The U.S. Preventive Services Task Force (USPSTF) in an updated guidance has concluded that there is insufficient evidence to assess the balance of benefits and harms in adding C-reactive protein levels measured by high-sensitivity assays (hs-CRP), coronary artery calcium (CAC) score, or ankle-brachial index (ABI) to traditional risk assessment for cardiovascular disease (CVD) in asymptomatic adults (JAMA 2018:320:272-80).
USPSTF found adequate evidence that adding these nontraditional risk factors to existing CVD risk assessment models contributed modestly to discrimination and to risk reclassification but noted that “the clinical meaning of these changes is largely unknown.”
The findings update USPSTF’s 2009 recommendations on using nontraditional factors to assess coronary heart disease risk and the panel’s 2013 recommendations on screening for peripheral artery disease and CVD risk assessment with the ABI. For the 2018 update USPSTF sought evidence on the health benefits and risks of adding these factors to assess CVD risk assessment and on how well these factors improve the calibration, discrimination, and risk classification of existing CVD risk assessment models.
USPSTF found and considered more studies evaluating hs-CRP levels than CAC or ABI; 25 rep-resenting 49 cohorts versus 19 and 10 representing 10 and 22 cohorts, respectively. The panel found that the evidence regarding hs-CRP was inconsistent but showed small improvements in discrimination and risk classification. Generally the studies examining calibration found that adding one of the nontraditional factors improved calibration.
Since “a substantial number” of studies already have shown an association between hs-CRP, ABI, CAC, and CVD outcomes, more such studies “are unlikely to add more information.” However, USPSTF called for more research to measure the effect of adding these factors on clinical decision thresholds and on patient outcomes, especially in more diverse populations.
Significant Variation in Lab Quality Control Practices
A survey of lab quality control (QC) practices for chemistry and immunochemistry testing at 21 major academic medical centers (AMC) found “significant variation and unexpected similarities” (Am J Clin Pathol 2018;150:96–104). The findings suggest an opportunity exists to define best QC practices for chemistry laboratories.
The researchers posed six questions to labs at AMCs chosen based on size and national reputation from the U.S. News & World Report best hospitals honor roll. The six questions explored the type of automated chemistry and immunochemistry instruments respondents used, how often they performed QC, the materials they used in QC, how they defined QC ranges, what QC rules they used, and whether they used moving averages.
The researchers found a “dramatic” 12-fold variation in chemistry QC frequency among respondents, ranging from every 2 hours (10%) to daily (14%). There was less variation in immunochemistry QC.
Three respondents reported using alternating level QC in which they would test one level of QC material at specified points in the day and a different level at other specified times. Three-quarters of respondents indicated that they exclusively use a QC range of 2 standard deviations (SD), while 14% reported using a combination between 2 and 3 SDs. The researchers did not expect this finding as no standard rule calls for this. Just two respondents indicated explicitly that they follow Westgard rules, a set of rules aimed at capturing both random and systemic error.
Only two respondents reported using moving averages, though four reported they were planning to implement moving averages in the near future. The researchers found this “surprising” as “moving averages are theoretically useful, as well as inexpensive and simple to implement.”
Two-step Screening for Congenital Hypothyroidism Identifies More Cases
A retrospective analysis of data from Utah’s newborn screening program highlights the “utility and power” of a two-step approach to screening for congenital hypothyroidism (MMWR Morb Mortal Wkly Rep 2018;67:782–5).
All states screen newborns for primary congenital hypothyroidism, but just 14, including Utah, per-form a second screen when babies are about 2 weeks old. Researchers from the state’s public health laboratory analyzed data from 359,432 infants screened between 2010 and 2016. During the study period, a thyroid stimulating hormone (TSH) level ≥40 µIU/mL on either first or second screen was considered abnormal.
Altogether, 130 babies were diagnosed with congenital hypothyroidism; 98 had an abnormal first screen, and 25 had an abnormal second. The researchers estimated that 20% of babies with the disease would not have been identified if only a single screen had been used.
The authors considered cutoff values for the two-step process and determined that a moderate adjustment using a 40 µIU/mL TSH cutoff on the first screen and a 20 µIU/mL cutoff on the second would improve the sensitivity and specificity of congenital hypothyroidism screening. Referring for further workup infants with TSH values higher than each screen’s cutoff would modestly increase the workload for evaluating congenital hypothyroidism. About 950 babies now undergo this testing each year and an estimated 1,000 babies would be evaluated with the updated cutoffs.
Identifying every case during the study period with a single screening test would have required a cutoff of 5 µIU/mL and would have led to about 282,850 false-positive cases, or about 79% of the screened population.