk 823, 348, 41 en 25 meldingen binnen; de aantallen zijn in lijn met de voorgaande jaren. De genoemde infecties zijn meldingsplichtig, omdat tijdige maatregelen, zoals de besmettingsbron of contacten opsporen, belangrijk kunnen zijn om uitbraken of verdere verspreiding van de ziekte te voorkomen.

In de winter 2015/2016 was er een griepepidemie in de eerste elf weken van 2016.Dit griepseizoen week niet sterk af van een gemiddeld griepseizoen, met naar schatting ruim 200 duizend huisartsbezoeken voor griepachtige klachten, 96 duizend huisartsbezoeken voor longontstekingen en 3900 doden bovenop het verwachte aantal doden gedurende de elf weken van de epidemie. In de eerste weken van de epidemie werd vooral het influenzavirus A(H1N1)pdm09 aangetroffen. Later was dat vooral het influenzavirus B (Victoria-lijn). De effectiviteit van het griepvaccin (44 procent) leek beter dan vorig jaar, hoewel het influenzavirus B van de Victoria-lijn er niet in was opgenomen. Daar was voor gekozen omdat in voorgaande jaren vooral een ander influenzavirus B (Yamagata-lijn) circuleerde. De Wereldgezondheidsorganisatie heeft geadviseerd om volgend jaar de Victoria-lijn te gebruiken in plaats van de Yamagata-lijn. Het influenzavirus A(H1N1)pdm09 had wel een goede match met het vaccin van dit jaar. Het RIVM heeft dit jaar voor het eerst in twee ziekenhuizen geregistreerd hoeveel mensen zijn opgenomen vanwege complicaties van de griep. Vanuit andere ziekenhuizen is via de media vernomen dat een ongewoon hoog aantal relatief jonge patiënten was opgenomen met ernstige luchtwegklachten. Dit was niet terug te zien in de RIVM-data, maar onderstreept het belang van een uitgebreidere surveillance in ziekenhuizen. Van de meldingsplichtige luchtweginfectieziekten kwam in 2015 zowel tuberculose (867 meldingen) als legionellose (419 meldingen) meer voor dan voorgaande jaren. Bij tuberculose heeft dit vooral te maken met het toegenomen aantal asielzoekers. Bij legionellose komt dit waarschijnlijk door het warme en natte weer. Het aantal meldingen van psittacose (47) en Q-koorts (20) was niet opvallend. Dit aantal is echter een onderschatting van het werkelijke aantal, omdat bij longontsteking vaak de oorzaak niet wordt vastgesteld.

An international cohort of asphalt workers was assembled to study cancer risk after bitumen exposure. This article describes the combination of the exposure assessment with the exposure-response for a quantitative risk assessment for lung cancer mortality within the Dutch component of the study. We identified a retrospective cohort of 3,709 workers with at least one season of employment. Semi-quantitative exposure to bitumen fume was estimated by a job-exposure matrix. Exposure-response relations were fitted by Poisson regression, and excess lifetime risks through age 75 were calculated by a life table method. Working lifetime cumulative exposure to bitumen fume was calculated under different scenarios, representing past and future exposures. For workers with exposures accumulated in the past, excess risks for lung cancer varied from 7.8 to 14.3%. Calculations for future exposures resulted in considerably lower excess risks ranging from 0.6 to 2.6%. The calculated excess risks for lung cancer mortality after working lifetime exposure to bitumen fume depend strongly on when exposure was experienced and to some extent on the exposure-response model chosen, while confounding by smoking cannot be ruled out. Nevertheless, the excess lifetime risk for lung cancer in this Dutch cohort of asphalt workers is above benchmark risks as applied by the Dutch Health Council. Current exposure levels have decreased this risk considerably, but further exposure control may be required.

Background Using data from a Dutch cohort of workers in road construction and asphalt mixing companies, this article describes possible confounding of the association between exposure to bitumen fume and lung cancer mortality by smoking. Methods A retrospective cohort of 3,714 workers with at least one season of employment was identified. Semi‐quantitative exposure to bitumen fume was assessed by a job‐exposure matrix. Information on smoking habits was available for a sub‐cohort of 1,138 workers, who underwent medical examinations by the occupational health services in the past. Results Smoking habits differed between occupational title groups and there was a positive association between cumulative exposure and smoking. Internal analyses using the non‐exposed subjects as reference category, showed a positive association between semi‐quantitative bitumen fume exposure and lung cancer risk. After adjusting for differences in smoking habits, all relative risks were reduced, but a weak positive association could still be observed. Conclusion Confounding by smoking on the association between exposure to bitumen fume and lung cancer mortality is possible, although the positive trend (not statistically significant) for lung cancer mortality remained. Only a nested case‐control study may allow proper treatment of potential (residual) confounding by smoking in this population. Am. J. Ind. Med. 43:79–87, 2003. © 2003 Wiley‐Liss, Inc.

Background: Several toxicologic and epidemiologic studies have produced evidence that occupational exposure to polycyclic aromatic hydrocarbons (PAH) is a risk factor for ischemic heart disease (IHD). However, a clear exposure-response relation has not been demonstrated. Methods: We studied a relation between exposure to PAH and mortality from IHD (418 cases) in a cohort of 12,367 male asphalt workers from Denmark, Finland, France, Germany, Israel, The Netherlands and Norway. The earliest follow up (country-specific) started in 1953 and the latest ended in 2000, averaging 17 years. Exposures to benzo(a)pyrene were assessed quantitatively using measurement-driven exposure models. Exposure to coal tar was assessed in a semiquantitative manner on the basis of information supplied by company representatives. We carried out sensitivity analyses to assess potential confounding by tobacco smoking. Results: Both cumulative and average exposure indices for benzo(a)pyrene were positively associated with mortality from IHD. The highest relative risk for fatal IHD was observed for average benzo(a)pyrene exposures of 273 ng/m 3 or higher, for which the relative risk was 1.64 (95% confidence interval = 1.13-2.38). Similar results were obtained for coal tar exposure. Sensitivity analysis indicated that even in a realistic scenario of confounding by smoking, we would observe approximately 20% to 40% excess risk in IHD in the highest PAH-exposure categories. Conclusions: Our results lend support to the hypothesis that occupational PAH exposure causes fatal IHD and demonstrate a consistent exposure-response relation for this association. Copyright © 2005 by Lippincott Williams & Wilkins.

Item does not contain fulltext The hypothesis that asphalt workers are at increased risk of mortality from industrial accidents and other external causes was tested. Mortality rates for external and violent causes of death in a cohort of asphalt industry employees from seven European countries and Israel were compared to that of the general population. There was no evidence that mortality from external causes was increased among long term employees in asphalt application and mixing. There was an increased risk for mortality due to external causes among short term workers. However, none of the fatal accidents among short term workers appear to have occurred during employment in the studied asphalt companies. Overall, no evidence was found supporting the hypothesis that asphalt workers are at increased risk of fatal industrial or road accidents. Mortality from other external causes did not increase in this population as a whole, but increased risks among short term workers deserve further attention.

Concerns about public health risks of intensive animal production in the Netherlands continue to rise, in particular related to outbreaks of infectious diseases. The aim was to investigate associations between the presence of farm animals around the home address and Q fever and pneumonia.Electronic medical record data for the year 2009 of all patients of 27 general practitioners (GPs) in a region with a high density of animal farms were used. Density of farm animals around the home address was calculated using a Geographic Information System. During the study period, a large Q fever outbreak occurred in this region. Associations between farm exposure variables and pneumonia or 'other infectious disease', the diagnosis code used by GPs for registration of Q fever, were analyzed in 22,406 children (0-17 y) and 70,142 adults (18-70 y), and adjusted for age and sex. In adults, clear exposure-response relationships between the number of goats within 5 km of the home address and pneumonia and 'other infectious disease' were observed. The association with 'other infectious disease' was particularly strong, with an OR [95%CI] of 12.03 [8.79-16.46] for the fourth quartile (>17,190 goats) compared with the first quartile (

OBJECTIVE: To establish whether the number of physicians interested in a career in academia (i.e. research) is declining. DESIGN: Descriptive. METHOD: The researchers analysed the pre- and post-doctoral careers of PhD students at 3 university medical centres (VU Amsterdam, Nijmegen and Maastricht) in 4 separate reference years (1989, 1994, 1999 and 2003), using information from doctoral dissertations and the Dutch medical address book. The researchers recorded the gender of the students and the timing of the doctorate in relation to specialist training, university education and employment, as applicable. RESULTS: The total number of dissertations produced at the 3 medical faculties in the 4 reference years increased gradually by nearly a factor of 2 (1989: 112; 1994: 152; 1999: 198; 2003: 213). In terms of absolute numbers, the number of dissertations authored by physicians increased from 1989 to 1994 and again in 1999 (64, 90 and 105), but decreased slightly in 2003 (96). The percentage of female physicians obtaining a doctorate doubled during this period (1989: 9/64 (14); 2003: 28/96 (29)). Increasingly, physicians prepared their dissertation before or during their training as specialists or general practitioners (1989: 15/64 (23%); 2003: 51/96 (53%)). Ofthe clinical specialists who had received their doctorate, approximately half continued to work in an academic setting after obtaining their degree. This percentage remained approximately the same in all reference years (1989: 13/26 (50); 1994:19/35 (54); 1999: 21/45 (47); 2003: 21/40 (53)). CONCLUSION: Although the number of physicians performing scientific research as part of their doctoral degree project declined slightly in 2003 following an initial rise, our data indicate no cause for major concern. One reason may be increased interest in Clinical Research Fellow programmes. However, the future of medical research would look brighter if young physicians with doctorates had better career prospects within academic centres. To follow the academic careers of clinicians in The Netherlands, a national registry is needed to collect the type of data analysed in this study continually.

Background An increased risk of lung cancers among asphalt workers has been suggested in epidemiological studies based on large scale statistical analyses. Methods In a multi‐country study of 29,820 male workers employed in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers and 17,757 other workers from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality that was documented from 1953–2000. Exposures to bitumen fume, coal tar, 4–6 ring polycyclic aromatic hydrocarbons, organic vapor, diesel exhaust, asbestos, and silica dust were assessed via a job‐exposure matrix. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates, as well as relative risks (RRs) based on Poisson regression models were calculated. Results The SMR of lung cancer among workers exposed to bitumen fume (1.08, 95% CI 0.99–1.18) was comparable to that of non‐exposed workers (SMR 1.05, 95% CI 0.92–1.19). In a sub‐cohort of bitumen‐exposed workers without exposure to coal tar, the SMR of lung cancer was 1.23 (95% CI 1.02–1.48). The analysis based on the semi‐quantitative, matrix‐based exposures in the whole cohort did not suggest an increased lung cancer risk following exposure to bitumen fume. However, in an analysis restricted to road pavers, based on quantitative estimate of bitumen fume exposure, a dose‐response was suggested for average level of exposure, applying a 15‐year lag, which was marginally reduced after adjustment for co‐exposure to coal tar. The results for cancer of the head and neck were similar to those of lung cancer, although they were based on a smaller number of deaths. There was no clear suggestion of an association with bitumen fume for any other neoplasm. Conclusions The results of the analysis by bitumen fume exposure do not allow us to conclude on the presence or absence of a causal link between exposure to bitumen fume and risk of cancer of the lung and the head and neck. Am. J. Ind. Med. 43:28–39, 2003. © 2003 Wiley‐Liss, Inc.

Background An exposure matrix (EM) for known and suspected carcinogens was required for a multicenter international cohort study of cancer risk and bitumen among asphalt workers. Methods Production characteristics in companies enrolled in the study were ascertained through use of a company questionnaire (CQ). Exposures to coal tar, bitumen fume, organic vapor, polycyclic aromatic hydrocarbons, diesel fume, silica, and asbestos were assessed semi‐quantitatively using information from CQs, expert judgment, and statistical models. Exposures of road paving workers to bitumen fume, organic vapor, and benzo(a)pyrene were estimated quantitatively by applying regression models, based on monitoring data, to exposure scenarios identified by the CQs. Results Exposures estimates were derived for 217 companies enrolled in the cohort, plus the Swedish asphalt paving industry in general. Most companies were engaged in road paving and asphalt mixing, but some also participated in general construction and roofing. Coal tar use was most common in Denmark and The Netherlands, but the practice is now obsolete. Quantitative estimates of exposure to bitumen fume, organic vapor, and benzo(a)pyrene for pavers, and semi‐quantitative estimates of exposure to these agents among all subjects were strongly correlated. Semi‐quantitative estimates of exposure to bitumen fume and coal tar exposures were only moderately correlated. EM assessed non‐monotonic historical decrease in exposures to all agents assessed except silica and diesel exhaust. Conclusions We produced a data‐driven EM using methodology that can be adapted for other multicenter studies. Am. J. Ind. Med. 43:3–17, 2003. © 2003 Wiley‐Liss, Inc.

Background Inhalation of bitumen fumes is potentially carcinogenic to humans. Methods We conducted a study of 29,820 male workers exposed to bitumen in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers unexposed to bitumen, and 17,757 workers not classifiable as bitumen workers, from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality follow‐up during 1953–2000. We calculated standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates. Poisson regression analyses compared mortality of bitumen workers to that of building or ground construction workers. Results The overall mortality was below expectation in the total cohort (SMR 0.92, 95% CI 0.90–0.94) and in each group of workers. The SMR of lung cancer was higher among bitumen workers (1.17, 95% CI 1.04–1.30) than among workers in ground and building construction (SMR 1.01, 95% CI 0.89–1.15). In the internal comparison, the relative risk (RR) of lung cancer mortality among bitumen workers was 1.09 (95% CI 0.89–1.34). The results of cancer of the head and neck were similar to those of lung cancer, based on a smaller number of deaths. There was no suggestion of an association between employment in bitumen jobs and other cancers. Conclusions European workers employed in road paving, asphalt mixing and other jobs entailing exposure to bitumen fume might have experienced a small increase in lung cancer mortality risk, compared to workers in ground and building construction. However, exposure assessment was limited and confounding from exposure to carcinogens in other industries, tobacco smoking, and other lifestyle factors cannot be ruled out. Am. J. Ind. Med. 43:18–27, 2003. © 2003 Wiley‐Liss, Inc.

Background We compared performance of different exposure assessment approaches in a cohort study of cancer risk among European asphalt workers. Methods Three bitumen fume exposure indices (duration of exposure (years), average exposure (mg/m3) and cumulative exposure (mg/m3*years)) and two latency models (with and without a 15 year lag) were considered for an association between lung cancer mortality and bitumen fume. Results There was no association between lung cancer risk and either duration or cumulative exposure. However, there was the suggestion of an increase in lung cancer risk accompanying rise in average exposure. Only models with average bitumen fume exposure (with or without lag) improved model fit, albeit to the same extent. Conclusions Constructing quantitative indices of exposure intensity was justified because they produced the greatest improvement in fit of models that explored possible relationship between bitumen fume exposure and lung cancer risk. The identified associations require further investigation. Am. J. Ind. Med. 43:40–48, 2003. © 2003 Wiley‐Liss, Inc.

Item does not contain fulltext Work in the asphalt industry has been associated with nonmalignant respiratory morbidity and mortality, but the evidence is not consistent. A historical cohort of asphalt workers included 58,862 men (911,209 person-years) first employed between 1913 and 1999 in companies applying and mixing asphalt in Denmark, Finland, France, Germany, Israel, the Netherlands, and Norway. The relations between mortality from nonmalignant respiratory diseases (including the obstructive lung diseases: chronic bronchitis, emphysema, and asthma) and specific chemical agents and mixtures were evaluated using a study-specific exposure matrix. Mortality from obstructive lung diseases was associated with the estimated cumulative and average exposures to polycyclic aromatic hydrocarbons and coal tar (p values of the test for linear trend = 0.06 and 0.01, respectively). The positive association between bitumen fume exposure and mortality from obstructive lung diseases was weak and not statistically significant; confounding by simultaneous exposure to coal tar could not be excluded. The authors lacked data on smoking and full occupational histories. In conclusion, exposures to polycyclic aromatic hydrocarbons, originating from coal tar and possibly from bitumen fume, may have contributed to mortality from obstructive lung diseases among asphalt workers, but confounding and bias cannot be ruled out as an explanation for the observed associations.

Background An exposure matrix (EM) for known and suspected carcinogens was required for a multicenter international cohort study of cancer risk and bitumen among asphalt workers. Methods Production characteristics in companies enrolled in the study were ascertained through use of a company questionnaire (CQ). Exposures to coal tar, bitumen fume, organic vapor, polycyclic aromatic hydrocarbons, diesel fume, silica, and asbestos were assessed semi‐quantitatively using information from CQs, expert judgment, and statistical models. Exposures of road paving workers to bitumen fume, organic vapor, and benzo(a)pyrene were estimated quantitatively by applying regression models, based on monitoring data, to exposure scenarios identified by the CQs. Results Exposures estimates were derived for 217 companies enrolled in the cohort, plus the Swedish asphalt paving industry in general. Most companies were engaged in road paving and asphalt mixing, but some also participated in general construction and roofing. Coal tar use was most common in Denmark and The Netherlands, but the practice is now obsolete. Quantitative estimates of exposure to bitumen fume, organic vapor, and benzo(a)pyrene for pavers, and semi‐quantitative estimates of exposure to these agents among all subjects were strongly correlated. Semi‐quantitative estimates of exposure to bitumen fume and coal tar exposures were only moderately correlated. EM assessed non‐monotonic historical decrease in exposures to all agents assessed except silica and diesel exhaust. Conclusions We produced a data‐driven EM using methodology that can be adapted for other multicenter studies. Am. J. Ind. Med. 43:3–17, 2003. © 2003 Wiley‐Liss, Inc.

Understanding why metazoan Hox/HOM-C genes are expressed in spatiotemporal sequences showing colinearity with their genomic sequence is a central challenge in developmental biology. Here, we studied the consequences of ectopically expressing Hox genes to investigate whether Hox-Hox interactions might help to order gene expression during very early vertebrate embryogenesis. Our study revealed conserved autoregulatory loops for the Hox4 and Hox7 paralogue groups, detected following ectopic expression Hoxb-4 or HOXD4, and Hoxa-7, respectively. We also detected specific induction of 5' posterior Hox genes; Hoxb-5 to Hoxb-9, following ectopic expression of Hoxb-4/HOXD4; Hoxb-8 and Hoxb-9 following ectopic expression of Hoxa-7. Additionally, we observed specific repression of 3' anterior genes, following ectopic expression of Hox4 and Hox7 paralogues. We found that induction of Hoxb-4 and Hoxb-5 by Hoxb-4 can be direct, whereas induction of Hoxb-7 is indirect, suggesting the possibility of an activating cascade. Finally, we found that activation of Hoxb-4 itself and of posterior Hox genes by Hoxb-4 can be both non-cell-autonomous, as well as direct. We believe that our findings could be important for understanding how a highly ordered Hox expression sequence is set up in the early vertebrate embryo.