Risk of traumatic intracranial haemorrhage is increased in older people exposed to oral anticoagulation with phenprocoumon.

BACKGROUND: Hospital admissions resulting from traumatic intracranial haemorrhages (TIH) in older people are increasing. There are concerns regarding an increased risk of a TIH in people taking oral anticoagulants (OAC) like phenprocoumon. AIMS: The aim of this study was to estimate the incremental risk of a TIH associated with OAC in older people. Furthermore, this study explored differences in risk according to functional status. METHODS: The study took data from a large German health insurance provider and combined hospital diagnoses with data regarding drug dispensing to estimate rates of a TIH in people with and without exposure to phenprocoumon. Analyses were stratified by sex and by severe functional impairment as disclosed by the long-term care insurance provider. RESULTS: Overall, exposure to OAC resulted in 2.7 times higher rates of TIH. People with severe functional impairment had a higher baseline risk of TIH than people without severe functional impairment. However, the incremental risk in those exposed to OAC was similar among people with and without severe functional impairment (standardised incidence rate difference 15.73 (95% CI 7.84; 23.61) and 12.10 (95% CI 9.63; 14.57) per 10,000 person-years, respectively). CONCLUSIONS: OAC increases the risk of TIH considerably. The incremental risk of TIH in those exposed to OAC is comparable between people with and without severe functional impairment. The presence of severe functional impairment per se should not exclude such patients from the potential benefits of OAC. For now, the prescription should be personalized based on individual fall risk factors and risk-taking behaviour.

Analysis of mortality after hip fracture on patient, hospital, and regional level in Germany.

Knowledge about risk factors of mortality after hip fracture might encourage prevention and further improvements in care. This study identified patient risk factors as well as hospital and regional characteristics associated with a decreased risk. Variation of mortality was largest on patient level and modest on hospital and regional level. INTRODUCTION: Among numerous studies analyzing mortality as worst consequence after hip fracture, the majority focused on patient level and fewer on hospital and regional level. Comprehensive knowledge about contributing factors on all levels might help to reveal relevant inequalities, which would encourage prevention and further improvements in care. This study aimed at investigating variation of mortality after hip fracture on patient, hospital, and regional level in Germany. METHODS: We performed a retrospective cohort study on hip fracture patients aged 65 and older using statutory health insurance claims data from Jan 2009 through Dec. 2012 and additional information from the Federal Statistical Office Germany. Regions were classified based on two-digit postal code. We applied a multilevel Cox proportional hazard model with random intercepts on hospital and regional level to investigate the risk factors for mortality within 6 and 12 months after hip fracture. RESULTS: The dataset contained information on 123,119 hip fracture patients in 1014 hospitals in 95 German regions. Within 6/12 months, 20.9%/27.6% of the patients died. On patient level, male sex, increasing age, increased pre-fracture care level, and increasing comorbidity were associated with an increased hazard of mortality. Hospitals with increasing hip fracture volume or with orthogeriatric co-management and regions with increased population density were associated with a decreased hazard. Variation was largest on patient level and rather modest on hospital and regional level. CONCLUSIONS: The identification of patient-related risk factors enables prognosticating mortality after hip fracture. After adjusting for those, variation seemed to be attributable rather to hospitals than to regions.

Risk of institutionalization following fragility fractures in older people.

Previously independent living older people suffering fractures of the hip have a high risk of new admission to a nursing home during the subsequent months. This study shows that older people admitted to hospital for fractures of the pelvis and spine have a similar risk of admission to a nursing home. INTRODUCTION: Fall-related fractures are a serious threat to the health and well-being of older persons. Long-term consequences of hip fractures such as institutionalization and mortality are well-known. The impact of other fragility fractures is less well-understood. The aim of this study was to estimate risks of institutionalization and death for different fragility fractures and compare them with the corresponding risks after hip fracture. METHODS: Data was retrieved from a German health insurance company. Between 2005 and 2008 more than 56,000 community-dwelling people with a hospital admission or discharge diagnosis of a fracture of the femur, spine, pelvis, proximal humerus, distal radius, tibia, or fibula were included. Crude and age-adjusted 6-month incidence rates for institutionalization and death were calculated. To compare the risks of institutionalization or mortality of non-hip fractures with the risk after hip fracture, multivariate regression models were applied. RESULTS: Crude institutionalization rates and mortality were highest in patients with hip fracture. However, after adjustment for age, functional status, and comorbidity, risks of institutionalization after fractures of pelvis (relative risk (RR), 0.94; 95% confidence interval (CI) 0.86; 1.02 in women and 0.89; 95% CI 0.70; 1.12 in men), and spine (RR, 0.95; 95% CI 0.87; 1.03 in women and 0.91; 95% CI 0.76; 1.08 in men) were not statistically different compared to the risk after hip fracture. CONCLUSIONS: The risk of institutionalization after fractures of the spine and pelvis was similar to the risk after hip fracture. These fracture sites seem to be associated with a significant decline in physical function.

Osteoarthritis-patterns, cardio-metabolic risk factors and risk of all-cause mortality: 20 years follow-up in patients after hip or knee replacement.

Osteoarthritis (OA) is a common musculoskeletal disorder and occur in different patterns. However, its impact on long-term all-cause-mortality is inconclusive. STUDY AIMS: Investigate 20-year all-cause-mortality in patients with hip/knee arthroplasty (recruited 1995/1996, N = 809) from the Ulm Osteoarthritis Study-cohort, in comparison to general population. Furthermore, to enlighten the triangle between baseline life-style and cardio-metabolic risk factors, phenotypic OA-patterns (laterality, generalization, cause) and all-cause-mortality. Mortality was assessed during 20 years follow-up. Standardized mortality ratios (SMR), adjusted odds ratios and hazard ratios (aHR) were calculated. After five years cohort-mortality was reduced compared to the general population, however 20 years later assimilated (SMR = 1.11; 95%-CI 0.73-1.49). OA-patterns were associated with age, cholesterol, and overweight/obesity. In comparison to primary OA decreased mortality was observed for patients with secondary OA (aHR = 0.76; 95%-CI 0.61-0.95) adjusted for age, smoking, overweight/obesity, diabetes, hypertension, cardiac insufficiency, uric acid, and lower cholesterol. There was no increased mortality in patients after 20 years follow-up compared to general population. Significantly decreased mortality in secondary compared to primary OA suggests a subtype-specific involvement of systemic co-factors in determination of all-cause-mortality. Because cardio-metabolic risk factors were associated with increased risk of bilateral OA and lower long-term survival, those risk factors should be consequently targeted in OA-patients.

Fracture risk in people with developmental disabilities: results of a large claims data analysis.

Age- and sex-specific fracture rates of 18,000 people with developmental disabilities aged 0-69 years were compared to the general population. Age-standardized incidence of femoral fracture was 4.8- and 7.1-fold higher in women and men, respectively. Comparable fracture risks to the general population occurred 10-15 years earlier in females and 20-40 years earlier in males. INTRODUCTION: Previous studies suggested that fracture risks in people with developmental disabilities (DD) may be higher than in people in the general population. However, there are no current sufficiently large studies to compare age- and sex-specific fracture rates of single fracture types. METHODS: People with DD and incident fractures were identified by routine data of a health insurance company. Fractures in the general population were derived from the official fracture statistics. Age-specific and age-standardized fracture incidences were analyzed. To compare fracture risks in people with DD with that of the general population incidence ratios were calculated. RESULTS: Between 2008 and 2010, 148 femoral fractures and 469 other fractures were observed in nearly 18,000 people with DD aged 0-69 years. The three most frequent fracture types leading to hospital admission were fractures of the femur, lower leg/ankle, and shoulder/arm. For femoral fractures, a particularly high risk was observed in children and adolescents with DD. In adults with DD, the risk of femoral fractures increased with increasing age. Even if the youngest age category was not considered, the age-standardized incidence was 4.8- and 7.1-fold higher in women and men, respectively. For all other fracture types, except fractures of forearm/hand and of pelvis, people with DD had also higher fracture incidences than the general population. CONCLUSIONS: People with DD have a high fracture burden. Comparable risks of femoral fracture, for example, occurred about 10-15 years earlier in females and even 20-40 years earlier in males with DD than in the general population.

Risk of osteoporotic fractures following stroke in older persons.

UNLABELLED: The aim of this study was to explore the increased risk of stroke survivors to different sustained osteoporotic fractures. We used hospital data and data on functional impairment. We found a higher risk in stroke survivors without functional impairment with the risk higher for lower than for upper extremity fractures. INTRODUCTION: Stroke survivors are at high risk of osteoporotic fractures due to frequent falls and an increased risk to develop osteoporosis. Data on their relative risk to sustain other than hip fractures is limited. Furthermore, the role of severe functional impairment on their fracture risk has not been considered yet. The aim of this study was to determine the relative risk of stroke survivors to sustain different osteoporotic fractures with regard to the presence of severe functional impairment. METHODS: Data from 2004 to 2009 of more than 1.2 million individuals aged 65 years or older and insured at a large German health insurance company were used for the analyses. Incident stroke and fractures were obtained from hospital diagnoses. Analyses were stratified by gender and information on severe functional impairment. Persons without preceding incident stroke were used as the reference group. Multistate models were used to estimate hazard ratios. RESULTS: Stroke survivors had a higher risk for fractures. However, a strong effect modification by functional impairment was apparent. Stroke survivors with functional impairment had no significantly increased risk for any fractures site compared to the corresponding reference group with functional impairment. In contrast, stroke survivors without functional impairment had a clearly and significantly increased fracture risk for most fracture sites. In these persons, the relative fracture risk for fractures of the lower extremities was higher than for fractures of the upper extremities. CONCLUSION: To evaluate the relative risk of stroke survivors for osteoporotic fractures, functional status appears to be a relevant parameter.

Dampness and moulds in relation to respiratory and allergic symptoms in children: results from Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC Phase Two).

BACKGROUND: Many studies report that damp housing conditions are associated with respiratory symptoms. Less is known about mechanisms and possible effect modifiers. Studies of dampness in relation to allergic sensitization and eczema are scarce. OBJECTIVE: We study the influence of damp housing conditions world-wide on symptoms and objective outcomes. METHODS: Cross-sectional studies of 8-12-year-old children in 20 countries used standardized methodology from Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC). Symptoms of asthma, rhinitis and eczema, plus residential exposure to dampness and moulds, were ascertained by parental questionnaires (n = 46 051). Skin examination, skin prick tests (n = 26 967) and hypertonic saline bronchial challenge (n = 5713) were performed. In subsamples stratified by wheeze (n = 1175), dust was sampled and analysed for house dust mite (HDM) allergens and endotoxin. RESULTS: Current exposure to dampness was more common for wheezy children (pooled odds ratio 1.58, 95% CI 1.40-1.79) and was associated with greater symptom severity among wheezers, irrespective of atopy. A significant (P < 0.01) adverse effect of dampness was also seen for cough and phlegm, rhinitis and reported eczema, but not for examined eczema, nor bronchial hyperresponsiveness. HDM sensitization was more common in damp homes (OR 1.16, 1.03-1.32). HDM-allergen levels were higher in damp homes and were positively associated with HDM-sensitization, but not wheeze. CONCLUSION: A consistent association of dampness with respiratory and other symptoms was found in both affluent and non-affluent countries, among both atopic and non-atopic children. HDM exposure and sensitization may contribute, but the link seems to be related principally to non-atopic mechanisms.

Asthma and allergies: is the farming environment (still) protective in Poland? The GABRIEL Advanced Studies.

BACKGROUND: Evidence exists that a farming environment in childhood may provide protection against atopic respiratory disease. In the GABRIEL project based in Poland and Alpine regions of Germany, Austria and Switzerland, we aimed to assess whether a farming environment in childhood is protective against allergic diseases in Poland and whether specific exposures explain any protective effect. METHODS: In rural Poland, 23 331 families of schoolchildren completed a questionnaire enquiring into farming practices and allergic diseases (Phase I). A subsample (n = 2586) participated in Phase II involving a more detailed questionnaire on specific farm exposures with objective measures of atopy. RESULTS: Farming differed between Poland and the Alpine centres; in the latter, cattle farming was prevalent, whereas in Poland 18% of village farms kept ≥1 cow and 34% kept ≥1 pig. Polish children in villages had lower prevalences of asthma and hay fever than children from towns, and in the Phase II population, farm children had a reduced risk of atopy measured by IgE (aOR = 0.72, 95% CI 0.57, 0.91) and skin prick test (aOR = 0.65, 95% CI 0.50, 0.86). Early-life contact with grain was inversely related to the risk of atopy measured by IgE (aOR = 0.66, 95% CI 0.47, 0.92) and appeared to explain part of the farming effect. CONCLUSION: While farming in Poland differed from that in the Alpine areas as did the exposure-response associations, we found in communities engaged in small-scale, mixed farming, there was a protective farming effect against objective measures of atopy potentially related to contact with grain or associated farm activities.

Exposure to microbial agents in house dust and wheezing, atopic dermatitis and atopic sensitization in early childhood: a birth cohort study in rural areas.

BACKGROUND: Early-life exposure to environmental microbial agents may be associated with development of wheezing and allergic diseases. OBJECTIVE: To assess the association of microbial exposure in rural homes with the risk of asthma, wheezing, atopic dermatitis and sensitization. METHODS: Birth cohorts of rural children (n = 1133), half from farmer families, were followed up from birth to 2 years of age by questionnaires in five European centres. Endotoxin and extracellular polysaccharides (EPS) of Penicillium and Aspergillus spp. were determined from living room floor and mother's mattress dust samples collected at 2 months of age. Specific IgE against 19 allergens was measured at 1 year of age. Discrete-time hazard models, generalized estimations equations (GEE) and logistic regression were used for statistical analyses. RESULTS: The incidence of asthma was inversely associated with the amount of dust (adjusted odds ratio (aOR) 0.73, 95% CI 0.58-0.93) and the loads (units/m(2)) of EPS (aOR 0.75, 95% CI 0.55-1.04) and endotoxin (aOR 0.79, 95% CI 0.60-1.05) in the mother's mattress. Similar associations were seen with wheezing and with living room floor dust. The microbial markers were highly correlated and their effects could not be clearly separated. The inverse associations were seen especially among non-farmers. The risk of sensitization to inhalant allergens increased with increasing endotoxin exposure from mattress dust. No associations were observed with concentrations (units/g) or with atopic dermatitis. CONCLUSION AND CLINICAL RELEVANCE: The amount and microbial content of house dust were inversely associated with asthma and wheezing, but due to high correlations between microbial agents and amount of dust, it was not possible to disentangle their individual effects. New ways to better measure and represent exposure to environmental microbes, including indexes of biodiversity, are needed especially among farmers.

Exposure to moulds and actinomycetes in Alpine farms: a nested environmental study of the PASTURE cohort.

Several studies have suggested that children exposed to a farm environment are protected against allergies and asthma. The present work is an environmental study nested within the PASTURE cohort and includes 97 farmers and 74 non-farmers in three regions of the Alpine Arc (Switzerland, France and Germany). The objectives were to determine and compare the fungi and actinomycetes present in farming and non-farming environments (children's bedrooms and cowsheds), and to identify the agricultural practices associated with an increase in airborne fungi and actinomycetes in cowsheds. Air samples were collected by air pump and were analysed by culture and by direct counting of spores on membranes. During their stay in bedrooms, children living on farms were exposed to significantly greater amounts of Absidia spp., Eurotium spp., Cladosporium spp., Penicillium spp. and mesophilic actinomycetes than children who did not live on farms. Depending on the season, the levels of moulds, yeasts and actinomycetes were from 14 to 82 times higher in cowsheds before feeding the cattle than in children's bedrooms, and from 12 to 464 times higher in cowsheds after feeding than in children's bedrooms. Feeding cattle in cowsheds was associated with a significant peak in airborne moulds and actinomycetes, and this peak was higher in winter than in summer. Silage distribution was associated with low amounts of moulds and actinomycetes. Other significant agricultural factors were the type of cowshed, cowshed volume, method of food distribution to cattle and use of fresh grass. An assessment of the microbiological diversity on farms and in children's rooms may help to determine the factors protecting children from asthma and atopic diseases.

Birth-related factors and doctor-diagnosed wheezing and allergic sensitization in early childhood.

BACKGROUND: To investigate the associations between clinical obstetric factors during birth and doctor-diagnosed wheezing and allergic sensitization during early childhood. METHODS: We followed 410 Finnish women from late pregnancy until 18 months age of their children. All children were delivered at term. Doctor-diagnosed wheezing among children was established by questionnaires, while specific immunoglobulin E antibodies to inhalant and food allergens were measured in 388 children at 1 year of age. Data on maternal obstetric variables were recorded at the time of delivery. RESULTS: Children of mothers with longer duration of ruptured fetal membranes before birth had significantly higher risk of doctor-diagnosed wheezing during early childhood compared to those children with shorter period of ruptured fetal membranes (III vs I quartile; aOR 6.65, 95% CI 1.99-22.18; P < 0.002 and IV vs I quartile; aOR 3.88, 95% CI 1.05-14.36, P < 0.043). Children who were born by Cesarean delivery had significantly less allergic sensitization at the age of 1 year compared to those who were born by vaginal route (16.0%vs 32.2%; aOR 0.34, 95% CI 0.14-0.80; P < 0.013). Furthermore, allergic sensitization tended to be more common in children with longer duration of labor before birth. No other birth-related obstetric factors, such as induction, the type of fetal membrane rupture during birth or quality of amniotic fluid were associated significantly with the examined outcomes. CONCLUSION: The longer duration of the ruptured fetal membranes possibly reflected the higher risk of intrapartum infection at birth, and further increased the risk of doctor-diagnosed wheezing among offspring.

Maternal vitamin D intake during pregnancy increases gene expression of ILT3 and ILT4 in cord blood.

BACKGROUND: Recent studies indicate that prenatal vitamin D intake may protect against the development of atopic diseases in young children. Vitamin D has been shown to induce tolerogenic antigen-presenting cells such as dendritic cells. Whether the allergy-protective potential of prenatal vitamin D is mediated through such mechanisms is, however, unknown. OBJECTIVE: To evaluate the association between prenatal vitamin D supplementation and tolerogenic antigen-presenting cells in cord blood (CB) as determined by mRNA measurement of immunoglobulin-like transcripts (ILT)3 and ILT4. METHODS: A prospective multi-centre birth cohort was established in rural areas of five European countries. Information on maternal exposures including vitamin D intake was collected by questionnaires during pregnancy. The gene expression of ILT3 and ILT4 was analysed by real-time PCR in the CB of 927 children. Maternal vitamin D supplementation was assessed in Finland and France (n=349). RESULTS: Maternal vitamin D supplementation during pregnancy was associated with an increase in the gene expression of ILT3 (P=0.012) and ILT4 (P<0.001). This association remained significant for ILT4 (P=0.020) and showed a positive trend for the gene expression of ILT3 (P=0.059) after multivariate analysis controlling for various confounders. CONCLUSIONS: Vitamin D supplementation during pregnancy may increase the mRNA levels of ILT3 and ILT4 in CB. This finding may point towards an early induction of tolerogenic immune responses by maternal vitamin D intake.

How well do questionnaires perform compared with physical examination in detecting flexural eczema? Findings from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two.

BACKGROUND: Questionnaires are widely used in epidemiological studies to measure eczema symptom prevalence, but there are concerns regarding their accuracy if used as a diagnostic tool. OBJECTIVES: To compare the performance of a validated eczema symptom questionnaire and a standardized skin examination protocol employed in the second phase of the International Study of Asthma and Allergies in Childhood (ISAAC). METHODS: A total of 30,358 schoolchildren aged 8-12 years from 18 countries were examined for flexural eczema. Parents also completed an eczema symptom questionnaire. We compared prevalence estimates at the population level based on the questionnaire vs. physical examination. We also compared the skin examination and the ISAAC questionnaire in making a diagnosis of flexural eczema. RESULTS: The point prevalences for flexural eczema at centre level based on a single examination were lower than the questionnaire-based 12-month period prevalences (mean centre prevalence 3.9% vs. 9.4%). Correlation between prevalences of both outcome measures was high (r = 0.77, P < 0.001). At the individual level, questionnaire-derived symptoms of 'persistent flexural eczema in the past 12 months' missed < 10% of cases of flexural eczema detected on physical examination. However, between 33% and 100% of questionnaire-based symptoms of 'persistent flexural eczema in the past 12 months' were not confirmed on examination. CONCLUSIONS: ISAAC questionnaire-derived symptom prevalences are sufficiently precise for comparisons between populations. Where diagnostic precision at the individual level is important, questionnaires should be validated and potentially modified in those populations beforehand, or a standardized skin examination protocol should be used.

Double-lumen central venous catheters impregnated with chlorhexidine and silver sulfadiazine to prevent catheter colonisation in the intensive care unit setting: a prospective randomised study.

Antimicrobial- and antiseptic-impregnated catheters are strategies recommended to prevent central venous catheter (CVC) colonisation. Few data regarding chlorhexidine/silver sulfadiazine-impregnated catheters in intensive care unit (ICU) patients have been reported. We performed a prospective, randomised study comparing the colonisation rates of chlorhexidine/silver sulfadiazine-impregnated CVCs (group 1) against standard CVCs (group 2). In order to assess catheter colonisation rates, a 4cm segment from the tips of aseptically removed catheters was cultured by the roll-plate method. In all, 109 patients were enrolled with successful catheter insertion, 51 of them in group 1 and 58 in group 2. There were no statistically significant differences between the two groups with regards to age, Sequential Organ Failure Assessment (SOFA) score, ICU admission diagnosis, infection risk, catheter insertion sites or catheter length of stay. The colonisation rates were 29.4% (15 catheters) for group 1 and 34.5% (20 catheters) for group 2 (P=0.50). Double-lumen CVCs impregnated with chlorhexidine and silver sulfadiazine were not effective in reducing the incidence of catheter colonisation in ICU patients.

Effect of breastfeeding on asthma, lung function and bronchial hyperreactivity in ISAAC Phase II.

The association between breastfeeding and wheezing, lung function and atopy was evaluated in the International Study of Asthma and Allergy in Childhood (ISAAC) Phase II. Cross-sectional studies were performed in 27 centres in 20 countries. Information on disease and exposure factors was collected by parental questionnaires. Data from 54,000 randomly selected school children (aged 8-12 yrs, 31,759 with skin prick testing) and a stratified subsample (n = 4,888) were used for testing the correlation of breastfeeding with bronchial hyperreactivity and lung function. Random effect models for meta-analysis were applied to calculate combined odds ratios (ORs). Any breastfeeding was associated with less wheeze both in affluent (adjusted OR (OR(adj)) 0.87, 95% confidence interval (CI) 0.78-0.97) and nonaffluent countries (OR(adj) 0.80, 95% CI 0.68-0.94). Further analyses revealed that this was true only for nonatopic wheeze in nonaffluent countries (OR(adj) 0.69, 95% CI 0.53-0.90). Breastfeeding was not associated with atopic wheeze and objective measures of allergy in both affluent and nonaffluent countries. In contrast, breastfeeding was associated with higher predicted forced expiratory volume in one second in affluent countries only (mean ratio 1.11, 95% CI 1.02-1.20). Breastfeeding is associated with protection against nonatopic wheeze, which becomes particularly evident in nonaffluent countries. Overall, breastfeeding was not related to any measure of allergy. These findings may explain some of the controversy regarding breastfeeding, since the direction of the association with breastfeeding depends on the predominating wheeze phenotype (e.g. atopic, nonatopic).

Specific IgE to allergens in cord blood is associated with maternal immunity to Toxoplasma gondii and rubella virus.

BACKGROUND: Various studies have found reduced prevalences of atopic sensitization and atopic diseases in children previously exposed to infections or living conditions with a high microbial burden, such as the farming environment. OBJECTIVE: We sought to determine the relationships of cord blood immunoglobulin E (IgE) with maternal health conditions before and during pregnancy. METHODS: Pregnant women living in rural areas in five European countries were recruited in the third trimester of pregnancy. Information on maternal health during pregnancy was collected from maternity records and by questionnaires (n = 497). Specific IgE for inhalant and food allergens was assessed in cord blood and peripheral blood samples of the mothers. RESULTS: Inverse associations of cord blood IgE to seasonal allergens with positive maternal records for Toxoplasma gondii (adjusted odds ratio = 0.37 [0.17-0.81]) and rubella virus (adjusted odds ratio = 0.35 [0.13-0.96]) were found. The previously described effect of prenatal farm exposure on IgE to seasonal allergens was partly confounded by a positive maternal record for T. gondii. The number of maternal siblings, maternal contact to cats during pregnancy or during her first year of life, predicted a positive maternal record for T. gondii. CONCLUSIONS: Maternal immunity to T. gondii and rubella may impact on atopic sensitization in the fetus. A positive T. gondii record explained the previously identified effect of prenatal farm exposure on IgE to seasonal allergens only to a minor extent.

International variation in prevalence of rhinitis and its relationship with sensitisation to perennial and seasonal allergens.

The relative importance of atopy in the aetiology of rhinitis is largely unknown. The present study investigated the geographical variations in rhinitis in relation to atopy. The cross-sectional study involved 54,178 children (aged 8-12 yrs) from 30 study centres in 22 countries worldwide. Symptoms of rhinoconjunctivitis and rhinitis without conjunctivitis in the last 12 months were reported in parental questionnaires and children were skin-prick tested. The prevalence of rhinoconjunctivitis and rhinitis without conjunctivitis varied widely (1.5-24.5% and 1.4-45.2%, respectively). For rhinoconjunctivitis, the population attributable fraction (PAF) varied 0-71% for a positive skin-prick test to one or more seasonal allergens and 0-41% for perennial allergens. The PAF for sensitisation to seasonal and perennial allergens was higher in affluent countries (36 and 25%, respectively) than nonaffluent countries (1.3 and 12.6%, respectively). For rhinitis without conjunctivitis, the PAF for perennial allergens was 8 and 4% for affluent and nonaffluent countries, respectively. No significant PAF was found for seasonal allergens. Overall, atopy explained only a limited proportion of rhinitis symptoms, suggesting that the importance of other environmental factors has been under emphasised, particularly in less affluent countries. Atopy seems to be only marginally relevant for rhinitis without conjunctivitis, which seems mainly to reflect nonatopic rhinitis.

The microcirculation in critically-ill patients.

The microcirculation plays a major role in oxygen delivery and organ perfusion, and is largely involved in the pathophysiological alterations of shock states. It has been a focus of research for a long time, but human clinical and physiological studies have been limited by a lack of reliable techniques available at the bedside. Intravital microscopy, although of interest in experimental studies, is not feasible in human studies. Laser Doppler techniques can measure blood flow, but do not take into account the heterogeneity of the microcirculation. Recently, the Orthogonal Polarized Spectral (OPS) imaging technique has enabled the study of the microcirculation in humans. This technique has allowed a better definition of microcirculatory alterations in disease states, defined the role of some medical interventions, and been used to predict outcome. In this text, we briefly describe the techniques available to study the microcirculation and review experimental and human studies in this domain.

[Differences in small area prevalence of respiratory diseases in children: challenges of an investigation initiated by parents]. / Kleinräumige Prävalenzunterschiede von Atemwegserkrankungen bei Kindern: Grenzen der Erkenntnismöglichkeiten einer von Eltern angeregten Studie.

OBJECTIVE: The aim of our study was to assess the prevalence of respiratory diseases in children living in a rural area in Bavaria in a systematic and standardised way to clarify whether a disease cluster exists. Reports from a parents' initiative claiming an increase of diseased children and assuming an association with air pollution due to nearby industrial sources and heavy traffic were the reason for the study. METHODS: Parents of all children living in small towns specified by the parents' initiative as affected region (central area) and parents of those children aged 6-7 or 13-14 years living in adjacent areas (control area) were asked to complete a written questionnaire. In bivariate analysis, differences in prevalences between the central area and the control area were assessed by the chi (2) test. In multivariate analysis, confounder-adjusted odds ratios with 95 % confidence intervals were calculated by logistic regression. In addition, generalized linear mixed models were used to control for potential clusters in families. RESULTS: The response rate was rather low (total 46 %, central area 53 %, control area 34 %). The study population comprised 121 girls and 141 boys. There was a pattern of increased prevalences of cough, wheeze and respiratory diseases caused by infections in children living in the central area compared to the control area. However, statistical significance was rarely observed. No systematic differences were observed for the prevalence of allergic rhinitis and atopic dermatitis. Selection bias due to varying response rates in the central versus the control area and information bias introduced by the preceding intensive public discussion could not be excluded. The comparison of prevalences detected in the small area with published data from other epidemiological studies in Germany did not indicate a systematically increased prevalence of respiratory symptoms or physician-diagnosed respiratory diseases in children from the whole area as well as in children from the central area only. CONCLUSION: This study exemplifies the challenges of small area investigations initiated by the residential community to clarify an assumed disease cluster caused by environmental pollution. The prior comparison of small area prevalence data with results of other epidemiological studies aids the decision making as to whether a detailed study with comprehensive assessment of individual exposure is justifiable.

[The use of randomisation in clinical studies in rehabilitation medicine: basics and practical aspects]. / Randomisierung in klinischen Studien in der Rehabilitationsforschung: Grundlagen und praktische Aspekte.

New therapies in rehabilitation medicine have to be evaluated with clinical trials. For drug approval the methodology of clinical trials is standardized world wide and the results of these studies are widely accepted. This standard should be achieved in clinical trials in rehabilitation research, too. One of the standards is the existence of a control group, comparing the effect of the new intervention against controls. In addition, the investigational and control groups must be equal in terms of the structure of possible confounders. Randomisation is the best possibility to distribute the patients to the therapy-groups, confounders will be equally distributed by chance. Other procedures for assignment to the study groups can result in confounding and lead into biased results. In spite of these advantages, randomisation is not generally accepted in rehabilitation research up to now. There are some reservations, mostly ethical, organisational and methodological ones. However, randomised clinical trials should be conducted in rehabilitation research in order to obtain more convincing results. Our intention is to bring some input in this debate and to present basics and practical aspects of randomisation.