Corrigendum to "Uptake of community pharmacist prescribing over a three-year period" [Exploratory Research in Clinical and Social Pharmacy, Volume 9, March 2023, 100221].

[This corrects the article DOI: 10.1016/j.rcsop.2023.100221.].

High concordance of blood glucose measurement in cats between a beta prototype glucometer device and a reference laboratory standard in a clinical setting.

OBJECTIVE: The objective of this study was to evaluate the accuracy of a beta prototype version of a new portable blood glucose meter in feline patients. ANIMALS: 60 client-owned cats. METHODS: In this prospective study, 3-mL blood samples were collected from each cat and analyzed in triplicate using a beta prototype device (AlphaTRAK 3 [AT3]) and by a reference lab standard immediately after collection. Accuracy of the AT3 device was determined in accordance with the International Organization of Standardization (ISO) 15197:2013 criteria, including Bland-Altman plotting and consensus error grid analysis. A Passing-Bablok regression analysis was also performed. RESULTS: 96% of feline measurements fell within the ISO accuracy threshold, and 100% of measurements fell within zones A and B of the consensus error grid, meeting the ISO accuracy requirements. There was no significant bias in the data according to the Bland-Altman analysis. Within the full range of glucose concentrations (20 to 750 mg/dL) the correlation coefficient between the AT3 and the reference lab standard was 0.99. There was no significant constant or proportional bias present in the data. CLINICAL RELEVANCE: The AT3 device met the ISO requirements and is accurate for measurement of blood glucose concentrations in cats.

An early clinical phenotype of necrotizing meningoencephalitis in the Pug reveals similarities to multiple sclerosis in humans.

Necrotizing meningoencephalitis (NME) is a fatal neuroinflammatory disease that previously carried a uniformly grave prognosis. Our recent identification of a novel early form of NME in Pugs suggests that disease onset and progression are likely more insidious than previously recognized and provides new hope that early therapeutic intervention may halt disease progression and ultimately prevent or cure NME. This novel perspective also sheds new light on the clinical similarities to multiple sclerosis (MS) in humans and provides a rationale for cross-species translation. The history of recent scientific discoveries in NME and new parallels between MS and NME will be reviewed.

Retrospective evaluation of the impact of hypoxemia during thoracic surgery in dogs on outcome: a multicenter analysis of 94 cases.

OBJECTIVE: To investigate the statistical association of severe intraoperative hypoxemia in thoracic surgery with mortality, postoperative hospitalization times and cost of care. STUDY DESIGN: Retrospective study. ANIMALS: Dogs that underwent thoracic surgery in three veterinary hospitals between October 1, 2018 and October 1, 2020. METHODS: Anesthesia and hospitalization records from 112 dogs were reviewed and 94 cases met inclusion criteria. Recorded data included signalment, disease etiology, pulmonary or extrapulmonary nature of disease, surgical procedure performed, episodes of severe intraoperative hypoxemia defined as a pulse oximetry reading (SpO2) <90% of 5 minutes or longer duration, survival to discharge, time from extubation to hospital discharge and total invoice cost for clinical visit. Dogs were divided into two groups, those that experienced severe hypoxemia (group A) and those in which SpO2 reading <90% was not observed throughout the procedure (group B). RESULTS: Group A had a greater risk of mortality (odds ratio 10.6, 95% confidence interval 1.9-106.7; p = 0.002), prolonged hospitalization (median 62 hours versus 46 hours; p = 0.035) and more expensive cost of care (median US$10,287 versus $8506; p = 0.056) than group B. No significant difference was found for the type of surgical procedure or pulmonary versus extrapulmonary nature of disease. CONCLUSIONS AND CLINICAL RELEVANCE: Severe intraoperative hypoxemia was statistically associated with an increased risk of mortality and longer postoperative hospitalization times. Although not achieving statistical significance, there was a trend toward increased costs to the client for animals with intraoperative hypoxemia.

Outcomes of surgical treatment with patterns of bacterial culture and antimicrobial susceptibility testing in cases of cervical abscessation in dogs: 82 cases (2018-2021).

OBJECTIVE: The objective of this study was to summarize the presentation, diagnosis, and outcome for dogs surgically treated for chronic cervical abscessation following suspected or reported cervical or oropharyngeal trauma, as well as to report on culture results and antimicrobial susceptibility patterns. RESULTS: Eighty-two dogs were identified by retrospective review. Successful surgical outcome was achieved in 92.7% of dogs. Abscess recurrence was confirmed or suspected in 6/82 (7.3%) cases, and surgical intervention for abscess recurrence was performed in 4/82 (4.9%) cases. Foreign material was identified at surgery in 5/82 (6%) cases. Incisional healing complications were noted in 9/82 (10.9%) cases and required additional surgery in 5/82 (6%) cases. Twenty-three (28%) dogs had negative culture results. The results of antimicrobial sensitivity testing led to a change in antimicrobial treatment in only 9% of cases.Surgically treated cervical abscessation carries a good prognosis with a low incidence of recurrence in this cohort (in contrast to previous reports), despite low frequency of foreign body removal or identification of the underlying cause of the abscess. Excision of chronic inflammatory tissue may not be necessary for a successful outcome, contrary to previous recommendations. Multi-pathogen infections and anaerobic infections are commonly encountered.

Trajectories of the socioeconomic gradient of mental health: Results from the CLSA COVID-19 Questionnaire Study.

As the coronavirus disease (COVID-19) pandemic prolongs, documenting trajectories of the socioeconomic gradient of mental health is important. We describe changes in the prevalence and absolute and relative income-related inequalities of mental health between April and December 2020 in Canada. We used data from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Questionnaire Study and the pre-pandemic CLSA Follow-up 1. We estimated the prevalence proportion, the concentration index (relative inequality), and the generalized concentration index (absolute inequality) for anxiety and self-reported feeling generally unwell at multiple points in April-December 2020, overall, by sex and age group, by region, and among those who reported poor or fair overall health and mental health pre-pandemic. Overall, the prevalence of anxiety remained unchanged (22.45 to 22.10%, p = 0.231), but self-reported feeling generally unwell decreased (9.83 to 5.94%, p = 0.004). Relative and absolute income-related inequalities were unchanged for both anxiety and self-reported feeling generally unwell, with exceptions of an increased concentration of self-reported feeling generally unwell among the poor, measured by the concentration index, overall (-0.054 to -0.115, p = 0.004) and in Ontario (-0.035 to -0.123, p = 0.047) and British Columbia (-0.055 to -0.141, p = 0.044). The COVID-19 pandemic appeared to neither exacerbate nor ameliorate existing income-related inequalities in mental health among older adults in Canada between April and December 2020. Continued monitoring of inequalities is necessary.

Associations of abdominal discomfort and length of clinical signs with surgical procedure in 181 cases of canine small intestinal foreign body obstruction.

BACKGROUND: Gastrointestinal foreign bodies are a common indication for abdominal exploratory surgery. OBJECTIVES: The objective of this study was to evaluate the relationship of pre-operative abdominal discomfort and duration of clinical signs with surgical resolution of canine small intestinal foreign body obstructions (SIFBO). METHODS: We performed a retrospective study of 181 canine abdominal exploratory surgeries for confirmed SIFBO at two referral hospitals. Animals were categorized into five surgical groups (gastrotomy after manipulation into the stomach, enterotomy, resection-and-anastomosis [R&A], manipulated into colon, already in colon) and further grouped by whether entry into the gastrointestinal tract (GIT) was required. RESULTS: Abdominal discomfort was noted in 107/181 cases (59.1%), but no significant differences in abdominal discomfort rates were present among the surgical groups or between GIT entry and no entry groups. Clinical sign duration was associated with surgical procedure; median durations were R&A = 3 days (range, 1-9), enterotomy = 2 days (range, 1-14), gastrotomy = 2 days (range, 1-6), already in colon = 1.5 days (range, 1-2), and manipulated into colon = 1 day (range, 1-7). In a pairwise comparison, differences in the duration of clinical signs were found for obstructions manipulated into the colon versus R&A, gastrotomy versus R&A, and in colon versus R&A. When patients were grouped according to GIT entry, cases with entry had a longer duration of clinical signs (median = 2 days [range, 1-14] versus 1 day [range, 1-7], respectively). CONCLUSIONS: Abdominal discomfort was not associated with surgical complexity; however, the duration of clinical signs was associated with surgical complexity, with longer duration being associated with entry into the GIT and R&A. Despite statistical significance, the maximum difference of 2 days between surgical groups is unlikely to be clinically relevant.

Uptake of community pharmacist prescribing over a three-year period.

Objectives: Pharmacists in Nova Scotia have had legislated authority to prescribe since 2011. This study aimed to describe the prescribing activities of pharmacists and the characteristics of patients who used pharmacist prescribing services. Methods: Using provincial health administrative databases we identified all community pharmacists who prescribed during the study period (October 2016 to March 2020) and correspondingly patients who had medications prescribed by a pharmacist during this period. Differences in, and predictors of the quantity of pharmacist prescribing over three fiscal years (April 2017 to March 2020) were described. Pharmacist prescribing activity was compared across the fiscal years of the study period with One-way Analysis of Variance. Negative binomial regression examined patient factors associated with use of pharmacist prescribing services. Analysis was carried out using SAS ENTERPRISE GUIDE v.8.2 (SAS Institute Cary, NC, USA). Key findings: A total of 1182 pharmacist prescribers were identified, who on average prescribed 24.6, 26.3, and 32.5 (p < 0.001) times per month in fiscal years 2018, 2019, 2020, respectively. The patient cohort contained 372,203 Nova Scotians over the 3-year period. For approved common and minor ailment prescribing in Nova Scotia, gastroesophageal reflux disease, vaccines (non-travel), contraceptive management, herpes zoster treatment, and allergic rhinitis had the highest number of prescriptions over the study period. Patient factors most strongly related to receiving more prescribing services by a pharmacist included receiving income assistance without copay (Incidence rate ratio (IRR) = 1.70), having >2 comorbidities (IRR = 1.51), male sex (IRR = 1.03), and greater age (IRR = 1.01). Those from an urban area (IRR = 0.92) or having a higher income (IRR = 0.95) received fewer pharmacist prescribing services (all p < 0.0001). Conclusions: Pharmacist prescribing increased over the 3-year period. Patients who were older and those with multiple comorbidities used pharmacist prescribing services most often. Prescribing activities represent an increasingly utilized role for pharmacists in primary care.

Patterns of Antipsychotic Dispensation to Long-Term Care Residents.

OBJECTIVES: To describe dispensing patterns of antipsychotic medications to long-term care (LTC) residents and assess factors associated with continuation of an antipsychotic after a fall-related hospitalization. DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: Nova Scotia Seniors Pharmacare Program (NSSPP) beneficiaries age 66 years and older who resided in LTC and received at least 1 dispensation of an antipsychotic within the study period of April 1, 2009, to March 31, 2017. METHODS: Linkage of administrative claims data from the NSSPP and the Canadian Institute of Health Information Discharge Abstract Database identified LTC residents with an antipsychotic dispensation and from the subgroup of those dispensed antipsychotic medications who experienced a fall-related hospitalization. Antipsychotic dispensing patterns were reported with counts and means. Predictors of continuation of an antipsychotic after a fall-related hospitalization (sex, length of stay, days supplied, age, year of admission, rural/urban) were reported and analyzed with multiple logistic regression. RESULTS: There were 19,164 unique NSSPP beneficiaries who were dispensed at least 1 prescription for an antipsychotic medication. Of those who received at least 1 antipsychotic dispensation 90% (n = 17,201) resided in LTC. A mean of 40% (n = 2637) of LTC residents received at least 1 antipsychotic dispensation in each year. Risperidone and quetiapine were dispensed most frequently. Of the 544 beneficiaries residing in LTC who survived a fall-related hospitalization, 439 (80.7%) continued an antipsychotic after hospital discharge. Female sex [OR 1.7, 95% CI (1.013‒2.943)], age 66‒69 [OR 4.587, 95% CI (1.4‒20.8)], 75-79 [OR 2.8, 95% CI (1.3‒6.3)], and 80‒84 years [OR 3.1, 95% CI (1.6‒6.4)] (compared with age 90+ years) were associated with increased risk of antipsychotic continuation. CONCLUSIONS AND IMPLICATIONS: With 90% of antipsychotic dispensations in Nova Scotia being to LTC residents and 40% of LTC residents being dispensed antipsychotics in any year there is a need to address this level of antipsychotic dispensation to older adults.

Comparison of the pharmacokinetics of continuous and intermittent infusions of ampicillin-sulbactam in dogs with septic peritonitis.

OBJECTIVE: To evaluate the time-course of ampicillin-sulbactam and percentage of time that its concentration is above a given MIC (T% > MIC) in dogs with septic peritonitis when delivered as either a continuous infusion (CI) or intermittent infusion (II). ANIMALS: 11 dogs with septic peritonitis. PROCEDURES: Dogs were randomized to receive ampicillin-sulbactam as either CI or II. Continuous infusions were delivered as a 50 mg/kg bolus IV followed by a rate of 0.1 mg/kg/min. Intermittent infusions were administered as 50 mg/kg IV q8h. Serum ampicillin-sulbactam concentrations were measured at hours 0, 1, 6, and every 12 hours after until patients were transitioned to an oral antimicrobial equivalent. All other care was at the discretion of the attending clinician. Statistical analysis was used to determine each patient's percentage of time T% > MIC for 4 MIC breakpoints (0.25, 1.25, 8, and 16 µg/mL). RESULTS: No dogs experienced adverse events related to ampicillin-sulbactam administration. Both CI and II maintained a T% > MIC of 100% of MIC 0.25 µg/mL and MIC 1.25 µg/mL. The CI group maintained a higher T% > MIC for MIC 8 µg/mL and MIC 16 µg/mL; however, these differences did not reach statistical significance (P = .15 and P = .12, respectively). CLINICAL RELEVANCE: This study could not demonstrate that ampicillin-sulbactam CI maintains a greater T% > MIC in dogs with septic peritonitis than II; however, marginal differences were noted at higher antimicrobial breakpoints. While these data support the use of antimicrobial CI in septic and critically ill patients, additional prospective trials are needed to fully define the optimal doses and the associated clinical responses.

Has medical assistance in dying changed end-of-life care in the ICU? A qualitative survey of Canadian intensivists.

PURPOSE: Since 2016, Canada has permitted medical assistance in dying (MAID). Our aims were to understand how Canadian intensivists view MAID and the impact of MAID on end-of-life care in the ICU. MATERIAL AND METHODS: This was a descriptive qualitative study of responses from a 41-item questionnaire. We recruited intensivists and trainees from 11 pediatric ICU programs and 14 adult ICU programs across Canada between December 2019 and May 2020. Two qualitative researchers inductively coded responses and then conducted preliminary thematic analysis. Themes were subsequently refined through group discussion. RESULTS: We obtained 150 complete questionnaires (33% response rate), of which 50% were adult practitioners and 50% pediatric. We identified six main themes including: intensivists have a wide range of opinions on MAID; MAID has not changed ICU practice; and moral distress has a diverse impact on practice. Physicians also discussed the role of provider intent and the importance of treating withdrawal of life-sustaining treatments (WLST) as a process to protect patients, families, and providers. CONCLUSIONS: Canadian intensivists hold a wide range of opinions on MAID, but most agree it has not changed ICU practice. Importantly, intensivists also hold differing views on the relevance of physician intent in medical ethics.

Genomic landscapes of canine splenic angiosarcoma (hemangiosarcoma) contain extensive heterogeneity within and between patients.

Cancer genomic heterogeneity presents significant challenges for understanding oncogenic processes and for cancer's clinical management. Variation in driver mutation frequency between patients with the same tumor type as well as within an individual patients' cancer can shape the use of mutations as diagnostic, prognostic, and predictive biomarkers. We have characterized genomic heterogeneity between and within canine splenic hemangiosarcoma (HSA), a common naturally occurring cancer in pet dogs that is similar to human angiosarcoma (AS). HSA is a clinically, physiologically, and genomically complex canine cancer that may serve as a valuable model for understanding the origin and clinical impact of cancer heterogeneity. We conducted a prospective collection of 52 splenic masses from 43 dogs (27 HSA, 15 benign masses, and 1 stromal sarcoma) presenting for emergency care with hemoperitoneum secondary to a ruptured splenic mass. Multi-platform genomic analysis included matched tumor/normal targeted sequencing panel and exome sequencing. We found candidate somatic cancer driver mutations in 14/27 (52%) HSAs. Among recurrent candidate driver mutations, TP53 was most commonly mutated (30%) followed by PIK3CA (15%), AKT1 (11%), and CDKN2AIP (11%). We also identified significant intratumoral genomic heterogeneity, consistent with a branched evolution model, through multi-region exome sequencing of three distinct tumor regions from selected primary splenic tumors. These data provide new perspectives on the genomic landscape of this veterinary cancer and suggest a cross-species value for using HSA in pet dogs as a naturally occurring model of intratumoral heterogeneity.

Pharmacokinetic Exposures Associated With Oral Administration of Sorafenib in Dogs With Spontaneous Tumors.

Sorafenib is a multi-kinase small molecule inhibitor that targets serine/threonine and tyrosine kinases including the RAF kinase family, VEGFR-2, and PDGFR. The aim of this study was to evaluate the systemic pharmacokinetics of a previously defined tolerable oral dose of sorafenib in tumor-bearing dogs. Six client-owned dogs with a cytologic or histologic diagnosis of cancer were enrolled in this open-label, tolerability study. Dogs were administered sorafenib at an intended dose of 3 mg/kg and serum samples were obtained for analysis of sorafenib serum concentrations at 0, 1, 2, 6, 12, 24, 48, 72, 96, and 168 h post-drug administration. Median time to peak serum sorafenib concentration occurred at 4 h (range 2-12 h) resulting in an average serum concentration of 54.9 ± 33.5 ng/mL (118.2 ± 72.1 nM). Mean sorafenib levels declined by over 70% relative to peak serum concentrations by 24 h in all dogs, suggesting the value of at least twice daily administration. Doses of 3 mg/kg were well-tolerated and no patients in the study experienced adverse events that were attributable to sorafenib. Future trials in dogs with cancer are recommended at this dosing schedule to assess the effect of sorafenib administration on anti-tumor efficacy signals and relevant pharmacodynamic target modulation in vivo.

Simultaneous monitoring of HIV viral load and screening of SARS-CoV-2 employing a low-cost RT-qPCR test workflow.

The COVID-19 pandemic interrupted routine care for individuals living with HIV, putting them at risk of virologic failure and HIV-associated illness. Often this population is at high risk for exposure to SARS-CoV-2 infection, and once infected, for severe disease. Therefore, close monitoring of HIV plasma viral load (VL) and screening for SARS-CoV-2 infection are needed. We developed a non-proprietary method to isolate RNA from plasma, nasal secretions (NS), or both. The extracted RNA is then submitted to RT-qPCR to estimate the VL and classify HIV/SARS-CoV-2 status (i.e., HIV virologic failure or suppressed; SARS-CoV-2 as positive, presumptive positive, negative, or indeterminate). In contrived samples, the in-house RNA extraction workflow achieved a detection limit of 200-copies per mL for HIV RNA in plasma and 100-copies per mL for SARS-CoV-2 RNA in NS. Similar detection limits were observed for HIV and SARS-CoV-2 in pooled plasma/NS contrived samples. When comparing in-house with standard extraction methods, we found high agreement (>0.91) between input and measured RNA copies for HIV LTR in contrived plasma; SARS-CoV-2 N1/N2 in contrived NS; and LTR, N1, and N2 in pooled plasma/NS samples. We further evaluated this workflow on 133 clinical specimens: 40 plasma specimens (30 HIV-positive), 67 NS specimens (31 SARS-CoV-2-positive), and 26 combined plasma/NS specimens (26 HIV-positive with 10 SARS-CoV-2-positive), and compared the results obtained using the in-house RNA extraction to those using a commercial kit (standard extraction method). The in-house extraction and standard extraction of clinical specimens were positively correlated: plasma HIV VL (R2 of 0.81) and NS SARS-CoV-2 VL (R2 of 0.95 and 0.99 for N1 and N2 genes, respectively); and pooled plasma/NS HIV VL (R2 of 0.71) and SARS-CoV-2 VL (R2 of 1 both for N1 and N2 genes). Our low-cost molecular test workflow ($1.85 per pooled sample extraction) for HIV RNA and SARS-CoV-2 RNA could serve as an alternative to current standard assays ($12 per pooled sample extraction) for laboratories in low-resource settings.

A potential early clinical phenotype of necrotizing meningoencephalitis in genetically at-risk pug dogs.

BACKGROUND: Necrotizing meningoencephalitis (NME) in the pug dogs is a fatal neuroinflammatory disease associated with rapid progression and poor response to conventional immunosuppressive therapy. Diagnosis is typically made after severe neurological abnormalities have manifested. HYPOTHESIS/OBJECTIVE: Pug dogs at genetic risk for NME might manifest neurological abnormalities before developing pathognomonic clinical signs of NME. ANIMALS: Thirty-six pug dogs less than 4 years of age asymptomatic for NME. METHODS: Prospective observational cohort study with germline genome-wide genotyping. Neurological examinations were performed 4 weeks apart to document reproducible findings of central nervous system disease. Magnetic resonance imaging, cerebrospinal fluid analysis, and testing for infectious diseases were performed in all pugs with reproducible abnormalities detected on neurological examination. RESULTS: The overall risk allele frequency in this cohort was 40%; 5 (14%) dogs were high risk, 19 (53%) dogs were medium risk, and 12 (33%) dogs were low genetic risk for NME. Reproducible abnormalities detected on neurological examination were identified in 8/24 (33%) genetically at-risk dogs and 0/12 (0%) low risk dogs. Clinical abnormalities included multifocal spinal pain in 8/8, reduced menace response in 5/8, and lateralizing postural reaction deficits in 5/8 pugs. There was a strong association between genotype risk and the presence of this clinical phenotype (P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Our findings suggest the presence of a novel early clinical phenotype of NME in apparently asymptomatic genetically at-risk pugs which might be used to plan early diagnostic and therapeutic clinical trials.

Prevalence and clinical features of thoracolumbar intervertebral disc-associated epidural hemorrhage in dogs.

BACKGROUND: Intervertebral disc-associated epidural hemorrhage (EH) in dogs is a poorly understood neurological condition. OBJECTIVE: To compare the clinical presentation, magnetic resonance imaging (MRI) changes, and clinical outcome of dogs with acute thoracolumbar intervertebral disc herniation (TL-IVDH) with and without EH. ANIMALS: One hundred sixty client-owned dogs that underwent MRI and hemilaminectomy for acute TL-IVDH at a private practice in Colorado, including 63 dogs with EH and 97 dogs without EH. METHODS: Retrospective review of medical record data from 160 dogs presenting sequentially to a single practice with acute TL-IVDH that underwent MRI and hemilaminectomy surgery. RESULTS: Sixty-three of 160 (39%) dogs had confirmed EH. French Bulldogs were significantly overrepresented (23/63; odds ratio [OR]: 4.1; 95% confidence interval [CI]: 1.8-9.0; P < .001) of the EH cases. Dogs with EH were more likely to present with clinical signs less than 48 hours than were dogs without EH (24-48 vs 48-72 hours; OR: 2.4; 95% CI: 1.2-4.6; P = .02) and were more likely to be nonambulatory on presentation (OR: 2.1; 95% CI: 1.0-4.1; P = .04). Dogs with EH were more likely to have <50% cross-sectional spinal cord compression than dogs without EH (OR: 2.3 vs. 0.4; 95% CI: 1.2-4.4 and 0.2-0.9, respectively), longer longitudinal spinal cord compression (3 spaces vs 1 space, P < .001), and greater intrinsic spinal cord change (grade 3/severe vs grade 1/mild; P < .001) based on MRI. The location of the intervertebral disc herniation in French Bulldogs with EH was more likely to be thoracolumbar (OR: 10.8; 95% CI: 2.1-55.7; P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: French Bulldogs have a high prevalence of intervertebral disc-associated EH. Dogs with EH have a shorter clinical course and are more likely to be nonambulatory on initial presentation.

Children With Medical Complexity in the Canadian Maritimes: Protocol for a Mixed Methods Study.

BACKGROUND: Ongoing developments in the medical field have improved survival rates and long-term management of children with complex chronic health conditions. While the number of children with medical complexity is small, they use a significant amount of health resources across various health settings and sectors. Research to date exploring this pediatric population has relied primarily on quantitative or qualitative data alone, leaving significant gaps in our understanding of this population. OBJECTIVE: The objective of this research is to use health administrative and family-reported data to gain an in-depth understanding of patterns of health resource use and health care needs of children with medical complexity and their families in the Canadian Maritimes. METHODS: An explanatory sequential mixed methods design will be used to achieve our research objective. Phase 1 of this research will leverage the use of health administrative data to examine the prevalence and health service use of children with medical complexity. Phase 2 will use case study methods to collect multiple sources of family-reported data to generate a greater understanding of their experiences, health resource use, and health care needs. Two cases will be developed in each of the 3 provinces. Cases will be developed through semistructured interviews with families and their health care providers and health resource journaling. Findings will be triangulated from phase 1 and 2 using a joint display table to visually depict the convergence and divergence between the quantitative and qualitative findings. This triangulation will result in a comprehensive and in-depth understanding into the population of children with medical complexity. RESULTS: This study will be completed in May 2022. Findings from each phase of the research and integration of the two will be reported in full in 2022. CONCLUSIONS: There is a current disconnect between the Canadian health care system and the needs of children with medical complexity and their families. By combining health administrative and family-reported data, this study will unveil critical information about children with medical complexity and their families to more efficiently and effectively meet their health care needs. Results from this research will be the first step in designing patient-oriented health policies and programs to improve the health care experiences, health system use, and health outcomes of children with medical complexity and their families. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/33426.

Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesions.

Comparative studies of naturally occurring canine cancers have provided new insight into many areas of cancer research. Development and validation of circulating tumor DNA (ctDNA) analysis in pet dogs can help address diagnostic needs in veterinary as well as human oncology. Dogs have high incidence of naturally occurring spontaneous cancers, demonstrate molecular heterogeneity and clonal evolution during therapy, allow serial sampling of blood from the same individuals during the course of disease progression, and have relatively compressed intervals for disease progression amenable to longitudinal studies. Here, we present a feasibility study of ctDNA analysis performed in 48 dogs including healthy dogs and dogs with either benign splenic lesions or malignant splenic tumors (hemangiosarcoma) using shallow whole genome sequencing (sWGS) of cell-free DNA. To enable detection and quantification of ctDNA using sWGS, we adapted two informatic approaches and compared their performance for the canine genome. At the time of initial clinical presentation, mean ctDNA fraction in dogs with malignant splenic tumors was 11.2%, significantly higher than dogs with benign lesions (3.2%; p = 0.001). ctDNA fraction was 14.3% and 9.0% in dogs with metastatic and localized disease, respectively (p = 0.227). In dogs treated with surgical resection of malignant tumors, mean ctDNA fraction decreased from 11.0% prior to resection to 7.9% post-resection (p = 0.047 for comparison of paired samples). Our results demonstrate that ctDNA analysis is feasible in dogs with hemangiosarcoma using a cost-effective approach such as sWGS. Additional studies are needed to validate these findings, and determine the role of ctDNA to assess burden of disease and treatment response in dogs with cancer.

Novel ECL Method for the Determination of Skatole in Porcine Adipose Tissue.

A new method for the determination of skatole present in porcine adipose tissue samples utilizing the electrochemiluminescence of skatole is presented. It has been observed that oxygen radicals produced at a high cathodic voltage can react with oxidized skatole to create an excited intermediate molecule that then relaxes, generating peak photon emission at around 480 nm. A strong electrochemiluminescence or electrogenerated chemiluminescence (ECL) signal using boron-doped diamond (BDD) electrodes was observed optimally when a reduction potential of -1.8 V was applied, held for 40 s, before holding an oxidation potential of 0.8 V for 10 s. Using this principle, a calibration curve using known concentrations of skatole showed good linearity (range 0.025-2 µM) and a very low detection limit (LOD, 0.7 nM). A method that demonstrates for the first time an approach that utilizes this ECL reaction, and has the potential to be developed into an analytical device for use in the slaughterhouse, has been developed. This was achieved by extracting skatole out of the porcine adipose tissues into acetonitrile - giving an extraction efficiency of 67.6%. This method was then validated by analyzing the skatole content of 33 pig fat samples that had been previously tested using a standard technique, high-performance liquid chromatography (HPLC), containing a range of concentrations (0.02-2.58 µg/g). This ECL method exhibited excellent reliability and correlation with HPLC, giving a R2 coefficient of 0.911, thus demonstrating the potential for this method to be developed for an on-line skatole detector.

Magnitude, Direction, Temporal Patterns, and Frequency of Loss of Distal Radius Fracture Reduction in Women 50 Years and Older.

PURPOSE: To determine the magnitude, direction, temporal patterns, and frequency of reduction loss following nonsurgical, closed treatment of distal radius fractures in women 50 years and older and correlate these observations with bone mineral density and age. METHODS: We reviewed registry data on 1,148 patients 50 years and older with distal radius fractures managed by closed reduction and cast immobilization. Radial inclination (RI), ulnar variance (UV), and radial tilt (RT) were measured immediately and at 1, 2, 3, 6, 9, and 12 weeks after reduction. Magnitude, direction, frequency, and patterns of change were compared at each time point and correlated with bone mineral density T-scores and age using paired t tests in a mixed effects model. RESULTS: Over 12 weeks, RI decreased by 3° ± 5°, the majority occurring in the first 2 weeks and significantly correlated with bone mineral density T-score and age. Unexpectedly, RI increased over time in 5% of patients. Ulnar variance increased by 2.3 ± 1.7 mm, the majority occurring in the first 3 weeks and correlated with age. Radial tilt changed by 7° ± 11° in those displacing dorsally and 8° ± 12° in those displacing volarly at 12 weeks, with the majority occurring in the first 3 weeks and significantly correlating with age. Ulnar variance and RT continued to change by small increments between weeks 3 and 6. Nearly 90% of our cohort experienced measurable loss of reduction and 50% changed at least 5° RI, 11° RT, and 2 mm UV. CONCLUSIONS: Most distal radius fracture managed with closed reduction and casting have some loss of reduction, the majority occurring in the first 3 weeks and correlated with increased age and osteoporosis. This guides clinicians in informing patients about expected reduction loss, frequency of clinical and radiographic follow-up, and timing of discussions regarding the need for surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.