Publications

There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques.

OBJECTIVE

To inform development of intensive management programs for high-cost patients, this study investigated the relationship between psychiatric diagnoses and patterns of health care utilization among high-cost patients in the Department of Veterans Affairs (VA) health care system.

METHODS

The costliest 5% of patients who received care in the VA in fiscal year 2010 were assigned to five mutually exclusive hierarchical groups on the basis of diagnosis codes: no mental health condition, serious mental illness, substance use disorder, posttraumatic stress disorder (PTSD), and depression. Multivariable linear regression was used to examine associations between diagnostic groups and use of mental health and non-mental health care and costs of care, with adjustment for sociodemographic characteristics. The proportion of costs generated by mental health care was estimated for each group.

RESULTS

Among 261,515 high-cost VA patients, rates of depression, substance use disorder, PTSD, and serious mental illness were 29%, 20%, 17%, and 13%, respectively. Individuals in the serious mental illness and substance use disorder groups were younger and had fewer chronic general medical conditions and higher adjusted rates of mental health care utilization; they also had a greater proportion of costs generated by mental health care (41% and 31%, respectively) compared with individuals in the PTSD and depression groups (18% and 11%, respectively).

CONCLUSIONS

Optimal management of high-risk, high-cost patients may require stratification by psychiatric diagnoses, with integrated care models for patients with multiple chronic conditions and comorbid mental health conditions and intensive mental health services for patients whose primary needs stem from mental health conditions.

OBJECTIVE

There is a need to determine which response measures in lupus nephritis trials are most predictive of good long-term renal function. We used data from the Euro-Lupus Nephritis Trial to evaluate the performance of proteinuria, serum creatinine (Cr), and urinary red blood cells (RBCs) as predictors of good long-term renal outcome.

METHODS

Patients from the Euro-Lupus Nephritis Trial with proteinuria, serum Cr, and urinary RBC measurements at 3, 6, or 12 months and with a minimum of 7 years of followup were included (n = 76). We assessed the ability of these clinical biomarkers at 3, 6, and 12 months after randomization to predict good long-term renal outcome (defined as a serum Cr value ≤1.0 mg/dl) at 7 years. Receiver operating characteristic curves were generated to assess parameter performance at these time points and to select the best cutoff for individual parameters. Sensitivity and specificity were calculated for the parameters alone and in combination.

RESULTS

A proteinuria value of <0.8 gm/day at 12 months after randomization was the single best predictor of good long-term renal function (sensitivity 81% and specificity 78%). The addition of serum Cr to proteinuria as a composite predictor did not improve the performance of the outcome measure; addition of urinary RBCs as a predictor significantly decreased the sensitivity to 47%.

CONCLUSION

This study demonstrates that the level of proteinuria at 12 months is the individual best predictor of long-term renal outcome in patients with lupus nephritis. Inclusion of urinary RBCs as part of a composite outcome measure actually undermined the predictive value of the trial data. We therefore suggest that urinary RBCs should not be included as a component of clinical trial response criteria in lupus nephritis.