PubMed · 3526382
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M D Feldman. 1986. Pica: current perspectives.. https://doi.org/10.1016/s0033-3182(86)72659-5
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BACKGROUND: Glomerular filtration rate (GFR) is a heritable trait, and hyperfiltration (GFR increment in remnant nephrons) may accelerate renal functional decline in chronic kidney disease (CKD). Mesangial and vascular smooth myocytes control GFR by contraction, dependent on voltage-gated Ca(2+) influx, which is controlled by the regulatory β₁-subunit (KCNMB1) of large-conductance heteromeric K+ ('BK') channels. KCNMB1 gain-of-function variant Glu65Lys results in generalized vasorelaxation and thus protection against systemic hypertension. Here we asked whether the Glu65Lys variant influences GFR, in the basal state or during progressive renal decline. METHODS: We explored Glu65Lys effects on GFR in three populations spanning two ethnicities and two diseases (hypertension and nephrosclerosis). GFR was either estimated (eGFR from serum creatinine) or directly measured (iothalamate clearance). RESULTS: The 65Lys variant was relatively common, occurring on ∼5-10% of chromosomes in different biogeographic ancestry groups, and 65Lys carriers exhibited higher eGFR in two primary care populations: extreme BP values in Kaiser clinics (p = 0.029, accounting for ∼0.2% of trait variance), or treated hypertensives in VA clinics (p = 0.017, accounting for ∼0.9% of trait variance). In blacks with progressive renal disease (NIDDK AASK), 65Lys carriers displayed a steeper slope in GFR chronic decline (p = 0.030, accounting for ∼0.4% of trait variance), and Glu65Lys genotype also predicted time of onset of renal failure (log rank p = 0.019). CONCLUSIONS: Common KCNMB1 gain-of-function variant Glu65Lys influences GFR, and 65Lys carriers exhibit not only elevated baseline GFR, but also more rapid GFR decline (and consequent development of renal failure) in CKD. The results suggest that profiling patients at Glu65Lys can assist in gauging renal prognosis as well as selection of rational therapy in hypertension with progressive renal disease.
Our goal was to review and extend statistical methods for discriminating between normal subjects and those with dementia or cognitive impairment. We compared six different methods to one constructed by expert opinion, in their brevity and predictive power. The methods include logistic regression and neural networks, with standard and least absolute shrinkage and selection operator (LASSO) variable selection, as well as decision trees with and without boosting. These methods were applied to the baseline data of a subgroup of subjects in a dementia study, using their screening interview items to predict their clinical diagnosis of normal or non-normal (cognitively impaired or demented). The derived models were then validated on a different subgroup of subjects in the same study who had the screening and clinical diagnosis two to five years later. Performance of different models was compared based on their sensitivity and specificity in the validation sample. Generally, the six statistical methods performed slightly to moderately better than the expert-opinion model. Neural networks generally performed better than the logistic and decision tree models. LASSO improved the performance of logistic and neural network models, but it eliminated few input variables in the neural network. The single decision tree performed at least as well as the standard logistic model, and with fewer items, making it an attractive pre-screening tool. Using the boosting option for decision trees did not substantially improve the performance. We recommend that for each situation, different methods of classification should be attempted to obtain optimal results for a given purpose.
BACKGROUND: African Americans are diagnosed more frequently with colorectal carcinoma at a later stage compared with Caucasians. One potential reason for the disparity is a lower rate of screening examinations. METHODS: Using Outpatient and Physician-Supplier claims for all Medicare beneficiaries age > or = 65 years in 1999, indications for fecal occult blood testing (FOBT), sigmoidoscopy, colonoscopy, and barium enema were divided into diagnostic, surveillance, or screening categories. Annualized rates were calculated based on the number of eligible fee-for-service months. RESULTS: Rates of FOBT (18.24% vs. 11.86%; P < 0.001) and sigmoidoscopy (3.07% vs. 2.17%; P < 0.001) were higher in Caucasians compared with African Americans, whereas rates of barium enema were higher in African Americans (2.26% vs. 1.88%; P < 0.001). Colonoscopy use was more frequent among men only in Caucasians compared with African-Americans (8.00% vs. 6.97%; P < 0.001). For FOBT, sigmoidoscopy, and colonoscopy, the racial differences in procedures performed for diagnostic purposes were of smaller magnitude than for screening; and, for colonoscopy, the use of diagnostic procedures actually was higher for African Americans. CONCLUSIONS: Racial disparities exist not only in the use of colorectal procedures but also in the indications for such testing, with African Americans less likely to undergo screening tests. The differences are consistent with delay in diagnosis until symptoms or signs develop and may contribute to disparities in cancer mortality.