Frequently Asked Questions

Academic detailing is a tested method of delivering tailored training and technical assistance to health care providers in an effort to establish the use best practices.[2,3]  Academic detailing involves the deployment of structured visits to health care practices for the purpose of educational outreach.[1]  Historically, academic detailing has been delivered face-to-face, but Web-based and other technologies can provide alternative channels of communication and educational dissemination.  Academic detailing has been used across many preventive, acute, and chronic disease care settings to provide education and improve best practices, clinical service delivery, and quality of care. [4,5,6,7] Field experts often build relationships over time with health systems by helping health care providers and administrators understand how to address a specific clinical or quality issue.[8] 

References

1. Barth, Kelly S. DO; Ball, Sarah PharmD; Adams, Rachel S. PhD, MPH; Nikitin, Ruslan MS, BA; Wooten, Nikki R. PhD, LISW-CP; Qureshi, Zaina P. PhD, MPH, MS, DMM, RPh; Larson, Mary J. PhD, MPA. Development and feasibility of an academic detailing intervention to improve prescription drug monitoring program use among physicians. Journal of Continuing Education in the Health Professions 37(2):p 98-105, Spring 2017. | DOI: 10.1097/CEH.0000000000000149
2. Thomson O’Brien MA, Oxman AD, Davis DA, Haynes RB, Freemantle N, Harvey EL. Educational outreach visits: Effects on professional practice and health care outcomes. The Cochrane Database of Systematic Reviews. 2000(2):CD000409.
3. Mazmanian PE, Davis DA. Continuing medical education and the physician as a learner: Guide to the evidence. JAMA. 2002;288(9):1057-1060.
4. Soumerai SB, Avorn J. Principles of educational outreach (‘academic detailing’) to improve clinical decision making. JAMA. 1990;263(4):549-556.
5. Meehan TP, Van Hoof TJ, Giannotti TE, Tate JP, Elwell A, Curry M, et al. A descriptive study of educational outreach to promote use of quality improvement tools in primary care private practice. American Journal of Medical Quality. 2009;24(2):90-98.
6. Van Hoof TJ, Miller NE, Meehan TP. Dop published studies of educational outreach provide documentation of potentially important characteristics? American Journal of Medical Quality. 2013.
7. Avorn J, Fischer M. ‘Bench to behavior’: Translating comparative effectiveness research into improved clinical practice. Health Affairs. 2010;29(10):1891-1900.

Baldwin, Laura-Mae MD, MPH; Fischer, Michael A. MD, MS; Powell, Jennifer MPH, MBA; Holden, Erika BA; Tuzzio, Leah MPH; Fagnan, Lyle J. MD; Hummel, Jeff MD, MPH; Parchman, Michael L. MD, MPH . Virtual Educational Outreach Intervention in Primary Care Based on the Principles of Academic Detailing. Journal of Continuing Education in the Health Professions. 2018;38(4):p 269-275.DOI: 10.1097/CEH.0000000000000224

The interpretation of urine specimen drug tests can be challenging due to inconsistent screening and confirmation results.  Enzyme-mediated immunoassays (EIAs) use antibodies to specific drug-binding antibodies to produce a measurable reaction. Gas spectrometry separates different molecules in a drug sample followed by mass spectroscopy to compare patterns to a benchmarked standard for identification.  False positive screens result from cross-reactivity to the antibody in EIA tests. This can be due to the ingestion of specific medications or direct drug binding to the antibody and/or interference caused by lactate and lactate dehydrogenase. Pantoprazole (Protonix) a medication commonly used to treat gastric reflux can produce a false positive for THC.[1]  Aripiprazole (Abilify) is one of several antipsychotic drugs that can produce false positive for amphetamine in the urine drug screen [2], as well as chlorpromazine and thioridazine (due to similarities in structure) may produce false  methadone, and phencyclidine (PCP) results.[3] First generation antipsychotics (FGAs) chlorpromazine, prochlorperazine, haloperidol, and thioridazine may all cause false-positive lysergic acid diethylamide (LSD) results. 

Nearly all tricyclic antidepressants (TCAs) including amitriptyline, desipramine, doxepin and imipramine can produce false LSD. Desipramine and doxepin have also been reported to produce false amphetamine results.[3]  Quinolone antibiotics potentially produce false positives for opiates with levofloxacin and ofloxacin having the greatest risk of doing so. Ofloxacin has also been reported to produce false positive amphetamine test results.[3]  High dose diphenhydramine may produce a false-positive methadone result. Non-steroidal anti inflammatory agents (NSIADs) including both ibuprofen and naproxen when taken in large amounts, may produce false-positive results for barbiturate and cannabinoid.[3] Selegiline and amantadine are drugs used to treat Parkinson's disease and may yield a false-positive result for amphetamines.[4] Medications that contain ephedra may produce false-positive methamphetamine results, including over-the counter nasal drops and certain powder supplements that contain ephedra. It is important to recognize that 0.75 gm methamphetamine can be produced from 1 gm of ephedrine.[5] 

References

1. Gomila I, Barceló B, Rosell A , Avella S, Sahuquillo L, Dastis M. Cross-Reactivity of Pantoprazole with Three Commercial Cannabinoids Immunoassays in Urine.J Anal Toxicol. 2017 Nov 1;41(9):760-764. doi: 10.1093/jat/bkx047.
2. Kaplan J, Shah P, Faley B, Siegel ME. Case Reports of Aripiprazole Causing False-Positive Urine Amphetamine Drug Screens in Children. Pediatrics. 2015 Dec;136(6):e1625-8. doi:10.1542/peds.2014-3333. 
3. Schwebach A, Ball J. Urine Drug Screening: Minimizing False-Positives and False-Negatives to Optimize Patient Care. US Pharm. 2016;41(8):26-30. 
4. Wang G, Bai X, Chen X, Ren Y, Han J. Development of a Genus-Universal Nucleotide Signature for the Identification and Supervision of Ephedra-Containing Products. Molecules. 2022 Apr 6;27(7): 2342. doi:10.3390/molecules27072342
5. Kaewpunya N, Tungtananuwat W, Viriyavejakel A, Yongpanich P.  Screening of patients receiving selegiline from methamphetamine abusers using the urinary amphetamine/methamphetamine ratio. Thai Journal of Pharmaceutical Sciences. December 2015. 39(4):161-170.

Urine drug screens come in several panel sizes measuring the most common to a complex series of drugs. Therefore, all urine drug screens do not measure the same things. Many emergency departments (ED) will obtain a ‘drugs of abuse panel.’ A 9-panel drugs of abuse screen may cover: THC, Cocaine, Opiates, Oxycodone, Phencyclidine, Amphetamines, MDMA (ecstasy), barbiturates, benzodiazepine, methadone, propoxyphene. The ‘drugs of abuse’ panel is one of the oldest drug screens available. It continues to test for propoxyphene which was removed from the market by the FDA in 2010. The more common panels used in the ED setting were designed for rapid detection of a wide range of drugs resulting in reduced sensitivity for any specific drug.1

These less specific panels will identify opiates but may not provide breakdown of the base compound(s).

One needs to be aware of what particular substances are included in a urine drug screen. Urine drug screens are screening tests with high sensitivity but may not be specific for the antigen that they are testing for.  Furthermore, these screening tests are immunoassay tests which means that an antibody is used to bind to a particular part of the molecular structure of the substance in question. Ideally, the location of the antibody binding would be exclusive to the desired substance. However, there are instances where two compounds have similar/related molecular structures that can result in false positives. 

Most point-of-care urine drug screens provide a multiple drug panel. Point-of-care tests are based on competitive binding immunoassay to qualitatively determine the presence of certain drugs. The tests are efficient and they do not require difficult specimen treatment, sophisticated instrumentation or a high level of skill to use. Results are available in 10 minutes or less.3  When a point-of-care urine sample reveals a positive finding, it is typically subject to confirmatory testing using liquid or gas chromatography. The mass spectrometer produces multiple ions from the urine sample. Various ions are identified by their individual mass-to-charge ratio (m/z).2  When ordering a urine drug screen, it is important to note that the screening immunoassays ‘cutoffs’ are the concentration levels for the drug, above which the assay is reported as positive. That is, any drug below that cutoff level will be reported as negative on an immunoassay screen even though it may indeed be present.1 

Reference:

1. Comprehensive drug screen limits of detection. Department of Laboratory Medicine & Pathology. University of Washington, 2023.  https://testguide.labmed.uw.edu/guideline/comp_drug_screen_detection_limits?
2. Bodor GS. Pain management testing by liquid chromatography tandem mass spectrometry. Clin Lab Med. 2018 Sep;38(3):455-470. doi: 10.1016/j.cll.2018.05.005. Epub 2018 Jul 20. PMID: 30115391. 

Lager PS, Attema-de Jonge ME, Gorzeman MP, Kerkvliet LE, Franssen EJF. Clinical value of drugs of abuse point of care testing in an emergency department setting. Toxicology Reports. 2018;5:12-17. https://doi.org/10.1016/j.toxrep.2017.12.001

Rapid opioid tapering should be avoided due to the risk of significant withdrawal unless there is serious risk of overdose. Rapid tapering or sudden discontinuation in physically dependent patients may result in acute withdrawal symptom, pain exacerbation, psychological distress, illicit drug -seeking or suicidal ideation.1  Limiting opioid prescribing to situations where benefits outweigh the risks improves individual and population health. However, rapidly decreasing or abruptly stopping opioid analgesia can increase the risk of adverse events leading to hospitalizations and emergency department visits.2  Tapering plans and opioid dosage reduction should be individualized. An optimal taper minimizes a patient’s pain, anxiety, loss of function, and any withdrawal signs and symptoms. Consider supplying the patient with adjuvant analgesic medications and drugs for withdrawal symptom management to optimize successful taper outcomes.  Taper can be considered burdensome because it may require more frequent office visits. The 2016 VHA Opioid Taper Decision Tool  identified most common tapers involves a 5% to 20% morphine-equivalent dose reduction per month.3

The updated 2022 Veterans Health Administration guidelines recommend an evidence-based collaborative, patient-centered approach to tapering. This recommendation is derived from the large variability in patient preferences that can affect the tapering process, including hesitancy, anxiety, poor response or alternately, having a high motivation to stop taking opiods.3,4

Opioid analgesia, taken for acute pain typically is tapered off by the individual as the healing process takes place and the pain naturally starts to subside. Patients who have been using opioids for chronic pain often require slower tapers that take into account patient preference and behavioral health stability. Individual patients who have been taking opioids for over a year, may require tapering over longer intervals, such as weeks to months, between dose reductions for sustained adherence. A patient-centered approach recognizes that it may be necessary to pause the taper at specific intervals based on patient tolerance, increased pain, sleep disturbance, or withdrawal symptoms.5

Example: Mr. J’s chronic back pain was being treated with a total of 330 morphine milligram equivalents (MME) per day. His medications consisted of one Fentanyl 100 mcg/hr patch q3-days and one immediate release Morphine 30 mg oral tablet TID. It took 3 to 4 months of motivational interviewing about a tapering before the patient was willing to try. Shared-decision-making ensued. The patient expressed concern about withdrawal, so a one-week supply of withdrawal medications was provided for possible symptom management. To reduce anxiety and provide the patient with some level of control, the Fentanyl 100 was reduced to 75 mcg/hr patch, but the 30 MME dose reduction in Fentanyl was replaced with morphine extended release tablets 15 mg, one every twelve hours. The patient was informed he had the same amount of total MME and was asked to perform try and reduce by one (go without one 15mg ER tab) a day for the first week or two and if successful, go without both 15 mg ER tablets (total 30mg of morphine ER) until he was seen the next month. The goal was to not have any major increase in his pain. The patient was very successful and the taper continued in this fashion over the course of 8 to 9 months with at least one pause at the patient’s request. He is currently using Fentanyl 25 mcg/hr patch q3-day and morphine immediate release 15 mg oral tab TID (105 total daily MME). HThe patient acknowledged a noticeable decrease in the amount of medication he was taking for constipation and also he felt ‘brighter’ and expressed feeling as though had more energy. 

Reference:

1. HHS Guide for Clinicians on the Appropriate Dosage Reduction or Discontinuation of Long-Term Opioid Analgesics. Centers for Disease Medicaid and Medicare Services. 2019. 
2. Dowell D, Compton WM, Giroir BP. Patient-centered reduction or discontinuation of long-term opioid analgesic: The HHS Guide for Clinicians. JAMA. 2019;322(19):1855-1856. doi:10.1001/jama.2019.16409
3. Veterans Health Administration. PBM Academic Detailing Service. Pain management opioid taper decision tool. A VA clinician’s guide. October 2016. https://www.pbm.va.gov/AcademicDetailingService/Documents/Pain_Opioid_ Taper_Tool_IB_10_939_P96820.pdf 
4. Dowell D, Ragan KR, Jones CM, Baldwin GT,Chou R. Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR.2022;71(3):1-95. https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm?s_cid=rr7103a1_w

Conversion of opioid dosing to Morphine Milligram Equivalents (MME) is a necessary method to estimate opioid potency in a standardized manner. There are no major mathematical calculations required as the conversion tables do most of the work for you. The following table is from the Centers for Disease Control and Prevention.

NOTE: Use caution when converting methadone. Due to the prolonged half-life of the drug the conversion factor for methadone increases as the dose increases and also remains variable based on the duration of use. There is no MME conversion when dosing buprenorphine (< 2mg) for chronic pain management. 

Calculating MME:

1. Determine the total daily amount of each opioid the patient takes.
   1. OxyContin 20 mg tablet, 1 tablet by mouth every 12 hours
   2. Hydrocodone-acetaminophen 5-300 mg tablet, 1 tablet by mouth four times daily 
2. Convert each opioid to MMEs by multiplying the daily dosage for each opioid by its conversion factor (CF).
   1. OxyContin 20 mg (long-acting oxycodone): x 2 tabs daily = 40mg of oxycodone
      1. 40 mg x 1.5  (CF) = 80 MME
   2. Hydrocodone-acetaminophen 5-300 mg (the conversion only involves the opioid component of 5mg of hydrocodone): x 4 tablets = 20 mg
      1. 20 mg x 1 (CF) = 20 mg
3. Add all opioid MMEs together.
   1. OxyContin 80 MME + Hydrocodone-acetaminophen 20 MME = 100 MME/daily

NOTE: For fentanyl, it does not matter whether you are prescribing q3-days (q-72 hrs)  or off-label at q2-days (q-48 hrs), the manufacturer’s product delivery system does not change. There is no additional calculus involved for how many days the patch is in place. 

• Fentanyl patch 25 mcg/hr q3-day (every 72 hours) = 25 x 2.4 (CF) = 60 MME
• Fentanyl patch 25 mcg/hr q2-day (every 48 hours) =  25 x 2.4 (CF) = 60 MME

Reference:

Calculating Total Daily Dose of Opioids for Safer Dosage. https://www.cdc.gov/opioids/providers/prescribing/pdf/calculating-total-daily-dose.pdf

Short acting opioids should always be the agent of choice initially for both acute pain and chronic pain.Extended release and long-acting opioids should not be prescribed for acute, initial, or intermittent pain management due to the longer half-life and longer duration of effects, particularly respiratory depression.1  Long-acting opioid analgesia should be used for chronic, persistent pain in patients whose treatment currently exceeds 60 MME/day. Adult patients are considered opioid-tolerant when they have been taking at least 60 mg oral morphine/day for one-week or more.2  Long-acting opioids require less frequent dosing, help reduce ‘end of dose pain’ and ‘clock watching’ and they help to reduce large fluctuations in peak and trough levels of drug allowing  for more consistent pain control. Initiating long-acting opioid analgesia requires the patient to be on at least 60 MME/day. Converting your patient to long-acting opioid analgesia at or after reaching 60 MME should be based on shared decision-making. The change should be patient centered, and in line with provider-patient shared goals of improving functional and quality of life. 

1. Determine if the patient would benefit from long-acting coverage or if the pain intensity  waxes and wanes with activity, perhaps continuing with a short-acting agent is more effective. 
2. Calculate the total MME daily dose. Determine if the pain pattern and symptoms management are better served with a 100% conversion to long-acting agents or if activity and patient’s sense of control are best served with converting 25-50% of the total daily MME into long-acting with additional short-acting for breakthrough pain management. 
3. Be aware of the potential for incomplete cross tolerance between different opioids, particularly if the long-acting opioid analgesic differs from the original short acting agent.

Reference:

1. Dowell D, Ragan KR, Jones CM, Baldwin GT,Chou R. Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR.2022;71(3):1-95. https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm?s_cid=rr7103a1_w
2. Food and Drug Administration. FDA blueprint for prescriber education for extended-release and long-acting opioid analgesics. Silver Spring, MD: US Department of Health and HumanServices, Food and Drug Administration; 2017.

https://www.fmda.org/2017/Blueprint%20Opioid%20LA.ER%20REMS%20as%20of%201.20.2017.pdf

The main indications for urine drug testing are to determine adherence, monitor for abstinence, and to detect relapse. A drug metabolite is defined as the process of metabolism where a substance is created as the body breaks down food, drugs or chemicals, or its own tissue.[1] Normally, when a drug is ingested via the gastrointestinal tract, it is absorbed and distributed to the rest of the body after it is metabolized in the liver and other organs and eventually eliminated, primarily in the urine. The rate or speed of metabolism varies for different drugs. Target analytes, that is time of first detection for the parent drug or metabolite will also differ for different drugs. For the parent drug amphetamine, it continues to be detected in the urine. For most other drugs, metabolites are detectable for a longer time than the parent drug, making it important to know common metabolites for most opioid analgesics.

Most drugs will first appear in the urine 1 to 2 hours after intake. When a drug appears in the urine without the presence of any of its known metabolites, it is possible to infer that the drug has recently been ingested and not routinely taken as prescribed; or if the urine drug screen only demonstrates the parent drug, a piece of the actual drug may have been directly placed in the specimen cup, inferring the possibility of drug diversion versus actual drug use. 

Small drug doses may be detected for 1 to 3 days in the urine. Transient or small dose cannabinoids should clear in about 30 days. However, heavy or chronic drug use delays the body’s ability to clear the drug. Amphetamine use can be detectable for 10 days. Cannabinoids may be detected for 3 months. Cocaine metabolites may last up to 3 weeks. Heroin metabolites can be detectable for 11 days. Urine drugs screens provide a more accurate assessment of drug monitoring as most plasma detection times are shorter, often 1 to 2 days.[2]   Many factors can affect drug detection time, including:

1. body mass
2. hydration levels
3. urine acidity 
4. length of time since last drug use

       Table 1. Drug Detection Times  [3]

Reference(s):

1. Metabolite. National Cancer Institute. No date. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/metabolite
2. Verstraete AG, Mukhdomi T. Clinical drug testing. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Jan. 2023. https://www.ncbi.nlm.nih.gov/books/NBK557523/
3. Casolin A. Comparison of urine and oral fluid for workplace drug testing. Journal of Analytical Toxicology. 2016;40:479–485 doi: 10.1093/jat/bkw055

The early stages of diabetes mellitus that cause increased thirst in the undiagnosed patient may produce inconclusive drug test results. Diluted urine may provide a specimen that measures the drug below cut off levels.[1]  A case study involving a patient with marked glucosuria and the presence of bacteria in the urine exemplifies how a patient receiving chronic pain management can develop a false-positive due to urine fermentation. Sugar, microbes and time can produce ethanol detection in the urine resulting from the production of microbial fermentation of glucose. Ethyl-glucuronide (ETG) and ethyl sulfate (ETS) are direct metabolites of ethanol that can present in urine after the ingestion of products containing ethyl alcohol.[2]  For patients with uncontrolled diabetes, it is important to remember that the ‘condition of diabetes’ does not create ethyl alcohol (ethanol) in the human body. You should not expect to find a positive ethanol result in a patient with well controlled diabetes mellitus. 

Reference:

1. Drug testing: Diabetes, glucose and sample fermentation. National Drug Court Institute. 2019. https://www.ndci.org/wp-content/uploads/2019/10/43287-NADCP-FAQ-Handouts-2.pdf
2. Foley K. A Positive Urine Alcohol with Negative Urine Ethyl-Glucuronide. Laboratory Medicine.2018;49:3:276-279 DOI: 10.1093/labmed/lmy008

There are three primary methods for drug screening. Urine drug screens include rapid (point-of-care), instrument-read testing or laboratory based testing at a SAMHSA-1 certified lab. Rapid tests are fast and convenient, taking as little as three minutes to perform. Laboratory confirmations should be required for any preliminary aberrant results. Oral fluid tests are considered convenient, gender-neutral specimen collections that combine the accuracy of scientifically accepted and approved test methods. Oral fluid (saliva) tests protect against specimen adulteration and tampering. Oral fluid tests also provide a better ‘recent-use’ indicator than urine. Hair drug tests provide an analysis of trends of drug use over time or drug abstinence. The test involves a simple, non-invasive collection procedure that detects drug use over several months-to-years, depending on the length of the hair sample. [1]

Reference:

1. Comprehensive Solution. EScreenExpress.com https://escreenexpress.com/?msclkid=.com  

The increased potency and modification of fentanyl with varying compounds have resulted in multiple analogs to the fentanyl drug family. Most immunoassays (IA) do not readily detect synthetic and semisynthetic opioids and their metabolites (ARUP, 2023). The tests are rapid and sensitive to synthetic opioids such as fentanyl but due to cross-reactivity, they do not accurately identify or distinguish among many of the emerging fentanyl analogs (LaRue, 2019).  

Exposure to illicit fentanyl may be unintentional and can come from several sources including counterfeit opioid tablets, heroin contaminated with fentanyl, illicit or pharmaceutical sourced fentanyl patches, and contaminated stimulants such as cocaine or methamphetamine (Kenney et al., 2018). Rapid response fentanyl test strips (FTS) use an enzyme IA that employs an antibody bond with an antigen to signal the qualitative presence of fentanyl. The FTS has a detection limit of 0.13 μg/ml and has been shown to be highly sensitive and specific (Sherman & Green, 2018). 

Fentanyl drug testing may be implemented using point-of-care (POC) screening devices (urine cups), laboratory IA, and mass spectrometry (MS) technologies. Teselection should be aligned with the goals of testing and may include screening alone; screen and definitive confirmation (for positive results); and direct, definitive, targeted testing performed using MS technology. Targeted mass spectrometry technology is the gold standard for fentanyl detection from a presumptive positive UDS (Osmosule, 2022).  

Reference:

1. ARUP. Drug testing. 2023. Retrieved from https://arupconsult.com/content/pain-and-addiction-management#drug-hybrid 
2. Leah LaRue L, Twillman RK, Dawson E, Whitley P, Frasco MA, Huskey A, Guevara MG. Rate of fentanyl positivity among urine drug test results positive for cocaine or methamphetamine. JAMA Netw Open. 2019 Apr; 2(4): e192851. doi:10.1001/jamanetworkopen.2019.2851

3. Kenney SR, Anderson BJ, Conti MT, Bailey GL, Stein MD. Expected and actual fentanyl exposure among persons seeking opioid withdrawal management. J Subst Abus Treat. 2018;86:65–9.

4. Sherman S, Green T. Fentanyl overdose reduction checking analysis study (FORECAST). Baltimore: Bloomberg American Health Initiative; 2018. CL. Should clinical laboratories confirm fentanyl analogs by LC/MS-MS in urine drug tests? American Association for Clinical Chemistry (AACC). September 27, 2022. Retrieved from https://www.aacc.org/science-and-research/scientific-shorts/2022/should-clinical-laboratories-confirm-fentanyl-analogs#

5. Omosule CL. Should clinical laboratories confirm fentanyl analogs by LC/MS-MS in urine drug tests? American Association for Clinical Chemistry (AACC). September 27, 2022. Retrieved from https://www.aacc.org/science-and-research/scientific-shorts/2022/should-clinical-laboratories-confirm-fentanyl-analogs#