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False negatives...Pitfalls of U...

I am always looking for information on the effectiveness and accuracy of the drug test we have to endure. I have just come across this one from Early this year.
It has alot of information on how the UA works and why they are inconclusive most of the time.
I am including the link as I have not posted everything in the article.
The VA study I have posted in my journal and refer members to was done in 2004 I believe. I continue to look for updated material on this as we do get members who have to deal with the mysterious results of a false negatives alot.
I will also post this link in the health pages and journal for future reference.
I have several other studies I am looking at also that addresses false negatives.
With so many having to deal with this problem I try and keep the newest information up here in the community.
When someone has received a false positive it is good to have reference material to do to the doctor with and show that this is an all to common problem.
I do hope it will help someone:)

Drug monitoring in pain practice is often a two-stage process [Leavitt 2005]:

A.Preliminary Screening of patient-provided specimens, usually urine, at the point-of-care (POC) to detect the presence or absence of a limited number of prescribed and non-prescribed drugs of interest. The accuracy and reliability of relatively inexpensive POC screening assays are limited; although, more costly laboratory-performed assays can be of higher quality.

B.Confirmatory Testing techniques, using high-quality methods (eg, GC-MS, LC-MS), are more expensive but highly accurate and reliable. A problem is that these methods sometimes can be too good, detecting small amounts of irrelevant agents or metabolites that are diagnostically unhelpful or confusing.

While it would be presumptuous to caution against the use of urine drug monitoring, there are a number of potential pitfalls worth noting. Here are several common as well as less well-known considerations:

•Detection cutoff-levels do not always take into account passive (innocent) exposure to marijuana or cocaine consumed by others, consumption of poppy seeds (natural opiate), and the use of OTC products that may cross-react with the assay to produce false results [Evans et al. 2009; Reisfield 2009].

•A number of opioids are metabolized by liver (CYP450) enzymes: eg, codeine, hydrocodone, oxycodone, methadone, buprenorphine, tramadol, and fentanyl. Individual patients may have genetic variants of the enzymes, or may be taking inducer or inhibitor drugs, that strongly influence opioid metabolism and, hence, their detectable presence or absence in urine (or blood, or oral fluid if used) [see, Carlozzi et al. 2008; Smith 2009]. For example, the unexpected absence of one of the above opioid analgesics upon testing can be due to rapid metabolism in a patient rather than therapeutic noncompliance or drug diversion.

•Morphine preparations typically contain low levels of codeine as an impurity, which may be detected by high-quality assays in patients who have not been prescribed codeine [Evans et al. 2009].

•Patients prescribed high doses of oxycodone also may test positive for hydrocodone, which is believed to be present as an impurity; analytically this is a true positive, but diagnostically it is a false positive [Evans et al. 2009].

•It has been clinically observed that unanticipated conversions between opioids going beyond common metabolic pathways may occur, and these can be detected by high-quality assays [Haddox 2005]. For example, patients prescribed only codeine might test positive for codeine and morphine, and also hydrocodone and hydromorphone. Patients taking only morphine might also test positive for hydrocodone and/or hydromorphone. While mechanism behind this metabolic phenomenon are not understood, such findings could falsely suggest that patients are taking unauthorized opioids.

•Proprietary, computerized methods have been developed for quantifying the amount of opioid agents in testing samples; these have been based on controlled conditions examining carefully-selected patients [Couto et al. 2009] or pharmacologically adjusted values [Kell 1994, 1995]. Relying on quantitative tests to help determine whether a patient is properly taking the specifically prescribed dose of opioid can be questionable, especially in patients who do not fit typical patterns of metabolism or have other confounding factors. Due to their limitations, quantitative assessments have been eschewed by government agencies where the consequences of misinterpretation could be severe (eg, Drug Courts).

•Even the most high-quality laboratory testing may not deter persons seeking opioids for illicit purposes — they know how to cheat. An entire industry has sprung up offering advice and products to “beat the test” (just insert that phrase into any search engine to see the myriad of solutions being promoted).

•Case reports have noted false-negative results for opioids and cannabinoids in the presence of tolmetin, an NSAID, and for amphetamines due to interference by chlorpromazine (eg, Thorazine®) metabolites. The antifungal agent fluconazole may interfere with the detection of cocaine [Reisfield 2009]. Persons determined to “beat the test” may know about this.

•A popular and effective way to beat the test is by substituting “untainted” urine for one’s own by carrying a concealed specimen into the bathroom. The only way to thwart this is by supervised urine collection (ie, a staff member observing urine leave the patient’s body and fill the cup). While this is required for forensic urine testing, it could be the ruin of a typical medical practice; it is upsetting for patients and demoralizing for staff.

•To avoid the possibility of urine specimen substitution, oral fluid can be collected for use with screening devices employing technology similar to on-site, POC urine screens. Sensitivity and specificity of oral fluid screening and testing are acceptable, but subject to the same limitations of interpretation and confounding factors as urinalysis [Leavitt 2005].

•Urinalysis is unhelpful for detecting alcohol misuse or abuse [Moeller et al. 2008], and alcohol can be more hazardous in combination with opioids than many other drugs.

The above list is certainly not all-inclusive [eg, also see, Carlozzi et al. 2008; Reisfield et al. 2007b]; however, in view of the many caveats, healthcare providers may want to reconsider what they expect to accomplish by drug monitoring as a component of pain care and if it will adequately serve them and their patients
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