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In this special feature article, we discuss the development of collaborative care models in chronic disease management and the need for such initiatives in chronic kidney disease (CKD). We identify telemedicine as a potential key element to collaborative care in CKD. Telenephrology—as telemedicine would be referred to as it is applied in CKD—would be comprised of various technology platforms and applications, which are described here. We describe a range of scenarios in which telenephrology would facilitate collaborative care in CKD and how it would be the basis for patient-oriented research to assess improvements in outcomes in the future. [ABSTRACT FROM PUBLISHER]

The risk for cardiovascular events conferred by decreased renal function is curvilinear with exponentially greater increases in risk as estimated glomerular filtration rate (eGFR) declines. In 13 non-diabetic pre-dialysis chronic kidney disease (CKD) patients, we employed quantitative F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) as a means to measure myocardial metabolic changes. Methods: Dynamic cardiac FDG PET images were acquired after 6 h fasting and glucose loading. Corrections for attenuation, scatter, randoms, dead time and decay were applied to the PET data and myocardial glucose utilization (MGU) was calculated using the Patlak method in conjunction with standardized myocardial regions of interest and an image-derived input function (left atrium). MGU was compared with eGFR based on a serum creatinine drawn within 2 weeks of the study date. Results: MGU was relatively uniform between the myocardial sectors (coefficient of variation = 16.2 ± 6.8%) within each patient. Between patients, whole myocardium MGU varied considerably with a range of 37.3–156.2 μmol/min/100 g and a mean of 68.9 ± 38.3 μmol/min/ 100 g. eGFR ranged from 11–89 ml/min/1.73 m2 with a mean of 42.8 ± 26.9 ml/min/1.73 m2. There was an inverse correlation between whole myocardium MGU and eGFR (Spearman’s rho correlation = –0.615, p = 0.025). In multivariate analysis, the relationship between MGU and eGFR was sustained with adjustment for age, race and gender (adjusted β = –1.56 ± 0.48, p = 0.01). There was no correlation between cardiac workload and eGFR (p = NS). Conclusions: A significant inverse correlation between MGU and eGFR is supportive of the hypothesis that CKD is associated with myocardial metabolic changes, which could not be attributed to demographic factors or cardiac workload. Dynamic FDG PET could provide a sensitive, non-invasive, quantitative tool for investigating pre-clinical myocardial abnormalities in patients with CKD. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background In the older population, anemia has been associated with poor outcomes including disability and mortality. Understanding the mechanisms leading to anemia is essential to plan better treatment and prevention strategies. We tested the hypothesis that the age-related decline in kidney function is associated with an increased prevalence of anemia and that such an increase is accompanied by a concomitant decrement in erythropoietin levels. Methods Data were from the InCHIANTI study, a population-based study performed in a sample of community-dwelling older (≥65 years) persons living in Italy. This analysis included 1005 participants with complete data on hemoglobin and erythropoietin levels and markers of renal function. Results The prevalence of anemia according to the World Health Organization criteria (hemoglobin level <12 g/dL for women and <13 g/dL for men) was 12.0% and increased with age in both sexes. After adjusting for age, diseases, and other confounders, only participants with a creatinine clearance (CrCl) of 30 mL/min or lower (≤0.50 mL/s) had a higher prevalence of anemia compared with those with a CrCl higher than 90 mL/min (>1.50 mL/s) (P<.01). Consistently, participants with a CrCl of 30 mL/min or lower (≤0.50 mL/s) had significantly lower age- and hemoglobin-adjusted erythropoietin endogenous levels. After excluding men and women with CrCl of 30 mL/min or lower (≤0.50 mL/s) and adjusting for confounders, we found a trend toward an increase in prevalence of anemia with decreasing renal function; however, it was not statistically significant. Conclusions Severe age-related decline in renal function is associated with a reduced erythropoietin secretion and anemia. Whether moderate kidney impairment in older persons is associated with a progressively increasing risk of anemia remains to be determined. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) are at increased risk of harm as a consequence of errors in medical care. Hug and colleagues highlight the significance of adverse drug events in hospitalized patients with CKD. Their findings demonstrate the role adverse drug events play in the safety of patients with CKD and underscore the importance of novel strategies intended to reduce such medical errors. [ABSTRACT FROM AUTHOR]

The article explores the impact of chronic kidney disease (CKD) treatments on the serum potassium levels of patients. A study conducted by the Renal Research Institute (RRI) analyzed the possible effects of disturbances in serum potassium levels resulting from CKD treatments. Researchers analyzed the association between serum potassium level and the incidence of end-stage renal disease (ESRD) and mortality. They found that CKD patients have a higher risk of developing hypokalemia than from hyperkalemia.

Discusses the etiology and exacerbation of hypertension patients with end-stage renal disease (ESRD) requiring renal replacement. Relationship between hypertension and ESRD patient mortality; Existence of multiple factors contributing to hypertension in ESRD patients; Impact of ultra-filtration on the condition of ESRD patients. [ABSTRACT FROM AUTHOR]

Background: The serotonin transporter (SERT) mRNA was previously reported to be a quantitative and pathophysiology‐based biomarker of heavy drinking in 5HTTLPR:LL genotype‐carriers treated with ondansetron. Here, we validated the potential use of SERT mRNA for quantitative prediction of recent alcohol consumption (in the absence of treatment) and compared it with the known biomarkers ethyl glucuronide (EtG) and ethyl sulfate (EtS). Methods: Binge drinking men and women of European ancestry aged 21 to 65 years were enrolled in a 12‐day, in‐patient, randomized, double‐blind, crossover study, where they were administered three beverage doses (placebo, 0.5 g/kg [0.4 g/kg] ethanol, and 1 g/kg [0.9 g/kg] ethanol for men [women]) individually in three 4‐day periods (experiments), separated by minimum 7‐day washout period. Diet, sleep, and physical activity were controlled throughout the inpatient experiments. Twenty‐nine participants were randomized to receive beverage doses counterbalancing the sequence of treatment and gender within subgroups stratified by SERT genotypes 5HTTLPR:LL+rs25531:AA (LALA) versus 5HTTLPR:LS/SS. Peripheral venous blood was collected daily for (1) quantification of SERT mRNA (the primary outcome measure) using qRT‐PCR and (2) plasma EtG and EtS levels using tandem mass‐spectrometry. Results: The association between administered beverage dose and SERT mRNA from completers of at least one 4‐day experiment (N = 18) assessed by a linear mixed model was not statistically significant. Significant positive associations were found with beverage dose and plasma EtG, EtS and EtG/EtS ratio (β = 5.8, SE = 1.2, p < 0.0001; β = 1.3, SE = 0.6, p = 0.023; and β = 3.0, SE = 0.7, p < 0.0001, respectively; the C‐statistics for discriminating outcomes were 0.97, 0.8, and 0.92, respectively). Additionally, we observed a sequence effect with a greater placebo effect on SERT mRNA when it was administered during the first experiment (p = 0.0009), but not on EtG/EtS measures. Conclusion: The findings do not validate the use of SERT as a biomarker of heavy drinking. Larger and more innovative studies addressing the effects of placebo, race, gender, and response to treatment with serotonergic agents are needed to fully assess the utility of SERT as a biomarker of heavy and binge drinking. [ABSTRACT FROM AUTHOR]

Metformin has been shown to repress transcription of the bile salt export pump (BSEP) in human primary hepatocytes. The primary objective of this study was to assess the effect of oral metformin on the human pharmacokinetics (PKs) of two BSEP probe substrates: pravastatin and chenodeoxycholic acid (CDCA; also known as chenodiol). Endogenous bile acid levels were assessed as a secondary measure of metformin impact. An open‐label, randomized, single‐dose, placebo‐controlled, fasted, crossover PK study was conducted in 12 healthy adult volunteers. Metformin (500 mg b.i.d.) or placebo (b.i.d.) was administered orally for 6 days. On day 7, a single dose of the BSEP substrates pravastatin (80 mg) and CDCA (250 mg) were administered orally. Plasma samples were quantified for pravastatin, CDCA, and endogenous bile acids. Compared to placebo, metformin increased pravastatin plasma exposure, did not impact CDCA plasma exposure, and reduced conjugated primary bile acid levels in the blood. These results are consistent with metformin repressing BSEP expression. This differential effect reflects the degree of enterohepatic recirculation of victim substrates. [ABSTRACT FROM AUTHOR]

Purpose: Despite no broad, direct evidence in humans, there is a potential concern that surfactants alter active or passive drug intestinal permeation to modulate oral drug absorption. The purpose of this study was to investigate the impact of the surfactant polysorbate 80 on active and passive intestinal drug absorption in humans. Methods: The human (n = 12) pharmacokinetics (PK) of three probe substrates of intestinal absorption, valacyclovir, chenodeoxycholic acid (CDCA), and enalaprilat, were assessed. Endogenous bile acid levels were assessed as a secondary measure of transporter and microbiota impact. Results: Polysorbate 80 did not inhibit peptide transporter 1 (PepT1)- or apical sodium bile acid transporter (ASBT)-mediated PK of valacyclovir and CDCA, respectively. Polysorbate 80 did not increase enalaprilat absorption. Modest increases in unconjugated secondary bile acid Cmax ratios suggest a potential alteration of the in vivo intestinal microbiota by polysorbate 80. Conclusions: Polysorbate 80 did not alter intestinal membrane fluidity or cause intestinal membrane disruption. This finding supports regulatory relief of excipient restrictions for Biopharmaceutics Classification System-based biowaivers. [ABSTRACT FROM AUTHOR]

Background: Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function. Methods: Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory. Results: LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p<0.001), IL-1RA (1.23 [1.13, 1.34], p<0.0001), IL-6 (1.25 [1.14, 1.36], p<0.001) and TNF-α (1.14 [1.04, 1.25], p = 0.004) were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 [1.18, 1.48], p<0.001) and IL-6 (1.34 [1.21, 1.49], p<0.001). Only hs-CRP was associated with diastolic dysfunction (1.14 [1.04, 1.26], p = 0.005). Conclusion: In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To compare population-level baseline characteristics, individual-level utilization, and costs between antihypertensive medication users versus nonusers in adults with diabetes and concomitant hypertension. Methods: This longitudinal retrospective observational research used Medical Expenditure Panel Survey household component pooled years 2006 to 2009 to analyze adults 18 years or older with nongestational diabetes and coexistent essential hypertension. Two groups were created: 1) antihypertensive medication users and 2) no antihypertensive pharmacotherapy. We examined average annualized health care costs and emergency department and hospital utilization. Accounting for Medical Expenditure Panel Survey’s complex survey design, all analyses used longitudinal weights. Logistic regressions examined the likelihood of utilization and anytihypertensive medication use, and log-transformed multiple linear regression models assessed costs and antihypertensive medication use. Results: Of the 3261 adults identified with diabetes, 66% (n = 2137) had concomitant hypertension representing 38.7 million individuals during 2006 to 2009. Significantly, the 16% (n = 338) no antihypertensive pharmacotherapy group showed greater mean nights hospitalized (3.6 vs. 1.7, P = 0.0120), greater all-cause hospitalization events per 1000 patient months (41 vs. 24, P = 0.0.007), and lower mean diabetes-related and hypertension-related ambulatory visits. After adjusting for confounders, non-antihypertensive medication users showed 1.64 odds of hospitalization, 29% lower total, and 27% lower average annualized medical expenses compared with antihypertensive medication users. Conclusions: In adults with diabetes and coexistent hypertension, we observed significantly greater hospitalizations and lower costs for the non antihypertensive pharmacotherapy group versus those using antihypertensive medications. The short-term time horizon greater hospitalizations with lower expenses among non-antihypertensive medication users with diabetes and concomitant hypertension warrant further study. [Copyright &y& Elsevier]

Background Patients with chronic kidney disease (CKD) face risks of not only end-stage kidney disease (ESKD), cardiovascular disease (CVD) and death, but also decline in kidney function, quality of life (QOL) and mental and physical well-being. This study describes the multidimensional trajectories of CKD using clinical events, kidney function and patient-reported outcome measures (PROMs). We hypothesized that more advanced CKD stages would associate with more rapid decline in each outcome. Methods Among 3939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study, we evaluated multidimensional disease trajectories by G- and A-stages of enrollment estimated glomerular filtration rate (eGFR) and albuminuria, respectively. These trajectories included clinical events (ESKD, CVD, heart failure and death), eGFR decline and PROMs [kidney disease QOL (KDQOL) burden, effects and symptoms questionnaires, as well as the 12-item short form mental and physical component summaries]. We also evaluated a group-based multitrajectory model to group participants on the basis of longitudinal PROMs and compared group assignments by enrollment G- and A-stage. Results The mean participant age was 58 years, 45% were women, mean baseline eGFR was 44 mL/min/1.73 m2 and median urine albumin:creatinine ratio was 52 mg/g. The incidence of all clinical events was greater and eGFR decline was faster with more advanced G- and A-stages. While baseline KDQOL and physical component measures were lower with more advanced G- and A-stage of CKD, changes in PROMs were inconsistently related to the baseline CKD stage. Groups formed on PROM trajectories were fairly distinct from existing CKD staging (observed agreement 60.6%) and were associated with the risk of ESKD, CVD, heart failure and death. Conclusions More advanced baseline CKD stage was associated with a higher risk of clinical events and faster eGFR decline, and was only weakly related to changes in patient-reported metrics over time. [ABSTRACT FROM AUTHOR]

Background: Adults with chronic kidney disease (CKD) are hospitalized more frequently than those without CKD, but the magnitude of this excess morbidity and the factors associated with hospitalizations are not well known. Methods and findings: Data from 3,939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 and 2008 at 7 clinical centers in the United States were used to estimate primary causes of hospitalizations, hospitalization rates, and baseline participant factors associated with all-cause, cardiovascular, and non-cardiovascular hospitalizations during a median follow up of 9.6 years. Multivariable-adjusted Poisson regression was used to identify factors associated with hospitalization rates, including demographics, blood pressure, estimated glomerular filtration rate (eGFR), and proteinuria. Hospitalization rates in CRIC were compared with rates in the Nationwide Inpatient Sample (NIS) from 2012. Of the 3,939 CRIC participants, 45.1% were female, and 41.9% identified as non-Hispanic black, with a mean age of 57.7 years, and the mean eGFR is 44.9 ml/min/1.73m2. CRIC participants had an unadjusted overall hospitalization rate of 35.0 per 100 person-years (PY) [95% CI: 34.3 to 35.6] and 11.1 per 100 PY [95% CI: 10.8 to 11.5] for cardiovascular-related causes. All-cause, non-cardiovascular, and cardiovascular hospitalizations were associated with older age (≥65 versus 45 to 64 years), more proteinuria (≥150 to <500 versus <150 mg/g), higher systolic blood pressure (≥140 versus 120 to <130 mmHg), diabetes (versus no diabetes), and lower eGFR (<60 versus ≥60 ml/min/1.73m2). Non-Hispanic black (versus non-Hispanic white) race/ethnicity was associated with higher risk for cardiovascular hospitalization [rate ratio (RR) 1.25, 95% CI: 1.16 to 1.35, p-value < 0.001], while risk among females was lower [RR 0.89, 95% CI: 0.83 to 0.96, p-value = 0.002]. Rates of cardiovascular hospitalizations were higher among those with ≥500 mg/g of proteinuria irrespective of eGFR. The most common causes of hospitalization were related to cardiovascular (31.8%), genitourinary (8.7%), digestive (8.3%), endocrine, nutritional or metabolic (8.3%), and respiratory (6.7%) causes. Hospitalization rates were higher in CRIC than the NIS, except for non-cardiovascular hospitalizations among individuals aged >65 years. Limitations of the study include possible misclassification by diagnostic codes, residual confounding, and potential bias from healthy volunteer effect due to its observational nature. Conclusions: In this study, we observed that adults with CKD had a higher hospitalization rate than the general population that is hospitalized, and even moderate reductions in kidney function were associated with elevated rates of hospitalization. Causes of hospitalization were predominantly related to cardiovascular disease, but other causes contributed, particularly, genitourinary, digestive, and endocrine, nutritional, and metabolic illnesses. High levels of proteinuria were observed to have the largest association with hospitalizations across a wide range of kidney function levels. Hsiang-Yu Chen and colleagues report the factors associated with hospitalization in patients with Chronic Kidney Disease. Author summary: Why was this study done?: Chronic kidney disease (CKD) (or non-dialysis-dependent kidney disease) is increasingly common globally, and individuals with CKD have a high risk of health complications, including hospitalizations. Many of the hospitalizations experienced by those with CKD are thought to be due to cardiovascular disease, but little else is known about the other causes for hospitalization or why people with kidney disease are at higher risk of hospitalizations. Learning more about causes of hospitalization and risk factors for hospitalizations can guide outpatient management. Research to date on hospitalizations in kidney disease has mainly focused on those with dialysis-dependent kidney disease. What did the researchers do and find?: We looked at hospitalization data from adults with CKD who were followed for nearly 10 years. We classified hospitalizations by the primary discharge code and found that non-cardiovascular causes, such as genitourinary-, digestive-, and endocrine-related causes, comprised the majority of hospitalizations and that the largest single contributor to hospitalizations was due to cardiovascular reasons. We modeled the risk of hospitalizations with patient characteristics, such as age and sex, and clinical factors, such as level of kidney function, blood pressure, and proteinuria, and found that high levels of proteinuria were found to have a high risk of hospitalization regardless of kidney function level, and the risk of hospitalizations occurred even at moderate levels of kidney function. We also compared the hospitalization data from individuals with known CKD to a sample of the general hospitalized population in the United States and found that adults with CKD have higher hospitalization rates than this general sample. What do these findings mean?: These findings highlight the need for developing better approaches to identifying patients at risk for severe complications of CKD and to guiding outpatient management strategies to improve outcomes in CKD. The findings may be particularly relevant to health care providers in general medicine since the increased risk of hospitalization occurred with even moderate reductions in kidney function, which do not typically correspond to being under the care of a kidney disease expert. Our study's findings might not be applicable to other CKD populations since the study enrolled volunteers, who might be healthier than other populations. [ABSTRACT FROM AUTHOR]

Persons with chronic kidney disease (CKD) are at high risk of infection. While low-grade inflammation could impair immune response, it is unknown whether inflammatory markers are associated with infection risk in this clinical population. Using 2003–2013 data from the Chronic Renal Insufficiency Cohort Study (3,597 participants with CKD), we assessed the association of baseline plasma levels of 4 inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 receptor antagonist (IL-1RA), and transforming growth factor-β (TGF-β)) with incident hospitalization with major infection (pneumonia, urinary tract infection, cellulitis and osteomyelitis, and bacteremia and sepsis). During follow-up (median 7.5 years), 36% (n  = 1,290) had incident hospitalization with major infection. In multivariable Cox analyses with each inflammatory marker modeled as a restricted cubic spline, higher levels of IL-6 and TNF-α were monotonically associated with increased risk of hospitalization with major infection (for 95th vs. 5th percentile, hazard ratio = 2.11 (95% confidence interval: 1.68, 2.66) for IL-6 and 1.88 (95% confidence interval: 1.51, 2.33) for TNF-α), while corresponding associations for IL-1RA or TGF-β were nonsignificant. Thus, higher plasma levels of IL-6 and TNF-α, but not IL-1RA or TGF-β, were significantly associated with increased risk of hospitalization with major infection. Future studies should investigate whether inflammatory pathways that involve IL-6 and TNF-α increase susceptibility to infection among individuals with CKD. [ABSTRACT FROM AUTHOR]

Background and Objective: Hypoglycemia is a common safety event when attempting to optimize glycemic control in diabetes (DM). While electronic medical records provide a natural ground for detecting and analyzing hypoglycemia, ICD codes used in the databases may be invalid, insensitive or non-specific in detecting new hypoglycemic events. We developed text preprocessing methods to improve automatic detection of hypoglycemia from analysis of clinical encounter text notes.Methods: We set out to improve hypoglycemia detection from clinical notes by introducing three preprocessing methods: stop word filtering, medication signaling, and ICD narrative enrichment. To test the proposed methods, we selected clinical notes from VA Maryland Healthcare System, based on various combinations of three criteria that are suggestive of hypoglycemia, including ICD-9 code of diabetes and hypoglycemia, laboratory glucose values < 70 md/dL, and text reference to a proximate hypoglycemia event. In addition, we constructed one dataset of 395 clinical notes from year 2009 and another of 460 notes from year 2014 to test the generality of the proposed methods. For each of the datasets, two physician judges manually reviewed individual clinical notes to determine whether hypoglycemia was present or absent. A third physician judge served as a final adjudicator for disagreements.Results: Each of the proposed preprocessing methods contributed to the performance of hypoglycemia detection by significantly increasing the F1 score in the range of 5.3∼7.4% on one dataset (p < .01). Among the methods, stop word filtering contributed most to the performance improvement (7.4%). Combining all the preprocessing methods led to greater performance gain (p < .001) compared with using each method individually. Similar patterns were observed for the other dataset with the F1 score being increased in the range of 7.7%∼9.4% by individual methods (p < .001). Nevertheless, combining the three methods did not yield additional performance gain.Conclusion: The proposed text preprocessing methods improved the performance of hypoglycemia detection from clinical text notes. Stop word filtering achieved the most performance improvement. ICD narrative enrichment boosted the recall of detection. Combining the three preprocessing methods led to additional performance gains. [ABSTRACT FROM AUTHOR]

Background Clinical guidelines caution against nonsteroidal anti-inflammatory drug (NSAID) use in older adults. The study objective was to quantify the 30-day risk of acute kidney injury (AKI) and hyperkalemia in older adults after NSAID initiation and to develop a model to predict these outcomes. Methods We conducted a population-based retrospective cohort study in Ontario, Canada from 2007 to 2015 of patients ≥ 66 years. We matched 46 107 new NSAID users with 46 107 nonusers with similar baseline health. The primary outcome was 30-day risk of AKI and secondary outcomes were hyperkalemia and all-cause mortality. Results NSAID use versus nonuse was associated with a higher 30-day risk of AKI {380 [0.82%] versus 272 [0.59%]; odds ratio (OR) 1.41 [95% confidence interval (CI) 1.20–1.65]} and hyperkalemia [184 (0.40%) versus 123 (0.27%); OR 1.50 (95% CI 1.20–1.89); risk difference 0.23% (95% CI 0.13–0.34)]. There was no association between NSAID use and all-cause mortality. A prediction model incorporated six predictors of AKI or hyperkalemia: older age, male gender, lower baseline estimated glomerular filtration rate, higher baseline serum potassium, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use or diuretic use. This model had moderate discrimination [C-statistic 0.72 (95% CI 0.70–0.74)] and good calibration. Conclusions In older adults, new NSAID use compared with nonuse was associated with a higher 30-day risk of AKI and hyperkalemia but not all-cause mortality. Prescription NSAID use among many older adults may be safe, but providers should use caution and assess individual risk. [ABSTRACT FROM AUTHOR]

Background: Predialysis nephrology care for adults with late stage chronic kidney disease (CKD) is associated with improved outcomes. Less is known about the effects of nephrology care in earlier stages of CKD.Objective: We aimed to evaluate the effect of nephrology care on management of CKD risk factors and complications, CKD progression, incident cardiovascular disease (CVD), and death.Design: This was a prospective cohort study.Participants: Participants included 3855 men and women aged 21 to 74 years enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study with a mean (SD) estimated glomerular filtration rate (eGFR) at entry of 45 (17) ml/min/1.73 m(2), followed for a median of 6.6 years.Main Measures: The main predictor was self-reported prior contact with a nephrologist at study enrollment. Outcomes evaluated included CKD progression (≥ 50 % eGFR loss or end-stage renal disease), incident CVD, and death.Results: Two-thirds (67 %) of the participants reported prior contact with a nephrologist at study enrollment. They were younger, more likely to be male, non-Hispanic white, and had lower eGFR and higher urine protein (p < 0.05). A subgroup with eGFR 30- < 60 ml/min/1.73 m(2) and prior contact with a nephrologist were more likely to receive pharmacologic treatment for CKD-related complications and to report angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB) use. After propensity score matching (for reporting prior contact with a nephrologist vs. not) and adjusting for demographic and clinical variables, prior contact with a nephrologist was not significantly associated with CKD progression, incident CVD or death (p > 0.05).Conclusions: One-third of CRIC participants had not seen a nephrologist before enrollment, and this prior contact was subject to age, sex, and ethnic-related disparities. While prior nephrology care was associated with more frequent treatment of CKD complications and use of ACEi/ARB medications, there was neither an association between this care and achievement of guideline-recommended intermediate measures, nor long-term adverse outcomes. [ABSTRACT FROM AUTHOR]

Background. No randomized trials have examined the effect of contact precautions or universal glove and gown use on adverse events. We assessed if wearing gloves and gowns during all patient contact in the intensive care unit (ICU) changes adverse event rates. Methods. From January 2012 to October 2012, intervention ICUs of the 20-site Benefits of Universal Gloving and Gowning cluster randomized trial required that healthcare workers use gloves and gowns for all patient contact. We randomly sampled 1800 medical records of adult patients not colonized with antibiotic-resistant bacteria and reviewed them for adverse events using the Institute for Healthcare Improvement Global Trigger Tool. Results. Four hundred forty-seven patients (24.8%) had 1 or more ICU adverse events. Adverse events were not associated with universal glove and gown use (incidence rate ratio [IRR], 0.81; 95% confidence interval [CI], .48- 1.36). This did not change with adjustment for ICU type, severity of illness, academic hospital status, and ICU size, (IRR, 0.91; 95% CI, .59-1.42; P = .68). Rates of infectious adverse events also did not differ after adjusting for the same factors (IRR, 0.75; 95% CI, .47-1.21; P = .24). Conclusions. In ICUs where healthcare workers donned gloves and gowns for all patient contact, patients were no more likely to experience adverse events than in control ICUs. Concerns of adverse events resulting from universal glove and gown use were not supported. Similar considerations may be appropriate regarding use of contact precautions. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated impact of the gene encoding apolipoprotein L1 (APOL1) variants on chronic kidney disease progression. It describes design, oversight and procedures of the African American Study of Kidney Disease and Hypertension (AASK) and the Chronic Renal Insufficiency Cohort (CRIC) study. It also explores end-stage renal disease risk for African American patients, APOL1 risk based on proteinuria status and APOL1 risk based on randomized blood pressure.

• Quantifying use-error risk can aid in maximizing system performance and safety. • Heterogeneous user populations present challenges for design validation studies. • An expert-driven methodology for quantifying human performance is proposed. • Method serves as a supplemental alternative to live participant studies. • The method is demonstrated on a diabetes population medical device use case study. Heterogeneous product user populations are common across many safety–critical domains. Catering to variable user needs is critical for designing safe and effective systems. Despite this, it is common for a 1-size-fits-all approach to be applied in design for these populations. Quantifying risk of use error throughout the design process can justify design decisions that maximize system performance and safety. Many regulatory agencies require consideration of user variability in design validation activities. However, there are practical challenges for integrating variable users into these activities. Adequately representing populations requires significant time and monetary commitments for subject recruitment. In addition, population access may be difficult in some cases. In this work, an alternative to traditional human factors design validation efforts is presented. Expert elicitation is proposed as a cost-effective means to quantify heterogenous user performance in the formative product design stages. The approach relies on the generation of generic physical and cognitive tasks that can be applied across use cases. The approach is demonstrated on the diabetes population, specially focusing on medical device use. The output of the demonstration are performance distributions for 27 task-user group pairs that can be integrated into design validation efforts to identify human error risks that require mitigation. [ABSTRACT FROM AUTHOR]

Background There is limited data available on the use of red blood cell (RBC) transfusions in younger chronic kidney disease patients not on dialysis (CKD-ND), for whom the consequences of developing antibodies to foreign antigens (allosensitization) may be particularly relevant. Methods We used the Ingenix medical claims database, comprising data on ∼40 million commercially insured US individuals, to identify annual (2002–08) cohorts of patients 18–64 years of age with newly diagnosed CKD. We followed each cohort for 1 year to estimate RBC transfusion rates and used Cox proportional hazards regression to identify patient characteristics associated with time to first transfusion. Results We identified 120 790 newly diagnosed CKD patients for the years 2002–08; 54% were 50–64 years of age. Overall, the transfusion rate was 2.64/100 person-years (PYs) (95% CI: 2.52–2.77). Rates were higher among those with diagnosed anemia [9.80/100 PYs (95% CI: 9.31–10.3)] and among those who progressed to end-stage renal disease (ESRD) [28.0/100 PYs (95% CI: 23.7–33.0)]. For those progressing to ESRD, transfusion rates more than doubled between 2002 and 2008. Of the factors evaluated, transfusion history and the presence of heart failure and diabetes were most strongly associated with a receipt of a transfusion. Conclusions RBC transfusions are relatively common and on the rise among younger CKD-ND patients who are anemic and progress to ESRD. Efforts to decrease the use of transfusions may be important for potential transplant candidates who progress to ESRD. [ABSTRACT FROM AUTHOR]

In 2007 the Maryland Medical Examiner noted a potential cluster of fatal vascular access hemorrhages among hemodialysis patients, many of whom died outside of a health-care setting. To examine the epidemiology of fatal vascular access hemorrhages, we conducted a retrospective case review in District of Columbia, Maryland, and Virginia from January 2000 to July 2007 and a case-control study. Records from the Medical Examiner and Centers for Medicare and Medicaid Services were reviewed, from which 88 patients were identified as fatal vascular access hemorrhage cases. To assess risk factors, a subset of 20 cases from Maryland was compared to 38 controls randomly selected among hemodialysis patients who died from non-vascular access hemorrhage causes at the same Maryland facilities. Of the 88 confirmed cases, 55% hemorrhaged from arteriovenous grafts, 24% from arteriovenous fistulas, and 21% from central venous catheters. Of 82 case-patients with known location of hemorrhage, 78% occurred at home or in a nursing home. In the case-control analysis, statistically significant risk factors included the presence of an arteriovenous graft, access-related complications within 6 months of death, and hypertension; presence of a central venous catheter was significantly protective. Psychosocial factors and anticoagulant medications were not significant risk factors. Effective strategies to control vascular access hemorrhage in the home and further delineation of warning signs are needed. [ABSTRACT FROM AUTHOR]

Elevated serum levels of uric acid consistently correlate with hypertension, but the directionality of the association remains debated. To help define this relationship, we used a controlled setting within a homogeneous Amish community and the Mendelian randomization of a nonsynonymous coding single-nucleotide polymorphism, rs16890979 (Val253Ile), in the SLC2A9 gene. This gene expresses the GLUT9 transporter that also transports uric acid and is associated with lower serum uric acid levels. We studied the unconfounded association between genotype and blood pressure in 516 Amish adults, each placed for 6 days on standardized diets, first with high sodium, followed by low sodium, with an intervening washout period. Blood pressure, measured using 24-h ambulatory monitoring, during both diet periods was used as the primary outcome. All participants were free of diuretic or other antihypertensive medications and the relationships between GLUT9 genotype and both serum uric acid and blood pressure were assessed. Each copy of the GLUT9 minor Ile allele was found to confer a significant 0.44 mg/dl reduction in serum uric acid and was associated with a significant mean decrease in the systolic blood pressure of 2.2 and 1.5 mm Hg on the high- and low-sodium diet, respectively. Thus, a Mendelian randomization analysis using variants in the GLUT9 gene indicates that a decrease in serum uric acid has a causal effect of lowering blood pressure. [ABSTRACT FROM AUTHOR]

Erythropoiesis-stimulating agents (ESAs) are effective in ameliorating anemia in chronic kidney disease (CKD). A recent trial in diabetic patients with CKD, however, suggested a greater risk of stroke associated with full correction of anemia with ESAs. Using national Veterans Affairs data we performed a case-control study examining the association of incident ESA use with acute stroke in patients with estimated glomerular filtration rate <60 cm3/min per 1.73 m2 and outpatient hemoglobin <12 g/dl. Using diagnosis codes, we identified 2071 acute hospitalized stroke cases and matched them 1:5 with controls without stroke, resulting in 12,426 total patients for analysis. Conditional logistic regression was used to estimate the association of ESA use with stroke, adjusting for potential confounders. After multivariate adjustment, ESA use in 1026 patients was associated with greater odds of stroke (odds ratio 1.30). There was significant interaction between ESA use and cancer, with greater odds of stroke among ESA-treated cancer patients (odds ratio 1.85), but not in ESA-treated patients without cancer (odds ratio 1.07). ESA-treated patients with cancer received a median initial dose 2.5-4 times greater than ESA-treated patients without cancer, but pre-ESA hemoglobin and its rate of change did not differ between these groups. Hence, in a large national sample of anemic patients with CKD, ESA treatment was associated with an increased risk of acute stroke with the greatest effect among patients with cancer. [ABSTRACT FROM AUTHOR]

The article reports on the study that determines the incidence of hyperkalemia in chronic kidney disease (CKD). It found that the adjusted rate of hyperkalemia was higher in patients with CKD than those without CKD among individuals treated with renin-angiotensin-aldosterone system (RAAS) blokers. It also reveals that the adjusted odds ratio of death with a moderate and severe hyperkalemia event was highest with no CKD. It suggests that the risk of hyperkalemia in increased with CKD and its occurrence increases the odds of mortality within one day of event.

Background. Smoking is a modifiable behaviour that may hasten the progression of chronic kidney disease (CKD). Cotinine, a nicotine metabolite, is measurable in body fluids, including urine, and can be utilized as an objective measure of smoking exposure. Its use has not been examined in the CKD population. [ABSTRACT FROM PUBLISHER]

Although steroid withdrawal in simultaneous kidney pancreas transplantation has been shown to be feasible, the results of early steroid withdrawal in immunologically solitary pancreas transplantation are not well known. This study evaluated an early steroid withdrawal protocol in this group. The results of steroid withdrawal at 21 d post-transplant in solitary pancreas transplant recipients was compared with a control group consisting of solitary pancreas transplant recipients maintained on steroids (MG). Additional immunosuppression consisted of rabbit anti-thymocyte globulin induction followed by tacrolimus and mycophenolate mofetil in both groups. The withdrawal group (WG, n = 22) consisted of 11 pancreas transplant alone (PTA), six pancreas after kidney (PAK), and five simultaneous cadaveric pancreas living kidney (SPLK) recipients. The steroid maintenance group (MG, n = 32) consisted of 8 PTA, 11 PAK, and 13 SPLK recipients. Recipient and donor demographic characteristics were similar. Seventy eight percent of MG patients had infection-related complications in the first year compared with 50% of the WG patients (p = 0.04). The one-yr rejection, pancreas graft, and patient survival rates were 27.3% 95.5%, and 100% in the WG, and 37.5%, 81.3%, and 93.8% in the MG respectively and not significantly different. We conclude that early corticosteroid withdrawal in isolated pancreas transplantation results in fewer infections and can be achieved without an increased risk of rejection or graft loss over the first year. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Comorbidities are often included in risk-factor models for nosocomial antibiotic-resistant bacterial infections, and aggregate comorbidity measures are valuable because they allow one variable to represent many. This study aimed to develop new aggregate comorbidity measures based upon the Chronic Disease Score (CDS) for assessing the comorbidity-attributable risk of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) nosocomial infections. Study Design and Setting: For each outcome, two retrospective cohort studies of hospitalized patients were conducted. Outcomes were a first MRSA or VRE positive clinical culture obtained 48 hours or more postadmission. Each cohort was divided into development (July 1998–2001) and validation (August 2001–2003) samples. New comorbidity measures were created for MRSA (CDS-MRSA), VRE (CDS-VRE), or any nosocomial infection outcome (CDS-ID) using logistic regression and subsequently validated. Model discrimination was measured using the c-statistic. Results: Discrimination of the CDS-MRSA (c =0.60), CDS-VRE (c =0.65), and CDS-ID (MRSA: c =0.57; VRE: c =0.64) was greater than that of the original CDS (MRSA: c =0.52; VRE: c =0.57). Conclusion: The CDS-MRSA, CDS-VRE, and CDS-ID are new infectious disease specific comorbidity risk-adjustment measures that will be useful for the quality of future epidemiologic studies of MRSA, VRE, and other infectious diseases. [Copyright &y& Elsevier]

Background: Recombinant human erythropoietin (rHuEPO) is recommended pre-dialysis to correct the anemia of chronic kidney disease. This study evaluated the impact of pre-dialysis rHuEPO on mortality in incident end-stage renal disease (ESRD) patients with varying levels of pre-ESRD care. Methods: The study included 15,807 individuals whose exposure to rHuEPO was determined from HCFA 2728 forms. Results: Median follow-up after starting dialysis was 32.8 months. Pre-ESRD rHuEPO use occurred in only 3,994 (25.3%) subjects and was more common in individuals with insurance, currently employed, started on outpatient dialysis, and initiated on peritoneal dialysis. During the study, 8,608 (54.5%) patients died. The risk of death was lower for rHuEPO-treated patients versus non-treated (relative risk 0.87, 95% CI 0.82–0.92). The survival benefit with rHuEPO was greatest early after dialysis initiation (relative risk at 1 vs. 7 years post-dialysis 0.73, 95% CI 0.66–0.80 vs. 0.87, 95% CI 0.82–0.92, respectively), did not vary across several surrogates for quality of care, and was greatest in those with the highest achieved hematocrit pre-ESRD. Conclusion: Pre-dialysis rHuEPO confers a survival benefit that depends on achieved hematocrit and diminishes post-dialysis, but is independent of several surrogates for quality of care except for insurance status pre-ESRD. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: We examined the impact of kidney transplantation on left ventricular ejection fraction (LVEF) in end-stage renal disease (ESRD) patients with congestive heart failure (CHF). Background: The ESRD patients with decreased LVEF and a poor New York Heart Association (NYHA) functional class are not usually referred for transplant evaluations, as they are considered to be at increased risk of cardiac and surgical complications. Methods: Between June 1998 and November 2002, 103 recipients with LVEF ≤40% and CHF underwent kidney transplantation. The LVEF was re-assessed by radionuclide ventriculography gated-blood pool (MUGA) scan at six and 12 months and at the last follow-up during the post-transplant period. Results: Mean pre-transplant LVEF% increased from 31.6 ± 6.7 (95% confidence interval [CI] 30.3 to 32.9) to 52.2 ± 12.0 (95% CI 49.9 to 54.6, p = 0.002) at 12 months after transplantation. There was no perioperative death. After transplantation, 69.9% of patients achieved LVEF ≥50% (normal LVEF). A longer duration of dialysis (in months) before transplantation decreased the likelihood of normalization of LVEF in the post-transplant period (odds ratio 0.82, 95% CI 0.74 to 0.91; p < 0.001). The NYHA functional class improved significantly in those with normalization of LVEF (p = 0.003). After transplantation, LVEF >50% was the only significant factor associated with a lower hazard for death or hospitalizations for CHF (relative risk 0.90, 95% CI 0.86 to 0.95; p < 0.0001). Conclusions: Kidney transplantation in ESRD patients with advanced systolic heart failure results in an increase in LVEF, improves functional status of CHF, and increases survival. To abrogate the adverse effects of prolonged dialysis on myocardial function, ESRD patients should be counseled for kidney transplantation as soon as the diagnosis of systolic heart failure is established. [Copyright &y& Elsevier]

Quasi-experimental study designs, sometimes called nonrandomized, pre-post-intervention study designs, are ubiquitous in the infectious diseases literature, particularly in the area of interventions aimed at decreasing the spread of antibiotic-resistant bacteria. Little has been written about the benefits and limitations of the quasi-experimental approach. This article outlines a hierarchy of quasi-experimental study design that is applicable to infectious diseases studies and that, if applied, may lead to sounder research and more-convincing causal links between infectious diseases interventions and outcomes. [ABSTRACT FROM AUTHOR]

Long-term impact of discontinued or reduced calcineurin inhibitor in patients with chronic allograft nephropathy. Background. Chronic allograft nephropathy is the major cause of progressive renal failure in renal transplant recipients. It has no definitive treatment. Methods. One hundred eighteen renal transplant recipients with declining kidney function and biopsy-proven chronic allograft nephropathy had their cyclosporine or tacrolimus dose reduced or discontinued with either the addition or continuation of mycophenolate mofetil and low-dose steroids at a mean of 853.3 days post-transplantation. Their renal function was modeled before and after this intervention by two methods: A least-square regression was used to assess the decay of renal function after the intervention and to compare that with the slope pre-intervention, whereas a hinge regression line method was used to assess the correlation of the intervention with the inflection point and the impact of the intervention on the decay of renal function. Mean follow-up was 651.0 days after the intervention. Serum creatinine at the time of intervention was 2.8 ± 0.9 mg/dL in the reduced dose cyclosporine (N = 67) and reduced dose tacrolimus (N = 33) groups, and was 2.7 ± 0.7 mg/dL in the group with discontinued calcineurin inhibitor (N = 18). Results. Using the least-square method, 91.7% of the no calcineurin inhibitor group, 51.6% of the reduced dose cyclosporine group, and 59.3% of the reduced dose tacrolimus group had improved or lack of deterioration in slope after the intervention. Using the hinge regression line method, there was a statistically significant correlation of the inflection point with the intervention (P = 0.001). Moreover, there was a similar relationship with stabilized or improved graft function observed with the hinge regression line method and the least-square method, as 72.2% of the calcineurin inhibitor withdrawal group, 54.4% of reduced-dose cyclosporine group, and 40% of the reduced-dose tacrolimus group had improved the slope of decay of renal function or lack of deterioration after the inflection point. The difference between the calcineurin inhibitor withdrawal group and the reduced-dose cyclosporine/tacrolimus groups on the decay in renal function was significant (P = 0.038) with the least-square method and nearly significant (P = 0.056) using the hinge regression line method. Conclusion. This intervention was safe, well tolerated, and associated with a minimal risk of acute rejection. We conclude that the reduction and possible withdrawal of calcineurin inhibitors may be necessary to slow the rate of loss of renal function in patients with chronic allograft nephropathy and deteriorating renal function. [ABSTRACT FROM AUTHOR]

Background: Adults with chronic kidney disease (CKD) are hospitalized more frequently than those without CKD, but the magnitude of this excess morbidity and the factors associated with hospitalizations are not well known.Methods and Findings: Data from 3,939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 and 2008 at 7 clinical centers in the United States were used to estimate primary causes of hospitalizations, hospitalization rates, and baseline participant factors associated with all-cause, cardiovascular, and non-cardiovascular hospitalizations during a median follow up of 9.6 years. Multivariable-adjusted Poisson regression was used to identify factors associated with hospitalization rates, including demographics, blood pressure, estimated glomerular filtration rate (eGFR), and proteinuria. Hospitalization rates in CRIC were compared with rates in the Nationwide Inpatient Sample (NIS) from 2012. Of the 3,939 CRIC participants, 45.1% were female, and 41.9% identified as non-Hispanic black, with a mean age of 57.7 years, and the mean eGFR is 44.9 ml/min/1.73m2. CRIC participants had an unadjusted overall hospitalization rate of 35.0 per 100 person-years (PY) [95% CI: 34.3 to 35.6] and 11.1 per 100 PY [95% CI: 10.8 to 11.5] for cardiovascular-related causes. All-cause, non-cardiovascular, and cardiovascular hospitalizations were associated with older age (≥65 versus 45 to 64 years), more proteinuria (≥150 to <500 versus <150 mg/g), higher systolic blood pressure (≥140 versus 120 to <130 mmHg), diabetes (versus no diabetes), and lower eGFR (<60 versus ≥60 ml/min/1.73m2). Non-Hispanic black (versus non-Hispanic white) race/ethnicity was associated with higher risk for cardiovascular hospitalization [rate ratio (RR) 1.25, 95% CI: 1.16 to 1.35, p-value < 0.001], while risk among females was lower [RR 0.89, 95% CI: 0.83 to 0.96, p-value = 0.002]. Rates of cardiovascular hospitalizations were higher among those with ≥500 mg/g of proteinuria irrespective of eGFR. The most common causes of hospitalization were related to cardiovascular (31.8%), genitourinary (8.7%), digestive (8.3%), endocrine, nutritional or metabolic (8.3%), and respiratory (6.7%) causes. Hospitalization rates were higher in CRIC than the NIS, except for non-cardiovascular hospitalizations among individuals aged >65 years. Limitations of the study include possible misclassification by diagnostic codes, residual confounding, and potential bias from healthy volunteer effect due to its observational nature.Conclusions: In this study, we observed that adults with CKD had a higher hospitalization rate than the general population that is hospitalized, and even moderate reductions in kidney function were associated with elevated rates of hospitalization. Causes of hospitalization were predominantly related to cardiovascular disease, but other causes contributed, particularly, genitourinary, digestive, and endocrine, nutritional, and metabolic illnesses. High levels of proteinuria were observed to have the largest association with hospitalizations across a wide range of kidney function levels. [ABSTRACT FROM AUTHOR]

Objective: Thirty-day hospital readmission (30-day RA) rates are a metric of healthcare quality. Limited data is available, whether increased glucose variability (GV) during the last day of hospital stay is associated with an increased risk of 30-day RA. Design: Nationwide cohort of 1,042,859 admissions of patients with diabetes in the non-critical care setting in 129 Veteran Affairs hospitals, between 2001-2014. Coefficient of Variation (CV) was measured using point of care- glucometer values and was used as measurement of GV, divided into ten equal categories (tentiles). Covariates, including demographics, socio-economic and hospital related factors and up to 30 comorbidities were collected. Poisson regression was used to determine if CV during the last stay day of the hospitalization was associated with 30-day RA. Results: After adjusting for age, gender and race (Model 1), there was a gradual increase in 30-day RA ratio among admissions with higher CV. Following adjusting for all the covariates collected (Model 2), only admissions with the highest CV demonstrated an increased 30-day RA. The rate ratios and 95% CIs were 1.049 (1.026, 1.073, p<0.0001), 1.038 (1.015,1.061, p=0.0011), 1.065 (1.042,1.089, p<0.0001), for the 8th, 9th and the 10th tentiles respectively, compared to those with CV in the 1st tentile. In Model 3, after adjusting for covariates used in Model 2 and for hypoglycemia, results remained statistically significant for those admissions with the highest CV [rate ratios and 95% CIs are 1.044 (1.021,1.068, p=0.0001), 1.028 (1.006,1.052, p=0.014), 1.042 (1.018,1.067, p=0.0005) for the 8th, 9th and the 10th tentiles]. Conclusions: Higher glucose variability during the last day of hospitalization was associated with increased 30-day RA rates after adjustment for multiple covariates and hypoglycemia. Disclosure: E. Spanakis: None. L.G. Singh: None. T. Siddiqui: None. J.D. Sorkin: None. G. Notas: None. M.F. Magee: Consultant; Self; Mytonomy. Research Support; Self; Lilly Diabetes, Mytonomy, Sanofi. Speaker's Bureau; Self; PRIMED. J.C. Fink: None. M. Zhan: None. G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. Funding: U.S. Department of Veterans Affairs (1I01CX001825-01) [ABSTRACT FROM AUTHOR]