Presence of Parent Cocaine in the Absence of Benzoylecgonine in Urine.

Cocaine (COC) is widely abused and associated with significant adverse effects. Forensic and clinical laboratories often test for COC intake through detection of the primary metabolite, benzoylecgonine (BZE) in urine. Testing for BZE alone may result in false-negative determinations in situations where COC is recently administered or metabolism is impaired. To our knowledge, no data have been provided demonstrating the utility of adding parent COC to urine confirmation testing in routine analyses. For this study, random urine specimens from patients undergoing treatment for pain management and/or addiction were collected over six months from 800 clinics across 39 states. A total of 7,587 urine specimens tested positive for a COC marker (COC and/or BZE). A positive result was determined using a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method with a limit of quantitation of 50 ng/mL. Of the positive specimens, 26% and 97% were positive for COC and BZE, respectively. Positive BZE-only specimens represented 74% of total positive specimens. However, 231 of the 7,587 urine specimens (3% of positive specimens) were positive for COC in the absence of BZE. The 231 COC-only positive specimens were collected from 206 patients, and two of these patients provided four COC-only positive specimens. Of a select group of COC-only specimens tested by both LC-MS-MS and immunoassay (IA) (N = 32), 81% were negative by IA, demonstrating the limitation of screening with BZE-specific IAs. A false-negative COC result can have profound impacts such as a delay in patient referral to addiction treatment, unintentional prescribing of a controlled substance to a patient actively abusing an illicit substance, or undetected cocaine use in the workplace. This study highlights the importance of testing for COC in addition to BZE in forensic and healthcare settings.

Drug-Drug Interaction Assessment and Identification in the Primary Care Setting.

BACKGROUND: Drug-drug interactions (DDIs) are ubiquitous, harmful and a leading cause of morbidity and mortality. With an aging population, growth in polypharmacy, widespread use of supplements, and the rising opioid abuse epidemic, primary care physicians (PCPs) are increasingly challenged with identifying and preventing DDIs. We set out to evaluate current clinical practices related to identifying and treating DDIs and to determine if opportunities to increase prevention of DDIs and their adverse events could be identified. METHODS: In a nationally representative sample of 330 board-certified family and internal medicine practitioners, we evaluated whether PCPs assessed DDIs in the care they provided for three simulated patients. The patients were taking common prescription medications (e.g. opioids and psychiatric medications) along with other common ingestants (e.g. supplements and food) and presented with symptoms of DDIs. Physicians were scored on their ability to inquire about the patient's medications, investigate possible DDIs, evaluate the patient, and provide treatment recommendations. We scored the physicians' care recommendations against evidence-based criteria, including overall care quality and treatment for DDIs. RESULTS: Average overall quality of care score was 50.5% ± 12.0%. Despite >99% self-reported use of medication reconciliation practices and tools, physicians identified DDIs in only 15.3% of patients, with 15.5% ± 20.3% of DDI-specific treatment by the physicians. CONCLUSIONS: PCPs in this study did not recognize or adequately treat DDIs. Better methods are needed to screen for DDIs in the primary care setting.

Impact of Definitive Drug-Drug Interaction Testing on Medication Management and Patient Care.

BACKGROUND AND OBJECTIVE: Aegis Sciences Corporation developed a test (InterACT Rx™) that objectively and definitively identifies substances known to interact with drug-drug interaction-prone medications commonly prescribed in the treatment of chronic pain and behavioral health disorders. The objective of this study was to assess the severity of identified drug-drug interactions, the reduction in the frequency and severity of identified drug-drug interactions, and the impact of the test on healthcare utilization. METHODS: Patients with chronic pain, behavioral health disorders, or both who had one or more drug-drug interaction tests and one or more drug-drug interactions identified in the study period were included. Drug-drug interaction test results described the number and severity of interactions and detected substances involved in drug-drug interactions. Patients' electronic medical records were obtained to analyze outpatient visits and prescription medications. The cost of outpatient visits was based on the Medicare Physician Fee Schedule. Outcomes were compared between the pre- and post-study index periods to determine the impact of the drug-drug interaction test on patient care. RESULTS: A total of 262 patients were included. The majority of drug-drug interactions detected (77.9%) at index were of moderate severity. The number of monthly all-cause and pain-related outpatient visits was reduced in the post-index period compared with the pre-index period (0.74-0.54 and 0.69-0.49, respectively). Associated costs were reduced from US$64.92 to US$51.20, and from US$62.42 to US$47.62, (p < 0.0001 for both) for all-cause and pain-related outpatient visits, respectively. Follow-up drug-drug interaction testing for 43 patients revealed that previously reported drug-drug interactions at the index test were no longer identified in the subsequent test for 39.5% of patients. CONCLUSIONS: Employing a definitive test to detect substances whose interactions may cause adverse drug events can enhance a provider's insights, drive clinical decision making, and improve patient outcomes.

Characterization of drug-drug interactions in patients whose substance intake was objectively identified by detection in urine.

BACKGROUND: Identification of drug-drug interactions (DDIs) typically relies on patient medication lists which are prone to inaccuracies. This study describes use of a mass spectrometry test to detect recently ingested substances in urine with subsequent identification of DDIs. RESEARCH DESIGN AND METHODS: This was a retrospective analysis of the prevalence of DDIs identified in patients with chronic pain, addiction and/or behavioral health conditions in the U.S. Relationships between patient demographics, polypharmacy and the occurrence of DDIs were also described. RESULTS: Of 15,004 patients, 2964 (20%) had a DDI identified. There was a positive association between the number of substances detected in urine and the number of interactions identified (r = 0.5033, p-value = 0.0001). Of patients with polypharmacy, 15.6% had contraindicated or severe interactions identified compared to only 3.2% of those without polypharmacy. For polypharmacy patients, the youngest population studied had a much higher likelihood of having one or more DDIs identified compared to the other age groups (p-value = 0.0002). CONCLUSIONS: By utilizing a mass spectrometry test to objectively detect recently ingested substances followed by identification of DDIs, healthcare providers may be able to better characterize the true incidence of DDIs. Study findings may not be generalizable to healthcare populations outside of pain management, addiction treatment, and behavioral health.

Urine drug testing results and paired oral fluid comparison from patients enrolled in long-term medication-assisted treatment in Tennessee.

Urine drug testing is recommended for individuals receiving medication-assisted treatment. It provides objective information for practitioners to consider and may serve as a protective factor against drug-related mortality. The primary objective of our study was to describe urine drug testing results for patients undergoing long-term medication-assisted treatment (≥6months). The secondary objective was to provide further evidence to establish oral fluid as a reliable alternative to urine. All subjects (n=639) included in the study were enrolled in one of five treatment centers in the state of Tennessee, and all urine specimens were positive for either methadone or buprenorphine. Nicotine (87%), caffeine (70%), marijuana (15%), alcohol (14%) and gabapentin (10%) were the most prevalent substances identified through urine drug testing. The presence of non-maintenance opioids (prescription and/or heroin) may represent relapse; these drugs were present in 10% of specimens tested. Evidence of illicit drug use (cocaine, heroin, marijuana and/or methamphetamine) was detected in 19% specimens. For 126 of the 639 subjects included in the study, paired oral fluid and urine test results were compared for agreement. Of the total paired urine and oral fluid tests, approximately 7% were positive for a drug in both specimen types and 91% were negative in both, resulting in an overall agreement of 98%. The study demonstrates continued use of illicit and commercially available medications in a medication-assisted treatment population undergoing long-term treatment. The results affirm the reliability of oral fluid as an alternative specimen type for compliance testing in this population.

Prevalence of heroin markers in urine for pain management patients.

Surveys of current trends indicate heroin abuse is associated with nonmedical use of pain relievers. Consequently, there is an interest in evaluating the presence of heroin-specific markers in chronic pain patients who are prescribed controlled substances. A total of 926,084 urine specimens from chronic pain patients were tested for heroin/diacetylmorphine (DAM), 6-acetylmorphine (6AM), 6-acetylcodeine (6AC), codeine (COD), and morphine (MOR). Heroin and markers were analyzed using liquid chromatography tandem mass spectrometry (LC-MS-MS). Opiates were analyzed following hydrolysis using LC-MS-MS. The prevalence of heroin use was 0.31%, as 2871 were positive for one or more heroin-specific markers including DAM, 6AM, or 6AC (a known contaminant of illicit heroin). Of these, 1884 were additionally tested for the following markers of illicit drug use: 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), methamphetamine (MAMP), 11-nor-9-carboxy-Δ(9)-tetracannabinol (THCCOOH), and benzoylecgonine (BZE); 654 (34.7%) had positive findings for one or more of these analytes. The overall prevalence of heroin markers were as follows: DAM 1203 (41.9%), 6AM 2570 (89.5%), 6AC 1082 (37.7%). MOR was present in 2194 (76.4%) and absent (