American Association for Clinical Chemistry
Better health through laboratory medicine
June 2011 Clinical Laboratory News: Diagnostic Profiles

Wide Variations Found in Test Result Follow-up

A systematic review by Australian researchers found that studies have reported a “wide variation” in the extent to which test results are not followed-up appropriately, but in general concluded that this is a “substantial problem” for hospitalized patients that affects patient safety (BMJ Qual Safe 2011;20:194–199). Problems were particularly notable with critical test results and results for patients moving across healthcare settings, such as from the emergency department (ED) to inpatient care.

The researchers found only 12 studies that quantified the extent to which lab or radiology test results for hospitalized or ED patients were not appropriately followed-up. They defined failure to follow-up as the ordering physician or another provider neglecting to document a follow-up of test results. The authors excluded studies that looked at lab or radiology staff not reporting results.

Reported failure to follow-up ranged from 20–61.9% for hospitalized patients and from 1–75% for ED patients. In the area of critical results, one study found that 28.8% of urgent biochemistry results during a 6-month period had not been accessed electronically. Studies that looked at result follow-up in the ED found failure to follow-up varied by type of test, with microbiology ranging from 3–75% and 44.7% of urgent biochemistry tests not followed-up.

The researchers found that follow-up problems existed regardless of whether electronic health record, hybrid paper-electronic, or all paper systems were used. They concluded that the “complexity of the test management process and high volume of test results requires significant review and reform of work practices to allow electronic endorsement to occur easily.” They also called for systems, policies, and practices to facilitate better communication of patient information across care settings.

Increased CK-MB, cTn I Levels Linked to Poor CABG Survival

A team of Canadian, Australian, and U.S. researchers recently reported finding a strong, graded, and independent association between elevated creatine kinase (CK-MB) and cardiac troponin I (cTn I) levels and mortality following coronary artery bypass graft (CABG) surgery (JAMA 2011;305:585–91). The study, which analyzed results from 18,908 patients in seven other studies, is the first to be sufficiently large and inclusive to demonstrate that even small enzyme elevations detected soon after surgery are associated with worsened long-term prognosis, according to the authors.

Increases in CK-MB and cTn I levels are common following CABG, and small rises have been regarded as insignificant, even though there is limited evidence supporting the view that only large increases are associated with worse prognosis. As a result, it is unclear what levels of CK-MB and cTn I should be used to assess prognosis in patients undergoing CABG. To address this issue, the researchers pooled and analyzed data from clinical trials and registries that measured CK-MB or cTn I levels and assessed survival status following CABG.

The investigators calculated ratios for the analytes as the ratio between the peak level and the upper limit of normal for that analyte at the participating lab in each study. For both CK-MB and cTn I ratios, they found a strong, graded, and independent association with mortality for all ratios >1. 

Diabetic Retinopathy Risk Thresholds Proposed

Based upon a longitudinal study assessing glycemic levels and retinopathy, French researchers have proposed thresholds of 108 mg/dL for fasting plasma glucose (FPG) and 6% for hemoglobin A1c (HbA1c) levels as identifying those at risk for developing retinopathy within 10 years (Arch Ophthalmol 2011; 192:188–95). The findings add to evidence about the well-established relationship between hyperglycemia and microvascular complications.

Landmark studies dating to the early 1990s showed that signs of retinopathy were rare at FPG <126 mg/dL, and that prevalence increased substantially above that level. However, those studies used inferior methods to detect diabetic retinopathy, according to the authors. In addition, more recent analyses have found increased prevalence of retinopathy with increasing FPG levels, but without a clear diagnostic cutoff. The contemporary studies also found signs of retinopathy in 7–13% of the population with FPG levels <126 mg/dL.

In this context, the authors sought to explore the frequency of retinopathy 10 years after baseline readings of FPG and HbA1c, and to evaluate positive predictive values for retinopathy at various levels of FPG and HbA1c. They also evaluated potential risk factors associated with retinopathy at baseline and after 10 years.

The study involved 700 subjects ages 30–65 at the time of enrollment, who were invited for examinations at 3, 6, and 9 years. After the 9th year examination, the 321 participants who either had been treated for diabetes or had a FPG ≥126 mg/dL at some point during the study were invited for further examination. The researchers found FPG and HbA1c levels to be most associated with retinopathy after 10 years. In the case of both analytes, the investigators observed a gradual increase in positive predictive values for retinopathy but then a steeper slope starting at 108 mg/dL for FPG and 6% for HbA1c. Based upon the positive and negative predictive values, sensitivity, and specificity at these levels, the researchers suggest they could be considered thresholds for defining those at risk for retinopathy.

Long-term Study Finds Little Mortality Benefit from PSA Screening

A randomized prostate cancer screening trial with 20 years’ follow-up found the prostate cancer-related death rate did not differ significantly between men in the screening and control groups (BMJ 2011;342:d1539). The researchers concluded that the risk ratio for prostate cancer-specific death did not indicate significant benefit from prostate cancer screening.

The study involved 9,026 men from Norrköping, Sweden, 1,494 of whom were randomly allocated to be screened every third year, the first two times by digit rectal exam (DRE) only and subsequently by DRE combined with prostate-specific antigen (PSA) testing. The screenings took place between 1987 and 1996; this study reported on mortality 20 years after follow-up.

Overall, there were 85 cases (5.7%) of prostate cancer in the screening arm versus 292 (3.9%) in the control group. The percentage of men with localized tumors was significantly higher in the screened group (56.5%) versus controls (26.7%), and prostate cancer-specific mortality was 35% for men in the screening arm versus 45% in the control group. However, the risk ratio for prostate cancer-specific death was 1.16, leading researchers to conclude that screening and treatment of men with tumors detected through screening would be unlikely to reduce prostate cancer mortality by more than a third.

Since this reduced mortality would come at the risk of over-detection and over-treatment, the investigators suggested that before undergoing PSA screening, asymptomatic men should be informed about the potential hazards of treatment, such as erectile dysfunction and urinary incontinence, should prostate cancer be detected.