Drug Testing

Drug Testing Pearls

Today’s presenter is Miriam Schizer, Medical Director of the Adolescent Substance Abuse and Addiction Program at Boston Children’s Hospital, Assistant Professor of Pediatrics at Ha rvard Medical School, and Dsiplomat at General Pediatrics and Addiction Medicine. And with that, I’ll hand it over to Mimi. Let me give you, uh, control.

Thank you, Virginia. Yep. All right. Welcome everyone, and thank you for joining us for our third session for this curriculum. I have no financial disclosures, but I will disclose that we’re covering a lot of material. So towards the end, there’s a chance I may not go through every slide, but you will have them for your own review.

All right, so let’s talk about drug testing. In this part of the talk, we’re gonna go over the indications for drug testing. Very importantly, how to collect, uh, urine specimens with proper collection technique. And then we’re gonna talk about how to interpret drug test results with the two important categories of false negative results and false positive results.

We’ll also go over how to share the positive drug test result with the adolescent. And his or her parents. And then we’re gonna finish by discussing how to use weekly or regular drug testing in the treatment of patients with known substance use disorders. So there are a number of different biological matrices that can be tested for drugs.

Um, and we’re gonna go over these, but the focus of today’s talk is gonna be urine drug testing, and that’s what we do at asap. So you are aware of, uh, breath testing. We know this is well established for alcohol testing. This is use of a breathalyzer. The disadvantage is that this is really only valuable for alcohol and other volatile substances.

There’s a [00:02:00] relatively short window of detection. Uh, I’ve never seen this in a clinical setting, so we know this is done for, uh, law enforcement, but not for clinical settings. I think you are gonna hear more about oral fluid testing in the years to come. There are a number of advantages. It’s non-invasive.

You can directly observe specimen collection. You can collect someone’s saliva, that’s not invasive. It’s relatively easy to collect, and I think we’re gonna see this more in what we call point of care testing. The disadvantages, as you’ll learn, compared to urine, there’s a shorter window of detection. Um, you do it, if you’re gonna do it the proper way, you do need to supervise the patient for about 30 minutes prior to collection so they don’t manipulate the test, and that’s pretty impractical.

Some patients have a dry mouth and will have difficulty generating the required specimen. Blood testing is something that I rarely see. Um, certainly you can detect recent use through blood testing, and this is [00:03:00] established. I’ve seen this mainly in inpatient and emergency room settings. The disadvantages compared to urine testing, you have a relatively limited window of detection after use.

It’s invasive. This requires phlebotomy, and you need someone who’s specially trained to collect a specimen. I’ve actually never seen this. Um, but you can theoretically test the sweat for drugs. Uh, there’s a sweat patch that was approved by the F D A. The patient comes in, has it put on, comes in, has it taken off, and you can detect use in about a three to seven day window.

Again, I’ve never seen it. I think it’s not widely available, and the patient can always accidentally, or not, remove the patch. I have heard about hair testing from time to time. This is done in some legal settings. The advantage of hair testing is you have the longest window of detection. Generally about three months after use.

You can easily, directly observe. You can cut off a piece of someone’s hair, and it’s difficult to substitute or adulterate. [00:04:00] The disadvantages because of the way hair grows, you’re not gonna detect use that’s occurred within the past seven to 10 days. It’s difficult to interpret results. Apparently hair type can influence results, so that makes it, um, not the most objective test.

And then the specimen can always be removed by shaving. So in ASAP, in our program, we use urine drug testing. I think this is really the gold standard. It’s well-studied, standardized, non-invasive, compared to getting somebody’s blood specimen. And we know that the concentrations of either the parent drug or the metabolite are relatively high in the urine and you have a pretty long window.

You’re gonna learn that it’s on average 48 to 72 hours after use, uh, to detect it in the urine. So indications for drug testing, this can be particularly useful when you’re evaluating an adolescent and you suspect substance use or a substance use disorder. As we’ve learned in the practice of medicine, the lab test is never the most important part of the evaluation, and that’s true in this case as well.

And so before you make that determination, you wanna perform a history, talk to the parents if you can, and do a physical exam. Towards the end of the talk, we’re gonna talk about drug testing. Not just for, um, one time use, but for monitoring for patients with known substance use. So just a few reminders when you’re taking a history of an adolescent with suspected substance use, we talk a lot in ASAP about red flags, and there are certain elements in the history that would make you concerned about a substance use problem.

And this includes a change in academic performance, a child who’s suddenly skipping school. Um, loss of interest in previous activities. It’s a big one. We know that adolescents are moody by nature, but kind of exaggerated moodiness can suggest substance use, as well as, uh, change in friends and changes in the sleep and wake cycle.

Given that we’re talking about drug testing today, as you’re evaluating the patient, it’s [00:06:00] important to know what medications they’re taking.

Physical exam findings. Um, you will hear me say that for the majority of adolescents, even those with serious substance use disorders, the physical exam is gonna be unremarkable, but it’s important to check, particularly a few things. Uh, you wanna always monitor for weight loss. That can be a sign of ongoing substance use.

Decreased attention to personal hygiene I’ve actually almost never seen that. Uh, you wanna always check inside of the nose to look for injury to the nasal epithelium. Insufflation is the medical term for snorting, uh, and then it would be bad form to miss track marks or injection sites. We typically check the upper and the lower extremities.

So drug testing should be considered when there are some elements of either/or and /or the history and the physical, which suggests recent drug use, but the adolescent is denying. So we’re gonna go over a series of very [00:07:00] short cases, which are used to illustrate some points. So the first case is where there’s smoke, there’s fire.

Billy is a 15 year old boy, you’re following him in your practice. He has previous problem use of cannabis, which means that he didn’t meet DSM five criteria for, uh, cannabis use disorder, but there has been some use. He’s done super well with new use in the past three months. He comes home from a school dance.

His eyes are red. His parents can smell cannabis. They call you the next morning and they request a drug test. So just for fun, um, anyone who’s already super awake, can you put in the chat, um, do you wanna do a drug test? Do you wanna hear more? Just a kind of a quick survey of ideas. Who is interested in getting a drug test for Billy with this clinical scenario?

Any takers?

All right. “He smells like pot.” “I think we should talk to Billy first because if he admits it, it’s not worth testing.” “Of course he’s using.” Alright. Thank you. Thank you for the people who participated. Alright, so all very good thoughts. So this slide goes over, um, when it’s more useful to think about getting a drug test versus less useful.

Um, so in this case we have specific symptoms of intoxication. That means it’s more useful. In this case it was red eyes. You can have a patient with a, um, alcohol on the breath nodding off as a classic sign of opioids. Um, in general, drug testing is gonna be more useful clinically if you are aware of the substance that you’re concerned about.

And also as we’ve talked about, or as I suggested earlier on, the timeframe is really important. So to think about doing a drug test, you are, um, looking for use that’s occurred within about 72 hours prior to the discussion. On the, um, on the right would be, uh, less useful. Uh, Um, scenarios generally, if a parent comes to you with vague concerns, they’re worried about substance use, running in the family.

Uh, I remember being a resident, you never wanted to be accused of doing a fishing expedition. That was not a good thing. Um, so again, if it’s vague in general, you wanna have a discussion with the parents about their concerns, but you wouldn’t necessarily, uh, be in a rush to do a urine drug test. It’s important to know that some substances are not easily detectable in the urine.

Inhalants really are the best example. If you’re concerned that a patient is huffing, then a drug test wouldn’t help you because there are no metabolites that make it to the urine. Um, if there’s concern about use, but it occurred weeks ago, then again you wanna discuss it, but not necessarily do a drug test.

Back to Billy. He denies cannabis use. He does agree to a drug test. The results are, uh, the screen is positive for cannabis. The urine creatinine is 150. We’re gonna talk about what that means, and the GCMS confirmation is positive for cannabis. So you talk to Billy, he says, no way, no. How It must have been secondhand smoke.

What do you do next? Um, any thoughts about that? And again, this is just meant to kind of make sure everyone’s had their coffee and is awake. Do people like that it’s secondhand smoke or not so much? Any thoughts for the chat?

Alright, you wanna hear more? Well, let’s see what I have to say. So now I’d like to go over when you order a urine drug test, what you’re getting. And the answer is you’re getting two separate components. The first component is, uh, uses immunoassay technology. This is the quick and inexpensive part of the test.

As you can see by my panel, the picture, you are, you’re able to screen for multiple drugs at the same time. And it’s very important to understand that this is concentration based. So for each drug that you’re testing for, uh, there’s a ]predetermined cutoff value, which means if the drug or the metabolite is present in the urine above that concentration, the screen will be read as positive.

If it’s below that concentration, it will be read as negative. So this is generally a good screening test with a good sensitivity. The downside is there are, uh, gonna be a lot of false positives. And that’s why it’s important that it be coupled with a confirmatory test, which is either gonna be gas chromatography or liquid chromatography, mass spectrometry.

So you might see GCMS or LCMS. This is the gold standard in drug testing. This will give you highly specific results so you know exactly what’s in the urine. You can also get quantitative levels, which we’re gonna talk about as useful for THC. This is where the cost lies. This is really the expensive part

of the test when you order it. So when you order a urine drug test on a patient, uh, get to know your lab. It’s really important to know what’s included in the custom panel at your lab. They all vary a little bit. We’re gonna talk today about how you can order additional tests as needed based on what you’re concerned about.

And then this is a really important point… when you’re talking to an adolescent about getting a drug test, set the ground rules before you get the test, which is who will get the results. So if the adolescent agrees that parents will get the result, you wanna establish that in advance. So back to Billy.

Um, if we were in the same room, I’d ask, uh, by a show of hands who’s familiar with Hotboxing. This is a phenomenon where teens are usually in a small enclosed space. Some will be using the substance (?) Cannabis, some will not. But even the ones who are not using are in that small space intentionally with the um, with interest in getting the effects.

And so unfortunately, this often takes place in cars. Um, my daughter was at Brown. She said they there would be hot boxing in the shower. I’d never heard of that. So in general, this is intentional use. This was the case with Billy, and it should be considered a positive drug test. All right, case number two, big gulp.

Alex is a 16 year old who was caught with cannabis. He was suspended from school. He says, absolutely not. I’ve not used cannabis. I was holding it for a friend. Um, he agrees to drug test and this is his result. So the screen was negative, the urine creatinine was 6 with a specific gravity of 1.001. So you’re all thinking about what this result means.

All right, so now we’re gonna talk about the first category of interpretation, which is false negative drug test results. So there are five categories that I wanna review, which are common sources of false negative drug test results. The first, which was the case for Alex, was intentional dilution of a urine sample.

Number two would be adulteration of a urine sample. A chemical is added to interfere with the testing. Number three is substitution of a different urine sample. Four and five are a little more nuanced, but I would also consider them [00:14:00] false negative test results. Number four, the patient has used a substance, but it’s not gonna be detectable by the drug panel that you’re using.

And number five is the patient did use a substance, in the panel, but it was outside of the timeframe detectable by the test. So these are the five important categories of false negative drug test results. Probably the most important and the one you’re most likely to see is dilution. This is one of the most common methods for attempting to defeat a urine drug test.

Uh, In this case, most of the time the patient consumes a large amount of fluids, which is in vivo dilution in order to dilute the specimen. And remember that this immunoassay is concentration based, so if they’ve managed to dilute the sample, you might miss the present of the drug or the metabolite in the urine.

Patients can also do this, uh, in vitro, which is adding fluid to the actual urine specimen. And that’s why it’s really important when you’re ordering a urine drug test to make sure you check the random urine creatinine. [00:15:00] As well as the specific gravity. So as a product of normal muscle metabolism, there is creatinine in the urine.

Normally it should be present at a number above 50. So if you see a creatinine above 50, it’s all good. For creatinine between 20 and 50, that’s really borderline. This is moderately dilute. This could be a patient who tried intentional dilution, but it can also be a well hydrated patient. So if that’s the case, I would recommend that you, uh, repeat the test with specific instructions to the patient to limit their fluid intake in the two hours before giving you a urine sample.

It gets a little more interesting when the creatinine is between 5 and 20. This is. Very, very dilute and and should be considered a positive test because it’d be difficult to get a urine this dilute without really making an effort. Every now and then we’ll see a creatinine of 0 or 1, which is not consistent with human urine, and that means someone has given you something other than urine, which of course is positive as well.

Uh, so for dilution, a patient can drink a large volume of fluid. They can get fancy and use diuretics. Patients who are using creatine, which you can get at health food stores, can be tricky because that can give you an artificially high creatinine in the urine and so you might miss dilution. Um, I met one patient who was using vitamin B, which can actually increase the pigment of the urine, so you can miss the fact visually of how diluted it is.

The next category for false negative testing, uh, was adulteration. And this means that someone has added a chemical to the test to interfere with either the immunoassay or the confirmatory test. And a number of relatively common household products such as these listed on the slide can be used for this purpose.

Uh, unfortunately, there’s a thriving business available on the internet where you can look for products to try to defeat a drug test. These are some examples. You can purchase synthetic urine, a urine detoxifier, which is an adulterant, [00:17:00] or uh, you could purchase real powdered urine, a 10 pack. So this is someone who’s undergoing some form of regular testing.

So all is not lost. Uh, it’s just important how you collect the sample and then you could really minimize, uh, the effects of, of this manipulation. The gold standard for urine drug testing is direct observation. We sometimes take advantage of that in our practice. For families who are doing home collection, we’ll suggest that a parent,

a same sex parent, be in the bathroom with their child, particularly if the child’s already tried to manipulate the test. Um, there are times when this is not appropriate or seems too invasive, and then there’s something called the Department of Transportation Protocol, which is available, uh, certain labs will offer this service.

And if not, you can use elements of this protocol when you ask families to do home collection. So in the lab, the patient has to show a picture ID, they’re required to empty their pockets before they go into the laboratory, so they don’t have, um, someone else’s urine or any kind of adulterant in their pockets. In the laboratory, there’s no running water.

The toilet water has dye blue. This is so water can’t be added to the specimen. And then immediately after voiding the patient hands the specimen to the lab technician who checks the temperature, and it should be body temperature if they’ve just voided. Um, you can also ask your lab to do, um, do some heavy lifting for you.

It’s really important to get specimen validity testing as part of the lab test that you order. This includes the pH. Um, adulterants will sometimes interfere with the pH and patients will sometimes store their urine and try to use old urine, and that will often have an … uh, an alkaline pH. We already talked about checking the creatinine, and then some labs will actually give you a specific test for oxidants or adulterants. Um, substitution,

so the patient has gotten hold of someone else’s urine or their own urine before they used a substance and they’re using it, um, for the test. Unfortunately, there are devices available on the internet such as this one, which will maintain body temperature if you’re using a substituted urine. There’s a lot of creativity on the internet for this, unfortunately.

So the last two categories of false negative tests, a patient might be using a substance that’s not included in your panel. So it’s generally important to have a good sense of what you’re worried about and what tests you can add to the panel if they’re not already included. Um, but as I mentioned, some of the designer drugs and inhalants really are not,

um, you’re not gonna be able to test for them in the urine. So that’s something you’ll, you’ll have to ascertain in another way. So missed window of detection is my last category. This is a, a slide that shows you a typical lab panel. So you can look at the eight substances on the left. That’s what would be included in this panel.

And then on the right would be the detection window for each substance. I would encourage you to remember two to three days as the window that’s applicable for most substances. Cocaine is interesting. It’s a slightly shorter window, so you have to be a little more aggressive with drug testing if you’re worried about cocaine.

Uh, THC, you could see there’s a broad detection window. I’m gonna explain that in just a few minutes. All right. My third case is unexpected result. Angela is a 15 year old. Her parents come to you because they’re concerned about nicotine vaping and they think she’s also using cannabis occasionally.

They’re not worried about anything else at this point. She is on sertraline for an anxiety disorder. She agrees to drug test. So her screening test is positive for benzodiazepines as well as nicotine and cotinine. We like the random urine creatinine, and then the confirmatory test is only positive for nicotine and cotinine.

So what’s the story with the benzodiazepines? That’s my segue to talk about the next category of interpretation, which is false positive test results. So we’ve talked about how the initial part of the urine drug test is an immunoassay. Um, and I told you that there are a large number of false positives that can be generated, and this is because the immunoassay can recognize other, other substances that could have a similar structure chemically.

And so they react to the immunoassay. Um, but then what you need to know is the confirmatory test will be negative. And that’s why it’s really important when you order a lab test to make sure that you’re also getting the confirmatory test. So a very common example would be, uh, benzodiazepines, which do cause a.

I’m sorry, sertraline, and I’m sure you have a number of patients in your practice who are taking sertraline or Zoloft. This will often yield a positive test result for benzodiazepines, but the confirmatory test is the test that you should rely on, and that will be negative. Um, another example is if a patient has used dextromethorphan, uh, they might have a positive screen for PCP which is very frightening if you see it, except that the confirmatory test will be negative.

So with Angela, that was the story. Um, she was not using benzodiazepines. This was simply because she was taking sertraline. And so, again, always remember to order a confirmatory test. Um, and most, most labs will give you a reflex confirmatory test for all positive screens. Usually that’s what you get, but it’s always important to confirm.

I like to show this slide just because, um, amphetamine has the most, um, the largest number of medication that will cross-react with the immunoassay. This is a favorite board’s question on the addiction medicine boards. If you have a patient on any of these medications and you’re doing a urine drug test, they might have a positive screen for amphetamine, but again, the confirmatory test, which is what you should go by, will be negative.

This is another category of false positive results, but you can see I have quotation marks around it because this is not, um, generally, what we mean by false positives. But my point is you will get a positive immunoassay [00:23:00] and a positive confirmatory test in these cases, but the patient is not illicitly using a substance.

It would be licit use of either a food or a medication. And so, uh, any Seinfeld fans in the audience, this is a picture of an everything bagel. Poppy seeds are interesting. They, they are derived from opium and so if a patient eats an everything bagel, you will potentially see morphine and codeine in their urine, both by screen and by confirmation.

Um, and then this is because of their ingestion. Uh, another important example would be if they’re prescribed a stimulant for ADHD. Certainly they will have a positive confirmatory test for amphetamine, but this would be licit use. This isn’t, um, necessarily illicit use of amphetamines. All right, so we’ve talked about false negative drug test results.

We’ve talked about false positives, and now I just wanna mention a few other things that you should know, um, as you, uh, work on drug testing your patients. So cannabis is an interesting story. Remember on my, on my list it said detection for 3 to 30 days. The way to think about cannabis is, um, we talked at our last session about how it’s lipophilic.

THC is lipophilic and stored in adipose tissue. What you need to know is if a patient is using cannabis occasionally, let’s say someone is using it once a week, then you’ll be able to detect THC in their urine for about three to four days as you would any other substance. The exception is patients who are heavy users of cannabis.

Um, let’s say, let’s say I use daily and then I stop using on January 1st. Because I will have accumulated THC stores, then I could still have THC in my urine drug tests for up to four to six weeks. After I stop using, and that’s because you’re seeing this phenomenon of delayed excretion. That’s where it’s valuable to get quantitative levels, because if the patient has actually stopped, then the levels will come down in a linear fashion until they hit zero.

So we’re talking about adolescents in this, um, learning curriculum, so it’s really important to test them for alcohol in a urine drug test. Interestingly, ethanol is very fleeting in the urine. You’re only gonna bet get about a 12 hour window to detect ethanol after someone has used it. And so what we recommend and what labs will offer is you wanna test for alcohol metabolites in the urine.

And typically these are. Glucuronide and ethyl sulfate. These are detectable for up to 80 hours, usually three to five days after use. You often won’t see this on a standard panel, but you can request, um, to test for these metabolites. Um, you can add this to what you’re testing. We’ve done a lot of testing in the last few years for nicotine and cotinine given the number of patients we see who are vaping nicotine.

Um, usually these tests include cotinine, which is the primary metabolite of nicotine, which has a longer detection window than nicotine. So you can see cotinine usually for about three days in the urine after a patient has used nicotine, either by smoking or by vaping. This is typically not included in a custom pa in a panel, but you can add it on request. In just a few minutes

we’re gonna be talking about opioids. Um, the language is important. It’s important to know what your panel includes. If there’s an opiate screen that’s gonna test for morphine and codeine, which is usually heroin use. Um, It’s important to make sure the lab is also testing for oxycodone, which is what you’re gonna see if a patient has used a prescription opioid.

And then fentanyl will not show up in either an opiate screen or an oxycodone screen. You need to test separately for fentanyl and these days, that’s super important. All right. Case number four. It’s my right to refuse a drug test. Um, so all of the patients so far have very conveniently agreed to drug test.

That’s not always gonna be the case. So Adam is 16. The school is very worried about him because of a number of red flags that they’ve observed. So they’ve contacted his parents and they’ve asked his parents to bring him to see you for an evaluation. You meet with Adam. He’s, um, you know, not impressed that he’s there.

He says, yes, occasional cannabis, occasional alcohol. He’s not acknowledging any other use, and he seems irritated that he’s in your office about this. Then you have a separate meeting with his parents for a collateral history, and you hear about a number of concerning historical factors, and so you ask Adam for a drug test and he refuses.

So the way this plays out is, uh, you’re not gonna force Adam to do a drug test. Adam’s parents say, you know what? We’re really worried about you, Adam. We’re not comfortable with you driving because we’re not sure what’s going on. And so we’re not gonna let you drive until you participate in weekly random drug testing.

So Adam says, not gonna do it. Then about a week goes by and he agrees to drug test so he can have his car back. The first test comes back for a low level of cannabis. Adam says that’s old. His parents let him continue [00:28:00] driving. And then the second test is positive for cannabis and oxycodone. Uh, and the idea is if you do, uh, more than one test, if there is ongoing use, the odds are very strong that you’re gonna catch it.

And that was the case with Adam. So the American Academy of Pediatrics is very explicit that physicians should not order a drug test without the adolescent’s knowledge or consent. I remember someone asked me about this at the last session, and it was a great question. So, if a patient refuses a drug test, then the answer is to set limits using logical consequences.

You’re not gonna drive test. I’m worried that you’re using something so you, you’re not gonna drive, or something similar to that. And there is a clinical report published by the AAP talking about testing for drugs and children and adolescents. And this is a direct quote, “drug testing of a competent adolescent without his or her consent, is it best impractical?

And without his or her knowledge is unethical and illegal.” Uh, every now and then we’ll see someone in ASAP who, uh, was tested without his consent. But I would say if you get a positive test, how do you begin to have the conversation? Because the adolescent didn’t even know that he or she was being drug tested.

So now we’re gonna talk about how to talk to an adolescent about a positive drug test. In general, when you have a test, it’s always better to meet with the patient face-to-face, either in person or via zoom. You wanna talk to the adolescent first without the parent present, and, uh, get a sense of what’s going on.

We have a trick in ASAP that we never lead with a test result. You don’t say your test was positive for cannabis and oxycodone. We’ll say there was an unexpected test result. You know, tell me what you’ve been using, tell me what’s going on. And the advantage of that technique is they might tell you about use that you, you didn’t have in the test.

So it’s a way to get free information if you will. Once you’ve had this conversation, you tell the adolescent what the result was. Um, and then again, if you’ve established that parents will get the result, you’ll talk to the adolescent about sharing that result with the parent. Occasionally, an adolescent might wanna tell the parent on his or her own, in which case you would need to just verify afterwards that the conversation took place.

Um, ideally if there’s a positive drug test, the adolescent has agreed to some form of treatment, either to see a behavioral health clinician or to do another drug test next week so that there’s something that you can present to the parents as the adolescents advocate. So I’ve had a number of these conversations in my lifetime.

They can be ugly. You really wanna kind of keep it to what you’re reporting. You’re sharing the drug test result and then you’re saying, this is what we’re gonna do next. We’re gonna get a drug test. Um, what’s my example here? Joe is committed to not using drugs. He’s gonna continue testing and see a counselor.

So that should be, you wanna diffuse the situation and just focus on, okay, what are we gonna do now? All right, so for the last few minutes of this topic, we’re gonna talk about how to use drug testing [00:31:00] for, uh, as a therapeutic tool. So we talked about screening. You have patients in your practice with known substance use disorders.

This can be a very convenient, uh, a very useful way to monitor them. Um, often this type of regular drug testing is paired with what we call contingency management. So there are predetermined positive consequences for improving results and negative consequences or restrictions for ongoing use. As we discussed, a patient may initially refuse drug testing, but um, you know, using MI and consequences, you can sometimes influence that decision.

So we have a, a robust drug testing program at ASAP typically will suggest 12 weeks, which is just a nice length of time to get started. Uh, it’s important that the testing be random so the adolescent doesn’t try to use around the testing date. Our patients will do, um, collection either in lab, we use Quest Diagnostics, or at home.

I would say we prefer home supervised collection cuz you have a little bit more control over how it’s done. Uh, and we always encourage getting the first morning void because it tends to be the most concentrated. So you don’t have to worry about a low creatinine and what’s this intentional? If a patient has a result that you weren’t expecting,

um, we typically, uh, as I just mentioned, we like to talk to the adolescent face-to-face. Um, if we get a result such as fentanyl or cocaine that we were not expecting, then we treat that as an emergency and we call the parent urgently, just, um, from a safety standpoint. So we do a lot of, uh, drug testing for patients with cannabis use disorder.

Maybe they’re not willing to stop, but we try to incentivize them to at least cut back on their use. And so we look at quantitative THC levels in the urine, um, and we get these levels. I’m gonna show you an example. We take the raw THC value, divide by the urine creatinine, and multiply by a hundred.

And this gives us a number that we can compare from test to test, cuz we’re factoring out concentration. Um, This is my own categorization. It’s not in the literature, but generally there are three categories. The below levels, which fall below a hundred, the bell-shaped curve is really between a hundred to a thousand, which is where a lot of these levels live.

And then the highest levels are in the four digits. These are typically patients who are using a high potency cannabis device on a regular basis. They’re gonna get the highest values. So this is an example of a patient, uh, urine drug test results that we followed in ASAP. Uh, he liked using cannabis.

Parents said, you know what? We’re not gonna let you drive until you’ve stopped. This was based on our recommendation. So he came to see us on December 11th, agreed to stop using cannabis. This is an example of the delayed excretion that I told you about, where even though he stopped on December 11th, it took a few weeks for him to clear THC. And so you can see that there’s a significant dropping in the levels over time. He saw us on January 21st and we said, yes, he’s allowed to drive. He hasn’t [00:34:00] used. So we’re gonna end this part of the talk with a few, um, urine drug test results just so you can see what these look like. And these are ASAP patients.

Luke was a 16 year old who was seeing us with severe cannabis and nicotine use disorder. He would come in monthly to review his drug test results. He was contemplative and so we were working with him on cutting down on his use. This is a nice tool for patients with ambivalence. So I just wanna show you, um, how we do the calculation.

You’ll see the raw score is 1778. We divide it by the creatinine and then multiply by a hundred. So this would give you a value of 926, which is on the high end of moderate use. Uh, I remember Aiden, who was a 15 year old from the Cape with severe cannabis and nicotine use disorder. Also a very significant mental health history.

I’d always get nervous when he came in to see me. So we got an unexpected drug test result. Um, as you can see, his test was positive for methamphetamine. I’ve only seen this a handful of times in my years at ASAP. Um, but it’s out there so it’s important. And, and you see amphetamine, it’s important to know that methamphetamine breaks down into amphetamine, not the other way around.

So you’re only gonna see methamphetamine if the patient used methamphetamine. Dennis was a 14 year old with a cannabis use disorder. We didn’t know of any other substance use. And so, uh, lo and behold, uh, Dennis had a positive screen for opiates with a relatively low level of morphine in his urine. This is consistent with dietary ingestion.

So we talked to, uh, Dennis and his parents and he had eaten and everything bagel within a day or so prior to giving us the urine sample. So we asked him to please avoid poppy seeds for the duration of the testing. Uh, this patient was very difficult to treat. 23 year old with severe opioid and alcohol use disorder.

She would, um, come back and forth to ASAP after going to a higher level of care. She had a history of multiple non-fatal overdoses, um, and her mom was sectioning her a number of times because of her, uh, life threatening condition. And so we thought she was doing well, but we got this urine drug test. You can see she was taking buprenorphine, um, as prescribed, but she was also using fentanyl, um, alcohol and cocaine.

So this is basically a floridly positive urine drug test. Jessica was a 15 year old who came to ASAP with marijuana and nicotine use. She seemed like a relatively light user by our history, so we were surprised when we got this urine drug test with a random urine creatinine of less than one. And it turns out she had given her mother, um, I don’t remember if it was Kool-Aid or something like that, but this was not consistent with urine, and her next urine drug test was positive for nicotine.

She didn’t want her mother to know. For some patients, lab testing may not be an option, um, perhaps if insurance won’t cover it or something like that. And so you, um, it’s perfectly kosher to use home drug testing. You wanna encourage your families to use CLIA waved tests. That’s a form of quality control.

The advantage of home testing is you’ll be able to get immediate results. The disadvantage is that this is typically aminoassay based. You don’t have a confirmatory test when you get home tests, so you might have a false positive. Uh, you usually won’t get alcohol included or nicotine as part of a panel, although you can get a separate home test for cotinine.

Those are becoming more widely available. You’re not gonna get the quantitative THC levels, which we like to use to follow patients. And I would say for a patient who’s complicated and is using a number of different substances, you really wanna use a lab for, for comprehensive testing. So to wrap up this part of our talk today, uh, urine drug testing is complicated, but actually very gratifying.

It’s a really great way to get information, um, to help your patients. You wanna make sure you’re using proper collection procedures, always check for dilution, always use confirmatory testing. Know what you’re worried about as best you can for a patient, and, um, add additional tests as necessary. And then always use caution in interpreting tests.

Urine Drug Testing

MIRIAM SCHIZER: Good morning, everyone. It’s a pleasure to be here this morning to be talking to you. My name is Dr. Miriam Schizer. I work at the Adolescent Substance Use and Addiction Program. We call ourselves ASAP at Boston Children’s Hospital. And I’ll be speaking with you this morning about urine drug testing in adolescents.

I would like to thank the Opioid Response Network for sponsoring this talk. So we have a lot to cover in the next 30 minutes. These are my objectives. We’re going to start with the discussion of the indications for drug testing. When would you want to order a drug test on a patient?

Then we’re going to review proper urine collection procedures which is very important. And then we’ll segway into a discussion of how to interpret drug test results? And I’m going to be focusing specifically on potential false negative and false positive test results. We’re going to review optimal strategies for sharing a positive test result with the adolescent and the parents. And then we’re going to finish by looking at weekly drug testing or serial drug testing for the treatment of patients with known substance use disorders.

So there are a number of biological matrices that can be tested for drugs. Our talk today will focus on urine drug testing, but it’s good to know what else is out there. We do have the capacity to test breath, saliva, blood, sweat, and hair.

Breath testing would be breathalyzer testing. Saliva I think you will be hearing more about in the years to come. That’s becoming more popular. Blood testing is really only used in emergency department settings. Sweat testing is uncommon. The advantage of hair testing is that you do have a longer detection window on the order of weeks to months.

So that being said, at ASAP up at my program we use urine drug testing. And this is very reliable. We know that this is well studied, standardized, non-invasive compared to testing blood. We also know that the concentration of the parent drug or the metabolite is relatively high in the urine. And we have a relatively long window of excretion after the patient uses a substance in which we can detect it. Generally speaking this is about 48 to 72 hours.

So let’s think about the indications for drug testing. We know that this can be a useful adjunct when you’re evaluating a patient with suspected substance use or suspected substance use disorder. We’ve been taught that the lab test is never the most important part of an evaluation. This is also true for drug testing. So before you consider ordering this test, you would want to make sure to do a history, do a physical.

In this work it’s also very important to talk to parents. We call that obtaining a collateral history to find out what’s going on. I will also say at the end that we use drug testing in the treatment of patients with known substance use.

So this slide goes over what to look for in the history when you’re evaluating a patient for potential substance use. There are a number of what we refer to as red flags that suspect this might be going on. I want to highlight a few which include academic difficulties, falling grades, skipping school. We know that adolescents are moody by nature, but if parents are reporting exaggerated moodiness, increased hostility, loss of interest in previous activities, that’s a big one, change in friends, and then noticeable changes in sleep and awake cycles.

Because we’re talking about drug testing today, it’s also important to ask the adolescent what prescription medication and over-the-counter medication they might be taking. This slide goes over physical exam findings. I will say that the majority of cases, the physical exam will be normal even in a patient with a severe substance use disorder.

On the other hand, you do want to look for any recent weight loss, decreased attention to personal hygiene. It’s always a good idea to look in the nose for injury to the nasal epithelium. This would be from snorting. The medical word for snorting is insufflation. And certainly you would never want to miss track marks or injection sites. We usually check the upper and lower extremities to look for those.

All right. So we’ve done the history. We’ve done the physical. Drug testing should be considered when there’s something in the history and/or the physical which is suggesting recent drug use, but the adolescent is denying. So this slide reviews when drug testing would be more useful column on the left versus less useful when you’re assessing an adolescent.

Generally speaking if there are specific symptoms of intoxication noted, you’re going to have a higher yield with your urine drug test. Examples would be the eyes are red. That would be cannabis. Alcohol on the breath. Nodding off is a classic sign of opioid use.

In general, if you’re ordering a drug test, if you know the specific substance that you’re worried about you’re more likely to get a positive test. And of course, the time frame is very important. As I mentioned earlier, we generally have about 72 hours after use to see the drug or metabolite in the urine.

The column on the right reviews less useful scenarios. Generally, if a parent is reporting vague concerns in general, any kind of vague concerns, you certainly want to talk to the parent about that. But your go to wouldn’t necessarily be a urine drug test.

It’s also worth noting that there are a number of substances that are not detectable in the urine. The best example would be inhalants. So if you’re concerned about inhalant use, urine drug testing would not help you. And again, the time frame is really important. If you’re concerned about use that might have taken place a month ago, you wouldn’t necessarily want to follow up with a urine drug test.

Now we’re going to talk about what the test is comprised of when you order a urine drug test. Typically there are two different components. The first component that is done is the screening test, which is the immunoassay. Generally this is the inexpensive component of the test.

It allows you to screen for multiple drugs at the same time. You can see the panel appearing on the right using immunoassay technology. What’s really important about the screening test is that it’s concentration based. And so the screen will read as positive if the metabolite is present in the urine above a certain concentration.

So for example, for cannabis, if THC is present in the urine greater than 50 nanograms per mL you’ll get a positive screen. If it’s below that, the screen will be read as negative. So as you might expect with the screening test, this gives you a good sensitivity but the prices there’s a high rate of false positives.

So it’s very important that the urine drug test also include a confirmatory component, which is typically gas or liquid chromatography mass spectrometry. You might see GCMS or LCMS written on the test. This is your gold standard. This will give you a highly specific result. You won’t get the false positives with a confirmatory test.

We also get quantitative levels. And I’m going to review how we use those. This is where the cost lies. So this is the more expensive component. And I have seen labs in the community over the years that omit this step, but then you don’t have a solution for your false positives.

So in general when you’re ordering a urine drug test for a patient, it’s really important to know exactly what you’re ordering. Know what’s included in the lab’s custom panel. These vary by site. And you would have the capacity to order additional tests as needed based on the patient’s history. So you’ll get a panel and then you could add potentially extra tests to that.

It’s also really important when you order a drug test that you establish with the family who’s going to get the result once it’s available. So if the parents are going to know then everyone understands that at the get go.

This is an example of a typical test result. We use Quest Diagnostics at Boston Children’s Hospital. And so you’ll see in the bottom of the screen, these would be the components of the panel. This is what we’re testing for. This patient tested positive for cannabis.

We are adding a lot of nicotine cotinine testing because of the vaping crisis that we’re dealing with. So you’ll see that pictured on the top. And that was an add on. All right.

Now we’re going to talk about interpreting urine drug test results. And the first topic would be false negative test results. So there are a number of ways you could get a false negative. And generally what I mean by a false negative is the patient is using a substance and for one of these reasons your test will be negative.

So probably the most common reason would be intentional dilution of the urine sample. We’re going to talk about that. The patient may add a chemical to the urine sample that interferes with the test. That is called adulteration. You might be getting a urine sample that is not the patient’s urine. That would be substitution.

The last four categories are a little more nuanced. We’re talking about for category number four the patient is using a substance that you’re not testing for. So that would be the explanation for the false negative. And then the last category is the patient is using a substance that you’re testing for, but use fell outside of the detection window.

So it’s really important to understand dilute tests. This is probably the most common way that individuals will try to defeat a urine drug test. And generally speaking, the patient will consume a large amount of fluid shortly before the urine drug test. And what this does is remember the immunoassay is concentration based.

So if the drug is present below the screening concentration, the test will be read as negative. So the way that you get around this is it’s very important to check the concentration of the urine sample so you’ll know if there’s a problem with dilution. And we usually recommend checking not just the specific gravity, but also the random urine creatinine.

So creatinine is present in urine. It’s a product of muscle metabolism. If you see the number greater than 50, you’re good. That means the specimen is adequately concentrated. In general, if the random urine creatinine is in that 25 to 50 range this suggests that the patient might have tried to dilute the sample, but it’s not conclusive. And so in this case, you would ask the patient to give you another sample with specific instructions to limit fluid intake for 2 hours before giving the test.

Generally speaking, a creatinine lower than 25 is a slam dunk. You can think of that as intentional dilution and that can be considered a positive test. Every now and then to make life interesting we’ll get a creatinine of 0 or 1, which means that someone has given you a sample that isn’t human urine. So that’s always interesting.

The next category for false negative tests would be adulteration. And so someone has added something to the urine sample which interferes with either the immunoassay or the confirmatory testing. And what’s interesting is relatively common household products such as those listed on the slide can achieve that result.

Certainly patients turn to the internet if they’re looking to defeat a drug test. This is a sample of what’s available. You can purchase synthetic urine. You can purchase a urine detoxify. There’s your adulterant. And you can even purchase a 10 pack of real powdered urine.

So the importance in avoiding these categories would be to add specimen validity testing to your test. As I mentioned, you want to make sure you’re checking the concentration. Urine ph is valuable. You want to make sure that the ph of the specimen falls between 4.5 and 9. With adulterants it can sometimes be very low or very high. And as I mentioned, you want to check the specific gravity. Some labs will perform specific testing for adulterants, which is a valuable service.

So as I mentioned earlier, it’s important how you collect the urine specimen. The gold standard would be direct observation would be to have someone in the room when the patient voids. Sometimes this is invasive or clinically inappropriate. So the next best option would be to use what we call the department of transportation protocol. And labs will often use this or you could teach parents how to do something similar in the home.

So if this is in a laboratory when the patient arrives, they’re required to show their picture identification so they are who they say they are. They empty their pockets before going into the testing room and they wash their hands. In the laboratory, it’s important that there’s no running water. They can’t add water to their sample. Similarly, the toilet water is dyed blue.

And then very important when they hand the sample to the technician or to a parent, the temperature of the urine is checked immediately. Urine should be body temperature right after voiding. All right.

So the last couple of categories for false negative testing would be that you’re ordering a test, but the patient is using a substance that’s not covered by the testing panel. And that’s why I encourage you to know what you’re testing for and add tests as indicated. For example, very few labs will include fentanyl in their panel. So you might want to add fentanyl. We can add dextromethorphan, synthetic cannabinoids, et cetera. So it’s always a good idea to know what substances are most prevalent in your community and to make sure that you’re testing for them.

As I said, the last category for false negatives is yes, the patient used a substance included in the panel, but outside of the window of detection. And so this slide goes over what would be a standard testing panel and then what the detection window is for these substances. I will tell you if you want to remember one time frame 48 to 72 hours is accurate for most substances.

You can see that for amphetamines, cocaine, and opiates. That’s pretty reliable. There are a few exceptions to the rule. Benzodiazepines, methadone typically are detectable in the urine for longer periods of time.

And I want to mention the cannabis story because that’s really a unique story. In terms of how long you have to detect cannabis in the urine, there are really two different populations for patients who are using cannabis sporadically let’s say once a week. You have about 3 to 5 days to detect THC in the urine for occasional users.

For patients who are using heavily, let’s say patients who are using cannabis daily, what happens is they accumulate stores of THC in their adipose tissue. It’s highly lipophilic. And so even after they stop using, you’ll be able to detect THC in the urine for up to 4 to 6 weeks. If you’re getting a quantitative value, you will see that value go down linearly in that time period until it eventually hits zero.

I did want to mention testing for alcohol because it’s very important with adolescents. If you have ethanol in your panel then you’re only going to be able to detect it for about 12 hours. It’s a very short detection window. And so what we recommend is testing for a couple of metabolites of alcohol. And these are ethyl gluconate and ethyl sulfate. These will be detectable for about 3 to 5 days after detection. So you should see if your lab has the capacity to check for these two metabolites.

And then for opioids it’s always important just to review the terminology. Opiates refer specifically to morphine and codeine. If a patient used heroin, they’ll have a positive test for opiates. Opioid is a broader term which includes prescription opioids. If you’re looking for prescription opioids, you’ll want to make sure that oxycodone is included in your testing panel.

And as I mentioned earlier, fentanyl is a separate test. If you’re looking for fentanyl, you would need to order a fentanyl and metabolite test. All right. So we’ve talked about false negative test results.

Now I’d like to mention false positive test results, which is an important category. So the way this works is we’ve talked about how the immunoassay is the initial screen. The immunoassay can recognize a structure that’s similar to the drug that you’re looking for. And this can result in a false positive screen.

On the other hand if you do the confirmatory test, that will be able to rule out false positives because your confirmatory test will then be negative. As an example looking at this slide, if a patient is taking amoxicillin they could theoretically or actually have a positive screening test for cocaine, but the confirmatory test will be negative because that test is highly specific and will be able to tell the difference.

I like to show this slide because it turns out that the amphetamine immunoassay has the most false positives of any of the components of a immunoassay. So all of these medications if a patient is taking them these might trigger a positive screening test for amphetamine. But as I mentioned, the confirmatory test will be negative.

Urine drug testing in general is very reliable if you’re doing both the screening test and the confirmatory test. You can feel confident in the results that you’re achieving. You’re going to identify 95% to 98% of true negative results. So you can trust your negative tests. And you’re going to identify 99% to 100% of the actual positives. So again, the most important advice is to make sure you’re doing both the screen and the confirmatory test.

This category is slightly different. Now I’m talking about clinical false positives. This is in quotes. This is different from the false positive category I just mentioned. In this in this situation, a patient has ingested a food or is taking a medication which will yield a positive result, but they’re not actually using illicit substances.

So if you see the picture on this slide, this is a poppy seed bagel. And it is true that poppy seeds are broken down to morphine encoding. So a patient who’s eaten an everything bagel could definitely have a positive test for opiates. Both the screen and the confirmatory test will be positive.

If you get a history, you’ll discover that this was dietary and this was not use of heroin. Another important example would be a patient who’s taken a stimulant for treatment of ADHD certainly will have a positive test for amphetamine, but this doesn’t represent illicit use.

All right. So now if you’ve asked a patient for a drug test and they refuse, what do you do? I really want to make sure everyone understands that you’re not supposed to get a drug test without the patient’s consent. This is absolutely a no no. The American Academy of Pediatrics is explicit that physicians should not order a drug test without the adolescent’s knowledge or consent.

If a patient refuses a drug test obviously that’s going to make you highly concerned about what’s going on. The best solution would be to work with the parents who could use appropriate consequences. So a good example would be the patient refuses a drug test so the parents say, well, I’m really worried and I’m not sure what you’re doing. So I’m not going to let you drive the family car until you’ve consented to a drug test. That would be a very appropriate way to manage the patient’s refusal.

All right. So let’s say you’ve gotten a drug test, you have the positive result, now what do you do with it? We always recommend that you meet with the patient privately without the parents present to go over the test result. And again, in the old days this was in person. Now we’re doing a lot of this virtually.

So our strategy when you have a positive test result is to be vague with the adolescent. So you say to the adolescent, we have an unexpected test result or there was a problem with your test. And then you ask them to tell you what they may have used. The advantage of this strategy is they don’t actually know what you have in the urine drug test so they might give you more information than you actually have.

So if you’ve established an advance that the result will be shared with the parent as you wrap up with the adolescent you’re going to say, OK, this is what I’m going to tell your parents. And again, less is more. You can just focus on the drug test result. The patient might ask that they tell their parents themselves. You can do that if it feels comfortable and then you just want to make sure you have a follow up conversation to make sure that the conversation took place.

These conversations can get very heated when you’re telling parents about test results. And I would recommend really keeping the report simple and brief. So an example would be Joe had a dilute drug test and told me he used cannabis and took some pills last week. So you’re giving them the facts.

As I mentioned, these conversations can become heated. Parents sometimes don’t take the news well. But when you’re in the room, you want to be the advocate for the adolescent. You want to focus on what they are willing to do. So if they’re willing to see a counselor or give you another drug test next week, that’s what you’re going to focus on just to keep the conversation from becoming a shouting match.

So the last thing that we’re going to cover is using drug testing for longitudinal care of patients with substance use disorders. And this is something that we do in our program all the time. We typically recommend weekly random drug testing to monitor the patient’s progress. You’re also inviting them to make progress and cut back. And then you’ll be able to see that.

So this works best when it’s paired with a contingency management approach. So patients can sometimes be offered small and appropriate rewards if their drug tests are showing improvement. As I mentioned earlier, the patient may initially refuse drug testing but you can work with parents to make it a little more appealing by using consequences.

So at ASAP in my program typically we do weekly testing for a 12 week window. Random testing is important so the adolescent doesn’t know the date in advance. Typically our collection is done either in the lab or at home. I think if the parents can swing supervised collection at home that tends to work best. And we usually prefer the first morning sample because typically that’s the most concentrated and we don’t have to worry about intentional dilution.

As I mentioned, if the patient has an unexpected drug test result or a positive test, we would try to see the patient for an appointment to discuss the result. If we get something that’s suggestive of very high risk use and unexpected such as getting a test for fentanyl, cocaine, oxycodone, typically the parent will get a call immediately as soon as we have that result for safety.

So as I mentioned, confirmatory testing does give you quantitative levels. And we find this very helpful when we’re monitoring a patient with a cannabis use disorder. And what you can do is you can compare these levels from test to test.

Here’s a little math trick. So to compare the tests, the THC values you take the raw THC, you divide it by the random urine creatinine, and you multiply by 100. I’m going to show you an example of this. And then that gives you a value that you can compare from test to test because you’ve corrected for differences in concentration.

Generally speaking, levels can fall in one of three categories. If the corrected THC is less than 100, that’s on the low end. Moderate use would be 100 to 1000 typically. And then the kids who are using most heavily typically very concentrated THC as well will have levels in the four digits.

So this is an example of an ASAP patient who was using cannabis. Parents said, you know what, we’re not going to allow you to drive until you’ve stopped which is what we recommend. And so the patient did weekly drug testing. He met with us in early December. And you could see after that if you follow the levels, they are decreasing because he stopped using. And then in mid-January he got his car keys back.

I’d like to finish with a few slides that show examples of actual drug tests from actual ASAP patients. All right. So Aidan is a 15-year-old boy with severe cannabis and nicotine use disorders who was participating in our drug testing program. So he does have marijuana. Just to go over the calculation that I showed you, so you would take the marijuana metabolite, which is 14, divide it by the creatinine, which is 172.5, multiplied by 100, you would get a value of 8 which is a low level.

The reason I’m showing you this slide is his test was positive for methamphetamine. We’re not seeing thankfully a lot of this in eastern Massachusetts. So this was a very alarming and unusual result for us.

Dennis is a 14-year-old boy with a moderate cannabis use disorder. No history of other substance use who was participating in our drug testing program. So if you look at this test result, yes, he had a positive test for marijuana as we expected. And then he also had a positive test for opiates. You can see that his morphine level was 139.

We talked to Dennis and it turns out he had eaten an everything bagel before giving the urine test. So that would be a result consistent with dietary ingestion. All right.

I remember Kristen well. She’s a 23-year-old young woman with a severe opioid and alcohol use disorder. She was in and out of outpatient treatment. She had a history of recurrent overdoses. She would go to residential treatment. She would come back. And we had a very hard time treating her effectively.

So this is an example of a [INAUDIBLE] positive urine drug test result. You will see that she was prescribed buprenorphine. She was taking it. You could see it in her urine, but it wasn’t effective because you can also see fentanyl and norfentanyl in her urine. She was also using cocaine. Benzoylecgonine is the cocaine metabolite we see in the urine. And these are the alcohol metabolites that we talked about. Ethyl glucuronide and ethyl sulfate. All right.

So Jessica is a 15-year-old girl who came to us with marijuana and nicotine use. We thought she had a relatively not serious problem. And then she gave us a urine drug test. So as you can see this creatinine was less than one. I’m not sure what beverage she gave us is her urine sample, but this was not consistent with human urine. All right.

So for some patients you might consider home drug testing. Particularly if insurance isn’t covering weekly drug testing. It certainly can be an option for some patients. You should always use CLIA waived tests. If you see that on the test, that’s essentially quality control. The advantage of home testing is families get immediate results.

The disadvantage though is these typically rely only on immunoassay or enzyme testing. And so you certainly can have false positives with this mode of testing. Panels are generally not as elaborate as what I’ve showed you is what Quest gives us. You’re not going to get the quantitative THC levels. So I would suggest if there’s a patient with use of multiple substances, a patient that you’re really worried about, they’re not a great candidate for home testing.

So in summary, hopefully I have shown you and convinced you that urine drug testing is a relatively complex, but still doable procedure. It’s very important to use proper collection procedures. You want to check for dilution. You want to use confirmatory testing for all of your positive screens.

Definitely think about what substance you’re looking for and use an extended panel if indicated by the patient’s history. And always use some degree of caution in interpreting tests. Thank you so much.