Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study

International audienceBACKGROUND:Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH.METHODS:In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation.RESULTS:We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23–100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15–80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2–2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6–3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4–1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1–0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7–50 months), with a cumulative hazard of 47% at 10 years.CONCLUSIONS:The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted

Long-Term Outcomes in Patients with Spontaneous Cerebellar Hemorrhage: An International Cohort Study

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH. METHODS: In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation. RESULTS: We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23-100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15-80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2-2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6-3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4-1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1-0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7-50 months), with a cumulative hazard of 47% at 10 years. CONCLUSIONS: The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

BACKGROUND: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. METHODS: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. FINDINGS: Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. INTERPRETATION: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Monitoring and evaluation of bioaerosol exposure

Bioaerosols are defined as aerosols or particulate matter of microbial, plant or animal origin. Bioaerosols may consist of pathogenic or non-pathogenic live or dead bacteria and fungi, viruses, allergens, bacterial endotoxins, mycotoxins, peptidoglycans, ß(1 -3)-glucans, pollens, plant fibres, erc. Exposures to bioaerosols in the occupational environment are associated with a wide range ofhealth effects, including infectious diseases, toxic effecrs, allergies, and cancer [Douwes er aJ.,2003]. 'W'orkers from a large number of industries are potentially at risk including workers in agriculture, meat production, food and animal feed industry waste recycling and composting industr¡ detergent industr¡ wood and paper industr¡ metal machining industries, biotechnology industries, the medical and public health sector, as well as, veterinarians, pet shop keepers, laboratory animal workers, etc

Do farming exposures cause or prevent asthma? Results from a study of adult Norwegian farmers

Background: A protective effect of endotoxin exposure on atopy and asthma in farmers’ children has been postulated. Studies of adult farmers have shown conflicting results but often lack exposure data. The prevalence of asthma in farmers with different exposure levels to microbial agents and irritant gases was compared. Methods: Atopy was defined as a positive response to multiple radioallergosorbent tests (RAST) with a panel of 10 common respiratory allergens, and asthma was ascertained by a questionnaire using a stratified sample (n = 2169) of a farming population from south-eastern Norway. Exposure of farmers to total dust, fungal spores, bacteria, endotoxins, and ammonia was assessed by exposure measurements. Results: The prevalence of asthma was 3.7% for physician diagnosed asthma and 2.7% for current asthma. The prevalence of atopy was 14%, but most asthmatic subjects were non-atopic (80%). Compared with farmers without livestock, (1) asthma was significantly higher in cattle farmers (ORadj 1.8, 95% CI 1.1 to 2.8) and pig farmers (ORadj 1.6, 95% CI 1.0 to 2.5), (2) non-atopic asthma was significantly higher in pig farmers (ORadj 2.0, 95% CI 1.2 to 3.3) and in farmers with two or more types of livestock (ORadj 1.9, 95% CI 1.1 to 3.3), and (3) atopic asthma was less common in farmers with two or more types of livestock (ORadj 0.32, 95% CI 0.11 to 0.97). Exposure to endotoxins, fungal spores, and ammonia was positively associated with non-atopic asthma and negatively associated with atopic asthma. No associations were found with atopy. Conclusions: Exposure to endotoxins and fungal spores appears to have a protective effect on atopic asthma but may induce non-atopic asthma in farmers

Bioaerosol health effects and exposure assessment: progress and prospects

Exposures to bioaerosols in the occupational environment are associated with a wide range of health effects with major public health impact, including infectious diseases, acute toxic effects, allergies and cancer. Respiratory symptoms and lung function impairment are the most widely studied and probably among the most important bioaerosol-associated health effects. In addition to these adverse health effects some protective effects of microbial exposure on atopy and atopic conditions has also been suggested. New industrial activities have emerged in recent years in which exposures to bioaerosols can be abundant, e.g. the waste recycling and composting industry, biotechnology industries producing highly purified enzymes and the detergent and food industries that make use of these enzymes. Dose–response relationships have not been established for most biological agents and knowledge about threshold values is sparse. Exposure limits are available for some contaminants, e.g. wood dust, subtilisins (bacterial enzymes) and flour dust. Exposure limits for bacterial endotoxin have been proposed. Risk assessment is seriously hampered by the lack of valid quantitative exposure assessment methods. Traditional culture methods to quantify microbial exposures have proven to be of limited use. Non-culture methods and assessment methods for microbial constituents [e.g. allergens, endotoxin, β(1→3)-glucans, fungal extracellular polysaccharides] appear more successful; however, experience with these methods is generally limited. Therefore, more research is needed to establish better exposure assessment tools and validate newly developed methods. Other important areas that require further research include: potential protective effects of microbial exposures on atopy and atopic diseases, inter-individual susceptibility for biological exposures, interactions of bioaerosols with non-biological agents and other potential health effects such as skin and neurological conditions and birth effects

Inter- and intraindividual variation of endotoxin- and beta(1 --> 3)-glucan-induced cytokine responses in a whole blood assay

Inflammatory airway responses to bioaerosols and to their active compounds, such as endotoxin and β(1 → 3)- glucan, vary between individuals. These differences may be explained by variation in cytokine responsiveness, which can be assessed by in vitro stimulation tests with isolated blood leukocytes or lung macrophages. In large- scale population studies, ex vivo induced cytokine production may also be tested with a more simple `whole blood assay’ (WBA). However, applicability of a WBA to characterize a subject’s responsiveness depends largely on its reproducibility. This study was conducted to: 1) assess the within- and between-subject variability in cytokine production in a WBA after stimulation with endotoxin or β(1 → 3)-glucan; and 2) to determine under which conditions this test is most discriminating between subjects and most reproducible within subjects. Blood was collected from 14 healthy volunteers, of whom 10 also participated on a second occasion. Each blood sample was used in two WBA tests; the first WBA was initiated two hours and the second 26 hours after venapuncture. The WBA test itself comprised overnight incubation with serial dilutions of endotoxin [lipopolysaccharide (LPS)] and curdlan (a β(1 → 3)-glucan), after which blood cell supernatant was collected. Interleukin(IL)-1, IL6, IL8 and tumor necrosis factor (TNF) were determined in the supernatant. In all individuals, a dose-dependent production of cytokines was observed for both LPS and curdlan. For all cytokines, variation between subjects was higher than within subjects, and this was most pronounced for IL1 and IL6. There was moderate-to-high correlation in the induced release of all four cytokines, and between cytokine release induced by LPS or curdlan. Optimal stimulation concentrations were 6.25 and 12.5 ng/mL for endotoxin and 12 500 and 25 000 ng/mL for curdlan. Cytokine production in WBA initiated 26 hours after venapuncture showed lower between-subject and larger within-subject variance, thus favoring an early initiation of the assay. In conclusion, measuring endotoxin-or glucan-induced cytokine production in a WBA initiated within two hours after venapuncture appears to be an effective method to determine a person’s cytokine responsiveness, at least in healthy naive subjects. Toxicology and Industrial Health 2002; 18: 15-27

Overview of personal occupational exposure levels to inhalable dust, endotoxin, beta(1-->3)-glucan and fungal extracellular polysaccharides in the waste management chain.

INTRODUCTION: In the past decade, we studied occupational bioaerosol exposures in various sites of the waste management chain. In this paper we present an overview of exposure levels of inhalable dust, endotoxin, beta(1-->3)-glucan (known or probable inducers of airways inflammation), and extracellular polysaccharide antigens of Aspergillus and Penicillium species (EPS-Pen/Asp; a common and probably more specific marker of fungal exposure). METHODS: Over 450 personal bioaerosol samples were taken. Mixed regression analyses were performed to estimate exposure determinants, between- and within-worker variance of exposure, and determinants of these variances. Furthermore, we explored whether the type of waste affected the bioaerosol composition of the dust. RESULTS: Endotoxin and glucan exposure levels were relatively low and comparable for waste collection and transferral, green waste composting and use of biomass in power plants. Exposure levels were 5-20 times higher in domestic waste transferral with sorting, and composting of both domestic and domestic and green waste ( approximately 300-1000 EU m(-3) for endotoxin, and 5-10 mug m(-3) for glucan). Observed exposure exceeded Dutch occupational exposure limits at all sites. EPS-Pen/Asp exposure was detected in 20% of waste collectors and 49% of compost workers. Exposure variability within tasks was large (geometric standard deviation > 2), with smaller between-worker than within-worker variance. Type of company and waste largely explained between-worker variance (40-90%), although within companies no major task-related determinants could be established. Markers of exposure correlated moderately to strongly. Relative endotoxin and glucan content in the dust was only weakly associated with handled waste. CONCLUSIONS: Occupational bioaerosol exposure in the waste management chain is lowest for outdoor handling of waste and highest when waste is handled indoors. However, exposure variability is large, with greater within-worker than between-worker variance. Occupational exposure limits for organic dust and endotoxins are frequently exceeded, suggesting workers are at risk of developing adverse health effects

Atopic and non-atopic asthma in a farming and a general population

Background In a previous study inverse associations between asthma and exposure to fungal spores and endotoxins in atopic farmers and positive associations with the same factors in non‐atopic farmers were documented. No external reference population had been included. We, therefore, compared this farming population with the general population from an adjacent region. Methods Random samples of a farming (n = 2,106) and a rural (n = 351) and urban (n = 727) general population were selected. Atopy was assessed by serum IgE and asthma by questionnaires. Results The asthma prevalence was 4.0% among farmers, 5.7% in the rural, and 7.6% in the urban population. Atopy was similar (9–10%). Most asthmatics were not atopic, 67–75%. Farmers had asthma less often than the general population OR 0.52 (95% CI 0.36–0.75); both atopic (OR 0.33 (95% CI 0.15–0.69)) and non‐atopic asthma (OR 0.60 (95% CI 0.39–0.93)). Conclusion This may indicate a protective effect of the farm environment on asthma but a healthy worker effect may also play a role. Am. J. Ind. Med. 46:396–399, 2004. © 2004 Wiley‐Liss, Inc

Monitoring and evaluation of bioaerosol exposure

Bioaerosols are defined as aerosols or particulate matter of microbial, plant or animal origin. Bioaerosols may consist of pathogenic or non-pathogenic live or dead bacteria and fungi, viruses, allergens, bacterial endotoxins, mycotoxins, peptidoglycans, ß(1 -3)-glucans, pollens, plant fibres, erc. Exposures to bioaerosols in the occupational environment are associated with a wide range ofhealth effects, including infectious diseases, toxic effecrs, allergies, and cancer [Douwes er aJ.,2003]. 'W'orkers from a large number of industries are potentially at risk including workers in agriculture, meat production, food and animal feed industry waste recycling and composting industr¡ detergent industr¡ wood and paper industr¡ metal machining industries, biotechnology industries, the medical and public health sector, as well as, veterinarians, pet shop keepers, laboratory animal workers, etc