Effect of positive urine fentanyl screen on attitudes toward heroin use.

BACKGROUND: It is unknown if targeted risk reduction counseling in the health care setting, after documented exposure to fentanyl, can affect behavior change to reduce risks and increase utilization of evidence-based overdose prevention strategies. METHODS: We conducted a retrospective analysis of results (7/2018-6/2019) from questionnaire-facilitated counseling by recovery coaches in the emergency department (ED) and primary care settings following disclosure of a urine toxicology positive for fentanyl. RESULTS: Seventy-five percent of N = 101 respondents were neither aware of nor expecting fentanyl in their substances of use. Fifty-three (70 %) of those initially unaware answered that learning about exposure to and the risks from fentanyl changed their thoughts about reducing or abstaining from use. A greater proportion of patients seen in the ED expressed desire to stop or reduce opioid use as compared to ambulatory clinic patients (91 % vs. 46 %, p < 0.001). Of those not already engaged in treatment, 18 % and 15 % were interested in medication and behavioural health treatment, respectively, and each of them indicated a change in thought based on the counseling. Forty-five percent of individuals not yet receiving naloxone endorsed interest in receiving it, and 22 % of all respondents were somewhat or very interested in access to safe consumption sites. CONCLUSION: This study suggests a novel clinical utility in toxicology screens to inform behavior in the setting of illicit fentanyl exposure. In addition to linkages to evidence-based treatment, linkages to harm-mitigating strategies associated with ongoing substance use may be critical to a comprehensive overdose prevention strategy in the clinical setting.

Determination of thallium in urine, blood, and hair in illicit opioid users in Iran.

CONTEXT: Heavy metals, including thallium and lead, are introduced to illicit drug users' body as a result of using drugs such as cocaine and heroin. OBJECTIVE: This study aimed to determine urine, blood, and hair thallium (Tl) concentrations in illicit opioid users along with the relevant clinical signs and symptoms consistent with thallotoxicosis and to compare them with the corresponding variables in the control non-opioid user group. MATERIALS AND METHODS: This case-control study was conducted on 50 illicit opioid users who had abused opioids continuously for more than a year, referred to Amirie Drug Abuse Treatment Clinic in Kashan, Iran. The control group included 50 non-opioid users. Thallium concentrations in urine, blood, and hair were assessed in both groups (n = 100) using electrothermal (graphite furnace) atomic absorption spectrometry (ET AAS, GF AAS). RESULTS: In the studied group, the median (interquartile range) concentrations of thallium in urine, blood, and hair were 54.8 ± 79.9 µg/L, 14.5 ± 11.1 µg/L, and 5.4 ± 3.7 µg/g, respectively; these values were 4.8 ± 5.2 µg/L, 2.5 ± 2.4 µg/L, and 1.4 ± 1.1 µg/g, respectively, in the control group. There were significant differences in urine, blood, and hair thallium concentrations between the study group and the control group (p < 0.001). There were significant correlations between duration of illicit opioid use and urine thallium concentrations (r = 0.394, p = 0.005) and hair thallium concentrations (r = 0.293, p = 0.039), but not with blood thallium concentrations (r = 0.246, p = 0.085). Urine and blood thallium concentrations of illicit opioid users with clinical signs and symptoms consistent with thallotoxicosis of weakness (p = 0.01), depression (p = 0.03), and headache (p = 0.03) were higher than users without these problems. DISCUSSION AND CONCLUSION: The results of the study showed that thallium concentrations in urine, blood, and hair in illicit opioid users were significantly higher than the comparable concentrations in the control group. This can be due to the use of illicit opioids adulterated with thallium. Also, this study showed long-term illicit opioid use may lead to thallium exposure. In addition, cigarette smoking was associated with increased thallium exposure.

Managing Chronic Pain in Cancer Survivors Prescribed Long-Term Opioid Therapy: A National Survey of Ambulatory Palliative Care Providers.

CONTEXT: Chronic pain, or pain lasting more than three months, is common among cancer survivors, who are often prescribed long-term opioid therapy (LTOT). OBJECTIVE: Our objective was to explore palliative care providers' experiences with managing chronic pain in cancer survivors prescribed LTOT, specifically in ambulatory palliative care settings, and their strategies for overcoming challenges. METHODS: We recruited providers through leading national palliative care organizations who manage chronic pain in cancer survivors. Asked to consider only cancer survivors with chronic pain when responding, participants completed an online survey that included questions about use of opioid risk mitigation tools, confidence in addressing opioid misuse behaviors and discussing/recommending management approaches, and access to addiction treatment. RESULTS: Of 157 participants, most were physicians (83%) or nurse practitioners (15%). Most reported using opioid risk mitigation tools such as urine drug testing (71%), opioid treatment agreements (85%), and practitioner database monitoring programs (94%). Participants were confident (7-8/10) managing the most commonly encountered opioid misuse behaviors (missing appointments, marijuana use, and using more opioids than prescribed) and in their ability to recommend nonpharmacologic and nonopioid pharmacologic treatments for chronic pain (10/10). They were least confident prescribing naloxone or managing addiction (5/10); only 27% reported having training or systems in place to address addiction. Only 13% had a waiver to prescribe buprenorphine. CONCLUSION: Palliative care providers are comfortable with many aspects of managing chronic pain in cancer survivors on LTOT, although challenges persist, including the lack of systems-based approaches and training in addiction treatment.

Fentanyl exposure among patients seeking opioid treatment.

AIM: Overdoses attributed to the potent opioid agonist fentanyl have substantially increased in recent years. Despite these serious public health consequences, many opioid treatment providers do not currently include a fentanyl assay in their urine toxicology testing. As a result, extent of fentanyl exposure and related risks among individuals with opioid use disorder often remains unknown. We examined the prevalence of fentanyl exposure among patients seeking or enrolled in opioid agonist treatment. METHODS: Six hundred urine specimens were collected from adults entering (n = 100) or enrolled in (n = 500) opioid agonist treatment and analyzed using the clinic's standard opioid panel, supplemented with a 100 ng/ml fentanyl assay. RESULTS: Of the 100 specimens collected from patients at treatment intake, 19 (19%) tested positive for fentanyl. Importantly, 17 (90%) of those fentanyl-positive specimens were also positive for heroin. Of the 500 collected from patients in treatment, 17 (3%) of specimens tested positive for fentanyl. Of those, 11 (92%) were also positive for heroin. CONCLUSION: These data illustrate a concerning degree of fentanyl exposure among patients seeking treatment and suggest that much of this exposure may have stemmed from fentanyl-containing heroin. Given the unprecedented recent surges in fentanyl-related overdoses, efforts to identify fentanyl exposure are critical. In particular, the point of treatment entry permits a rare systematic opportunity for medical and clinical staff to address fentanyl use and risks with incoming patients.

Balancing opioid analgesia with the risk of nonmedical opioid use in patients with cancer.

The current opioid crisis has brought renewed attention and scrutiny to opioid prescriptions. When patients receiving opioid therapy for pain engage in nonmedical opioid use (NMOU) or diversion, untoward consequences can occur. New evidence suggests that patients with cancer might be at a higher risk of NMOU than was previously thought, but clinical evidence still supports the use of opioid analgesics as the gold standard to treat cancer-related pain, creating a dilemma in patient management. Clinicians are encouraged to adopt a universal precautions approach to patients with cancer receiving opioids, which includes screening all patients; discussing the risks, benefits, adverse effects and alternatives of opioid therapy; and providing education on safe use, storage and disposal. Use of urine drug tests, prescription drug monitoring programmes and close observation of behaviours related to opioid use help to ensure treatment adherence, detect NMOU and support therapeutic decision-making. These measures can optimize the risk-benefit ratio while supporting safe opioid use. In this Review, we examine the role of opioids in cancer pain, the risk of substance use disorder and methods to achieve the right balance between the two in order to ensure safe opioid use.

Examining of Thallium in Cigarette Smokers.

Smoking is one of the sources of thallium which is considered as a toxic heavy metal. The aim of this study was to determine urinary thallium levels and related variables in smokers, compared to a control group. The study was conducted on 56 participants who had smoked continuously during the year before they were referred to Kashan Smoking Cessation Clinic. Fifty-three nonsmokers who were family members or friends of the smokers were selected as the control group. Urinary thallium was measured in both groups (n = 109) using atomic absorption spectrophotometry. The mean value (with SD) for urinary thallium in the smokers (10.16 ± 1.82 µg/L) was significantly higher than in the control group (2.39 ± 0.63 µg/L). There was a significant relationship between smoking duration and urinary thallium levels (P = 0.003). In a subgroup of smokers who was addicted to opium and opium residues (n = 9), the mean level of thallium (37.5 ± 13.09 µg/L) was significantly higher than in the other smokers (4.93 ± 4.45; P = 0.001). Multiple regression analysis showed opioid abuse, insomnia, and chronic obstructive pulmonary disease (COPD), together were strong predictors of urinary thallium levels in smokers. There was no significant difference in thallium level in hookah smokers (P = 0.299) or in those with COPD compared to other smokers (P = 0.375). Urinary thallium levels of smokers with clinical signs of depression, sleep disorders, memory loss, and sweating were higher than those of smokers without these signs. Since thallium, as other toxic metals is accumulated in the body, and cigarette smoking also involves carcinogenic exposures and health hazards for passively exposed people, the need for cigarette control policies is emphasized.

Urine and oral fluid drug testing in support of pain management.

In recent years, the abuse of opioid drugs has resulted in greater prevalence of addiction, overdose, and deaths attributable to opioid abuse. The epidemic of opioid abuse has prompted professional and government agencies to issue practice guidelines for prescribing opioids to manage chronic pain. An important tool available to providers is the drug test for use in the initial assessment of patients for possible opioid therapy, subsequent monitoring of compliance, and documentation of suspected aberrant drug behaviors. This review discusses the issues that most affect the clinical utility of drug testing in chronic pain management with opioid therapy. It focuses on the two most commonly used specimen matrices in drug testing: urine and oral fluid. The advantages and disadvantages of urine and oral fluid in the entire testing process, from specimen collection and analytical methodologies to result interpretation are reviewed. The analytical sensitivity and specificity limitations of immunoassays used for testing are examined in detail to draw attention to how these shortcomings can affect result interpretation and influence clinical decision-making in pain management. The need for specific identification and quantitative measurement of the drugs and metabolites present to investigate suspected aberrant drug behavior or unexpected positive results is analyzed. Also presented are recent developments in optimization of test menus and testing strategies, such as the modification of the standard screen and reflexed-confirmation testing model by eliminating some of the initial immunoassay-based tests and proceeding directly to definitive testing by mass spectrometry assays.

Characterizing fentanyl use in methadone-maintained clients.

AIMS: Deaths attributed to fentanyl have increased in the United States. However, little is known about fentanyl use among substance abuse treatment clients. To fill this gap, we assessed prevalence of fentanyl exposure, characteristics of clients testing positive for fentanyl, other substances detected concurrently or simultaneously with fentanyl, and clients' perception of how many people are actively seeking to use fentanyl. METHODS: A retrospective chart review was conducted of all clients at one methadone maintenance treatment clinic between January 2015 and May 2016 in Wayne County, Michigan. Urine drug screens (UDS) including fentanyl (and its metabolite norfentanyl) were conducted clinically. To obtain additional data, 113 clients in this clinic subsequently completed an anonymous survey. RESULTS: Of 368 unique clients with UDS, 38.0% had at least one and 26.1% had ≥2 fentanyl-positive UDS results. None had a fentanyl prescription. Clients ever testing positive for fentanyl were significantly (p<0.05) more likely to use cocaine, have multiple treatment admissions to the clinic, and leave treatment sooner. Fentanyl-positive UDS results coincided most commonly with metabolites of cocaine- and heroin-positive UDS results. Of the anonymously surveyed clients, most (67.3%) reported they did not know anyone seeking fentanyl, a proportion significantly higher than for heroin, cocaine, alprazolam, hydrocodone and morphine. CONCLUSIONS: Fentanyl was commonly detected during this period with some clients having multiple fentanyl-positive UDS. Most clients did not know anyone seeking to obtain fentanyl. Regardless, the high exposure underscores that naloxone training and distribution is needed.

Using Client's Routine Urinalysis Records From Multiple Treatment Systems to Model Five-Year Opioid Substitution Treatment Outcomes.

BACKGROUND: At global, national, and local level, the need for ongoing, timely and cost efficient, comprehensive drug treatment monitoring, and evaluation systems have clearly been well recognized. OBJECTIVES: To test the feasibility of linking laboratory data and client intake data and its usefulness for modeling retrospectively, for the first time, 5-year longitudinal drug treatment outcomes in an Irish opiate treatment setting. METHODS: A multisite, retrospective, longitudinal cohort study was implemented to evaluate outcomes for opiate users based on 1.7 million routine urinalysis results collected from 4,518 individuals presenting for opioid substitution treatment in Ireland from January 2006 to December 2010. RESULTS: Analysis of opiates, cocaine, benzodiazepine, and cannabis use at treatment intake, 6 months and at 1-5 year follow-ups revealed differences in urinalysis protocols; significant differences in age of first drug use between those using and not using opiates at 5 years; significant decreases in opiate use; increases in benzodiazepine use and significant increasing effects of concurrent cocaine and benzodiazepine use on the odds of using opiates. Time series analysis of weekly proportions opiate positive predicted 16% (95% confidence interval: 7%-25%) of clients would be opiate positive 5 years postinitial intake. CONCLUSIONS IMPORTANCE: Underutilized urinalysis data can be used to address the need for cost effective, efficient evidence of drug-treatment outcomes across time, place, and systems. Linking and matching the cross-sectional data across sites and times also revealed where improvements in electronic records could be made.

The impact of non-concordant self-report of substance use in clinical trials research.

BACKGROUND: Studies comparing self-report substance use data to biochemical verification generally demonstrate high rates of concordance. We argue that these rates are due to the relatively high true negative rate in the general population, and high degree of honestly in treatment seeking individuals. We hypothesized that high risk individuals not seeking treatment would demonstrate low concordance and a high false negative rate of self-reported substance use. METHODS: A sample of 500 individuals from a smoking cessation clinical trial was assessed over 1 year. Assessments included semi-structured interviews, questionnaires (e.g. Addiction Severity Index, etc.), and urine drug screen assays (UDS). Generalized estimating equations (GEEs) were used to predict false negative reports for various substances across the study and determine the influence of substance use on the primary study outcome of smoking cessation. RESULTS: Participants demonstrated high false negative rates in reporting substances use, and the false negative rates increased as the study progressed. Established predictors of false negatives generalized to the current sample. High concordance and low false negative rates were found in self-report of nicotine use. A small but significant relationship was found in for effect of biochemically verified substance use on smoking cessation. CONCLUSIONS: Biochemical verification of substance use is needed in high risk populations involved in studies not directly related to the treatment of substance use, especially in populations with high threat of stigmatization. Testing should continue through the time period of the study for maximal identification of substance use.

Primary care providers' experiences with urine toxicology tests to manage prescription opioid misuse and substance use among chronic noncancer pain patients in safety net health care settings.

BACKGROUND: Guideline recommendations to reduce prescription opioid misuse among patients with chronic noncancer pain include the routine use of urine toxicology tests for high-risk patients. Yet little is known about how the implementation of urine toxicology tests among patients with co-occurring chronic noncancer pain and substance use impacts primary care providers' management of misuse. Clinicians' perspectives on the benefits and challenges of implementing urine toxicology tests in the monitoring of opioid misuse and substance use in safety net health care settings are presented in this paper. METHODS: Twenty-three primary care providers from 6 safety net health care settings whose patients had a diagnosis of co-occurring chronic noncancer pain and substance use were interviewed. Interviews were transcribed, coded, and analyzed using grounded theory methodology. RESULTS: The benefits of implementing urine toxicology tests for primary care providers included less reliance on intuition to assess for misuse and the ability to identify unknown opioid misuse and/or substance use. The challenges of implementing urine toxicology tests included insufficient education and training about how to interpret and implement tests, and a lack of clarity on how and when to act on tests that indicated misuse and/or substance use. CONCLUSIONS: These data suggest that primary care clinicians' lack of education and training to interpret and implement urine toxicology tests may impact their management of patient opioid misuse and/or substance use. Clinicians may benefit from additional education and training about the clinical implementation and use of urine toxicology tests. Additional research is needed on how primary care providers implementation and use of urine toxicology tests impacts chronic noncancer pain management in primary care and safety net health care settings among patients with co-occurring chronic non cancer pain and substance use.

Analysis of codeine positivity in urine of pain management patients.

The opioids codeine and morphine have legitimate uses in managing chronic pain conditions, but they are frequently abused. Patients prescribed opioids submit urine samples for medication compliance monitoring, and the interpretation of the results is complex. The purpose of this study was to evaluate the percentage of codeine- and morphine-positive urine drug tests that result from morphine use only, with the positive codeine result arising from low levels of codeine present in pharmaceutical formulations of morphine. This study included 80 urine samples which tested positive for codeine and morphine after pre-analytical hydrolysis and analysis by gas chromatography-mass spectrometry. Quantitative results were correlated with patient prescription information and immunoassay results to classify patients into one of four categories: heroin users (50%), codeine users (34%), codeine and morphine users (5%), and morphine users (11%). The percentage of codeine-positive resulting from morphine use was higher than previous estimates. Urine from patients prescribed morphine only was found to contain codeine at <1% of the morphine concentration, a ratio that was also observed in patients who used heroin. Careful analysis of urine drug testing results, including assessing the ratio of codeine to morphine (C/M), can help providers determine if patients are compliant with their pain management regimens.

History of drug use predicts opioid treatment agreement violation.

OBJECTIVE: To determine reasons and describe characteristics of patients who violate their opioid treatment agreement. DESIGN: Cross-sectional retrospective study. PARTICIPANTS: New patients aged 18 years or above attending a multidisciplinary comprehensive pain management clinic from January 2012 to June 2012. MAIN OUTCOME MEASURE: Reason for discharge from the clinic. RESULTS: Of the 234 subjects in the study, 38.5 percent were discharged due to treatment agreement violation. A majority had a self-reported history of tobacco use, followed by alcohol and marijuana. The mean age of discharge was 45.1 years (SD 11.6) and they were discharged on average in 7.4 months after their first clinic visit. The primary reason for discharge was for an inappropriate urine drug screen (UDS) with illicit drug use being the most common at 40 percent and marijuana being the most common illicit drug. Subjects reporting a history of any drug use were nearly seven times more likely to be discharged. Hydrocodone was the most common nonprescribed opioid found in the UDS for those discharged for using nonprescribed opioids. CONCLUSION: Inappropriate UDS is a main factor for discharge due to violation of the opioid treatment agreement. Those with self-reported current or prior drug use were more likely to be discharged from the clinic.

Pethidinic acid: corroboration of a doctor's denial of pethidine re-use.

Pethidine (meperidine), a synthetic opiate, formally used as an analgesic in surgery and obstetrics, has been an abused drug of choice for some doctors. A case is presented in which a doctor, who previously admitted to using pethidine, was suspected of re-using, following a second positive urine test. A laboratory had reported the presence of pethidine in the doctor's urine; however, the doctor denied re-use. The norpethidine (normeperidine) metabolite, normally found in urine, had not been detected, raising concern over the laboratory's conclusion and necessitating an independent investigation. Because the major metabolite of pethidine is pethidinic acid (meperidinic acid), accounting for approximately 40% of the excreted dose, its presence or absence were deemed to be important criteria in interpreting the laboratory result. Pethidinic acid was synthesized by alkaline hydrolysis of pethidine and used as a control. Urine samples from a patient receiving pethidine for pain, from the previous pethidine use of the doctor, and the urine under question plus the control were analyzed for the presence of pethidinic acid using electrospray mass spectrometry. Pethidinic acid was found in all samples except the one under dispute. The absence of pethidinic acid appeared to corroborate the doctor's denial of re-use.

Evaluation of buprenorphine LUCIO immunoassay versus GC-MS using urines from a workplace drug testing program.

The buprenorphine (BUP) LUCIO Nal Von Minden screening assay was evaluated. Urine samples from subjects enrolled in a workplace drug testing program were screened according to the manufacturer's instruction using a Roche COBAS Integra 800 analyser. For gas chromatography-mass spectrometry (GC-MS) confirmatory analysis, samples were submitted to enzymatic hydrolysis with ß-glucuronidase and mixed-mode solid-phase extraction. Imprecision (coefficient of variation) for 3.0, 7.0, and 13.0 ng/mL calibrators varied within 2.8-8.7 intra-day (n = 20) and 7.7-8.6 inter-day (n = 19). Inaccuracy (bias) was between -5.6-30.5 intra-day and -13.2-4.2 inter-day. At the 5 ng/mL cut-off, the immunoassay showed 100% sensitivity and 88% specificity, with an overall agreement of 94% between immunoassay and GC-MS. Raising the cut-off to 10 ng/mL provided an identical overall agreement between immunoassay and GC-MS (94%), despite the decrease in sensitivity (90%) and the increase in specificity (100%). According to these results, the BUP LUCIO Nal Von Minden screening assay provides adequate sensitivity and specificity for BUP screening in urine samples using a cut-off concentration of 5 ng/mL.

Comparison of random and postaccident urine drug tests in southern Indiana coal miners.

BACKGROUND: This study examines the relationship between the use of 9 classes of substances (amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, methadone, opioids, phencyclidine, and propoxyphene) and coal-mining accidents. METHODS: The control sample (n = 215) made up of miners that presented for random urine drug testing. The study sample (n = 100) consists of miners that presented for postaccident urine drug testing. Nonparametric Mann-Whitney U tests of creatinine normalized urine drug levels were conducted to compare the medians of the groups. RESULTS: The mean drug concentrations were higher in the postaccident group for each drug tested except marijuana. Two-tailed testing demonstrated statistically significant differences for marijuana (P = 0.000), cocaine (P = 0.008), and opiates (P = 0.037). CONCLUSIONS: The study demonstrates statistically significant higher cocaine and opioid concentrations and lower marijuana concentrations in postaccident urine drug tests of coal miners when compared with random tests.

Identification and management of pain medication abuse and misuse: current state and future directions.

Long-term opioid therapy poses a risk for abuse and misuse in some patients. Identifying which patients may potentially be at risk prior to initiation of therapy, and identifying patients in whom these problems develop during therapy, are significant challenges. Outcome prediction is impeded by the complexity of the problem, where considerable heterogeneity results from psychological and socioeconomic factors, as well as interindividual variation in biological pathways due to genetic and epigenetic factors. Screening tools designed to detect opioid misuse and urine drug testing are both used clinically; scant evidence currently exists to allow the formulation of an algorithm for judicious use of these tools. Moreover, these tools may not be addressing the underlying alterations in biological pathways that occur owing to the development of chronic pain or in response to chronic opioid administration. An evidence-based algorithmic approach to risk mitigation that can be applied in a cost-effective manner to guide therapy is urgently needed.

Interpretation of urine drug testing in pain patients.

BACKGROUND: Traditionally, urine drug screens have only been concerned with positive or negative results. Those results provide physicians treating patients for pain with chronic opioid therapy with information about medication compliance, use of nonprescribed medications, and use of illicit drugs. However, the analysis of urine for drugs offers additional information that, when compiled and accurately interpreted, may also be of great value to these doctors. PURPOSE: The aim of this article was to discuss the interpretation of urine drug tests and their application to pain physician practices. METHOD: We utilized a selection of recent articles on urine drug screening applicable to the pain patient population. RESULTS AND CONCLUSIONS: The article provides pertinent information about interpretation of urine drug testing, which is separated into six categories: which drugs and metabolites to test for; which analytical cutoffs to use; pain medication metabolism; identification of alcohol use; determination of patient compliance; and which patient groups to consider for more frequent testing.