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Objective: Acute geriatric care (geriatric early rehabilitative treatment) and sub-acute (inpatient) geriat-ric rehabilitation are delivered to geriatric patients in Germany after hip fracture. The aim of this study was to compare patients' outcomes after hip fracture between 3 German federal states (Hesse, Bavaria, and Baden-Wuerttemberg) that nearly exclusively offered one of the two geriatric care systems., Design: Retrospective cohort study with patient-related health insurance claims data., Patients: Analyses were performed with data from 2009-2012 of over 30,000 patients aged ≥80 years with incident hip fracture., Methods: Primary outcomes: "increase in care dependency", "nursing home admission"; secondary outcomes: "rehospitalization", "mortality". Multivariate regression models were applied., Results: Compared with Hesse, the state with acute geriatric care, the risks of an "increase in care dependency" were lower in Bavaria (adjusted ratio = 0.84; 95% confidence interval (95% CI) 0.81-0.87) and Baden-Wurttemberg (0.88; 0.85-0.92), the 2 federal states with sub-acute geriatric rehabilitation. A reduction in the risk of nursing home admission was observed in Baden-Wuerttemberg (0.77; 95% CI 0.69-0.87), but not in Bavaria. Rehospitalization rates were lower in Bavaria and Baden-Wuerttemberg compared with Hesse. There was no difference in mortality., Conclusion: Some, but not all, outcomes were more favourable in the federal states with sub-acute geriatric rehabilitation than in the federal state with acute geriatric care.

Background: To meet the special needs of older patients with fragility fractures, models for collaborative orthogeriatric care have been developed. The objective of our study was to analyze the association of orthogeriatric co-management with mortality following hip fracture in older patients in Germany., Methods: This observational study was based on health insurance claims data from 58 001 patients (79.4% women) aged ≥80 years admitted to the hospital with hip fracture between January 2014 and March 2016. They were treated in 828 German hospitals with or without orthogeriatric co-management. The outcome measure was cumulative mortality with adjustment of the regression analyses., Results: The crude 30-day mortality was 10.3% for patients from hospitals with orthogeriatric co-management and 13.4% for patients from hospitals without orthogeriatric co-management. The adjusted 30-day mortality was 22% lower for patients in hospitals with orthogeriatric co-management (rate ratio 0.78; 95% CI [0.74; 0.82]; adjusted absolute difference -2.48%; 95% CI [-2.98; -1.98]). The difference in 30-day mortality remained nearly unchanged over the first 6 months. The risk reduction with orthogeriatric co-management was consistently observed in both women and men, across age groups, and in patients with and without care needs. The mean length of the index stay was 19.8 days in hospitals with orthogeriatric co-management and 14.4 days in hospitals without orthogeriatric co-management., Conclusion: A multidisciplinary orthogeriatric approach is associated with lower mortality and a longer index stay in hospital after hip fracture.

This study aimed to assess associations between serum cartilage oligomeric matrix protein (sCOMP) and phenotypic characteristics in late-stage hip and knee Osteoarthritis (OA) as well as its correlation with further serum markers of possible comorbidities in the Ulm Osteoarthritis Study. Moreover, the prognostic relevance of preoperative sCOMP concentrations for short-term functionality and pain outcomes after hip or knee joint replacement was explored. Preoperative serum samples and detailed information about the health status (i.e., WOMAC scores, Hannover Functionality Status (FFbH)) of 754 OA patients undergoing total joint replacement were included. Spearman rank-correlation coefficients and multiple linear regression models were used to evaluate the relationships between sCOMP, other serum markers, and health outcomes. There was a significant positive association between sCOMP and markers of renal (cystatin C, creatinine, and eGFR) and cardiac (e.g., NT-proBNP) impairment. Since renal failure might cause accumulation of sCOMP, additional adjustment with eGFR was performed. Preoperative sCOMP levels in knee OA but not hip OA patients were positively associated with FFbH, WOMAC function sub-scale and total WOMAC scale as well as the post-operative WOMAC stiffness sub-scale six months after surgery. Our data clearly demonstrate an association between sCOMP and renal function as well as other confounding factors, which should be considered in future biomarker studies.

Background: The aim of this study was to assess the effect of day of the week and wearing a device (reactivity) on objectively measured physical activity (PA) in older people., Methods: Walking duration as a measure for PA was recorded from 1333 German community-dwelling older people (≥65 years, 43.8% women) over 5 days using accelerometers (activPAL). Least-square means of PA with 95%-confidence intervals (95%-CI) from multi-level analysis were calculated for each day of the week and each measurement day (days after sensor attachment)., Results: Walking duration on Sundays was significantly lower compared to working days (Sunday vs. Monday-Friday: - 12.8 min (95%-CI: - 14.7; - 10.9)). No statistically significant difference compared to working days was present for Saturdays. The linear slope for measurement day and walking duration was marginal and not statistically significant., Conclusions: Studies using PA sensors in older people should assess Sundays and working days to adequately determine the activity level of the participants., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

Background: A hip or pelvic fracture is a major fall-related injury which often causes a decline in mobility performance and physical activity. Over 40% of patients with hip fracture have cognitive impairment or dementia and poorer rehabilitation outcomes than those without cognitive impairment. In this subgroup, there is a lack of evidence on the best practices supporting recovery. The main aim of this study is to investigate the effects of a transitional care intervention after inpatient rehabilitation on physical activity and functional performance in this group of cognitively impaired patients., Methods/design: This dual-centre, randomised controlled trial compares a multifactorial intervention with usual care as control condition. Two hundred and forty community-dwellers (≥ 65 years) with a hip or pelvic fracture and mild to moderate cognitive impairment (MMSE 17-26) are recruited at the end of inpatient rehabilitation. The four-month intervention consists of (a) an individually tailored, progressive home exercise program and physical activity promotion delivered by professional instructors and lay instructors (two home visits per week) and (b) a long-term care counselling approach addressing unmet care needs, pleasurable activities, and caregiver issues if needed. Primary outcome parameters are physical activity, measured as daily walking duration with an accelerometer-based activity monitor (activPAL™) over 72 h, and functional performance, assessed with Short Physical Performance Battery sum scores. Secondary outcome parameters are fear of falling, fall related self-efficacy, falls, quality of life, depression and activity of daily living. Data are collected at the end of rehabilitation, before the intervention at the patient's home (baseline), after four months (post-intervention), and seven months (follow-up). In addition to completer and intent-to-treat analyses of outcomes, economic data and incremental cost-effectiveness are analysed., Discussion: Existing service models of volunteer services and legal counselling provided by care counsellors were considered when developing the intervention protocol. Therefore, it should be feasible to translate and deliver the intervention into real-world practice if it has been demonstrated to be effective., Trial Registration: German Clinical Trials Register, DRKS00008863 (Accessed 17 Apr 2019), ISRCTN registry, ISRCTN69957256 (Accessed 17 Apr 2019).

Objectives: Hip fractures are common consequences of falls in older adults and, among other negative health outcomes, often lead to care dependence in the long term. Until 2016, the German long-term care insurance classified care recipients according to a standardized classification system consisting of 3 care levels. It was based on required assistance in performing activities of daily living and assessed by a qualified physician or nurse. Thus, care level reflects the degree of care dependence. The aim of this study was to determine relevant patient characteristics, which are related to the likelihood of increasing care dependence in terms of worsening care level after hip fracture., Design: Retrospective cohort study., Setting and Participants: Statutory health insurance claims data including 122,922 insured individuals living in Germany and aged 65 years or older, who sustained a hip fracture from 2009 through 2011., Measures: The association of patient characteristics with worsening care level in the quarterly period after hip fracture was investigated by means of multinomial logit regression analysis. Death constitutes a competing risk and was modeled as additional nominal outcome., Results: Among all patients, crude rates were 30.9% for worsening care level, 54.8% for unchanged care level, and 14.4% for death after hip fracture. The multivariate analysis revealed that patient factors male sex, increasing age, increasing comorbidity, increasing inpatient length of stay, and a lack of inpatient rehabilitation were significantly associated with a worsening care level., Conclusions/implications: This study uses the German standardized measurement of care dependence in terms of worsening care level after hip fracture and finds various related patient characteristics. Knowledge of these characteristics helps to identify possible risk groups for care dependence after hip fracture, for which special attention can be provided regarding treatment and prevention of hip fractures., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Specific training reduces the risk of falls and fall-related injuries in older persons. The availability of specific exercise programs in Germany, especially in rural areas is scarce. Therefore, a healthcare fund driven program osteoporotic fracture prevention program in rural areas (OFRA) (German name: "Trittsicher durchs Leben") was implemented in rural areas in 47 counties of 5 federal states. The most important components of the program are the "Trittsicher" mobility course and falls prevention classes organized by members of the German Association of Rural Women and executed by exercise instructors of the German Gymnastics Association or physiotherapists. Since the start of the program in October 2015 more than 2300 classes have been carried out., Aim: The study analyzed the structural characteristics of the first 1092 "Trittsicher" mobility courses and the characteristics of the 12,246 participants., Method: The analysis is based on data of a standardized course documentation sheet and information from an internal database of a health insurance company. Additionally, the distance between the location of the course and place of residence was determined for a subgroup of the participants., Results: The classes were conducted in communal and confessional rooms, in sports associations, kindergartens and restaurants. The majority of the 12,246 participants were female (89.1%), the median age was 75 years. The average size of the classes was 11.2 participants per course. More than half of the participants attended all six sessions. Half of the participants of the courses had to travel less than 1.7 km between the place of residence and the location of the courses., Conclusion: "Trittsicher" mobility courses are a new specific offer to improve mobility and reduce the risk of falling. They contribute to a better care of older people in rural areas.

Background: Hip fractures are regarded as a worldwide epidemic and a major public health concern. Changing risk factors, local differences and temporal trends contribute to the particular epidemiology of hip fractures. This overview gives a comprehensive insight into the epidemiology of hip fractures and reviews where German data have contributed to the literature., Methods: The review of the epidemiology of hip fractures in Germany is based on a systematic literature search in PubMed. Information about the global epidemiology of hip fractures was provided by a selective literature review focusing on specific aspects of the epidemiology of hip fractures., Results: Hip fracture rates vary more than 100-fold between different countries. In most high-income countries, a rise in age-standardized hip fracture rates was observed until the 1980s and 1990s and a decrease thereafter. Such a decrease has not been observed for Germany so far. Many factors, diseases and drugs have been found to be associated with hip fractures and there is some evidence that fracture risk in later life is already programmed during fetal life and early childhood. Of the hip fracture burden 50% occur in people with disability and in need of care. In nursing homes approximately 4 fractures can be expected in 100 women per year. In people with intellectual or developmental disabilities comparable risks of hip fracture occur 10-40 years earlier than in the general population. Incidence of disability, institutionalization and death are frequent consequences of hip fractures., Conclusion: The epidemiology of hip fractures is characterized by a high burden of disease, local differences, temporal trends, well-defined high-risk populations and many established risk factors.

Background: In aging societies osteoporotic fractures are a major health problem with high economic costs. Targeting prevention at individuals at high risk is important to reduce the future burden of fractures. Available risk assessment tools (e.g., FRAX®, QFracture, the algorithm provided by the German Osteology Society (DVO-Tool)) rely on self-reported patient information to predict fracture risk. Time and resource constraints, limited access to clinical data, and (un)willingness to participate may hamper the use of these tools. To overcome such obstacles, the aim is to develop a fracture risk assessment tool based on claims data that may be directly used on an institutional level., Methods: Administrative claims data of an elderly (≥65years) population (N=298,530) for the period from 2006 through 2014 was used. Major osteoporotic fractures (MOF) were identified based on hospital diagnoses. We applied Cox proportional hazard regression to determine the association of individual risk factors and fracture risk. Hazard ratios were used to construct a risk score. The discriminative ability of the score was evaluated using C-statistics., Results: We identified 7864 MOF during follow-up. The median time to first fracture during follow-up was 371.5days. Individuals with a MOF during follow-up had a higher mean and median risk score (mean: 4.53; median: 4) than individuals without MOF (mean: 3.07; median: 3). Adding drug-related risk factors slightly improved discrimination compared to a simple model with age, gender, and prior fracture., Conclusion: We developed a fracture risk score model based on in-hospital treated subjects to predict MOF that can be used on an institutional level. The score included age, sex and prior fracture as risk factors. Adding other risk factors involved very small improvement in discrimination., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Persons with osteoporotic fracture history are subject to an increased risk for subsequent fractures and mortality. The aim of this retrospective study was to investigate the impact of a previous osteoporotic low-impact (fragility) index fracture (eg, forearm, lower leg) on mortality of a subsequent femoral fracture., Design: Retrospective cohort study., Participants/measurements: Claims data of a German health insurance agency including >1.2 million insurants aged 65 years or older and observed between 2004 and 2009., Methods: A multistate model was developed handling index fractures and care need as time-dependent exposures, while age was chosen as the underlying time scale. Excess risks were expressed as differences in cause-specific hazards. Nelson-Aalen estimates were used for their nonparametric estimation. Time-simultaneous statistical inference was based on confidence bands provided by wild bootstrap resampling., Results: Excess femoral fracture risk increased with progressive age and was highest in persons with care need. It was observed starting from an age of 79 years in women and 85 years in men onward. A prior index fracture increased mortality after a femoral fracture by increasing femoral fracture risk, while leaving the hazard of death after a subsequent femoral fracture unchanged., Conclusions: The results indicated that increased mortality of a subsequent femoral fracture is not triggered by an intrinsically increased mortality hazard but an increased femoral fracture incidence., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Fragility fractures are one of the leading causes for disability in old people. The main underlying mechanisms are osteoporosis and falls. Evidence-based measures to prevent either falls or fractures are available. However, coordinated preventive approaches combining bone health and fall prevention are rare. The objective of the study is to evaluate a health care fund driven program, which encourages insured persons to adhere to national guidelines regarding bone health and physical activity and falls prevention. The health care fund cooperates with the 'German Association of Rural Women' and the 'German Gymnastics Association'. The program consists of mobility and falls prevention classes, the examination of bone health by a DXA scan, and a consultation about 'safety in the living environment'., Methods: Cluster-randomized study in 47 intervention and 143 control districts in 5 federal states of Germany. The program is offered to a) community-living women and men aged 70 to <85 years with a prior fragility fracture or b) community-living women aged 75 to <80 years. Within two years more than 10,000 persons will be directly contacted and motivated to make use of the components of the program. The primary outcome is a combined measure of incident osteoporotic fractures. Secondary outcomes include the rate of referrals to a mobility and falls prevention class or a bone mass density measurement. An economic evaluation will be conducted., Discussion: The study evaluates a complex preventive intervention in a routine health care setting which may serve as model for similar approaches in other areas or countries., Trial Registration: DRKS-ID: DRKS00009000 ; date of registration: 06.08.2015.

Introduction: Hospital admissions due to traumatic brain injuries (TBIs) in older persons are increasing. Falls are the leading mechanism of injury in this age group. TBIs are associated with unfavorable outcomes such as mortality and institutionalization., Objectives: To estimate rates of TBIs in older persons with severe functional limitations, expressed as "care need," living in the community, and in older persons with care need living in nursing homes compared with older persons without care need., Participants: More than 1.2 million persons aged 65 years and older living in Bavaria, Germany, and insured with one of the largest German health insurances (health care and long-term care insurance)., Methods: Age-standardized rates were calculated based on hospital claims data and claims data of the long-term care insurance and were compared between groups. The 3 groups were defined by claims data of the long-term care insurance., Results: TBI in older persons account for 4.8 hospital admissions per 1000 person-years. Overall TBI rates do not differ significantly between men and women. TBI rates are lowest in persons without care need and are highest for older persons living in nursing homes. Their contribution to the overall burden of TBI is lower than their contribution to the burden of fragility fractures., Conclusion: TBIs in older persons are common. Those with severe functional limitations are at increased risk for TBI. Nursing home residents have the highest rates of TBI. Fall prevention programs should seek to prevent not only fragility fractures but also head impact., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to assess concurrent validity between activPAL and activPAL3 accelerometers in a sample of 53 community-dwelling older adults ≥ 65 years. Physical activity (PA) was measured simultaneously with activPAL and activPAL3 while performing scripted activities. The level of agreement between both devices was calculated for sitting/lying, standing, and walking. In addition, PA was measured over one week using activPAL to estimate the expected agreement with activPAL3 in real life. Overall agreement between activPAL and activPAL3 was 97%. Compared with activPAL, the largest disagreement was seen for standing, with 5% categorized as walking by activPAL3. For walking and sitting/lying, the disagreement was 2%, respectively. The expected daily differences between activPAL3 and activPAL were +15.0 min (95% CI: 11.3-18.8) for walking and +29.5 min (95% CI: 6.2-52.7) for standing. ActivPAL and activPAL3 showed good agreement in older adults. However, if using these devices interchangeably, observed differences might still bias results.

Objective: To analyze the burden of institutionalizations after femoral fracture and compare it with other "catastrophic" disease entities like stroke, myocardial infarction, or pneumonia., Design/setting/participants: Routine data of 414,000 hospitalized German patients aged 66 years and older were used to calculate institutionalization risks after femoral fracture, stroke, myocardial infarction, pneumonia or a combined group of "all other hospitalizations.", Measurements: Institutionalization was defined as nursing home admission within 6 months after discharge from hospital. Age- and sex-specific incidence and incidence rates of institutionalization were calculated. To compare the risk of institutionalization between the disease entities, age-standardized rates were computed and proportional hazards models were applied. In-house mortality and mortality after discharge from hospital were also calculated., Results: The risk of institutionalization increased exponentially with age in all disease entities. For example, the risk of institutionalization after femoral fracture increased from 3.6% in women aged 65 to 69 years to 34.8% in women aged 95 years and older. The highest institutionalization rates were observed in patients with stroke, followed by femoral fracture, pneumonia, and myocardial infarction. In men, the age-standardized risk of institutionalization was almost as high after femoral fracture as after stroke (7.5% vs 8.0%). In contrast to myocardial infarction and pneumonia, femoral fracture and stroke were more likely to be followed by institutionalization rather than death., Conclusion: Femoral fractures result in high burden of institutionalizations. Prevention of falls, diagnosis and treatment of osteoporosis, and high-quality rehabilitation are challenges to tackle the burden of institutionalization in these patients in the future., (Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Childhood obesity and asthma are increasing worldwide. A possible link between the two conditions has been postulated., Methods: Cross-sectional studies of stratified random samples of 8-12-year-old children (n = 10 652) (16 centres in affluent and 8 centres in non-affluent countries) used the standardized methodology of ISAAC Phase Two. Respiratory and allergic symptoms were ascertained by parental questionnaires. Tests for allergic disease were performed. Height and weight were measured, and overweight and obesity were defined according to international definitions. Prevalence rates and prevalence odds ratios were calculated., Results: Overweight (odds ratio = 1.14, 95%-confidence interval: 0.98; 1.33) and obesity (odds ratio = 1.67, 95%-confidence interval: 1.25; 2.21) were related to wheeze. The relationship was stronger in affluent than in non-affluent centres. Similar results were found for cough and phlegm, rhinitis and eczema but the associations were mostly driven by children with wheeze. There was a clear association of overweight and obesity with airways obstruction (change in FEV1/FVC, -0.90, 95%-confidence interval: -1.33%; -0.47%, for overweight and -2.46%, 95%-confidence interval: -3.84%; -1.07%, for obesity) whereas the results for the other objective markers, including atopy, were null., Conclusions: Our data from a large international child population confirm that there is a strong relation of body mass index with wheeze especially in affluent countries. Moreover, body mass index is associated with an objective marker of airways obstruction (FEV1/FVC) but no other objective markers of respiratory and allergic disorders.

Background/objective: Falls are common in nursing homes and cause a high burden of injuries. The objective of this study was to analyze factors associated with serious consequences of falls in nursing home residents., Design: Prospective observational study., Setting: Falls were recorded over 1 year, covering all residents from 528 nursing homes in Bavaria, Germany., Participants: The database consisted of 70,196 falls., Measurements: The standardized form included information about date, time, sex, age, functional status, location of fall, activity leading to the fall, footwear, and about potential consequences, such as transfer to hospital or a suspected fracture. Transfer to hospital was the main outcome and served as surrogate for a serious fall. The association of potential risk factors with hospital transfer after a fall was estimated in multiple logistic regression models., Results: Serious falls were associated with increasing age, being female, and less restricted functional status. Walking compared with transferring, and particularly the morning hours were also associated with a serious fall. Compared with midday, for example, the time period between 6 am and 8 am was associated with a more than 60% increased chance of transfer to hospital. Inappropriate footwear and weekends were associated with serious falls only in women., Conclusion: Some observed factors or indicators associated with transfer to hospital are modifiable and targeted interventions may reduce injuries or costs after a fall., (Copyright © 2014 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Impaired balance is a major problem in patients with idiopathic Parkinson's disease (PD) resulting in an increased risk of falls and fall-related fractures. Most studies which analyzed the risk of femoral fractures in patients with idiopathic PD were performed either in specialized centers or excluded very frail patients. The current study used a large population-based dataset in order to analyze the risk of femoral fractures in patients with idiopathic PD., Methods: Data from more than 880.000 individuals aged 65 years or older and insured between 2004 and 2009 at a large German health insurance company were used for the analyses. Persons with idiopathic PD were identified by the dispensing of Parkinson-specific medication and by hospital diagnoses, if available. People without PD served as the reference group. Incident femoral fractures were obtained from hospital diagnoses. Analyses were stratified by gender and information on severe functional impairment (care need) as provided by reimbursement claims., Results: Compared with the reference group, persons with idiopathic PD had a more than doubled risk to sustain a femoral fracture. The risk was higher in men (HR = 2.61; 95%-CI: 2.28-2.98) than in women (HR = 1.79; 95%-CI: 1.66-1.94). The increased risk was only observed in people without severe functional impairment. The sensitivity analysis using a refined definition of idiopathic PD patients yielded similar results., Conclusion: The findings confirm the increased risk of femoral fractures in patients with idiopathic PD. The relative risk is particularly high in male PD patients and in patients without severe functional impairment.

Background: Falls and fall-related injuries pose a major threat to older peoples' health, and are associated with increased morbidity and mortality. In the course of demographic changes, development and implementation of fall prevention strategies have been recognized as an urgent public health challenge. Various risk factors for falls and a number of effective interventions have been recognized. A substantial proportion of falls occur for people who are neither frail nor at high risk. Therefore, population-based approaches reaching the entire older population are needed., Objective: The objective of the study presented is the development, implementation, and evaluation of a population-based intervention for the prevention of falls and fall-related injuries in a medium sized city in Germany., Methods: The study is designed as a population-based approach. The intervention community is a mid sized city named Reutlingen in southern Germany with a population of 112,700 people. All community dwelling inhabitants 65 years and older are addressed. There are two main measures that are defined: (1) increase of overall physical activity, and (2) reduction of modifiable risk factors for falls such as deficits in strength and balance, home and environmental hazards, impaired vision, unsafe footwear, and improper use of assistive devices. The implementation strategies are developed in a participatory community planning process. These might include, for example, training of professionals and volunteers, improved availability of exercise classes, and education and raising awareness via newspaper, radio, or lectures., Results: The study starts in September 2010 and ends in December 2013. It is evaluated primarily by process evaluation as well as by telephone survey., Conclusions: Physical activity as a key message entails multiple positive effects with benefits on a range of geriatric symptoms. The strength of the design is the development of implementation strategies in a participatory community planning. The problems that we anticipate are the dependency on the stakeholders' willingness to participate, and the difficulty of evaluating population-based programs by hard end points.

Objectives: There are limited data on the epidemiology of pelvic fractures. The purpose of this study was to calculate incidence rates of pelvic fractures leading to hospital admission and to compare incidence rates between residents of nursing homes and community-dwelling persons with and without care need., Methods: Data were retrieved from a database of the largest health insurance company in Bavaria, Germany. Between 2004 and 2009, 10,170 pelvic fractures were observed in 751,101 women and 491,098 men. Age- and gender-specific incidence rates were calculated. Incidence rates were further stratified by setting (nursing home versus community) and functional status (no care need versus care need for those in the community). In addition, the average cumulative risk for a pelvic fracture at different ages was calculated., Results: The incidence rate increased from 0.54 and 0.38 per 1000 person-years in women and men aged 65 to 69 years to 9.35 and 4.45 per 1000 person-years in women and men aged 90 years and older, respectively. Persons living in a nursing home or living at home with care need had considerably higher incidence rates than community-dwelling older persons without care need. The average cumulative risk at the age of 65 years for an incident pelvic fracture until the age of 90 years was 6.9% in women and 2.8% in men., Conclusion: The incidence of pelvic fractures leading to hospital admission is higher in women than in men and rises dramatically with increasing age. Persons with care need have a particularly high risk for pelvic fracture., (Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Exposure to farming environments and siblings is associated with reduced risks of childhood hay fever and atopy. We explored the independence and interaction of these protective effects in the GABRIELA study., Methods: Questionnaire surveys on farming, asthma, and allergies were conducted in four central European areas among 79,888 6-12-yr-old children. Aeroallergen-specific serum IgE was measured in a stratified sample of 8,023 children. Multiple logistic regression was used to compare gradients in allergy prevalence by sibship size across three categories of exposure to farming environments., Results: The prevalence of hay fever ranged from 2% (95% confidence interval 1.6%; 2.7%) among farmers' children with more than two siblings to 12% (11.2%; 13.0%) among children with no farm exposure and no siblings. Farming families were larger on average. More siblings and exposure to farming environments independently conferred protection from hay fever and atopy. There was no substantial effect modification between family size and exposure to farming environments. The odds ratios for hay fever per additional sibling were 0.79 among unexposed non-farm children, 0.77 among farm-exposed non-farm children, and 0.72 among children from farming families (2df interaction test: p = 0.41)., Conclusion: The inverse association of exposure to farming environments with hay fever is found in all sizes of family, with no substantial tendency to saturation or synergism. This suggests that different biological mechanisms may underlie these two protective factors. Combinations of a large family and exposure to farming environments markedly reduce the prevalence of hay fever and indicate the strength of its environmental determinants., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Objective: to estimate femoral fracture rates in community-dwelling older people without care need (CCN(-)), in community-dwelling older people with care need (CCN(+)) and in residents of nursing homes (RNH) and to determine their contribution to the overall burden of femoral fractures., Methods: routine data of more than 1.2 million German people aged 65 years and more were used to calculate sex- and age-specific femoral fracture rates in the three groups CCN(-), CCN(+) and RNH. Those people receiving benefits of the long-term care insurance were defined as having care need. The percentile contribution of the three subpopulations to the overall burden of femoral fractures was determined., Results: during 5,319,438 person-years, 44,000 femoral fractures were recorded. In each of the three subpopulations female and male fracture rates increased with increasing age. Femoral fracture rates of the total subpopulations were 6.13, 34.53 and 43.05 femoral fractures/1,000 person-years in CCN(-), CCN(+) and RNH in women and 2.66, 20.34 and 31.09 in men, respectively. The contribution of people with care need to the overall burden of femoral fractures in older people was about 50%., Conclusion: the incidence of femoral fractures was considerably higher in people with care need than in people without care need. This should be considered when planning medical care or targeting preventive measures.

Background: Previous studies have demonstrated that children raised on farms are protected from asthma and allergies. It is unknown whether the farming effect is solely mediated by atopy or also affects nonatopic wheeze phenotypes., Objective: We sought to study the farm effect on wheeze phenotypes and objective markers, such as lung function and exhaled nitric oxide, and their interrelation with atopy in children., Methods: The GABRIEL Advanced Studies are cross-sectional, multiphase, population-based surveys of the farm effect on asthma and allergic disease in children aged 6 to 12 years. Detailed data on wheeze, farming exposure, and IgE levels were collected from a random sample of 8023 children stratified for farm exposure. Of those, another random subsample of 858 children was invited for spirometry, including bronchodilator tests and exhaled nitric oxide measurements., Results: We found effects of exposure to farming environments on the prevalence and degree of atopy, on the prevalence of transient wheeze (adjusted odds ratio, 0.78; 95% CI, 0.64-0.96), and on the prevalence of current wheeze among nonatopic subjects (adjusted odds ratio, 0.45; 95% CI, 0.32-0.63). There was no farm effect on lung function and exhaled nitric oxide levels in the general study population., Conclusions: Children living on farms are protected against wheeze independently of atopy. This farm effect is not attributable to improved airway size and lung mechanics. These findings imply as yet unknown protective mechanisms. They might include alterations of immune response and susceptibility to triggers of wheeze, such as viral infections., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Objectives: To investigate the effect of dog and cat contacts on the frequency of respiratory symptoms and infections during the first year of life., Methods: In this birth cohort study, 397 children were followed up from pregnancy onward, and the frequency of respiratory symptoms and infections together with information about dog and cat contacts during the first year of life were reported by using weekly diaries and a questionnaire at the age of 1 year. All the children were born in eastern or middle Finland between September 2002 and May 2005., Results: In multivariate analysis, children having dogs at home were healthier (ie, had fewer respiratory tract symptoms or infections) than children with no dog contacts (adjusted odds ratio, [aOR]: 1.31; 95% confidence interval [CI]: 1.13-1.52). Furthermore, children having dog contacts at home had less frequent otitis (aOR: 0.56; 95% CI: 0.38-0.81) and tended to need fewer courses of antibiotics (aOR: 0.71; 95% CI: 0.52-0.96) than children without such contacts. In univariate analysis, both the weekly amount of contact with dogs and cats and the average yearly amount of contact were associated with decreased respiratory infectious disease morbidity., Conclusions: These results suggest that dog contacts may have a protective effect on respiratory tract infections during the first year of life. Our findings support the theory that during the first year of life, animal contacts are important, possibly leading to better resistance to infectious respiratory illnesses during childhood.

Background: Environmental factors can affect the development of atopic dermatitis, and this was described to be already effective during pregnancy and in early life. An important early postnatal exposure is nutrition, although its association with allergic disease remains unclear., Objective: We sought to determine prospectively whether early postnatal exposures, such as the introduction to complementary food in the first year of life, are associated with the development of atopic dermatitis, taking into account the reverse causality., Methods: One thousand forty-one children who participated in the Protection Against Allergy-Study in Rural Environments birth cohort study were included in the current study. Atopic dermatitis was defined by a doctor's diagnosis reported by the parents of children up to 4 years of age, by questionnaires, and/or by positive SCORAD scores from 1 year of age and according to the age of onset within or after the first year of life. Feeding practices were reported by parents in monthly diaries between the 3rd and 12th months of life., Results: The diversity of introduction of complementary food in the first year of life was associated with a reduction in the risk of having atopic dermatitis with onset after the first year of life (adjusted odds ratio for atopic dermatitis with each additional major food item introduced, 0.76; 95% CI, 0.65-0.88). The introduction of yogurt in the first year of life also reduced the risk for atopic dermatitis (adjusted odds ratio, 0.41; 95% CI, 0.23-0.73)., Conclusion: As early-life exposure, the introduction of yogurt and the diversity of food introduced in the first year of life might have a protective effect against atopic dermatitis., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Studies on the association of farm environments with asthma and atopy have repeatedly observed a protective effect of farming. However, no single specific farm-related exposure explaining this protective farm effect has consistently been identified., Objective: We sought to determine distinct farm exposures that account for the protective effect of farming on asthma and atopy., Methods: In rural regions of Austria, Germany, and Switzerland, 79,888 school-aged children answered a recruiting questionnaire (phase I). In phase II a stratified random subsample of 8,419 children answered a detailed questionnaire on farming environment. Blood samples and specific IgE levels were available for 7,682 of these children. A broad asthma definition was used, comprising symptoms, diagnosis, or treatment ever., Results: Children living on a farm were at significantly reduced risk of asthma (adjusted odds ratio [aOR], 0.68; 95% CI, 0.59-0.78; P< .001), hay fever (aOR, 0.43; 95% CI, 0.36-0.52; P< .001), atopic dermatitis (aOR, 0.80; 95% CI, 0.69-0.93; P= .004), and atopic sensitization (aOR, 0.54; 95% CI, 0.48-0.61; P< .001) compared with nonfarm children. Whereas this overall farm effect could be explained by specific exposures to cows, straw, and farm milk for asthma and exposure to fodder storage rooms and manure for atopic dermatitis, the farm effect on hay fever and atopic sensitization could not be completely explained by the questionnaire items themselves or their diversity., Conclusion: A specific type of farm typical for traditional farming (ie, with cows and cultivation) was protective against asthma, hay fever, and atopy. However, whereas the farm effect on asthma could be explained by specific farm characteristics, there is a link still missing for hay fever and atopy., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: It is unclear which weather parameters effect the motion-sensor-based measurement of physical activity in terms of walking duration in older people., Methods: Between March 2009 and April 2010, the physical activity of 1324 German community-dwelling older people (≥65 years, 56.4% men) was recorded over 5 days using accelerometers. Multilevel linear regression analysis was used to estimate the effect of local daily weather parameters (daylight, maximum temperature, total global radiation, average precipitation, average wind speed and average humidity) on walking duration., Results: Mean daily walking duration was comparable for men and women, with 104.4±50.7 min and 102.9±47.8 min, respectively. A linear relationship with walking duration was seen for all considered weather parameters. The strongest effect was found for global radiation, which involved an increase in walking duration of 16.1 min in men and 19.2 min in women between an average winter day (with about 0.8 kWh/m(2) radiation) and an average summer day (with about 6 kWh/m(2) radiation); similar patterns were found for daily maximum temperature and daylight. Furthermore, physical activity decreased significantly with increasing wind speed, precipitation and humidity., Conclusions: Studies on physical activity in community dwelling older people should consider weather conditions.

Objective: Falls and fall-related injuries are leading problems in residential aged care facilities. The objective of this study was to provide descriptive data about falls in nursing homes., Design/setting/participants: Prospective recording of all falls over 1 year covering all residents from 528 nursing homes in Bavaria, Germany., Measurements: Falls were reported on a standardized form that included a facility identification code, date, time of the day, sex, age, degree of care need, location of the fall, and activity leading to the fall. Data detailing homes' bed capacities and occupancy levels were used to estimate total person-years under exposure and to calculate fall rates. All analyses were stratified by residents' degree of care need., Results: More than 70,000 falls were recorded during 42,843 person-years. The fall rate was higher in men than in women (2.18 and 1.49 falls per person-year, respectively). Fall risk differed by degree of care need with lower fall risks both in the least and highest care categories. About 75% of all falls occurred in the residents' rooms or in the bathrooms and only 22% were reported within the common areas. Transfers and walking were responsible for 41% and 36% of all falls respectively. Fall risk varied during the day. Most falls were observed between 10 am and midday and between 2 pm and 8 pm., Conclusion: The differing fall risk patterns in specific subgroups may help to target preventive measures., (Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Farm milk consumption has been identified as an exposure that might contribute to the protective effect of farm life on childhood asthma and allergies. The mechanism of action and the role of particular constituents of farm milk, however, are not yet clear., Objective: We sought to investigate the farm milk effect and determine responsible milk constituents., Methods: In rural regions of Germany, Austria, and Switzerland, a comprehensive questionnaire about farm milk consumption and other farm-related exposures was completed by parents of 8334 school-aged children, and 7606 of them provided serum samples to assess specific IgE levels. In 800 cow's milk samples collected at the participants' homes, viable bacterial counts, whey protein levels, and total fat content were analyzed. Asthma, atopy, and hay fever were associated to reported milk consumption and for the first time to objectively measured milk constituents by using multiple regression analyses., Results: Reported raw milk consumption was inversely associated to asthma (adjusted odds ratio [aOR], 0.59; 95% CI, 0.46-0.74), atopy (aOR, 0.74; 95% CI, 0.61-0.90), and hay fever (aOR, 0.51; 95% CI, 0.37-0.69) independent of other farm exposures. Boiled farm milk did not show a protective effect. Total viable bacterial counts and total fat content of milk were not significantly related to asthma or atopy. Increased levels of the whey proteins BSA (aOR for highest vs lowest levels and asthma, 0.53; 95% CI, 0.30-0.97), α-lactalbumin (aOR for interquartile range and asthma, 0.71; 95% CI, 0.52-0.97), and β-lactoglobulin (aOR for interquartile range and asthma, 0.62; 95% CI, 0.39-0.97), however, were inversely associated with asthma but not with atopy., Conclusions: The findings suggest that the protective effect of raw milk consumption on asthma might be associated with the whey protein fraction of milk., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Exposure to farming environments has been shown to protect substantially against asthma and atopic disease across Europe and in other parts of the world. The GABRIEL Advanced Surveys (GABRIELA) were conducted to determine factors in farming environments which are fundamental to protecting against asthma and atopic disease. The GABRIEL Advanced Surveys have a multi-phase stratified design. In a first-screening phase, a comprehensive population-based survey was conducted to assess the prevalence of exposure to farming environments and of asthma and atopic diseases (n = 103,219). The second phase was designed to ascertain detailed exposure to farming environments and to collect biomaterial and environmental samples in a stratified random sample of phase 1 participants (n = 15,255). A third phase was carried out in a further stratified sample only in Bavaria, southern Germany, aiming at in-depth respiratory disease and exposure assessment including extensive environmental sampling (n = 895). Participation rates in phase 1 were around 60% but only about half of the participating study population consented to further study modules in phase 2. We found that consenting behaviour was related to familial allergies, high parental education, wheeze, doctor diagnosed asthma and rhinoconjunctivitis, and to a lesser extent to exposure to farming environments. The association of exposure to farm environments with asthma or rhinoconjunctivitis was not biased by participation or consenting behaviour. The GABRIEL Advanced Surveys are one of the largest studies to shed light on the protective 'farm effect' on asthma and atopic disease. Bias with regard to the main study question was able to be ruled out by representativeness and high participation rates in phases 2 and 3. The GABRIEL Advanced Surveys have created extensive collections of questionnaire data, biomaterial and environmental samples promising new insights into this area of research., (© 2011 Blackwell Publishing Ltd.)

Objectives: To evaluate the effectiveness of a multifactorial intervention to reduce the use of physical restraints in residents of nursing homes., Design: Cluster-randomized controlled trial., Setting: Forty-five nursing homes in Germany., Participants: Three hundred thirty-three residents who were being restrained at the start of the intervention., Intervention: Persons responsible for the intervention in the nursing homes attended a 6-hour training course that included education about the reasons restraints are used, the adverse effects, and alternatives to their use. Technical aids, such as hip protectors and sensor mats, were provided. The training was designed to give the change agents tools for problem-solving to prevent behavioral symptoms and injuries from falls without using physical restraints., Measurements: The main outcome was the complete cessation of physical restraint use on 3 consecutive days 3 months after the start of the intervention. Secondary outcomes were partial reductions in restraint use, percentage of fallers, number of psychoactive drugs, and occurrence of behavioral symptoms., Results: The probability of being unrestrained in the intervention group (IG) was more than twice that in the control group (CG) at the end of the study (odds ratio=2.16, 95% confidence interval=1.05-4.46). A partial reduction of restraint use was also about twice as often achieved in the IG as in the CG. No negative effect was observed regarding medication or behavioral symptoms. The percentage of fallers was higher in the IG., Conclusion: The intervention reduced restraint use without a significant increase in falling, behavioral symptoms, or medication., (© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.)

Background: Cross-sectional studies have suggested that prenatal farm exposures might protect against allergic disease and increase the expression of receptors of the innate immune system. However, epidemiologic evidence supporting the association with atopic dermatitis remains inconsistent., Objective: To study the association between prenatal farm-related exposures and atopic dermatitis in a prospective study. We further analyzed the association between the expression of innate immune genes at birth and atopic dermatitis., Methods: A total of 1063 children who participated in a birth cohort study, Protection against Allergy-Study in Rural Environments, were included in this study. Doctor diagnosis of atopic dermatitis was reported by the parents from 1 to 2 years of age by questionnaire. Gene expression of Toll-like receptors (TLRs) and CD14 was assessed in cord blood leukocytes by quantitative PCR., Results: Maternal contact with farm animals and cats during pregnancy had a significantly protective effect on atopic dermatitis in the first 2 years of life. The risk of atopic dermatitis was reduced by more than half among children with mothers having contact with 3 or more farm animal species during pregnancy compared with children with mothers without contact (adjusted odds ratio, 0.43; 95% CI, 0.19-0.97). Elevated expression of TLR5 and TLR9 in cord blood was associated with decreased doctor diagnosis of atopic dermatitis. A significant interaction between polymorphism in TLR2 and prenatal cat exposure was observed in atopic dermatitis., Conclusion: Maternal contact with farm animals and cats during pregnancy has a protective effect on the development of atopic dermatitis in early life, which is associated with a lower expression of innate immune receptors at birth., (Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Asthma is a disease in which both genetic and environmental factors play important roles. The farming environment has consistently been associated with protection from childhood asthma and atopy, and interactions have been reported with polymorphisms in innate immunity genes., Objective: To detect gene-environment interactions for asthma and atopy in the farming environment., Methods: We performed a genome-wide interaction analysis for asthma and atopy by using 500,000 genotyped single nucleotide polymorphisms (SNPs) and farm-related exposures in 1708 children from 4 rural regions of Central Europe. We also tested selectively for interactions between farm exposures and 7 SNPs that emerged as genome-wide significant in a large meta-analysis of childhood asthma and 5 SNPs that had been reported previously as interacting with farm exposures for asthma or atopy., Results: Neither the asthma-associated SNPs nor the SNPs previously published for interactions with asthma showed significant interactions. The genome-wide interaction study did not reveal any significant interactions with SNPs within genes in the range of interacting allele frequencies from 30% to 70%, for which our study was well powered. Among rarer SNPs, we identified 15 genes with strong interactions for asthma or atopy in relation to farming, contact with cows and straw, or consumption of raw farm milk., Conclusion: Common genetic polymorphisms are unlikely to moderate the protective influence of the farming environment on childhood asthma and atopy, but rarer variants, particularly of the glutamate receptor, metabotropic 1 gene, may do so. Given the limited statistical power of our study, these findings should be interpreted with caution before being replicated in independent farm populations., (Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Rationale: Bronchial responsiveness is an objectively measurable trait related to asthma. Its prevalence and association with asthma symptoms among children in many countries are unknown., Objectives: To investigate international variations in bronchial responsiveness (BR) and their associations with asthma symptoms and atopic sensitization., Methods: Bronchial challenge tests were conducted in 6,826 schoolchildren (aged 8-12 years) in 16 countries using hypertonic (4.5%) saline. FEV(1) was measured at baseline and after inhalation for 0.5, 1, 2, 4, and 8 min. BR was analyzed both as a dichotomous (bronchial hyperreactivity, BHR, at least 15% decline in FEV(1)) and as a continuous variable (time-response slope, BR slope, individual decline in FEV(1) per log(min))., Results: Prevalence of wheeze last year ranged from 4.4% in Tirana (Albania) to 21.9% in Hawkes Bay (New Zealand) and of BHR from 2.1% in Tirana to 48% in Mumbai (India). The geometric mean BR slope varied between 3.4%/log(min) in Tirana and 12.8%/log(min) in Mumbai and Rome (Italy). At the individual level, BHR was positively associated with wheeze during the past 12 months both in affluent countries (OR = 3.6; 95% CI: 2.7-5.0) and non-affluent countries (OR = 3.0; 1.6-5.5). This association was more pronounced in atopic children. There was a correlation (rho = 0.64, P = 0.002) between center-specific mean BR slope and wheeze prevalence in atopic, but not in non-atopic children., Conclusions: BR to saline in children varied considerably between countries. High rates of BR were not confined to affluent countries nor to centers with high prevalences of asthma symptoms. The association between wheeze and BHR at the individual level differed across centers and this heterogeneity can be largely explained by effect modification by atopy. Pediatr. Pulmonol. 2010; 45:796-806. (c) 2010 Wiley-Liss, Inc., (Copyright 2010 Wiley-Liss, Inc.)

Purpose: To evaluate the effects of fluid administration on microcirculatory alterations in sepsis., Methods: With a Sidestream Dark Field device, we evaluated the effects of fluids on the sublingual microcirculation in 60 patients with severe sepsis. These patients were investigated either within 24 h (early, n = 37) or more than 48 h (late, n = 23) after a diagnosis of severe sepsis. Hemodynamic and microcirculatory measurements were obtained before and 30 min after administration of 1,000 ml Ringer's lactate (n = 29) or 400 ml 4% albumin (n = 31) solutions., Results: Fluid administration increased perfused small vessel density from 3.5 (2.9-4.3) to 4.4 (3.7-4.9) n/mm (p < 0.01), through a combined increase in the proportion of perfused small vessels from 69 (62-76) to 79 (71-83) %, p < 0.01) and in small vessel density from 5.3 (4.4-5.9) to 5.6 (4.8-6.3) n/mm (p < 0.01). Importantly, microvascular perfusion increased in the early but not in the late phase of sepsis: the proportion of perfused small vessels increased from 65 (60-72) to 80 (75-84) % (p < 0.01) in the early phase and from 75 (66-80) to 74 (67-81) (p = ns) in the late phase. These microvascular effects of fluids were not related to changes in cardiac index (R(2) = 0.05, p = ns) or mean arterial pressure (R(2) = 0.04, p = ns)., Conclusions: In this non-randomized trial, fluid administration improved microvascular perfusion in the early but not late phase of sepsis. This effect is independent of global hemodynamic effects and of the type of solution.

Background: Traditional farming represents a unique model situation to investigate the relationship of early-life farm-related exposure and allergy protection., Objectives: To investigate associations between maternal farm exposures and cytokine production in cord blood (CB) mononuclear cells in a prospective multinational birth cohort of 299 farm and 326 nonfarm children and their families., Methods: Supernatants from phorbol 12-myristate 13-acetate/ionomycin-stimulated CB mononuclear cells were assessed for the production of IFN-gamma, TNF-alpha, IL-5, IL-10, and IL-12., Results: Significantly higher levels of IFN-gamma and TNF-alpha in farm compared with nonfarm children were found, whereas IL-5, IL-10, and IL-12 levels did not differ between study groups. Maternal contact with different farm animal species and barns and consumption of farm-produced butter during pregnancy enhanced the production of proinflammatory CB cytokines, whereas maternal consumption of farm-produced yogurt resulted in significant lower levels of IFN-gamma and TNF-alpha in umbilical blood., Conclusion: Maternal exposure to farming activities and farm dairy products during pregnancy modulated cytokine production patterns of offspring at birth., (Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

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.

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).

Background: Children from farming families have less allergies than their peers. Consumption of farm milk or unpasteurized milk has been shown to explain (part of) the farming effect or protect against allergies independent of farming status., Objectives: We investigated whether the protective effect of farm milk consumption can be explained by higher levels of bacterial endotoxin in milk., Methods: We measured endotoxin in approximately 400 farm milk and shop milk samples from farming and non-farming families, respectively, with the kinetic chromogenic Limulus Amebocyte Lysate test and compared endotoxin levels between groups defined by farming status and type of milk (farm milk/shop milk)., Results: Endotoxin levels were significantly higher in milk samples from non-farming families compared to farming families [adjusted geometric means ratio (95% confidence interval)=2.61 (1.53-4.43)]. No significant difference in endotoxin levels was found between shop milk and farm milk samples [adjusted geometric means ratio (95% confidence interval)=1.56 (0.94-2.58)]. The difference between farming and non-farming families could be explained completely for farm milk and partially for shop milk by storage conditions and temperature during transportation to the fieldworker's home., Conclusion: The farming effect and the effect of farm milk consumption cannot be explained by higher levels of endotoxin in milk from farmers and farm milk, respectively.

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.

Background: It is currently discussed whether allergic sensitization may start in utero under the influence of the maternal immune system and environmental determinants., Objective: To investigate the relationship between allergen-specific cord blood (CB) IgE levels, parental sensitization, CB cytokine production, and environmental influences., Methods: As part of an ongoing multicenter birth cohort study, allergen-specific IgE antibodies against 20 common seasonal, perennial, and food allergens were measured in blood samples from 922 neonates, 922 mothers, and 835 fathers. Supernatants from stimulated CB cells were assessed for the production of IL-5, IFN-gamma, IL-10, and TNF-alpha., Results: Allergen-specific IgE antibodies were detectable in 23.9% of newborns. Contamination with maternal serum was excluded by several means of analyses, including the absence of IgA antibodies. Clear correlation between maternal and fetal IgE was found only for hen's egg, cow's milk, and soybean allergen. Fetal IgE correlated negatively with the level of IFN-gamma production, but not with IL-5 and IL-10., Conclusion: Allergen-specific IgE antibodies most probably of fetal origin are detectable in CB and correlate with a lowered CB IFN-gamma production.

Background: Previous cross-sectional surveys have suggested that maternal exposure to animal sheds during pregnancy exerted a protective effect on atopic sensitization in children lasting until school age., Objective: We sought to evaluate the effects of maternal exposure to animal sheds and other farm-related exposures during pregnancy on cord blood IgE levels in a prospective birth cohort., Methods: Pregnant women living in rural areas in Austria, Finland, France, Germany, and Switzerland were recruited in the third trimester of pregnancy. Information on maternal farm-related exposures, nutrition, and health during pregnancy was obtained by means of interviews. Specific IgE levels for food and common inhalant allergens were assessed in cord blood of 922 children and peripheral blood samples of their mothers., Results: Different sensitization patterns in cord blood of farm and nonfarm children were observed. In multivariable analysis consumption of boiled, but not unboiled, farm milk during pregnancy was positively associated with specific IgE to cow's milk independently from maternal IgE. In contrast, there was an inverse relationship between maternal exposure to animal sheds and cord blood IgE levels against seasonal allergens (adjusted odds ratio, 0.38; 95% CI, 0.21-0.70). This association was not confounded by maternal IgE levels. Maternal contact with hay enhanced the protective effect of exposure to animal sheds on IgE levels to grass pollen in cord blood., Conclusions: Maternal exposure during pregnancy influences atopic sensitization patterns in cord blood. The (microbial) context of allergen contact possibly modifies the risk of atopic sensitization.

Objectives: To evaluate the effectiveness of a multifactorial fall prevention program in prespecified subgroups of nursing home residents., Design: Secondary analysis of a cluster-randomized, controlled trial., Setting: Six nursing homes in Germany., Participants: Seven hundred twenty-five long-stay residents; median age 86; 80% female., Intervention: Staff and resident education on fall prevention, advice on environmental adaptations, recommendation to wear hip protectors, and progressive balance and resistance training., Measurements: Time to first fall and the number of falls. Falls were assessed during the 12-month intervention period. Univariate regression analyses were performed, including a confirmatory test of interaction., Results: The intervention was more effective in people with cognitive impairment (hazard ratio (HR)=0.49, 95% confidence interval (CI)=0.35-0.69) than in those who were cognitively intact (HR=0.91, 95% CI=0.68-1.22), in people with a prior history of falls (HR=0.47, 95% CI=0.33-0.67) than in those with no prior fall history (HR=0.77, 95% CI=0.58-1.01), in people with urinary incontinence (HR=0.59, 95% CI=0.45-0.77) than in those with no urinary incontinence (HR=0.98, 95% CI=0.68-1.42), and in people with no mood problems (incidence rate ratio (IRR)=0.41, 95% CI=0.27-0.61) than in those with mood problems (IRR=0.74, 95% CI=0.51-1.09)., Conclusion: The effectiveness of a multifactorial fall prevention program differed between subgroups of nursing home residents. Cognitive impairment, a history of falls, urinary incontinence, and depressed mood were important in determining response.

Background: Obesity is associated with substantial metabolic changes and subclinical inflammation. We explored associations between body mass index (BMI) and cardiometabolic biomarkers and their clustering in overweight and obese schoolchildren., Methods: In this population-based, cross-sectional study among 450 children 10 years old, we measured adiponectin, leptin, inflammatory markers, apolipoprotein (apo) AI and B, and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)). Except for adiponectin and apoAI (10th percentile) the 90th percentile was used as cutoff point. Body weight was categorized in age- and sex-specific BMI percentiles and overweight and obesity according to International Obesity Task Force definitions., Results: In linear regression models, all cardiometabolic markers except apoB were statistically significantly associated with overweight. In logistic regression models, compared with the reference category (25th-75th percentile of BMI), overweight was associated with increased concentrations of leptin [odds ratio (OR) 59.80; 95% CI 16.68-214.39], C-reactive protein (6.30; 2.95-13.45), fibrinogen (2.82; 1.33-6.01), and low apoAI (2.62; 1.19-5.75). Overweight was positively associated with interleukin-6, Lp-PLA(2), and apoB concentrations and inversely with adiponectin concentrations. Most importantly, in obese children 35% showed one, 20% two, 10% three, and 15% four or more abnormal cardiometabolic biomarkers. The number of abnormal cardiometabolic markers increased in overweight (p(trend) <0.001) and obese (p(trend) <0.001) children., Conclusions: Overweight and obesity in children are associated with complex metabolic changes and a low-grade inflammatory response, and thus might not only accelerate cardiovascular disease later on, but may also be associated with the initiation of atherosclerosis in early life.

Background: The association between allergic sensitization and eczema has been debated for years., Objective: We sought to determine and compare the strength of the association between allergen skin sensitization and eczema in both developing and industrialized countries., Methods: Twenty-eight thousand five hundred ninety-one randomly selected 8- to 12-year-old schoolchildren in 20 countries were physically examined for flexural eczema and received skin prick testing to Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat hair, Alternaria tenuis, mixed tree and grass pollen, and allergens of local relevance., Results: The age- and sex-adjusted odds ratios (ORs) for a positive association between flexural eczema and atopy ranged between 0.74 (95% CI, 0.31-1.81) and 4.53 (95% CI, 1.72-11.93), with a significantly stronger association in affluent compared with nonaffluent countries (combined age- and sex-adjusted OR(affluent) = 2.69 [95% CI, 2.31-3.13] and OR(nonaffluent) = 1.17 [95% CI, 0.81-1.70]). The combined population attributable fraction for atopy in flexural eczema was 27.9% for affluent and 1.2% for nonaffluent-country centers. Correlating gross national per-capita income with either ORs or population attributable fractions for atopy in flexural eczema confirmed a highly significant positive association (P = .006 and P < .001, respectively)., Conclusions: The association between atopy and flexural eczema is weak and more variable than previously suggested, and the strength of this association is positively linked to gross national income.

Background: Between 1962 and 2002 the average life expectancy in Germany has increased from 67.1 years to 75.6 years in men and from 72.7 years to 81.3 in women., Methods: The cumulative and annual contributions of different age- and disease-groups on life expectancy were calculated using Pollard's actuarial method of decomposing mortality rates. Mortality data were provided by the German Statistical Office., Results: Considering the cumulative contribution over the period of 40 years, the largest contributions came from persons with at least 65 years of age (2.9 years in men and 4.0 years in women). Reductions in cardiovascular disease mortality had the greatest cumulative impact on life expectancy (2.7 years in men and 3.0 years in women). The contribution from reduced cancer mortality on life expectancy was substantially lower (0.6 and 0.9 years, respectively). The annual contributions of several disease-groups varied considerably over time. The positive contribution from cardiovascular diseases started only after 1970, and in men it became solid only after 1980. Regarding malignant neoplasms, the largest cumulative contribution came from stomach cancer (0.4 in both sexes). The annual analyses showed increasing contributions from reduced cancer mortality after 1990. These were strongly influenced by lung, stomach, prostate and colorectal cancer in men, and by breast, colorectal and stomach cancer in women., Conclusions: While life expectancy has increased by about 2.2 years per decade the observed variations in the age- and disease-specific contributions over time have implications for future health care planning and prevention strategies.

Rationale: Atopic sensitization has long been known to be related to asthma in children, but its role in determining asthma prevalence remains to be elucidated further., Objectives: To investigate the role of atopic sensitization in the large international variation in the prevalence of childhood asthma., Methods: Cross-sectional studies of random samples of 8- to 12-year-old children (n = 1,000 per center) were performed according to the standardized methodology of Phase Two of the International Study of Asthma and Allergy in Childhood (ISAAC). Thirty study centers in 22 countries worldwide participated and reflect a wide range of living conditions, from rural Africa to urban Europe. Data were collected by parental questionnaires (n = 54,439), skin prick tests (n = 31,759), and measurements of allergen-specific IgE levels in serum (n = 8,951). Economic development was assessed by gross national income per capita (GNI)., Measurements and Main Results: The prevalence of current wheeze (i.e., during the past year) ranged from 0.8% in Pichincha (Ecuador) to 25.6% in Uruguaiana (Brazil). The fraction of current wheeze attributable to atopic sensitization ranged from 0% in Ankara (Turkey) to 93.8% in Guangzhou (China). There were no correlations between prevalence rates of current wheeze and atopic sensitization, and only weak correlations of both with GNI. However, the fractions and prevalence rates of wheeze attributable to skin test reactivity correlated strongly with GNI (Spearman rank-order coefficient rho = 0.50, P = 0.006, and rho = 0.74, P < 0.0001, respectively). In addition, the strength of the association between current wheeze and skin test reactivity, assessed by odds ratios, increased with GNI (rho = 0.47, P = 0.01)., Conclusions: The link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development.

Measurement of bronchial responsiveness to hypertonic saline was applied in 22 study centers worldwide as part of Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC Phase Two). Because the amount of inhaled saline was difficult to standardize during the stepwise protocol with inhalation periods of increasing duration, we evaluated different statistical procedures based on inhalation time in relation to wheeze and current asthma. Data on random samples on 9 to 11-year-old children (n = 1,418) from two German centers were analyzed. The following statistical approaches were evaluated: (1) bronchial hyperreactivity (BHR) defined dichotomously as a fall in FEV1 (forced expiratory volume in 1 s) >or=15%; (2) PT15: the provocation time causing BHR using survival-analyses methods; (3) time-response-slope (continuous) of the individual FEV1-courses calculated by a linear model after comparing different mathematical models. The sensitivity and specificity of BHR versus current asthma were 47% and 87%, respectively. Analyses of the provocation time indicated an increased risk (adjusted hazard-ratio: 4.3; 95% CI: 2.8-6.5) for a fall in FEV1 >or= 15% among children with current asthma in comparison to those without. The time-response-slope differed markedly between children with and without wheeze and current asthma (P < 0.0001). BHR is meaningful and relatively easy to use, but has low sensitivity. Time-response-slopes utilize the available information from the stepwise protocol better than BHR and survival-analysis based on PT15. Response parameters based on inhalation time discriminate well between children with and without asthma and will be compared in the analyses of ISAAC Phase Two data., ((c) 2006 Wiley-Liss, Inc.)