Mineral and Bone Metabolism Disorders in Minority Incident ESRD Patients in an Inner-City Hemodialysis Unit

Background: Chronic kidney disease (CKD) predisposes patients to mineral and bone metabolism disorder (CKD- MBD), which is a well-known risk factor for increased mortality. Because Medical Evidence Form 2728 from the Centers for Medicare and Medicaid Services for incident end-stage renal disease (ESRD) patients does not require documentation of CKD-MBD markers, MBD status on incident patients remains unknown. Objective: Retrospective observational study to determine the prevalence of mineral and bone metabolism disorder in minority incident ESRD patients. Methods: We studied all incident ESRD patients in our hemodialysis unit between January 2000 and September 2008. Patients followed for less than three months were excluded. Target values for CKD stage 5 were defined as per 2003 Kidney Disease Outcome Quality Initiative guidelines. Results: One hundred seventy-four patients were stud- ied, with a mean age of 53.7±16.1 years, mean body mass index of 26.67±5.98 kg/m2, and mean estimated glomerular filtration rate of 6.7±4.03 mL/min/1.73m2. Mean lab values with one standard deviation were as follows: corrected calcium 8.5±1.3 mg/dL, serum albumin 3.05±0.77 g/dL, phosphorus 5.5±2.2 mg/dL, calcium-phosphorus product 46.7±18.5 mg2/dL2, and intact parathyroid hormone (iPTH) 440.9±397.8 pg/mL. Target values for cal- cium, phosphorus, calcium-phosphorus product, and iPTH were met in 34%, 42%, 72%, and 31% of the patients, respectively, while only 6% of the patients met all four target values. Conclusions: CKD-MBD is widely prevalent in minority incident dialysis patients at initiation of therapy. Its management continues to be a challenge and warrants early recognition and therapy in CKD patients.

Generalized Smoluchowski equation with correlation between clusters

In this paper we compute new reaction rates of the Smoluchowski equation which takes into account correlations. The new rate K = KMF + KC is the sum of two terms. The first term is the known Smoluchowski rate with the mean-field approximation. The second takes into account a correlation between clusters. For this purpose we introduce the average path of a cluster. We relate the length of this path to the reaction rate of the Smoluchowski equation. We solve the implicit dependence between the average path and the density of clusters. We show that this correlation length is the same for all clusters. Our result depends strongly on the spatial dimension d. The mean-field term KMFi,j = (Di + Dj)(rj + ri)d-2, which vanishes for d = 1 and is valid up to logarithmic correction for d = 2, is the usual rate found with the Smoluchowski model without correlation (where ri is the radius and Di is the diffusion constant of the cluster). We compute a new rate: the correlation rate K_{i,j}^{C} (D_i+D_j)(r_j+r_i)^{d-1}M{\big(\frac{d-1}{d_f}}\big) is valid for d \leq 1(where M(\alpha) = \sum+\infty i=1i\alphaNi is the moment of the density of clusters and df is the fractal dimension of the cluster). The result is valid for a large class of diffusion processes and mass radius relations. This approach confirms some analytical solutions in d 1 found with other methods. We also show Monte Carlo simulations which illustrate some exact new solvable models

The Peculiar Motions of Early-Type Galaxies in Two Distant Regions VI: The Maximum Likelihood Gaussian Algorithm

The EFAR project is designed to measure the properties and peculiar motions of early-type galaxies in two distant regions. Here we describe the maximum likelihood algorithm we developed to investigate the correlations between the parameters of the EFAR database. One-, two-, and three-dimensional gaussian models are constructed to determine the mean value and intrinsic spread of the parameters, and the slopes and intrinsic parallel and orthogonal spread of the Mgb'-Mg2, Mg2-sigma, Mgb'-sigma relations, and the Fundamental Plane. In the latter case, the cluster peculiar velocities are also determined. We show that this method is superior to ``canonical'' approaches of least-squares type, which give biased slopes and biased peculiar velocities. We test the algorithm with Monte Carlo simulations of mock EFAR catalogues and derive the systematic and random errors on the estimated parameters. We find that random errors are always dominant. We estimate the influence of systematic errors due to the way clusters were selected and the hard limits and uncertainties in the selection function parameters for the galaxies. We explore the influence of uniform distributions in the Fundamental Plane parameters and the errors. We conclude that the mean peculiar motions of the EFAR clusters can be determined reliably. In particular, the placement of the two EFAR sample regions relative to the Lauer and Postman dipole allows us to strongly constrain the amplitude of the bulk motion in this direction.Comment: 43 pages, 19 figures, accepted for publication in MNRA

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Sarcopenia, Obesity, and Mortality in US Adults With and Without Chronic Kidney Disease

In predialysis chronic kidney disease (CKD), the association of muscle mass with mortality is poorly defined, and no study has examined outcomes related to the co-occurrence of low muscle mass and excess adiposity (sarcopenic obesity). Methods: We examined abnormalities of muscle and fat mass in adult participants of the National Health and Nutrition Examination Survey 1999–2004. We determined whether associations of body composition with all-cause mortality differed between participants with CKD compared to those without. Results: CKD modified the association of body composition with mortality (P = 0.01 for interaction). In participants without CKD, both sarcopenia and sarcopenic obesity were independently associated with increased mortality compared with normal body composition (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.07–1.93, and HR = 1.64, 95% CI = 1.26–2.13, respectively). These associations were not present among participants with CKD. Conversely, obese persons had the lowest adjusted risk of death, with an increased risk among those with sarcopenia (HR = 1.43, 95% CI = 1.05–1.95) but not sarcopenic-obesity (P = 0.003 for interaction by CKD status; HR = 1.21, 95% CI = 0.89–1.65), compared with obesity. Discussion: Sarcopenia associates with increased mortality regardless of estimated glomerular filtration rate, but excess adiposity modifies this association among persons with CKD. Future studies of prognosis and weight loss and exercise interventions in CKD patients should consider muscle mass and adiposity together rather than in isolation