Amphetamine-Related Emergency Department Visits in Ontario, Canada, 2003-2020.

OBJECTIVES: Despite unregulated amphetamine use increasing, there are limited data on related emergency department (ED) visits in Canada. Our primary objective was to examine trends in amphetamine-related ED visits over time in Ontario, including by age and sex. Secondary objectives were to examine whether patient characteristics were associated with ED revisit within 6 months. METHODS: Using administrative claims and census data, we calculated annual patient- and encounter-based rates of amphetamine-related ED visits from 2003 to 2020 among individuals 18+ years of age. We also performed a retrospective cohort study of individuals with amphetamine-related ED visits between 2019 and 2020 to determine whether select factors were associated with ED revisit within 6 months. Multivariable logistic regression modelling was used to measure associations. RESULTS: The population-based rate of amphetamine-related ED visits increased nearly 15-fold between 2003 (1.9/100,000 Ontarians) and 2020 (27.9/100,000 Ontarians). Seventy-five percent of individuals returned to the ED for any reason within 6 months. Psychosis and use of other substances were both independently associated with ED revisit for any reason within 6 months (psychosis: AOR = 1.54, 95% CI = 1.30-1.83; other substances: AOR = 1.84, 95% CI = 1.57-2.15), whereas having a primary care physician was negatively associated with ED revisit (AOR = 0.77, 95% CI = 0.60-0.98). CONCLUSIONS: Increasing rates of amphetamine-related ED visits in Ontario are cause for concern. Diagnoses of psychosis and the use of other substances may serve to identify individuals who are most likely to benefit from both primary and substance-specific care.

Amphetamine-related care in the USA, 2003-2014: cross-sectional analyses examining inpatient trends and factors associated with hospitalisation outcomes.

OBJECTIVES: Although amphetamine use is a growing health problem in the USA, there are limited data on amphetamine-related hospitalisations. The primary objective of our study was to examine trends in amphetamine-related hospitalisations in the USA between 2003 and 2014, including by age and sex. Our secondary objectives were to examine whether demographic, clinical and care setting characteristics were associated with select outcomes of amphetamine-related hospitalisations, including in-hospital mortality, prolonged length of stay and leaving against medical advice. DESIGN, SETTING AND PARTICIPANTS: Using the 2003-2014 National Inpatient Sample, we estimated the rate of amphetamine-related hospitalisations for each year in the USA among individuals 18+ years of age, stratified by age and sex. Subgroup analyses examined hospitalisations due to amphetamine causes. Unconditional logistic regression modelling was used to estimate the adjusted odds of admission outcomes for sociodemographic, clinical and hospital indicators. PRIMARY AND SECONDARY OUTCOMES: Our primary outcome was amphetamine-related hospitalisations between 2003 and 2014; secondary outcomes included in-hospital mortality, prolonged length of stay and leaving against medical advice. RESULTS: Amphetamine-related hospitalisation rates increased from 27 to 69 per 100 000 population between 2003 and 2014. Annual rates were consistently greater among younger (18-44 years) individuals and men. Regional differences were observed, with admission to Western hospitals being associated with increased mortality (adjusted OR, AOR 5.07, 95% CI 1.22 to 21.04) and shorter (0-2 days) lengths of stay (AOR 0.70, 95% CI 0.58 to 0.83) compared with Northeast admissions. Males (AOR 1.26, 95% CI 1.15 to 1.38; compared with females) and self-pay (AOR 2.30, 95% CI 1.90 to 2.79; compared with private insurance) were associated with leaving against medical advice. CONCLUSIONS: Increasing rates of amphetamine-related hospitalisation risk being overshadowed by other public health crises. Regional amphetamine interventions may offer the greatest population health benefits. Future studies should examine long-term outcomes among patients hospitalised for amphetamine-related causes.

Survival and Health Care Use After Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVES: To compare long-term survival of Parkinson's disease (PD) patients with deep brain stimulation (DBS) to matched controls, and examine whether DBS was associated with differences in injurious falls, long-term care, and home care. METHODS: Using administrative health data (Ontario, Canada), we examined DBS outcomes within a cohort of individuals diagnosed with PD between 1997 and 2012. Patients receiving DBS were matched with non-DBS controls by age, sex, PD diagnosis date, time with PD, and a propensity score. Survival between groups was compared using the log-rank test and marginal Cox proportional hazards regression. Cumulative incidence function curves and marginal subdistribution hazard models were used to assess effects of DBS on falls, long-term care admission, and home care use, with death as a competing risk. RESULTS: There were 260 DBS recipients matched with 551 controls. Patients undergoing DBS did not experience a significant survival advantage compared to controls (log-rank test p = 0.50; HR: 0.89, 95% CI: 0.65-1.22). Among patients <65 years of age, DBS recipients had a significantly reduced risk of death (HR: 0.49, 95% CI: 0.28-0.84). Patients receiving DBS were more likely than controls to receive care for falls (HR: 1.56, 95% CI: 1.19-2.05) and home care (HR: 1.59, 95% CI: 1.32-1.90), while long-term care admission was similar between groups. CONCLUSIONS: Receiving DBS may increase survival for younger PD patients who undergo DBS. Future studies should examine whether survival benefits may be attributed to effects on PD or the absence of comorbidities that influence mortality.

Disparities in Deep Brain Stimulation Use for Parkinson's Disease in Ontario, Canada.

OBJECTIVE: To examine whether sociodemographic characteristics and health care utilization are associated with receiving deep brain stimulation (DBS) surgery for Parkinson's disease (PD) in Ontario, Canada. METHODS: Using health administrative data, we identified a cohort of individuals aged 40 years or older diagnosed with incident PD between 1995 and 2009. A case-control study was used to examine whether select factors were associated with DBS for PD. Patients were classified as cases if they underwent DBS surgery at any point 1-year after cohort entry until December 31, 2016. Conditional logistic regression modeling was used to estimate the adjusted odds of DBS surgery for sociodemographic and health care utilization indicators. RESULTS: A total of 46,237 individuals with PD were identified, with 543 (1.2%) receiving DBS surgery. Individuals residing in northern Ontario were more likely than southern patients to receive DBS surgery [adjusted odds ratio (AOR) = 2.23, 95% confidence interval (CI) = 1.15-4.34]; however, regional variations were not observed after accounting for medication use among older adults (AOR = 1.04, 95% CI = 0.26-4.21). Patients living in neighborhoods with the highest concentration of visible minorities were less likely to receive DBS surgery compared to patients living in predominantly white neighborhoods (AOR = 0.27, 95% CI = 0.16-0.46). Regular neurologist care and use of multiple PD medications were positively associated with DBS surgery. CONCLUSIONS: Variations in use of DBS may reflect differences in access to care, specialist referral pathways, health-seeking behavior, or need for DBS. Future studies are needed to understand drivers of potential disparities in DBS use.

Interventions to reduce wait times for primary care appointments: a systematic review.

BACKGROUND: Accessibility and availability are important characteristics of efficient and effective primary healthcare systems. Currently, timely access to a family physician is a concern in Canada. Adverse outcomes are associated with longer wait times for primary care appointments and often leave individuals to rely on urgent care. When wait times for appointments are too long patients may experience worse health outcomes and are often left to use emergency department resources. The primary objective of our study was to systematically review the literature to identify interventions designed to reduce wait times for primary care appointments. Secondary objectives were to assess patient satisfaction and reduction of no-show rates. METHODS: We searched multiple databases, including: Medline via Ovid SP (1947 to present), Embase (from 1980 to present), PsychINFO (from 1806 to present), Cochrane Central Register of Controlled Trials (CENTRAL; all dates), Cumulative Index to Nursing and Allied Health (CINAHL; 1937 to present), and Pubmed (all dates) to identify studies that reported outcomes associated with interventions designed to reduce wait times for primary care appointments. Two independent reviewers assessed all identified studies for inclusion using pre-defined inclusion/exclusion criteria and a multi-level screening approach. Our study methods were guided by the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Our search identified 3,960 articles that were eligible for inclusion, eleven of which satisfied all inclusion/exclusion criteria. Data abstraction of included studies revealed that open access scheduling is the most commonly used intervention to reduce wait times for primary care appointments. Additionally, included studies demonstrated that dedicated telephone calls for follow-up consultation, presence of nurse practitioners on staff, nurse and general practitioner triage, and email consultations were effective at reducing wait times. CONCLUSIONS: To our knowledge, this is the first study to systematically review and identify interventions designed to reduce wait times for primary care appointments. Our findings suggest that open access scheduling and other patient-centred interventions may reduce wait times for primary care appointments. Our review may inform policy makers and family healthcare providers about interventions that are effective in offering timely access to primary healthcare.

Risk factors for serious underlying pathology in adult emergency department nontraumatic low back pain patients.

BACKGROUND: Nontraumatic low back pain (LBP) is a common emergency department (ED) complaint and can be caused by serious pathologies that require immediate intervention or that lead to death. OBJECTIVE: The primary goal of this study is to identify risk factors associated with serious pathology in adult nontraumatic ED LBP patients. METHODS: We conducted a health records review and included patients aged ≥ 16 years with nontraumatic LBP presenting to an academic ED from November 2009 to January 2010. We excluded those with previously confirmed nephrolithiasis and typical renal colic presentation. We collected 56 predictor variables and outcomes within 30 days. Outcomes were determined by tracking computerized patient records and performance of univariate analysis and recursive partitioning. RESULTS: There were 329 patients included, with a mean age of 49.3 years; 50.8% were women. A total of 22 (6.7%) patients suffered outcomes, including one death, five compression fractures, four malignancies, four disc prolapses requiring surgery, two retroperitoneal bleeds, two osteomyelitis, and one each of epidural abscess, cauda equina, and leaking abdominal aortic aneurysm graft. Risk factors identified for outcomes were: anticoagulant use (odds ratio [OR] 15.6; 95% confidence interval [CI] 4.2-58.5), decreased sensation on physical examination (OR 6.9; CI 2.2-21.2), pain that is worse at night (OR 4.3; CI 0.9-20.1), and pain that persists despite appropriate treatment (OR 2.2; CI 0.8-5.6). These four predictors identified serious pathology with 91% sensitivity (95% CI 70-98%) and 55% specificity (95% CI 54-56%). CONCLUSION: We successfully identified risk factors associated with serious pathology among ED LBP patients. Future prospective studies are required to derive a robust clinical decision rule.

Role of reactive oxygen species in the neural and hormonal regulation of the PNMT gene in PC12 cells.

The stress hormone, epinephrine, is produced predominantly by adrenal chromaffin cells and its biosynthesis is regulated by the enzyme phenylethanolamine N-methyltransferase (PNMT). Studies have demonstrated that PNMT may be regulated hormonally via the hypothalamic-pituitary-adrenal axis and neurally via the stimulation of the splanchnic nerve. Additionally, hypoxia has been shown to play a key role in the regulation of PNMT. The purpose of this study was to examine the impact of reactive oxygen species (ROS) produced by the hypoxia mimetic agent CoCl(2), on the hormonal and neural stimulation of PNMT in an in vitro cell culture model, utilizing the rat pheochromocytoma (PC12) cell line. RT-PCR analyses show inductions of the PNMT intron-retaining and intronless mRNA splice variants by CoCl(2) (3.0- and 1.76-fold, respectively). Transient transfection assays of cells treated simultaneously with CoCl(2) and the synthetic glucocorticoid, dexamethasone, show increased promoter activity (18.5-fold), while mRNA levels of both splice variants do not demonstrate synergistic effects. Similar results were observed when investigating the effects of CoCl(2)-induced ROS on the neural stimulation of PNMT via forskolin. Our findings demonstrate that CoCl(2)-induced ROS have synergistic effects on hormonal and neural activation of the PNMT promoter.

Protective effects of polyphenolic compounds on oxidative stress-induced cytotoxicity in PC12 cells.

To investigate the beneficial properties associated with polyphenols, we screened 12 polyphenols for their ability to increase the viability of PC12 cells subjected to oxidative stress via CoCl2 and H2O2. Cell viability data demonstrate that 50 micromol/L methyl gallate and 50 micromol/L fisetin significantly increase viability of H2O2-stressed cells. Further, viability data suggest that 100 micromol/L epigallocatechin gallate (EGCG) increases basal viability, but has no rescue effect on cells stressed with CoCl2 or H2O2. Analysis of intracellular reactive oxygen species (ROS) shows that EGCG, methyl gallate, and gallic acid are effective in reducing CoCl2-derived ROS, and that methyl gallate is effective in attenuating H2O2-derived ROS. Examination of nitric oxide concentrations shows that methyl gallate significantly increases nitric oxide, both in nonstressed and H2O2-stressed cells, whereas EGCG results are consistent with the scavenging of nitric oxide under nonstressed and stressed conditions. Furthermore, analysis of total glutathione levels reveals that EGCG, methyl gallate, and gallic acid pretreatments with and without H2O2 stress have the ability to significantly alter glutathione metabolism. These findings suggest that EGCG, methyl gallate, and gallic acid may have potential therapeutic properties.

Protective effects of methyl gallate on H2O2-induced apoptosis in PC12 cells.

Neurodegenerative disorders are a class of diseases that have been linked to apoptosis induced by elevated levels of reactive oxygen species (ROS). ROS activates the apoptotic cascade through mitochondrial dysfunction and damage to lipids, proteins and DNA. Recently, fruit and tea-derived polyphenols have been found to be beneficial in decreasing oxidative stress and increasing overall health. Further, polyphenols including epigallocatechin gallate (EGCG) have been reported to inhibit apoptotic signaling and increase neural cell survival. In an effort to better understand the beneficial properties associated with polyphenol consumption, the aim of this study was to explore the neuroprotective effects of EGCG, methyl gallate (MG), gallic acid (GA) and N-acetylcysteine (NAC) on H(2)O(2)-induced apoptosis in PC12 cells and elucidate potential protective mechanisms. Cell viability data demonstrates that MG and NAC pre-treatments significantly increase viability of H(2)O(2)-stressed cells, while pre-treatments with EGCG and GA exacerbates stress. Quantitation of apoptosis and mitochondrial membrane potential shows that MG pre-treatment prevents mitochondria depolarization, however does not inhibit apoptosis and is thus evidence that MG can inhibit mitochondria-mediated apoptosis. Subsequent analysis of DNA degradation and caspase activation reveals that MG inhibits activation of caspase 9 and has a partial inhibitory effect on DNA degradation. These findings confirm the involvement of both intrinsic and extrinsic apoptotic pathways in H(2)O(2)-induced apoptosis and suggest that MG may have potential therapeutic properties against mitochondria-mediated apoptosis.