Jay R. McDonald

Rate of Kidney Function Decline Associates with Mortality

The effect of rate of decline of kidney function on risk for death is not well understood. Using the Department of Veterans Affairs national databases, we retrospectively studied a cohort of 4171 patients who had rheumatoid arthritis and early stage 3 chronic kidney disease (CKD; estimated GFR 45 to 60 ml/min) and followed them longitudinally to characterize predictors of disease progression and the effect of rate of kidney function decline on mortality. After a median of 2.6 years, 1604 (38%) maintained stable kidney function; 426 (10%), 1147 (28%), and 994 (24%) experienced mild, moderate, and severe progression of CKD, respectively (defined as estimated GFR decline of 0 to 1, 1 to 4, and >4 ml/min per yr). Peripheral artery disease predicted moderate progression of CKD progression. Black race, hypertension, diabetes, cardiovascular disease, and peripheral artery disease predicted severe progression of CKD. After a median of 5.7 years, patients with severe progression had a significantly increased risk for mortality (hazard ratio 1.54; 95% confidence interval 1.30 to 1.82) compared with those with mild progression; patients with moderate progression exhibited a similar trend (hazard ratio 1.10; 95% confidence interval 0.98 to 1.30). Our results demonstrate an independent and graded association between the rate of kidney function decline and mortality. Incorporating the rate of decline into the definition of CKD may transform a static definition into a dynamic one that more accurately describes the potential consequences of the disease for an individual.

Infection-associated clinical outcomes in hospitalized medical evacuees after traumatic injury: trauma infectious disease outcome study.

Infections have long been known to complicate care in patients following traumatic injury frequently leading to excess morbidity and mortality.1, 2 In no setting is this more well-recognized than the challenging environment of combat casualty care. During the current military conflicts in Iraq and Afghanistan, Operations Iraqi and Enduring Freedom (OIF/OEF), major advances resulting in increased survival among wounded personnel have been observed. These include enhanced training of medics, forward deployment of surgical assets, rapid medical evacuation, and improvements in body armor.3–5 The significant advances leading to survival are coupled with major challenges in care due to the extensive nature of the injuries, profound bone and soft tissue disruption, and extensive wound contamination.6, 7 In addition, the rapid transit of these patients through multiple echelons of medical care places significant obstacles on infection control in an era of increasing risk due to hospital-associated multidrug resistant (MDRO) organisms.8, 9 The U.S. Department of Defense (DoD) has implemented a range of measures to improve combat casualty care and mitigate risk of infectious complications. A Joint Theater Trauma System and Joint Theater Trauma Registry (JTTR) have been developed to benchmark metrics and to provide a timely assessment of performance improvement interventions.5, 10, 11 Efforts to prevent infection include the development of guidelines for the prevention of infection related to combat injuries through comprehensive review of current evidence and consensus review by military and civilian experts in trauma, infectious disease, infection control, preventive medicine, and surgical specialties.12 In addition, standardized infection control measures across echelons of care accompanied by enhanced MDRO surveillance and serial evaluation have also been implemented.13, 14 Despite the growing literature describing infectious complications of combat-related trauma, there is still a lack of prospectively collected standardized infection data that includes specific therapy, microbiological findings and clinical outcomes across treatment facilities. This report describes the initial data and current status of an ongoing 5-year prospective observational cohort study of infectious complications associated with traumatic injury sustained during deployment, the DoD-Department of Veterans Affairs (VA) Trauma Infectious Disease Outcomes Study (TIDOS).

TNF-α Antagonist Use and Risk of Hospitalization for Infection in a National Cohort of Veterans With Rheumatoid Arthritis

Medications used to treat rheumatoid arthritis (RA) may confer an increased risk of infection. We conducted a retrospective cohort study of veterans with RA followed in the United States Department of Veterans Affairs health care system from October 1998 through September 2005. Risk of hospitalization for infection associated with tumor necrosis factor (TNF)-&agr; antagonists therapy was measured using an extension of Cox proportional hazards regression, adjusting for demographic characteristics, comorbid illnesses, and other medications used to treat RA.A total of 20,814 patients met inclusion criteria, including 3796 patients who received infliximab, etanercept, or adalimumab. Among the study cohort, 1465 patients (7.0%) were hospitalized at least once for infection. There were 1889 hospitalizations for infection. The most common hospitalized infections were pneumonia, bronchitis, and cellulitis. Age and several comorbid medical conditions were associated with hospitalization for infection. Prednisone (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.88-2.43) and TNF-&agr; antagonist use (HR, 1.24; 95% CI, 1.02-1.50) were associated with hospitalization for infection, while the use of disease-modifying antirheumatic drugs (DMARDs) other than TNF-&agr; antagonists was not. Compared to etanercept, infliximab was associated with risk for hospitalization for infection (HR, 1.51; 95% CI, 1.14-2.00), while adalimumab use was not (HR, 0.95; 95% CI, 0.68-1.33). In all treatment groups, rate of hospitalization for infection was highest in the first 8 months of therapy.We conclude that patients with RA who are treated with TNF-&agr; antagonists are at higher risk for hospitalization for infection than those treated with other DMARDs. Prednisone use is also a risk factor for hospitalization for infection.Abbreviations: CI = confidence interval, DMARD = disease-modifying antirheumatic drug, HFI = hospitalization for infection, HR = hazard ratio, ICD-9-CM = International Classification of Diseases, Version 9, Clinical Modification, NHDS = National Hospital Discharge Survey, RA = rheumatoid arthritis, TNF-&agr; = tumor necrosis factor-&agr;, VA = Veterans Affairs.

Enterococcal prosthetic valve infective endocarditis: report of 45 episodes from the International Collaboration on Endocarditis-merged database

Enterococcal prosthetic valve infective endocarditis (PVE) is an incompletely understood disease. In the present study, patients with enterococcal PVE were compared to patients with enterococcal native valve endocarditis (NVE) and other types of PVE to determine differences in basic clinical characteristics and outcomes using a large multicenter, international database of patients with definite endocarditis. Forty-five of 159 (29%) cases of definite enterococcal endocarditis were PVE. Patients with enterococcal PVE were demographically similar to patients with enterococcal NVE but had more intracardiac abscesses (20% vs. 6%; p=0.009), fewer valve vegetations (51% vs. 79%; p<0.001), and fewer cases of new valvular regurgitation (12% vs. 45%; p=0.01). Patients with either enterococcal PVE or NVE were elderly (median age, 73 vs. 69; p=0.06). Rates of in-hospital mortality, surgical intervention, heart failure, peripheral embolization, and stroke were similar in both groups. Patients with enterococcal PVE were also demographically similar to patients with other types of PVE, but mortality may be lower (14% vs. 26%; p=0.08). Notably, 93% of patients with enterococcal PVE came from European centers, as compared with only 79% of patients with enterococcal NVE (p=0.03). Thus, patients with enterococcal PVE have higher rates of myocardial abscess formation and lower rates of new regurgitation compared to patients with enterococcal NVE, but there are no differences between the groups with regard to surgical or mortality rates. In contrast, though patients with enterococcal PVE and patients with other types of PVE share similar characteristics, mortality is higher in the latter group. Importantly, the prevalence of enterococcal PVE was higher in the European centers in this study.

Acute Infective Endocarditis

Acute infective endocarditis is a complex disease with changing epidemiology and a rapidly evolving knowledge base. To consistently achieve optimal outcomes in the management of infective endocarditis, the clinical team must have an understanding of the epidemiology, microbiology, and natural history of infective endocarditis, as well as a grasp of guiding principles of diagnosis and medical and surgical management. The focus of this review is acute infective endocarditis, though many studies of diagnosis and treatment do not differentiate between acute and subacute disease, and indeed many principles of diagnosis and management of infective endocarditis for acute and subacute disease are identical.

Increased Body Mass Index Is Associated With Improved Survival in United States Veterans With Diffuse Large B-Cell Lymphoma

PURPOSE Obesity increases the risk of death from many malignancies, including non-Hodgkins lymphoma (NHL). In diffuse large B-cell lymphoma (DLBCL), the most common form of NHL, the association between body mass index (BMI) at diagnosis and survival is unclear. PATIENTS AND METHODS We evaluated the association between BMI at diagnosis and overall survival in a retrospective cohort of 2,534 United States veterans diagnosed with DLBCL between October 1, 1998 and December 31, 2008. Cox modeling was used to control for patient- and disease-related prognostic variables. RESULTS Mean age at diagnosis was 68 years (range, 20 to 100 years); 64% of patients were overweight (BMI, 25 to < 30) or obese (BMI, ≥ 30). Obese patients were significantly younger, had significantly fewer B symptoms, and trended toward lower-stage disease, compared with other BMI groups. Cox analysis showed reduced mortality in overweight and obese patients (overweight: hazard ratio [HR], 0.73; 95% CI, 0.65 to 0.83; obese: HR, 0.68; 95% CI, 0.58 to 0.80), compared with normal-weight patients (BMI, 18.5 to < 25). Treatment during the rituximab era reduced the risk of death without affecting the association between BMI and survival. Disease-related weight loss occurred in 29% of patients with weight data 1 year before diagnosis. Cox analysis based on BMI 1 year before diagnosis continued to demonstrate reduced risk of death in overweight and obese patients. CONCLUSION Being overweight or obese at the time of DLBCL diagnosis is associated with improved overall survival. Understanding the mechanisms responsible for this association will require further study.

Tumor necrosis factor-α blockade, cardiovascular outcomes, and survival in rheumatoid arthritis

The effect of TNF-α blockade on the risk of cardiovascular outcomes and long-term survival in patients with rheumatoid arthritis (RA) is not known. We assembled a cohort of 20,811 (75,329 person-years) U.S. veterans who were diagnosed with RA between October 1998 and September 2005, and who were treated with a disease-modifying anti-rheumatic drug (DMARD). Cox survival models were built to examine the effect of TNF-α antagonists on the risk of a composite endpoint of cardiovascular outcomes defined as the occurrence of atherosclerotic heart disease, congestive heart failure, peripheral artery disease, or cerebrovascular disease, and on the risk of death. Treatment with TNF-α antagonists was not associated with a significant effect on the composite endpoint of cardiovascular outcomes. When each outcome was examined separately, the use TNF-α antagonists was not associated with an increased risk of atherosclerotic heart disease, congestive heart failure, or peripheral artery disease, but it was associated with decreased risk of cerebrovascular disease (hazard ratio [HR] = 0.83; confidence interval [CI] = 0.70-0.98). The use of TNF-α antagonists did not affect the risk of death (HR = 0.99; CI = 0.87-1.14). In subgroup analyses, the use TNF-α antagonists was associated with a reduced risk of cardiovascular outcomes (HR = 0.90, CI = 0.83-0.98) in patients younger than the median age of our cohort (63 years). The use TNF-α antagonists was not associated with a change in the risk of death in any other subgroup. These results show that the risk of cardiovascular events and survival in patients who receive TNF-α antagonists is not different than those who receive other DMARDs.

Mental health disorders and the risk of AIDS-defining illness and death in HIV-infected veterans.

Objective:Mental health comorbidities are common in HIV-infected veterans and can impact clinical outcomes for HIV. We examined the impact of mental health diagnoses on progression to AIDS-defining illness (ADI) and death in a large cohort of HIV-infected veterans who accessed care between 2001 and 2006. Design:Retrospective cohort study using the national Veterans Health Administration (VHA) HIV Clinical Case Registry. Methods:We identified HIV-infected veterans initiating combination antiretroviral therapy (cART) within the VHA between 2000 and 2006. The prevalences of the following mental health diagnoses were examined: schizophrenia, bipolar disorder, depression, anxiety, and substance use disorder. Cox proportional hazards models were constructed to examine the relationship between mental health conditions and two outcomes, all-cause mortality and ADI. Models were computed before and after adjusting for confounding factors including age, race, baseline CD4 cell count, comorbidities and cART adherence. Results:Among 9003 veterans receiving cART, 31% had no mental health diagnosis. Age, race, baseline comorbidity score, CD4, and cART adherence were associated with shorter time to ADI or death. All-cause mortality was more likely among veterans with schizophrenia, bipolar disorder and substance use, and ADI was more likely to occur among veterans with substance use disorder. Conclusions:Our results demonstrate the high prevalence of mental health diagnoses among HIV-infected veterans. In the era of highly active antiretroviral therapy, presence of psychiatric diagnoses impacted survival and development of ADI. More aggressive measures addressing substance abuse and severe mental illness in HIV-infected veterans are necessary.

Greater variability in kidney function is associated with an increased risk of death

Intra-individual variability in kidney function is a common phenomenon; however, predictors of kidney function variability and its prognostic significance are not known. To examine this question, we assembled a cohort of 51,304 US veterans with an estimated glomerular filtration rate (eGFR) <60 ml/min at the end of the study period and who had at least two eGFR measurements during the previous 3 years. Variability in kidney function was defined for each patient as the coefficient of variation of the regression line fitted to all outpatient measures of eGFR during this time frame. In adjusted analyses, blacks, women, and those with Current Procedural Terminology and ICD-9-CM diagnostic codes for hypertension, diabetes, cardiovascular disease, peripheral artery disease, chronic lung disease, hepatitis C, dementia, acute kidney injury, and those with a greater number of hospitalizations had greater variability in eGFR. After a median follow-up of 4.9 years, there were 23.66%, 25.68%, and 31.23% deaths among patients in the lowest, intermediate, and highest tertiles of eGFR variability, respectively. Compared with the referent (those in the lowest tertile), patients in the highest tertile had a significantly increased risk of death with a hazard ratio of 1.34 (1.28-1.40), an association consistently present in all sensitivity analyses. Thus, our results demonstrate that greater variability in kidney function is independently associated with increased risk of death.

Mycobacterium avium-intracellulare cellulitis occurring with septic arthritis after joint injection: a case report.

BackgroundCellulitis caused by Mycobacterium avium-intracellulare has rarely been described. Mycobacterium avium-intracellulare is a rare cause of septic arthritis after intra-articular injection, though the causative role of injection is difficult to ascertain in such cases.Case presentationA 57-year-old with rheumatoid arthritis treated with prednisone and azathioprine developed bilateral painful degenerative shoulder arthritis. After corticosteroid injections into both acromioclavicular joints, he developed bilateral cellulitis centered over the injection sites. Skin biopsy showed non-caseating granulomas, and culture grew Mycobacterium avium-intracellulare. Joint aspiration also revealed Mycobacterium avium-intracellulare infection.ConclusionAlthough rare, skin and joint infections caused by Mycobacterium avium-intracellulare should be considered in any immunocompromised host, particularly after intra-articular injection. Stains for acid-fast bacilli may be negative in pathologic samples even in the presence of infection; cultures of tissue specimens should always be obtained.