Population-Based Evidence for the Use of Serum Neurofilaments as Individual Diagnostic and Prognostic Biomarkers in Amyotrophic Lateral Sclerosis.

OBJECTIVE: Neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains (pNfH), established as diagnostic and prognostic biomarkers in hospital-based amyotrophic lateral sclerosis (ALS) cohorts, are now surrogate markers in clinical trials. This study extends their evaluation to a population level, with the aim of advancing their full establishment and assessing the transferability of biomarker findings from controlled cohorts to real-world ALS populations. METHODS: We measured serum NfL and pNfH levels in all ALS patients (n = 790) and general population controls (n = 570) with available baseline samples participating in the epidemiological ALS Registry Swabia, providing platform-specific (ELLA™) reference data and Z-scores for controls, as well as reference data, disease-specific Z-scores and longitudinal data in ALS. We evaluated the diagnostic and prognostic utility of neurofilaments and quantified the impact of ALS-related factors and non-ALS confounders. RESULTS: Neurofilaments showed high diagnostic and prognostic utility at the population level, with NfL superior to pNfH. The novel concept of a population-based ALS Z-score significantly improved the prognostic utility compared to absolute raw values. Both biomarkers increased more strongly with age in controls than in ALS, and age adjustment improved diagnostic accuracy. Our data show that disease progression rates, ALS phenotype, body mass index (BMI), and renal function need to be considered when interpreting neurofilament levels; longitudinal neurofilament levels were generally stable in individual patients, especially when adjusted for age and baseline levels. INTERPRETATION: Population-based assessment enhances the utility of particularly serum NfL as a diagnostic and prognostic biomarker in ALS and improves the translation of findings from controlled cohorts to real-world populations. ANN NEUROL 2024.

Evaluation of costs, osteoporosis treatment, and re-fractures in German collaborative orthogeriatric care after fragility fractures.

Orthogeriatric co-management (OGCM) may provide benefits for geriatric fragility fracture patients in terms of more frequent osteoporosis treatment and fewer re-fractures. Yet, we did not find higher costs in OGCM hospitals for re-fractures or antiosteoporotic medication for most fracture sites within 12 months, although antiosteoporotic medication was more often prescribed. PURPOSE: Evidence suggests benefits of orthogeriatric co-management (OGCM) for hip fracture patients. Yet, evidence for other fractures is rare. The aim of our study was to conduct an evaluation of economic and health outcomes after the German OGCM for geriatric fragility fracture patients. METHODS: This retrospective cohort study was based on German health and long-term care insurance data. Individuals were 80 years and older, sustained a fragility fracture in 2014-2018, and were treated in hospitals certified for OGCM (ATZ group), providing OGCM without certification (OGCM group) or usual care (control group). Healthcare costs from payer perspective, prescribed medications, and re-fractures were investigated within 6 and 12 months. We used weighted gamma and two-part models and applied entropy balancing to account for the lack of randomization. All analyses were stratified per fracture site. RESULTS: We observed 206,273 patients within 12-month follow-up, of whom 14,100 were treated in ATZ, 133,353 in OGCM, and 58,820 in other hospitals. Total average inpatient costs per patient were significantly higher in the OGCM and particularly ATZ group for all fracture sites, compared to control group. We did not find significant differences in costs for re-fractures or antiosteoporotic medication for most fracture sites, although antiosteoporotic medication was significantly more often observed in the OGCM and particularly ATZ group for hip, pelvic, and humerus fractures. CONCLUSION: The observed healthcare costs were higher in ATZ and OGCM hospitals within 12 months. Antiosteoporotic medication was prescribed more often in both groups for most fracture sites, although the corresponding medication costs did not increase.

Pre-existing sleep problems as a predictor of post-acute sequelae of COVID-19.

Several months after COVID-19 many individuals still report persisting symptoms, the so-called 'post-COVID-19 syndrome'. An immunological dysfunction is one of the main pathophysiological hypotheses. As sleep is central to the functioning of the immune system, we investigated whether self-reported pre-existing sleep disturbance might be an independent risk factor for the development of post-COVID-19 syndrome. A total of 11,710 participants of a cross-sectional survey (all tested positive for severe acute respiratory syndrome coronavirus-2) were classified into probable post-COVID-19 syndrome, an intermediate group, and unaffected participants at an average of 8.5 months after infection. The case definition was based on newly occurring symptoms of at least moderate severity and ≥20% reduction in health status and/or working capacity. Unadjusted and adjusted odds ratios were calculated to investigate the association between pre-existing sleep disturbances and subsequent development of post-COVID-19 syndrome while controlling for a variety of demographic, lifestyle, and health factors. Pre-existing sleep disturbances were found to be an independent predictor of subsequent probable post-COVID-19 syndrome (adjusted odds ratio 2.7, 95% confidence interval 2.27-3.24). Sleep disturbances as part of the post-COVID-19 syndrome were reported by more than half of the participants and appeared to be a new symptom and to occur independent of a mood disorder in most cases. Recognition of disturbed sleep as an important risk factor for post-COVID-19 syndrome should promote improved clinical management of sleep disorders in the context of COVID-19. Further, it may stimulate further research on the effect of improving sleep on the prognosis of COVID-19 long-term sequelae and other post-viral conditions.

Effects of exercise referral schemes enhanced with behavioural self-management strategies on functional capacity and self-reported disability in community-dwelling older adults. Secondary results from the SITLESS multi-country, three-armed randomized controlled trial.

BACKGROUND: Exercise referral schemes (ERS) are an effective strategy for increasing physical activity (PA) in older adults. Behavioural self-management strategies (SMS) may augment the maintenance of PA and associated benefits in this population, resulting in preservation of the functional capacity and prevention of disability over the long-term. AIM: The primary aim was to investigate the long-term (22-months) effects of ERS enhanced with SMS on functional capacity assessed by the Short Physical Performance Battery (SPPB) compared to ERS (primary comparison) and a control condition (CTRL).Secondarily, between-group effects after 4 and 16 months on the SPPB and self-reported disability outcomes were investigated. METHODS: 1360 physically inactive community-dwelling older adults ≥65 years from four European countries were randomized into (i) 16 weeks ERS enhanced with SMS (ERS-SMS), (ii) ERS alone and (iii) CTRL. In addition to SPPB, self-reported function and disability were assessed by the short-form late life function and disability index and with a six-item activity of daily living questionnaire. RESULTS: No long-term effects were found for the SPPB-score in ERS-SMS vs ERS (0.21 point, 95% CI [-0.04, 0.46]). Significant group × time effects were observed for the SPPB-score after 4 months in favour of ERS-SMS over CTRL (0.51 point, 95% CI [0.29, 0.73]) and ERS (0.46 point, 95% CI [0.24, 0.68]). CONCLUSION: The study did demonstrate differences, in favour of ERS + SMS, but on SPPB these were small, and not sustained over time. The additional effect of SMS was inconsistent and uncertain.

Association of two geriatric treatment systems with anti-osteoporotic drug treatment and second hip fracture in patients with an index hip fracture: retrospective cohort study.

BACKGROUND: In Germany, geriatricians deliver acute geriatric care during acute hospital stay and post-acute rehabilitation after transfer to a rehabilitation clinic. The rate patients receive acute geriatric care (AGC) or are transferred to post-acute rehabilitation (TPR) differs between hospitals. This study analyses the association between the two geriatric treatment systems (AGC, TPR) and second hip fracture in patients following an index hip fracture. METHODS: Nationwide health insurance data are used to identify the rate of AGC and TPR per hospital following hip fracture surgery in patients aged ≥ 80 years. Outcomes are a second hip fracture after surgery or after discharge within 180 or 360 days and new specific anti-osteoporotic drugs. Cox proportional hazard models and generalised linear models are applied. RESULTS: Data from 29,096 hip fracture patients from 652 hospitals were analysed. AGC and TPR are not associated with second hip fracture when follow-up started after surgery. However, during the first months after discharge patients from hospitals with no AGC or low rates of TPR have higher rates of second hip fracture than patients from hospitals with high rates of AGC or high rates of TPR (Hazard Ratio (95% CI) 1.35 (1.01-1.80) or 1.35 (1.03-1.79), respectively). Lower rates of AGC are associated with lower probabilities of new prescriptions of specific anti-osteoporotic drugs. CONCLUSIONS: Our study suggests beneficial relationships of geriatric treatment after hip fracture with a) the risk of second hip fractures during the first months after discharge and b) an improvement of anti-osteoporotic drug treatment.

Health-economic evaluation of orthogeriatric co-management for patients with pelvic or vertebral fragility fractures.

BACKGROUND: Orthogeriatric co-management (OGCM) addresses the special needs of geriatric fracture patients. Most of the research on OGCM focused on hip fractures while results concerning other severe fractures are rare. We conducted a health-economic evaluation of OGCM for pelvic and vertebral fractures. METHODS: In this retrospective cohort study, we used German health and long-term care insurance claims data and included cases of geriatric patients aged 80 years or older treated in an OGCM (OGCM group) or a non-OGCM hospital (non-OGCM group) due to pelvic or vertebral fractures in 2014-2018. We analyzed life years gained, fracture-free life years gained, healthcare costs, and cost-effectiveness within 1 year. We applied entropy balancing, weighted gamma and two-part models. We calculated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. RESULTS: We included 21,036 cases with pelvic (71.2% in the OGCM, 28.8% in the non-OGCM group) and 33,827 with vertebral fractures (72.8% OGCM, 27.2% non-OGCM group). 4.5-5.9% of the pelvic and 31.8-33.8% of the vertebral fracture cases were treated surgically. Total healthcare costs were significantly higher after treatment in OGCM compared to non-OGCM hospitals for both fracture cohorts. For both fracture cohorts, a 95% probability of cost-effectiveness was not exceeded for a willingness-to-pay of up to €150,000 per life year or €150,000 per fracture-free life year gained. CONCLUSION: We did not obtain distinct benefits of treatment in an OGCM hospital. Assigning cases to OGCM or non-OGCM group on hospital level might have underestimated the effect of OGCM as not all patients in the OGCM group have received OGCM.

Health-economic evaluation of orthogeriatric co-management for patients with forearm or humerus fractures: an analysis of insurance claims data from Germany.

Orthogeriatric co-management (OGCM) describes a collaboration of orthopedic surgeons and geriatricians for the treatment of fragility fractures in geriatric patients. While its cost-effectiveness for hip fractures has been widely investigated, research focusing on fractures of the upper extremities is lacking. Thus, we conducted a health economic evaluation of treatment in OGCM hospitals for forearm and humerus fractures.In a retrospective cohort study with nationwide health insurance claims data, we selected the first inpatient stay due to a forearm or humerus fracture in 2014-2018 either treated in hospitals that were able to offer OGCM (OGCM group) or not (non-OGCM group) and applied a 1-year follow-up. We included 31,557 cases with forearm (63.1% OGCM group) and 39,093 cases with humerus fractures (63.9% OGCM group) and balanced relevant covariates using entropy balancing. We investigated costs in different health sectors, length of stay, and cost-effectiveness regarding total cost per life year or fracture-free life year gained.In both fracture cohorts, initial hospital stay, inpatient stay, and total costs were higher in OGCM than in non-OGCM hospitals. For neither cohort nor effectiveness outcome, the probability that treatment in OGCM hospitals was cost-effective exceeded 95% for a willingness-to-pay of up to €150,000.We did not find distinct benefits of treatment in OGCM hospitals. Assigning cases to study groups on hospital-level and using life years and fracture-free life years, which might not adequately reflect the manifold ways these fractures affect the patients' health, as effectiveness outcomes, might have underestimated the effectiveness of treatment in OGCM hospitals.

Relationship between hemoglobin and grip strength in older adults: the ActiFE study.

INTRODUCTION: Although anemia is associated with low muscle strength, hemoglobin has been rarely studied considering ferritin. AIM: To analyze the association between hemoglobin and grip strength in community-dwelling older adults. METHODS: We used data from a German cohort of adults ≥ 65 years, excluding those with CRP > 10 mg/L or taking iron supplements. Grip strength (kg) was measured using a Jamar dynamometer. Analysis was performed using multiple linear regression, adjusted for established confounders. Due to interaction, age-stratified (< 80, 80 +), further sex-stratified analysis in those < 80 years old and ferritin-stratified in men < 80 years were performed. RESULTS: In total, 1294 participants were included in this analysis (mean age 75.5 years, 549 (42.3%) women, 910 (70.3%) < 80 years). On average, hemoglobin and grip strength were 14.9 g/dL and 41.3 kg for men, 13.9 g/dL and 25.1 kg for women. Hemoglobin was significantly positively associated with grip strength only among women < 80 years (ß 0.923 [95% CI 0.196, 1.650]). For men < 80 years, the association was significant when ferritin was ≥ 300 µg/L (ß 2.028 [95% CI 0.910, 3.146]). No association was detected among those participants 80 + . DISCUSSION AND CONCLUSIONS: Our data show an association between hemoglobin and grip strength only in women < 80 years old. For men < 80 years, the association was only significant with ferritin levels ≥ 300 µg/L. Considering the decreasing levels of hemoglobin and grip strength and the high prevalence of iron deficiency in older adults further analyses investigating this relationship with more iron specific parameters such as transferrin saturation are warranted.

Maternal child maltreatment and trajectories of offspring behavioural and emotional difficulties from age 4 to 7 years - results from a prospective birth cohort study.

Maternal experience of child maltreatment (CM) has been associated with maternal and child mental health. However, evidence about the course of child mental health and maternal CM is scarce. Therefore, this study aims to compare trajectories of mental health in children according to maternal CM exposure and maternal mental health. We included 327 mothers and their singleton child from the Ulm SPATZ Health Study, a prospective birth cohort study. Child mental health was determined by the Strength and Difficulties Questionnaire (SDQ) at the age of 4, 5, 6, and 7 years and maternal CM by the Childhood Trauma Questionnaire (CTQ). Results display that maternal CM is associated with more behavioural and emotional difficulties in children, a trend that tends to increase with older child age. The sum of maternal mental health problems across this time course mediates this association. Male child sex is associated with more mental health problems in the child and the mother. These results provide an important first insight into the relevance of maternal CM on the trajectories of mental health in the offspring and highlight the importance of chronicity and severity of maternal mental health. Further prospective research in cohorts with longer follow-ups up into adolescence and adulthood is needed.

[Cooperation of geriatrics and trauma surgery in certified geriatric trauma centers : Insights into different care models and the implementation of requirements resulting from certification]. / Zusammenarbeit von Geriatrie und Unfallchirurgie in zertifizierten alterstraumatologischen Zentren : Einblicke in unterschiedliche Versorgungsmodelle und in die Umsetzung von Anforderungen, die sich aus der Zertifizierung ergeben.

BACKGROUND: In Germany, different models of orthogeriatric co-management have been implemented in certified geriatric trauma centers. So far, it is not clear how the different models are implemented and what influence the certification has on the structures and processes within the centers. The present study examined the extent of cooperation between surgery and geriatrics and if the quality of care had changed since the certification of the centers. METHODS: In this study 4 guided focus group interviews (FGI) were conducted in different teams of certified geriatric trauma centers in 3 federal states with 16 participants. To specify the content of the FGI, two additional interviews were conducted with system auditors. Both types of interview were analyzed by content analysis. RESULTS: The certification supported the implementation of structures and processes in the different orthogeriatric models; however, the quality of care and cooperation between surgery and geriatrics depends on the spatial proximity and the orthogeriatric care model in the geriatric trauma centers. Simultaneously, challenges in the area of geriatric syndromes and the recruitment of skilled staff became relevant. DISCUSSION: The results can help to reflect processes in the certified geriatric trauma centers and to treat geriatric syndromes more effectively. In the future, the challenge will be to establish geriatric care under the existing shortage of skilled staff.

Health-Economic Evaluation of the German Osteoporotic Fracture Prevention Program in Rural Areas (OFRA): Mobility and Falls Prevention Classes, Examination of Bone Health, and Consultation on Safety in the Living Environment.

BACKGROUND: Fragility fractures are one of the leading causes of disability in older adults. Yet, evidence for effectiveness and cost-effectiveness of preventive approaches combining bone health and fall prevention is rare. OBJECTIVE: To conduct a health-economic evaluation of the German osteoporotic fracture prevention program in rural areas (OFRA). DESIGN: Secondary cluster-randomized intervention study based on routine data. PARTICIPANTS: All districts in five federal states in Germany were cluster-randomized as intervention or control districts. OFRA was offered to community-living (a) women aged 75-79 years or (b) women and men aged 70-84 years with a prior fragility fracture in the intervention districts. Individuals who meet these criteria in the control districts were assigned to the control group. INTERVENTION: OFRA comprised mobility and falls prevention classes, examination of bone health by bone density measurement, and consultation on safety in the home living environment. MAIN MEASURES: We measured health-care costs and effectiveness in terms of time to fragility fracture or death within 1 year after initial contact, based on health insurance claims data. Implementation costs were recorded by the intervention performers. We calculated an incremental cost-effectiveness ratio (ICER) and employed the net-benefit approach to construct a cost-effectiveness acceptability curve (CEAC). KEY RESULTS: There were 9408 individuals in the intervention group and 27,318 in the control group. Mean time to fragility fracture or death (difference: 0.82 days) and health-care costs (difference: 111.73€, p < .01) were reduced, but mean intervention costs (difference: 260.10€) increased total costs (difference: 148.37€, p < .001) in the intervention group. The ICER per fracture-free year of survival was 66,094.63€. The CEAC showed no acceptable probability of cost-effectiveness at a reasonable willingness to pay. CONCLUSION: OFRA showed reduced rates of fragility fractures, but had high implementation costs, resulting in an unfavorable ICER. The cost-effectiveness of OFRA may improve with a longer follow-up.

Potential sex differences in human milk fatty acids and their association with atopic dermatitis: Results of the Ulm SPATZ health study.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) in human milk are essential in immune system maturation and might play a role in the development of allergic conditions, such as atopic dermatitis (AD) in infants. Immune system responses are modulated by sex, but data on the sex-specific associations with PUFAs are limited. We therefore explored sex-specific differences in human milk PUFAs and their association with AD up to 2 years. METHODS: PUFAs were measured in human milk samples from the Ulm SPATZ Health Study at 6 weeks (n = 512) and 6 months (n = 367). Associations with AD up to 2 years were evaluated using crude and multivariable logistic regression. Interactions between infant sex and PUFAs were explored by including the product term. RESULTS: No significant associations were observed with 6-week data. At 6 months, the median relative proportion of docosahexaenoic acid (DHA) was significantly higher in milk for female than male infants (p = .001). Female infants whose milk was lower in quintile proportions of alpha-linolenic acid (ALA) at 6 months had lower odds of AD compared to males [first vs. fifth quintile OR (95% confidence interval): 0.13 (0.02, 0.66), p = .02]. This interaction was not significant when correcting for multiple testing (α threshold: p = .004). No other statistically significant associations were observed. CONCLUSION: Individual quintile PUFA proportions in human milk were not associated with AD, overall and in a sex-specific manner. More comprehensive and statistically powered longitudinal studies are needed to determine whether potential sex differences in human milk, if any, could be of clinical relevance for infants including the investigation of mediating factors.

Medical care and biomarker-based assessment of mortality in two cohorts of patients with chronic coronary syndrome 10 years apart.

BACKGROUND: This study aimed to describe the characteristics and mortality of two cohorts of patients with chronic coronary syndrome (CCS) recruited with identical study designs in the same rehabilitation clinics but approximately 10 years apart. METHODS: The KAROLA cohorts included patients with CCS participating in an inpatient cardiac rehabilitation programme in Germany (KAROLA-I: years 1999/2000, KAROLA-II: 2009-2011). Blood samples and information on sociodemographic factors, lifestyle, and medical treatment were collected at baseline, at the end of rehabilitation, and after one year of follow-up. A biomarker-based risk model (ABC-CHD model) and Cox regression analysis were used to evaluate cardiovascular (CV) and non-CV mortality risk. RESULTS: We included 1130 patients from KAROLA-I (mean age 58.7 years, 84.4% men) and 860 from KAROLA-II (mean age 60.4 years, 83.4% men). Patients in the KAROLA-I cohort had significantly higher concentrations of CV biomarkers and fewer patients were taking CV medications, except for statins. The biomarker-based ABC-CHD model provided a higher estimate of CV death risk for patients in the KAROLA-I cohort (median 3-year risk, 3.8%) than for patients in the KAROLA-II cohort (median 3-year risk, 2.7%, p-value for difference < 0.001). After 10 years of follow-up, 91 (8.1%) patients in KAROLA-I and 45 (5.2%) in KAROLA-II had died from a CV event. CONCLUSIONS: Advances in disease management over the past 20 years may have led to modest improvements in pharmacological treatment during cardiac rehabilitation and long-term outpatient care for patients with CCS. However, modifiable risk factors such as obesity have increased in the more recent cohort and should be targeted to further improve the prognosis of these patients.

Pre- and early postpartum psychosocial stress trajectories in mothers and child body mass index at 3 years: a birth cohort study.

BACKGROUND: Child overweight remains a prevalent public health concern, but the impact of maternal psychosocial stress and related constructs, the timing, and possible trajectories on child body mass index (BMI) is controversial. We aimed to investigate the association of maternal stress, depression and anxiety symptoms, and maternal hair cortisol concentrations (HCC) at delivery, 6, and 12 months postpartum with child BMI and age- and sex-standardized BMI (BMI-SDS) at age 3 years. METHODS: Data were derived from the Ulm SPATZ Health Study with a baseline examination between 04/2012 and 05/2013 at the University Medical Centre Ulm, Germany, the only maternity clinic in Ulm, with a good representation of the source population. Adjusted regression analyses based on BMI/BMI-SDS (dependent) and trajectories of stress, depression, and anxiety (independent variables) were investigated in 596 mothers and children. Multiple imputation of missing covariates was performed. RESULTS: Various trajectories in independent variables were identified, trajectories of maternal anxiety symptom differed between child sexes. We did not find an association between trajectories of maternal chronic stress, depression symptoms, or HCC and child BMI/BMI-SDS. However, trajectories of low-increasing maternal anxiety symptoms were linked to higher child BMI compared to a low-stable trajectory group (b = 0.58 kg/m2, 95% Confidence Interval: 0.11; 1.04) in girls. CONCLUSIONS: Trajectories of maternal anxiety symptoms were associated with the child's BMI/BMI-SDS in girls at age 3 years. However, further large scale studies should include variables to determine the causal pathway and enlighten sex-specific differences.

Effect of an osteoporotic fracture prevention program on fracture incidence in routine care: a cluster-randomized trial.

BACKGROUND: Fractures are a major health problem in aging societies. Preventive approaches combining bone health and fall prevention are rare. The osteoporotic fracture prevention program in rural areas (OFRA) is a health care fund-driven program for older people in randomly selected districts in Germany. The components of the program were falls prevention exercise classes, examination of bone health by a dual-energy X-ray absorptiometry (DXA) scan, and a consultation about "safety in the living environment." The aim of this study was to evaluate this complex preventive intervention in a routine health care setting. METHODS: This cluster-randomized trial was performed from October 2015 to October 2018 and took place in 186 administrative districts in five federal states, 47 districts served as intervention districts, and 139, as controls. Within these districts, we included (a) all community-living women and men aged 70-85 years with prior fragility fractures and (b) all community-living women aged 75-80 years. The analysis used routine data collected by a health insurance company. The primary endpoint was all fragility fractures combined. Fracture types, mortality, and nursing home admission were explorative endpoints. Cox frailty models were used for comparative analyses with a median follow-up time of 365 days (interquartile range: 0 days). RESULTS: Nine thousand four hundred eight individuals were approached to participate in one of the program components, 27,318 individuals served as controls. The mean age was 78.7 years. Of those approached to participate, nearly 30% joined the exercise classes. DXA measurement was reimbursed for 13.6%, and 51.8% received advice about measures to increase "safety in the living environment." The incidence of fragility fractures did not differ between the intervention and the control group (HR 0.94; 95% CI 0.80-1.11). However, femoral fractures, the most frequent fracture type, were reduced in the intervention group (HR 0.76; 95% CI 0.59-0.99). Mortality and nursing home admission did not differ between the intervention and the control group. CONCLUSIONS: A comprehensive fracture prevention program for older people living in rural areas was implemented. The program did not affect the primary endpoint of all fragility fractures combined. It has to be considered that we used a modified intention to treat approach based on geographic randomization and information about endpoints relied exclusively on routine data of the health care insurance. TRIAL REGISTRATION: German Clinical Trials Register DRKS-ID: 00009000.

Novel biomarkers of inflammation, kidney function and chronic kidney disease in the general population.

BACKGROUND: Inflammatory processes have been implicated in the development of chronic kidney disease (CKD). We investigated the association of a large panel of inflammatory biomarkers reflecting aspects of immunity with kidney function and CKD incidence. METHODS: We used data from two independent population-based studies, KORA F4 (discovery, n = 1110, mean age 70.3 years, 48.7% male) and ESTHER (replication, n = 1672, mean age 61.9 years, 43.6% male). Serum levels of biomarkers were measured using proximity extension assay technology. The association of biomarkers with estimated glomerular filtration rate (eGFR) at baseline and with incident CKD was investigated using linear and logistic regression models adjusted for cardiorenal risk factors. Independent results from prospective analyses of both studies were pooled. The significance level was corrected for multiple testing by false-discovery rate (PFDR < 0.05). RESULTS: In the KORA F4 discovery study, 52 of 71 inflammatory biomarkers were inversely associated with eGFR based on serum creatinine. Top biomarkers included CD40, TNFRSF9 and IL10RB. Forty-two of these 52 biomarkers were replicated in the ESTHER study. Nine of the 42 biomarkers were associated with incident CKD independent of cardiorenal risk factors in the meta-analysis of the KORA (n = 142, mean follow-up 6.5 years) and ESTHER (n = 103, mean follow-up 8 years) studies. Pathway analysis revealed the involvement of inflammatory and immunomodulatory processes reflecting cross-communication of innate and adaptive immune cells. CONCLUSIONS: Novel and known biomarkers of inflammation were reproducibly associated with kidney function. Future studies should investigate their clinical utility and underlying molecular mechanisms in independent cohorts.

Trajectory and determinants of agreement between parental and physicians' reports of childhood atopic dermatitis.

BACKGROUND: Parent self-administered reports are commonly used in studies on childhood atopic dermatitis (AD) but data on its validity are sparse. We aimed to examine the agreement between parent- and physician-reported measures of childhood AD throughout early life and identify the determinants. METHODS: In this prospective cohort study, we used data of 449 infants and their mothers recruited in the Ulm SPATZ Health Study in Germany. Longitudinal data of parental and children's caring physicians' reports were used to assess the point and cumulative agreement of parent- and physician-reported AD diagnoses, AD onset age, and trend of agreement at child ages between 1 and 6 years overall and by child and parent demographics and health conditions. A Generalized Estimating Equation model was fitted to identify factors associated with the sensitivity of parent reports. RESULTS: The point agreement between parent- and physician-reported AD was substantial at the age of 1 (kappa = 0.63, 95% CI: 0.51-0.75) but declined with age and became fair after the age of 3 (kappa < 0.40). The cumulative agreement remained moderate at the age of 6 (kappa = 0.51, 95% CI: 0.43-0.60). Parents had a bias towards delayed reporting of the AD onset age. The AD severity was the only strong determinant for the agreement of AD diagnoses and largely explained the variance of the sensitivity of parent reports. CONCLUSION: The disagreement between parent- and physician-reported AD increases with child age, likely due to the change of AD severity. Using parent-reported data might miss a substantial portion of mild childhood AD cases.

Human milk oligosaccharide profiles and child atopic dermatitis up to 2 years of age: The Ulm SPATZ Health Study.

BACKGROUND: Human milk oligosaccharides (HMOs) have several biological functions. Yet, very few studies have investigated the effect of HMOs on the development of allergies and even fewer on their specific associations with atopic dermatitis (AD) during early childhood. OBJECTIVE: This study investigated whether individual HMO concentrations, measured at two time points of lactation, were associated with reported diagnosis of AD in children up to two years of age. METHOD: Outcome data were available for HMOs measured in human milk samples collected at 6 weeks (n = 534) and 6 months (n = 356) of lactation. Associations of HMOs with AD, ascertained from parents and pediatricians at ages one and two years, were assessed in crude and adjusted logistic regression models. RESULTS: Few associations were statistically significant at the conventional level (p < .05), for example, 6-week Lacto-N-neotetraose with 2-year AD [OR 95%CI: 0.82 (0.66, 1.00)] and 6-month 3'-sialyllactose among non-secretor mothers with 1-year AD [2.59 (1.53, 6.81)]. Importantly, accounting for multiple testing, these and all further associations were not statistically significant (all p > .0031, which is the threshold for statistical significance after correction for multiple testing). CONCLUSION: Our findings suggest that the intake of different levels (or even absence) of the individual HMOs measured at 6 weeks and 6 months of lactation, in the current study, is not significantly associated with the development of AD in early childhood. Given the exploratory nature of our study and the limited sample size, these results should be interpreted with caution. The specific HMOs for which we show plausible associations at conventional level may warrant further research and investigation.

Food allergy in infants assessed in two German birth cohorts 10 years after the EuroPrevall Study.

BACKGROUND: The prevalence of food allergies (FA) in children increased rapidly at the turn of the century. The EuroPrevall study identified Germany as a country with very high prevalence of FA at that time. Using two large German birth cohorts, we provide an update of the status quo 10 years later. METHODS: KUNO Kids and Ulm SPATZ Health studies are two ongoing prospective birth cohorts. Information on FA was obtained by questionnaires at birth and after 6, 12, and 24 months. Univariable and multivariable logistic regression analyses were performed to investigate risk factors during pregnancy, birth, and early childhood. RESULTS: In 1139 and 1006 children from KUNO Kids and SPATZ, the point prevalence of parent-reported FA symptoms at the ages of 1 and 2 years was 13.2% (95% CI: 11.2-15.2) and 13.9% (95% CI: 11.5-17.2) in KUNO Kids. Doctor's diagnosed FA at 1 and 2 years was 2.4% (95% CI: 1.6-3.4) and 2.7% (95% CI: 1.2-4.3) in KUNO Kids and 2.3% (95% CI: 1.3-3.6) and 3% (95% CI: 2.0-4.5) in SPATZ. Cow's milk and citrus fruits were most frequently suspected by parents to cause FA symptoms. Atopy in the child was associated with a higher frequency of FA at any time, whereas atopy in first-degree relatives was only associated with FA at year 1. Smoke exposure during pregnancy was a risk for FA at age 2. CONCLUSION: The prevalence of food allergy seems to have plateaued in the last 10 years in Germany. FA is often suspected by parents but only rarely diagnosed by oral food challenge. Risk factor analysis may help to establish personalized health approaches.

Association of two geriatric treatment systems on care home admission and mortality in patients with hip fracture.

BACKGROUND: In Germany, geriatricians deliver acute geriatric care during an acute hospital stay and subacute rehabilitation after transfer to a rehabilitation clinic. However, the proportion of patients who receive acute geriatric care (AGC) or are transferred to subacute rehabilitation (TSR) differs considerably between hospitals. The aim of this study was to analyse the association between the two geriatric treatment systems and care home admission or mortality in patients following hip fracture. METHODS: Health insurance claims data were used to identify the rate of AGC per hospital and the rate of TSR per hospital following hip fracture surgery in patients aged ≥ 80 years. Outcomes were cumulative admission to a care home and cumulative mortality within 6 months after hospital admission. RESULTS: Data from 23,046 hip fracture patients from 561 hospitals were analysed. The rate of AGC was not associated with care home admission. However, compared to high rates of AGC medium rates or no AGC were associated with increased death rates by 12% or 20%, respectively. Treatment in hospitals with low rates of TSR was associated with a 8% higher risk of care home admission and a 10% increased risk of death compared to treatment in hospitals with high rates of TSR. CONCLUSIONS: Our study suggests potential effects of geriatric treatment: reduction of mortality in hospitals with high rates of AGC or reduction of care home admission and mortality in hospitals with high rates of TSR.