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.

Siloed mentality, health system suboptimization and the healthcare symphony: a Canadian perspective.

Measuring and optimizing a health system is challenging when patient care is split between many independent organizations. For example, patients receive care from their primary care provider, outpatient specialist clinics, hospitals, private providers and, in some instances, family members. These silos are maintained through different funding sources (or lack of funding) which incentivize siloed service delivery. A shift towards prioritizing patient outcomes and keeping the patient at the centre of care is emerging. However, competing philosophies on patient needs, how health is defined and how health is produced and funded is creating and engraining silos in the delivery of health services. Healthcare and health outcomes are produced through a series of activities conducted by diverse teams of health professionals working in concert. Health professionals are continually learning from each patient interaction; however, silos are barriers to information exchange, collaborative evidence generation and health system improvement. This paper presents a systems view of healthcare and provides a systems lens to approach current challenges in health systems. The first part of the paper provides a background on the current state and challenges to healthcare in Canada. The second part presents potential reasons for continued health system underperformance. The paper concludes with a system perspective for addressing these challenges.

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.

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.

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.

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.

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.

Improved care and management of paediatric neurological patients evaluated at a paediatric Rapid Access Neurology clinic: A pilot study.

AIM: Referral wait times for paediatric neurological patients are increasing, leading to an increased burden on the emergency department (ED). The paediatric Rapid Access Neurology (pRAN) clinic was created for paediatric patients who are clinically stable, but require an urgent paediatric neurology consultation. The objectives were to evaluate the pathways of referral, accuracy of referring diagnoses, adherence to clinic appointments, impact of clinic visitation on ED visits and patient satisfaction. METHODS: Data were collected from the pRAN clinic from March 2018 until April 2019. Information was obtained from patient charts including the referring and final diagnosis, management plan and the number of visits made to the ED before and after visiting the pRAN clinic. RESULTS: Of the 256 referred patients, 91 met inclusion criteria. The most frequent referral diagnosis was a seizure. Referring physicians and pRAN clinic neurologists differed significantly in the level of diagnostic agreement for patients <2 years of age (P = 0.03; 95% confidence interval (CI) -0.294, 0.373). There was a significant reduction in visits to the ED made by patients 3 months after the pRAN appointment compared with before the visit (P < 0.001; 95% CI -0.9070, -0.4088). The majority of patients felt that the clinic had high value and were satisfied with their follow-up plan. CONCLUSION: This pilot study showed that a pRAN clinic can improve the accuracy of neurological diagnoses and management, especially for children <2 years of age. In addition, pRAN clinic patients make fewer subsequent visits to the ED and express high satisfaction with their care.

Interobserver Agreement in the Assessment of Clinical Findings in Children with Headaches.

OBJECTIVE: To determine the interobserver agreement of history and physical examination findings in children undergoing evaluation in the emergency department (ED) for headaches. STUDY DESIGN: We conducted a prospective, cross-sectional study of children aged 2-17 years evaluated at 3 tertiary-care pediatric EDs for non-traumatic headaches. Two clinicians independently completed a standardized assessment of each child and documented the presence or absence of history and physical examination variables. Unweighted κ statistics were determined for 68 history and 24 physical examination variables. RESULTS: We analyzed 191 paired observations; median age was 12 years, with 19 (9.9%) children younger than 7 years. Interrater reliability was at least moderate (κ ≥ 0.41) for 41 (60.3%) patient history variables. Eleven (61.1%) of 18 physical examination variables for which κ statistics could be calculated had a κ that was at least moderate. CONCLUSIONS: A substantial number of history and physical examination findings demonstrated at least moderate κ statistic values when assessed in children with headaches in the ED. These variables may be generalizable across different types of clinicians for evaluation of children with headaches. If also found to predict the presence or absence of emergent intracranial abnormalities, the more reliable clinical findings may be helpful in the development of clinical prediction rules or risk stratification models that could be used across settings for children with headaches.

No association between metoclopramide treatment in ED and reduced risk of post-concussion headache.

OBJECTIVE: There is a lack of definitive pediatric literature on effective pharmacotherapy for persistent post-concussion headache symptoms. This study assessed whether acute metoclopramide treatment in the Emergency Department (ED) was associated with a reduction in persistent headache in children at 1- and 4-weeks post-concussion. METHODS: Children aged 8-17years with acute concussion presenting to 9-Canadian Pediatric EDs were enrolled in a prospective cohort study, from August 2013-June 2015. Primary and secondary outcomes were persistent headache at 1- and 4-week post-injury respectively. Headache persistence was based on the one and four-week headache scores minus recalled pre-injury score using the Post-Concussion Symptom Inventory. The association between metoclopramide and headache persistence at 1- and 4-weeks were examined using unadjusted and adjusted regression and 1:4 propensity score matching model. RESULTS: Baseline assessments were completed in 2095 participants; 65 (3.1%) received metoclopramide within 48-hours of injury. At 1- and 4-weeks, 54% (963/1808) and 26% (456/1780) of participants had persistent headache relative to baseline respectively. In unadjusted analysis, no association between metoclopramide and headache persistence at 1-week was found [treated vs. untreated: 1-week (53% vs. 53%; relative risk (RR)=1.0 (95%CI: 0.8, 1.3); 4-weeks (27.3% vs. 25.6%; RR=1.0 (95% CI: 0.9, 1.2)]. Metoclopramide was not associated with lower headache risk on propensity score matching [treated vs. untreated: 1-week, n=220 (52% vs. 59.4%; RR=0.8 (95%CI: 0.6, 1.2) and 4-weeks, n=225 (27.1% vs. 32.8%; RR=0.9 (95%CI: 0.8, 1.1)]. CONCLUSION: Metoclopramide administration was not associated with a reduction in headache persistence in children seeking ED care due to a concussion. Further research is necessary to determine which pharmacotherapies may be effective for acute and persistent post-concussive headache.

Quantitative phenotypic and network analysis of 1q44 microdeletion for microcephaly.

As genome wide techniques become more common, an increasing proportion of patients with intellectual disability (ID) are found to have genetic defects allowing genotype-phenotype correlations. Previously, AKT3 deletion was suggested to be responsible for microcephaly in patients with 1q43-q44 deletion syndrome, but this does not correspond to all cases. We report a case of a de novo 1q44 deletion in an 8-year-old boy with microcephaly in whom AKT3 is not deleted. We used a systematic review of the literature, our patient, and network analysis to gain a better understanding of the genetic basis of microcephaly in 1q deletion patients. Our analysis showed that while AKT3 deletion is associated with more severe (≤3 SD) microcephaly in 1q43-q44 deletion patients, other genes may contribute to microcephaly in AKT3 intact patients with microcephaly and 1q43-44 deletion syndrome. We identified a potential role for HNRNPU, SMYD3, NLRP3, and KIF26B in microcephaly. Overall, our study highlights the need for network analysis and quantitative measures reporting in the phenotypic analysis of a complex genetic syndrome related to copy number variation.

The Economic Contribution of Industry-Sponsored Pharmaceutical Clinical Trials.

PURPOSE: In pharmaceutical clinical trials, industrial sponsors pay for study drugs and related healthcare services. We conducted a study to determine industry's economic contribution of these trials to the Alberta healthcare system.  Methods: We used data from two trial centers for cancer and non-cancer trials at the University of Alberta. For each trial (cancer, non-cancer), we calculated the cost of drugs provided by the sponsors using the market price, the cost of clinical services, and the cost of administrative services that they paid. We extrapolated these results to all trials in Alberta based on information obtained from the registration website ClinicalTrials.gov.  Results: Our sample consisted of 40 non-cancer and 39 cancer drug trials which were initiated in 2012. The monetary value of the industry sponsors' contribution was $799,055 per non-cancer and $630,243 per cancer drug trial. Drugs (in-trial and post-trial) accounted for 84% of the total contribution of the non-cancer drug trials whereas it represented 93% of all trial-related contributions in the cancer category. The total province-wide contribution of industry-sponsored drug trials which were initiated in 2012 was estimated to be $101 million, including open-label drugs in the non-cancer category.  Conclusions: Industry-sponsored pharmaceutical trials represent a major economic contributor to clinical research within the province.

Drugs for the acute treatment of migraine in children and adolescents.

BACKGROUND: Numerous medications are available for the acute treatment of migraine in adults, and some have now been approved for use in children and adolescents in the ambulatory setting. A systematic review of acute treatment of migraine medication trials in children and adolescents will help clinicians make evidence-informed management choices. OBJECTIVES: To assess the effects of pharmacological interventions by any route of administration versus placebo for migraine in children and adolescents 17 years of age or less. For the purposes of this review, children were defined as under 12 years of age and adolescents 12 to 17 years of age. SEARCH METHODS: We searched seven bibliographic databases and four clinical trial registers as well as gray literature for studies through February 2016. SELECTION CRITERIA: We included prospective randomized controlled clinical trials of children and adolescents with migraine, comparing acute symptom relieving migraine medications with placebo in the ambulatory setting. DATA COLLECTION AND ANALYSIS: Two reviewers screened titles and abstracts and reviewed the full text of potentially eligible studies. Two independent reviewers extracted data for studies meeting inclusion criteria. We calculated the risk ratios (RRs) and number needed to treat for an additional beneficial outcome (NNTB) for dichotomous data. We calculated the risk difference (RD) and number needed to treat for an additional harmful outcome (NNTH) for proportions of adverse events. The percentage of pain-free patients at two hours was the primary efficacy outcome measure. We used adverse events to evaluate safety and tolerability. Secondary outcome measures included headache relief, use of rescue medication, headache recurrence, presence of nausea, and presence of vomiting. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables. MAIN RESULTS: We identified a total of 27 randomized controlled trials (RCTs) of migraine symptom-relieving medications, in which 9158 children and adolescents were enrolled and 7630 (range of mean age between 8.2 and 14.7 years) received medication. Twenty-four studies focused on drugs in the triptan class, including almotriptan, eletriptan, naratriptan, rizatriptan, sumatriptan, sumatriptan + naproxen sodium, and zolmitriptan. Other medications studied included paracetamol (acetaminophen), ibuprofen, and dihydroergotamine (DHE). More than half of the studies evaluated sumatriptan. All but one study reported adverse event data. Most studies presented a low or unclear risk of bias, and the overall quality of evidence, according to GRADE criteria, was low to moderate, downgraded mostly due to imprecision and inconsistency. Ibuprofen was more effective than placebo for producing pain freedom at two hours in two small studies that included 162 children (RR 1.87, 95% confidence interval (CI) 1.15 to 3.04) with low quality evidence (due to imprecision). Paracetamol was not superior to placebo in one small study of 80 children. Triptans as a class of medication were superior to placebo in producing pain freedom in 3 studies involving 273 children (RR 1.67, 95% CI 1.06 to 2.62, NNTB 13) (moderate quality evidence) and 21 studies involving 7026 adolescents (RR 1.32, 95% CI 1.19 to 1.47, NNTB 6) (moderate quality evidence). There was no significant difference in the effect sizes between studies involving children versus adolescents. Triptans were associated with an increased risk of minor (non-serious) adverse events in adolescents (RD 0.13, 95% CI 0.08 to 0.18, NNTH 8), but studies did not report any serious adverse events. The risk of minor adverse events was not significant in children (RD 0.06, 95% CI - 0.04 to 0.17, NNTH 17). Sumatriptan plus naproxen sodium was superior to placebo in one study involving 490 adolescents (RR 3.25, 95% CI 1.78 to 5.94, NNTB 6) (moderate quality evidence). Oral dihydroergotamine was not superior to placebo in one small study involving 13 children. AUTHORS' CONCLUSIONS: Low quality evidence from two small trials shows that ibuprofen appears to improve pain freedom for the acute treatment of children with migraine. We have only limited information on adverse events associated with ibuprofen in the trials included in this review. Triptans as a class are also effective at providing pain freedom in children and adolescents but are associated with higher rates of minor adverse events. Sumatriptan plus naproxen sodium is also effective in treating adolescents with migraine.

Clinical Risk Score for Persistent Postconcussion Symptoms Among Children With Acute Concussion in the ED.

IMPORTANCE: Approximately one-third of children experiencing acute concussion experience ongoing somatic, cognitive, and psychological or behavioral symptoms, referred to as persistent postconcussion symptoms (PPCS). However, validated and pragmatic tools enabling clinicians to identify patients at risk for PPCS do not exist. OBJECTIVE: To derive and validate a clinical risk score for PPCS among children presenting to the emergency department. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter cohort study (Predicting and Preventing Postconcussive Problems in Pediatrics [5P]) enrolled young patients (aged 5-<18 years) who presented within 48 hours of an acute head injury at 1 of 9 pediatric emergency departments within the Pediatric Emergency Research Canada (PERC) network from August 2013 through September 2014 (derivation cohort) and from October 2014 through June 2015 (validation cohort). Participants completed follow-up 28 days after the injury. EXPOSURES: All eligible patients had concussions consistent with the Zurich consensus diagnostic criteria. MAIN OUTCOMES AND MEASURES: The primary outcome was PPCS risk score at 28 days, which was defined as 3 or more new or worsening symptoms using the patient-reported Postconcussion Symptom Inventory compared with recalled state of being prior to the injury. RESULTS: In total, 3063 patients (median age, 12.0 years [interquartile range, 9.2-14.6 years]; 1205 [39.3%] girls) were enrolled (n = 2006 in the derivation cohort; n = 1057 in the validation cohort) and 2584 of whom (n = 1701 [85%] in the derivation cohort; n = 883 [84%] in the validation cohort) completed follow-up at 28 days after the injury. Persistent postconcussion symptoms were present in 801 patients (31.0%) (n = 510 [30.0%] in the derivation cohort and n = 291 [33.0%] in the validation cohort). The 12-point PPCS risk score model for the derivation cohort included the variables of female sex, age of 13 years or older, physician-diagnosed migraine history, prior concussion with symptoms lasting longer than 1 week, headache, sensitivity to noise, fatigue, answering questions slowly, and 4 or more errors on the Balance Error Scoring System tandem stance. The area under the curve was 0.71 (95% CI, 0.69-0.74) for the derivation cohort and 0.68 (95% CI, 0.65-0.72) for the validation cohort. CONCLUSIONS AND RELEVANCE: A clinical risk score developed among children presenting to the emergency department with concussion and head injury within the previous 48 hours had modest discrimination to stratify PPCS risk at 28 days. Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility.

Tic versus TAC: differentiating the neuralgias (trigeminal neuralgia) from the cephalalgias (SUNCT and SUNA).

Trigeminal neuralgia, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA) are classified as distinct disorders in the International Classification of Headache Disorders 3 beta (ICHD-3 beta). SUNCT and SUNA are primary headache disorders included among the trigeminal autonomic cephalalgias. Trigeminal neuralgia is classified under painful cranial neuropathies and other facial pains. The classification criteria of these conditions overlap significantly which could lead to misdiagnosis. The reported overlap among these conditions has called into question whether they should be considered distinct entities or rather a continuum of the same disorder. This review explores the known overlap and how other features not included in the ICHD-3 beta criteria may better differentiate the "Tics" (trigeminal neuralgia) from the "TACs" (SUNCT and SUNA).

Randomized controlled trial of treatment expectation and intravenous fluid in pediatric migraine.

OBJECTIVE: (1) The primary objectives were (1) to assess the response to intravenous (IV) fluid in children presenting to the ED with migraine and; (2) to assess the effect of treatment expectation on the response to I. BACKGROUND: Despite a lack of evidence for the practice, many emergency department (ED) migraine treatment protocols include a bolus of IV fluid. This study assessed the overall response to IV fluid hydration and the effect of expected medication treatment on the pain response among children and adolescents with migraine in an urban ED. METHODS: A single-blind, randomized parallel arm trial of 10 mL/kg IV 0.9% sodium chloride for children and adolescents aged 5-17 years presenting to a pediatric ED with migraine. Patients were randomized into group A (no expectation of medication in combination with IV fluid) and group B (expectation that medication may be given simultaneously). All participants were treated with standard care following the 30-minute assessment. RESULTS: Forty-seven participants were randomized and 2 were excluded; mean age was 13.3 years and 31 (67.4%) were females. Demographics and baseline characteristics were similar between groups. Overall, there was no statistically significant difference for the primary outcome - change from baseline on the visual analog scale (VAS) at 30 minutes with a mean change of -12.3 mm (standard deviation [SD] 17.9) in group A and -12.7 mm (SD 13.2) in group B (P = .936). The standardized difference between the 2 means (Cohen's d effect size) was low at 0.024 (95% confidence interval [CI] -0.56 to 0.61). Overall, complete headache relief was observed in only 1 participant; 16 of 45 (35.6%; 95% CI 21.8 to 51.2) had a reduction in headache of 33% or more and 8 of 45 (17.8%; 95% CI 6.1 to 29.4%) had a minimum clinical significant difference of 30 mm or more on VAS with 4 in each group. Thirteen of 39 patients with follow-up data (33.3%; 95% CI 19.1 to 50.2%) reported a moderate or severe headache at the 24-hour follow up with no difference between groups; only 3 patients returned to the ED. One participant reported a minor IV-related adverse event. CONCLUSIONS: The overall decrease in pain with IV fluid is small and clinically insignificant. Treatment expectation did not significantly influence headache relief at 30 minutes with IV fluid hydration in children or adolescents with migraine in the ED. The average relief of headache with IV fluid alone was small; however, a clinically meaningful response was observed in 17.8%. Recurrence of headache is common in 33% after ED discharge.

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.