Care for adult non-ICU Covid-19 patients: early experiences from a Belgian tertiary care centre.

The current Covid-19 outbreak poses many challenges on hospital organisation and patient care. Our hospital lies at the epicentre of the Belgian epidemic. On April 1st, a total of 235 Covid-19 patients had been admitted to our hospital. This demanded an unprecedented adaptation of our hospital organisation, and we have met many clinical issues in the care for Covid-19 patients. In this article, we share our experience in the handling of some of the practical and organisational issues in the care for Covid-19 patients.

Assessing the public health impacts of urban air pollution in 25 European cities: results of the Aphekom project.

INTRODUCTION: The Aphekom project aimed to provide new, clear, and meaningful information on the health effects of air pollution in Europe. Among others, it assessed the health and monetary benefits of reducing short and long-term exposure to particulate matter (PM) and ozone in 25 European cities. METHOD: Health impact assessments were performed using routine health and air quality data, and a common methodology. Two scenarios were considered: a decrease of the air pollutant levels by a fixed amount and a decrease to the World Health Organization (WHO) air quality guidelines. Results were economically valued by using a willingness to pay approach for mortality and a cost of illness approach for morbidity. RESULTS: In the 25 cities, the largest health burden was attributable to the impacts of chronic exposure to PM2.5. Complying with the WHO guideline of 10 µg/m(3) in annual mean would add up to 22 months of life expectancy at age 30, depending on the city, corresponding to a total of 19,000 deaths delayed. The associated monetary gain would total some €31 billion annually, including savings on health expenditures, absenteeism and intangible costs such as well-being, life expectancy and quality of life. CONCLUSION: European citizens are still exposed to concentrations exceeding the WHO recommendations. Aphekom provided robust estimates confirming that reducing urban air pollution would result in significant health and monetary gains in Europe. This work is particularly relevant now when the current EU legislation is being revised for an update in 2013.

Asthma attacks and deprivation: gradients in use of mobile emergency medical services.

BACKGROUND: To test whether rates of emergency telephone calls for asthma attacks are associated with contextual socioeconomic deprivation in the Strasbourg metropolitan area (France). METHODS: Two mobile emergency medical service networks provided all data for 2000-2005 about emergency calls for asthma attacks, georeferenced by census block. Contextual deprivation was measured for each census block by a composite index, constructed by principal component analysis. Emergency call rates were calculated for each census block and for different age groups. Empirical Bayesian smoothing was used to reduce the instability of outlying rates. RESULTS: Positive spatial autocorrelation was detected in both the health and the socioeconomic datasets. In all age groups, rates of calls for asthma attacks increased linearly with deprivation. Correlation coefficients between these two factors varied according to age group: 0.53 for the group aged 0-9 years, 0.46 for 10-19 years, 0.65 for 20-39 years, 0.70 for 40-64 years, 0.68 for 65 and older, and 0.77 for the age-standardised incidence ratio. These correlation coefficients were highly significant (p<0.01), even after spatial autocorrelation was taken into account. CONCLUSION: The socioeconomic gradients observed are consistent with those observed for severe forms of asthma and asthma hospitalisations in Western countries.

Short-term associations between fine and coarse particles and hospital admissions for cardiorespiratory diseases in six French cities.

OBJECTIVES: Little is known about the potential health effects of the coarse fraction of ambient particles. The aim of this study is to estimate the links between fine (PM(2.5)) and coarse particle (PM(2.5-10)) levels and cardiorespiratory hospitalisations in six French cities during 2000-2003. METHODS: Data on the daily numbers of hospitalisations for respiratory, cardiovascular, cardiac and ischaemic heart diseases were collected. Associations between exposure indicators and hospitalisations were estimated in each city using a Poisson regression model, controlling for confounding factors (seasons, days of the week, holidays, influenza epidemics, pollen counts, temperature) and temporal trends. City-specific findings were combined to obtain excess relative risks (ERRs) associated with a 10 mug/m(3) increase in PM(2.5) and PM(2.5-10 )levels. RESULTS: We found positive associations between indicators of particulate pollution and hospitalisations for respiratory infection, with an ERR of 4.4% (95% CI 0.9 to 8.0) for PM(2.5-10 )and 2.5% (95% CI 0.1 to 4.8) for PM(2.5). Concerning respiratory diseases, no association was observed with PM(2.5), whereas positive trends were found with PM(2.5-10), with a significant association for the 0-14-year-old age group (ERR 6.2%, 95% CI 0.4 to 12.3). Concerning cardiovascular diseases, positive associations were observed between PM(2.5) levels and each indicator, although some did not reach significance; trends with PM(2.5-10 )were weaker and non-significant except for ischaemic heart disease in the elderly (ERR 6.4%, 95% CI 1.6 to 11.4). CONCLUSIONS: In accordance with other studies, our results indicate that the coarse fraction may have a stronger effect than the fine fraction on some morbidity endpoints, especially respiratory diseases.

[Estimating mortality attribuable to PM10 particles in 9 French cities participating in the European programme Apheis]. / Estimation de la mortalité attribuable aux particules (PM10) dans les 9 villes françaises participant au programme européen Apheis.

The relationship between air pollution and mortality is now admissible with a sufficiently high level of causality proven. This link allows for health impact assessment to be carried out with a significant degree of accuracy, such as the case for the results which are presented here from the nine French cities involved in the Apheis programme. This health impact assessment is based on the methodology developed by the World Health Organization. The number of avoidable deaths is contained between categories ranging from 2.0 to 4.3, 4.0 to 8.9, and from 15.0 to 31.5 per 100,000 inhabitants according to very short term effects, short term effects and long term effects, respectively. There are two scenarios which can be envisioned for the reduction of fine particles levels which are capable of obtaining similar results for both very short term and short term effects. The first involves diminishing the daily concentrations which are above 20 microg/m3 until they reach this value, and the second entails systematically decreasing the daily levels by 5 microg/m3. The first strategy of reducing values to stabilize at 20 microg/m3 has been shown to be the one most favourable and promising for the long term effects. This strategy therefore confirms the reliability and strength of the recommendation formulated at the national level.

Gene expression analysis in a murine model of allergic asthma reveals overlapping disease and therapy dependent pathways in the lung.

Accumulating evidence in animal models and human asthma support a central role for IL-13 signaling in disease pathogenesis. In order to identify asthma and therapy associated genes, global transcriptional changes were monitored in mouse lung following antigen challenge (ovalbumin (OVA)), either alone or in the presence of a soluble IL-13 antagonist. Changes in whole lung gene expression after instillation of mIL-13 were also measured both in wild type and STAT6 deficient mice. A striking overlap in the gene expression profiles induced by either OVA challenge or mIL-13 was observed, further strengthening the relationship of IL-13 signaling to asthma. Consistent with results from functional studies, a subset of the OVA-induced gene expression was significantly inhibited by a soluble IL-13 antagonist while IL-13-modulated gene expression was completely attenuated in the absence of STAT6-mediated signaling. Results from these experiments greatly expand our understanding of asthma and provide novel molecular targets for therapy and potential biomarkers of IL-13 antagonism.

Twenty five year mortality and air pollution: results from the French PAARC survey.

AIMS AND METHODS: Long term effects of air pollution on mortality were studied in 14,284 adults who resided in 24 areas from seven French cities when enrolled in the PAARC survey (air pollution and chronic respiratory diseases) in 1974. Daily measurements of sulphur dioxide, total suspended particles, black smoke, nitrogen dioxide, and nitric oxide were made in 24 areas for three years (1974-76). Cox proportional hazards models controlling for individual confounders (smoking, educational level, body mass index, occupational exposure) were applied, and frailty models used to take into account spatial correlation. Indicators of air pollution were the mean concentration. RESULTS: Models were run before and after exclusion of six area monitors influenced by local traffic (NO/NO2 >3 in ppb). After exclusion of these areas, analyses showed that adjusted risk ratios (95% CI) for TSP, BS, NO2, and NO for non-accidental mortality were 1.05 (1.02 to 1.08), 1.07 (1.03 to 1.10), 1.14 (1.03 to 1.25), and 1.11 (1.05 to 1.17) for 10 microg/m3 respectively. Consistent patterns for lung cancer and cardiopulmonary causes were observed. CONCLUSIONS: Urban air pollution assessed in the 1970s was associated with increased mortality over 25 years in France.

[The impact of air pollution on health. The "Programme de Surveillance Air et Santé 9 villes" (Air and Health surveillance program in 9 cities)]. / Retentissement de la pollution atmosphérique sur la santé. Le Programme de Surveillance Air et Santé 9 villes.

OBJECTIVES: To quantify the short term effects of air pollution on mortality and hospitalisation for cardiovascular or respiratory disorders in the nine French cities (Bordeaux, Le Havre, Lille, Lyon, Marseille, Paris, Rouen, Strasbourg and Toulouse) of the Surveillance Air et Santé program. METHODS: Data were available on mortality and hospitalisation were available, respectively, from 1990 to 1997 and 1995 to 1999. Exposure data were the concentrations of sulphur dioxide, particles with a diameter of less than or equal to 10 mm, black smoke, nitrogen dioxide, ozone, and carbon monoxide. The analysis assessed the relationships, in each of the cities, between the daily numbers of deaths and hospitalisations and the daily levels of polluting agents, taking into account confounding factors. A combined relative risk was calculated for all the cities. The number of deaths and hospitalisations attributable to air pollution was then estimated for each of the cities, based on the relative risk. RESULTS: Significant relationships were found for mortality, from whatever cause, and for hospitalisations for respiratory disorders in children aged under 15. If the levels of air pollution were reduced to 10 microg/m3 in the nine cities, 2800 premature deaths and 750 hospitalisations for respiratory disorders in children would be avoided, every year. CONCLUSION: Today, it is possible to assess the benefits of reducing air pollution in terms of health in the short term. These analyses would provide a sanitary dimension to the strategies for the reduction of urban pollution on local and European level.

[Short-term relationships between urban atmospheric pollution and respiratory mortality: time series studies]. / Relations à court terme entre la pollution atmosphérique urbaine et la mortalité respiratoire: la place des études temporelles.

Time series studies conducted in the field of air pollution aim at testing and quantifying short-term relations which can exist between daily air pollution levels and daily health effects. The method used for this type of survey has sometimes been misunderstood mainly because individual factors and indoor exposure to air pollutants were not taken into account. The adjustment on these individual confounding factors commonly used in classic epidemiologic studies (case-control studies, cohort studies) is not adequate to times series studies which are based on aggregate data. This is different for those factors that change over time according to the levels of air pollution (meteorological conditions, influenza epidemics, trend of health cases) which, when being analysed, must be taken into account either indirectly through time modelling or directly through non-linear modelling processes. During this last decade, numerous studies using the time series method have been published and have found short-term associations between daily levels of air pollution commonly observed and daily respiratory mortality. The consistency of the numerous results published in the international literature are more arguments in favour of non-confounding short-term relations between air pollution and respiratory mortality.

Prevalence of genotypic resistance among antiretroviral drug-naive HIV-1-infected patients in Belgium.

OBJECTIVES: To estimate the prevalence and the evolution over time (1995-1998) of genotypic resistance to antiviral drugs in antiretroviral drug-naive HIV-1-infected patients in Belgium. DESIGN: Belgian Aids Reference Laboratories provided retrospective samples and clinical data from antiretroviral drug-naive HIV-1-infected patients who visited the hospital for the first time in 1995 (n=45), 1997 (n=75) and 1998 (n=111). Genotypic resistance to the three available classes of drugs was monitored using the Line Probe Assay (Innogenetics, Gent, Belgium). Additionally, ARMS-151 was performed for scoring multinucleoside resistance. RESULTS: The prevalence of genotypic resistance at baseline to nucleoside analogue reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were each between 10% and 20% for 1995, 1997 and 1998 without an increasing trend over time. For NRTIs, resistance mutations were mainly related to zidovudine in 1995, whereas in 1997 and 1998 baseline resistance was scored for zidovudine, lamivudine or for both drugs simultaneously. No patients displayed the multi-nucleoside resistance Q151M mutation. Baseline resistance mutations to protease inhibitors (PIs) did not rise significantly: 4.4% in 1995, 8% in 1997 and 9.9% in 1998. When scoring any resistance-related mutation, 26.6% displayed genotypic baseline resistance in 1995, 26.6% in 1997 and 31.5% in 1998. DISCUSSION: The prevalence of genotypic baseline resistance to any drug, as scored with LiPA, in naive HIV-1 patients in Belgium is 29%, with baseline resistance mutations to one or several drugs from all available classes of antiviral drugs. The ability of LiPA to pick up minor variants could be an explanation for the higher overall prevalence we observe, when compared to recent estimates in other countries of 16.3% and 22%, which were based on sequencing methods. According to the European guidelines for resistance testing, resistance testing in Belgium before starting antiviral therapy should be considered.

[Surveillance of short-term effects of urban air pollution on mortality. Results of a feasibility study in 9 French cities]. / Surveillance des effets à court terme de la pollution atmosphérique sur la mortalité en milieu urbain. Résultats d'une étude de faisabilité dans 9 villes françaises.

BACKGROUND: This study aims at quantifying air pollution effects on mortality and at evaluating the feasibility of a standardized epidemiological surveillance system of air pollution in 9 French cities. METHODS: Data collection and analysis followed a standardized protocol. Data pollution depended on the development of local air quality surveillance networks (number of indicators, number of stations.). The Generalised Additive Models (GAM) were used to quantify the association between air pollution and mortality. RESULTS: In the 9 studied areas, associations between all causes, cardiovascular and respiratory mortality, and air pollution indicators were observed. These associations were linear without threshold. Depending on the pollutants, excess in mortality related to an interquartile increase in acid-particulate pollution varied between 0.3 and 3.5% for total mortality, 0.5 and 6.3% for cardiovascular mortality, and between 0.1 and 12% for respiratory mortality. Photochemical air pollution varied between 0.4 and 7.3% for total mortality, 1.4 and 6.7% for cardiovascular mortality, and between 1.7 and 30.4% for respiratory mortality. CONCLUSION: In spite of a standardized common protocol, some disparities, inherent to the local characteristics, were noted (length of time series, numbers of ambient urban stations selected and pollutants available.). Nevertheless, this pilot study showed that multicentric epidemiological monitoring of air pollution effects on health was feasible. Yet, this requires to validate the results obtained through a re-analysis of the mortality data on a longer period of study. It also requires to study the feasibility and the relevance of the use of other health indicators, such as hospital admissions.

[Short-term effects of ozone on respiratory health of children in Armentières, North of France]. / Effets à court terme de l'ozone sur la santé respiratoire d'enfants d'Armentières, Nord de la France.

BACKGROUND: We studied short-term respiratory effects of ozone in a panel of 91 ten-year old children from a school in Armentières, North of France. METHODS: Each child reported twice daily peak expiratory flow rate measurements (mini-Wright) and daily occurrence of respiratory symptoms, from April 1, 1996 to June 30, 1996. Outdoor ozone measurements were obtained from a continuous fixed monitor, located at 850 meters from the school. Ozone effect was examined by regression models, using generalized estimating equations (GEE), with time and weather covariates. RESULTS: A 30 mg/m(3) increase in the daily maximum 8-hour mean level of ozone was associated with a 1.91 L x min(-1) decrement in evening peak expiratory flow (95% confidence interval [-0.02; 3.84]) and with increased daily prevalence of cough (odds ratio=1.17, 95% confidence interval [0.97; 1.40]), whereas ozone levels stayed moderate (1-hour level<180 microg/m(3)) during the study period. CONCLUSION: These results suggest that moderate levels of ozone have still an effect on children's lung.

Prognostic factors in myelodysplastic syndromes: critical analysis of the impact of age and gender and failure to identify a very-low-risk group using standard mortality ratio techniques.

We studied the prognostic value of age and gender by survival, and by standard mortality ratio (SMR) analyses, in 203 untreated patients with myelodysplastic syndromes (MDS); 57 refractory anaemia (RA), 23 refractory anaemia with ringed sideroblasts, 41 refractory anaemia with excess blasts (RAEB), 3 RAEB in transformation (RAEB-T) and 79 chronic myelomonocytic leukaemia (CMML), aged 23-89 years (median 69, M/F 0.5), who were all karyotyped. Median survival was 36 months. Adverse prognostic factors were: high bone-marrow blast percentage, complex karyotype, low platelet count, age > 60 years, low or high WBC count, haemoglobin < 10 g/dl, male gender. However, the standard mortality ratio (i.e. mortality compared to that of an age- and sex-adjusted population) was not different between male and female patients. Patients < 60 had a higher SMR than older patients. Therefore the prognostic values of age and gender for survival in MDS patients may reflect, at least in part, a characteristic of the population. Furthermore, even in low-risk groups defined by scoring system we were unable to define a subgroup of patients with a mortality similar to that of the normal population, especially in MDS patients aged < 60.

Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele.

The endothelial cell-specific vascular endothelial growth factor (VEGF) and its cellular receptors Flt-1 and Flk-1 have been implicated in the formation of the embryonic vasculature. This is suggested by their colocalized expression during embryogenesis and the impaired vessel formation in Flk-1 and Flt-1 deficient embryos. However, because Flt-1 also binds placental growth factor, a VEGF homologue, the precise role of VEGF was unknown. Here we report that formation of blood vessels was abnormal, but not abolished, in heterozygous VEGF-deficient (VEGF+/-) embryos, generated by aggregation of embryonic stem (ES) cells with tetraploid embryos (T-ES) and even more impaired in homozygous VEGF-deficient (VEGF-/-) T-ES embryos, resulting in death at mid-gestation. Similar phenotypes were observed in F1-VEGF+/- embryos, generated by germline transmission. We believe that this heterozygous lethal phenotype, which differs from the homozygous lethality in VEGF-receptor-deficient embryos, is unprecedented for a targeted autosomal gene inactivation, and is indicative of a tight dose-dependent regulation of embryonic vessel development by VEGF.

[Urinary excretion of fluorides in children living around an aluminum smelter]. / Excrétion urinaire de fluorures chez des enfants vivant autour d'un site de production d'aluminium.

Aluminium industry discharges fluoride into the atmosphere and several studies have shown a slight but significant contribution to the intake of fluoride by children living around aluminium smelters. A monitoring system was set up in 1991, just before a new aluminium smelter came into operation in Loon-Plage, on the North Sea coast, to study the evolution of the urinary fluoride excretion in children around the plant. Every year, 250 children under 14 are sampled in infant clinics, nursery schools and a secondary school. Urinary fluoride excretion was assessed by a potentiometric method on a spot morning urine sample and information on exposure factors was obtained by questionnaire. Urinary fluoride levels decreased with age (r = 0.31) and were higher in children drinking a local bottled water rich in fluoride (geometric mean in mg per gram of creatinine: 0.69 vs 0.52) or taking fluoride tablets (0.82 vs 0.52). The mean urinary fluoride excretion in children did not vary significantly between 1991 (geometric mean: 0.70 mg per gram of creatinine, 95% CI: [0.64-0.77]), 1992 (0.68 [0.62-0.75]) and 1993 (0.68 [0.61-0.76]), even after adjustment for potential confounding factors and despite a moderate increase in atmospheric fluoride levels.

[Temporomandibular joint symptoms in orthognathic surgery: a retrospective study]. / Kaakgewrichtssymptomen in orthognatische chirurgie: een retrospectief onderzoek.

The records of 152 consecutive patients who underwent orthognathic surgery in the Division of Maxillofacial Surgery A.Z. St.-Jan, Brugge, between 1/10/90 and 1/10/91 were evaluated for pre- and postoperative temporo-mandibular joint (TMJ) symptoms. Fewer TMJ symptoms were found postoperatively, than preoperatively (14.4% versus 19.7%). In the mandibular retrognathism group there were twice as much TMJ symptoms preoperatively in the low and normal mandibular angle patient group than in the high mandibular angle group (26% versus 13%). After surgery, there was a decrease of TMJ symptoms in the low and normal angle patient group (83% improvement). In the high angle absolute mandibular retrognathism group however, more new TMJ symptoms were seen postoperatively (21%). Bimaxillary surgical correction of a high angle absolute mandibular retrognathism case may provoke condylar resorption. Advice for follow-up and suggestions to reduce this annoying complication are given.

Long-term outcome of follicular low-grade lymphoma. A report of 91 patients.

We retrospectively analyzed overall survival and survival after progression in 91 patients with low-grade follicular lymphoma (LGFL). Histological subtype was B in 75 patients and C in 16 patients. Twelve patients with localized disease received involved-field radiotherapy; seven patients without bulky disease had no initial therapy. The remaining 72 patients received long-term chlorambucil (9 patients), MOPP or COPBleo (42 patients), or a CHOP-derived regimen (21 patients). Forty-two patients (46%) achieved a complete remission (CR) and 28 patients (31%) achieved a partial remission; 48 of these 70 patients relapsed or progressed. Nineteen of the other 21 patients with stable LGFL progressed. Two other patients failed to respond and rapidly died. Thirty-two of the 67 patients with progressive or relapsed LGFL have died. Median overall survival was 111 months. Age > or = 70 years, male sex, B symptoms, histological subtype follicular mixed-cell NHL, tumor size > or = 10 cm, number of extranodal sites of disease > or = 2, pleural effusion, and Ann Arbor stage III or IV were found to adversely influence overall survival. Failure-free survival < 24 months, failure to achieve a CR after the progression, initial histological subtype follicular mixed cell, initial Ann Arbor stage III or IV, and initial tumoral size > or = 10 cm were found to adversely influence survival after progression. Our results suggest that most prognostic factors for overall survival in LGFL are related to histological subtype or tumor burden. Some initial adverse prognostic factors for survival may be also associated with a poor survival after progression.

Denta Scan: CT software program used in the anatomic evaluation of the mandible and maxilla in the perspective of endosseous implant surgery.

A radiological technique, using a new CT software program for the evaluation of alveolar process height and width, is presented. Irradiation is kept within acceptable limits when this technique is used. Measurements obtained with this technique were compared with those obtained on panoramic radiographs in 40 "half-jaws" (21 maxillar and 19 mandibular). We found that new indications for implantation emerge in the mandibular region because 'Denta Scan' can sometimes show possibilities to place implants on the buccal side of the canal (2 of 19 mandibular cases) when no possibilities are present above the canal on both the panoramic radiographs and Denta Scan images. In the maxillar region Denta Scan avoids unnecessary interventions by demonstrating the insufficient width of the alveolar ridge, often missed on panoramic radiographs (4 of 21 maxillar cases). Moreover the use of Denta Scan allows the use of implants with optimal length and diameter (23 of the 40 cases), giving better long-term results.