Seizures due to pyridoxine deficiency in Parkinson's disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized not only by its hallmark motor symptoms but also by a myriad of non-motor manifestations, including cognitive decline, autonomic manifestations, and gastrointestinal disturbances. Amidst these, a lesser-known but critical aspect is the increased risk of functional deficiency of pyridoxine (vitamin B6) in patients with PD, which is linked to an increased risk of seizures. This review investigates the intersection of PD, new-onset seizures, and pyridoxine deficiency, aiming to elucidate the significance of these associations and their contributions to the neurologic burden in PD. Case reports documenting the occurrence of seizures in patients with PD, particularly in the context of high-dose dopaminergic therapy and the subsequent revelation of pyridoxine deficiency were included. These cases, which often featured extensive workups revealing unremarkable findings aside from pyridoxine deficiency, underscore the multifaceted nature of PD and its treatment-related complications. The findings in these case reports suggest that dietary insufficiencies, gastrointestinal dysfunctions, and drug-nutrient interactions may eventually precipitate pyridoxine deficiency, which in turn may lead to seizures by disrupting GABAergic neurotransmission. This sheds the light on the need for increased clinical awareness and routine monitoring of pyridoxine levels in patients with PD, especially those undergoing significant therapeutic adjustments or exhibiting comorbidities that might interfere with their dietary intake such as gastrointestinal manifestations or depression. Such proactive measures could potentially mitigate the impact of this complication in patients with PD, ultimately enhancing patient care and quality of life.

"Everybody is impacted. Everybody's hurting": Grief, loss and the emotional impacts of overdose on harm reduction workers.

BACKGROUND: The emotional impacts of witnessing and responding to overdose and overdose-related deaths have been largely overlooked during the drug toxicity overdose crisis in North America. Scarce research has analyzed these impacts on the health and well-being of harm reduction workers, and the broader determinants of harm reduction work. Our study investigates the experiences and impacts of witnessing and responding to frequent and escalating rates of overdose on harm reduction workers in Toronto, Canada. METHODS: Using semi-structured interviews, 11 harm reduction workers recruited from harm reduction programs with supervised consumption services in Toronto, Canada, explored experiences with and reactions to overdose in both their professional and personal lives. They also provided insights on supports necessary to help people cope with overdose-related loss. We used thematic analysis to develop an initial coding framework, subsequent iterations of codes and emergent themes. RESULTS: Results revealed that harm reductions workers experienced physical, emotional, and social effects from overdose-related loss and grief. While some effects were due to the toll of overdose response and grief from overdose-related losses, they were exacerbated by the lack of political response to the scale of the drug toxicity overdose crisis and the broader socio-economic-political environment of chronic underfunding for harm reduction services. Harm reduction workers described the lack of appropriate workplace supports for trauma from repeated overdose response and overdose-related loss, alongside non-standard work arrangements that resulted in a lack of adequate compensation or access to benefits. CONCLUSIONS: Our study highlights opportunities for organizational practices that better support harm reduction workers, including formal emotional supports and community-based supportive care services. Improvement to the socio-economic-political determinants of work such as adequate compensation and access to full benefit packages are also needed in the harm reduction sector for all workers.

Trends in opioid toxicities among people with and without opioid use disorder and the impact of the COVID-19 pandemic in Ontario, Canada: A population-based analysis.

BACKGROUND: Across Canada, the COVID-19 pandemic occurred amidst an ongoing drug toxicity crisis. Although elevated rates of substance-related harms have been observed nationally, it remains unknown if the pandemic state of emergency led to disproportionate increases in opioid toxicities among people with opioid use disorder (OUD) compared to those without. METHODS: We conducted a population-based repeated cross-sectional time series analysis of fatal and non-fatal opioid toxicities between January 1, 2014, and December 31, 2021, in Ontario, Canada. We used interventional autoregressive integrated moving average models to examine the impact of the pandemic on monthly rates of opioid toxicities per 100,000 Ontario residents stratified by people with and without OUD. RESULTS: We identified 80,296 opioid toxicities of which 53.5 % occurred among people with OUD. Among 52,052 unique individuals, 60.5 % were male and 46.2 % were 25-44 years old. Between January 2014 and December 2021, the rate of opioid toxicities increased from 2.6 to 10.5 per 100,000 (rate ratio [RR]=4.07). The magnitude of this increase differed among people with OUD (0.8 to 7.4 per 100,000; RR=9.35) and without OUD (1.8 to 3.1 per 100,000; RR=1.74). We observed a significant ramp increase in the overall rate of opioid toxicities following the declaration of the pandemic emergency in March 2020 (+0.19 per 100,000 monthly, 95 % CI: 0.029, 0.36, p = 0.021). In a stratified analysis, we found a similar ramp increase among people with OUD (+0.19 per 100,000 monthly, 95 % CI: 0.10, 0.28, p < 0.001); however, this was not observed among people without OUD (p = 0.95). CONCLUSIONS: The rate of opioid toxicities accelerated across Ontario following the pandemic-related state of emergency, with the majority of this increase among people with OUD. The important differences observed among people with OUD compared with those without, highlights the critical need for improved access to harm reduction and treatment interventions among this population.

Validation of case-ascertainment algorithms using health administrative data to identify people who inject drugs in Ontario, Canada.

OBJECTIVES: Health administrative data can be used to improve the health of people who inject drugs by informing public health surveillance and program planning, monitoring, and evaluation. However, methodological gaps in the use of these data persist due to challenges in accurately identifying injection drug use (IDU) at the population level. In this study, we validated case-ascertainment algorithms for identifying people who inject drugs using health administrative data in Ontario, Canada. STUDY DESIGN AND SETTING: Data from cohorts of people with recent (past 12 months) IDU, including those participating in community-based research studies or seeking drug treatment, were linked to health administrative data in Ontario from 1992 to 2020. We assessed the validity of algorithms to identify IDU over varying look-back periods (ie, all years of data [1992 onwards] or within the past 1-5 years), including inpatient and outpatient physician billing claims for drug use, emergency department (ED) visits or hospitalizations for drug use or injection-related infections, and opioid agonist treatment (OAT). RESULTS: Algorithms were validated using data from 15,241 people with recent IDU (918 in community cohorts and 14,323 seeking drug treatment). An algorithm consisting of ≥1 physician visit, ED visit, or hospitalization for drug use, or OAT record could effectively identify IDU history (91.6% sensitivity and 94.2% specificity) and recent IDU (using 3-year look back: 80.4% sensitivity, 99% specificity) among community cohorts. Algorithms were generally more sensitive among people who inject drugs seeking drug treatment. CONCLUSION: Validated algorithms using health administrative data performed well in identifying people who inject drugs. Despite their high sensitivity and specificity, the positive predictive value of these algorithms will vary depending on the underlying prevalence of IDU in the population in which they are applied.

Nasal Glial Hamartoma: A New Type of Sinonasal Hamartomas.

Hamartomas are rare, tumour-forming, benign lesions that have been reported throughout the body that can resemble other malignant entities. Hamartoma subtypes can be distinguished based on their histological features. Sinonasal hamartomas may have presenting symptoms and radiological features that mimic other nasal neoplastic lesions. Therefore, it is essential to diagnose it accurately, as the treatment approaches can range from radical surgeries in malignant cases to a simple excision in hamartoma. In this paper, we report a novel case of sinonasal hamartoma, which demonstrates an unprecedented histological feature of glial tissue with astrocyte-like cells. Furthermore, we present the unconventional presenting symptoms and radiological features seen in this case that mimic the behaviours of nasal inverted papilloma (IP) lesions, thereby highlighting the need for careful investigation of such patients in order to distinguish both glial hamartoma and IP lesions. Concluding that identification of glial hamartoma as a new subtype of sinonasal hamartoma is crucial, as mistaking it for other lesions may subject patients to overly aggressive treatment and potential unnecessary harm.

Overdose mortality incidence and supervised consumption services in Toronto, Canada: an ecological study and spatial analysis.

BACKGROUND: Supervised consumption services (SCS) prevent overdose deaths onsite; however, less is known about their effect on population-level overdose mortality. We aimed to characterise overdose mortality in Toronto, ON, Canada, and to establish the spatial association between SCS locations and overdose mortality events. METHODS: For this ecological study and spatial analysis, we compared crude overdose mortality rates before and after the implementation of nine SCS in Toronto in 2017. Data were obtained from the Office of the Chief Coroner of Ontario on cases of accidental death within the City of Toronto for which the cause of death involved the use of an opiate, synthetic or semi-synthetic opioid, or other psychoactive substance. We assessed overdose incident data for global spatial autocorrelation and local clustering, then used geographically weighted regression to model the association between SCS proximity and overdose mortality incidence in 2018 and 2019. FINDINGS: We included 787 overdose mortality events in Toronto between May 1, 2017, and Dec 31, 2019. The overdose mortality rate decreased significantly in neighbourhoods that implemented SCS (8·10 deaths per 100 000 people for May 1-July 31, 2017, vs 2·70 deaths per 100 000 people for May 1-July 31, 2019; p=0·037), but not in other neighbourhoods. In a geographically weighted regression analysis that adjusted for the availability of substance-use-related services and overdose-related sociodemographic factors by neighbourhood, the strongest local regression coefficients of the association between SCS and overdose mortality location ranged from -0·60 to -0·64 per mile in 2018 and from -1·68 to -1·96 per mile in 2019, suggesting an inverse association. INTERPRETATION: We found that the period during which SCS were implemented in Toronto was associated with a reduced overdose mortality in surrounding neighbourhoods. The magnitude of this inverse association increased from 2018 to 2019, equalling approximately two overdose fatalities per 100 000 people averted in the square mile surrounding SCS in 2019. Policy makers should consider implementing and sustaining SCS across neighbourhoods where overdose mortality is high. FUNDING: The Canadian Institutes of Health Research.

Economic Evaluations of Establishing Opioid Overdose Prevention Centers in 12 North American Cities: A Systematic Review.

OBJECTIVES: Overdose prevention centers (OPCs) provide a safe place where people can consume preobtained drugs under supervision so that a life-saving medical response can be provided quickly in the event of an overdose. OPCs are programs that are established in Canada and have recently become legally sanctioned in only a few United States jurisdictions. METHODS: We conducted a systematic review that summarizes and identifies gaps of economic evidence on establishing OPCs in North America to guide future expansion of OPCs. RESULTS: We included 16 final studies that were evaluated with the Consolidated Health Economic Evaluation Reporting Standards and Drummond checklists. Eight studies reported cost-effectiveness results (eg, cost per overdose avoided or cost per quality-adjusted life-year), with 6 also including cost-benefit; 5 reported only cost-benefit results, and 3 cost offsets. Health outcomes primarily included overdose mortality outcomes or HIV/hepatitis C virus infections averted. Most studies used mathematical modeling and projected OPC outcomes using the experience of a single facility in Vancouver, BC. CONCLUSIONS: OPCs were found to be cost-saving or to have favorable cost-effectiveness or cost-benefit ratios across all studies. Future studies should incorporate the experience of OPCs established in various settings and use a greater diversity of modeling designs.

How to improve initial diagnostic accuracy of kidney tumours in childhood?-A non-invasive approach.

Non-invasive differentiation of paediatric kidney tumours is particularly important in the SIOP-RTSG protocols, which recommend pre-operative chemotherapy without histological confirmation. The identification of clinical and tumour-related parameters may enhance diagnostic accuracy. Age, metastases, and tumour volume (TV) were retrospectively analysed in 3306 patients enrolled in SIOP/GPOH 9, 93-01, and 2001 including Wilms tumour (WT), congenital mesoblastic nephroma (CMN), clear cell sarcoma (CCSK), malignant rhabdoid tumour of the kidney (MRTK), and renal cell carcinoma (RCC). WT was diagnosed in 2927 (88.5%) patients followed by CMN 138 (4.2%), CCSK 126 (3.8%), MRTK 58 (1.8%) and RCC 57 (1.7%). CMN, the most common localized tumour (71.6%) in patients younger than 3 months of age, was diagnosed earliest and RCC the latest (median age [months]: 0 and 154, respectively) both associated with significantly smaller TV (median TV [mL]: 67.2 and 45.0, respectively). RCC occurred in >14% of patients older than 120 months or older than 84 months with TV <100 mL. Receiver operating characteristic analyses discriminated WT from CMN, RCC and MRTK regarding age (AUC = 0.976, 0.929 and 0.791) and TV (AUC = 0.768, 0.813 and 0.622). MRTK had the highest risk of metastasis (37.9%) despite young age, whereas the risk of metastasis increased significantly with age in WT. Age and TV at diagnosis can differentiate WT from CMN and RCC. MRTK must be considered for metastatic tumours at young age. Identification of CCSK without histology remains challenging. Combined with MRI-characteristics, including diffusion-weighted imaging, and radiomics and liquid biopsies in the future, our approach allows optimization of biopsy recommendations and prevention of misdiagnosis-based neoadjuvant treatment.

Episodic disability questionnaire (EDQ) measurement properties among adults living with HIV in Canada, Ireland, United Kingdom, and United States.

BACKGROUND: The Episodic Disability Questionnaire (EDQ) is a generic 35-item patient-reported outcome measure of presence, severity and episodic nature of disability. We assessed the measurement properties of the Episodic Disability Questionnaire (EDQ) with adults living with HIV. METHODS: We conducted a measurement study with adults living with HIV in eight clinical settings in Canada, Ireland, United Kingdom, and United States. We electronically administered the EDQ followed by three reference measures (World Health Organization Disability Assessment Schedule; Patient Health Questionnaire; Social Support Scale) and a demographic questionnaire. We administered the EDQ only 1 week later. We assessed the internal consistency reliability (Cronbach's alpha; > 0.7 acceptable), and test-retest reliability (Intra Class Correlation Coefficient; > 0.7 acceptable). We estimated required change in EDQ domain scores to be 95% certain that a change was not due to measurement error (Minimum Detectable Change (MDC95%)). We evaluated construct validity by assessing 36 primary hypotheses of relationships between EDQ scores and scores on the reference measures (> 75% hypotheses confirmed indicated validity). RESULTS: Three hundred fifty nine participants completed the questionnaires at time point 1, of which 321 (89%) completed the EDQ approximately 1 week later. Cronbach's alpha for internal consistency ranged from 0.84 (social domain) to 0.91 (day domain) for the EDQ severity scale, and 0.72 (uncertainty domain) to 0.88 (day domain) for the EDQ presence scale, and 0.87 (physical, cognitive, mental-emotional domains) to 0.89 (uncertainty domain) for the EDQ episodic scale. ICCs for test-retest reliability ranged from 0.79 (physical domain) to 0.88 (day domain) for the EDQ severity scale and from 0.71 (uncertainty domain) to 0.85 (day domain) for the EDQ presence scale. Highest precision was demonstrated in the severity scale for each domain (MDC95% range: 19-25 out of 100), followed by the presence (MDC95% range: 37-54) and episodic scales (MDC95% range:44-76). Twenty-nine of 36 (81%) construct validity hypotheses were confirmed. CONCLUSIONS: The EDQ possesses internal consistency reliability, construct validity, and test-retest reliability, with limited precision when administered electronically with adults living with HIV across in clinical settings in four countries. Given the measurement properties, the EDQ can be used for group level comparisons for research and program evaluation in adults living with HIV.

Substance use care innovations during COVID-19: barriers and facilitators to the provision of safer supply at a toronto COVID-19 isolation and recovery site.

BACKGROUND: Early in the COVID-19 pandemic, there was an urgent need to establish isolation spaces for people experiencing homelessness who were exposed to or had COVID-19. In response, community agencies and the City of Toronto opened COVID-19 isolation and recovery sites (CIRS) in March 2020. We sought to examine the provision of comprehensive substance use services offered to clients on-site to facilitate isolation, particularly the uptake of safer supply prescribing (prescription of pharmaceutical opioids and/or stimulants) as part of a spectrum of comprehensive harm reduction and addiction treatment interventions. METHODS: We conducted in-depth, semi-structured interviews with 25 clients and 25 staff (including peer, harm reduction, nursing and medical team members) from the CIRS in April-July 2021. Iterative and thematic analytic methods were used to identify key themes that emerged in the interview discussions. RESULTS: At the time of implementation of the CIRS, the provision of a safer supply of opioids and stimulants was a novel and somewhat controversial practice. Prescribed safer supply was integrated to address the high risk of overdose among clients needing to isolate due to COVID-19. The impact of responding to on-site overdoses and presence of harm reduction and peer teams helped clinical staff overcome hesitation to prescribing safer supply. Site-specific clinical guidance and substance use specialist consults were crucial tools in building capacity to provide safer supply. Staff members had varied perspectives on what constitutes 'evidence-based' practice in a rapidly changing, crisis situation. CONCLUSION: The urgency involved in intervening during a crisis enabled the adoption of prescribed safer supply, meeting the needs of people who use substances and assisting them to complete isolation periods, while also expanding what constitutes acceptable goals in the care of people who use drugs to include harm reduction approaches.

The multiple makings of a supervised consumption service in a hospital setting.

BACKGROUND: Whereas supervised consumption services (SCSs) are common in many community settings, they are seldomly found in acute care hospitals. As hospitals present unique circumstances that can shape the impacts of an SCS, careful consideration of local implementation contexts and practices is required. We explored the pre-implementation stage of an SCS, to examine how an SCS is made and made differently in relation to the material-discursive context of the hospital. METHODS: We conducted 11 focus groups with 83 staff and clinicians at an inner-city hospital in Toronto, Canada. Data analysis followed principles of grounded theory and was informed by an 'evidence making interventions' framework. RESULTS: While most participants indicated they would support the establishment of an SCS at the hospital, multiple enactments of an SCS emerged. An SCS was enacted: as a means to reduce drug-related risks for all people who use drugs, as an opportunity to intervene on patients' drug use, as a means to centralize drug use, and as a transformative intervention for the hospital. In our findings, harm reduction, abstinence, security, and risk mitigation goals existed closely together, yielding overlaying realities. CONCLUSION: Our findings revealed various enactments of an SCS, some of which are likely to negatively affect people who use drugs and service access. As more hospitals consider the implementation of an SCS, understanding how an SCS is made in practice will be key to building a service that focuses on the needs of people who use drugs.

Tissue formation and host remodeling of an elastomeric biodegradable scaffold in an ovine pulmonary leaflet replacement model.

In pursuit of a suitable scaffold material for cardiac valve tissue engineering applications, an acellular, electrospun, biodegradable polyester carbonate urethane urea (PECUU) scaffold was evaluated as a pulmonary valve leaflet replacement in vivo. In sheep (n = 8), a single pulmonary valve leaflet was replaced with a PECUU leaflet and followed for 1, 6, and 12 weeks. Implanted leaflet function was assessed in vivo by echocardiography. Explanted samples were studied for gross pathology, microscopic changes in the extracellular matrix, host cellular re-population, and immune responses, and for biomechanical properties. PECUU leaflets showed normal leaflet motion at implant, but decreased leaflet motion and dimensions at 6 weeks. The leaflets accumulated α-SMA and CD45 positive cells, with surfaces covered with endothelial cells (CD31+). New collagen formation occurred (Picrosirius Red). Accumulated tissue thickness correlated with the decrease in leaflet motion. The PECUU scaffolds had histologic evidence of scaffold degradation and an accumulation of pro-inflammatory/M1 and anti-inflammatory/M2 macrophages over time in vivo. The extent of inflammatory cell accumulation correlated with tissue formation and polymer degradation but was also associated with leaflet thickening and decreased leaflet motion. Future studies should explore pre-implant seeding of polymer scaffolds, more advanced polymer fabrication methods able to more closely approximate native tissue structure and function, and other techniques to control and balance the degradation of biomaterials and new tissue formation by modulation of the host immune response.

The Financial Burden Associated With Conservatively Managed Epistaxis.

AIM: Each year, approximately 25,000 patients present to NHS hospitals in the UK with epistaxis. This study aims to investigate the financial implications of epistaxis, focusing on cases managed conservatively. Specifically, the research explores the average cost of hospital bed stays, the length of hospitalization, and the impact of blood thinners on healthcare expenses.  Methods: A retrospective study spanning June 2022 to June 2023 collected data from electronic health records at our local district general hospital. Patients meeting inclusion criteria were analyzed for demographic information, duration of hospital stay, use of blood thinners, and outcomes. Statistical software (SAS and Excel) was used for data analysis. RESULTS: Out of 126 patients, conservatively managed epistaxis cases (n = 119) had an average age of 73.9 years, with 53.6% males. The mortality rate was 4.5%. The average hospital stay was 2.92 days. Approximately 57% of patients were taking blood thinners. The average cost of a hospital bed stay for epistaxis patients was £1,712.84, with a £259.69 difference between those on blood thinners and those not. CONCLUSION: Epistaxis imposes a significant financial burden on hospitals, with conservatively managed cases incurring substantial costs. Recognizing and addressing the financial implications of epistaxis is essential for healthcare providers and policymakers. Investment in preventative medicine and patient education can potentially reduce the incidence of epistaxis and alleviate the financial burden on healthcare systems.

Glandular Fever Testing in Patients Presenting With Tonsillitis: A Retrospective Study.

BACKGROUND: Tonsillitis, the inflammation of the palatine tonsils, typically arises from infections and predominantly affects children of primary school age. Most cases stem from viral or bacterial infections. Glandular fever, a subtype, is primarily caused by the Epstein-Barr virus (EBV). This specific type of tonsillitis can lead to severe complications, including splenic rupture, encephalitis, chronic fatigue, and acute acalculous cholecystitis. As a result, early identification is vital to establish proper safety measures and prevent the onset of these potentially dangerous complications in patients. OBJECTIVES: This study aims to determine the number of missed glandular fever cases diagnosed as simple tonsillitis and raises considerations in managing these patients. METHODS: A 12-month retrospective single-centre cohort study was carried out in Lincoln County Hospital, Lincoln, England. A total of 185 patients diagnosed with tonsillitis were included, along with their presenting symptoms and investigations, including liver blood tests and glandular fever screening. RESULTS: Among the 185 patients, averaging 26 years old, 112 were screened for EBV infection, revealing 35 positive cases (31.3%). Notably, 74% of these positive cases (26 out of 35) displayed abnormal liver function test results. CONCLUSION: Applying the percentage of EBV-positive cases to the 73 unscreened patients results in a likelihood of 23 missed cases of EBV infection. These form 12% of the study group, indicating a significant potential missed number of cases. Given the associated risks and complications with EBV, we note the importance of screening to identify cases and apply relevant considerations in their management.

Initiation of opioid agonist therapy after hospital visits for opioid poisonings in Ontario.

BACKGROUND: Emergency department visits and hospital admissions for opioid toxicity are opportunities to initiate opioid agonist therapy (OAT), which reduces morbidity and mortality in patients with opioid use disorder (OUD). The study objectives were to evaluate OAT initiation rates after a hospital encounter for opioid toxicity in Ontario, Canada, and determine whether publication of a 2018 Canadian OUD management guideline was associated with increased initiation. METHODS: We conducted a retrospective, population-based serial cross-sectional study of hospital encounters for opioid toxicity among patients with OUD between Jan. 1, 2013, and Mar. 31, 2020, in Ontario, Canada. The primary outcome was OAT initiation (methadone, buprenorphine-naloxone, or slow-release oral morphine) within 7 days of discharge, measured quarterly. We examined the impact of the release of the OUD management guideline on OAT initiation rates using Autoregressive Integrated Moving Average models. RESULTS: Among 20 702 hospital visits for opioid toxicity among patients with OUD, the median age was 35 years, and 65.1% were male. Over the study period, the percentage of visits leading to OAT initiation within 7 days rose from 1.7% or less (Q1 2013) to 5.6% (Q1 2020); however, the publication of the Canadian OUD management guideline was not associated with a significant increase in these rates (0.14% slope change, 95% confidence interval -0.11% to 0.38%; p = 0.3). INTERPRETATION: Among hospital encounters for opioid toxicity, despite rising prevalence over time, only 1 in 18 patients were dispensed OAT within a week of discharge in early 2020. These findings highlight missed opportunities to initiate therapies proven to reduce mortality in patients with OUD.

Initiations of safer supply hydromorphone increased during the COVID-19 pandemic in Ontario: An interrupted time series analysis.

AIMS: Calls to prescribe safer supply hydromorphone (SSHM) as an alternative to the toxic drug supply increased during the COVID-19 pandemic but it is unknown whether prescribing behaviour was altered. We aimed to evaluate how the number of new SSHM dispensations changed during the pandemic in Ontario. METHODS: We conducted a retrospective interrupted time-series analysis using provincial administrative databases. We counted new SSHM dispensations in successive 28-day periods from March 22, 2016 to August 30, 2021. We used segmented Poisson regression methods to test for both a change in level and trend of new dispensations before and after March 17, 2020, the date Ontario's pandemic-related emergency was declared. We adjusted the models to account for seasonality and assessed for over-dispersion and residual autocorrelation. We used counterfactual analysis methods to estimate the number of new dispensations attributable to the pandemic. RESULTS: We identified 1489 new SSHM dispensations during the study period (434 [mean of 8 per 28-day period] before and 1055 [mean of 56 per 28-day period] during the pandemic). Median age of individuals initiating SSHM was 40 (interquartile interval 33-48) with 61.7% (N = 919) male sex. Before the pandemic, there was a small trend of increased prescribing (incidence rate ratio [IRR] per period 1.002; 95% confidence interval [95CI] 1.001-1.002; p<0.001), with a change in level (immediate increase) at the pandemic date (relative increase in IRR 1.674; 95CI 1.206-2.322; p = 0.002). The trend during the pandemic was not statistically significant (relative increase in IRR 1.000; 95CI 1.000-1.001; p = 0.251). We estimated 511 (95CI 327-695) new dispensations would not have occurred without the pandemic. CONCLUSION: The pandemic led to an abrupt increase in SSHM prescribing in Ontario, although the rate of increase was similar before and during the pandemic. The absolute number of individuals who accessed SSHM remained low throughout the pandemic.

Identifying the white matter pathways involved in multiple sclerosis-related tremor using diffusion tensor imaging.

Background: Tremor affects up to 45% of patients with Multiple Sclerosis (PwMS). Current understanding is based on insights from other neurological disorders, thus, not fully addressing the distinctive aspects of MS pathology. Objective: To characterize the brain white matter (WM) correlates of MS-related tremor using diffusion tensor imaging (DTI). Methods: In a prospective case-control study, PwMS with tremor were assessed for tremor severity and underwent MRI scans including DTI. PwMS without tremor served as matched controls. After tract selection and segmentation, the resulting diffusivity measures were used to calculate group differences and correlations with tremor severity. Results: This study included 72 PwMS. The tremor group (n = 36) exhibited significant changes in several pathways, notably in the right inferior longitudinal fasciculus (Cohen's d = 1.53, q < 0.001) and left corticospinal tract (d = 1.32, q < 0.001), compared to controls (n = 36). Furthermore, specific tracts showed a significant correlation with tremor severity, notably in the left medial lemniscus (Spearman's coefficient [rsp] = -0.56, p < 0.001), and forceps minor of corpus callosum (rsp = -0.45, p < 0.01). Conclusion: MS-related tremor is associated with widespread diffusivity changes in WM pathways and its severity correlates with commissural and sensory projection pathways, which suggests a role for proprioception or involvement of the dentato-rubro-olivary circuit.

c-Kit Receptors as a Therapeutic Target in Cancer: Current Insights.

c-Kit is a type III receptor tyrosine kinase (RTK) that has an essential role in various biological functions including gametogenesis, melanogenesis, hematopoiesis, cell survival, and apoptosis. c-KIT aberrations, either overexpression or loss-of-function mutations, have been implicated in the pathogenesis and development of many cancers, including gastrointestinal stromal tumors, mastocytosis, acute myeloid leukemia, breast, thyroid, and colorectal cancer, making c-KIT an attractive molecular target for the treatment of cancers. Therefore, a lot of effort has been put into investigating the utility of tyrosine kinase inhibitors for the management of c-KIT mutated tumors. This review of the literature illustrates the role of c-KIT mutations in many cancers, aiming to provide insights into the role of TKIs as a therapeutic option for cancer patients with c-KIT aberrations. In conclusion, c-KIT is implicated in different types of cancer, and it could be a successful molecular target; however, proper detection of the underlying mutation type is required before starting the appropriate personalized therapy.

Modeling as Visioning: Exploring the Impact of Criminal Justice Reform on Health of Populations with Substance Use Disorders.

In the context of historic reckoning with the role of the criminal-legal system as a structural driver of health harms, there is mounting evidence that punitive drug policies have failed to prevent problematic drug use while fueling societal harms. In this explainer article, we discuss how simulation modeling provides a methodological framework to explore the potential outcomes (beneficial and harmful) of various drug policy alternatives, from incremental to radical. We discuss potential simulation modeling opportunities while calling for a more active role of simulation modeling in visioning and operationalizing transformative change. Highlights: This article discusses opportunities for simulation modeling in projecting health and economic impacts (beneficial and harmful) of drug-related criminal justice reforms.We call on modelers to explore radical interventions to reduce drug-related harm and model grand alternative futures in addition to more probable scenarios, with a goal of opening up policy discourse to these options.

Client experiences using a new supervised consumption service in Sudbury, Ontario: A qualitative study.

Overdoses are increasing in the province of Ontario, Canada, where northern communities such as Sudbury have witnessed disproportionately elevated rates, with opioid-related deaths double that of the provincial average. To address this issue, governments have implemented supervised consumption services (SCS) where people who use drugs (PWUD) can use their pre-obtained substances onsite under trained supervision. In September 2022, the city of Sudbury opened its first SCS, 'The Spot', but the site's sustainability is contingent on demonstrating benefit to PWUD and the neighboring community. We undertook a qualitative study exploring experiences among clients who used the consumption service inside The Spot. In December 2022, clients of The Spot were invited to participate in a brief survey which collected socio-demographic information and substance use profiles, followed by an in-person semi-structured qualitative interview. Participant survey and interview data were combined with administrative site utilization data provided by site staff of all clients who accessed the consumption service from September 2022 to August 2023 to examine overall service utilization and uptake. Qualitative data were analyzed using iterative thematic analysis techniques, and results were informed by common responses to research questions. The responses were narratively presented. Administrative site utilization data highlighted a relatively stable increase in uptake and utilization of the site since its inception. A total of 20 clients participated in the survey and semi-structured interviews. Participants described the importance of the site in preventing and responding to overdoses, providing a safe and comfortable environment to consume their drugs, and decreasing public drug use, which they suggested may potentially reduce stigmatization in the community. However, clients also suggested challenges, including issues regarding site operational policies that hindered consumption room utilization. Service suggestions made by clients to improve site utilization include the addition of inhalation services, relocating the site to a location in downtown Sudbury where PWUD commonly congregate, and extending operational hours. Positive impacts and recommendations can be drawn on and considered by other northern or rural communities interested in implementing similar harm reduction services.