Good morning, my name is Kevin Severino and today we're going to be talking about lab testing in the assessment of substance use disorders. I'm armed with my cup of coffee, which will keep me going. See, no coffee, no worky. We're going to be focusing mainly on clinical uses of lab testing as opposed to forensic uses, though I will touch on that. And we'll mainly focus on what most clinicians will be used to, which is urine drug testing. Target audience overarching goal of PCSS is to train all health care professionals in evidence based practices for the prevention and treatment of OUDs, particularly for prescribing medications. But here we're going to be talking about urine drug testing and other drug testing. So our educational objectives for today, we want to discuss clinical issues in performing urine drug testing. And I'll refer to that as UDT, describe the basic types of UDT and when they should be used, define the metabolism of opioids and benzodiazepines, because you'll need that to understand how to interpret UDT results, and then describe other laboratory testing used as part of substance use disorder evaluations. And our outline will pretty much follow that. We'll have purpose and use of UDT, the types and interpretation of UDT, some forensic issues in UDT because there the collection is different and other lab testing other than for urine. We have a case vignette in each of our SUD101 presentations. In the following, we'll meet Bill, a patient you treat with buprenorphine naloxone. He provides a urine drug screen positive for opioids and buprenorphine. And we'll discuss how to interpret this result and as well as other aspects of the case moving forward. So first, let's talk about the purpose and practicalities of conducting drug testing. And a key resource I'd like you to keep in hand, you can download it is by ASAM. It was published in 2017. It's called The Appropriate Use of Drug Testing in Clinical Addiction Medicine. It's an excellent summary of the topic and include that also at the references at the end. So first, let's talk about the goals of drug testing and in this case, urine drug testing. It's important to think of it as a clinical tool. It's not gotcha. It's not meant to catch somebody in the act of doing something wrong. Rather, what you're trying to do is facilitate clinician patient communication, provide objective information on how your treatment is going, confirm the use of prescribed medications and lack of use of non-prescribed medications in legal settings. It may be used as a condition of parole or probation for custody or parental issues and in workplace testing. The choice of matrix. Why do we talk so much about urine? Urine is by far the most widely used matrix. It's got a probably the most flexible detection window of hours to days, although some such as those that chronically use cannabinoids or PCP, that window will be lengthened. Its advantages. It's fairly easy to collect. It's cheap. It's a mature technology that many people understand, and it allows for point of care testing, which we'll talk about more disadvantages. It is prone, very prone to tampering, and that can include adulteration, substitution, dilution. And if you need to confirm the results or confirm the absence of a substance, then you need to move on to gas chromatography, mass spec or other confirmatory testing, which is more expensive. There's always the debate about whether this testing should be observed or unobserved. We'll talk more about that. And you do in the field have the ability to screen for adulterants and as well normalize to things like creatinine, temperature, specific gravity, et cetera, to confirm the validity of your sample. Let's talk about why we're going to be talking about urine so much. The choice. Other matrices. Breath has a window of detection of only up to hours. It is most widely used point of care for alcohol. In other words, breathalyzer testing. There is some trying development for this for cannabinoids, but it doesn't exist. And again, the cons for this would be easily contaminated by what has been ingested other than the substance and volume effects. Blood has a window of detection. It's also fairly short. It's often used in emergency rooms and for forensic purposes. It's more invasive. It's more costly and so not widely used in in outpatient offices. Oral fluids such as saliva minutes to days is the window of detection. It's easily collected and observed. It's got much lower sensitivity than urine because you're in your kidneys concentrate metabolites. Your saliva does not. And it's prone to contamination. This probably will be the earliest field detection for cannabis that is going to be rolled out. Sweat. The window of detection is hours to weeks. It's resistant to tampering, but it's only perspective. In other words, moving forward, patches are often can often come off or be off. And hair and nails. This is used long term because your window of detection is months. It actually won't collect data on what happened in the last two weeks or so. It's actually not that great for cannabis detection. There's a hair bias in that those with darker colored hair tend to retain higher levels of the cannabinoids and hair treatments can affect it. Let's talk about practical issues of collecting urines. Many of you probably are already familiar with this first, whether you're going to do this as a point of care testing or do you have an on site lab or do you send it off? I've been privileged to work in the VA for many years. So our urine samples go right to an on site lab. This is a very controversial next issue, whether your collection is random or scheduled. Now, the ASAM guidelines heavily favor random collection. The difficulty with this, and this was even true in the VA, is to truly have a random connection, you basically need to call the patient in, often not when they have scheduled appointments, because if scheduled appointments would not be random. So that's a lot of extra travel and patients may not be willing to do it. And some of your patients may not have a good way of contacting them. One way around this is to say you have a scheduled appointment every two weeks. You might run the urine, say, only one out of four of those visits. But a truly random collection is not easy. Again, do you do this completely unsupervised, send them to a lab and have them go into a bathroom? Do we do it supervised where you make sure nobody else is in the collection room, the bathroom? At the time, they're there and check their pockets before they go in, et cetera. Or do you actually observe the collection, which is really falling out of favor because patients with with sexual trauma in the past or shy bladder, et cetera, usually can't provide a urine under those conditions. And then when we talk about forensics, it becomes much more stringent in terms of requirements. There's maintaining what's called a chain of custody, and I'll describe what that means. Recent trends that have changed in urine. First of all, we don't refer to urines as, quote, dirty anymore. That's a pejorative statement that prejudices things against those with substance use disorders. Use nonjudgmental terms like explained, unexplained, expected, unexpected, positive or negative. Testing is going to become more individualized, especially private insurance will be leery of wanting to approve a broad panel of testing when there hasn't been any evidence of abuse of certain substances. Say there's no evidence of abuse of PCP. The question will be asked, why are you collecting that? Testing should reflect regional drug trends. So I'm in the Northeast. I'm not going to see methamphetamine often at all. Whereas in California or the South and now the Midwest, I'm going to see methamphetamine far more commonly than cocaine. So know what your regional drug trends are. If ecstasy starts becoming prominent in your area. Remember, you'll need to make a special request for that part of your test in your panel because MDMA is not normally in a panel, we'll talk more about that. As I said, the direct observation of urine is is becoming far less frequent to insurance companies and to yourself, justification of urine drug testing should be based on medical need or medical necessity. And I've listed what are some of the more common reasons you would request it, baseline testing, which in the beginning should be broad based, assessing adherence or assessing abstinence, assessing abstinence of something like fentanyl. So especially field testing of fentanyl has become very important in terms of confirming for people using opioids that there's not fentanyl, which could be deadly in what they're using. If you suspect that the behavior by based on behavior, that in fact there may be use of a substance. If you want to confirm the safety of prescribing, you may be uncomfortable prescribing opioids if somebody is commonly misusing benzodiazepines or alcohol. Although I should point out that harm reduction approach would be not to take somebody off their opioid medication, medication for opioid use disorder, but in fact, try to treat the benzodiazepine or alcohol use. And if they're in situations where it would be common for relapse to occur. These are some practical points I'd like to give you on how to discuss urine drug testing. For those not addiction physicians, you may not be used to some of this. If a new patient is being initiated on a treatment of a controlled substance or initiating a treatment in your office at all, you want to emphasize this is routine practice, that you're not singling them out. You want to use this to determine how well treatment is used, not to punish them, that it is consistent with standards of care and it can help you and the patient understand some unexplained symptoms. If the patient's been in treatment for a while and you want to initiate urine drug testing, they're going to ask why now? Your clinic may have initiated a new policy, but even not. You should say, I have become aware that this is really standard of care. If the patient said, but I don't have an issue with substances, you want to point out this is universal, a routine testing. It's consistent with standards of care. For example, I've got many patients who would say I have absolutely no problem with alcohol. I don't drink at all and they don't include beer in that or they don't want to reveal to you that they've got a medical marijuana card and that they're using cannabis fairly regularly, so that may explain sometimes why treatment is not working as well as you and the patient think it should. If the patient refuses, harm reduction would say you want to do all you can to continue treatment anyway. But there may be certain meds you won't want to prescribe and you can say, I can't prescribe certain meds if we're unable to routinely, safely monitor things and have a treatment contract. And emphasize again, you're not here to judge, but need to treat addiction as a disease. There's always the sticky question of somebody who absolutely refuses testing. If there's not a psychosis and a paranoia involved, you do have to wonder why that is, although some people are very protective of their their rights. But there may be some non life saving drugs that you'll refuse to prescribe if a patient won't allow testing such as psychostimulants for ADHD. Let's talk about point of care testing, which a lot of offices do point of care testing, POCT. It's rapid. But remember, A, not as sensitive and B, you need confirmatory testing to confirm any of these immunologically based tests, which I'll describe in a bit. So it's detrimental if treatment or other important decisions are based on unconfirmed results. Point of care testing does not give quantitative or met metabolite information. So in other words, you shouldn't depend on a buprenor bup ratio, that being the metabolite of buprenorphine based on POCT. The cutoffs of POCT may not provide adequate sensitivity. That's a key limitation. FDA approval technically is required for at home use. POCT kits most rigorously tested are those that are CLIA waived. That is the Clinical Laboratory Improvement Amendments waived. At present, there are only two FDA approved kits for in-home use for fentanyl and none as far as I'm aware today, June 22nd, none is CLIA waived. And spot testing for nitrites, PCC, glutaraldehyde changes in pH and creatinine are you can get those on the side of your sample cup, which helps in terms of validity testing. To conduct a urine POCT, to bill for it, you as the provider need to obtain a CLIA waiver, certificate of waiver through the U.S. Department of Health and Human Services. And that's form SMS 166. You should use products that are FDA approved and CLIA waived, which means demonstrated by the manufacturer to be accurate and of low risk when used by untrained personnel and approved for home use. CMS will allow billing for a single test per patient a counter. So you can't bill for like, well, I tested for fentanyl. I tested for this for multiple agents. The usual code now, I think, is G0434. But I am not a billing expert. Strategies that patients use to falsify urine drug tests, there can be evasion or refusal, there can be substitution. So they're providing a urine that somebody else gave you. They're providing a urine that they reconstituted from powdered urine like Tang, so I don't think substituted urine was anything the astronauts ever drank. Dilution. They could hydrate it. They could use diuretics. They could add water directly to it. Doping means you added an unexpected agent like sample to it and adulteration, which is also adding other agents. And we'll talk more about those. To the rough way to confirm the validity of your collected sample, the sample should be between 90 and 100 degrees, pH 4.5 to 8.5. Creatinine should be greater than 20 mgs per deciliter, but there are a lot of patients that do have a hard time peeing or providing a sample. And so they drink a lot of water and that can lower the creatinine. So in my experience, anything below a lot of five is really a red flag. You can use the color and shape test. If it foams up a lot, there's soap in there. If it doesn't foam up at all, there's no protein in there and it's unlikely to be urine. Specific gravity should be 1.02 or greater. Your kidneys really can't get down to one, even with SIADH. 1.01 I've rarely seen is valid. And both cups and dipsticks have validity tests on them. What are some of the adulterants in general, which will kind of cloud immunologic results for anything, bleach, glutaraldehyde, pyridinium, THC. You can use visine even in the urine, vinegar, peroxides, potassium nitrate, something called goldenseal and zinc, goldenseal. That should be a new James Bond movie. Benzolecognine, that is the metabolite of cocaine. That's ammonia and zinc, amphetamines, goldenseal. There it is again in zinc, PCP, ammonia, opioids, peroxides. And it's important to remember in our summary that just like all your charting results and information you obtain, information about drug use and drug use disorders is protected by CFR 42 Part 2. So these UDT results have special protection. They should not just be sent out to anybody that requests them. You should counsel both your staff and your patients about these rights. And I just give you the kind of legislative gory details of where we've gotten to our most recent modification, which is in 2020, which is meant to improve a little bit the communication with PCPs. So in summary of this section, urine is the most widely used matrix. Decisions whether to use point of care testing and whether to make collection observed or random are important decisions. And illegal validity will require a chain of custody collection, which I'll describe later. Remember, these are protected, they're special protected results. Discuss UDT with a patient as a universal precaution. I do feel strongly that in most cases, adequate treatment requires collection of a urine drug test. Validity testing is helpful to detect urine drug testing falsification. Now, let's talk about the types and interpretation so that you understand why the initial screening tests, immunologic tests are less specific than the confirmatory testing. So urine drug testing methodologies, the most common one is presumptive. Other terms for this are immunoassay, qualitative or preliminary. That'll include in enzyme immunoassays, if you send it out, or point of care testing with dipsticks. It won't definitively identify a specific analyte. It only detects things that cross react with the antibody used in the testing. It's less expensive, it's quick. But there are significant false positive and negative rates. Definitive testing or quantitative and confirmatory testing is usually done by gas chromatography mass spec or gas chromatography dual mass spec or liquid chromatography dual mass spec. There are no false positives. A fingerprint on this is absolutely definitively confirmatory. It'll identify specific analytes. In other words, if somebody's urine comes back with opiate positive on presumptive testing and you do confirmatory, you may see oxymorphone, you may identify oxycodone, you may identify 6-methylacetylmorphine, 6-MAM. And it has better sensitivity because the cutoffs are lower. And interestingly, because the cutoffs are lower, you may use confirmatory testing to seek out a substance that you think should be there. So in clonazepam, often if people are prescribed less than, say, 1.5 or 1 milligram a day, say 0.5 mg BID, presumptive testing won't pick that up. But confirmatory testing will. So if you want to assess for compliance with that medication, you use confirmatory testing. Urine drug testing by immunoassay, as I said, it's prone to cross reactions. This is a screening tool. And actually for all but cannabis, it's a screening tool. There are very few false positives for cannabinoids with immunologic testing. Most standard panels include amphetamines, benzodiazepines, opioids. Now, those are the natural opioids. So oxycodone, natural opioids would be codeine, heroin and 6-MAM. Often now they've added oxycodone and methanol to these panels, the cocaine metabolite, cannabis and PCP. But until now, most have not included fentanyl. They don't detect or don't include buprenorphine. They don't look for synthetic cannabinoids, et cetera. So you've got to ask for those separately. You need to know what's in your panels. I'm not going to go through all these, but these this is a good up to date list of reported things that if a patient is prescribed can cause false positives. I note that PCP isn't usually very often found. If you're still testing for PCP, remember, there can be a lot of false positives. The most common difficulties come with amphetamines, which are often false positive. But if somebody is on, for example, bupropion, fluoxetine, trazodone, rinitidine. So there are a lot of people on these meds that can be a false positive. So don't immediately jump to the conclusion that somebody is using methamphetamine. False positives for opioids can include some actually true positives, large amounts of poppy seeds that you can see there, dextromethorphan, which is also another abuse substance, diphenhydramine, Benadryl can be a false positive, not so many for buprenorphine, but there are some, including, believe it or not, morphine and methadone and tramadol and codeine and then methadone. Not too many, but again, diphenhydramine and quetiapine are in there. Let me explain a little more about urine drug testing for opioids. The natural opioids are codeine and morphine and thebane and opium. And that's what's in this class. And in fact, you're in drug testing for opioids, looks for morphine and all of those other substances metabolized to morphine. And that's why they're well detected. The semisynthetics, hydrocodone, oxycodone, oxymorphone, hydromorphone are less well detected. There are some panels that have now included these as routine, and that's included in the Mandatory Guidelines for Federal Workplace Testing. Those are abbreviated as URMG. If you have high levels of semi-synthetic opioids like oxycodone, then they do end up being detected in EIA opiate screens. Buprenorphine is a semi-synthetic, but it is not detected in standard screens. Methadone, fentanyl, meparidine, tramadol are synthetic opioids, and they are not detected. So all of those, buprenorphine and those on the bottom, require separate requests if they're not in your panel. Definitive testing, when do you do that? So a standard test may be $10 or so. A definitive test nowadays in high-volume labs may be $60 or so. You use it when the results are contested by the patient, when they're not explained by patient self-report, when you're guiding clinical decision-making, such as whether somebody needs to be on an increased dose of buprenorphine, or when it's done for forensic purposes because then you need to definitively identify a specific analyte. Then the immunoassay needs to be confirmed with liquid chromatography and dual mass spec. Where practicable, it's recommended that substances, all except for cannabinoids, per Barthwell, 2018. So that's an article I include reference at the end, she strongly favors doing confirmatory testing on many more samples than often some of us will. I tend to go by how clinically the patient's doing, whether there are any warning signs coming up. Although in the beginning, I will screen for a wide range of substances. This is what definitive testing looks like. First, gas chromatography, usually based on ionic charge, can be based on lipophilicity, and liquid chromatography, which is often based on lipophilicity or size, separates out things. So you can see here, I don't know if my arrows are showing it, there's two large peaks. Those may be collected and then sent into a mass spec. So a mass spec, you put the sample on a probe, it dries there, you put the probe in there, and then it gets blasted by a bunch of atoms or whatnot. And you get a definitive fingerprint based on size of what fragments result, and that's the mass spec. And those fingerprints are absolutely dead on. You can see that the sensitivity for most things is set lower for gas chromatography mass spec than immunoassay. So you've got at the top, the psychoactive substance in cannabis, then the metabolite of cocaine, then the natural opioids, then PCP, and then amphetamines. This is actually set fairly high to avoid false positives, but many labs lower this to 300 or so for the GC mass spec, not necessarily for the immunoassay. Opioid metabolism, I'd like you to print this and stick it on your wall. This is important for interpreting what you see, especially in confirmatory testing. So in confirmatory testing, if I find that somebody has morphine in his urine, it doesn't mean that they're using morphine sulfate and injecting it. They could be using codeine in a metabolized to morphine. They could be using heroin, poppy seeds. They go through morphine. By the way, you need a lot of poppy seeds for this. But if they're using heroin, if you find 6-MAM, then that's pathognomonic for use of heroin, because morphine doesn't go the other way. But also note, you could find hydromorphone in there. Codeine will go through hydrocodone. Hydromorphone usually won't go to hydrocodone. And then these are the final metabolites. So you need to understand this metabolism and understand that a synthetic such as oxycodone doesn't go through morphine at all. There's noroxycodone, oxymorphone, and noroxymorphone. But oxycodone should not generate any of these. And similarly, methadone only goes to its metabolite, EDDP. Buprenorphine to norbuprenorphine doesn't go through morphine or those other metabolites. Naloxone, similarly, doesn't go through those. I include in here a little ditty on the use of buprenorphine, norbuprenorphine ratios, which some clinicians like to use in terms of confirming that somebody's actually taking this not in an IV route or not doping their urine, but actually taking it and having it metabolized as it should. In the ratio of norbuprenorphine to buprenorphine should be greater than one based on the half-life of the two agents. In other words, buprenorphine is metabolized quicker to norbuprenorphine than buprenorphine is degraded. But there are people that use very conservative ratios of 0.02 or higher as saying that there's not spiking. So in other words, a 0.02 or less, then there's spiking. Some don't even use a ratio, Holt et al, use a bup concentration of greater than 700 nanograms per mil in the urine. An elevated naloxone in the urine may support spiking or IV use because normally the naloxone is very poorly bioavailable and very little should show up in the urine. But I've included the references discussing this because it's really kind of a complex discussion that's a little, goes beyond what we can have time for here. This is an example of why we would use confirmatory testing. Somebody who is on oxycodone comes back with an opiate-positive urine and an oxycodone-positive urine in your screen. You wanna make sure that this doesn't mean somebody's using heroin or codeine. So you do confirmatory testing and all you come back with is oxycodone, which you would have expected, and oxymorphone. Now, does that make sense? If we go back here, you can see that oxycodone does go to oxymorphone. So in fact, that confirms that your patient is, your urine drug test is consistent with only the use of oxycodone. And this was just a false positive based on how much of the oxycodone they were taking. Benzodiazepines are another set of substances that are a little complicated to interpret. Clonazepam and lorazepam, anything that doesn't go through oxazepam is not well-detected. There have been modification of test cutoffs which cause variability. So some labs will detect these more readily than other by immunoassay. Confirmatory testing is often needed to not only identify what's in a positive screening, but also to look at what could be in a negative screening that was missed, in other words, a false negative. This is the slide, another slide you can put up showing the ones that are well-detected. Diazepam, temazepam, chlordiazepoxide and chlorazepate all go through oxazepam, which is, Serax, which is actually the moiety being detected in benzodiazepine immunoassays. Clonazepam, alprazolam, lorazepam, flunitropam all go to specific metabolites that are not oxazepam and so are not as well-detected. Usually if people are misusing, however, alprazolam or lorazepam, they're using high enough amounts that they may show up in the enzyme immunoassay. It's also important to understand the detection times. Cannabis, because it's lipophilic, will have its detection window increased as somebody becomes dependent on it. And that's also true for PCP. Amphetamines, and then I show the detection times for the others. Barbiturates can be varied because they are long-lasting. There are long formulations and short formulations of barbiturates. Most are gone within a week or less. For the opioids, it also varies on the half-life of the agent. So methadone would be a much longer detection window. Diazepam is a very long detection window because its metabolites can hang around for a long time, which is why I don't like to use it in the elderly. But it's a very popular agent to use as a muscle relaxant. And you can see that buprenorphine can be a little long. And I've found in my practice sometimes, up to 14 days out, it may be detected. One of the issues with cannabinoids, which show up a lot in my rounds, is whether somebody that has a positive result while they're in their day program and it stays positive for a while, is whether there's any evidence for current positive result as opposed to a slow decline in the level because of release from fats. One approach has been to use the following, a THC to creatinine ratio. The rule of thumb is that that ratio should decrease by 50% every two to 10 days. In other words, it should fairly steadily decline. However, it will bump up if somebody exercises, gets a fever, becomes dehydrated. So you don't interpret any increase as use. You wanna look at the longer term trend. A lighter and frequent user will decrease faster. But if it increases 50% or more from a preceding interval, that usually is the indication that there's some active use. So in summary, in comparing immunoassays to definitive testing, you begin with an immunoassay, but it's a screening, and then do definitive testing if needed. This is not ideal because there's about a 15% negative rate. So in other words, if you just do immuno-based screenings and you use those as the trigger for whether you do confirmatory testing, you've got about a 15% negative rate. False positives are common, especially for amphetamines and PCP. Least common for cannabis and cocaine. False negatives are common for the semisynthetic and synthetic opioids and many benzodiazepines. And something I harp on, it's important to understand the catabolism. In other words, the breakdown of opioids and benzodiazepines to accurately interpret presumptive and definitive testing results. Forensic issues. I'm not gonna touch on this more broadly because those that don't work with those involved in the judicial system or in correction settings, this is less of a focus. Federal government regulates urine drug testing for federal employees, public private sector workers in transportation and pipeline industries. In other words, Department of Transportation rules because people are crossing state lines. All other drug testing is regulated by the states. Only about half of states have drug testing statutes at all for their employees. Requirements for forensic collection are much more stringent than clinical collection. You need to confirm appropriate collection site. It needs proper space equipment and security. You need trained personnel. In other words, they need to be certified. Need to inspect the sample immediately after collection. There's gonna be a chain of custody form where at each step there's a sign off. Specimen has to be within the view of the testee and the collector at all times until labeled. So it's observed and the testee needs to confirm the label. You need to immediately record the temperature and pH, immediate meaning under four minutes. And then you complete a log book signed by the collector and the testee certifies the certification statement. The collector completes the famous CCF, the chain of custody form. The sample must be securely stored. You must use colored toilet water. Any handling or transfer of the sample has to be noted and initialed by the person receiving the sample in the CCF. The container's gotta be sealed with tape, signed, delivered, and approved for transportation to a certified lab. And then that has to be attached and the CCF has to be attached. In 2001, we established regulations for certification of medical review officers. So some may be interested in doing this. You need to be a licensed physician. You need to have clinical experience in substance use disorders. You attend a training course every three years and you become certified by the MRO Coordinating Council or the American Association of MROs. What do you do if you're a medical review officer for a corporation, for a hospital, et cetera? This is mainly for employment reasons. If you have a negative sample, the MRO must review that the chain of custody form is valid and that the specimen was within expected parameters for temperature and creatinine. If it's positive, it first has to be confirmed. The cutoffs are meant to eliminate results from passive exposure. It's reported as invalid. In other words, not meeting criteria for creatinine and temperature. It's reported as test canceled. Adulterated or substituted samples are reported as refusal to test. If there's a prescribed substance, such as a patient is prescribed or an employee is prescribed Adderall and the sample comes through as positive for amphetamines, you did not release that to the employer, that sample is reported as negative. So that may be one of the most important functions of a medical review officer. So in summary to this brief section, federal government regulates UDT for certain classes of employees. The chain of custody requirements must be understood and followed. And the MRO provides interpretation of the results to protect the testee. And then let's talk briefly about other lab testing. You may need this for diagnosis, for treatment monitoring, for detection of physical sequelae, such as hep B or C, for detection of comorbidities, which may affect what other medications you prescribe or who you might refer your patient to. So to complement the H and P for chronic alcohol use, it's important to look for some of the longer term sequelae such as macrocytosis with your MCV or low platelets. You can test the urine for ETG and ETS. You can test the blood for PETH. Biomarkers include something that unfortunately is not available for most panels, carbohydrate deficient transferase, much less specific RGGT, NSGOT, NSGPT ratios, a rough rule of thumb is if somebody's actively using alcohol NSGOT might be two times what SGPT is. Check the B12, folate, magnesium, phosphorus, bleeding times, and stool guaiac if you're a PCP. Elevated bilirubins with a normal SGOT, SGPT can be seen in cirrhosis. In other words, the lever's burned out, can't release transaminases anymore, and you might find elevated amylase in pancreatitis or lipase. For people who inject drugs, look for signs of infection. Always screen for hep B, C, and HIV. If uncommon infections such as aspergillosis might suggest injection of drug use. And for substance use disorders in general, indices of malnutrition, sexually transmitted infections may be indicative of risky sexual behavior and as I've noted below, hep A, B, C, HIV, and tuberculosis. So let's talk about our case vignette to close things out. I hope I haven't put you all to sleep. Your patient Bill is maintained on buprenorphine naloxone and he provides a urine drug screen positive for opiates and buprenorphine. So you notice I've used the term opioids throughout. Opiates is actually a term you can use for the naturally occurring opioids. Is this expected for somebody on buprenorphine? So I'll give you a little time to think about that. Maybe play the Jeopardy music in your background. And here we go. And the question is, what's the correct answer? Yes, because buprenorphine is a semi-synthetic opioid. No, the UDT should be positive for bup only. Yes, because naloxone is an opioid derivative. Yes, because buprenorphine will metabolize to opioids. And no, buprenorphine should have metabolized completely to opioids. And the answer is no. The UDS should be positive for buprenorphine only. You can see buprenorphine does not go through any of these natural opioids, the opiates. Buprenorphine should not show up as a, it's a false positive, it shows up as an opioid. So, what would you do next? From my talk, you might say, do confirmatory testing next. But these are the options. Ask the patient what happened. Discharge the patient. Raise the patient's bup-nal dose, because it shows that he's using opioids. Begin to taper the bup-nal dose, the opposite response. Or do the lab test again. And the correct answer is, so notice I don't even have confirmatory testing in here. But this is what I always do first when I have an unexpected result. I ask the patient what's happened. Ask them if they've used anything else. They may immediately say, yeah, I got a couple of my friend's Percocets and I used because I, you know, broke my toe or something. If the patient's actually been doing well up until then, the next thing to ask him is, well, you're on buprenorphine, did the Percocet do anything? In the old days, we would always expect the answer to be no. Nowadays, there are definitely patients, or what not, that do continue to get analgesia from Percocet. Now remember, there's Tylenol in there too. But there also appears to be not full blockade of an opioid effect. But at any rate, I feel the correct answer here is the answer to number two, is ask the patient what happened. If the result supports heroin or codeine use, poppy seeds can be a contaminant with opium milk during harvesting. For harvesting for a few hours after eating a baked product, you may test positive. If you obtain more history to help with insight and motivation, assess their cravings, as well as you check your state's prescription monitoring program. And you may need to consider raising the dose of bup, if not done at your clinic's max dose, if you're not at your clinic's max dose, and if adherence triggers, et cetera, do not explain the lapse. So, the result in this case, since it shouldn't have been there, and if their explanation doesn't explain it, you would do confirmatory testing at that point, in which case it seems likely you're going to find some relapse, in which case you then want to adjust your clinical treatment plan. These are the references. I know they're very small here, but you can print that out. Remember the ASAM appropriate use guidelines. I like the Barthwell article to discuss definitive or confirmatory lab testing. And there are several others that I think are quite good. And I just want to mention the PCSS Mentoring Program. It's designed to offer general information to clinicians about evidence-based clinical practices in providing medications for opioid use disorders. And we have, more recently, or say the federal government has expanded its purview to understand both psychostimulant use disorders as well, since they so commonly co-occur with opioid use disorders. PCS Mentor Programs, which PCSS can link you to, is a national network, which has expertise in pain management and addictions, which I encourage you to try to make use of. And they've got here a three-tiered approach, allows every mentee-mentee relationship to be unique and cater to the specific needs of the mentee. And there's no cost, which I think is important. This is how you get in touch with PCSS, as you can see down below. And if you have a clinical question, it says a simple way to receive an answer related to medications for opioid use disorder is also a PCSS link. And these are the important partners to PCSS. You can see this is a huge range of partners. So you can find a mentor in virtually any area in which you specialize or wanna know information. And this is a picture of a wonderful child who is calling out Educate, Train, and Mentor because she's gonna become an addiction physician in the future. I wanna thank you for your time today. I know some of this was a little technical, but really to understand urine drug testing, it's A, a very important tool to use, but B, important to use correctly. So with that, I want to thank you all and bid you adieu as I go brew another cup of coffee. Thank you.

lab testing

substance use disorders

urine drug testing

clinical settings

treatment progress

prescribed medications

non-prescribed substances

urine matrix