Urine Drug Monitoring Research Articles

Quantitation of propofol metabolites by LC–MS/MS demonstrating long detection window for urine drug monitoring

IntroductionChromatographic methods for analysis of propofol and its metabolites have been widely used in pharmacokinetic studies of propofol distribution, metabolism, and clearance. Application of chromatographic methods is also needed in clinical and forensic laboratories for detecting and monitoring propofol misuse. ObjectiveWe report a method for sensitive analysis of propofol, propofol 1-glucuronide (PG), 4-hydroxypropofol 1-glucuronide (1-QG), 4-hydroxypropofol 4-glucuronide (4-QG) and 4-hydroxypropofol 4-sulfate (4-QS) in urine by LC–MS/MS analysis. The method employs a simple dilute-and-analyze sample preparation with stable isotope internal standardization. ResultsValidation studies demonstrate a linear calibration model (100–10,000 ng/mL), with dilution integrity verified for the extended range of concentrations experienced in propofol use. Criteria-based validation was achieved, including an average coefficient of variation of 6.5 % and a percent bias of −4.2 ng/mL. The method was evaluated in 12 surgical patients, with monitoring periods lasting up to 30 days following intravenous propofol administrations of 100–3000 mg on the day of surgery. While the concentration ratio of PG to 4-hydroxy propofol metabolite decreased significantly in the days following surgery, PG maintained the highest concentration in all specimens. Both PG and 1-QG were detectable throughout the monitoring periods, including in a patient monitored for 30 days. Lower concentrations were determined for 4-QG and 4-QS, with evidence of detection up to 20 days. Propofol was not detectable in any urine specimens, thereby proving ineffective for identifying drug use. ConclusionThe validated method for quantifying propofol metabolites demonstrates its applicability for the sensitive detection of propofol misuse over a long window of drug-use detection.

A New Protocol of Methamphetamine Dependence Treatment with Taper-Up-Off Treatment of Opium Tincture, a New Hope to Cure the Methamphetamine Addiction

Methamphetamine is a neurotoxic drug and highly addictive stimulant, which causes a significant psychological dependence in use disorder and potential brain damage even in the first use disorder. Despite decades of research, no approved pharmacotherapy is available for methamphetamine (METH) use disorder, and behavioral therapies are faced with a great lack of long-term recovery and a high rate of relapse. Opium tincture is air-dried Papaver somniferum latex, formulated for oral administration. The present study aimed to evaluate the effectiveness of the new protocol for taper up-off method of opium tincture used for treatment of methamphetamine addiction in Iran, for more than 10 years. In the present study, the effectiveness of the Opium tincture taper-up-off treatment method for methamphetamine dependence called “Dezhakam step time (DST) for methamphetamine” was assessed. We used data collected via the “Congress 60” a nongovernmental organization in Iran, dedicated to addiction treatment with the DST method, from Jan 2018 until December 2020. We evaluated the treatment safety, success, and relapse rate in methamphetamine dependents treated in the “Congress 60” organization with the DST for methamphetamine method. All subjects were tested using Urine drug monitoring for both opioid and methamphetamine use after the treatment period and during the next two years as a follow-up. Findings revealed 89 percent of successful treatments for methamphetamine dependence and only 11 percent of substance abuse relapses in two years follow up. Also, less than one percent of the subjects that finished the treatment program abused opioids in two years follow up. Findings suggest the safety and effectiveness of the Opium tincture taper-up-off method in the treatment of methamphetamine dependence. The findings of the study may help to a better understanding of a safe potential novel method for methamphetamine dependence treatment and its effects on psychological dependence on psychostimulants.

Compliance or Abuse? Detectable hydromorphone in patients taking oxycodone

Abstract A middle-aged woman with recent cervical diskectomy with spinal fusion at C3-C4 suffered a mechanical fall with bilateral upper extremity paresthesia requiring admission but no surgical intervention. Patient was seen by orthopedic service and was recommended to continue using Aspen collar and oxycodone for pain. Following discharge, a drug urine screen test was performed, and showed positive for oxycodone by immunoassay. Confirmatory urine test by liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed detectable oxycodone, oxymorphone and hydromorphone. In patients treated with opioid therapy for chronic pain, urine drug monitoring is an important tool to ensure that patients are adhering to the prescribed medication. Hydrocodone and hydromorphone are not metabolites of oxycodone. However, hydrocodone can be present in oxycodone preparations with an estimated impurity of <1%. Hydrocodone can be metabolized into hydromorphone, although, there is no literature reporting detectable hydromorphone in patients’ urine with prescribed oxycodone only. This case resulted in a quality improvement project where we evaluated the detection of hydrocodone and hydromorphone in positive oxycodone urine samples using LC-MS/MS. We analyzed 322 oxycodone positive urine samples. Twenty-one samples (6%) had detectable hydrocodone and/or hydromorphone below 100 ng/mL. Twelve out of the 21 were from patients taking no opioid medication other than oxycodone in the last week, with 33.3% showing detectable hydromorphone and 75% for hydrocodone below 100 ng/dL. The calculated hydrocodone/oxycodone (HC/OC) and hydromorphone/oxycodone (HM/OC) ratios were on average 0.26% HC/OC = 0.26% (0.05-0.69% SD 0.002; HM/OC = 0.26% (0.18-0.37% SD 0.001)] each (<1%). Patients taking oxycodone and other opioids had ratios >1% [HC/OC = 168% (3-563% SD 2.53; HM/OC = 699% (1.09-6585% SD 15.96)] and had higher detected levels (>100 ng/mL). Pain management can be very challenging; therefore, laboratory testing provides an objective assessment of drug exposure and adherence to treatment. Cut-off values for considering positive the detection of hydrocodone and hydromorphone may change the interpretation of the drug urine tests in patients with prescribed oxycodone. Using higher cutoff (100 ng/mL) and the ratios HC/OC and HM/OC (<1%) may be useful to determine that the detection of these components is due to impurity of oxycodone formulation.

Assessment of urine sample quality by the simultaneous measurement of urinary γ-glutamyltransferase and lactate dehydrogenase enzyme activities: possible application to unravel cheating in drugs of abuse testing.

Evaluation of the simultaneous measurement of urinary γ-glutamyltransferase (γGT) and lactate dehydrogenase (LDH) to discriminate fresh from previously frozen specimens in urine drug monitoring. Two widely available photometric tests (Siemens Healthineers Atellica) were used to determine the range of urinary γGT and LDH excretion and to study the decay in urinary enzyme activity under various storage conditions (room temperature, 4-8°C,-18°C,-80°C). From these data, cut-off values were established and evaluated in split (fresh/frozen) specimens. Both assays allow robust, reliable, and simultaneous determination of urinary γGT and LDH. In healthy subjects, the 95% reference intervals for enzyme activity in native urine were γGT: 24.4-100.4U/g Crea (creatinine) and LDH: 2.5-45.8U/g Crea. Frozen storage for at least 7days at-18°C resulted in a loss of activity to less than 50% in both enzymes. Cut-offs for frozen samples were γGT≤33.2U/g Crea and LDH≤ 8.4U/g Crea. When applied to 100 sample pairs (fresh/frozen), 86.5% (173/200) of the measurements were conclusive and the combination of concordant enzyme measurements (low γGT/low LDH or high γGT/high LDH) was able to predict the mode of storage with a sensitivity of 96.3% and a specificity of 96.7%. The additional measurements of urinary γGT and LDH can be used to detect previously frozen urine specimens. A simple protocol is proposed to provide additional information on sample quality when deceit is suspected. The procedure can be easily integrated into the standard workflow of urinary drug monitoring.

Developing LC-MS/MS methods to quantify rivaroxabanin human plasma and urine: Application to therapeutic drug monitoring.

Rivaroxaban is an oral anticoagulant directly inhibiting the activity of Factor Xa, which is widely used for the prophylaxis of thromboembolic disorders. Therapeutic drug monitoring (TDM) is required during therapy for individual dosage adjustment. This study aimed at developing a liquid chromatography/tandem mass spectrometry method that was suitable for rivaroxaban TDM in human plasma and urine and exploring the feasibility of urine drug monitoring in medical care. A 3 min run time of the LC-MS/MS methods was established by employing an Acquity UPLC BEH C18 (2.1 × 50 mm, 1.7μm) column using gradient elution of 10mmol/L ammonium acetate containing 0.1% formic acid-0.1% formic acid acetonitrile as a mobile phase at a flow rate of 0.4ml/min with calibration ranges of 0.5-400 and 10-10,000 ng/ml for human plasma and urine, respectively. Rivaroxaban was detected on a triple quadrupole tandem mass spectrometer with an electrospray ionization source in positive ion mode. The methods showed good linearity within the calibration range. The precision and accuracy, matrix effect, extraction recovery and stability in both human matrices were all validated and meet the international guideline requirements. These validated methods were successfully applied to support the TDM of an aged patient receiving rivaroxaban for therapy.

Application and Clinical Value of Definitive Drug Monitoring in Pain Management and Addiction Medicine.

To assess routine application and clinical value of definitive urine drug monitoring (UDM) for drug detection, inconsistent drug use, and prescription adherence, along with a comparison to immunoassay screening (IAS). Direct-to-definitive UDM performance was analyzed retrospectively in 5000 patient specimens. Drug findings, medication inconsistencies, and detection sensitivity were assessed, and definitive UDM versus IAS monitoring was studied. Definitive testing resulted in 18,793 drug findings with 28,403 positive drug and metabolite tests. Definitive testing expanded monitoring with 11,396 drug findings that would not be tested by IAS. The opioids accounted for the highest frequency of inconsistent positive drug-use findings, at 12%. Conversely, inconsistent negative drug findings, used as an index of prescription non-adherence, were determined in 1,751 of 15,409 monitored medications and included a high frequency of antidepressants and antipsychotics inconsistencies. Direct comparison of definitive UDM and IAS showed false-positives by IAS as well as a high rate of false-negatives that would be missed using current confirmation protocols. Results from routine application of direct-to-definitive UDM demonstrate the clinical value of drug-use identification and the objective evaluation of inconsistencies in drug misuse and medication adherence in pain management and addiction medicine practice. Without conversion to direct-to-definitive UDM, continuing use of IAS will limit the scope of drugs being tested, will result in an indeterminate rate of false negatives and will require confirmation testing to eliminate the reporting of false-positive IAS tests. The findings in this study provide evidence-based support for recommended use of a direct-to-definitive drug testing protocol.

Trends in Urine Drug Monitoring Among Persons Receiving Long-Term Opioids and Persons with Opioid Use Disorder in the United States

Practice guidelines recommend urine drug monitoring (UDM) at least annually in the setting of chronic opioid therapy as an objective assessment of substance use. However, empirical evidence on who gets tested and how often testing occurs is lacking. This study investigates 10-year UDM trends in the United States based on 2 factors: (1) the duration of prescription opioid treatment, and (2) having an opioid use disorder (OUD) diagnosis and medications for opioid use disorder (MOUD) prescriptions. Observational cross-sectional study. Research was conducted using administrative claims data from Optum's deidentified Clinformatics Data Mart Database for the period 2007 to 2016. The dataset contained information on the plan enrollment and health care claims from 50 states and the District of Columbia. To examine trends in UDM based on the duration of prescription opioid treatment, persons receiving prescription opioid analgesics were categorized into 4 groups based on the number of days covered: (a) less than 90 days, (b) 90 to 179 days, (c) 180 to 269 days, and (d) at least 270 days. To examine trends based on an OUD diagnosis and MOUD prescriptions, persons diagnosed with OUD were identified and categorized based on the presence of MOUD prescriptions as follows: (a) OUD with buprenorphine (BPN) and naltrexone (NTX) in the same year; (b) OUD with BPN only; (c) OUD with NTX only; (d) OUD with chronic prescription opioid analgesics (>= 90 days); (e) OUD without prescription opioid analgesics, BPN, or NTX; and (f) chronic prescription opioid analgesics (>= 90 days) without an OUD diagnosis. For analysis, the percent receiving UDM was estimated per group per year. Then the data were restricted to those receiving at least one UDM to estimate the average number of UDM per person. Data included an average of 364,485 persons per year receiving prescription opioid analgesics for chronic use, and 10,277 per year receiving an OUD diagnosis. Among those receiving prescription opioid analgesics, less than 50% received UDM. For those receiving at least one UDM, one additional UDM was performed per person as the duration of opioids increased by 90 days. Among persons with OUD, the percent receiving UDM was the highest for those receiving both BPN and NTX (87%), followed by those receiving BPN only (80%), chronic opioids (79%), NTX only (72%), and those not receiving any MOUD/opioids (54%). Methadone dispensing for OUD treatments was not captured in administrative claims data. Although recommended for patients with chronic pain, UDM is provided less than half of the time for these patients. However, once patients received at least one UDM, they would continue to receive it on a fairly regular basis. Compared with those with chronic pain, persons diagnosed with OUD are more likely to receive UDM at a more frequent interval.

A Rapid Dilute-and-Shoot UPLC-MS/MS Assay to Simultaneously Measure 37 Drugs and Related Metabolites in Human Urine for Use in Clinical Pain Management

Monitoring of medication compliance and drug abuse is used by clinicians to increase patient prescription drug compliance and reduce illicit drug abuse and diversion. Despite available immunoassays, chromatography-mass spectrometry-based methods are considered the gold standard for urine drug monitoring owing to higher sensitivities and specificities. Herein, we report a fast, convenient ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay to detect or quantify 37 clinically relevant prescription drugs, drugs of abuse, and related glucuronides and other metabolites in human urine by single diluted sample injection. Analytes consisted of prescription and illicit opioids, benzodiazepines, and drugs of abuse, including parent compounds and glucuronidated and nonglucuronidated metabolites. Urine samples were diluted with water and supplemented with deuterated internal standards without enzymatic hydrolysis, analyte extraction, or sample purification. Analytes were separated by reversed-phase UPLC and quantified by positive-mode electrospray ionization and collision-induced dissociation MS. Assay validation followed Food and Drug Administration bioanalytical guidelines. Total analytical run time was 5.5 min. All analytes demonstrated acceptable inter- and intraassay accuracy, imprecision, and linearity throughout clinically relevant analytical ranges (1-2000 ng/mL, depending on analyte). All analytes demonstrated acceptable selectivity, stability, matrix effects, carryover, and performance compared to national reference laboratory or previously validated in-house methods. A total of 23 and 14 analytes were validated for quantitative and qualitative testing, respectively. A convenient UPLC-MS/MS assay for simultaneously monitoring 37 analytes in human urine was validated for use in pain management testing. Advantages of this multiplex assay include facile sample preparation and higher-throughput definitive detection including glucuronide metabolite quantification.

(225) - Heroin use among patients prescribed opioid therapy

Heroin and other opioids are claiming lives throughout the U.S. at a staggering rate. About 4 out of 5 heroin users abused prescription drugs first. With this review, we sought to explore the use of heroin in patients being treated for pain with prescribed opioids. We also explored whether the use of heroin was associated with the use of other illicit drugs or misuse of prescription medications in this demographic. A retrospective review was conducted utilizing a database of 171,061 urine samples received from patients prescribed opioids for pain and other prescription medications, and tested for the heroin metabolite, 6-monoacetylmorphine (6-MAM), from 2012–2014. Samples were classified as heroin positive (a positive liquid chromatography/tandem mass spectrometry result [LC/MS/MS] for 6-MAM) or heroin negative (6-MAM MS was performed and negative). Samples from patients prescribed morphine, methadone, or buprenorphine were excluded from the analysis. In addition to heroin, samples were evaluated for the presence of other illicit drugs (cocaine, MDMA, PCP, THC, synthetic cathinones, and synthetic cannabinoids), for the presence of their prescribed medication (opiates, stimulants, synthetic opioids, sedative/hypnotics), and the presence of non-prescribed medications (opiates, stimulants, synthetic opioids, sedative/hypnotics). Logistic regression analyses were used to calculate odds ratios and 95% CIs. Heroin was positive in 1.3% of urine samples tested. Demographic factors associated with a positive heroin test included: males, age, and insurance status. Samples from patients prescribed opioids that tested positive for heroin were more likely to test positive for other illicit drugs such as cocaine and marijuana. In addition, they were more likely to test positive for other non-prescribed medications and negative for medications that were prescribed. Clinicians should consider testing for heroin use when conducting urine drug monitoring in patients prescribed opioids.

Teaching Chronic Pain in the Family Medicine Residency.

Chronic pain is a significant condition affecting many Americans. Primary care physicians play an important role in chronic pain management, but many residents and physicians feel poorly prepared to manage it. Data were collected as part of the 2016 Council of Academic Family Medicine Educational Research Alliance (CERA) Program Director Survey, which was sent electronically to 484 program directors in the United States. The authors sought to determine whether residency directors' attitudes about treating chronic pain were associated with the amount of time devoted to teaching family medicine residents about chronic pain assessment, therapy (use of opioids, use adjuvant pain medications, use of other nonopioids, use of nonpharmacological treatments), and risk management (risk assessment, use of pain management contracts, informed consent when prescribing opioids, and urine drug monitoring). Attitudes were assessed by asking whether: (1) chronic pain is best managed by a primary care physician (PCP); (2) prescribing opioid medications is time consuming; (3) prescribing opioids is high-risk; (4) prescribing opioids contributes to opioid misuse; and (4) effective nonopioid treatments exist. An additional question assessed confidence in treating chronic pain. The response rate was 53%. The average family medicine residency devotes about 33 hours to education about pain management topics including 5.4 hours on chronic pain assessment, 16.2 hours on therapy, and 11.4 hours on risk assessment. Residency directors' belief that there are effective nonopioid treatments for chronic pain was the only attitude item that was associated with teaching about chronic pain. Residency directors' attitudes do not predict the time devoted to teaching chronic pain in family medicine residencies.

Rational Urine Drug Monitoring in Patients Receiving Opioids for Chronic Pain: Consensus Recommendations.

ObjectiveTo develop consensus recommendations on urine drug monitoring (UDM) in patients with chronic pain who are prescribed opioids.MethodsAn interdisciplinary group of clinicians with expertise in pain, substance use disorders, and primary care conducted virtual meetings to review relevant literature and existing guidelines and share their clinical experience in UDM before reaching consensus recommendations.ResultsDefinitive (e.g., chromatography-based) testing is recommended as most clinically appropriate for UDM because of its accuracy; however, institutional or payer policies may require initial use of presumptive testing (i.e., immunoassay). The rational choice of substances to analyze for UDM involves considerations that are specific to each patient and related to illicit drug availability. Appropriate opioid risk stratification is based on patient history (especially psychiatric conditions or history of opioid or substance use disorder), prescription drug monitoring program data, results from validated risk assessment tools, and previous UDM. Urine drug monitoring is suggested to be performed at baseline for most patients prescribed opioids for chronic pain and at least annually for those at low risk, two or more times per year for those at moderate risk, and three or more times per year for those at high risk. Additional UDM should be performed as needed on the basis of clinical judgment.ConclusionsAlthough evidence on the efficacy of UDM in preventing opioid use disorder, overdose, and diversion is limited, UDM is recommended by the panel as part of ongoing comprehensive risk monitoring in patients prescribed opioids for chronic pain.

(227) Medication Adherence Monitoring in Patients Prescribed Buprenorphine/Naloxone

We sought to assess the relationship between the frequency of urine drug monitoring (UDM) and adherence to prescribed buprenorphine/naloxone therapy, and use of illicit substances, non-prescribed opiates or benzodiazepines. Patients prescribed buprenorphine/naloxone were included if they had ≥2 urine samples (separated by ≥6 months) assessed between 2013 and 2016. Baseline and final samples were classified as positive or negative for: buprenorphine, and for any illicit substance, for non-prescribed opiates/synthetic opioids, and for benzodiazepines. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated using multiple logistic regression analysis with the following independent variables: gender, age decade, primary payor, geographic region, year tested, buprenorphine dose, and frequency of UDM. Because data were obtained from a de-identified database, this study was not submitted for IRB review. For 6,900 patients in the analysis, the rate of negative urines for buprenorphine was lower in the final urine compared to the baseline urines (10% vs 8%) and for the final sample, patients with ≥1 sample/month were significantly less likely to be negative for buprenorphine than those with 1 sample/3 months (10% vs 6%; aOR, 0.53; 95% CI, 0.41-0.70 for 1/month vs 1/3 months). A non-prescribed opiate was detected in 16% and 11% of first and last samples respectively, with the largest decline observed in those with the most frequent UDM testing (23% vs. 11%). A non-prescribed benzodiazepine was detected in 19% and 16% of first and last samples respectively, with the largest decline observed in those with the most frequent UDM testing (27% vs. 19%). Frequent urine drug monitoring may have the potential to increase adherence to prescribed buprenorphine/naloxone and decrease the use of non-prescribed opiates and benzodiazepines.

Low Risk of Producing an Opioid Use Disorder in Primary Care by Prescribing Opioids to Prescreened Patients with Chronic Noncancer Pain.

To examine the risk of developing aberrant behaviors that might lead to a substance use disorder (addiction) when prescribing opioids for the relief of chronic noncancer pain in primary care settings. Longitudinal, prospective, descriptive design with repeated measures. Private community-based internal medicine and family medicine clinics. Patients with chronic musculoskeletal pain. Standardized measures of patient status (pain, functional impairment, psychiatric disorders, family history) and treatments provided, urine drug monitoring, and medical chart audits (presence of aberrant drug-related behaviors) were obtained in a cohort of 180 patients at the time of initiating opioids for chronic noncancer pain and at three, six, and 12 months thereafter. Over the 12-month follow-up period, subjects demonstrated stable, mild to moderate levels of depression (PHQ-9 scores ranging from 9.43 to 10.92), mild anxiety (BAI scores ranging from 11.80 to 14.67), minimal aberrant drug-related behaviors as assessed by chart reviews, and a low percentage of illicit drug use as revealed by results of urine drug monitoring. Less than 5% of our study population revealed any evidence of substance use disorder. This prospective study suggests that patients without a recent or prior history of substance use disorder who were prescribed primarily short-acting opioids in low doses for chronic noncancer pain have a low risk for developing a substance use disorder. This finding supports the importance of prescreening patients being considered for opioid therapy and that prescription of opioids for noncancer pain may carry a lower risk of abuse in selected populations such as in private, community-based practices.

Quetiapine Carboxylic Acid and Quetiapine Sulfoxide Prevalence in Patient Urine.

Treatment adherence is often an issue with mental health patients. For those prescribed quetiapine (Seroquel®), the low levels of parent drug and plasma metabolite(s) (e.g., 7-hydroxyquetiapine) typically used in urine drug monitoring can result in false negatives with concomitant unfavorable impacts on patient care. Literature review coupled with liquid chromatography/time-of-flight mass spectrometry analysis of patient positive urine samples indicated the presence of quetiapine carboxylic acid and quetiapine sulfoxide as significant urinary metabolites of quetiapine. Analysis of these two metabolites determined that they are abundant in the urine of quetiapine patients and can result in apparent adherence rates that are improved relative to those determined using only quetiapine and 7-hydroxyquetiapine. For example, analysis of a random set of 114 patients who were prescribed quetiapine exhibited an apparent adherence rate of 47% using the quetiapine carboxylic acid and quetiapine sulfoxide metabolites. Traditional metabolite testing with quetiapine and 7-hydroxyquetiapine yielded apparent adherence rates of ~31% while all four analytes resulted in apparent adherence of 48%. The prevalence of these metabolites suggests that quetiapine urine drug testing would be more consistent with prescriptions when they are included in the analysis.

(205) Predictors of illicit substance use assessed by urine drug monitoring in patients prescribed opioid medications

Oral opioid therapy is widely used in pain management. This study evaluated the relationship between patient characteristics and the use of illicit substances assessed by urine drug monitoring in patients prescribed opioid medications. Urine samples from patients prescribed ≥1 opioid medication were analyzed using liquid chromatography/tandem mass spectrometry. Samples were tested for the presence of illicit substances (including cocaine metabolite [benzoylecgonine], heroin metabolite [6-MAM], marijuana metabolite [THC], MDMA, and phencyclidine). Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated using multiple logistic regression analysis with the following independent variables: sex, age decade, geographic region, and primary payer. Between January 2013 and June 2015, a total of 450,018 samples were tested, of which 46,592 (10.4%) were positive for ≥1 illicit substance(s). Marijuana (38,158 [12.2%] samples) and cocaine (8574 [2.0%] samples) were the most commonly detected illicit substances, whereas heroin was detected in only 1649 samples and no other illicit substances were detected in >125 samples. The factors most strongly associated with likelihood of detecting an illicit substance were sex (men, 13.1% vs women, 8.2%; aOR, 1.76; 95% CI, 1.73-1.80), age (progressive decrease from 18.3% for 20-29 years of age to 0.4% for 80-99 years; aOR for 80-99 years compared with 20-29 years was 0.02; 95% CI, 0.01-0.03), and primary payer (highest rate for Medicaid [16.4%] and lowest rate for Medicare [8.1%] compared with self-pay [12.5%]; aOR for Medicaid was 1.34; 95% CI, 1.29-1.38; aOR for Medicare was 0.63; 95% CI, 0.61-0.65). Among patients prescribed opioid medications, use of illicit substances was common and varied with patient characteristics. Understanding factors associated with the likelihood of positive urine testing for illicit substances may better inform strategies for using urine drug testing in the clinical management of patients on prescribed opiate therapy. Support: Ameritox Ltd.

(207) Predictors of medication adherence assessed by urine drug monitoring in patients prescribed opioid medications: relationship with opioid dose

Medication monitoring is recommended for patients prescribed an opioid for an extended period. This study evaluated the relationship between the prescribed dose of hydrocodone and the likelihood of finding hydrocodone or its metabolites with urine testing. Urine samples submitted to the laboratory between January 2013 and June 2015 from patients documented on the laboratory requisition to have been prescribed hydrocodone as their sole opiate medication were analyzed. The first sample obtained from each patient was tested for the presence of hydrocodone and its metabolites using liquid chromatography/tandem mass spectrometry. Samples were classified as positive for hydrocodone if parent drug and/or metabolite(s) were confirmed and negative if neither were detected. Adjusted odds ratio (aOR) and 95% confidence interval (CI) were calculated using multiple logistic regression analysis with the following independent variables: sex, age decade, primary payor, geographic region, year tested, and dose category. Of 178,582 unique samples analyzed, 28.4% were classified as negative for hydrocodone. Demographic factors most strongly associated with potential nonadherence were age (highest rate for age 20-29 years [37.6%] and lowest rate for age ≥60 years [23.2%]) and payor type (highest rate for Medicaid [36.2%] and lowest rates for workers’ compensation [25.0%] and commercial insurance [25.4%]). The rate of potential nonadherence decreased as prescribed hydrocodone dose increased, from 37.1% for patients prescribed 5 to 20 mg/day to 17.5% for those prescribed 60 to 120 mg/day (aOR, 0.35; 95% CI, 0.34-0.37). Among patients prescribed hydrocodone, potential nonadherence was common and varied with both patient characteristics and with prescribed dose. Understanding factors associated with potential nonadherence may inform strategies to use urine drug monitoring to better manage patients and improve treatment outcomes. Support: Ameritox Ltd.

Dramatic Reduction in Hydrocodone Prescriptions in an Urban Safety Net Health Care System: Has It Improved Patient Safety or Led to Increased Patient Suffering?

Pain management, chronic use of opioids for non-cancer pain, and opioid overdose have become nationwide public health challenges. According to a recent Institute of Medicine report, up to one-third of U.S. adults report chronic pain [1]. Following nationwide policy changes, updated practice guidelines, and the loosening of opioid prescribing restrictions in the 1990s, a dramatic increase was seen in the prescriptions of opioids for non-cancer chronic pain [2]. In addition, over the last 20 years there has been a dramatic increase in opioid-related accidental overdoses and deaths, with 16,651 deaths attributed to prescription opioids in 2010 [3,4]. The majority of these deaths are attributable to long-acting opioids and methadone [5]. The increased mortality rate is due not simply to the overall increase in prescriptions but also to prescriber knowledge deficits, patient behaviors and co-morbidities, and payor and system policies [5,6]. In addition to the risk of accidental overdose and death, chronic use of opioids creates other risks to patient safety including abuse, addiction, transition to heroin use, diversion, and accidents [7]. Lastly, opioids can be associated with numerous adverse effects, such as constipation, sedation, hormonal imbalance, and hyperalgesia [8–10]. At the same time, opioids are necessary to meet a critical need for adequate control of both acute and chronic pain in certain patient populations. Withholding and restricting necessary medical treatment may cause undue patient suffering [11]. In addition, prescriber bias and societal stigmas may result in unintended and problematic barriers to improved quality of life for certain groups [12]. In response to increases in opioid-related morbidity and mortality, various recommendations have been made for safe opioid prescribing, including urine drug monitoring, state prescription monitoring databases, and treatment agreements …

What Steps Should be Taken to Integrate Marijuana into Pain Regimens?

Pain ManagementVol. 5, No. 4 OpinionWhat steps should be taken to integrate marijuana into pain regimens?Mark Wallace & Timothy FurnishMark Wallace*Author for correspondence: E-mail Address: mswallace@ucsd.edu Division of Pain Medicine, Department of Anesthesiology, UCSD School of Medicine, 9300 Campus Point Drive, #7651, La Jolla, CA 92037, USASearch for more papers by this author & Timothy Furnish Division of Pain Medicine, Department of Anesthesiology, UCSD School of Medicine, 9300 Campus Point Drive, #7651, La Jolla, CA 92037, USASearch for more papers by this authorPublished Online:19 Jun 2015https://doi.org/10.2217/pmt.15.20AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleKeywords: clinicalmedicinalmarijuanapracticeReferences1 Abrams DI, Jay CA, Shade SB et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology 68(7), 515–521 (2007).Crossref, Medline, CAS, Google Scholar2 Ellis RJ, Toperoff W, Vaida F et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology 34(3), 672–680 (2009).Crossref, Medline, CAS, Google Scholar3 Ware MA, Wang T, Shapiro S et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ 182(14), E694–E701 (2010).Crossref, Medline, Google Scholar4 Wilsey B, Marcotte T, Deutsch R et al. Low-dose vaporized cannabis significantly improves neuropathic pain. J. Pain 14(2), 136–148 (2013).Crossref, Medline, CAS, Google Scholar5 Wilsey B, Marcotte T, Tsodikov A et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J. Pain 9(6), 506–521 (2008).Crossref, Medline, CAS, Google Scholar6 Physician recommendation of medical cannabis: guidelines of the Council on Scientific Affairs subcommittee on medical marijuana practice advisory (2011). www.mbc.ca.gov/Licensees/Prescribing/medical_marijuana_cma-recommend.pdf.Google Scholar7 Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ 178(13), 1669–1678 (2008).Crossref, Medline, Google Scholar8 Aryana A, Williams MA. Marijuana as a trigger of cardiovascular events: speculation or scientific certainty? Int. J. Cardiol. 118(2), 141–144 (2007).Crossref, Medline, Google Scholar9 Abrams DI, Vizoso HP, Shade SB et al. Vaporization as a smokeless cannabis delivery system: a pilot study. Clin. Pharmacol. Ther. 82(5), 572–578 (2007).Crossref, Medline, CAS, Google Scholar10 23 Legal medical marijuana states and DC: laws, fees, and possession limits. http://medicalmarijuana.procon.org/view.resource.php?resourceID=000881.Google Scholar11 Elikkottil J, Gupta P, Gupta K. The analgesic potential of cannabinoids. J. Opioid Manag. 5(6), 341–357 (2009).Crossref, Medline, Google Scholar12 Reisfield GM, Wasan AD, Jamison RN. The prevalence and significance of cannabis use in patients prescribed chronic opioid therapy: a review of the extant literature. Pain Med. 10(8), 1434–1441 (2009).Crossref, Medline, Google Scholar13 Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy 33(2), 195–209 (2013).Crossref, Medline, CAS, Google Scholar14 Grant I, Atkinson JH, Gouaux B, Wilsey B. Medical marijuana: clearing away the smoke. Open Neurol. J. 6, 18–25 (2012).Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited ByRational Urine Drug Monitoring in Patients Receiving Opioids for Chronic Pain: Consensus Recommendations1 December 2017 | Pain Medicine, Vol. 19, No. 1 Vol. 5, No. 4 Follow us on social media for the latest updates Metrics Downloaded 48 times History Published online 19 June 2015 Published in print July 2015 Information© Future Medicine LtdKeywordsclinicalmedicinalmarijuanapracticeFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Specimen validity testing in urine drug monitoring of medications and illicit drugs: clinical implications.

To discuss the importance of specimen validity testing (SVT) in urine drug testing (UDT) and the clinical role it plays in identifying efforts to subvert the UDT process. A discussion of the clinical impact of SVT is presented. A discussion of pH, specific gravity, creatinine, and oxidation for monitoring the adulteration of UDT samples is presented along with the clinical significance of such tests. SVT has a significant place in healthcare efforts to measure patient adherence, behavior, and honesty in communication with clinicians. SVT is typically ordered by treating clinicians who use the results to make therapeutic decisions regarding specific medical problems of their patient, including those related to medication and illicit drug use. In the absence of SVT, a healthcare provider may fail to identify a patient's adulteration of their urine sample in an attempt at deceiving the provider. Moreover, the presence of some underlying medical conditions may obfuscate the UDT results.

The use of urine drug monitoring in chronic opioid therapy: An analysis of current clinician behavior

The purpose of this study was to better quantify how urine drug monitoring (UDM) is used in clinical practice. Little is known about which patients are monitored, how often patients are monitored, which substances are important to detect, and under what circumstances clinicians modify the frequency of monitoring. An online survey was developed based on qualitative phone interviews with eight clinicians who use UDM as a routine component of clinical practice. One thousand fourteen randomly selected clinicians known to order urine toxicology screenings were invited by mail in June 2011 to respond to the online survey assessing their clinical needs and preferences regarding UDM. Of the 93 respondents, 76 percent (n = 72) require all new patients to have UDM performed when they enter their clinic. The majority administer UDM to patients four times a year. The most common reasons cited by clinicians for a change in the frequency of monitoring are patient history of substance abuse and aberrant behaviors. Overall, the respondents showed broad support to test patients consistently for the most common illicit drugs, the majority of opioids, and a handful of prescription medications associated with abuse. Despite a lack of agreement between guidelines informing the use of UDM, there appears to be a general consensus among practitioners that use UDM on: which patients to monitor, how often to monitor, and which substances are most important to detect.