Unnecessary Testing for Inherited Thrombophilia Might Cost in Excess of $500 Million Annually 

Unnecessary testing for inherited thrombophilia might be costing Medicare $300 million to $672 million annually, according to University of Michigan Health System researchers (J Hosp Med 2016;11:801–4). The findings underscore the impact of routine testing for inherited thrombophilia in the context of venous thromboembolism (VTE), which is “not clinically useful, cost-effective, or reliable,” according to the authors.

The authors conducted this analysis as part of the Choosing Wisely campaign’s Things We Do for No Reason series, which reviews practices that “have become common parts of hospital care but which may provide little value” to patients.

Inherited thrombophilia affects about 7% of the population, and these individuals have a relative risk of VTE 3- to 20-times higher than in the general population. Still, “available evidence suggests that testing for inherited thrombophilia is not recommended in most clinical settings,” according to the authors. Inherited thrombophilia testing results are unlikely to affect clinical management in most settings, they added.

Regardless of whether an underlying inherited thrombophilia is uncovered, patients with recurrent VTE generally receive long-term anticoagulation therapy, which would render inaccurate the inherited thrombophilia testing.

There is limited evidence about when testing for inherited thrombophilia is warranted. Evaluation of Genomic Applications in Practice and Prevention guidelines note that such testing generally is based on individual risk, while also observing that there is a “paucity of data” on managing or providing prophylaxis therapy to patients with homozygous or compound heterozygous FVL or P20210 mutations.

The authors estimated direct costs of $1,100 to $2,400 for thrombophilia panel testing, based on the experience of a large commercial laboratory. They multiplied this cost by the 280,000 claims for thrombophilia analysis submitted to Medicare in 2014 to arrive at their annual estimated cost. The investigators suggested that inherited thrombophilia testing should be considered on an individual basis in the outpatient setting and with appropriate genetic counseling.

Task Force Endorses FIT Over gFOBT for Colorectal Cancer Screening 

In a new consensus statement, the U.S. Multi-Society Task Force finds that one-time fecal immunochemical testing (FIT) has approximately 80% sensitivity for detecting colorectal cancer, and about 20–30% sensitivity for detecting advanced adenomas. As such, FIT out-performs three-card guaiac-based fecal occult blood testing (gFOBT) (Gastrointest Endosc 2016; doi.org/10.1016/j.gie.2016.09.025).

The Multi-Society Task Force includes representatives from three gastroenterology-related associations with a special interest in colorectal cancer. The group conducted this review to assist physicians in using FIT, to support organizations that might be developing colorectal cancer screening programs, and to address important clinical questions regarding FIT. The review includes a summary of FIT devices cleared by the Food and Drug Administration, as well as a list of FIT and FOBT manufacturers.

The task force also recommended a one-sample annual FIT screening. While the authors found that quantitative and qualitative FITs share similar performance characteristics, they recommended quantitative rather than qualitative tests, owing to the former’s “improved quality control with automated reading and the ability to adjust fecal hemoglobin cutoff concentrations to define a positive test.” 

The task force looked at whether FIT screening should be performed in warmer months of the year because of its reliance on a stable hemoglobin molecule but found insufficient evidence to recommend against distributing or mailing FITs when environmental temperatures are above a certain level. The authors also investigated whether FIT performance might be affected by FITs belatedly submitted to labs, which might deteriorate globin protein in the sample. While the group didn’t find strong evidence suggesting sample return delay affects performance, it advised that patients be counseled to return tests promptly. The authors found that <5% of FITs cannot be processed once received in laboratories. 

Circulating Tumor Cell Analysis Distinguishes Chemosensitive Versus chemorefractory Small Cell Lung Cancer 

University of Manchester (U.K.) researchers reported that analysis of copy-number changes in circulating tumor cells (CTCs) of small cell lung cancer (SCLC) patients distinguishes between chemosensitive and chemorefractory forms of this disease (Nat Med 2016; doi:10.1038/nm.4239). The findings could lay the groundwork for more effective treatment of this aggressive form of cancer, according to the study co-author, Caroline Dive, PhD.

“Unfortunately, we have very few treatment options for patients with SCLC, and none at all for those whose cancer is resistant to chemotherapy,” said Dive. “By identifying differences in the patterns of genetic faults between patients, we now have a starting point to begin to understand more about how drug resistance develops in patients with this aggressive form of lung cancer.”

Because SCLC patients only rarely undergo surgical resection and SCLC biopsies generally are of poor quality or small size, the SCLC genome has been less investigated than many other cancers, with fewer than 200 tumors reported thus far, according to the authors. Dive and her colleagues used CTCs as a means to better understand the link between SCLC genetic aberrations and clinical outcomes.

Using a training set of 13 samples from SCLC patients—six already determined to be chemorefractory, and seven chemosensitive—the researchers enriched and enumerated CTCs with a range of 27–20,815 CTCs per 7.5 mL of blood, then isolated individual and pooled CTCs as well as white blood cells. The investigators analyzed 13 genes known to be frequently amplified or deleted in SCLC but didn’t find a clear signature suggesting that a tumor was either chemorefractive or chemosensitive.

When the researchers performed a copy-number analysis, they found 2,281 loci with copy-number changes that differed between the chemosensitive and chemorefractive patients. The investigators developed 16 copy-number aberration profiles by clustering these copy-number changes according to chromosomal location and copy-number aberration status.

From the copy-number aberration profiles, the authors developed a predictive model, which they validated in the training samples, samples from another 18 SCLC patients, and CTCs derived from six SCLC explant tumors. Overall, the predictive model correctly assigned 83.3% of cases as either chemorefractive or chemosensitive. 

Acute Kidney Injury Common Among Children in ICU 

One-quarter of children and young adults admitted to pediatric intensive care units (ICU) develop acute kidney injury (AKI), placing them at increased risk of poor outcomes, including death (N Engl J Med 2016; doi:10.1056/NEJMoa1611391). Overall, this study of 4,683 patients admitted to 32 ICUs on four continents found that severe AKI developed in 11.6% of patients, and that those with severe AKI had a 1.77 adjusted odds ratio for death by day 28. The findings underscore “the need for systematic surveillance for [AKI] at the time of admission” to PICU, wrote the investigators.

The authors also found that assessing AKI by plasma creatinine level alone failed to identify AKI in two-thirds of patients who met the urine output criteria for AKI. This highlights the necessity to use both plasma creatinine level and urine output to define AKI, according to the authors.

The study involved patients 3 months to age 25 with a predicted ICU stay of at least 48 hours at the time of admission. The investigators estimated glomerular filtration rate using the original Schwartz formula and applied Kidney Disease: Improving Global Outcomes criteria to creatinine level and urine output to classify AKI. The authors observed a step-wise increase in 28-day mortality associated with worsening severity of AKI.