Iron Deficiency Testing Deficient in Ulcerative Colitis

Research from a nationwide cohort of anemic ulcerative colitis (UC) patients found that 31% did not undergo recommended tests for iron deficiency (ID), and of those tested, nearly half with iron deficiency anemia (IDA) were not treated with iron replacement therapy (Inflamm Bowel Dis 2016;0:1–8). The findings underscore the need for physician education about the need to diagnose and treat IDA in its early stages. 

Treatment guidelines issued in 2007 called for UC patients to be screened regularly for anemia and ID with hemoglobin (Hb), C-reactive protein (CRP), ferritin, and transferrin saturation (TSAT) testing. Uptake of this guideline, however, is “low,” according to the authors. Prior studies in Europe and at a single U.S. center showed that testing and treatment for ID in patients with UC was low, despite a high prevalence of IDA in this population. The authors sought to identify factors associated with testing and treatment frequency and thereby pinpoint quality improvement targets. 

The investigators accessed data from the Veterans Affairs (VA) pharmacy benefits management and corporate data warehouse databases to identify veterans newly diagnosed with UC during an 11-year period. They defined anemia as Hb <13 g/dL in men and <12 g/dL in women. The criteria for ID was ferritin <30 µg/L and/or TSAT <16%, or ferritin <100 µg/L and active disease, according to CRP levels, endoscopy reports, and use of prednisone. 

Overall, 70% of patients developed anemia during a median of 8 years’ follow-up. Of these patients, just 68.6% had an iron study evaluation. Less than half of patients with mild anemia (46%) were tested for ID, in comparison to 91% with severe anemia. The authors also found that patients who reside in the Midwest and South were less likely than those in the Northeast and West to undergo testing. 

Although the investigators cautioned that their study involved only VA patients, more likely to be middle-aged and elderly white men, they added that this population is similar socioeconomically to the general U.S. population. They suggested that their findings highlight physician attitudes that “anemia is an inevitable concomitant symptom of inflammatory bowel disease,” and that many delay testing and treatment for the disease until patients have symptoms of anemia. The authors also opined that physicians underappreciate the “profound impact of anemia” on patients’ quality of life, and recommended that testing for ID in patients with anemia should become a quality process indicator for UC. 

Early Procalcitonin Testing Associated With Favorable Sepsis-Related Outcomes

A retrospective study of administrative data from more than 130,000 patients has found that procalcitonin (PCT) testing on the day of intensive care unit (ICU) admission in patients with suspected or documented sepsis and related conditions was associated with significantly lower hospital and ICU length of stay (LOS) and decreased total cost (Chest 2016; doi/10.1016/j.chest.2016.06.046). While cautioning that the mechanisms behind these outcomes are “not immediately evident,” the authors suggested that “it is likely that PCT is being used both to help rule-out and rule-in sepsis on ICU admission.” 

The researchers conducted the study because although PCT has been a diagnostic criterion for sepsis since 2012, and other research has shown PCT has good specificity for causes of suspected infection, PCT testing has not been “uniformly adopted, in part because of cost considerations.” 

The authors accessed data during a 3-year period from 550 hospitals in the Premier Healthcare Database. They examined records on 33,569 patients who were at least 18 years old with an admitting or discharge diagnosis code consistent with suspected or documented sepsis, septicemia, systemic inflammatory response syndrome, or shock, and on 98,543 propensity-matched patients who did not have PCT testing. 

In comparing outcomes between the PCT versus non-PCT patients using multivariable regression analysis, PCT testing was associated with >1 day shorter hospital LOS, 0.2 day shorter ICU LOS, 0.72 days shorter antibiotic exposure, and nearly $3,000 less in hospital costs. In contrast to these trends, laboratory costs in patients with PCT testing was $81 higher than in those without PCT testing, perhaps reflecting the additional cost of PCT testing, according to the authors.  

Rapid Point-of-Care Assay for Acetaminophen-Related Liver Injury Compares Favorably to Reference Method

A proof-of-concept study showed that a competitive point-of-care (POC) immunoassay is highly concordant with the reference standard high pressure liquid chromatography with electrochemical detection (HPLC-EC) for detecting acetaminophen-associated acute liver injury (ALI) (Clin Gastroenterol Hepatol 2016; doi:10.1016/j.cgh.2016.09.007). This POC test might help guide clinical management of patients with acetaminophen-related ALI. 

The authors sought to develop a rapid, reliable POC assay to detect acetaminophen protein adducts as a way to address challenges in the diagnostic work-up of acetaminophen toxicity. Clinicians use the Rumack Nomogram to identify acetaminophen-related ALI and acute liver failure, but it is applicable for only the first 18–24 hours after overdose, due to the short elimination half-life of acetaminophen in the peripheral circulation and inaccurate patient reporting of acetaminophen exposure. HPLC-EC accurately detects acetaminophen-protein adducts formed after toxic intake of the drug, but it requires complex equipment and trained laboratory personnel. Prior studies have shown the median elimination half-life of acetaminophen protein-adducts to be 42 hours, versus 5.4 hours for the parent drug. 

The authors developed a competitive, lateral flow immunochromatographic assay that detects acetaminophen protein-adducts in patient serum and returns results as test-band amplitude. The proof-of-concept study compared the accuracy of this POC test with HPLC-EC in 19 healthy individuals with no liver injury, 29 patients without acetaminophen-related ALI, and 33 with acetaminophen-related ALI. 

The POC test took a median of 27 minutes to return results, and effectively distinguished the three groups of patients, including between acetaminophen-related ALI and non-acetaminophen-related ALI, with medium test band amplitude of 584 versus 3,678, respectively. The POC test yielded a 100% sensitivity, 86.2% specificity, 89.2% positive-predictive value, and 100% negative-predictive value for identifying patients with acetaminophen-associated ALI. 

Five Genes Added to Recommended Secondary Findings List

The American College of Medical Genetics and Genomics (ACMG) has updated its list of genes to be reported as secondary findings during whole exome or whole genome sequencing (Genet Med 2016; doi:10.1038/gim.2016.190). The list of 59 medically actionable genes recommended for return in clinical genomic sequencing includes five of six genes that had been submitted for consideration to ACMG’s Secondary Findings Maintenance Working Group. The working group also removed one gene, MYLK, associated with familial thoracic aortic aneurysm and dissection (FTAAD), on the grounds that known pathogenic variants of this gene are rare and that an effective confirmatory test, screening modality, or intervention to prevent or reduce FTAAD-related morbidity or mortality does not exist. 

The revised list reflects the first test of the working group’s process, announced in March 2015, for accepting and evaluating genes nominated for the secondary findings list. Some of the criteria for considering a gene include the clinical features associated with the gene, the likelihood of physicians making an early clinical diagnosis in patients with the gene, clinical genetic testing options for the gene, and medical actionability involving the gene. The latter criterion had included the severity of disease, likelihood of death or disease, efficacy of specific interventions, and the overall depth of knowledge about the gene and associated conditions. To these considerations, the working group added the acceptability of the proposed intervention based on its risks and benefits.