CLN Article

Diagnostic Profiles

Noninvasive Prenatal Testing Clinically Cost-Effective in Comparison to Other Methods

A cost-benefit analysis determined that noninvasive prenatal testing (NIPT) for trisomy 21 in high-risk pregnancies is both more effective clinically and less costly in comparison to first trimester combined or integrated screening (J Matern Fetal Neonatal Med 2013; doi:10.3109/14767058.2013.77-464). The study found that NIPT using cell-free DNA (cfDNA) analysis would lead to improved trisomy 21 detection and reduced euploid fetal loss, while requiring lower overall healthcare expenditures.

The researchers conducted the study because the new method of cfDNA has been shown in numerous studies to have a >99% detection rate for trisomy 21 with false positive rates <0.1% and recently has been endorsed by professional societies for use in high-risk pregnancies. However, cost-effectiveness analysis of NIPT has been limited to evaluating it as a contingent or secondary screening method.

The authors created a decision-analytic model to compare different prenatal screening strategies. The analysis compared NIPT to first trimester combined screening, which involves both serum markers—pregnancy associated plasma protein A and β-human chorionic gonadotropin (hCG)—and ultrasound, and integrated screening, which includes first trimester combined screening and quad screening of serum markers, alpha-fetoprotein, estriol, hCG, and inhibin A. They assumed that NIPT would be performed as the first-line test in women 35 years or older, or with other high-risk factors, or as the second-line test in those with a positive conventional screening test. Modeling was based on an estimated 4 million pregnant women in the U.S. undergoing first trimester prenatal screening.

Primary outcomes of the analysis were total costs for each screening strategy, the number of trisomy 21 cases detected, and the number of non-trisomy 21 fetal losses due to invasive procedures for each strategy. The researchers assumed the cost of NIPT to be $795.

The authors estimated that NIPT would detect 65% and 85% more trisomy 21 cases than first trimester combined screening and integrated screening, respectively, while reducing invasive procedures by >95% and euploid fetal losses by >99%. Total costs associated with NIPT also were lower than by the other two methods.

Marked Differences in Accuracy, Reliability Among Continuous Glucose Monitors

A comparative effectiveness analysis of three continuous glucose monitors (CGM) for blood glucose values from 36–563 mg/dL revealed marked differences in accuracy, precision, and reliability (Diabetes Care 2013;36:251–9). The researchers conducted the study because of the need to evaluate the accuracy and reliability of devices over large ranges of blood glucose values, multiple scheduled calibrations, and time rates of change in blood glucose levels.

The study involved six subjects with type 1 diabetes with a mean duration of disease of 32 years. Each subject participated in two 51-hour closed-loop blood glucose control experiments at the Massachusetts General Hospital Clinical Research Center. Subjects wore the three devices simultaneously in each experiment while reference-quality plasma glucose levels were assessed every 15 minutes for 48 hours. The researchers determined errors in paired plasma glucose-CGM measurements and data reporting percentages for each CGM device.

The CGM device with the best overall accuracy had an aggregate 48-hour mean absolute relative difference (MARD) of all paired points of 11.8±11.1%, compared with MARDs of 16.5±17.8%, and 20.3±18.0% for the other two devices, respectively. As a measure of reliability, two devices had 100% data reporting percentages, and one had 76%.

White Blood Cell Count Crucial for Predicting Course of B. pertussis Infection

A retrospective case review of infants hospitalized with Bordetella pertussis infection found that babies with more severe illness had higher mean and median white blood cell (WBC) counts and a more rapid rise in their total WBC counts (J Pediatric Infect Dis Soc 2013; doi:10.1093/JPIDS/PIS105). Based on their findings, the researchers concluded that even in infants with initially mild disease, early determination of WBC count and close WBC count monitoring is critical in predicting the severity and clinical course of B. pertussis infection.

The study took place at five Southern California hospitals and involved 31 infants who were no more than 90 days old when hospitalized for pertussis between 2009 and 2011. Infants who died or developed pulmonary hypertension were considered to have more severe pertussis.

Babies with severe disease had higher peak WBC counts in comparison to those with less severe disease, 74,100 versus 24,200. All infants with more severe pertussis had WBC counts ≥30,000, in comparison to just 36% of those with less severe infection. In babies with WBC counts ≥30,000, those with severe disease reached or exceeded the 30,000 threshold earlier in their disease course compared with those who had less severe illness, with a mean of 5.1 days versus 22.1 days from cough onset. Of the babies who had more than one WBC count taken within a 24-hour period, those with more severe disease were more likely to have a ≥50% increase in WBC count within a 24-hour period than those with less-severe disease, and all but one infant with severe disease experienced a ≥50% increase in WBC within 48 hours. In contrast, no infant with less severe infection experienced such an increase.

HBV Core Antibody Associated With HIV, Cleared and Chronic HCV

A longitudinal analysis of hepatitis B virus (HBV) serologic patterns revealed that isolated HBV core antibody (anti-HBc) is associated with HIV infection and both chronic and cleared hepatitis C virus (HCV) infection (Clin Infect Dis 2013;56:606–12). Anti-HBc also was found to be a stable pattern that rarely transitions to chronic hepatitis. The authors conducted this study because the physiological and clinical significance of isolated anti-HBc is unclear.

Isolated anti-HBc not found in conjunction with either hepatitis B surface antibody or hepatitis B surface antigen has been associated with coinfection with HIV, HCV, injection drug use, extremes of age, and lower CD4 T-cell count. However, only a few studies have looked longitudinally at HBV serologic patterns and they have been limited due to sample size, recruitment from areas with epidemic HBV, or exclusive enrollment of intravenous drug users.

The study involved 2,286 subjects from the Multicenter AIDS Cohort Study who were followed for 3.9 years and had complete HBV serologic data and one positive serology on at least one occasion from three different recruitment periods. The researchers performed HBV serologic testing and HCV antibody testing with enzyme immunoassays. If the latter was positive, HCV RNA testing was performed. Isolated anti-HBc was present in 14.2% of overall patient visits.

The investigators found that anti-HBc was most strongly associated with chronic HCV infection, with an odds ratio of 6.76, versus odds ratios of 3.03 and 2.19 for cleared HCV and HIV, respectively. Among subjects with HIV, highly active antiretroviral therapy was negatively associated with anti-HBc.