Peritoneal dialysis outcomes in a modern cohort of overweight patients

Background

The incidence of obesity is increasing both in the general population and in incident dialysis patients. While there is evidence that being overweight is associated with good outcomes in hemodialysis, the evidence in peritoneal dialysis (PD) patients is not very clear. We studied a modern cohort of PD patients to examine outcomes in large patients.

Methods

Forty-three patients who started PD, who weighed more than 90 kg at dialysis initiation, between January/2000 and June/2010 were matched with 43 control patients who weighed less than 90 kg. Detailed review of the charts was undertaken.

Results

The mean weight and body mass index of the wt < 90 kg group were 69.3 ± 11.3 kg and 25.0 ± 3.9 kg/m². The number of peritonitis episodes per year was 0.33 ± 0.6 (wt < 90 kg) and 0.82 ± 1.7 (wt ≥ 90 kg) (p = 0.26). The median time to first peritonitis showed a trend toward earlier peritonitis in larger patients [9.5 (4.3, 27) months in wt ≥ 90 kg, 19.1(7.9, 30.8) months in wt < 90 kg] but did not reach statistical significance (p = 0.12). Surprisingly, hernias and leaks were more common in the weight <90 kg group (44 vs. 18.6 % p = 0.02). There was no difference in total number of hospitalizations or the number of days hospitalized. Kaplan–Meier analysis of survival on PD showed no differences between the two groups (logrank p = 0.99). Cox regression analysis using age, race, cause of ESRD due to diabetes and Charlson comorbidity index as the covariates did not show weight to be associated with survival on PD.

Conclusions

Large patients tend to do just as well on PD, with survival on PD being no different compared to individuals with lower weight and body mass index.     

Differential Influence of Age on the Relationship between Genetic Mismatch and A(H1N1)pdm09 Vaccine Effectiveness

Assessment of influenza vaccine effectiveness (VE) and identification of relevant influencing factors are the current priorities for optimizing vaccines to reduce the impacts of influenza. To date, how the difference between epidemic strains and vaccine strains at genetic scale affects age-specific vaccine performance remains ambiguous. This study investigated the association between genetic mismatch on hemagglutinin and neuraminidase genes and A(H1N1)pdm09 VE in different age groups with a novel computational approach. We found significant linear relationships between VE and genetic mismatch in children, young adults, and middle-aged adults. In the children’s group, each 3-key amino acid mutation was associated with an average of 10% decrease in vaccine effectiveness in a given epidemic season, and genetic mismatch exerted no influence on VE for the elderly group. We demonstrated that present vaccines were most effective for children, while protection for the elderly was reduced and indifferent to vaccine component updates. Modeling such relationships is practical to inform timely evaluation of VE in different groups of populations during mass vaccination and may inform age-specific vaccination regimens.     

Importance of catalase in the disposal of hydrogen peroxide within human erythrocytes

The catalase within normal, intact human erythrocytes was completely inactivated with amino triazole. The rate of 14CO2 evolution, when the cells were subsequently incubated with 14C-labeled glucose, provided a measure of the rate at which NADPH was being oxidized by the glutathione peroxidase/reductase system for the disposal of H2O2. This rate was determined in control cells and in catalase-inactivated cells while the cells were exposed to H2O2, which was generated at various constant and predetermined rates by glucose oxidase. The results indicated that catalase handles approximately half of the generated H2O2. The glutathione peroxidase/reductase mechanism accounted for the other half. These results are in agreement with our earlier findings on erythrocytes of a subject with a genetic deficiency of catalase. However, an unexpected result with the present approach was the finding that the increased dependence on the glutathione peroxidase/reductase mechanism did not occur until greater than 98% of the catalase had been inactivated. The latter observation indicates that catalase and the glutathione peroxidase/reductase system function intracellularly in a manner very different from that previously ascribed to them. An explanation of the findings requires that the two methods of H2O2 disposal function in a coordinated way, such as a sequential action in which the glutathione peroxidase/reductase system is the rate-limiting step.     

Endothelial Activation and Chemoattractant Expression are Early Processes in Isolated Blast Brain Injury

Blast injuries are an increasing problem in military conflicts and terrorist incidents. Blast-induced traumatic brain injury has risen to prominence and represents a specific form of primary brain injury, with sufficiently different physical attributes (and possibly biological consequences) to be classified separately. There is increasing interest in the role of blast in initiating inflammatory responses, which may be linked to the pathological processes seen clinically. Terminally anaesthetised rats were exposed to a blast wave directed at the cranium, using a bench-top blast wave generator. Control animals were not exposed to blast. Animals were killed after 8 h, and the brains examined for evidence of an inflammatory response. Compared to controls, erythropoietin, endothelial integrins, ICAM and sVCAM, and the pro-inflammatory cytokine, monocyte chemoattractant protein-1 (MCP-1) were significantly elevated. Other pro-inflammatory cytokines, including MIP-1α, were also detectable, but levels did not permit accurate quantification. Six inflammatory genes examined by qRT-PCR exhibited a biologically significant increase in activity in the blast-exposed animals. These included genes supporting chemokines responsible for monocyte recruitment, including MCP-1, and chemokines influencing T cell movement. Brain injury is usually accompanied by pathological neuro-inflammation. This study shows that blast brain injury is no exception, and the data provide important mechanistic clues regarding the drivers of such inflammation. Whilst this effect alone is unlikely to be responsible for the totality of consequences of blast brain injury, it suggests a mechanism that may be priming the cerebral inflammatory response and rendering cerebral tissue more susceptible to the deleterious effects of systemic inflammatory reactions.     

Safety and Effectiveness of Drug-Eluting Versus Bare-Metal Stents in Saphenous Vein Bypass Graft Percutaneous Coronary Interventions : Insights From the Veterans Affairs CART Program

Background

Stenosis of saphenous vein grafts (SVGs) after coronary artery bypass grafting (CABG) is common and often requires percutaneous coronary interventions (PCI) for treatment. However, data for the effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) in SVG-PCI are unclear.

Objectives

This study sought to examine the association between DES versus BMS used during SVG PCI and clinical outcomes in the national Veterans Affairs integrated healthcare system.

Methods

We studied a national cohort of 2,471 post-CABG veterans undergoing SVG-PCI between 2008 and 2011 at all Veterans Affairs hospitals and compared clinical outcomes of between those receiving DES and BMS. Clinical outcomes included procedural complications, myocardial infarction (MI), and all-cause mortality. Comparisons were made in a propensity-matched cohort using Cox proportional hazards regression models.

Results

DES were used in 1,549 SVG-PCI patients (63%) and the use of DES increased progressively with each calendar year (50% in 2008 to 69% in 2011). Incidence of procedural complications was low and comparable in both groups (2.8% among BMS vs. 2.3% among DES patients; p = 0.54). During long-term (>2 years) follow-up, use of DES was associated with lower mortality than BMS (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.57 to 0.89) and similar rates of MI (HR: 0.94; 95% CI: 0.71 to 1.24) in the propensity-matched cohort.

Conclusions

In a national cohort of veterans, we observed widespread and increasing use of DES during SVG-PCI. In long-term follow-up, compared with BMS, DES use was safe and effective in SVG-PCI patients.     

Building Strong Research Partnerships Between Public Health and Researchers: A VA Case Study

We are in a new era of partner-based implementation research, and we need clear strategies for how to navigate this new era. Drawing on principles from community-based participatory research, the Clinical Public Health group of the Department of Veterans Affairs and the HIV/Hepatitis Quality Enhancement Research Initiative (HHQUERI) forged a longstanding partnership that has improved the care of Veterans with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus. An exemplar HIV testing project epitomizes this partnership and is discussed in terms of the lessons learned as a result of our high level of collaboration around design, analysis, implementation, and dissemination across projects over the past several years. Lessons learned through this partnered testing program involve respecting different time horizons among the partners, identifying relevant research questions for both parties, designing flexible studies, engaging all partners throughout the research, and placing an emphasis on relationship building at all times. These lessons and strategies can benefit others conducting partner-based research both within the Veterans Health Administration (VA) and in other integrated healthcare systems.