Reverse Iontophoresis: Noninvasive Assessment of Topical Drug Bioavailability.

Assessing drug disposition in the skin after the application of a topical formulation is difficult. It is hypothesized that reverse iontophoresis (RI), which can extract charged/polar molecules for monitoring purposes, may provide a noninvasive approach for the assessment of local drug bioavailability. The passive and RI extraction of salicylic acid (SA) and nicotine (NIC) from porcine skin in vitro was assessed after a simple solution of the former and a transdermal patch of the latter had been applied for 24 and 8 h, respectively. Immediately after this "passive skin loading", the amount of drug in the stratum corneum (SC) and "viable" tissue (VT) was measured either (a) after tape-stripping and subsequent solvent extraction of both skin layers or (b) following RI extraction over 4 h. Parallel experiments were then performed in vivo in healthy volunteers; in this case, the VT was not sampled and the skin loading period for NIC was only 4 h. RI extraction of both drugs was significantly higher (in vitro and in vivo) than that achieved passively, and the cumulative RI extraction profiles as a function of time were mathematically analyzed using a straightforward compartmental model. Best-fit estimates of drug amounts in the SC and VT (ASC,0 and AVT,0, respectively) at the end of "loading" and two first-order rate constants describing transfer between the model compartments were then determined. The in vitro predictions of ASC,0 and AVT,0 were in excellent agreement with the experimental results, as was the value of the former in vivo. The rate constants derived from the in vitro and in vivo results were also similar. In summary, the results provide proof-of-concept that the RI method has the potential to noninvasively assess relevant metrics of drug bioavailability in the skin.

Extraction of phytochemicals from the pomegranate (Punica granatum L., Punicaceae) by reverse iontophoresis.

Plant metabolic profiling can provide a wealth of information regarding the biochemical status of the organism, but sample acquisition typically requires an invasive and/or destructive extraction process. Reverse iontophoresis (RI) imposes a small electric field across a biological membrane to substantially enhance the transport of charged and polar compounds and has been employed, in particular, to extract biomarkers of interest across human skin. The objective of this work was to examine the capability of RI to sample phytochemicals in a minimally invasive fashion in fructo (i.e., from the intact fruit). RI was principally used to extract a model, bioactive compound - specifically, ellagic acid - from the fruit peel of Punica granatum L. The RI sampling protocol was refined using isolated peel, and a number of experimental factors were examined and optimised, including preparation of the peel samples, the current intensity applied and the pH of the medium into which samples were collected. The most favourable conditions (3 mA current for a period of 1 hour, into a buffer at pH 7.4) were then applied to the successful RI extraction of ellagic acid from intact pomegranates. Multiple additional phytochemicals were also extracted and identified by liquid chromatography with tandem mass spectrometry (LC-MS/MS). A successful proof-of-concept has been achieved, demonstrating the capability to non-destructively extract phytochemicals of interest from intact fruit.

Spatio-Temporal Clustering of Multi-Location Time Series to Model Seasonal Influenza Spread.

Although seasonal influenza disease spread is a spatio-temporal phenomenon, public surveillance systems aggregate data only spatially, and are rarely predictive. We develop a hierarchical clustering-based machine learning tool to anticipate flu spread patterns based on historical spatio-temporal flu activity, where we use historical influenza-related emergency department records as a proxy for flu prevalence. This analysis replaces conventional geographical hospital clustering with clusters based on both spatial and temporal distance between hospital flu peaks to generate a network illustrating whether flu spreads between pairs of clusters (direction) and how long that spread takes (magnitude). To overcome data sparsity, we take a model-free approach, treating hospital clusters as a fully-connected network, where arcs indicate flu transmission. We perform predictive analysis on the clusters' time series of flu ED visits to determine direction and magnitude of flu travel. Detection of recurrent spatio-temporal patterns may help policymakers and hospitals better prepare for outbreaks. We apply this tool to Ontario, Canada using a five-year historical dataset of daily flu-related ED visits, and find that in addition to expected flu spread between major cities/airport regions, we were able to illuminate previously unsuspected patterns of flu spread between non-major cities, providing new insights for public health officials. We showed that while a spatial clustering outperforms a temporal clustering in terms of the direction of the spread (81% spatial v. 71% temporal), the opposite is true in terms of the magnitude of the time lag (20% spatial v. 70% temporal).

Non-destructive, reverse iontophoretic extraction of phytochemicals from Mangifera indica, Centella asiatica, Punica granatum, and Citrus sinensis.

For the commercial-scale isolation of phytochemicals, a suitable plant biomass source (including species, origin, growing season, etc.) must be identified, and frequent analytical verification is required to ensure that the phytochemicals are present at predefined minimum threshold concentrations. While the latter are typically assessed in the laboratory, a more efficient and less resource-intensive approach would involve non-destructive and environmentally friendly measurements in situ. Reverse iontophoretic (RI) sampling offers a potential solution to this challenge. OBJECTIVE: We aimed to demonstrate the non-destructive, RI sampling of phytochemicals of interest from biomass from four different sources. MATERIALS AND METHODS: RI experiments were performed in side-by-side diffusion cells using a current density of 0.5 mA/cm2 , for a predetermined time in a defined pH environment, using (1) fresh leaves from Mangifera indica and Centella asiatica and (2) isolated peel from Punica granatum and Citrus sinensis. RESULTS: Mangiferin, madecassoside, punicalagin, ellagic acid, and hesperidin were extracted from the different biomasses by RI. The amounts extracted ranged from 0.03 mg/100 mg of biomass for the cathodal extraction of madecassoside to 0.63 mg/100 mg of biomass for the anodal extraction of punicalagin. A linear relationship (r2  = 0.73) between the RI-extracted quantities of punicalagin and those determined using conventional methods was demonstrated. CONCLUSION: The non-destructive, in situ measurement of phytochemical levels by RI represents a feasible approach for timing the harvesting process.

Asymptomatic surveillance testing for COVID-19 in health care professional students: lessons learned from a low prevalence setting.

The novel coronavirus disease of 2019 (COVID-19) pandemic has severely impacted the training of health care professional students because of concerns of potential asymptomatic transmission to colleagues and vulnerable patients. From May 27th, 2020, to June 23rd 2021; at a time when B.1.1.7 (alpha) and B.1.617.2 (delta) were the dominant circulating variants, PCR testing was conducted on 1,237 nasopharyngeal swabs collected from 454 asymptomatic health care professional students as they returned to their studies from across Canada to Kingston, ON, a low prevalence area during that period for COVID-19. Despite 46.7% of COVID-19 infections occurring in the 18-29 age group in Kingston, severe-acute-respiratory coronavirus-2 was not detected in any of the samples suggesting that negligible asymptomatic infection occurred in this group and that PCR testing in this setting may not be warranted as a screening tool.

Opioid-related deaths in Kingston, Frontenac, Lennox and Addington in Ontario, Canada: the shadow epidemic. / Décès liés aux opioïdes dans la région de Kingston, Frontenac, Lennox et Addington en Ontario, Canada : l'épidémie invisible.

INTRODUCTION: In the Kingston, Frontenac, Lennox and Addington (KFL&A) health unit, opioid overdoses are an important preventable cause of death. The KFL&A region differs from larger urban centres in its size and culture; the current overdose literature that is focussed on these larger areas is less well suited to aid in understanding the context within which overdoses take place in smaller regions. This study characterized opioidrelated mortality in KFL&A, to enhance understanding of opioid overdoses in these smaller communities. METHODS: We analyzed opioid-related deaths that occurred in the KFL&A region between May 2017 and June 2021. Descriptive analyses (number and percentage) were performed on factors conceptually relevant in understanding the issue, including clinical and demographic variables, as well as substances involved, locations of deaths and whether substances were used while alone. RESULTS: A total of 135 people died of opioid overdose. The mean age was 42 years, and most participants were White (94.8%) and male (71.1%). Decedents often had the following characteristics: being currently or previously incarcerated; using substances alone; not using opioid substitution therapy; and having a prior diagnosis of anxiety and depression. CONCLUSION: Specific characteristics such as incarceration, using alone and not using opioid substitution therapy were represented in our sample of people who died of an opioid overdose in the KFL&A region. A robust approach to decreasing opioid-related harm integrating telehealth, technology and progressive policies including providing a safe supply would assist in supporting people who use opioids and in preventing deaths.

Risk factors for mechanical complications of peripherally inserted central catheters in children.

OBJECTIVE: To determine risk factors for mechanical (noninfectious) complications in peripherally inserted central catheters (PICCs) in children. DESIGN: Retrospective cohort study. SETTING: Pediatric tertiary-care center in Nova Scotia, Canada. PATIENTS: Pediatric patients with a first PICC insertion. METHODS: All PICCs inserted between January 2001 until 2016 were included. Age-stratified (neonates vs non-neonates) Fine-Grey competing risk proportional hazard models were used to model the association between each putative risk factor and the time to mechanical complication or removal of the PICC for reasons not related to a mechanical complication. Models were adjusted for confounding variables identified through directed acyclic graphs. RESULTS: Of 3,205 patients with PICCs, 706 had mechanical complications (22% or 14 events/1000 device days). For both neonates and older children, disease group, lumen count, and prior leak were all associated with mechanical complications in the adjusted proportional hazards model. Access vein and prior infection were also associated with mechanical complications for neonates, and age group was associated with mechanical complications among non-neonates. CONCLUSIONS: We have identified several risk factors for mechanical complications in patients with PICCs that will help improve best practices for PICC insertion and care.

Fertility preservation in uro-oncology.

PURPOSE OF REVIEW: The purpose of this review is to highlight the demand for fertility preservation among cancer survivors and to draw attention to areas where healthcare workers need to improve. As technology advances, maximizing cryopreservation rates will be paramount to increase the ability individuals to conceive after cancer treatment. RECENT FINDINGS: Guidelines recommending discussion of fertility for those diagnosed with cancer have been shown to increase patient satisfaction and overall quality of life. Our review demonstrated that increasing counseling rates remains an ongoing challenge and should remain an area of improvement for all healthcare professionals working in the oncology field. Formal programs to improve patient and provider education and access to fertility preservation increase uptake of fertility preservation. For men, many options exist to cryopreserve sperm; a slight delay to achieve fertility preservation has not been shown to lead to worse outcomes. Cryopreservation strategies differ based on puberty status and remain an active area of clinical research. SUMMARY: Improving fertility outcomes for cancer survivors is possible with appropriate counseling techniques at the time of cancer diagnosis. Clinicians should challenge current barriers for patient access to fertility preservation surrounding cancer treatments.

Delivering Chemotherapy to a Metastatic Poor Risk Testicular Cancer Patient on Hemodialysis.

A standard curative intent approach of chemotherapy treatment for metastatic testicular cancer has been well established. However, there is little guidance for patients undergoing hemodialysis (HD) who require chemotherapy for this disease. Thus, we describe our treatment approach and rationale for a patient on HD with poor risk metastatic nonseminomatous germ cell tumor involving the testicle, lymph nodes, liver, and bone. After orchiectomy, five cycles of cisplatin and modified dose etoposide were delivered and strategically timed with HD. Treatment was complicated by significant neuropathy. Surgical resection of two liver lesions was performed after chemotherapy. Ten years post-chemotherapy, he remains free of clinical, biochemical, or radiological recurrence. While our patient remains free of disease after this treatment, the optimal chemotherapy and dialysis dose and schedule to maximize cure and minimize toxicity remains unknown.

Chronic opioid use after joint replacement surgery in seniors is associated with increased healthcare utilization and costs: a historical cohort study.

PURPOSE: Postoperative opioid use may be associated with increased healthcare utilization and costs. We sought to examine the relationship between duration of postoperative opioid prescriptions and healthcare costs and resource utilization in senior patients following hip and knee replacement. METHODS: We conducted a historical cohort study evaluating postoperative opioid use and healthcare costs in patients over the age of 65 yr undergoing primary total hip or knee arthroplasty over a ten-year period from 1 April 2006 to 31 March 2016. The last follow-up date was 31 March 2017. We identified preoperative and postoperative opioid prescriptions, patient characteristics, and healthcare costs using deidentified Ontario administrative databases (Institute of Clinical Evaluative Sciences). Duration of postoperative opioid use was divided into four categories: short-term (1-90 days), prolonged (91-180 days), chronic (181-365 days), and undocumented. RESULTS: The study included 49,638 hip and 85,558 knee replacement patients. Although the initial hospitalization accounted for the greatest cost in all patients, over the following year patients in the short-term opioid use group incurred the lowest average costs, and those in the chronic group incurred the highest (hip, CAD 17,528 vs CAD 26,736; knee, CAD 16,043 vs CAD 23,007), driven by increased healthcare resource utilization. CONCLUSION: Chronic opioid use after arthroplasty was associated with higher resource utilization and healthcare costs during the year following surgery. These results can be used to develop predictors of longer opioid use and higher costs. Further research is planned to determine whether recently implemented opioid reduction strategies can reduce healthcare resource utilization.

RéSUMé: OBJECTIF: L'utilisation postopératoire d'opioïdes peut être associée à une augmentation de l'utilisation et des coûts des soins de santé. Nous avons cherché à examiner la relation entre la durée des ordonnances d'opioïdes postopératoires, les coûts des soins de santé et l'utilisation des ressources chez les patients âgés après une arthroplastie de la hanche et du genou. MéTHODE: Nous avons réalisé une étude de cohorte historique évaluant la consommation postopératoire d'opioïdes et les coûts des soins de santé chez les patients de plus de 65 ans subissant une arthroplastie totale primaire de la hanche ou du genou sur une période de dix ans allant du 1er avril 2006 au 31 mars 2016. La dernière date de suivi était le 31 mars 2017. Nous avons identifié les ordonnances pré- et postopératoires d'opioïdes, les caractéristiques des patients et les coûts des soins de santé à l'aide de bases de données administratives de l'Ontario désidentifiées (ICES). La durée de la consommation d'opioïdes postopératoires était divisée en quatre catégories : à court terme (1 à 90 jours), prolongée (91 à 180 jours), chronique (181 à 365 jours) et non documentée. RéSULTATS: L'étude a porté sur 49 638 patients ayant subi une arthroplastie de la hanche et 85 558 patients une arthroplastie du genou. Bien que l'hospitalisation initiale ait représenté le coût le plus élevé chez tous les patients, au cours de l'année suivante, les patients du groupe de consommation d'opioïdes à court terme ont encouru les coûts moyens les plus bas et ceux du groupe chronique les coûts les plus élevés (hanche, 17 528 CAD vs 26 736 CAD; genou, 16 043 CAD vs 23 007 CAD) en raison de l'utilisation accrue des ressources de soins de santé. CONCLUSION: La consommation chronique d'opioïdes après une arthroplastie a été associée à une augmentation de l'utilisation des ressources et des coûts des soins de santé au cours de l'année suivant la chirurgie. Ces résultats peuvent être utilisés pour développer des modèles de prédiction d'une consommation prolongée d'opioïdes et de coûts plus élevés. D'autres recherches sont prévues pour déterminer si les stratégies de réduction de la consommation d'opioïdes récemment mises en œuvre pourront réduire l'utilisation des ressources en soins de santé.

Long-term opioid use in seniors following hip and knee arthroplasty in Ontario: a historical cohort study.

PURPOSE: Canadian seniors who undergo hip and knee arthroplasty often experience significant postoperative pain, which could result in persistent opioid use. We aimed to document the impact of preoperative opioid use and other characteristics on postoperative opioid prescriptions in elderly patients following hip and knee replacement before widespread dissemination of opioid reduction strategies. METHODS: We conducted a historical cohort study to evaluate postoperative opioid use in patients over 65 yr undergoing primary total hip and knee replacement over a ten-year period from 1 April 2006 to 31 March 2016, using linked de-identified Ontario administrative data. We determined the use of preoperative opioids and the duration of postoperative opioid prescriptions (short-term [1-90 days], prolonged [91-180 days], chronic [181-365 days], or undocumented). RESULTS: The study included 49,638 hip and 85,558 knee replacement patients. Eighteen percent of hip and 21% of knee replacement patients received an opioid prescription within 90 days before surgery. Postoperatively, 51% of patients filled opioid prescriptions for 1-90 days, while 24% of hip and 29% of knee replacement patients filled prescriptions between 6 and 12 months, with no impact of preoperative opioid use. Residence in long-term care was a significant predictor of chronic opioid use (hip: odds ratio [OR], 2.64; 95% confidence interval [CI], 1.93 to 3.59; knee: OR, 2.46; 95% CI, 1.75 to 3.45); other risk factors included female sex and increased comorbidities. CONCLUSION: Despite a main goal of joint arthroplasty being relief of pain, seniors commonly remained on postoperative opioids, even if not receiving opioids before surgery. Opioid reduction strategies need to be implemented at the surgical, primary physician, long-term care, and patient levels. These findings form a basis for future investigations following implementation of opioid reduction approaches.

RéSUMé: OBJECTIF: Les aînés canadiens subissant une arthroplastie de la hanche ou du genou éprouvent souvent une douleur postopératoire importante, ce qui pourrait entraîner la consommation persistante d'opioïdes. Nous avons cherché à documenter l'impact d'une utilisation préopératoire d'opioïdes et d'autres caractéristiques sur les prescriptions postopératoires d'opioïdes chez les patients âgés suivant un remplacement de hanche ou de genou avant l'utilisation répandue de stratégies de réduction d'opioïdes. MéTHODE: Nous avons réalisé une étude de cohorte historique pour évaluer la consommation postopératoire d'opioïdes chez les patients de plus de 65 ans subissant une arthroplastie totale primaire de la hanche ou du genou sur une période de dix ans du 1er avril 2006 au 31 mars 2016, à l'aide de données administratives dépersonnalisées et codées de l'Ontario. Nous avons déterminé la durée des ordonnances préopératoires et postopératoires d'opioïdes (à court terme [1-90 jours], prolongées [91-180 jours], chroniques [181-365 jours] ou non documentées). RéSULTATS: L'étude a porté sur 49 638 patients ayant subi une arthroplastie de la hanche et 85 558 patients une arthroplastie du genou. Dix-huit pour cent des patients ayant subi une arthroplastie de la hanche et 21 % des patients ayant subi une arthroplastie du genou ont reçu une ordonnance d'opioïdes dans les 90 jours précédant leur chirurgie. En période postopératoire, 51 % des patients ont utilisé leurs ordonnances d'opioïdes pendant 1 à 90 jours, tandis que 24 % des patients d'arthroplastie de la hanche et 29 % des patients d'arthroplastie du genou ont utilisé leurs ordonnances entre six et 12 mois. Le fait d'habiter dans un établissement de soins de longue durée était un prédicteur important de consommation chronique d'opioïdes (hanche : rapport de cotes [RC], 2,64; intervalle de confiance [IC] à 95 %, 1,93 à 3,59; genou : RC, 2,46; IC 95 %, 1,75 à 3,45); le sexe féminin et l'augmentation des comorbidités constituaient d'autres facteurs de risque. CONCLUSION: Bien que l'un des principaux objectifs de l'arthroplastie articulaire soit le soulagement de la douleur, les personnes âgées continuent généralement à consommer des opioïdes en période postopératoire, même si elles ne prenaient pas d'opioïdes avant leur chirurgie. Il est nécessaire de mettre en œuvre des stratégies de réduction des opioïdes qui s'adressent aux chirurgiens, aux médecins traitants, aux soins de longue durée et aux patients. Ces constatations constituent la base d'études futures réalisées à la suite de la mise en œuvre d'approches de réduction des opioïdes.

Mechanical complications of central venous catheters in children: A cohort study.

BACKGROUND: Despite the numerous advantages of central venous catheters (CVCs), they have been associated with a variety of complications. Surveillance for mechanical complications of CVCs is not routine, so the true incidence and impact of this adverse patient outcome remains unclear. SETTING AND METHODS: Prospectively collected CVC data on mechanical complications were reviewed from a centralized database for all in-hospital patient days at our tertiary-care hospital from January 2001 to June 2016 in patients aged <19 years. Patient demographics, CVC characteristics, and rates of mechanical complications per 1,000 days of catheter use were described. RESULTS: In total, 8,747 CVCs were placed in 5,743 patients during the study period, which captured 780,448 catheter days. The overall mechanical complication rate was 6.1 per 1,000 catheter days (95% confidence interval [CI], 5.9-6.3). The highest complication rates were in nontunneled lines; this was consistent throughout the 15-year study period. Also, 521 CVCs (∼6%) were removed due to mechanical complications before therapy termination. Catheters with tip location in the superior vena cava or right atrium had the fewest complications. CONCLUSIONS: Mechanical complications of CVCs are a common and significant event in the pediatric population. We propose that CVC-associated mechanical complications become a routinely reported patient safety outcome.

Limited Propagation of SARS-CoV-2 among Children in a Childcare Center, Canada, 2021.

An outbreak of severe acute respiratory syndrome coronavirus 2 with no definitive source and potential exposure to variants of concern was declared at a childcare center in Ontario, Canada, in March 2021. We developed a robust outbreak management approach to detect, contain, and interrupt this outbreak and limit propagation among children.

Development and assessment of a hospital admissions-based syndromic surveillance system for COVID-19 in Ontario, Canada: ACES Pandemic Tracker.

BACKGROUND: The COVID-19 pandemic has continued to pose a major global public health risk. The importance of public health surveillance systems to monitor the spread and impact of COVID-19 has been well demonstrated. The purpose of this study was to describe the development and effectiveness of a real-time public health syndromic surveillance system (ACES Pandemic Tracker) as an early warning system and to provide situational awareness in response to the COVID-19 pandemic in Ontario, Canada. METHODS: We used hospital admissions data from the Acute Care Enhanced Surveillance (ACES) system to collect data on pre-defined groupings of symptoms (syndromes of interest; SOI) that may be related to COVID-19 from 131 hospitals across Ontario. To evaluate which SOI for suspected COVID-19 admissions were best correlated with laboratory confirmed admissions, laboratory confirmed COVID-19 hospital admissions data were collected from the Ontario Ministry of Health. Correlations and time-series lag analysis between suspected and confirmed COVID-19 hospital admissions were calculated. Data used for analyses covered the period between March 1, 2020 and September 21, 2020. RESULTS: Between March 1, 2020 and September 21, 2020, ACES Pandemic Tracker identified 22,075 suspected COVID-19 hospital admissions (150 per 100,000 population) in Ontario. After correlation analysis, we found laboratory-confirmed hospital admissions for COVID-19 were strongly and significantly correlated with suspected COVID-19 hospital admissions when SOI were included (Spearman's rho = 0.617) and suspected COVID-19 admissions when SOI were excluded (Spearman's rho = 0.867). Weak to moderate significant correlations were found among individual SOI. Laboratory confirmed COVID-19 hospital admissions lagged in reporting by 3 days compared with suspected COVID-19 admissions when SOI were excluded. CONCLUSIONS: Our results demonstrate the utility of a hospital admissions syndromic surveillance system to monitor and identify potential surges in severe COVID-19 infection within the community in a timely manner and provide situational awareness to inform preventive and preparatory health interventions.

COVID-19 outbreak in a personal service setting in Kingston, Ontario, 2020.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, Ontario created a three-phase reopening framework for the economy. Outbreaks were expected at each phase. One week after Phase Two of reopening in the provincial public health administration region of Kingston, Frontenac, Lennox and Addington (KFL&A), a positive case was reported after three weeks of zero new COVID-19 cases. The objective of this report is to describe this COVID-19 outbreak, linked to a personal service setting (PSS), and the public health response to contain the outbreak. METHODS: The outbreak investigation included all COVID-19 cases in KFL&A between June 20, 2020 and July 3, 2020. Public health inspectors and nurses were rapidly deployed to inspect the PSS. A multimodal approach to high-volume testing involved fixed assessment centres, drive-through testing capacity and targeted testing at the outbreak site. Testing was conducted through a real-time polymerase chain reaction assay at the local Public Health Ontario laboratory. RESULTS: Thirty-seven cases were associated with the outbreak: 38% through direct PSS exposure; 32% through household contact; and 30% through social and workplace contact. A superspreading event contributed to 38% of total cases. The majority of cases were in the low to mid-quintiles when analyzed for material deprivation. Testing rates increased four-fold compared to the prior baseline weeks in response to media attention and public health messaging, resulting in a low percent positivity. CONCLUSION: The interplay of aggressive accessible testing, quick lab turnaround time, contact tracing within 24 hours of positive laboratory results as per provincial standards, frequent public communication, rapid inspections, mandatory self-isolation and face coverings were measures successful in halting the outbreak. Inspections or self-audits should be required at all PSSs prior to reopening and outbreak management must work with PSSs to reduce the possibility of superspreading events.

Prescription opioid characteristics at initiation for non-cancer pain and risk of treated opioid use disorder: A population-based study.

BACKGROUND: Long-term prescription opioid use has been associated with adverse health outcomes, including opioid use disorder (OUD). We examined a population of opioid naïve individuals who initiated prescription opioids for non-cancer pain and investigated the associations between opioid prescription characteristics at initiation and time to treated OUD. METHODS: We conducted a retrospective population-based cohort study in Ontario, Canada among opioid naïve individuals aged 15 years and older dispensed an opioid for non-cancer pain between 2013 and 2016. We used the Narcotic Monitoring System to abstract opioid dispensing data. A multivariable Cox regression model was used to examine the association between average daily dose and time to treated OUD. RESULTS: We identified 1,607,659 opioid-naïve individuals who initiated a prescription opioid within the study period. The incidence of treated OUD within the study period was 86 cases per 100,000 person-years. Compared to an average daily dose of <20 morphine milligrams equivalent (MME), higher average daily doses at initiation were associated with greater hazard of treated OUD, 20-50 MME (HR 1.11, 95% CI: 1.02, 1.21), >50-90 MME (HR 1.29, 95% CI: 1.16, 1.44), >90-150 MME (HR 1.29, 95% CI: 1.06, 1.56), >150-200 MME (HR 2.49, 95% CI: 1.54, 4.03) and >200 MME (HR 4.15, 95% CI: 2.89, 5.97). Long-acting formulations and days' supply ≥11 days were also associated with greater hazard of treated OUD. CONCLUSION: Prescription opioid characteristics at initiation are associated with risk of treated OUD, identifying potentially important and modifiable risk factors among people initiating opioids for non-cancer pain.

Reverse Iontophoretic Extraction of Skin Cancer-Related Biomarkers.

Non-invasive methods for early diagnosis of skin cancer are highly valued. One possible approach is to monitor relevant biomarkers such as tryptophan (Trp) and kynurenine (Kyn), on the skin surface. The primary aim of this in vitro investigation was, therefore, to examine whether reverse iontophoresis (RI) can enhance the extraction of Trp and Kyn, and to demonstrate how the Trp/Kyn ratio acquired from the skin surface reflects that in the epidermal tissue. The study also explored whether the pH of the receiver medium impacted on extraction efficiency, and assessed the suitability of a bicontinuous cubic liquid crystal as an alternative to a simple buffer solution for this purpose. RI substantially enhanced the extraction of Trp and Kyn, in particular towards the cathode. The Trp/Kyn ratio obtained on the surface matched that in the viable skin. Increasing the receiver solution pH from 4 to 9 improved extraction of both analytes, but did not significantly change the Trp/Kyn ratio. RI extraction of Trp and Kyn into the cubic liquid crystal was comparable to that achieved with simple aqueous receiver solutions. We conclude that RI offers a potential for non-invasive sampling of low-molecular weight biomarkers and further investigations in vivo are therefore warranted.

Sentinel surveillance of Lyme disease risk in Canada, 2019: Results from the first year of the Canadian Lyme Sentinel Network (CaLSeN).

BACKGROUND: Lyme disease is an emerging vector-borne zoonotic disease of increasing public health importance in Canada. As part of its mandate, the Canadian Lyme Disease Research Network (CLyDRN) launched a pan-Canadian sentinel surveillance initiative, the Canadian Lyme Sentinel Network (CaLSeN), in 2019. OBJECTIVES: To create a standardized, national sentinel surveillance network providing a real-time portrait of the evolving environmental risk of Lyme disease in each province. METHODS: A multicriteria decision analysis (MCDA) approach was used in the selection of sentinel regions. Within each sentinel region, a systematic drag sampling protocol was performed in selected sampling sites. Ticks collected during these active surveillance visits were identified to species, and Ixodes spp. ticks were tested for infection with Borrelia burgdorferi, Borrelia miyamotoi, Anaplasma phagocytophilum, Babesia microti and Powassan virus. RESULTS: In 2019, a total of 567 Ixodes spp. ticks (I. scapularis [n=550]; I. pacificus [n=10]; and I. angustus [n=7]) were collected in seven provinces: British Columbia, Manitoba, Ontario, Québec, New Brunswick, Nova Scotia and Prince Edward Island. The highest mean tick densities (nymphs/100 m2) were found in sentinel regions of Lunenburg (0.45), Montréal (0.43) and Granby (0.38). Overall, the Borrelia burgdorferi prevalence in ticks was 25.2% (0%-45.0%). One I. angustus nymph from British Columbia was positive for Babesia microti, a first for the province. The deer tick lineage of Powassan virus was detected in one adult I. scapularis in Nova Scotia. CONCLUSION: CaLSeN provides the first coordinated national active surveillance initiative for tick-borne disease in Canada. Through multidisciplinary collaborations between experts in each province, the pilot year was successful in establishing a baseline for Lyme disease risk across the country, allowing future trends to be detected and studied.