Combined Effects of GSTM1 Null Allele and APOL1 Renal Risk Alleles in CKD Progression in the African American Study of Kidney Disease and Hypertension Trial.

Apolipoprotein L-1 (APOL1) high-risk alleles and the glutathione-S-transferase-µ1 (GSTM1) null allele have been shown separately to associate with CKD progression in the African American Study of Kidney Disease and Hypertension (AASK) trial participants. Here, we determined combined effects of GSTM1 null and APOL1 high-risk alleles on clinical outcomes in 682 AASK participants who were classified into four groups by GSTM1 null or active genotype and APOL1 high- or low-risk genotype. We assessed survival differences among these groups by log-rank test and Cox regression adjusted for important clinical variables for time to GFR event (change in GFR of 50% or 25-ml/min per 1.73 m2 decline), incident ESRD, death, or composite outcomes. The groups differed significantly in event-free survival for incident ESRD and composite outcomes (P≤0.001 by log-rank test). Compared with the reference GSTM1 active/APOL1 low-risk group, other groups had these hazard ratios for the composite outcome of incident ESRD and change in GFR: GSTM1 active/APOL1 high-risk hazard ratio, 2.13; 95% confidence interval, 0.76 to 5.90 (P=0.15); GSTM1 null/APOL1 low-risk hazard ratio, 2.05; 95% confidence interval, 1.08 to 3.88 (P=0.03); and GSTM1 null/APOL1 high-risk hazard ratio, 3.0; 95% confidence interval, 1.51 to 5.96 (P=0.002). In conclusion, GSTM1 null and APOL1 high-risk alleles deleteriously affect CKD progression among blacks with hypertension, and subjects with both GSTM1 null and APOL1 high-risk genotypes had highest risk of adverse renal outcomes. Larger cohorts are needed to fully explore interactions of GSTM1 and APOL1 genotypes in other subgroups.

Lab-on-a-Drone: Toward Pinpoint Deployment of Smartphone-Enabled Nucleic Acid-Based Diagnostics for Mobile Health Care.

We introduce a portable biochemical analysis platform for rapid field deployment of nucleic acid-based diagnostics using consumer-class quadcopter drones. This approach exploits the ability to isothermally perform the polymerase chain reaction (PCR) with a single heater, enabling the system to be operated using standard 5 V USB sources that power mobile devices (via battery, solar, or hand crank action). Time-resolved fluorescence detection and quantification is achieved using a smartphone camera and integrated image analysis app. Standard sample preparation is enabled by leveraging the drone's motors as centrifuges via 3D printed snap-on attachments. These advancements make it possible to build a complete DNA/RNA analysis system at a cost of ∼$50 ($US). Our instrument is rugged and versatile, enabling pinpoint deployment of sophisticated diagnostics to distributed field sites. This capability is demonstrated by successful in-flight replication of Staphylococcus aureus and λ-phage DNA targets in under 20 min. The ability to perform rapid in-flight assays with smartphone connectivity eliminates delays between sample collection and analysis so that test results can be delivered in minutes, suggesting new possibilities for drone-based systems to function in broader and more sophisticated roles beyond cargo transport and imaging.

Loss of GSTM1, a NRF2 target, is associated with accelerated progression of hypertensive kidney disease in the African American Study of Kidney Disease (AASK).

Oxidative stress is acknowledged to play a role in kidney disease progression. Genetic variants that affect the capacity to handle oxidative stress may therefore influence the outcome of kidney disease. We examined whether genetic variants of the GSTM1 gene, a member of a superfamily of glutathione S-transferases, influence the course of kidney disease progression in participants of the African American Study of Kidney Disease (AASK) trial. Groups with and without the common GSTM1 null allele, GSTM1(0), differed significantly in the time to a glomerular filtration rate (GFR) event or dialysis (P = 0.04) and in the time to GFR event, dialysis, or death (P = 0.02). The hazard ratios (HR) for the time to a GFR event or dialysis in those with two or one null allele relative to those possessing none were 1.88 [95% confidence interval (CI), 1.07 to 3.30, P = 0.03] and 1.68 (95% CI, 1.00 to 2.84, P < 0.05), respectively. For the time to GFR event, dialysis, or death, the HR for two null alleles was 2.06 (95% CI, 1.20 to 3.55, P = 0.01) and for one null allele 1.70 (95% CI, 1.02 to 2.81, P = 0.04). We demonstrated that GSTM1 directly regulates intracellular levels of 4-hydroxynonenal (4-HNE) in vascular smooth muscle cells. Furthermore, we showed that renal 4-HNE levels and GSTM1 are both increased after reduction of renal mass (RRM) in the mouse. We conclude that GSTM1 is normally upregulated in chronic kidney disease (CKD) in a protective response to increased oxidative stress. A genetic variant that results in loss of GSTM1 activity may be deleterious in CKD.

Assessment of intravascular volume status and volume responsiveness in critically ill patients.

Accurate assessment of a patient's volume status, as well as whether they will respond to a fluid challenge with an increase in cardiac output, is a critical task in the care of critically ill patients. Despite this, most decisions regarding fluid therapy are made either empirically or with limited and poor data. Given recent data highlighting the negative impact of either inadequate or overaggressive fluid therapy, understanding the tools and techniques available for accurate volume assessment is critical. This review highlights both static and dynamic methods that can be utilized to help in the assessment of volume status.

Therapeutic plasma exchange for renal-related conditions in the elderly: ten years experience in one center.

The elderly people, 65 years old and above, are growing in number. The structural and functional changes associated with aging place the elderly at risk when challenged by extracorporeal therapies, such as therapeutic plasma exchange (TPE). We retrospectively analyzed data on all patients who underwent TPE for renal indications at our institution between January 1, 2000 and June 30, 2010 and compared renal indications and mortality associated with the use of TPE in older versus younger patients. During this period, 621 patients underwent 4722 sessions of TPE. Of them, 191 patients were elderly (30.7%) and they underwent 1289 sessions (27.3%) of TPE. A total of 104 patients (16.7%) underwent 593 sessions of TPE because of renal-related indications: 26 patients in the elderly group and 78 in the younger. Side effects of dyspnea and hypotension were documented in only two patients, both in the elderly cohort. The main indication for TPE in the elderly was glomerulonephritis (GN) as compared with renal allograft rejection in the younger cohort, with a trend toward more death in the elderly (p = 0.07). The multivariable regression model which included age as a category, serum albumin, and initial serum creatinine were unable to predict mortality in this group of patients. In our experience, the main renal indications for TPE in elderly are different from those for younger patients, with GN being the most common renal indication in the elderly. The TPE used for renal indications in the elderly is relatively safe. Trends toward death in the elderly may be multifactorial and not necessarily related to TPE.

Using Safety Barrier Analysis to Facilitate Quality Improvement in Health Care: Improving Venous Thromboembolism Prophylaxis as a Proof of Concept.

Effective quality improvement is a key factor in optimizing the care of hospitalized patients. Unfortunately, the US health care system has a poor safety record when compared to other major industries. For example, at 250 000 per year, medical errors are the third leading cause of death in the United States. Safety barrier management, a widely used methodology in high-risk industries such as commercial airline transportation and oil drilling, has not been widely used in traditional quality improvement efforts in health care, which rely more on standard lean Six Sigma quality approaches. The authors describe a quality improvement project that uses safety barrier analysis to help inform solutions to improve venous thromboembolism prophylaxis in hospitalized patients. This study found that safety barrier analysis helped inform solutions to improve venous thromboembolism prophylaxis at the study institution and can be a useful adjunct to standard lean Six Sigma methodologies for quality improvement in health care.

Impact of hospitalist vs. non-hospitalist services on length of stay and 30-day readmission rate in hip fracture patients.

OBJECTIVES: Hip fracture is a common and morbid condition, affecting a patient population with significant medical co-morbidities. A number of medical co-management models have been studied, with conflicting reports of effect on patient outcomes. Our objective was to compare outcomes for patients with hip fracture managed by hospitalist vs. non-hospitalist services at an academic medical center. METHODS: We conducted a retrospective cohort study of patients with hip fracture over 1 year, comparing those on hospitalist vs. non-hospitalist services. Outcomes included 30-day readmission and hospitalization ≤7 days, with comparison between patients admitted to hospitalist vs. non-hospitalist services. We performed multivariate analysis, adjusting for age, gender, race/ethnicity, insurance type, ASA score, and blood transfusion during hospitalization and days from admission to surgery. RESULTS: We identified 124 hospitalist and 53 non-hospitalist patients. In unadjusted analysis, hospitalist patients were more likely to have hospitalization ≤7 days (84.7% vs. 67.9%, p = 0.01). In adjusted analysis, hospitalist patients had lower odds of 30-day readmissions (OR 0.2, 95% CI 0.04-0.97) but no difference in odds of hospitalization ≤7 days (OR 2.1, 95% CI 0.82-5.66). CONCLUSIONS: Patients with hip fracture managed by hospitalist vs. non-hospitalist services had lower odds of 30-day readmission after discharge. Our results suggest benefit to hospitalist co-management of hip fracture patients.

Computerized decision support systems: improving patient safety in nephrology.

Incorrect prescription and administration of medications account for a substantial proportion of medical errors in the USA, causing adverse drug events (ADEs) that result in considerable patient morbidity and enormous costs to the health-care system. Patients with chronic kidney disease or acute kidney injury often have impaired drug clearance as well as polypharmacy, and are therefore at increased risk of experiencing ADEs. Studies have demonstrated that recognition of these conditions is not uniform among treating physicians, and prescribed drug doses are often incorrect. Early interventions that ensure appropriate drug dosing in this group of patients have shown encouraging results. Both computerized physician order entry and clinical decision support systems have been shown to reduce the rate of ADEs. Nevertheless, these systems have been implemented at surprisingly few institutions. Economic stimulus and health-care reform legislation present a rare opportunity to refine these systems and understand how they could be implemented more widely. Failure to explore this technology could mean that the opportunity to reduce the morbidity associated with ADEs is missed.