Cover Story

Advances in clinical laboratory science continue to evolve at a rapid pace. Let ADVANCE be your guide to the latest must-have tools and technologies in the coming year. From the latest assays and biomarkers defining disease, to integrating information technology tools and trends, to molecular diagnostics' accelerated path, we're with you every step of the way.

Urinalysis

Urine, in diagnostic circles, is elevated to rarified status. Sue Selgren, marketing manager at Siemens, summed it up, "Urine testing remains a simple, painless and cost-effective way to gain significant information about a patient." She also noted that changes through the years have made for a more effective process. "Previously, 24-hour urine collections were needed to provide a precise measurement of urine albumin and protein. But collection of a timed urine sample is inconvenient and associated with errors, largely due to improper timing and missed samples," said Selgren. "Now our urinalysis strips include a urine creatinine test that corrects for varying urine concentration to assist in early detection of kidney disease."

This year has yielded more than a few headlines for the continued importance of urine testing:

• Urine Test With PSA

A new urine test developed at the University of Michigan, when used with PSA, can eliminate unnecessary prostate biopsies and reduce overtreatment. The test detects genetic biomarkers common in most prostate cancers.

• Autism Screening

Scientists from the University of Washington and Battelle Centers for Public Health Research and Evaluation have identified metabolites in urine that potentially could predict children at risk of developing autistic spectrum disorder. Certain kinds of porphyrins are much higher in the urine of some children with autism, compared with non-autistic children of the same age.

• Predicting Bone Fracture Risk

A urine test can indicate a premenopausal woman's risk of bone fracture, according to researchers from the University of Pittsburgh. Above-normal levels of N-Telopeptide (NTX), a byproduct of bones breaking down, in women in their 40s and early 50s indicate a greater risk of bone fracture.

• Screening for Precancerous Polyps

The University of Alberta, Ontario, has developed a simple urine test to detect pre-cancerous adenomatous polyps in the colon. The non-invasive test is conducted using metabolomics, which detects and profiles the small molecule end products of cellular metabolism.

• Predictor of Renal Failure

Researchers at Henry Ford Hospital, Detroit, have used a urine test to search for excess protein - an effective marker of acute renal failure in patients with severe sepsis. Investigators believe the test may allow early diagnosis of renal failure before substantial damage is done.

• Automation and Imaging

Erika Johnson, vice president of marketing, Iris Diagnostics, pointed toward increased use of automation and imaging in urine testing as positive game changers. "We have combined urine strip chemistry and urine microscopy in an automated system that reduces hands-on time for the technologist and standardizes the test so that results are better," said Johnson. This is accomplished by the use of two integrated instruments, with results returned in a single report giving an overall picture of patient condition.

-Excerpted from: Newitt V. Focus on: Urinalysis. ADVANCE for Administrators of the Laboratory, 21(10):38.

Information Systems

Middleware, in its most simplistic definition, is a translator. In a laboratory, middleware translates the language spoken by the hardware of an analyzer to the user interface of the laboratory information system (LIS). This conversion can be one way - from analyzer to LIS - or bidirectional, with the LIS sending information to the analyzer as well.

Hardware middleware translation eliminates the need for the laboratory staff to spend time coding results by hand, ordering extra tests based on results, and issuing new insurance authorization requests, therefore impacting productivity. Middleware eliminates the manual process as well as the potential for human-introduced errors.

Software middleware can translate and exchange data between the LIS and billing systems, electronic medical record (EMR) systems, hospital communications networks, websites and more. Middleware acts as the glue between multiple systems, and due to its ubiquitous nature, it has become all but indistinguishable from the standard interfaces we see in the LIS. Middleware is not something a user needs to see and it is not something that a manager should need to administer. Rather, it is the silent servant of the LIS, shuttling information between systems and equipment within the lab, between the lab and other departments as well as to external clients and facilities.

Items to consider when planning a fully integrated laboratory include:

• Determine which systems instruments and applications will speak to each other. What is the workflow necessary to support your business? Making an outline or data flow diagram is a good visual starting point.

• What processes require human intervention or manual labor?

• Are insurance billing and approval systems creating inefficiencies in payment and test completion times?

• What time and costs are required to implement a new system or maintain a current one? Can an existing one be upgraded or modified effectively to achieve the results or is a new investment worth it?

• Determine the ROI. Many middleware providers offset costs by requiring the end user to create rule-based systems and adjust settings on their end. This is not the lab's business or knowledge base and can add significant time, setbacks and cost. An ideal middleware solution outsources the entire process; the client defines the problem, and the middleware vendor provides the system integration, programming and training.

-Excerpted from: Clifford L-J. Middleware's multiple uses. ADVANCE for Administrators of the Laboratory, 21(8):20.

 Molecular Diagnostics

Despite the ease of use and popularity of the DNA probe approach for diagnosing Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG), nucleic acid analysis without amplification often has the disadvantage of low sensitivity (high detection limits). Nucleic acid amplification techniques increase sensitivity dramatically while retaining a high specificity. Polymerase chain reaction (PCR) is the best-developed and most widely used method of nucleic acid amplification. PCR is based on the ability of DNA polymerase to copy a strand of DNA by elongation of complementary strands initiated from a pair of closely spaced chemically synthesized oligonucleotide primers.

The first benchtop system to fully automate amplification and detection for PCR testing, the COBAS AMPLICOR CT/NG Test (Roche) incorporated PCR in a multiplex assay that allowed the simultaneous amplification using biotinylated primer pairs specific for NG and CT, capture of the bound amplification products using magnetic particles labeled with specific oligonucleotide probes, and detecting the bound products colorimetrically. It was the first commercial PCR assay approved by the FDA; implementation of the technology was rapid.

Testing methodologies and automation have improved testing for CT/NG. Sensitivity and specificity have been improved while cross contamination has decreased. The batch-based testing approach of most modern formats creates a real risk of internal or specimen-handling based contamination, leading to false-positive results. With the incorporation of internal process controls, manufacturers are moving toward correcting this problem (ProbeTec Qx Amplified DNA assay, BD, GenProbe Aptima assay).

Labs now have choices for testing (BD ProbeTec [Becton Dickinson], APTIMA COMBO 2 Assay [Hologic GenProbe], Infiniti CT/NG [Autogenomics], Abbott RealTime CT/NG, cobas 4900 CT/NG [Roche]). Next-gen testing with specific, sensitive and rapid detection using novel stable genetic targets for CT/NG allows labs to incorporate testing with ease and confidence. On-demand testing versus batch and minimal manipulation is of paramount importance (Xpert CT/NG, Cepheid).

-Excerpted from: Lowery-Nordberg M. Meeting the challenges of women's health. ADVANCE for Administrators of the Laboratory, MDx Special Edition, 21:6.