Geographical Variation In Medication and Health Resource Use In Multiple Sclerosis.

BACKGROUND: Understanding disease-modifying therapy (DMT) use and healthcare resource utilization by different geographical areas among people living with multiple sclerosis (pwMS) may identify care gaps that can be used to inform policies and practice to ensure equitable care. METHODS: Administrative data was used to identify pwMS on April 1, 2017 (index date) in Alberta. DMT use and healthcare resource utilization were compared between those who resided in various geographical areas over a 2-year post-index period; simple logistic regression was applied. RESULTS: Among the cohort (n = 12,338), a higher proportion of pwMS who resided in urban areas (versus rural) received ≥ 1 DMT dispensation (32.3% versus 27.4%), had a neurologist (67.7% versus 63.9%), non-neurologist specialist (88.3% versus 82.9%), ambulatory care visit (87.4% versus 85.3%), and MS tertiary clinic visit (59.2% versus 51.7%), and a lower proportion had an emergency department (ED) visit (46.3% versus 62.4%), and hospitalization (20.4% versus 23.0%). Across the provincial health zones, there were variations in DMT selection, and a higher proportion of pwMS who resided in the Calgary health zone, where care is managed by MS tertiary clinic neurologists, had an outpatient visit to a neurologist or MS tertiary clinic versus those who resided in other zones where delivery of MS-related care is more varied. CONCLUSIONS: Urban/rural inequalities in DMT use and healthcare resource utilization appear to exist among pwMS in Alberta. Findings suggest the exploration of barriers with consequent strategies to increase access to DMTs and provide timely outpatient MS care management, particularly for those pwMS residing in rural areas.

Poststroke Care Pathways and Spasticity Treatment: A Retrospective Study in Alberta.

BACKGROUND: Limited evidence exists regarding care pathways for stroke survivors who do and do not receive poststroke spasticity (PSS) treatment. METHODS: Administrative data was used to identify adults who experienced a stroke and sought acute care between 2012 and 2017 in Alberta, Canada. Pathways of stroke care within the health care system were determined among those who initiated PSS treatment (PSS treatment group: outpatient pharmacy dispensation of an anti-spastic medication, focal chemo-denervation injection, or a spasticity tertiary clinic visit) and those who did not (non-PSS treatment group). Time from the stroke event until spasticity treatment initiation, and setting where treatment was initiated were reported. Descriptive statistics were performed. RESULTS: Health care settings within the pathways of stroke care that the PSS (n = 1,079) and non-PSS (n = 22,922) treatment groups encountered were the emergency department (86 and 84%), acute inpatient care (80 and 69%), inpatient rehabilitation (40 and 12%), and long-term care (19 and 13%), respectively. PSS treatment was initiated a median of 291 (interquartile range 625) days after the stroke event, and most often in the community when patients were residing at home (45%), followed by "other" settings (22%), inpatient rehabilitation (18%), long-term care (11%), and acute inpatient care (4%). CONCLUSIONS: To our knowledge, this is the first population based cohort study describing pathways of care among adults with stroke who subsequently did or did not initiate spasticity treatment. Areas for improvement in care may include strategies for earlier identification and treatment of PSS.

Benzodiazepine use in medical cannabis authorization adult patients from 2013 to 2021: Alberta, Canada.

BACKGROUND: Benzodiazepines are a class of medications that are being frequently prescribed in Canada but carry significant risk of harm. There has been increasing clinical interest on the potential "sparing effects" of medical cannabis as one strategy to reduce benzodiazepine use. The objective of this study as to examine the association of medical cannabis authorization with benzodiazepine usage between 2013 and 2021 in Alberta, Canada. METHODS: A propensity score matched cohort study with patients on regular benzodiazepine treatment authorized to use medical cannabis compared to controls who do not have authorization for medical cannabis. A total of 9690 medically authorized cannabis patients were matched to controls. To assess the effect of medical cannabis use on daily average diazepam equivalence (DDE), interrupted time series (ITS) analysis was used to assess the change in the trend of DDE in the 12 months before and 12 months after the authorization of medical cannabis. RESULTS: Over the follow-up period after medical cannabis authorization, there was no overall change in the DDE use in authorized medical cannabis patients compared to matched controls (- 0.08 DDE, 95% CI: - 0.41 to 0.24). Likewise, the sensitivity analysis showed that, among patients consuming ≤5 mg baseline DDE, there was no change immediately after medical cannabis authorization compared to controls (level change, - 0.04 DDE, 95% CI: - 0.12 to 0.03) per patient as well as in the month-to-month trend change (0.002 DDE, 95% CI: - 0.009 to 0.12) per patient was noted. CONCLUSIONS: This short-term study found that medical cannabis authorization had minimal effects on benzodiazepine use. Our findings may contribute ongoing evidence for clinicians regarding the potential impact of medical cannabis to reduce benzodiazepine use. HIGHLIGHTS: • Medical cannabis authorization had little to no effect on benzodiazepine usage among patients prescribed regular benzodiazepine treatment in Alberta, Canada. • Further clinical research is needed to investigate the potential impact of medical cannabis as an alternative to benzodiazepine medication.

Effect of lower body negative pressure on cardiac and cerebral function in postural orthostatic tachycardia syndrome: A pilot MRI assessment.

Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of -25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2 ) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2 ; susceptometry-based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p < 0.001) with no group differences (HC: +9 ± 8 bpm; POTS: +13 ± 11 bpm; p = 0.35). Biventricular volumes, SV, and Qc decreased during LBNP (p < 0.001). CBF and SvO2 decreased with LBNP (p = 0.01 and 0.03, respectively) but not cerebral VO2 (effect of LBNP: p = 0.28; HC: -0.2 ± 3.7 mL/min; POTS: +1.1 ± 2.0 mL/min; p = 0.33 between groups). Regional cerebral perfusion decreased during LBNP (p < 0.001) but was not different between groups. These data suggest patients with POTS have preserved cardiac and cerebrovascular function.

Disease-modifying therapy use and health resource utilisation associated with multiple sclerosis over time: A retrospective cohort study from Alberta, Canada.

BACKGROUND: Estimating multiple sclerosis (MS) prevalence and incidence, and assessing the utilisation of disease-modifying therapies (DMTs) and healthcare resources over time is critical to understanding the evolution of disease burden and impacts of therapies upon the healthcare system. METHODS: A retrospective population-based study was used to determine MS prevalence and incidence (2003-2019), and describe utilisation of DMTs (2009-2019) and healthcare resources (1998-2019) among people living with MS (pwMS) using administrative data in Alberta. RESULTS: Prevalence increased from 259 (95% confidence interval [CI]: 253-265) to 310 (95% CI: 304, 315) cases per 100,000 population, and incidence decreased from 21.2 (95% CI: 19.6-22.8) to 12.7 (95% CI: 11.7-13.8) cases per 100,000 population. The proportion of pwMS who received ≥1 DMT dispensation increased (24% to 31% annually); use of older platform injection therapies decreased, and newer oral-based, induction, and highly-effective therapies increased. The proportion of pwMS who had at least one MS-related physician, ambulatory, or tertiary clinic visits increased, and emergency department visits and hospitalizations decreased. CONCLUSIONS: Alberta has one of the highest rates of MS globally. The proportion of pwMS who received DMTs and had outpatient visits increased, while acute care visits decreased over time. The landscape of MS care appears to be rapidly evolving in response to changes in disease burden and new highly-effective therapies.

Autonomic Cardioregulatory Function Does Not Correlate With Symptom Improvement After Concussion in Children and Adolescents.

Although there is significant variability in the manifestations of persisting post-concussive symptoms (PPCS), autonomic dysfunction has been reported to contribute to PPCS and could serve as a biomarker of recovery. The objective of this study was to evaluate cardiac autonomic reflexes and autonomic function after concussion injury comparing those with prolonged concussion symptoms to those without. This is a case-control study where a non-referred population of concussed children or adolescent participants were enrolled from the Emergency Department (ED) of the Stollery Children's Hospital, a tertiary pediatric hospital in Edmonton, Alberta, Canada. Children and adolescents 8 through <18 years of age who presented with mild traumatic brain injury were diagnosed with concussion. Our study reported concussion symptoms and standardized clinical cardiac autonomic reflex testing at 4 and 12 weeks after injury. Our findings showed that 28 participants with concussion completed the 4-week follow-up questionnaires, and that 17 (61%) were diagnosed with PPCS. Difficulty concentrating, fatigue, noise sensitivity, light sensitivity, and headache were most commonly reported at baseline among those who were later diagnosed with PPCS. The mean change in heart rate (HR) with head-up tilt was 44.2 bpm (standard deviation [SD] 9.1) in the non-PPCS group and 46.6 bpm (SD 14.1) in the PPCS group at 4 weeks and was not significant in the unadjusted (p = 0.2) or adjusted analysis for age and female sex (p = 0.2). Overall, 70% (19/27) had significant orthostatic tachycardia >40 bpm, but PPCS and non-PPCS groups were similar. Similar results were observed among 23 participants at 12-week follow-up. The median maximum decrease in systolic blood pressure (SBP) with head-up tilt was -26.9 mm Hg (interquartile range [IQR] -32.6, -22.3) in the non-PPCS group and -25.1 mm Hg (IQR -32.2, -18.2) in the PPCS group, and was not significantly different in the unadjusted (p = 0.8) or adjusted (p = 0.8) analysis. Overall, 19 of 26 participants (73%) demonstrated orthostatic hypotension (SBP change >20 mm Hg) with no significant difference between the PPCS and non-PPCS groups. Similar results were observed at 12-week follow-up. In conclusion, cardiac autonomic reflex responses are abnormal in most children and adolescents with a concussion injury at 4- and 12-week follow-up and may reflect ongoing autonomic dysfunction. However, autonomic function did not differentiate PPCS, indicating that reported symptoms are not sensitive to autonomic abnormalities.

Stratification of risk for emergent intracranial abnormalities in children with headaches: a Pediatric Emergency Care Applied Research Network (PECARN) study protocol.

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA in children with headaches based on clinically sensible and reliable variables. METHODS AND ANALYSIS: Prospective cohort study of 28 000 children with headaches presenting to any of 18 EDs in the Pediatric Emergency Care Applied Research Network (PECARN). We include children aged 2-17 years with a chief complaint of headache. We exclude children with a clear non-intracranial alternative diagnosis, fever, neuroimaging within previous year, neurological or developmental condition such that patient history or physical examination may be unreliable, Glasgow Coma Scale score<14, intoxication, known pregnancy, history of intracranial surgery, known structural abnormality of the brain, pre-existing condition predisposing to an intracranial abnormality or intracranial hypertension, head injury within 14 days or not speaking English or Spanish. Clinicians complete a standardised history and physical examination of all eligible patients. Primary outcome is the presence of an EIA as determined by neuroimaging or clinical follow-up. We will use binary recursive partitioning and multiple regression analyses to create and internally validate the risk stratification model. ETHICS AND DISSEMINATION: Ethics approval was obtained for all participating sites from the University of Utah single Institutional Review Board. A waiver of informed consent was granted for collection of ED data. Verbal consent is obtained for follow-up contact. Results will be disseminated through international conferences, peer-reviewed publications, and open-access materials.

Trajectory of health care resources among adults stopping or reducing treatment frequency of botulinum toxin for chronic migraine treatment in Alberta, Canada.

OBJECTIVE: Understand health resource, medication use, and cost of adults with chronic migraine who received guideline-recommended onabotulinumtoxinA (botulinum toxin) treatment frequency and then continued or reduced/stopped. BACKGROUND: Botulinum toxin may be a beneficial treatment for chronic migraine; the trajectory of health resources utilization among those with continued or reduced/stopped use is unclear. METHODS: A retrospective population-based cohort study utilizing administrative data from Alberta, Canada (2012-2020), was performed. A cohort of adults who received ≥5 botulinum toxin treatment cycles for chronic migraine over 18 months (6-month run-in; 1-year pre-index period) were grouped into those who (1) continued use (≥3 treatments/year), or (2) stopped or reduced use (stopped for 6 months then received 0 or 1-2 treatments/year, respectively) over a 1-year post-index period. Health resources and medication use were described, and pre-post costs were assessed. A second cohort that received ≥3 treatments/year immediately followed by 1 year of stopped or reduced use was considered in sensitivity analysis. RESULTS: Pre-post health resource, medication use, and costs were similar among those with continued use (n = 3336). Among those who stopped or reduced use (n = 1099; 756 stopped, 343 reduced), health resource, medication use, and costs were lower in the post- (total median per-person cost [IQR]: all-cause $4851 [$8090]; migraine-related $835 [$1915]) versus pre- (all-cause $6096 [$7207]; migraine-related $2995 [$1950]) index period (estimated cost ratios [95% CI]: total all-cause 0.86 [0.79, 0.95]; total migraine-related 0.44 [0.40, 0.48]). In the second cohort (n = 3763), return to continued use (≥3 treatments/year) occurred in up to 70.4% in those with reduced use. CONCLUSIONS: Of adults treated with botulinum toxin for chronic migraine, 75.2% had continued use, stable health resource and medication use, and costs over a 2 year period. In those that stopped/reduced use, the observed lower health resource and migraine medication use may indicate improved symptom control, but the resumption of guideline-recommended treatment intervals after reduced use was common.

Patient-reported outcomes of neurologic and neuropsychiatric symptoms in mild COVID-19: a prospective cohort study.

BACKGROUND: Various neurologic manifestations have been reported in patients with COVID-19, mostly in retrospective studies of patients admitted to hospital, but there are few data on patients with mild COVID-19. We examined the frequency and persistence of neurologic/neuropsychiatric symptoms in patients with mild COVID-19 in a 1-year prospective cohort study, as well as assessment of use of health care services and patient-reported outcomes. METHODS: Participants in the Alberta HOPE COVID-19 trial (hydroxychloroquine v. placebo for 5 d), managed as outpatients, were prospectively assessed 3 months and 1 year after their positive test result. They completed detailed neurologic/neuropsychiatric symptom questionnaires, the telephone version of the Montreal Cognitive Assessment (T-MoCA), the Kessler Psychological Distress Scale (K10) and the EuroQol EQ-5D-3L (measure of quality of life). Close informants completed the Mild Behavioural Impairment Checklist (MBI-C) and the Informant Questionnaire on Cognitive Decline in the Elderly. We also tracked use of health care services and neurologic investigations. RESULTS: The cohort consisted of 198 participants (87 female [43.9%] median age 45 yr, interquartile range 37-54 yr). Of the 179 participants with symptom assessments, 139 (77.6%) reported at least 1 neurologic symptom, the most common being anosmia/dysgeusia (99 [55.3%]), myalgia (76 [42.5%]) and headache (75 [41.9%]). Forty patients (22.3%) reported persistent symptoms at 1 year, including confusion (20 [50.0%]), headache (21 [52.5%]), insomnia (16 [40.0%]) and depression (14 [35.0%]); 27/179 (15.1%) reported no improvement. Body mass index (BMI), a history of asthma and lack of full-time employment were associated with the presence and persistence of neurologic/neuropsychiatric symptoms; female sex was independently associated with both (presence: odds ratio [OR] adjusted for age, race, BMI, history of asthma and neuropsychiatric history 5.04, 95% confidence interval [CI] 1.58 to 16.10). Compared to participants without persistent symptoms, those with persistent symptoms had more hospital admissions and family physician visits, and worse MBI-C scores and less frequent independence for instrumental activities at 1 year (83.8% v. 97.8%, p = 0.005). Patients with any or persistent neurologic symptoms had worse psychologic distress (K10 score ≥ 20: adjusted OR 12.1, 95% CI 1.4 to 97.2) and quality of life (median EQ-5D-3L visual analogue scale rating 75 v. 90, p < 0.001); 42/84 (50.0%) had a T-MoCA score less than 18 at 3 months, as did 36 (42.9%) at 1 year. Participants who reported memory loss were more likely than those who did not report such symptoms to have informant-reported cognitive-behavioural decline (1-yr MBI-C score ≥ 6.5: adjusted OR 15.0, 95% CI 2.42 to 92.60). INTERPRETATION: Neurologic/neuropsychiatric symptoms were commonly reported in survivors of mild COVID-19, and they persisted in 1 in 5 patients 1 year later. Symptoms were associated with worse participant- and informant-reported outcomes. Trial registration: ClinicalTrials.gov, no. NCT04329611.

Analgesic Use Among Adults with a Trauma-Related Emergency Department Visit: A Retrospective Cohort Study from Alberta, Canada.

INTRODUCTION: A better understanding of current acute pain-driven analgesic practices within the emergency department (ED) and upon discharge will provide foundational information in this area, as few studies have been conducted in Canada. METHODS: Administrative data were used to identify adults with a trauma-related ED visit in the Edmonton area in 2017/2018. Characteristics of the ED visit included time from initial contact to analgesic administration, type of analgesics dispensed during and upon being discharged home directly from the ED (≤ 7 days after), and patient characteristics. RESULTS: A total of 50,950 ED visits by 40,505 adults with trauma were included. Analgesics were administered in 24.2% of visits, of which non-opioids were dispensed in 77.0% and opioids were dispensed in 49.0%. Time to analgesic initiation occurred more than 2 h after first contact. Upon discharge, 11.5% received a non-opioid and 15.2% received an opioid analgesic, among whom 18.5% received a daily dose ≥ 50 morphine milligram equivalents (MME) and 30.2% received > 7 days of supply. Three hundred and seventeen adults newly met criteria for chronic opioid use after the ED visit, among whom 43.5% received an opioid dispensation upon discharge; of these individuals, 26.8% had a daily dose ≥ 50 MME and 65.9% received > 7 days of supply. CONCLUSIONS: Findings can be used to inform optimization of analgesic pharmacotherapy practices for the treatment of acute pain, which may include reducing the time to initiation of analgesics in the ED, as well as close consideration of recommendations for acute pain management upon discharge to provide ideal patient-centered, evidence-informed care.

Evaluation of Autonomic Nervous System Dysfunction in Childhood Obesity and Prader-Willi Syndrome.

The autonomic nervous system (ANS) may play a role in the distribution of body fat and the development of obesity and its complications. Features of individuals with Prader-Willi syndrome (PWS) impacted by PWS molecular genetic classes suggest alterations in ANS function; however, these have been rarely studied and presented with conflicting results. The aim of this study was to investigate if the ANS function is altered in PWS. In this case-control study, we assessed ANS function in 20 subjects with PWS (6 males/14 females; median age 10.5 years) and 27 body mass index (BMI) z-score-matched controls (19 males/8 females; median age 12.8 years). Standardized non-invasive measures of cardiac baroreflex function, heart rate, blood pressure, heart rate variability, quantitative sudomotor axon reflex tests, and a symptom questionnaire were completed. The increase in heart rate in response to head-up tilt testing was blunted (p < 0.01) in PWS compared to controls. Besides a lower heart rate ratio with Valsalva in PWS (p < 0.01), no significant differences were observed in other measures of cardiac function or sweat production. Findings suggest possible altered sympathetic function in PWS.

Hydroxychloroquine for treatment of non-hospitalized adults with COVID-19: A meta-analysis of individual participant data of randomized trials.

Hydroxychloroquine (HCQ) was initially promoted as an oral therapy for early treatment of coronavirus disease 2019 (COVID-19). Conventional meta-analyses cannot fully address the heterogeneity of different designs and outcomes of randomized controlled trials (RCTs) assessing the efficacy of HCQ in outpatients with mild COVID-19. We conducted a pooled analysis of individual participant data from RCTs that evaluated the effect of HCQ on hospitalization and viral load reduction in outpatients with confirmed COVID-19. We evaluated the overall treatment group effect by log-likelihood ratio test (-2LL) from a generalized linear mixed model to accommodate correlated longitudinal binary data. The analysis included data from 11 RCTs. The outcome of virological effect, assessed in 1560 participants (N = 795 HCQ, N = 765 control), did not differ significantly between the two treatment groups (-2LL = 7.66; p = 0.18) when adjusting for cohort, duration of symptoms, and comorbidities. The decline in polymerase chain reaction positive tests from day 1 to 7 was 42.0 and 41.6 percentage points in the HCQ and control groups, respectively. Among the 2037 participants evaluable for hospitalization (N = 1058 HCQ, N = 979 control), we found no significant differences in hospitalization rate between participants receiving HCQ and controls (odds ratio 0.995; 95% confidence interval 0.614-1.610; -2LL = 0.0; p = 0.98) when adjusting for cohort, duration of symptoms, and comorbidities. This individual participant data meta-analysis of 11 HCQ trials that evaluated severe acute respiratory syndrome-coronavirus 2 viral clearance and COVID-19 hospitalization did not show a clinical benefit of HCQ. Our meta-analysis provides evidence to support the interruption in the use of HCQ in mild COVID-19 outpatients to reduce progression to severe disease.

Economic impact of self-administered subcutaneous versus clinic-administered intravenous immunoglobulin G therapy in Alberta, Canada: a population-based cohort study.

BACKGROUND: Self-administered subcutaneous immunoglobulin G (SCIg) reduces nursing time and eliminates the need for treatment at ambulatory care clinics, as compared with clinic-based intravenously administered IgG (IVIg), and are therapeutically equivalent. Estimating the economic impact of self-administered SCIg versus clinic-administered IVIg therapy may guide treatment recommendations. METHODS: A retrospective population-based cohort study using administrative data from Alberta was performed; those treated with IgG between April 1, 2012 and March 31, 2019 were included. Costs for medical laboratory staff and nursing time, as well as ambulatory care visits were considered. Univariate generalized linear model regression with gamma distribution and log link was used to compare cost ($CDN 2020) between SCIg and IVIg administration. Stratified analysis by age (≥ 18-years; < 18-years) was performed. RESULTS: Among 7,890 (6,148 adults; 1,742 children) individuals who received IgG, the average administration cost per patient-year of self-administered SCIg was $5,386 (95% confidence interval [CI] $5,039, $5,734) lower than clinic-administered IVIg; per patient-year cost of self-administered SCIg was $817 (95% CI $723, $912) versus $6,204 (95% CI $6,100, $6,308) for clinic-administered IVIg. The per patient-year cost of self-administered SCIg was $5,931 (95% CI $5,543, $6,319) lower among adults and $3,177 (95% CI $2,473, $3,882) lower among children compared with clinic-administered IVIg. An estimated $31.0 million (95% CI $29.0, $33.0) in cost savings to the health system would be realised if 80% of individuals switched from clinic-administered IVIg to self-administered SCIg. CONCLUSIONS: Self-administered SCIg is substantially less costly from a health care payer perspective in Canada. Within this type of health system, switching to self-administered SCIg has the potential to reduce overall health care costs, lessen nursing burden, and may increase clinic-based capacity for others.

Early analgesic administration and headache presence 7 days post-concussion in children.

OBJECTIVE: This study investigates whether acute treatment with ibuprofen, acetaminophen, or both is associated with resolution of headache or reduction of headache pain at 7 days post-concussion in children and youth. METHODS: A secondary analysis of the Predicting and Preventing Post-concussive Problems in Pediatrics (5P) prospective cohort study was conducted. Individuals aged 5-18 years with acute concussion presenting to nine Canadian pediatric emergency departments (ED) were enrolled from August 2013 to June 2015. The primary outcome was the presence of headache at 7 days, measured using the Post-Concussion Symptom Inventory. The association between acute administration of ibuprofen, acetaminophen, or both and headache presence at 7 days was investigated with propensity scores and adjusted multivariate regression models. RESULTS: 2277 (74.3%) of 3063 participants had headache upon ED presentation. Of these participants, 1543 (67.8%) received an analgesic medication before or during their ED visit [ibuprofen 754 (33.1%), acetaminophen 445 (19.5%), both 344 (15.1%); or no medication 734 (32.2%)]. Multivariate analysis pertained to 1707 participants with propensity scores based on personal characteristics and symptoms; 877 (51.4%) reported headache at 7 days post-concussion. No association emerged between treatment and presence of headache at 7 days [ibuprofen vs. untreated: (relative risk (RR) = 1.12 (95% CI 0.99,1.26); acetaminophen vs untreated RR = 1.02 (95% CI 0.87,1.22); both vs untreated RR = 1.02 (95% CI 0.86,1.18)]. CONCLUSIONS: Exposure to ibuprofen, acetaminophen, or both in the acute phase does not decrease the risk of headache at 7 days post-concussion. Non-opioid analgesics like ibuprofen or acetaminophen may be prescribed for short-term headache relief but clinicians need to be cautious with long-term medication overuse in those whose headache symptoms persist.

RéSUMé: OBJECTIF: Cette étude vise à déterminer si un traitement aigu à l'ibuprofène, à l'acétaminophène ou aux deux est associé à la résolution des maux de tête ou à la réduction de la douleur des maux de tête 7 jours après la commotion cérébrale chez les enfants et les adolescents. MéTHODES: Une analyse secondaire de l'étude de cohorte prospective Predicting and Preventing Post-concussive Problems in Pediatrics (5P) a été réalisée. Des personnes âgées de 5 à 18 ans souffrant d'une commotion cérébrale aiguë se présentant dans neuf services d'urgence pédiatriques (SU) canadiens ont été inscrites d'août 2013 à juin 2015. Le résultat primaire était la présence de maux de tête à 7 jours, mesurée à l'aide du Post-Concussion Symptom Inventory. L'association entre l'administration aiguë d'ibuprofène, d'acétaminophène ou des deux et la présence de maux de tête à 7 jours a été étudiée à l'aide de scores de propension et de modèles de régression multivariés ajustés. RéSULTATS: 2277 (74,3%) des 3063 participants avaient des maux de tête lors de la présentation aux urgences. Parmi ces participants, 1 543 (67,8%) ont reçu un médicament analgésique avant ou pendant leur visite aux urgences [ibuprofène 754 (33,1%), acétaminophène 445 (19,5%), les deux 344 (15,1%); ou aucun médicament 734 (32,2%)]. L'analyse multivariée a porté sur 1707 participants avec des scores de propension basés sur les caractéristiques personnelles et les symptômes; 877 (51,4%) ont signalé des maux de tête 7 jours après la commotion cérébrale. Aucune association n'est apparue entre le traitement et la présence de céphalées à 7 jours [ibuprofène vs non traité: (risque relatif (RR) = 1,12 (95%CI:0,99,1,26); acétaminophène vs non traité RR = 1,02 (95% IC: 0,87,1,22); les deux vs non traité RR = 1,02 (95% IC: 0,86,1,18)]. CONCLUSIONS: L'exposition à l'ibuprofène, à l'acétaminophène ou aux deux dans la phase aiguë ne diminue pas le risque de céphalées 7 jours après la commotion. Les analgésiques non opioïdes comme l'ibuprofène ou l'acétaminophène peuvent être prescrits pour soulager les maux de tête à court terme, mais les cliniciens doivent faire attention à la surconsommation de médicaments à long terme chez les personnes dont les symptômes de maux de tête persistent.

Health resource utilization and cost before versus after initiation of second-generation long-acting injectable antipsychotics among adults with schizophrenia in Alberta, Canada: a retrospective, observational single-arm study.

BACKGROUND: Long-acting injectable (LAI) antipsychotics, along with community treatment orders (CTOs), are used to improve treatment effectiveness through adherence among individuals with schizophrenia. Understanding real-world medication adherence, and healthcare resource utilization (HRU) and costs in individuals with schizophrenia overall and by CTO status before and after second generation antipsychotic (SGA)-LAI initiation may guide strategies to optimize treatment among those with schizophrenia. METHODS: This retrospective observational single-arm study utilized administrative health data from Alberta, Canada. Adults (≥ 18 years) with schizophrenia who initiated a SGA-LAI (no use in the previous 2-years) between April 1, 2014 and March 31, 2016, and had ≥ 1 additional dispensation of a SGA-LAI were included; index date was the date of SGA-LAI initiation. Medication possession ratio (MPR) was determined, and paired t-tests were used to examine mean differences in all-cause and mental health-related HRU and costs (Canadian dollars), comprised of hospitalizations, physician visits, emergency department visits, and total visits, over the 2-year post-index and 2-year pre-index periods. Analyses were stratified by presence or absence of an active CTO during the pre-index and/or post-index periods. RESULTS: Among 1,211 adults with schizophrenia who initiated SGA-LAIs, 64% were males with a mean age of 38 (standard deviation [SD] 14) years. The mean overall antipsychotic MPR was 0.39 (95% confidence interval [CI] 0.36, 0.41) greater during the 2-year post-index period (0.84 [SD 0.26]) compared with the 2-year pre-index period (0.45 [SD 0.40]). All-cause and mental health-related HRU and costs were lower post-index versus pre-index (p < 0.001) for hospitalizations, physician visits, emergency department visits, and total visits; mean total all-cause HRU costs were $33,788 (95% CI -$38,993, -$28,583) lower post- versus pre-index ($40,343 [SD $68,887] versus $74,131 [SD $75,941]), and total mental health-related HRU costs were $34,198 (95%CI -$39,098, -$29,297) lower post- versus pre-index ($34,205 [SD $63,428] versus $68,403 [SD $72,088]) per-patient. Forty-three percent had ≥ 1 active CTO during the study period; HRU and costs varied according to CTO status. CONCLUSIONS: SGA-LAIs are associated with greater medication adherence, and lower HRU and costs however the latter vary according to CTO status.

Quality of life, respiratory symptoms, and health care utilization 1 year following outpatient management of COVID-19: a prospective cohort study.

The long-term impact of COVID-19 among those with mild infections is not well characterized. Among 81 adults who completed online assessments at 3- and 12-months following infection, quality of life scores did not significantly improve over time. Among 62 subjects who also completed telephone interviews, respiratory symptoms or exercise limitation were reported by 42% at a median follow-up of 387 days (IQR 251-402 days). Those with persistent respiratory symptoms scored lower on the EQ-5D visual analog score compared to those without. Persistent respiratory symptoms were associated with a lower likelihood of full-time employment at 1 year (aOR 0.09, 95%CI 0.01-0.91; P = 0.041). In an adjusted linear regression, persistent respiratory symptoms (P = 0.037) and female sex (P = 0.016) were both independent risks for increased visits to a primary care provider. This cohort study demonstrates that respiratory symptoms are frequent at 1 year following COVID-19 and more importantly, are associated with negative impacts on employment, quality of life, and health care utilization. Further research is needed to determine the pathophysiology and risk factors for persistent symptoms as well as optimal management strategies to improve the level of functioning and quality of life.

A randomized trial of ketorolac and metoclopramide for migraine in the emergency department.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of a common monotherapy (intravenous [iv] metoclopramide) compared to a combination strategy (adding iv ketorolac to metoclopramide) in children presenting for acute treatment of migraine headache in the emergency department (ED). METHODS: Children aged 5-17 years presenting for acute treatment of migraine headache at two pediatric EDs were enrolled in a double-blind randomized controlled trial. Children were randomly assigned to receive iv metoclopramide 0.2 mg/kg) and placebo or iv metoclopramide (0.2 mg/kg) and ketorolac (0.5 mg/kg). The primary outcome was a mean change in pain from baseline to 120 min via a 100 mm Visual Analog Scale (VAS). Follow-up was conducted 24-h after discharge. RESULTS: Fifty-three children were randomized and included in the analysis (monotherapy group [metoclopramide + placebo], n = 27; and ketorolac group [metoclopramide + ketorolac], n = 26); mean age was 12.9 ± 2.7 years and baseline pain severity on VAS was 67.3 ± 2.7 mm. The mean change in pain intensity at 120 min was -44 mm (SD: 24; 95% confidence interval [CI]: 32-57) for the monotherapy group and -36 mm (SD: 24; 95% CI: 23-49) for the ketorolac group, with a mean difference between groups of 8 mm (95% CI: -9-25; p = 0.360). Seventeen percent of the children (9/53; 95% CI: 7-27%) were pain-free at discharge. There was no difference in headache recurrence or adverse events between groups. CONCLUSIONS: The approach of combining iv metoclopramide with ketorolac failed to improve pain scores in children presenting for acute treatment of migraine headache in the ED compared to metoclopramide monotherapy. Most patients were discharged with residual pain. Further comparative studies are needed to test alternative ED treatments for migraine in children or adolescents.

Characteristics of Adults with Migraine in Alberta, Canada: A Population-Based Study.

BACKGROUND: Migraine, including episodic migraine (EM) and chronic migraine (CM), is a common neurological disorder that imparts a substantial health burden. OBJECTIVE: Understand the characteristics and treatment of EM and CM from a population-based perspective. METHODS: This retrospective population-based cross-sectional study utilized administrative data from Alberta. Among those with a migraine diagnostic code, CM and EM were identified by an algorithm and through exclusion, respectively; characteristics and migraine medication use were examined with descriptive statistics. RESULTS: From 79,076 adults with a migraine diagnostic code, 12,700 met the criteria for CM and 54,686 were considered to have EM. The majority of migraineurs were female, the most common comorbidity was depression, and individuals with CM had more comorbidities than EM. A larger proportion of individuals with CM versus EM were dispensed acute (80.6%: CM; 63.4%: EM) and preventative (58.0%: CM; 28.9%: EM) migraine medications over 1 year. Among those with a dispensation, individuals with CM had more acute (13.6 ± 32.2 vs. 4.6 ± 10.9 [mean ± standard deviation], 95% confidence interval [CI] 7.7-8.3), and preventative (12.6 ± 43.5 vs. 5.0 ± 12.6, 95% CI 6.9-8.4) migraine medication dispensations than EM, over 1-year. Opioids were commonly used in both groups (proportion of individuals dispensed an opioid over 1-year: 53.1%: CM; 25.7%: EM). CONCLUSIONS: Individuals with EM and CM displayed characteristics and medication use patterns consistent with other reports. Application of this algorithm for CM may be a useful and efficient means of identifying subgroups of migraine using routinely collected health data in Canada.

Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial.

BACKGROUND: Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death. METHODS: This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained. Outcomes were determined by telephone follow-up and administrative data. RESULTS: Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned, 111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49-1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with hydroxychloroquine and safety. INTERPRETATION: There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT04329611.

Opioid use in medical cannabis authorization adult patients from 2013 to 2018: Alberta, Canada.

BACKGROUND: The opioid overdose epidemic in Canada and the United States has become a public health crisis - with exponential increases in opioid-related morbidity and mortality. Recently, there has been an increasing body of evidence focusing on the opioid-sparing effects of medical cannabis use (reduction of opioid use and reliance), and medical cannabis as a potential alternative treatment for chronic pain. The objective of this study is to assess the effect of medical cannabis authorization on opioid use (oral morphine equivalent; OME) between 2013 and 2018 in Alberta, Canada. METHODS: All adult patients defined as chronic opioid users who were authorized medical cannabis by their health care provider in Alberta, Canada from 2013 to 2018 were propensity score matched to non-authorized chronic opioid using controls. A total of 5373 medical cannabis patients were matched to controls, who were all chronic opioid users. The change in the weekly average OME of opioid drugs for medical cannabis patients relative to controls was measured. Interrupted time series (ITS) analyses was used to assess the trend change in OME during the 26 weeks (6 months) before and 52 weeks (1 year) after the authorization of medical cannabis among adult chronic opioid users. RESULTS: Average age was 52 years and 54% were female. Patients on low dose opioids (< 50 OME) had an increase in their weekly OME per week (absolute increase of 112.1 OME, 95% CI: 104.1 to 120.3); whereas higher dose users (OME > 100), showed a significant decrease over 6 months (- 435.5, 95% CI: - 596.8 to - 274.2) compared to controls. CONCLUSIONS: This short-term study found that medical cannabis authorization showed intermediate effects on opioid use, which was dependent on initial opioid use. Greater observations of changes in OME appear to be in those patients who were on a high dosage of opioids (OME > 100); however, continued surveillance of patients utilizing both opioids and medical cannabis is warranted by clinicians to understand the long-term potential benefits and any harms of ongoing use.