Rapid Flu Tests Have Variable Detection at Lower Virus Concentrations

An evaluation of 11 commercially available rapid influenza diagnostic tests (RIDT) by the U.S. Centers for Disease Control and Prevention (CDC) found that while most tests detected viral antigens in high-concentration samples, detection varied by test and viral subtype at lower concentrations (Morb Mortal Wkly Rep 2012 Nov 2;61:873–76). The results suggest that clinicians and laboratorians should use RIDTs cautiously for diagnostic treatment and infection control decisions in clinical settings.

CDC conducted the study because there had not been a recent comprehensive analytical evaluation of RIDTs using a standard method and involving all 11 U.S. Food and Drug Administration-cleared RIDTs. In partnership with CDC, researchers at the Medical College of Wisconsin prepared swab samples or mock nasal wash specimens from several dilutions of 16 stock influenza A and seven influenza B viruses provided by CDC. The stock viruses were all representative of those circulating in the U.S. since 2006. The researchers measured concentrations of the viruses' nucleoproteins (NP) using isotope dilution tandem mass spectrometry, and the egg infectious dose per milliliter values were at least as high as those reported in human clinical specimens.

The investigators performed three separate tests for each virus/RIDT combination, with positivity defined as two positive results out of the three. Although all RIDTs detected virus at the highest virus concentrations, some did not detect at subsequent dilutions. Since part of this variation could be due to the use of different antibodies in the various tests, CDC recommended that users periodically evaluate RIDT performance in detecting current or recently circulating virus strains. CDC also cautioned that respiratory specimens should be collected when influenza virus is at its peak, with 24–72 hours of symptom onset.

HDL-C Predicts Diabetic Nephropathy but not Retinopathy

Lower baseline high-density lipoprotein cholesterol (HDL-C) level is a significant independent predictor of the development and progression of diabetic nephropathy, but not retinopathy, in type 2 diabetics (Diabetes Care 2012;35:2201–6). The results suggest that measuring HDL-C may be useful in tailoring screening and therapeutic strategies.

The ADVANCE study involved 11,140 patients with type 2 diabetes who were at least 55 years old at the time of enrollment and had at least one other cardiovascular disease risk factor. Baseline lipid levels, HbA1c, and creatinine levels were determined, and creatinine and HDL-C levels were repeated at 24 and 48 months. Urine samples also were collected at baseline, 24, and 48 months for calculation of the albumin-to-creatinine ratio (ACR).

Participants' mean baseline HDL-C level was 1.3 mmol/L. Nearly one-third developed new or worsening microvascular disease during follow-up, with 28% experiencing a renal event and 6% a retinal event. Compared with subjects in the highest third of HDL-C values, those in the lowest third had a 17% adjusted increased risk of microvascular event. Patients in the lowest third of HDL-C levels also were more likely to maintain or progress to a worse category of urinary ACR over time, compared with those in the middle or upper thirds of HDL-C levels. In contrast, the researchers observed no association between baseline HDL-C levels and development of retinopathy or any specific type of retinal event.

The findings suggest that there are differences between the pathophysiologies of the two types of microvascular disease. The authors called for further research to explore possible benefits of HDL-C-raising therapies in patients with type 2 diabetes.

Fructosamine, Glycated Albumin, and 1,5-AG all Independent Predictors of Diabetes Risk

Fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG) are strongly associated with subsequent development of diabetes, independent of baseline HbA1c and fasting glucose (Diabetes Care 2012;35:2265–70). The findings suggest that elevations in these analytes may be useful indicators of future diabetes risk.

The researchers investigated this association because fructosamine, glycated albumin, and 1,5-AG all have been of recent interest in assessing glycemic control in patients for whom use of HbA1c is problematic, including those with anemia, hemolysis, or renal disease. However, little investigation has taken place in terms of their levels in nondiabetic populations or association with future development of diabetes.

The study, a subset of the long-standing Artherosclerosis Risk in Communities study, involved 1,200 participants without an initial diagnosis of diabetes who were followed for a median of 3.3 years. During the study period, there were 119 new cases of diabetes. When compared with the lowest quartile, the highest quartile of baseline fructosamine and glycated albumin levels were significantly associated with diabetes risk, with hazard ratios of 3.99 and 5.22, respectively. These associations remained significant after adjustment for fasting glucose and HbA1c concentrations.

Higher baseline quartiles of 1,5-AG were inversely associated with incident diabetes, and remained so after adjustment for diabetes risk factors and fasting glucose and HbA1c levels.

The authors called for additional studies to evaluate more extensively the associations between all three markers and long-term complications of diabetes, as well as their potential clinical utility for monitoring glycemic control.

Meta-analysis Supports Age-independent Definition and Staging of CKD

A meta-analysis of 46 different cohorts involving more than 2 million participants found that both estimated glomerular filtration rate (eGFR) and high albuminuria were independently associated with mortality and end stage renal disease (ESRD) regardless of age across a wide range of populations (JAMA 2012;308: doi:10.1001/jama.2012.16817). The findings suggest that although clinicians might consider some variation in managing chronic kidney disease (CKD) based on age, cost, and benefits, with respect to risk of mortality and ESRD, a common definition and CKD staging based on eGFR and albuminuria regardless of age would be more appropriate.

The authors conducted this analysis because there has been interest in using eGFR and albuminuria to define and stage CKD. However, controversy exists about whether age modifies their independent and combined associations with clinical risk

The investigators found that risk of mortality and ESRD were higher at lower eGFR and higher albuminuria at every age category. Relative mortality risk for reduced eGFR decreased with increasing age. In the case of higher albuminuria, the reduction in relative risk with increasing age was less evident. In patients with CKD, the adjusted relative hazards of mortality did not decrease with age, and in all cohorts, the relative risk of ESRD associated with lower eGFR or higher albuminuria were comparable across age categories.

The findings indicate that kidney measures used for defining and staging CKD are strong predictors of clinical risk across the full range of ages, including patients older than age 75.