Evidence of Designer Benzodiazepine Use in Routine Healthcare Urine Drug Specimens.

OBJECTIVES: The illicit drug market continuously evolves, with new substances introduced to mimic prescription or other illicit drugs while evading detection by routine drug testing. The objective was to determine if designer benzodiazepines would be present in urine samples collected from patients in various healthcare settings. METHODS: Samples for which providers ordered testing for prescription benzodiazepines during the study period were diluted, subjected to enzymatic hydrolysis, and analyzed using liquid chromatography- tandem mass spectrometry. In addition to prescription benzodiazepines, samples were also analyzed for presence of any of the following designer benzodiazepines: etizolam, diclazepam, delorazepam, lormetazepam, flubromazepam, flubromazolam, and phenazepam. RESULTS: Of 38,073 samples tested, 40 samples contained a designer benzodiazepine and/or a metabolite. Of the 40 samples, 19 (47.5%) also tested positive for a prescription benzodiazepine. Twenty-one samples (52.5%) did not test positive for a prescription benzodiazepine, which would result in undetected benzodiazepine use had only traditional definitive testing methods been employed. Thirty-three (82.5%) samples contained an opioid, including 22 (55%) positive for buprenorphine and/or methadone. CONCLUSIONS: The potential harms from the use of designer benzodiazepines are widely unknown due to the lack of traditional pharmacokinetic studies and good manufacturing processes. Our analysis shows that when a designer benzodiazepine was present, over 80% of samples also contained an opioid or a prescription benzodiazepine, which may increase the risk of a drug interaction or adverse drug event. Providers may benefit from knowledge of their patients' designer benzodiazepine use when formulating risk mitigation strategies as part of a treatment plan.

Searching for Best Direction in Healthcare: Distilling Opportunities, Priorities and Responsibilities.

Canada's health and its care are evolving. Evidence from serial Health Care in Canada surveys of the public and health professionals over the last two decades reveal a persistent sense of care quality, despite an aging population, decreasing levels of good and excellent health, increasing prevalence of chronic illnesses; and sub-optimal access to timely and patient-centred care. Stakeholders are, however, somewhat pessimistic and many sense complete rebuilding, or major changes, may be necessary. To improve access, the primary health concern of all Canadians - increasing medical and nursing school enrolment, and requiring professionals to work in teams - have attracted increasingly high support from both the public and professionals. However, physicians' support lags behind that of nursing, pharmacy and administrative colleagues; and, currently, only a minority of patients and professionals are actively involved in team care programs. Another example in which high levels of support may not necessarily translate into priority implementation of promising interventions is the realm of patient-centred care. The public and all professionals report a very high level of general support for care provided in a caring and respectful manner. However, while the public rank it second in implementation priority, following timely access, the majority of professionals rank it only fourth. By contrast, there is remarkable pan-stakeholder concordance around interventions to improve the overall health system, with the majority of public and professional stakeholders rating the creation of national supply systems as their top priority to expedite the clinical and cost efficiency of new treatments. There is a similar pan-stakeholder concordance around priority of responsibility to drive innovations, the top three being: federal/provincial governments; research hospitals/regional health authorities; and the pharmaceutical industry. In summary, Canadians are at a healthcare crossroads. Population health is decreasing, chronic diseases are increasing and desire for timely access to patient-centred, team-delivered and technology-supported care remain top concerns. Despite some disconnects between theoretical support for, and priority to implement, promising innovations, there is universal support to optimize resources to make things better. And there is concordance around the leadership best suited to lead innovation. Things can be better.

Contributions and Challenges of Non-Professional Patient Care: A Key Component of Contemporary Canadian Healthcare.

The Canadian public is aging. Population levels of excellent, or very good, health are decreasing, and the prevalence of chronic diseases is increasing. Timely access to caring and respectful care from health professionals, with supporting information transfer, are key qualities in patients' sense of centricity and hope for best outcomes. Data from the 2013-2014 Health Care in Canada (HCIC) survey reveal, however, that 38% of such patients do not always, or often, access this support. The lack of timely access may be one underlying driver for non-professional caregivers to contribute to the care, as well as the personal and financial management, of family members or friends with chronic disease. Previous HCIC surveys, in 2005, 2006 and 2007, reported non-professional caregivers' prevalence in the adult public at 21, 23 and 26%, respectively, compared with 19% in the 2013-2014 survey. In all the surveys, a notable feature of non-professional care providers has been their universality of contribution, across age, sex, geography and time. Caregivers pay, however, a price. They have a lower level of self-related health, a higher incidence of chronic illness and net-negative impacts on relationships, career and finances, including use of personal savings (53%) and necessity of quitting their job (12%). Conversely, they infrequently claim available tax (12%) or compassionate care (11%) benefits. Interestingly, non-professional caregivers work in team-care settings with health professionals more frequently (29%) than patients in the general population with chronic illnesses (18%). Nonetheless, their current levels of always, or often, receiving assisting support (46%) and information (53%) from health professionals are lower than the respective results reported by the general public (65% and 68%). In conclusion, non-professional patient care in Canada is a common, longstanding and not-for-profit enterprise. It is more likely driven by altruistic caring or sense of duty that balance, or overwhelm, its associated personal, medical and financial burdens. In the short term, practical opportunities for enhancement include broader recognition of caregivers' contributions, their improved access to professional support and communication and wider use of available governmental financial support. All are likely to enhance both patient-centred care and lessen the practical burdens of caregivers. Things can be better.

Stakeholder surveys of Canadian healthcare performance: what are they telling us? Who should be listening? Who should be acting, and how?

Eleven Health Care in Canada (HCIC) surveys, spanning 1998-2014, offer a comprehensive overview of the changing perceptions of physician, nurse, pharmacist, administrator and public stakeholders of the nation's health status, its burden of illness and its quality and cost of care. Overall, there persists a universal sense of quality in our health system--despite evidence that national health status is declining, chronic illnesses are increasing, patients' timely access to care and ability to afford care are diminishing and all these indicators are predicted to worsen over time. Among the public and health professionals, key priorities for improving future patient care are increasing professional schools' output and team-based care, along with enhanced use of national supply systems to reduce costs of care. Among HCIC survey partners, the overarching goal has been, and remains, the utilization of knowledge gained from the surveys to facilitate evidence-driven health policy and improved patient care and outcomes. Practical foci are the development of knowledge translation (KT) activities and assessment of their impact. This paper outlines current initiatives to track reach of member and non-member audiences for HCIC information; to ascertain how they perceive and value the various KT messages, vehicles and metrics; and to potentially identify a hierarchy of efficacy for impact factors. The primary objective is to inform future HCIC survey design and reporting, especially identification of KT vehicles and venues that are most effective in terms of reach and impact in facilitating understanding of, and subsequent action around, the knowledge generated.

Prevalence of synthetic cannabinoids in U.S. athletes: initial findings.

A number of synthetic cannabinoids such as JWH-018 and JWH-073 have been incorporated into "spice" products. Despite having labels warning against human consumption, the products are smoked for their cannabinoid-like effects and the extent of their use by athletes has not been adequately described. Urine samples collected from 5,956 athletes were analyzed by high-performance liquid chromatography-tandem mass spectrometry for the presence of JWH-018, JWH-073, and their metabolites. Metabolites of JWH-018 and/or JWH-073 were detected in 4.5% of the samples. Metabolites of JWH-018 and JWH-073, only JWH-018, and only JWH-073 were detected in 50%, 49%, and approximately 1% of positive samples, respectively. In total, JWH-018 metabolites were detected in 99% (50% + 49%) and JWH-073 metabolites were detected in approximately 50% (49% + 1%) of the positive samples. Parent JWH-018, JWH-018-2-OH-indole, and JWH-018-4-OH-indole were not detected in any of the samples. All samples in which JWH-073 metabolites were detected contained JWH-073-N-butanoic acid. Parent JWH-073 and its N-(4-OH-butyl), 4-OH-indole, 5-OH-indole, and 7-OH-indole metabolites were not detected. Given the number of synthetic cannabinoids that have been synthesized, their limited regulation, and the prevalence of JWH-018 and JWH-073 metabolites detected in the athletes, these compounds should remain a priority for anti-doping programs.

Oral fluid drug testing of chronic pain patients. II. Comparison of paired oral fluid and urine specimens.

A clinical study was conducted to compare the use of oral fluid to urine for compliance monitoring of pain patients. Patients (n = 133) undergoing treatment for chronic pain at four clinics participated in the study and provided paired oral fluid and urine specimens. Oral fluid specimens were collected with Quantisal(TM) saliva collection devices immediately following urine collection. Oral fluid specimens were analyzed for 42 drugs and/or metabolites by validated liquid chromatography-tandem mass spectrometry procedures. Accompanying urine specimens were initially screened by immunoassay and non-negative results were confirmed. Of the 1544 paired tests, 329 (21.3%) drug analytes were positive, and 984 (63.7%) were negative for both specimens resulting in an overall agreement of 85%. There were 83 (5.4%) analyte results that were positive in oral fluid and negative in urine, and 148 (9.6%) were negative in oral fluid and positive in urine for an overall disagreement of 15%. Cohen's Kappa value was 0.64, indicating "substantial" agreement. The primary exceptions to agreement were the lower detection rates for hydromorphone, oxymorphone, and benzodiazepines in oral fluid compared to urine. The authors conclude that, overall, oral fluid tests produced comparable results to urine tests with some minor differences in detection rates for different drug classes.

Oral fluid drug testing of chronic pain patients. I. Positive prevalence rates of licit and illicit drugs.

Oral fluid compliance monitoring of chronic pain patients is an analytical challenge because of the limited specimen volume and the number of drugs that require detection. This study evaluated oral fluid for monitoring pain patients and compared results to urine studies of similar populations. Oral fluid specimens were analyzed from 6441 pain patients from 231 pain clinics in 20 states. Specimens were screened with 14 ELISA assays and non-negative specimens were confirmed by LC-MS-MS for 40 licit and illicit drugs and metabolites. There was an 83.9% positive screening rate (n=5401) of which 98.7% (n=5329) were confirmed at ≥ LOQ concentrations for at least one analyte. The prevalence of confirmed positive drug groups was as follows: opiates > oxycodone > benzodiazepines > methadone ≈ carisoprodol > fentanyl > cannabinoids ≈ tramadol > cocaine > amphetamines ≈ propoxyphene ≈ buprenorphine > barbiturates > methamphetamine. Approximately 11.5% of the study population of pain patients apparently used one or more illicit drugs (cannabis, cocaine, methamphetamine and/or MDMA). Overall, the pattern of licit and illicit drugs and metabolites observed in oral fluid paralleled results reported earlier for urine, indicating that oral fluid is a viable option for use in compliance monitoring programs of chronic pain patients.

Association and discrimination of diesel fuels using chemometric procedures.

Five neat diesel samples were analyzed by gas chromatography-mass spectrometry and total ion chromatograms as well as extracted ion profiles of the alkane and aromatic compound classes were generated. A retention time alignment algorithm was employed to align chromatograms prior to peak area normalization. Pearson product moment correlation coefficients and principal components analysis were then employed to investigate association and discrimination among the diesel samples. The same procedures were also used to investigate the association of a diesel residue to its neat counterpart. Current limitations in the retention time alignment algorithm and the subsequent effect on the association and discrimination of the diesel samples are discussed. An understanding of these issues is crucial to ensure the accuracy of data interpretation based on such chemometric procedures.

Chemometric analysis of diesel fuel for forensic and environmental applications.

Diesel fuel samples were analyzed using gas chromatography-mass spectrometry (GC-MS) and chemometric procedures to associate and discriminate samples for potential use in forensic and environmental applications. Twenty-five diesel samples, representing 13 different brands, were collected from service stations in the Lansing, Michigan area. From the GC-MS data, mass-to-charge ratios were identified to represent aliphatic (m/z 57) and aromatic (m/z 91 and 141) compounds. The total ion chromatogram (TIC) and extracted ion chromatograms (EICs) of the chosen ions were evaluated using Pearson product moment correlation (PPMC) and principal component analysis (PCA). Diesel samples from the same brand showed higher PPMC coefficients, while those from different brands showed lower values. EICs generally provided a wider range of correlation coefficients than the TIC, with correspondingly increased discrimination among samples for EIC m/z 91. PCA grouped the diesel samples into four distinct clusters for the TIC. The first cluster consisted of four samples from the same brand, two clusters contained one diesel sample each of different brands, and the fourth cluster contained the remaining diesel samples. The same trend was observed using each EIC, with an increase in the number of clusters formed for EIC m/z 57 and 91. Both statistical procedures suggest aromatic components (specifically, those with m/z 91) provide the greatest discrimination among diesel samples. This conclusion was supported by identifying the chemical components that contribute the most to the variance. The relative amount of aliphatic versus aromatic components was found to cause the greatest discrimination among samples in the data set.