Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study

Background: Decline of renal function is common in older persons and the prevalence of chronic kidney disease (CKD) is rising with ageing. CKD affects different outcomes relevant to older persons, additionally to morbidity and mortality which makes CKD a relevant health burden in this population. Still, accurate laboratory measurement of kidney function is under debate, since current creatinine-based equations have a certain degree of inaccuracy when used in the older population. The aims of the study are as follows: to assess kidney function in a cohort of 75+ older persons using existing methodologies for CKD screening; to investigate existing and innovative biomarkers of CKD in this cohort, and to align laboratory and biomarker results with medical and functional data obtained from this cohort. The study was registered at ClinicalTrials.gov, identifier NCT02691546, February 25th 2016. Methods/design: An observational, multinational, multicenter, prospective cohort study in community dwelling persons aged 75 years and over, visiting the outpatient clinics of participating institutions. The study will enroll 2450 participants and is carried out in Austria, Germany, Israel, Italy, the Netherlands, Poland and Spain. Participants will undergo clinical and laboratory evaluations at baseline and after 12 and 24 months-follow-up. Clinical evaluation also includes a comprehensive geriatric assessment (CGA). Local laboratory will be used for 'basic' parameters (including serum creatinine and albumin-to-creatinine ratio), whereas biomarker assessment will be conducted centrally. An intermediate telephone follow-up will be carried out at 6 and 18 months. Discussion: Combining the use of CGA and the investigation of novel and existing independent biomarkers within the SCOPE study will help to provide evidence in the development of European guidelines and recommendations in the screening and management of CKD in older people

Clinical implications of estimating glomerular filtration rate with three different equations among older people: preliminary results of the project 'Screening for Chronic Kidney Disease Among Older People Across Europe (SCOPE)'

We aimed at investigating to what extent CKD may be staged interchangeably by three different eGFR equations in older people, and evaluating the source of discrepancies among equations in a population of 2257 patients older than 75 years enrolled in a multicenter observational study. eGFR was calculated by CKD-EPI, BIS and FAS equations. Statistical analysis was carried out by Bland-Altman analysis. κ statistic was used to quantify the agreement between equations in classifying CKD stages. The impact of selected variables on the difference among equations was graphically explored. The average difference between BIS and FAS was -0.24 (95% limits of agreement (95%LA = -4.64-4.14) mL/min/1.73 m2. The difference between CKD-EPI and BIS and between CKD-EPI and FAS was 8.97 (95%LA = -2.90-20.84) and 8.72 (95%LA = -2.11-19.56) mL/min/1.73 m2, respectively. As regards CKD stage classification, κ value was 0.47 for both CKD-EPI vs. FAS and CKD-EPI vs. BIS, while BIS and FAS had similar classificatory properties (κ = 0.90). Muscle mass was found related to the difference between CKD-EPI and BIS (R2 = 0.11) or FAS (R2 = 0.14), but not to the difference between BIS and FAS. In conclusion, CKD-EPI and BIS/FAS equations are not interchangeable to assess eGFR among older people. Muscle mass may represent a relevant source of discrepancy among eGFR equations

Chronic kidney disease in the context of multimorbidity patterns: the role of physical performance

Background: Chronic kidney disease (CKD) is known to be associated with several co-occurring conditions. We aimed at exploring multimorbidity patterns associated with CKD, as well as the impact of physical performance and CKD severity on them in a population of older outpatients. Methods: Our series consisted of 2252 patients enrolled in the Screening of CKD among Older People across Europe multicenter observational study. Hypertension, stroke, transient ischemic attack, cancer, hip fracture, osteoporosis, Parkinson's disease, asthma, chronic obstructive pulmonary disease, congestive heart failure, angina, myocardial infarction, atrial fibrillation, anemia, CKD (defined as GFR < 60, <45 or < 30 ml/min/1.73 m(2)), cognitive impairment, depression, hearing impairment and vision impairment were included in the analyses. Physical performance was assessed by the Short Physical Performance Battery (SPPB) and used as stratification variable. Pairs of co-occurring diseases were analyzed by logistic regression. Patterns of multimorbidity were investigated by hierarchical cluster analysis. Results: CKD was among the most frequently observed conditions and it was rarely observed without any other co-occurring disease. CKD was significantly associated with hypertension, anemia, heart failure, atrial fibrillation, myocardial infarction and hip fracture. When stratifying by SPPB, CKD was also significantly associated with vision impairment in SPPB = 5-8 group, and hearing impairment in SPPB = 0-4 group. Cluster analysis individuated two main clusters, one including CKD, hypertension and sensory impairments, and the second including all other conditions. Stratifying by SPPB, CKD contribute to a cluster including diabetes, anemia, osteoporosis, hypertension and sensory impairments in the SPPB = 0-4 group. When defining CKD as eGFR< 45 or 30 ml/min/1.73 m(2), the strength of the association of CKD with hypertension, sensory impairments, osteoporosis, anemia and CHF increased together with CKD severity in pairs analysis. Severe CKD (eGFR< 30 ml/min/1.73 m(2)) contributed to a wide cluster including cardiovascular, respiratory and neurologic diseases, as well as osteoporosis, hip fracture and cancer. Conclusions: CKD and its severity may contribute significantly to specific multimorbidity patterns, at least based on the cluster analysis. Physical performance as assessed by SPPB may be associated with not negligible changes in both co-occurring pairs and multimorbidity clusters

Alien Registration- Blanchard, Josephine (Mexico, Oxford County)

https://digitalmaine.com/alien_docs/17689/thumbnail.jp

Kidney function and other factors and their association with falls updates The screening for CKD among older people across Europe (SCOPE) study

Background: Reduced kidney function has become a major public health concern, especially among older people, as Chronic Kidney Disease (CKD) is associated with increased risk of end stage renal disease and mortality. Falls are a serious negative health outcome in older persons with one third of people aged 65 years experiencing a fall per year and increasing fall rates with increasing age. The impact of CKD on falls in older community-dwelling persons is not well investigated. Additionally, lower urinary tract symptoms (LUTS) may also increase the risk of falls. Therefore, our aim was to investigate the impact of CKD and LUTS on falls as well as on injurious falls. Methods: The SCOPE study is an observational, multinational, multicenter, prospective cohort study involving communitydwelling older persons aged 75 years and more recruited from August 2016 to March 2018 in seven European countries. The main outcomes of the present study were any falls and any injurious falls during the 12 months before enrolment The cross-sectional association of estimated glomerular filtration rate (eGFR) and LUIS with study outcomes was investigated by logistic regression analysis adjusted for baseline characteristics of enrolled subjects. Results: Our series consisted of 2256 SCOPE participants (median age = 795 years, 55.7% female). Of them, 746 participants experienced a fall and 484 reported an injurious fall in the 12 months prior to baseline assessment CKD was not significantly associated with falls (OR = 0.95, 95%CI = 0.79-1.14 for eGFR< 60; OR = 1.02, 95%CI = 0.81-128 for eGFR< 45; OR = 1.08, 95%CI = 0.74-1.57 for eGFR< 30) or injurious falls (OR = 0.91, 95%CI = 0.67-124 for eGFR< 60; OR = 0.93, 95%CI = 0.63-137 for eGFR< 45; OR = 1.19, 95%CI = 0.62-2.29 for eGFR< 30). LUTS were found significantly associated with both falls (OR = 156, 95960 =129-1.89) and injurious falls (OR = 158, 95%0 =1.14-2.19), and such associations were confirmed in all multivariable models. Conclusions: Cross-sectional data suggest that CKD may not be associated with history of falls or injurious falls, whereas LUTS is significantly associated with the outcomes

Woods Operations

Historical Photographs taken by the Department of Inland Fisheries and Wildlife. Group of photos identified as Woods Operations

Is kidney function associated with cognition and mood in late life? : The Screening for CKD among Older People across Europe (SCOPE) study

Background: Chronic kidney disease (CKD), cognitive impairment and depression share common risk factors. Previous studies did not investigate the possible association between kidney function and cognitive and mood disorders in older persons in a broad range of kidney function. The present study explored associations between kidney function, cognition and mood in outpatients of 75 years and over. Methods: Baseline data of 2252 participants of the SCOPE study, an international multicenter cohort observational study,were used in which community-dwelling persons of 75 years and over were enrolled to screen for CKD Kidney function was estimated with the BIS1-eGFR equation, cognition was assessed with the Mini-Mental State Examination (MMSE) and mood with the Geriatric Depression Scale 15 items (GDS-15). Characteristics were compared across stages of CKD. Mean eGFR values were also compared across categories of MMSE (&lt; 24, 24-26, &gt;= 27) and between groups with high and low score on the GDS-15 (&gt; 5/&lt;= 5). Results: In total, 63% of the population had an eGFR &lt; 60 mL/min. In advanced stages of CKD, participants were older and more often men than in earlier stages (p &lt; 0.001). Cardiovascular diseases and diabetes mellitus were more often found in those in advanced stages of CKD (p &lt; 0.001), and also cumulative comorbidity scores were higher than in those in earlier stages (p &lt; 0.001). Median MMSE was 29 in CKD stage 1-2 and 3, and 30 in CKD stage 4, whereas median GDS-15 score was 2 in all stages of CKD. Mean values of eGFR did not differ across categories of MMSE or between groups with high and low score on the GDS-15. Stratification for albuminuria did not change these results. Conclusions: Older persons in more advanced stages of CKD did not have lower cognitive scores or higher rates of depressive symptoms than older persons in earlier stages. Future longitudinal studies might give information on the possible effect of kidney function on cognition and mood in late life

Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study

Abstract Background Decline of renal function is common in older persons and the prevalence of chronic kidney disease (CKD) is rising with ageing. CKD affects different outcomes relevant to older persons, additionally to morbidity and mortality which makes CKD a relevant health burden in this population. Still, accurate laboratory measurement of kidney function is under debate, since current creatinine-based equations have a certain degree of inaccuracy when used in the older population. The aims of the study are as follows: to assess kidney function in a cohort of 75+ older persons using existing methodologies for CKD screening; to investigate existing and innovative biomarkers of CKD in this cohort, and to align laboratory and biomarker results with medical and functional data obtained from this cohort. The study was registered at ClinicalTrials.gov, identifier NCT02691546, February 25th 2016. Methods/design An observational, multinational, multicenter, prospective cohort study in community dwelling persons aged 75 years and over, visiting the outpatient clinics of participating institutions. The study will enroll 2450 participants and is carried out in Austria, Germany, Israel, Italy, the Netherlands, Poland and Spain. Participants will undergo clinical and laboratory evaluations at baseline and after 12 and 24 months- follow-up. Clinical evaluation also includes a comprehensive geriatric assessment (CGA). Local laboratory will be used for ‘basic’ parameters (including serum creatinine and albumin-to-creatinine ratio), whereas biomarker assessment will be conducted centrally. An intermediate telephone follow-up will be carried out at 6 and 18 months. Discussion Combining the use of CGA and the investigation of novel and existing independent biomarkers within the SCOPE study will help to provide evidence in the development of European guidelines and recommendations in the screening and management of CKD in older people. Trial registration This study was registered prospectively on the 25th February 2016 at clinicaltrials.gov (NCT02691546)

Type III secretion system effectors form robust and flexible intracellular virulence networks

Infections with many Gram-negative pathogens, including Escherichia coli, Salmonella, Shigella, and Yersinia, rely on type III secretion system (T3SS) effectors. We hypothesized that while hijacking processes within mammalian cells, the effectors operate as a robust network that can tolerate substantial contractions. This was tested in vivo using the mouse pathogen Citrobacter rodentium (encoding 31 effectors). Sequential gene deletions showed that effector essentiality for infection was context dependent and that the network could tolerate 60% contraction while maintaining pathogenicity. Despite inducing very different colonic cytokine profiles (e.g., interleukin-22, interleukin-17, interferon-γ, or granulocyte-macrophage colony-stimulating factor), different networks induced protective immunity. Using data from >100 distinct mutant combinations, we built and trained a machine learning model able to predict colonization outcomes, which were confirmed experimentally. Furthermore, reproducing the human-restricted enteropathogenic E. coli effector repertoire in C. rodentium was not sufficient for efficient colonization, which implicates effector networks in host adaptation. These results unveil the extreme robustness of both T3SS effector networks and host responses