Pre-eclampsia Risk Prediction Model Proposed
An international consortium of researchers has developed and internally validated a model that predicts risk of
adverse outcomes associated with pre-eclampsia up to 7 days before complications arise (Lancet 2010 DOI:10.1016/S0140-6736(10)61351–7). While the investigators emphasize that the model needs to be externally validated, they suggest that it could lead to improved outcomes associated with pre-eclampsia and advances in pre-eclampsia-related research.
The authors, representing eight sites on three continents, considered 49 variables in the Pre-Eclampsia Integrated Estimate of Risk model (fullPIERS), but found six to be the most significant, including gestational age, presence of chest pain or dyspnea, oxygen saturation, platelet count, and creatinine and aspartate transaminase (AST) concentrations. The combined adverse maternal outcomes incorporated in the model were maternal mortality or one or more serious central nervous system, cardiorespiratory, hepatic, renal, or hematological morbidities.
The investigators developed the model in a prospective, multicenter study of 2,023 women who met their definition for pre-eclampsia. Of all the participants, 13% experienced an adverse maternal outcome at any time after enrolling in the study. The fullPIERS model classified nearly two-thirds of women as low-risk, with a predicted probability of adverse outcomes <0.25. Just 4% fell into the highest risk category, with a predicted probability of adverse outcomes ≥0.30. The model’s area under the receiver operating characteristic curve for predicting adverse maternal outcomes within 48 hours of enrollment was 0.88, and 0.70 for up to 7 days after enrollment.
The authors also found that using AST concentrations alone rather than a battery of AST, alanine transaminase, and lactate dehydrogenase testing provided adequate predictive power without loss of important information. Furthermore, they suggest that the model might eliminate the need for urea and routine coagulation studies.
A PIERS calculator is available on the study website.
Optimal HIV Screening, Treatment Algorithm Described
Yale and Stanford University researchers have determined that simultaneously expanding both screening for and treatment of human immunodeficiency virus (HIV) would offer the greatest health benefit and most cost-effective screening-treatment approach in the U.S. (Ann Intern Med 2010;153:778–89). The authors were interested in exploring this issue because the incidence of HIV infections has not decreased in recent years, highlighting the need to find better screening and treatment strategies. In addition, public health officials estimate that one-fifth of individuals living with HIV in the U.S. are unaware of their disease status, which suggests that expanded screening could directly benefit about 250,000 people.
To estimate the health benefits and cost of expanded HIV screening and antiretroviral therapy (ART), the investigators developed a dynamic HIV epidemic model that integrates epidemiologic, clinical, and economic data, and calculates population-level outcomes associated with varying combinations of screening and ART. This model projected that about 1.23 million new HIV infections would occur over 20 years, nearly three-quarters in high-risk populations, such as men who have sex with men. The authors assumed that HIV-infected individuals would be eligible to start ART when their CD4 cell count was 0.350 x 109 cells/L, but also considered the impact of starting treatment earlier, as well as different levels of ART utilization among eligible individuals. They considered different screening strategies, ranging from screening everyone annually to screening low-risk individuals once and those at high risk annually.
The authors found that one-time screening of low-risk individuals, combined with annual screening of those at high-risk while at the same time expanding ART utilization to 75% of those eligible for the therapy would prevent 17.3% of new infections at a cost of $21,580 quality adjusted life years, and that this was the most cost-effective strategy.
KRAS Mutations Associated with Worse Colorectal Cancer Outcomes
A systematic evidence review found that KRAS mutations were consistently associated with increased rates of treatment failure and reduced survival in patients with advanced colorectal cancer treated with anti-epidermal growth factor receptor (EGFR) therapy (Ann Intern Med 2011;154:37–49). According to the authors, the findings support recent Food and Drug Administration labeling changes restricting the use of anti-EGFR monoclonal antibodies to patients with colorectal cancer that test negative for KRAS mutations.
Several previous analyses of randomized controlled trials comparing anti-EGFR therapy with alternate treatments have evaluated whether KRAS mutations predict clinical outcomes. The researchers sought to summarize evidence about whether KRAS mutation status modifies the effect of anti-EGFR therapies versus other treatments, and to summarize whether KRAS status predicts clinically relevant outcomes in patients who receive anti-EGFR drugs.
The authors found that in comparison to KRAS wild-type patients, those who were KRAS-positive had shorter median overall survival, progression-free survival and time-to-progression. They also found higher treatment failure rates in patients with KRAS mutations than in wild-type patients. In a random-effects bivariate meta-analysis, the summary sensitivity of KRAS mutations for predicting lack of response was 0.49, and summary specificity was 0.93.Proteinuria Predicts Post-CABG Outcomes
New research indicates that preoperative proteinuria is a predictor of cardiac surgery-associated acute kidney injury (CSA-AKI) among patients undergoing coronary artery bypass graft (CABG) procedures (J Am Soc Nephrol 2011; doi: 10.1681/ASN.2010050553). These findings demonstrate that preoperative proteinuria “is an important, yet neglected, predictor for AKI after cardiac surgery,” according to the authors.
The investigators were interested in exploring this issue because CSA-AKI is one of the most significant and severe complications of cardiac surgery. Proteinuria has been strongly linked to adverse outcomes, and recent epidemiological studies have found that patients with proteinuria have a higher risk of adverse outcomes than those without proteinuria in the same chronic kidney stage. The latter studies suggested that glomerular filtration rate (GFR) and proteinuria should be used together to identify patients at risk.
The study involved 1,052 patients who underwent CABG, 17.4% of whom developed CSA-AKI. Overall, nearly 30% of patients had mild proteinuria prior to surgery, while 13.1% had heavy proteinuria. A step-wise logistic regression model indicated that mild proteinuria, heavy proteinuria, and stage 4 chronic kidney disease (CKD) were significantly associated with postoperative AKI. Mild proteinuria increased the risk of a patient with stage 3 CKD to equal that of stage 4 CKD. The authors also found that when mild proteinuria was present in patients with preserved GFR ≥60 mL/min per 1.73 m2, their risk was comparable to patients with stage 3 CKD. “These types of patients have previously been neglected, although they made up 33% of our cohort. This means that one third of patients undergoing surgery who are at an increased risk are not identified by the current risk scoring systems only based on serum creatinine or GFR measurements,” the authors wrote.