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Objective: To assess the accuracy of lipid screening strategies to identify individuals at increased risk of coronary heart disease mortality.Patients: The 15% random sample of adults recruited into the Lipid Research Clinic Prevalence and Follow-up Studies, which included 3678 men and women aged 35 to 74 years. Total plasma cholesterol levels, lipoprotein fractions, and other coronary risk factors at study entry were compared with subsequent coronary heart disease mortality (mean follow-up, 12.2 years).Main Outcome Measures: The areas under receiver operating characteristic curves for blood lipids, lipid ratios, the screening guidelines proposed by the National National Cholesterol Education Program, those of the Canadian Consensus Conference on Cholesterol, and a coronary risk model that used Framingham data.Main Results: The current National Cholesterol Education Program guidelines (area under the curve, 0.74) were significantly (P = .03) more accurate than the old National Cholesterol Education Program guidelines (area, 0.72). The ratio of total plasma cholesterol level to high-density lipoprotein cholesterol level (area, 0.72) was as accurate as current National Cholesterol Education Program guidelines. The coronary risk model (area, 0.85) was superior (P < .003) to all other screening maneuvers. Compared with the current National Cholesterol Education Program guidelines, the risk model demonstrated superior test sensitivity (70% vs 45%) with only slightly reduced specificity (82% vs 86%).Conclusion: The ratio of total plasma cholesterol level to high-density lipoprotein cholesterol level is as accurate as current American screening guidelines. Future guidelines should better incorporate high-density lipoprotein cholesterol levels and nonlipid risk factors to target high-risk individuals accurately. [ABSTRACT FROM AUTHOR]

Discovery tools are emerging in libraries. These tools offer library patrons the ability to concurrently search the library catalog and journal articles. While vendors rush to provide feature-rich interfaces and access to as much content as possible, librarians wonder about the usefulness of these tools to library patrons. In order to learn about both the utility and usability of EBSCO Discovery Service, James Madison University conducted a usability test with eight students and two faculty members. The test consisted of nine tasks focused on common patron requests or related to the utility of specific discovery tool features. Software recorded participants’ actions and time on task, human observers judged the success of each task, and a post-survey questionnaire gathered qualitative feedback and comments from the participants. Overall, participants were successful at most tasks, but specific usability problems suggested some interface changes for both EBSCO Discovery Service and JMU’s customizations of the tool. The study also raised several questions for libraries above and beyond any specific discovery tool interface, including the scope and purpose of a discovery tool versus other library systems, working with the large result sets made possible by discovery tools, and navigation between the tool and other library services and resources. This article will be of interest to those who are investigating discovery tools, selecting products, integrating discovery tools into a library web presence, or performing evaluations of similar systems.

Background: The pattern of skin diseases varies form one country to another and across different parts within the same country. A two-day multispecialty medical camp was held among the local population at the district of Kausambi, Allahabad, UP, in October 2005. A cross section of pattern of skin diseases observed at the camp is reported and compared with similar studies in literature. Materials and Methods: All cases attending the medical camp were included in the study. All those with dermatological complaints were examined in detail, brief relevant history was elicited and clinical diagnosis was made. Results: Skin diseases comprised 7.86% of all those who attended the camp. The 11-20 year age group was the most common age group involved with 164 (31.4%) cases. Infective disorders were found in 59.1% and noninfective disorders in 40.9% of all the skin cases. Among the infective disorders, fungal infections were most common (54.52%), and among the noninfective dermatoses, eczemas were most common (39.2%) cutaneous disorders. Conclusion: Our study brought out a higher prevalence of infective dermatoses and a relatively higher, but statistically insignificant, prevalence of fungal infections, scabies and eczemas, thereby reflecting minor regional variance in our study group.

Idiopathic eruptive macular pigmentation (IEMP) is a rather under-reported condition of unknown etiology. Clinically consisting of benign hyperpigmented macules, the condition is characterized histopathologically by dermal melanization. It must be differentiated from lichen planus pigmentosus, erythema dyschromicum perstans, fixed drug eruption and mastocytosis.

Abstract This protocol outlines and evaluates a modified scanning procedure for a customized spectral domain optical coherence tomography (SD-OCT) imaging apparatus within the wild-type C57Bl/6 mouse posterior segment. This modified protocol allows for the capture of a 50 degree field of view spanning 3 mm by 3 mm perimeter with the optic disc as the central point. By utilizing this scanning protocol a more reliable measurement of retinal thickness can be achieved outside the fluctuating region of the optic disc. This protocol, when applied to this high resolution device, enables non-invasive in vivo histological imaging and biometric assessment of the various layers of the rodent posterior segment within a 20 – 30 min procedural time-frame. This protocol could establish a standardized method for evaluating morphological changes, with this commercial SDOCT device, when assessing longitudinal disease pathophysiology and treatment response in mouse models for future vision science research.

Abstract Introduction Spectral-domain optical coherence tomography findings in a patient with acute macular neuroretinopathy, and correlation with functional defects on microperimetry, are presented. Case presentation A 25-year old Caucasian woman presented with bitemporal field defects following an upper respiratory tract infection. Her visual acuity was 20/20 in both eyes and a dilated fundus examination revealed bilateral hyperpigmentary changes in the papillomacular bundle. Our patient underwent further evaluation with spectral-domain optical coherence tomography, infrared and fundus autofluorescence imaging. Functional changes were assessed by microperimetry. Infrared imaging showed the classic wedge-shaped defects and spectral-domain optical coherence tomography exhibited changes at the inner segment-outer segment junction, with a thickened outer plexiform layer overlying these areas. Fluorescein and indocyanine green angiography did not demonstrate any perfusion defects or any other abnormality. Microperimetry demonstrated focal elevation in threshold correlating with the wedge-shaped defects in both eyes. Conclusion Spectral-domain optical coherence tomography findings provide new evidence of the involvement of the outer plexiform layer of the retina in acute macular neuroretinopathy.

Abstract Background Optic nerve head drusen (ONHD) are white calcareous deposits, seen either superficially on the optic nerve head or buried within it. Diagnosis of ONHD is made by one or more ways: clinical exam, autofluorescence, ultrasound of the optic nerve, CT scan and/or visual field examination. The present study describes features of ONHD based on another diagnostic modality, the spectral-domain OCT (Spectralis). Methods This is a retrospective case series of 5 patients with bilateral ONHD with a best-corrected visual acuity of 20/20 and no other posterior segment pathology. All the patients underwent fundus photography, fundus autofluorescence, B-scan ultrasonography, Spectralis OCT and Humphrey 30-2 threshold visual fields. Results All 5 patients had surface ONHD which were autofluorescent and echodense on B-scan ultrasonography. Spectralis OCT findings in the corresponding areas include 'scattered spots with high reflectivity' casting a shadow underneath. The reflectivity can be distinctly differentiated from the blood vessels on the optic nerve. Two patients had an arcuate scotoma on the Humphrey visual fields. No correlation was found between the changes on Spectralis OCT with that of visual field. Conclusions Spectralis OCT is another useful ancillary investigation in the diagnosis of ONHD and we describe the features in the present study.

Abstract Background To compare the clinical efficacy of lidocaine 2% with tetracaine 0.5% for cataract surgery. Methods In a randomized, multi-surgeon, controlled clinical trial,122 consecutive cataract cases eligible for topical anesthesia, were randomly assigned to receive lidocaine 2% gel (1 ml) or tetracaine solution 0.5% (TetraVisc, 0.5 ml) before clear corneal phacoemulsification. Main outcome measure was visual analog scale (0 to 10), which was used to measure intra-operative pain. Secondary outcome measures included patients' discomfort due to tissue manipulation and surgeon graded patients' cooperation. Duration of surgery and intra-operative complications were also recorded. Results The mean age in TetraVisc (TV) group was 70.4 years and in the lidocaine gel group (LG) it was 70.6 years (p = 0.89). Patient reported mean intra-operative pain scores by visual analog scale were 0.70 ± 0.31 in TV group and 1.8 ± 0.4 in LG group (P < 0.001). Mean patient cooperation was also marginally better in the TV group (8.3 ± 0.3) compared to LG group (8.4 ± 0.6) (P = 0.25). 96% of patients in TV group showed intra-operative corneal clarity compared to 91% in LG group. TV group had less (1 out of 61 patients, 1.6%) intra-operative complications than LG group (3 out of 61 patients, 4.8%). No anesthesia related complications were noted in either group Conclusion Topical TetraVisc solution was superior to lidocaine 2% gel for pain control in patients undergoing clear corneal phacoemulsification. Lidocaine 2% gel is similar to TetraVisc in patient comfort and surgeon satisfaction. Trial Registration Clinical trials number: ISRCTN78374774

Background: The need for new therapies to improve survival and outcomes in pediatric oncology along with the lack of approval and accessible clinical trials has led to "out-of-trial" use of innovative therapies. We conducted a retrospective analysis of requests for innovative anticancer therapy in Canadian pediatric oncology tertiary centers for patients less than 30 years old between 2013 and 2020., Methods: Innovative therapies were defined as cancer-directed drugs used (a) off-label, (b) unlicensed drugs being used outside the context of a clinical trial, or (c) approved drugs with limited evidence in pediatrics. We excluded cytotoxic chemotherapy, cellular products, and cytokines., Results: We retrieved data on 352 innovative therapy drug requests. Underlying diagnosis was primary CNS tumor 31%; extracranial solid tumor 37%, leukemia/lymphoma 22%, LCH 2%, and plexiform neurofibroma 6%. RAS/MAP kinase pathway inhibitors were the most frequently requested innovative therapies in 28% of all requests followed by multi-targeted tyrosine kinase inhibitors (17%), inhibitors of the PIK3CA-mTOR-AKT pathway (8%), immune checkpoints inhibitors (8%), and antibody drug conjugates (8%). In 112 out of 352 requests, innovative therapies were used in combination with another anticancer agent. 48% of requests were motivated by the presence of an actionable molecular target. Compassionate access accounted for 52% of all requests while public insurance was used in 27%. Mechanisms of funding varied between provinces., Conclusion: This real-world data collection illustrates an increasing use of "out-of-trial" innovative therapies in pediatric oncology. This new field of practice warrants further studies to understand the impact on patient trajectory and equity in access to innovative therapies., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The presence of subclinical optic nerve (ON) injury in youth living with pediatric-onset MS has not been fully elucidated. Magnetization transfer saturation (MTsat) is an advanced magnetic resonance imaging (MRI) parameter sensitive to myelin density and microstructural integrity, which can be applied to the study of the ON., Objective: The objective of this study was to investigate the presence of subclinical ON abnormalities in pediatric-onset MS by means of magnetization transfer saturation and evaluate their association with other structural and functional parameters of visual pathway integrity., Methods: Eleven youth living with pediatric-onset MS (ylPOMS) and no previous history of optic neuritis and 18 controls underwent standardized brain MRI, optical coherence tomography (OCT), Magnetoencephalography (MEG)-Visual Evoked Potentials (VEPs), and visual battery. Data were analyzed with mixed effect models., Results: While ON volume, OCT parameters, occipital MEG-VEPs outcomes, and visual function did not differ significantly between ylPOMS and controls, ylPOMS had lower MTsat in the supratentorial normal appearing white matter (-0.26 nU, p  = 0.0023), and in both in the ON (-0.62 nU, p  < 0.001) and in the normal appearing white matter of the optic radiation (-0.56 nU, p  = 0.00071), with these being positively correlated (+0.57 nU, p  = 0.00037)., Conclusions: Subclinical microstructural injury affects the ON of ylPOMS. This may appear as MTsat changes before being detectable by other currently available testing.

The genetic and molecular basis of flagellar motility has been investigated for several decades, with innovative research strategies propelling advances at a steady pace. Furthermore, as the phenomenon is examined in diverse bacteria, new taxon-specific regulatory and structural features are being elucidated. Motility is also a straightforward bacterial phenotype that can allow undergraduate researchers to explore the palette of molecular genetic tools available to microbiologists. This study, driven primarily by undergraduate researchers, evaluated hundreds of flagellar motility mutants in the Gram-negative plant-associated bacterium Agrobacterium fabrum. The nearly saturating screen implicates a total of 37 genes in flagellar biosynthesis, including genes of previously unknown function., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Calvopina-Chavez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives To determine to what extent acute demyelinating episodes versus chronic degenerative phenomena drive retinal neuroaxonal damage in pediatric acquired demyelinating syndromes (ADS). Methods We acquired optical coherence tomography (OCT) data (follow-up range: 2 weeks - 5 years, at variable intervals from presentation) in pediatric participants who had multiple sclerosis (MS), monophasic ADS, or were healthy. Multivariable mixed effects models were used to assess the association of the number of demyelinating episodes (either optic neuritis [ON], or non-ON relapses) with changes in retinal nerve fiber layer (RNFL) or ganglion cell layer-inner plexiform layer (GCIPL) thickness. Results 64 OCT sans from 23 MS, and 33 scans from 12 monophasic ADS participants were compared with 68 scans from 62 healthy participants. The first ON episode had the biggest impact on RNFL or GCIPL thickness in monophasic ADS (RNFL: -7.9 µm, CI=5.5, p = 0.0056; GCIPL: -8.4 µm, CI=4.4, p = 0.0002) and MS (RNFL: -16 µm, CI = 3.7, p < 10 -6 ; GCIPL: -15 µm, CI = 2.6, p < 10 -6 ). Non-ON relapses were also associated with small but significant retinal thickness reductions in MS (RNFL: -2.6 µm/relapse, CI = 1.4, p = 0.0003; GCIPL: -2.8 µm/relapse, CI = 0.89, p < 10 -6 ). MS participants showed progressive GCIPL thinning independent of acute demyelinating episodes (-2.7 µm/year, CI = 1.9, p = 0.0058). Conclusions We showed a prominent impact of early ON episodes on OCT measures of neuroaxonal structure in patients with ADS. We also demonstrated negative effects of non-ON relapses, and the presence of chronic retinal neurodegenerative changes, in youth with MS., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Several outpatient coronavirus disease 2019 (COVID-19) therapies have reduced hospitalization in randomized controlled trials. The choice of therapy may depend on drug efficacy, toxicity, pricing, availability, and available infrastructure. To facilitate comparative decision-making, we evaluated the efficacy of each treatment in clinical trials and estimated the cost per hospitalization prevented., Methods: Wherever possible, we obtained relative risk for hospitalization from published randomized controlled trials. Otherwise, we extracted data from press releases, conference abstracts, government submissions, or preprints. If there was >1 study, the results were meta-analyzed. Using relative risk, we estimated the number needed to treat (NNT), assuming a baseline hospitalization risk of 5%, and compared the cost per hospitalization prevented with the estimate for an average Medicare COVID-19 hospitalization ($21 752). Drug pricing was estimated from GoodRx, from government purchases, or manufacturer estimates. Administrative and societal costs were not included. Results will be updated online as new studies emerge and/or final numbers become available., Results: At a 5% risk of hospitalization, the estimated NNT was 80 for fluvoxamine, 91 for colchicine, 72 for inhaled corticosteroids, 24 for nirmatrelvir/ritonavir, 50 for molnupiravir, 28 for remdesivir, 25 for sotrovimab, 29 for casirivimab/imdevimab, and 29 for bamlanivimab/etesevimab. For drug cost per hospitalization prevented, colchicine, fluvoxamine, inhaled corticosteroids, and nirmatrelvir/ritonavir were below the Medicare estimated hospitalization cost., Conclusions: Many countries are fortunate to have access to several effective outpatient therapies to prevent COVID-19 hospitalization. Given differences in efficacy, toxicity, cost, and administration complexity, this assessment serves as one means to frame treatment selection., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: This study quantified and compared weekday and weekend patterns of device-measured physical activity (PA) and sedentary behavior between youth with pediatric multiple sclerosis (MS) and controls for the purpose of informing future PA behavior change interventions., Methods: Participant data were obtained from 3 ongoing observational studies, and the sample included 40 participants with pediatric MS and 41 controls. Light PA (LPA), moderate to vigorous PA (MVPA), and sedentary behavior data were collected using activity monitors (ActiGraph LLC) over 1 week. The main analysis involved a 2-way mixed factor analysis of variance with group as a between-subjects factor (pediatric MS vs control) and day as a within-subjects factor (weekday vs weekend day)., Results: There was no group by day interaction from the analysis of variance for percentage of activity monitor wear time spent in LPA, MVPA, or sedentary behavior. There was no effect of group for LPA, MVPA, or sedentary behavior. There was an effect of day of week on percentage of day spent in LPA, MVPA, and sedentary behavior., Conclusions: These results suggest that youth with pediatric MS and controls were less physically active and more sedentary on weekends than on weekdays, but there were no differences between groups in PA and sedentary behavior overall or by day of the week. Physical activity interventions may be more successful by initially targeting weekend day activity., Competing Interests: Financial Disclosures: The authors declare no conflicts of interest., (© 2022 Consortium of Multiple Sclerosis Centers.)

The 2021 guidelines primary panel selected clinically relevant questions and produced updated recommendations, on the basis of important new findings that have emerged since the 2016 guidelines. In patients with clinical atherosclerosis, abdominal aortic aneurysm, most patients with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy continues to be recommended. We have introduced the concept of lipid/lipoprotein treatment thresholds for intensifying lipid-lowering therapy with nonstatin agents, and have identified the secondary prevention patients who have been shown to derive the largest benefit from intensification of therapy with these agents. For all other patients, we emphasize risk assessment linked to lipid/lipoprotein evaluation to optimize clinical decision-making. Lipoprotein(a) measurement is now recommended once in a patient's lifetime, as part of initial lipid screening to assess cardiovascular risk. For any patient with triglycerides ˃ 1.5 mmol/L, either non-high-density lipoprotein cholesterol or apolipoprotein B are the preferred lipid parameter for screening, rather than low-density lipoprotein cholesterol. We provide updated recommendations regarding the role of coronary artery calcium scoring as a clinical decision tool to aid the decision to initiate statin therapy. There are new recommendations on the preventative care of women with hypertensive disorders of pregnancy. Health behaviour modification, including regular exercise and a heart-healthy diet, remain the cornerstone of cardiovascular disease prevention. These guidelines are intended to provide a platform for meaningful conversation and shared-decision making between patient and care provider, so that individual decisions can be made for risk screening, assessment, and treatment., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Cardiovascular risk assessment has been shown to improve physicians' and patients' understanding of an individual's future risk of cardiovascular disease (CVD). It has also been shown to improve the management of cardiovascular risk factors including hypertension and dyslipidemia. Given the challenges of engaging patients to adhere to healthy lifestyle habits or take medications for hypertension and dyslipidemia, the primary role of CVD risk assessment should be to open a discussion about the patient's risk for CVD and associated conditions like adult-onset diabetes. Calculating a patient's long-term risk and estimating the benefits of lifestyle changes or risk factor management may then be used to support long-term patient adherence. However, risk assessment is only a first step and must be followed by evidence-based health-promotion strategies and risk factor medications that have been proven to work., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Thinning of the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCIPL) occur in the chronic phase after optic neuritis (ON) in children and reflect neuroaxonal injury. The objective of this study was to describe changes in RNFL and GCIPL thickness in the acute phase following pediatric ON., Methods: Data were collected prospectively from consecutive children presenting with ON as part of an incident acquired demyelinating event. Children with a final diagnosis of multiple sclerosis (n = 9, 10 ON-affected eyes) or monophasic demyelination (n = 16, 25 ON-affected eyes) who underwent spectral-domain optical coherence tomography (OCT) testing within 30 days of symptom onset were included. Standardized visual assessment was performed at presentation and 6-18 months follow-up. OCT measures were compared to those of healthy controls (n = 25, 50 eyes)., Results: Median (interquartile range [IQR]) global RNFL thickness was increased in ON-affected eyes (155 μm [114-199 μm]) compared to control eyes (104 μm [98.5-107.5 μm]; p < 0.0001). Compared to controls, fellow eyes demonstrated a reduced temporal quadrant RNFL thickness (59 μm [53-72 μm] versus 71.5 μm [65-81 μm]; p = 0.013) and lower GCIPL thickness (80.5 μm [74-88 μm] versus 87 μm [85-89 μm]; p = 0.003). The ON-affected eyes of children with monophasic demyelination demonstrated a greater global RNFL thickness (183.5 μm [146.5-206 μm]) compared to the ON-affected eyes of children with multiple sclerosis (108.5 μm [95-124 μm]; p = 0.01). OCT measures at presentation did not predict low-contrast visual acuity nor color vision at 6-18 months follow-up., Conclusion: Children with multiple sclerosis show less RNFL swelling in their ON-affected eyes at onset compared to children with monophasic demyelination. Lower GCIPL and temporal RNFL thickness in the clinically unaffected eyes of those children with unilateral ON suggests the presence of pre-existing neuroaxonal injury in children presenting with a first episode of ON. This finding may be driven by the subset of children with multiple sclerosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Hypertensive disorders of pregnancy (HDP) comprise an independent, sex-specific risk factor for cardiovascular disease (CVD) in women. This study examined the utility of CVD risk models proposed in the 2016 Canadian Cardiovascular Society (CCS) lipid guidelines to identify women requiring further screening or lipid treatment following HDP., Methods: Using data collected from the postpartum Maternal Health Clinic (MHC) at Kingston General Hospital in Kingston, Ontario and the Preeclampsia New Emerging Team (PE-NET) cohort study, the study investigators used the models recommended by the CCS guidelines and the cardiometabolic model of life expectancy in each cohort to estimate CVD risk in women after HDP. (Canadian Task Force Classification II-2)., Results: Using the 10-Year Modified Framingham Risk Score, all women were classified by the 2016 CCS Guidelines as low risk, requiring no follow-up. The 30-Year and Lifetime Risk Scores resulted in significant reclassification of women at risk in the PE-NET control and HDP groups (P < 0.001 and P < 0.0001, respectively); 49.2% of women with HDP were classified as high risk, requiring follow-up, compared with 14.3% of control subjects. Using the cardiometabolic model, median life expectancy was significantly lower and expected onset of CVD was earlier in the HDP group compared with the control group (P < 0.0001)., Conclusion: The 2016 CCS lipid guidelines' risk classification recommendations significantly underestimated lifelong CVD risk in the HDP group compared with the control group. Women with HDP also had a significant decrease in cardiometabolic life expectancy and an earlier predicted age at onset of CVD. Early primary prevention in this at-risk population may improve CVD outcomes and reduce the future burden on the health care system., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the results of a workplace wellness program that incorporates gamification principles., Design: In this prospective cohort study, the participation rate and observed health outcomes were evaluated after approximately 2 years., Setting and Participants: All permanent employees (n = 775) of a national company located in Canada were eligible to participate., Intervention: The wellness program included web-based challenges (team or individual) incorporating gamification strategies to improve exercise, nutrition, weight reduction, and mental health management behaviors., Measures and Analysis: The primary outcomes were employee participation rates. The secondary pre-specified outcomes were the sustained benefits of the program on physical and mental health measures., Results: Participation rates in the health screenings were 78% (baseline), 54% (year 1), and 56% (year 2). Participation in the 4 team web-based challenges ranged from 33% to 68% with 76% to 86% of participants tracking their activity on at least half of the days. After 2 years, there were significant clinical improvements in systolic blood pressure (-1.3mm Hg), total cholesterol/high-density lipoprotein (HDL) ratio (-0.14), glycated haemoglobin (HbA 1c ; -0.1%), weekly physical activity (+264 Metabolic Equivalents [METs]), perceived stress score (-17%), insomnia severity index (-16%), general fatigue (-10%), and reductions in the cardiovascular age gap (-0.3 years). Greater benefits occurred among employees at higher risk., Conclusions: Workplace wellness programs that evolve over time and focus primarily on fun and competitive challenges may support long-term participation, behavior change, and sustained improvements in clinical outcomes.

Objectives: To examine the longitudinal relationship between physical activity and fatigue and depression among youth with demyelinating conditions., Study Design: From September 2013 to March 2017, we performed a longitudinal study of consecutive youth diagnosed at their first visit with pediatric onset multiple sclerosis (POMS) or monophasic acquired demyelinating syndromes (mono-ADS) at a neuroinflammatory disorders clinic in a tertiary children's hospital. Fatigue was determined at each visit by the Pediatric Quality of Life Multidimensional Fatigue Scale, depressive symptoms by the Center of Epidemiologic Studies Depression Children Rating Scale, and physical activity level by the Godin Leisure Time Exercise Questionnaire. Mixed linear models were used to examine the associations of moderate-to-vigorous physical activity (MVPA) with fatigue and depression over time, adjusting for age, time from incident demyelination, sex, number of relapses, relapse within 30 days, and disability., Results: In 182 patients (48 POMS, age 15 ± 1.7 years, 35 female; and 134 mono-ADS, age 12 ± 3.6 years 67 female) with 538 visits (mean follow-up 3.6 ± 2.7 years and 4.2 ± 3.3 years, respectively), a trajectory of increased fatigue over time was observed in POMS (2.28 points/year, P = .008) and mono-ADS (1.33 points/year, P = .007) patients. Youth with POMS had more depressive symptoms (estimate = 11.4 points, P < .002) than mono-ADS. Depressive symptoms increased over time in female patients with POMS (estimate = 1.4 points/year, P < .02). MVPA was associated with lower depression (-0.09, P < .001) and general fatigue (0.13, P = .02) over time in POMS., Conclusions: Youth with POMS who have higher levels of MVPA demonstrate lesser depressive symptoms and lower fatigue over time. Our results may inform future interventions to manage mood and fatigue in POMS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Rates of medication nonadherence in youth with multiple sclerosis (MS) range from 10% to 60%. Qualitative studies of adherence can provide insight into children's own perspectives about barriers and facilitators to their adherence and inform future interventions. This qualitative longitudinal descriptive study included children with MS ( n = 28) participating in a randomized controlled trial focused on medication adherence ( clinicaltrials.gov : NCT02234713). Following established methods, three independent reviewers coded transcripts of motivational interviewing (MI) sessions (three interviews per subject, performed monthly over a 3-month period) for relevant themes. They were subsequently categorized using inductive content analysis. Youth described medication adherence as being dependent on the ability to build and maintain healthy habits related to medication use, including embodiment of these habits. Barriers and facilitators included remembering/forgetting, experiences with fatigue, and experiences with medication. These themes were maintained through the second and third interviews. Future research focus on barriers and facilitators to habit maintenance in this population.

Objective: To assess the association between daily moderate-to-vigorous physical activity (MVPA) and dentate gyrus volume (DGv) in pediatric patients with acquired demyelinating syndromes (ADSs) of the CNS., Methods: Cross-sectional analysis of accelerometry (7 days) and research protocol MRI data from 12 pediatric MS and 18 children with monophasic ADS (monoADS). Total brain and DGv were quantified using standardized methods. The association of daily minutes of MVPA with normalized DGv (nDGv) was assessed using multivariable generalized linear models., Results: Median (interquartile range) MVPA was lower in MS patients [9.5 (14)] and exhibited less variation than in monoADS patients [24.5 (47)]. nDGv did not differ significantly between groups [mean nDGv (SD) [cm 3 ]: MS 0.34 (0.1); monoADS 0.4 (0.1); p = 0.100]. In the monoADS group, every 1-minute increase in MVPA was associated with a 2.4-mm 3 increase in nDGv ( p = 0.0017), an association that was independent of age at incident demyelination, time from incident demyelination, sex, and brain white matter T2 lesion volume. No significant association was found between MVPA and nDGv (-2.6 mm 3 /min, p = 0.16) in the MS group., Conclusions: Higher MVPA associates with greater nDGv in children who have recovered from monophasic demyelination. Larger studies are required to determine whether MVPA can promote regional brain development, or limit tissue damage, in youth with MS.

Background: Medical school and residency training in ophthalmoscopic evaluation is limited, reducing diagnostic accuracy. We sought to evaluate the efficacy of self-study using an ophthalmoscopy simulator to improve the technical motor skills involved in direct funduscopy in postgraduate pediatric residents., Methods: In this randomized-controlled study, 17 pediatric residents (postgraduate years 1-3) were randomized to control (n=8) or intervention (n=9) groups. Participants were asked to correctly identify the funduscopic findings presented to them on an ophthalmoscopy simulator after being trained on its use. Each participant was asked to review 20 images of the fundus, and then record their multiple-choice response on a scantron sheet listing all possible funduscopic pathologies. Pre- and post-intervention testing was performed. Survey data assessing exposure to funduscopy skills during undergraduate and postgraduate training and overall experience with the simulator were collected., Results: Most (65% [11/17]) participants reported minimal or no formal teaching in ophthalmology during their undergraduate medical studies. Average pre-intervention score (of 20) was 10.24±1.75 (51%) for the entire group, with no statistically significant difference between average pre-score in the control (10.63±1.77) versus intervention (9.89±1.76, p=0.405) groups. Intervention subjects experienced a statistically significant improvement in scores (9.89±1.76 vs. 12.78±2.05, p=0.006 [95% confidence interval 4.80-0.98]), but control subjects did not., Conclusions: A single session with an ophthalmoscopy simulator can improve diagnostic accuracy in postgraduate pediatric trainees. Use of ophthalmoscopy simulation represents a novel addition to traditional learning methods for postgraduate pediatric residents that can help trainees to improve their confidence and accuracy in performing this challenging examination.

Background: Evolocumab, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, has been shown to reduce low-density lipoprotein levels by up to 60%. Despite the absence of a reduction in overall or cardiovascular mortality in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, some believe that, with longer treatment, such a benefit might eventually be realized. Our aim was to estimate the potential mortality benefit over a patient's lifetime and the cost per year of life saved (YOLS) for an average Canadian with established coronary artery disease. We also sought to estimate the price threshold at which evolocumab might be considered cost-effective for secondary prevention in Canada., Methods: We calibrated the Cardio-metabolic Model, a well-validated tool for predicting cardiovascular events and life expectancy, to the reduction in nonfatal events seen in the FOURIER trial. Assuming that long-term treatment will eventually result in mortality benefits, we estimated YOLSs and cost per YOLS with evolocumab treatment plus a statin compared to a statin alone. We then estimated the annual drug costs that would provide a 50% chance of being cost-effective at willingness-to-pay values of $50 000 and $100 000., Results: In secondary prevention in patients similar to those in the FOURIER study, evolocumab treatment would save an average of 0.34 (95% confidence interval [CI] 0.27-0.41) life-years at a cost of $101 899 (95% CI $97 325-$106 473), yielding a cost per YOLS of $299 482. We estimate that to have a 50% probability of achieving a cost per YOLS below $50 000 and $100 000 would require annual drug costs below $1200 and $2300, respectively., Interpretation: At current pricing, the use of evolocumab for secondary prevention is unlikely to be cost-effective in Canada., Competing Interests: Competing interests: None declared., (Copyright 2018, Joule Inc. or its licensors.)

The clinicaltrials.gov identifying number for the article titled "Impact of an electronic monitoring device and behavioral feedback on adherence to multiple sclerosis therapies in youth: results of a randomized trial" is NCT02234713 (https://clinicaltrials.gov/ct2/show/NCT02234713).

Objective: The aim of this study was to evaluate the impact of an employee wellness program in Canada., Methods: A comprehensive program including web-based lifestyle challenges was evaluated with annual health screenings., Results: Among 730 eligible employees, 688 (94%) registered for the program, 571 (78%) completed a health screening at baseline, and 314 (43%) at 1 year. Most (66%) employees tracked their activity for more than 6 weeks. At 1-year follow-up, there were significant clinical improvements in systolic blood pressure -3.4 mm Hg, and reductions in poor sleep quality (33% to 28%), high emotional stress (21% to 15%), and fatigue (11% to 6%). A positive dose-response was noted where the greatest improvements were observed among those who participated the most., Conclusion: The program had high employee engagement. After 1 year, the benefits included clinically important improvements in physical and mental health.

Background: Adherence to disease-modifying therapies (DMTs) in pediatric multiple sclerosis (MS) is not well understood. We examined the prevalence and risk factors for poor adherence in pediatric MS., Methods: This cross-sectional study recruited youth with MS from 12 North American pediatric MS clinics. In addition to pharmacy-refill data, patients and parents completed self-report measures of adherence and quality of life. Additionally, patients completed measures of self-efficacy and well-being. Factor analysis and linear regression methods were used., Results: A total of 66 youth (mean age, 15.7 years) received MS DMTs (33% oral, 66% injectable). Estimates of poor adherence (i.e. missing >20% of doses) varied by source: pharmacy 7%, parent 14%, and patient 41%. Factor analysis yielded two composites: adherence summary and parental involvement in adherence. Regressions revealed that patients with better self-reported physical functioning were more adherent. Parents were more likely to be involved in adherence when their child had worse parent-reported PedsQL School Functioning and lower MS Self-Efficacy Control. Oral DMTs were associated with lesser parental involvement in adherence., Conclusion: Rates of non-adherence varied by information source. Better self-reported physical functioning was the strongest predictor of adherence. Parental involvement in adherence was associated with worse PedsQL School Functioning and lower MS Self-Efficacy-measured confidence in controlling MS.

Purpose: To report the results of a randomized controlled trial using an electronic monitoring device (EM) plus a motivational interviewing (MI) intervention to enhance adherence to disease-modifying therapies (DMT) in pediatric MS., Methods: Fifty-two youth with MS (16.03 ± 2.2 years) were randomized to receive either MI (n = 25) (target intervention) or a MS medication video (n = 27) (attention control). Primary endpoint was change in adherence. Secondary outcomes included changes in quality of life, well-being and self-efficacy. Random effects modeling and Cohen's effect size computation evaluated intervention impact., Results: Longitudinal random effect models revealed that the MI group decreased their EM adherence (GroupxTime interaction = -0.19), while increasing frequency of parental DMT reminder (26.01)/administration (11.69). We found decreased EM use in the MI group at 6 months (Cohen's d = -0.61), but increased pharmacy refill adherence (d = 0.23). Parental reminders about medication increased in MI subjects vs controls (d = 0.59 at 3 months; d = 0.70 at 6 months). We found increases in self-reported adherence (d = 0.21) at 3 but not 6 months, fewer barriers to adherence at three (d = -0.58) and six months (d = -0.31), better physical (d = 0.23 at 3 months; d = 0.45 at 6 months), emotional (d = 0.25 at 3 months) and self-efficacy function (d = 0.55 at 3 months; 0.48 at 6 months), but worse well-being, including self-acceptance (d = -0.53 at 6 months) and environmental mastery (d = -0.42 at 3 and 6 months) in intervention as compared to control patients., Conclusions: Participants receiving MI + EM experienced worsening on objective measures of adherence and increased parental involvement, but improved on some self- and parent-reported measures. MI participants reported improvements in quality of life and self-efficacy, but worsened well-being.

Aicardi-Goutières syndrome (AGS) is an early-onset, genetic disease characterized by recurrent fever, multifocal lesions of the brain, and systemic autoimmunity. We report on 3 AGS patients, 2 siblings with an RNASEH2A gene mutation and 1 patient with a SAMHD1 gene mutation. Serial analysis of peripheral blood from all 3 AGS patients showed consistently elevated expression of the interferon-stimulated genes (ISGs): ISG15, RSAD2, and IFI27, not observed in unaffected family members. Enumeration of circulating white blood cells and platelets and examination of C-reactive protein showed no significant deviation from the normal range for Patient 2 with the RNASEH2A mutation and Patient 3 with the SAMHD1 mutation, even when Patient 2 had magnetic resonance imaging abnormalities and ongoing febrile episodes. Erythrocyte sedimentation rates fluctuated within the normal range for Patient 2, with some elevation, yet, were in the normal range during the second febrile episode when there were accompanying neurological abnormalities. These preliminary data suggest that ISG expression may be a more specific indicator of disease activity in comparison to standard inflammatory markers.

Objectives: To investigate physical activity levels in youth with multiple sclerosis and monophasic acquired demyelinating syndromes ([mono-ADS], ie, children without relapsing disease) compared with healthy controls and to determine factors that contribute to engagement in physical activity. We hypothesized that greater physical activity goal setting and physical activity self-efficacy would be associated with greater levels of vigorous physical activity in youth with multiple sclerosis., Study Design: A total of 68 consecutive patients (27 multiple sclerosis, 41 mono-ADS) and 37 healthy controls completed fatigue, depression, Physical Activity Self-Efficacy Scale, perceived disability, Exercise Goal-Setting scale, and physical activity questionnaires, and wore an accelerometer for 7 days. All patients had no ambulatory limitations (Expanded Disability Status Scale, scores all <4)., Results: Youth with multiple sclerosis engaged in fewer minutes per day of vigorous (P = .009) and moderate and vigorous physical activity (P = .048) than did patients with mono-ADS and healthy controls. A lower proportion of the group with multiple sclerosis (63%) reported participating in any strenuous physical activity than the mono-ADS (85%) and healthy control (89%) groups (P = .020). When we adjusted for age and sex, the Physical Activity Self-Efficacy Scale and Exercise Goal-Setting scale were associated positively with vigorous physical activity in the group with multiple sclerosis. Fatigue and depression did not predict physical activity or accelerometry metrics., Conclusions: Youth with multiple sclerosis participate in less physical activity than their counterparts with mono-ADS and healthy controls. Physical activity self-efficacy and exercise goal setting serve as potentially modifiable correlates of physical activity, and are measures suited to future interventions aimed to increase physical activity in youth with multiple sclerosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Knowledge regarding physical activity (PA) and its benefits in pediatric onset multiple sclerosis (POMS) is growing and suggests high levels of inactivity. The utility of a validated screening tool for clinical settings is unknown. This study evaluated the Godin Leisure-Time Exercise Questionnaire (GLTEQ) as a measure of PA in POMS., Methods: POMS patients (n=27) and healthy controls (n=45) wore an accelerometer over a 7-day period and then completed the GLTEQ., Results: The GLTEQ captured expected group differences in PA for vigorous, moderate, and moderate-to-vigorous physical activity (MVPA), confirmed by accelerometry. There was a large, positive correlation between GLTEQ and accelerometry scores for vigorous PA in POMS (r=0.736, p=0.001), and a nearly significant and moderate, positive correlation between MVPA scores (r=0.319, p=.053)., Conclusion: We provide evidence that supports the validity of GLTEQ scores as measures of vigorous and MVPA in POMS. Researchers and clinicians might adopt this scale for measuring PA., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To evaluate the association between physical activity (PA) and multiple sclerosis (MS) disease activity, depression, and fatigue in a cohort of children with MS and monophasic acquired demyelinating syndrome (mono-ADS)., Methods: In this cross-sectional study of consecutive patients attending a specialized pediatric MS clinic, we administered the PedsQL Multidimensional Fatigue Scale, Center for Epidemiological Studies Depression Scale, and Godin Leisure-Time Exercise Questionnaire. Quantitative MRI analysis was performed to obtain whole brain and T2 lesion volume in a subset of participants (n = 60)., Results: A total of 110 patients (79 mono-ADS; 31 MS; 5-18 years; M:F 1:1.2) were included. Patients with MS reported less strenuous (33.21 ± 31.88 metabolic equivalents [METs] vs 15.97 ± 22.73 METs, p = 0.002) and total (44.48 ± 39.35 METs vs 67.28 ± 59.65 METs; p = 0.0291) PA than those with mono-ADS. Patients with MS who reported greater amounts of moderate PA METs had fewer sleep/rest fatigue symptoms (r = -0.4). Participation in strenuous PA was associated with smaller T2 lesion volumes (r = -0.66) and lower annualized relapse rate (r = -0.66). No associations were found between total brain volume and participation in PA., Conclusions: Children with MS are less physically active than children with mono-ADS. Reasons for this are unclear, but may be related to ongoing disease activity, perceived limitations, or symptoms such as depression or fatigue. Children with MS reporting higher levels of strenuous PA had lower T2 lesion volumes and lower relapse rates, suggesting a potential protective effect of strenuous PA in this population. Further longitudinal studies are needed to establish the relationship of PA to MS symptoms and disease activity in this population., (© 2015 American Academy of Neurology.)

Three-quarters of children with multiple sclerosis (MS) experience fatigue or depression, and progressive neurocognitive decline may be seen as early as two years after MS diagnosis. Furthermore, a higher magnetic resonance imaging disease burden is seen in pediatric-onset MS compared with adult-onset MS. To date, limited knowledge exists regarding behavioral methods for managing symptoms and disease progression in pediatric MS. To that end, this paper builds an evidence-based argument for the possible symptomatic and disease-modifying effects of exercise and physical activity in pediatric MS. This will be accomplished through: (a) a review of pediatric MS and its consequences; (b) a brief overview of physical activity and its consequences in children and adults with MS; and (c) a selective review of research on the neurological benefits of physical activity in pediatric populations. This topical review concludes with a list of 10 questions to guide future research on physical activity and pediatric MS. The objective of this paper is the provision of a research interest, focus and agenda involving pediatric MS and its lifelong management though exercise and physical activity behavior. Such an agenda is critical as the effects and maintenance of physical activity and exercise track across the lifespan, particularly when developed in the early stages of life., (© The Author(s), 2015.)