Evaluating the association between urine drug screening frequency and retention in opioid agonist treatment in Ontario, Canada: a retrospective cohort study.

OBJECTIVE: The objective of this study was to evaluate how urine drug screening (UDS) frequency is associated with retention in opioid agonist treatment (OAT). METHODS: Data for this retrospective cohort study of 55 921 adults in OAT in Ontario, Canada, were derived from administrative sources between 1 January 2011 and 31 December 2015. All patient information was linked anonymously across databases using encrypted health card numbers. Descriptive statistics were calculated for comparing UDS frequency groups using standardised differences (d) where d less than 10% indicated a statistically significant difference. A logistic regression model was then used to calculate ORs adjusting for baseline covariates, including sex, age, location of residence, income quintile, mental disorders, HIV status and deep tissue infections. RESULTS: Over 70% of the cohort had four or more UDS tests per month (weekly or more UDS). Significant associations were observed between UDS frequency and 1-year treatment retention in OAT biweekly (adjusted OR (aOR)=3.20, 95% CI 2.75 to 3.75); weekly UDS (aOR=6.86, 95% CI 5.88 to 8.00) and more than weekly (aOR=8.03, 95% CI 6.87 to 9.38) using the monthly or less groups as the reference. CONCLUSION: This study identified an association between weekly UDS and 1-year treatment retention in OAT. There is an active discussion within Canada about the utility of UDS. The lack of evidence for the impact of UDS on retention has left it open to some to argue they simply provide a barrier to patient engagement. Therefore, it is timely of this study to demonstrate that more frequent urine testing is not associated with a reduction in treatment retention.

Evidence of Increased Age and Sex Standardized Death Rates Among Individuals Who Accessed Opioid Agonist Treatment Before the Era of Synthetic Opioids in Ontario, Canada.

Objective The objective of this study was to evaluate age-sex standardized death rates (ASDR) from all causes from 2011 to 2015 among people who have accessed opioid agonist treatment (OAT) and compare rates living in the Northern and Southern areas of Ontario. Methods Routinely collected administrative health data was used to calculate crude death rates and age-sex standardized death rates (ASDRs) per 1,000,000 population of individuals who accessed OAT and compared the rates geographically from 2011 to 2015. The weighted ASDRs for each year were calculated by using the mid-year population of these regions. The rate ratios were calculated considering the base year as 2011.  Results A total of 55,924 adults who accessed OAT were included between January 1, 2011, and December 31, 2015. The majority of patients in the cohort - 52.3% - were between 15 and 34 years old, 32.5% were female, 11.3% were in the lowest income group, 71.1% lived in Southern areas. Overall, the ASDR steadily increased during the study period and spiked in 2015. We found that among individuals who had accessed OAT, living in Southern Ontario was associated with a lower risk of all-cause mortality than those living in Northern Ontario. ASDR for Northern Ontario was 20.0 (95% confidence interval (CI)= 10.2-34.2) in 2011, and 103.5(95%CI=78.5-133.5) in 2015, which was a five-fold increase from 2011. Whereas in Southern Ontario, ASDR in 2011 was 13.8 (95% CI= 11.5-16.5), and in 2015 ASDR was 60.8 (95%CI=55.8-66.1), which was only a 4-fold increase from 2011 Conclusion Our findings demonstrate evidence of a steadily increasing ASDR among individuals who accessed OAT with higher rates in Northern areas of the province before the era of synthetic opioids in Ontario, Canada.

Preparation and characterization of cobalt-substituted anthrax lethal factor.

Anthrax lethal factor (LF) is a zinc-dependent endopeptidase involved in the cleavage of mitogen-activated protein kinase kinases near their N-termini. The current report concerns the preparation of cobalt-substituted LF (CoLF) and its characterization by electronic spectroscopy. Two strategies to produce CoLF were explored, including (i) a bio-assimilation approach involving the cultivation of LF-expressing Bacillus megaterium cells in the presence of CoCl(2), and (ii) direct exchange by treatment of zinc-LF with CoCl(2). Independent of the method employed, the protein was found to contain one Co(2+) per LF molecule, and was shown to be twice as active as its native zinc counterpart. The electronic spectrum of CoLF suggests the Co(2+) ion to be five-coordinate, an observation similar to that reported for other Co(2+)-substituted gluzincins, but distinct from that documented for the crystal structure of native LF. Furthermore, spectroscopic studies following the exposure of CoLF to thioglycolic acid (TGA) revealed a sequential mechanism of metal removal from LF, which likely involves the formation of an enzyme: Co(2+):TGA ternary complex prior to demetallation of the active site. CoLF reported herein constitutes the first spectroscopic probe of LF's active site, which may be utilized in future studies to gain further insight into the enzyme's mechanism and inhibitor interactions.