49 research outputs found
Development of Risk Prediction Equations for Incident Chronic Kidney Disease
IMPORTANCE â Early identification of individuals at elevated risk of developing chronic kidney diseaseÂ
could improve clinical care through enhanced surveillance and better management of underlying healthÂ
conditions.Â
OBJECTIVE â To develop assessment tools to identify individuals at increased risk of chronic kidneyÂ
disease, defined by reduced estimated glomerular filtration rate (eGFR).Â
DESIGN, SETTING, AND PARTICIPANTS â Individual level data analysis of 34 multinational cohorts fromÂ
the CKD Prognosis Consortium including 5,222,711 individuals from 28 countries. Data were collected from April, 1970 through January, 2017. A twoâstage analysis was performed, with each study firstÂ
analyzed individually and summarized overall using a weighted average. Since clinical variables were often differentially available by diabetes status, models were developed separately within participantsÂ
with diabetes and without diabetes. Discrimination and calibration were also tested in 9 externalÂ
cohorts (N=2,253,540).
EXPOSURE Demographic and clinical factors.Â
MAIN OUTCOMES AND MEASURES â Incident eGFR <60 ml/min/1.73 m2.Â
RESULTS â In 4,441,084 participants without diabetes (mean age, 54 years, 38% female), there wereÂ
660,856 incident cases of reduced eGFR during a mean followâup of 4.2 years. In 781,627 participantsÂ
with diabetes (mean age, 62 years, 13% female), there were 313,646 incident cases during a mean
followâup of 3.9 years. Equations for the 5âyear risk of reduced eGFR included age, sex, ethnicity, eGFR,
history of cardiovascular disease, ever smoker, hypertension, BMI, and albuminuria. For participantsÂ
with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interactionÂ
between the two. The risk equations had a median C statistic for the 5âyear predicted probability ofÂ
0.845 (25th â 75th percentile, 0.789â0.890) in the cohorts without diabetes and 0.801 (25th â 75th
percentile, 0.750â0.819) in the cohorts with diabetes. Calibration analysis showed that 9 out of 13 (69%)
study populations had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination wasÂ
similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 out of 18
(89%) had a slope of observed to predicted risk between 0.80 and 1.25.
CONCLUSIONS AND RELEVANCE â Equations for predicting risk of incident chronic kidney disease
developed in over 5 million people from 34 multinational cohorts demonstrated high discrimination andÂ
variable calibration in diverse populations
Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis.
Aims: Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium. Methods and results: We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9âyears. The average age was 55â±â16âyears, average eGFR was 83â±â23âmL/min/1.73âm2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2â±â0.4âmmol/L. The risk of serum potassium of >5.5âmmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5âmmol/L. Compared with a reference of 4.2âmmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5âmmol/L and 1.49 (95% CI 1.26-1.76) at 3.0âmmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts. Conclusions: Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
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Midlife omega-3 fatty acid intake predicts later life white matter microstructure in an age- and APOE-dependent manner
Omega-3 intake has been positively associated with healthy brain aging, yet it remains unclear whether high omega-3 intake beginning early in life may optimize its protective effects against brain aging. We examined whether omega-3 intake is associated with brain microstructure over 2 decades later among dementia-free older adults. The 128 participants (62% women; age at magnetic resonance imaging: 76.6â±â7.9) from the Rancho Bernardo Study of Healthy Aging completed at least 1 dietary assessment between 1984 and 1996 and underwent restriction spectrum imaging (RSI) 22.8â±â3.1 years later. We evaluated associations between prior omega-3 intake and RSI metrics of gray and white matter (WM) microstructure. Higher prior omega-3 intake was associated with greater restricted diffusion in the superior cortico-striatal fasciculus. A correlation between higher prior omega-3 intake and greater cingulum restricted diffusion was stronger among participants >80 years old. Higher omega-3 intake correlated with greater restricted diffusion in the inferior longitudinal and inferior fronto-occipital fasciculus more strongly for apolipoprotein E (APOE) Δ4 carriers than noncarriers. Associations were not modified by adjustment for dietary pattern, health, or lifestyle. High omega-3 intake in midlife may help to maintain WM integrity into older age, particularly in the latest decades of life and among APOE Δ4 carriers
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Pulse pressure trajectories predict brain microstructure in communityâdwelling older adults: Associations with executive function and modification by APOE
IntroductionEffects of chronic arterial stiffness on brain aging remain unclear. We, therefore, examined whether long-term trajectories of pulse pressure (PP) predicted brain microstructure, microstructure mediated PP-executive function associations, and APOE genotype modified PP-microstructure associations.MethodsWe examined associations of PP trajectories with brain microstructure measured using restriction spectrum imaging in 146 community-dwelling older adults, whether microstructure mediated PP trajectory-executive function associations, and whether PP-restriction spectrum imaging correlations were modified by APOE-Δ4 status.ResultsParticipants with trajectories of high PP had lower restricted isotropic diffusion (RI) compared to those with low PP trajectories and PP-executive function associations were mediated by subcortical and white matter RI. High PP more strongly correlated with lower RI and higher hindered diffusion among APOE-Δ4 carriers than non-carriers.DiscussionProlonged elevated PP predicts microstructural abnormalities which may contribute to impaired executive function. APOE-Δ4 carriers may be most vulnerable to the adverse effects of PP on brain microstructure
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Elevated Pure Tone Thresholds Are Associated with Altered Microstructure in Cortical Areas Related to Auditory Processing and Attentional Allocation.
BACKGROUND: Hearing loss is associated with cognitive decline and increased risk for Alzheimers disease, but the basis of this association is not understood. OBJECTIVE: To determine whether hearing impairment is associated with advanced brain aging or altered microstructure in areas involved with auditory and cognitive processing. METHODS: 130 participants, (mean 76.4±7.3 years; 65% women) of the Rancho Bernardo Study of Healthy Aging had a screening audiogram in 2003-2005 and brain magnetic resonance imaging in 2014-2016. Hearing ability was defined as the average pure tone threshold (PTA) at 500, 1000, 2000, and 4000âHz in the better-hearing ear. Brain-predicted age difference (Brain-pad) was calculated as the difference between brain-predicted age based on a validated structural imaging biomarker of brain age, and chronological age. Regional diffusion metrics in temporal and frontal cortex regions were obtained from diffusion-weighted MRIs. Linear regression analyses adjusted for age, gender, education, and health-related measures. RESULTS: PTAs were not associated with brain-PAD (ÎČ=â0.09; 95% CI: -0.084 to 0.243; pâ=â0.34). PTAs were associated with reduced restricted diffusion and increased free water diffusion primarily in right hemisphere temporal and frontal areas (restricted diffusion: ÎČsâ=â-0.21 to -0.30; 95% CIs from -0.48 to -0.02; psâ<â0.03; free water: ÎČsâ=â0.18 to 0.26; 95% CIs 0.01 to 0.438; psâ<â0.04). CONCLUSIONS: Hearing impairment is not associated with advanced brain aging but is associated with differences in brain regions involved with auditory processing and attentional control. It is thus possible that increased dementia risk associated with hearing impairment arises, in part, from compensatory brain changes that may decrease resilience
Modeling success: How to work effectively with your biostatistician
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/174824/1/jgs17888_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/174824/2/jgs17888.pd
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FRI-490 Repeatability of liver stiffness measurement by vibration-controlled transient elastography and controlled attenuation parameter in patients with cirrhosis
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Physical Activity and Trajectories of Cognitive Change in Community-Dwelling Older Adults: The Rancho Bernardo Study.
BackgroundAlthough physical activity has been associated with better cognitive function and reduced dementia risk, its association with cognitive decline in normal aging remains uncertain.ObjectiveTo determine whether physical activity in youth and older age are associated with age-related cognitive change.MethodsOver a period of 27 years, 2,027 community-dwelling adults (mean age 73.5; 60% women) of the Rancho Bernardo Study of Healthy Aging completed up to seven cognitive assessments, including tests of global cognitive function, executive function, verbal fluency, and episodic memory. At each visit, participants reported concurrent physical activity. At baseline (1988- 1992), participants additionally reported physical activity as a teenager and at age 30. For each age period, participants were classified as regularly active (3+ times/week) or inactive.ResultsAssociations between concurrent physical activity and better cognitive function were stronger with advancing age on all tests, even after accounting for education, health, and lifestyle factors, as well as survival differences (psâ<â0.05). Baseline physical activity did not predict rates of cognitive decline (psâ>â0.40). Individuals who were physically active at age 30 and older age maintained the highest global cognitive function with advancing age (pâ=â0.002).ConclusionRegular physical activity is associated with better cognitive function with advancing age. Physical activity in young adulthood may contribute to cognitive reserve, which together with physical activity in later years, may act to preserve cognitive function with age