Friendly visiting by a volunteer for reducing loneliness or social isolation in older adults: A systematic review.

Background: Loneliness and social isolation are currently among the most challenging social issues. Given their detrimental impact on physical and mental health, identifying feasible and sustainable interventions to alleviate them is highly important. Friendly visiting, a befriending intervention whereby older persons are matched with someone who visits them on a regular basis, seems promising. However, it is unclear if face-to-face (F2F) friendly visiting by a volunteer (FVV) is effective at reducing loneliness or social isolation, or both. Objectives: To assess the effect of F2F FVV on feelings of loneliness, social isolation (primary outcomes) and wellbeing (i.e., life satisfaction, depressive symptom experiencing and mental health; secondary outcomes) in older adults. Search Methods: We searched six electronic databases up until 11 August 2021. We also consulted 15 other resources, including grey literature sources and websites of organizations devoted to loneliness and ageing, between 25 October and 29 November 2021. Selection Criteria: We included experimental and observational studies that quantitatively measured the effect of F2F FVV, compared to no friendly visiting, on at least one of following outcomes in older adults (≥60 years of age): loneliness, social isolation or wellbeing. Data Collection and Analysis: Two reviewers independently performed study selection, data extraction and synthesis, risk of bias and GRADE assessment. If outcomes were measured multiple times, we extracted data for one short-term (≤1 month after the intervention had ended), one intermediate-term (>1 and ≤6 months), and one long-term time point (>6 months). Data from randomized controlled trials (RCTs) and non-RCTs were presented and synthesized separately. Synthesis was done using vote counting based on the direction of effect. Main Results: Nine RCTs and four non-RCTs, conducted primarily in the United States and involving a total of 470 older adults (mean or median ages: 72-83 years), were included. All studies were limited in size (20-88 participants each). Programmes lasted 6-12 weeks and mostly involved weekly visits by undergraduate students to community-dwelling older adults. Visits consisted mainly of casual conversation, but sometimes involved gameplaying and TV-watching. All studies had major shortcomings in design and execution. The current evidence about the effect of F2F FVV on loneliness in older adults is very uncertain, both in the short (one RCT in 88, and one non-RCT in 35 participants) and intermediate term (one RCT in 86 participants) (both very low-certainty evidence). The same goes for the effects on social isolation, again both in the short (one RCT in 88, and two non-RCTs in 46 participants) and intermediate term (two non-RCTs in 99 participants) (both very low-certainty evidence). Similarly, there is a lot of uncertainty about the effect of F2F FVV on outcomes related to wellbeing (all very low-certainty evidence). Authors' Conclusions: Due to the very low-certainty evidence, we are unsure about the effectiveness of F2F FVV with regard to improving loneliness, social isolation, or wellbeing in older adults. Decision-makers considering implementing FVV should take into account this uncertainty. More and larger high-quality studies that are better designed and executed, and preferably conducted in various settings, are needed.

Cost Effectiveness of Different Platelet Preparation, Storage, Selection and Dosing Methods in Platelet Transfusion: A Systematic Review.

BACKGROUND AND OBJECTIVE: Evidence-based guidelines on platelet transfusion therapy assist clinicians to optimize patient care, but currently do not take into account costs associated with different methods used during the preparation, storage, selection and dosing of platelets for transfusion. This systematic review aimed to summarize the available literature regarding the cost effectiveness (CE) of these methods. METHODS: Eight databases and registries, as well as 58 grey literature sources, were searched up to 29 October 2021 for full economic evaluations comparing the CE of methods for preparation, storage, selection and dosing of allogeneic platelets intended for transfusion in adults. Incremental CE ratios, expressed as standardized cost (in 2022 EUR) per quality-adjusted life-year (QALY) or per health outcome, were synthesized narratively. Studies were critically appraised using the Philips checklist. RESULTS: Fifteen full economic evaluations were identified. Eight investigated the costs and health consequences (transfusion-related events, bacterial and viral infections or illnesses) of pathogen reduction. The estimated incremental cost per QALY varied widely from EUR 259,614 to EUR 36,688,323. For other methods, such as pathogen testing/culturing, use of apheresis instead of whole blood-derived platelets, and storage in platelet additive solution, evidence was sparse. Overall, the quality and applicability of the included studies was limited. CONCLUSIONS: Our findings are of interest to decision makers who consider implementing pathogen reduction. For other preparation, storage, selection and dosing methods in platelet transfusion, CE remains unclear due to insufficient and outdated evaluations. Future high-quality research is needed to expand the evidence base and increase our confidence in the findings.

Cost-Effectiveness of Thrombopoietin Mimetics in Patients with Thrombocytopenia: A Systematic Review.

OBJECTIVES: Thrombopoietin (TPO) mimetics are a potential alternative to platelet transfusion to minimize blood loss in patients with thrombocytopenia. This systematic review aimed to evaluate the cost-effectiveness of TPO mimetics, compared with not using TPO mimetics, in adult patients with thrombocytopenia. METHODS: Eight databases and registries were searched for full economic evaluations (EEs) and randomized controlled trials (RCTs). Incremental cost-effectiveness ratios (ICERs) were synthesized as cost per quality-adjusted life year gained (QALY) or as cost per health outcome (e.g. bleeding event avoided). Included studies were critically appraised using the Philips reporting checklist. RESULTS: Eighteen evaluations from nine different countries were included, evaluating the cost-effectiveness of TPO mimetics compared with no TPO, watch-and-rescue therapy, the standard of care, rituximab, splenectomy or platelet transfusion. ICERs varied from a dominant strategy (i.e. cost-saving and more effective), to an incremental cost per QALY/health outcome of EUR 25,000-50,000, EUR 75,000-750,000 and EUR > 1 million, to a dominated strategy (cost-increasing and less effective). Few evaluations (n = 2, 10%) addressed the four principal types of uncertainty (methodological, structural, heterogeneity and parameter). Parameter uncertainty was most frequently reported (80%), followed by heterogeneity (45%), structural uncertainty (43%) and methodological uncertainty (28%). CONCLUSIONS: Cost-effectiveness of TPO mimetics in adult patients with thrombocytopenia ranged from a dominant strategy to a significant incremental cost per QALY/health outcome or a strategy that is clinically inferior and has increased costs. Future validation and tackling the uncertainty of these models with country-specific cost data and up-to-date efficacy and safety data are needed to increase the generalizability.

Societal volunteering and COVID-19 mortality in high-income countries: a cross-sectional study.

OBJECTIVES: This study aims to quantify the relationship between societal volunteering and the impact of COVID-19 in that society. DESIGN: Cross-sectional study. SETTING, PARTICIPANTS AND OUTCOME MEASURE: Data on societal volunteering were collected for 32 high-income countries (international analysis) and 50 US states (US analysis). Using regression analysis, the ability of this variable to explain COVID-19 mortality was compared with other variables put forward in the public debate (eg, vaccination rate, obesity, age). COVID-19 mortality was measured as the number of deaths due to COVID-19 per million inhabitants, from January 2020 until January 2022. RESULTS: Societal volunteering explains 43% (resp. 34%) of observed variation in COVID-19 mortality (R²) in the international (resp. US states) analysis. Compared with other variables, societal volunteering better explains the variation in COVID-19 mortality across countries and US states, with only the prevalence of smokers displaying a higher R² in the international analysis. CONCLUSIONS: Countries and states with more societal volunteering have been less impacted by COVID-19, even after accounting for differences in demographics, gross domestic product, healthcare investments and vaccination rates. Although this evidence is not causal, our findings suggest that factors beyond the public-private debate might impact the resilience of societies to a pandemic, with societal volunteering being one such factor.

Impact of the Use of Simulated Patients in Basic First Aid Training on Laypeople Knowledge, Skills, and Self-efficacy: A Controlled Experimental Study.

BACKGROUND: First aid training is a cost-effective way to improve public health, but the most effective methods to teach first aid are currently unclear. The aim of this research was to investigate the added value of simulated patients during first aid certification trainings. METHODS: Occupational first aid trainings organized by the Belgian Red Cross between September 2018 and August 2019 were allocated to either training with a simulated patient or regular training, for the topics "stroke" and "burns." Participants' knowledge and self-efficacy related to these topics were assessed at baseline, directly after training and after 1 year. First aid skills for "stroke" and "burns" and participant satisfaction were assessed after training. Knowledge and self-efficacy were measured via a questionnaire, and skills were assessed during a practical skills test. Data were analyzed using generalized linear mixed model analyses. RESULTS: A total of 1113 participants were enrolled, 403 in the simulated patient group and 710 in the control group. First aid knowledge and self-efficacy increased strongly immediately after training. These increases did not differ between groups, nor did the level of practical skills. The simulated patient group had a significantly increased retention in first aid knowledge after 1 year, compared with control, while retention in self-efficacy did not differ. Participant satisfaction with training was similar between groups. CONCLUSIONS: Using simulated patients during occupational first aid trainings for laypeople did not improve outcomes immediately after training but did improve retention of first aid knowledge after 1 year. These results support the use of simulated patients during first aid training.

Mass gathering events: a retrospective analysis of the triage categories, type of injury or medical complaint and medical usage rates.

BACKGROUND: Adequate on-site first aid delivery at mass gatherings (MGs) is one of the cornerstones to ensure safe and healthy MGs. We investigated medical usage rates, frequency of triage categories and type of injury or medical complaint, among attendees at MGs in Belgium. METHODS: We analysed the Medical Triage and Registration Informatics System database, which includes prospectively collected person-level data regarding individuals visiting on-site posts at MGs in Belgium. MGs attended by >10 000 people and organised ≥5 times between 2009 and 2018 were included. We determined the proportion of patients in each triage category ('first aid' vs 'medical condition' vs 'medical emergency' vs 'no treatment') and each type of injury or medical complaint, and we calculated patient presentation rate (PPR) and transfer to hospital rate (TTHR). RESULTS: Twenty-eight MGs, totalling 194 events, were included involving 148 265 patient visits. 'First aid' was the most common triage category (80%, n=118 514). The need for a nurse/physician ('medical condition'), and for the treatment of life-threatening conditions ('medical emergency') was rare (8.9%, n=13 052, and 0.6%, n=860, of all patient presentations, respectively), but remarkably higher during indoor electronic dance music (EDM) events (17.8% (n=26 391) and 4.0% (n=5930), of all patient presentations, respectively). 'Skin wounds' were the most common injury category (42.4%, n=62 275). 'Respiratory problems', 'neurological problems', 'intoxication', 'heart complaints' and 'gastrointestinal complaints' were more frequent during indoor (electronic) dance, whereas 'burns', 'fracture/contusion' and 'skin wounds' were higher during outdoor music, sports events and city festivals, respectively. PPR (per 10 000 attendees) was highest for outdoor EDM and outdoor music (median 130 (IQR 79) and 129 (IQR 104), respectively). TTHR (per 10 000 attendees) was highest for indoor EDM (median 4.4 (IQR 8.5)). CONCLUSION: Medical usage rates, proportion of patients in triage and injury or medical complaint categories varied across different MG categories, suggesting opportunities for planning medical coverage at these events.

Predicting medical usage rate at mass gathering events in Belgium: development and validation of a nonlinear multivariable regression model.

BACKGROUND: Every year, volunteers of the Belgian Red Cross provide onsite medical care at more than 8000 mass gathering events and other manifestations. Today standardized planning tools for optimal preventive medical resource use during these events are lacking. This study aimed to develop and validate a prediction model of patient presentation rate (PPR) and transfer to hospital rate (TTHR) at mass gatherings in Belgium. METHODS: More than 200,000 medical interventions from 2006 to 2018 were pooled in a database. We used a subset of 28 different mass gatherings (194 unique events) to develop a nonlinear prediction model. Using regression trees, we identified potential predictors for PPR and TTHR at these mass gatherings. The additional effect of ambient temperature was studied by linear regression analysis. Finally, we validated the prediction models using two other subsets of the database. RESULTS: The regression tree for PPR consisted of 7 splits, with mass gathering category as the most important predictor variable. Other predictor variables were attendance, number of days, and age class. Ambient temperature was positively associated with PPR at outdoor events in summer. Calibration of the model revealed an R2 of 0.68 (95% confidence interval 0.60-0.75). For TTHR, the most determining predictor variables were mass gathering category and predicted PPR (R2 = 0.48). External validation indicated limited predictive value for other events (R2 = 0.02 for PPR; R2 = 0.03 for TTHR). CONCLUSIONS: Our nonlinear model performed well in predicting PPR at the events used to build the model on, but had poor predictive value for other mass gatherings. The mass gathering categories "outdoor music" and "sports event" warrant further splitting in subcategories, and variables such as attendance, temperature and resource deployment need to be better recorded in the future to optimize prediction of medical usage rates, and hence, of resources needed for onsite emergency medical care.

Best Available Evidence on Communicative First Aid Interventions by Laypeople for Preventing and Relieving Posttraumatic Stress Disorder-Related Symptomatology Following Traumatic Events.

Trauma-exposed individuals are at risk of developing mental health problems, including posttraumatic stress disorder (PTSD). As an exposed individual's friend or family member may be the first person to provide posttrauma relief, informing and training laypeople in psychosocial first aid may benefit mental health outcomes of trauma-exposed individuals. We aimed to (a) collect the best available evidence on communication as a first aid intervention in assisting individuals following traumatic events and (b) formulate practical recommendations. Systematic literature searches were conducted in three databases (March 2019). Following study selection, the extracted data were tabulated and synthesized narratively. The evidence was appraised according to the GRADE methodology and evaluated by a multidisciplinary expert panel to formulate recommendations for practice. Out of 1,724 articles, no experimental studies were identified, showing a complete lack of high-quality controlled studies on the efficacy of communicative practices. However, when lower-quality study designs were included, nine cross-sectional studies constituted the best available evidence. The studies suggested that positive communication by family members, r = -.38, aOR = 0.26, ß = -.22, p < .001-p < .05, and expressive coping by the victim, ß = -.62, p < .001, were associated with PTSD diagnosis and/or symptom severity; however, the evidence was of very low certainty. The expert panel took the methodological limitations into account when formulating weak practical recommendations. Cross-sectional studies currently provide the best possible evidence for developing guidelines on psychosocial first aid. High-quality controlled studies are needed to establish casual associations and identify the most effective interventions.

Antithrombotic medication and endovascular interventions associated with short-term exposure to particulate air pollution: A nationwide case-crossover study.

Short-term exposure to air pollution has pro-thrombotic effects and triggers thrombo-embolic events such as myocardial infarction or stroke in adults. This study evaluates the association between short-term variation in air pollution and treatments for acute thrombo-embolic events among the whole Belgian population. In a bidirectional time-stratified case-crossover design, we included 227,861 events treated with endovascular intervention and 74,942 with antithrombotic enzymes that were reimbursed by the Belgian Social Security between January 1st, 2009 and December 31st, 2013. We compared the concentrations of particulate matter (PM) air pollution (PM10 and PM2.5), as estimated at the municipality level on the day of the event (lag 0) and two days earlier (lag 1 and lag 2) with those of control days from the same month, matched by temperature and accounting for day of the week (weekend vs week days). We applied conditional logistic regression models to obtain odds ratios (OR) and their 95% CI for an increase of 10 µg/m3 (PM10) or 5 µg/m3 (PM2.5) in pollutant concentrations over three lag days (lag 0, 1 and 2). We observed significant associations of PM10 and PM2.5 with treatment of acute thrombo-embolic events at the three lags. The strongest associations were observed for air pollution concentrations on the day of the event (lag0). Increases of 10 µg/m3 PM10 and 5 µg/m3 PM2.5 on lag0 increased the odds of events treated with endovascular intervention by 2.7% (95%CI:2.3%-3.2%) and 1.3% (95%CI:1%-1.5%), respectively, and they increased the odds of events treated with antithrombotic enzymes by 1.9% (95%CI:1.1-2.7%) and 1.2% (95%CI:0.7%-1.6%), respectively. The associations were generally stronger during autumn months and among children. Our nationwide study confirms that acute exposure to outdoor air pollutants such as PM10 or PM2.5 increase the use of medication and interventions to treat thrombo-embolic events.

Prediction modelling studies for medical usage rates in mass gatherings: A systematic review.

BACKGROUND: Mass gathering manifestations attended by large crowds are an increasingly common feature of society. In parallel, an increased number of studies have been conducted that developed and/or validated a model to predict medical usage rates at these manifestations. AIMS: To conduct a systematic review to screen, analyse and critically appraise those studies that developed or validated a multivariable statistical model to predict medical usage rates at mass gatherings. To identify those biomedical, psychosocial and environmental predictors that are associated with increased medical usage rates and to summarise the predictive performance of the models. METHOD: We searched for relevant prediction modelling studies in six databases. The predictors from multivariable regression models were listed for each medical usage rate outcome (i.e. patient presentation rate (PPR), transfer to hospital rate (TTHR) and the incidence of new injuries). The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the certainty of evidence. RESULTS: We identified 7,036 references and finally included 16 prediction models which were developed (n = 13) or validated (n = 3) in the USA (n = 8), Australia (n = 4), Japan (n = 1), Singapore (n = 1), South Africa (n = 1) and The Netherlands (n = 1), with a combined audience of >48 million people in >1700 mass gatherings. Variables to predict medical usage rates were biomedical (i.e. age, gender, level of competition, training characteristics and type of injury) and environmental predictors (i.e. crowd size, accommodation, weather, free water availability, time of the manifestation and type of the manifestation) (low-certainty evidence). Evidence from 3 studies indicated that using Arbon's or Zeitz' model in other contexts significantly over- or underestimated medical usage rates (from 22% overestimation to 81% underestimation). CONCLUSIONS: This systematic review identified multivariable models with biomedical and environmental predictors for medical usage rates at mass gatherings. Since the overall certainty of the evidence is low and the predictive performance is generally poor, proper development and validation of a context-specific model is recommended.

PROTOCOL: Friendly visiting by a volunteer for reducing loneliness and social isolation in older adults.

Loneliness and social isolation are reaching epidemic proportions in both children and adults, despite the increasing connectedness in our twenty-first century world. As a growing number of studies reveal their detrimental impact on physical and mental health, identifying and investing in feasible and sustainable interventions to alleviate social isolation and feelings of loneliness is of prime importance. Friendly visiting, a befriending intervention whereby older persons are matched with someone who visits them on a regular basis, seems to be a realistic and sustainable option for providing social support. However, until this day, it remains unclear if friendly visiting by a volunteer is effective at reducing loneliness and social isolation. Therefore, this systematic review aims to answer the following research question: what is the effect of friendly visiting by a volunteer on feelings of loneliness and social isolation (primary outcomes) and wellbeing (i.e. life satisfaction, depressive symptom experiencing and mental health; secondary outcomes) in older adults? The results of this review may provide useful information to policy-makers that are preparing to take on one the most challenging social issues facing our ageing society.

Air pollution and self-perceived stress and mood: A one-year panel study of healthy elderly persons.

BACKGROUND AND OBJECTIVES: Previous studies have suggested that air pollution is associated with depression and anxiety symptoms. Here, we investigate the association between personal exposure to NO2 and perceived stress and mood in a panel of healthy elderly persons. METHODS: In a one-year panel study, we included 20 healthy volunteers (10 male-female couples aged 58-76 years) with air pollution and health parameters measured every two months (120 observations). We measured personal exposure to NO2 in the previous 5 days, perceived stress using the Perceived Stress Scale (PSS) and positive and negative affect with the Positive and Negative Affect Schedule (PANAS). We used linear and Poisson mixed models to evaluate the associations between the health outcomes and NO2 adjusted for age, sex, temperature in the previous 5 days, sunlight in the previous day and physical activity (daily average number of steps on the previous week). Also, the interaction terms between NO2 and physical activity were tested. We report % changes for PSS scores and unit changes (ß) for positive and negative affect, and their 95% confidence intervals (CI), for changes in 10 µg/m3 of NO2. RESULTS: After adjustment, an increase by 10 µg/m3 in NO2 concentrations was associated with a decrease of 1.3 points in the positive affect (95% CI -2.49 to -0.17) and an increase of 0.11 points in the negative affect (95% CI 0.02 to 0.20). The association with positive affect was stronger when physical activity was below median value of 9,362 steps per day (ß = -2.68; CI: 4.87 to -0.49); p-value for interaction was 0.08. No statistically significant associations were observed with perceived stress. CONCLUSION: Short-term exposure to air pollution may produce non-pathological alterations in mood in healthy elderly population.

Changing places to study short-term effects of air pollution on cardiovascular health: a panel study.

BACKGROUND: Short-term exposure to ambient air pollution triggers acute cardiovascular events. Here, we evaluate the association of exposure to ambient air pollution with two intermediate cardiovascular endpoints: blood pressure and carotid stiffness. METHODS: In a one-year panel study, we included 20 healthy volunteers (10 male-female couples aged 59-75 years) with air pollution and health parameters measured every two months at their region of residence (Leuven, Belgium) and twice during two ten-day periods in two locations, one with higher (Milan, Italy) and one with lower (Vindeln, Sweden) air pollution levels (220 observations). We measured blood pressure, carotid arterial stiffness, personal exposure to NO2, and ambient concentrations of PM10, PM2.5, and NO2. We used linear mixed models to evaluate the associations between the health outcomes and the air pollutants. RESULTS: Compared with Leuven, exposure to pollutants was higher in Milan and lower in Vindeln, with the highest contrast for NO2 (median 20.7 µg/m3 (IQR:7.4) vs 65.1 µg/m3 (9.0) and 4.5 mg/m3 (0.8), respectively). We did not observe significant associations between either systolic or diastolic blood pressure and variations in air pollution. However, we found significant associations between arterial stiffness and 5 day average exposure to the studied pollutants. The strongest associations were observed for PM10 with carotid distensibility (DC) and compliance (CC) coefficients, and the young elastic modulus (YEM): 4.3% (95%CI:7.0;1.5) increase in DC, 4.7% (95%CI:7.1;2.3) increase in CC and 4.2% (95%CI:1.1;7.3) decrease in YEM for each 10 µg/m3 decreases in PM10. CONCLUSIONS: Our study suggests that short-term exposure to air pollution results in reductions in carotid elasticity among elderly population.

Mitochondrial DNA content in blood and carbon load in airway macrophages. A panel study in elderly subjects.

BACKGROUND: Mitochondria are sensitive to air pollutants due to their lack of repair capacity. Changes in mitochondrial DNA copy number (mtDNAcn) or content is a proxy of mitochondrial damage and has been associated with recent exposure to traffic-derived air pollutants, nitrogen dioxide (NO2) and black carbon (BC). Inhaled BC can be phagocytosed by airway macrophages (AMs), and its amount in AM reflects personal exposure to traffic-related air pollution. OBJECTIVES: The present study investigated the relation between the internal marker AM BC and ambient NO2 concentration and examined the associations of mtDNAcn with NO2 and AM BC. METHODS: A panel of 20 healthy retired participants (10 couples) living in Belgium underwent repeated assessments of health and air pollution exposure at 11 time points over one year. We increased exposure contrast temporarily by moving participants for 10 days to Milan, Italy (high exposure) and to Vindeln, Sweden (low exposure). Personal exposure to NO2 was measured during 5 consecutive days prior to each assessment time point. The amount of BC was assessed by image analysis in AMs retrieved from induced sputum collected at 7 time points. Blood mtDNAcn was determined by qPCR at each time point. Associations between AM BC and NO2, and of mtDNAcn with NO2 and AM BC were estimated using linear mixed effect models adjusted for covariates and potential confounders. RESULTS: Mean concentrations of 5-day average NO2 were higher in Milan (64 µg/m3) and lower in Vindeln (4 µg/m3) than Belgium (26 µg/m3). Each 10 µg/m3 increment in NO2 exposure during the last 5 days was associated with 0.07 µm2 (95% CI: 0.001 to 0.012) increase in median area of AM BC. A 10 µg/m3 increase in NO2 was associated with 3.9% (95% CI: 2.2 to 5.5%) decrease in mtDNAcn. Consistently, each 1 µm2 increment in median area of AM BC was associated with 24.8% (95% CI: 6.8 to 39.3%) decrease in mtDNAcn. CONCLUSION: In this quasi-experimental setting involving moving persons to places with high and low ambient air pollution, we found changes in AM BC according to ambient air pollution levels measured during the previous 5 days. Both higher ambient NO2 and the internal lung BC load, paralleled mitochondrial compromises as exemplified by lower mtDNA content.

Nanoparticles in the lungs of old mice: Pulmonary inflammation and oxidative stress without procoagulant effects.

Pulmonary exposure to nanoparticles (NPs) has been shown to induce pulmonary as well as cardiovascular toxicity. These effects might be enhanced in elderly subjects as a result of a compromised immunity and/or declined organ functions. To study the adverse in vivo effects of NPs in a model for the elderly, we exposed 18-month-old C75Bl/6 mice to multi-walled carbon nanotubes (MWCNTs) or ZnO NPs by intratracheal instillation once a week during 5 consecutive weeks. Pulmonary and hemostatic toxicity was determined 24 h (T1) and 8 weeks (T2) after the last administration. Both NP types significantly increased the pulmonary macrophages at both time points. The MWCNTs and ZnO NPs also induced a pulmonary influx of neutrophils, which was even larger at T2 compared to T1. All NPs induced only a modest increase of pulmonary IL-1ß, IL-6 and KC levels. Both types of NPs also increased blood neutrophils. Red blood cells were not significantly affected. Both NPs significantly increased coagulation factor VIII levels at both time points. Histological analysis revealed the presence of MWCNTs in the alveolar macrophages up to 8 weeks after the last administration and the ZnO NPs induced a pronounced alveolar inflammation. In these 18-month-old mice, NPs caused pulmonary inflammation (without evidence of oxidative stress) accompanied by large increases in coagulation factor VIII up to 8 weeks after the last NP exposure. The persistence of the MWCNTs in the lungs resulted in translocation from the lungs to the left heart and the ZnO NPs induced a fibrosis-like pathology.

Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients.

BACKGROUND: Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected patient cohorts is lacking. METHODS: Patients (n = 205) were defined as being "cytokine-low/high" if sputum mRNA expression of a particular cytokine was outside the respective 10th/90th percentile range of the control group (n = 80). Unsupervised hierarchical clustering was used to determine clusters based on sputum cytokine profiles. RESULTS: Half of patients (n = 108; 52.6%) had a classical T(h)2-high ("IL-4-, IL-5- and/or IL-13-high") sputum cytokine profile. Unsupervised cluster analysis revealed 5 clusters. Patients with an "IL-4- and/or IL-13-high" pattern surprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an "IL-5-, IL-17A-/F- and IL-25- high" profile were restricted to cluster 1 (n = 24) with increased sputum eosinophil as well as neutrophil counts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified: "IL-5-high or IL-10-high" (n = 16), "IL-6-high" (n = 8), "IL-22-high" (n = 25). Cluster 5 (n = 132) consists of patients without "cytokine-high" pattern or patients with only high IL-4 and/or IL-13. CONCLUSION: We identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus non-type 2 molecular phenotypes. www.clinicaltrials.gov NCT01224938. Registered 18 October 2010.

Preeclampsia and toxic metals: a case-control study in Kinshasa, DR Congo.

BACKGROUND: Preeclampsia is frequent in Kinshasa (Democratic Republic of Congo), especially during the dry season. We tested whether preeclampsia was associated with exposure to environmental metals. METHODS: Using a case-control design, 88 women hospitalized with preeclampsia (cases) and 88 healthy pregnant women from the antenatal clinic (controls) were included in the study; 67 and 109 women were enrolled during the rainy and dry season, respectively. The concentrations of 24 elements were quantified by inductively coupled plasma mass spectrometry (ICP-MS) in 24-h urine collections. Differences in the urinary excretion of metals were investigated between cases and controls, and the interaction with season was assessed. RESULTS: Cases and controls were well matched regarding age, parity and duration of pregnancy. In controls, the urinary concentrations of most elements were substantially higher than reference values for adults from industrially developed countries, e.g. for lead: geometric mean (GM) 8.0 µg/L [25(th)-75(th) percentile 3.1-13.8]. The daily urinary excretions of 14 metals were significantly higher in women with preeclampsia than in control women, e.g. for lead: GM 61 µg/day (25(th)-75(th) percentile 8-345) in women with preeclampsia vs 9 µg/day (25(th)-75(th) percentile 3-21) in controls (p < 0.001). A significant interaction was found between season and preeclampsia for several elements, with higher urinary excretions in preeclamptic women than controls during the dry season, but not during the rainy season. CONCLUSIONS: This study revealed not only that women with preeclampsia excrete higher amounts of several toxic metals, especially lead, than control women, but also that this excretion exhibits seasonal variation, thus possibly explaining the high incidence and seasonal variation of preeclampsia in Kinshasa. Although the exact sources of this exposure are unknown, these findings underscore the need for preventing environmental exposures to lead and other toxic metals.

Sleep disturbances and neurotoxicity in workers exposed to hydrocarbons. An observational study from Algeria.

BACKGROUND: Occupational exposure to solvents may lead to neurotoxicity and sleep disturbances. We aimed to investigate the association of occupational exposure to petroleum-derived hydrocarbons with neurotoxicity and sleep disturbance symptoms. METHODS: We included male workers handling/distributing petroleum products (exposed, n = 250) and electricians (non-exposed, n = 250) from two companies in Tlemcen (Algeria). Neurotoxicity was evaluated with the Q-16 questionnaire, and sleep disturbances with the Epworth and the Berlin questionnaires. Multivariable Poisson regression models with robust error variances were applied obtaining risk ratios (RR) and their 95% confidence interval (CI). RESULTS: Overall, the prevalence of reported neurotoxicity and sleep disturbance symptoms was higher in exposed than in non-exposed workers. Significant adjusted associations were observed for neurotoxicity, snoring, and excessive sleepiness (RR = 2.2, CI: 1.7-2.8; RR = 1.4; CI: 1.1-1.7; RR = 1.3, CI: 1.2-1.5, respectively). No significant associations were observed with the Epworth score. CONCLUSIONS: Our questionnaire-based cross-sectional study suggests that exposure to petroleum-derived hydrocarbons is associated with self-reported sleep disturbances and neurotoxicity symptoms.

Long-Term Exposure to Particulate Matter Air Pollution Is a Risk Factor for Stroke: Meta-Analytical Evidence.

BACKGROUND AND PURPOSE: Epidemiological studies suggest an association between stroke incidence and stroke mortality and long-term exposure to particulate matter (PM) air pollution. However, the magnitude of the association is still unclear. METHODS: We searched the Pubmed citation database for epidemiological studies and reviews on stroke and PM exposure. Then, we carried out a meta-analysis to quantify the pooled association between stroke incidence and mortality and long-term exposure to PM. Meta-analyses were performed for stroke events and stroke mortality and for PM10 and PM2.5 separately and jointly. RESULTS: We identified 20 studies, including a total of >10 million people, on long-term PM exposure and stroke event or stroke mortality. For exposure to PM10 (including estimated exposure to PM10 from studies using PM2.5), the pooled hazard ratio for each 10-µg/m3 increment in PM10 was 1.061 (95% confidence interval, 1.018-1.105) and 1.080 (0.992-1.177) for overall stroke events and stroke mortality, respectively. A stratified analysis by continent revealed that the association between stroke and long-term PM10 exposure was positive in North America (1.062 [1.015-1.110]) and Europe (1.057 [0.973-1.148]), but studies in Asia (1.010 [0.885-1.153]) showed a high degree of heterogeneity. Considering exposure to PM2.5 (Europe and North America combined), the hazard ratios for a 5-µg/m3 increment were 1.064 (1.021-1.109) and 1.125 (1.007-1.256) for stroke events and mortality, respectively. CONCLUSIONS: The scientific evidence of the past decade identifies long-term exposure to PM, and PM2.5 in particular, as a risk factor for stroke. However, we found some currently unexplained geographical variability in this association.