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The goal of this study was to determine the difference in participant understanding, satisfaction, timing and, preference between video consent and written informed consent in a pediatric rheumatology research setting. Participants were randomized to receive either video consent or written informed consent for a registry study. After completing the first consent method, they completed a comprehension and satisfaction questionnaire. Then they received the alternate consent method and completed a second set of questionnaires. Bayesian non-parametric tests determined the difference in comprehension, satisfaction, timing and preference between video consent and written informed consent. Ninety-nine caregivers and 76 patients were randomized into video consent (n = 88) and written informed consent (n = 87) groups. Comprehension (Max = 12) and satisfaction (Max = 5) were high in both groups. There was moderate evidence supporting no difference in comprehension (median video consent  = 11 and median written informed consent  = 10) and satisfaction (median video consent  = 4 and median written informed consent  = 5) between video consent and written informed consent (BF 10  = 0.225 and 0.32, respectively). The median time to complete video consent and written informed consent was 408 (95% Credible Interval (CrI): 397–412) and 360 (95% CrI: 329–391) seconds, respectively. There was decisive evidence that video consent increased the time of consent (in our sample by 48 seconds) compared to written informed consent (BF 10  = 713). There was decisive evidence for participants preferring video consent over written informed consent (BF 10  = 2.307x10 11 ) as they thought it was easier to follow. Overall, participant understanding and satisfaction were comparable between video consent and written informed consent. Even though video consent was slightly less time efficient compared to written informed consent, video consent was highly preferred by caregivers and patients, supporting its use to obtain informed consent.

Weiss et al, highlighted the inequities in the access of FPPs/1) Since the access of medical services follows the inverse care law,(3) older adults with lower socioeconomic status, education, and physical fitness are less likely to receive referrals and/or participate in FPPs/4) To address the gaps in FPP accessibility, the Naturally Occurring Retirement Communities (NORCs) Innovation Centre at the University Health Network has developed a community-led FPP approach working with local older adult leaders. Through our initial proofs-of-concepts, we have seen the creativity and commitment of communities in advocating for needs, encouraging neighbours to participate, and promoting peer education and modeling to sustain change. CONFLICT OF INTEREST DISCLOSURES We have read and understood the Canadian Geriatrics Journal's policy on conflicts of interest disclosure and declare we have none.

Secondary progressive multiple sclerosis, for which no satisfactory treatment presently exists, accounts for most of the disability in patients with multiple sclerosis. Simvastatin, which is widely used for treatment of vascular disease, with its excellent safety profile, has immunomodulatory and neuroprotective properties that could make it an appealing candidate drug for patients with secondary progressive multiple sclerosis. We undertook a double-blind, controlled trial between Jan 28, 2008, and Nov 4, 2011, at three neuroscience centres in the UK. Patients aged 18–65 years with secondary progressive multiple sclerosis were randomly assigned (1:1), by a centralised web-based service with a block size of eight, to receive either 80 mg of simvastatin or placebo. Patients, treating physicians, and outcome assessors were masked to treatment allocation. The primary outcome was the annualised rate of whole-brain atrophy measured from serial volumetric MRI. Analyses were by intention to treat and per protocol. This trial is registered with ClinicalTrials.gov, number NCT00647348. 140 participants were randomly assigned to receive either simvastatin (n=70) or placebo (n=70). The mean annualised atrophy rate was significantly lower in patients in the simvastatin group (0·288% per year [SD 0·521]) than in those in the placebo group (0·584% per year [0·498]). The adjusted difference in atrophy rate between groups was −0·254% per year (95% CI −0·422 to −0·087; p=0·003); a 43% reduction in annualised rate. Simvastatin was well tolerated, with no differences between the placebo and simvastatin groups in proportions of participants who had serious adverse events (14 [20%] vs nine [13%]). High-dose simvastatin reduced the annualised rate of whole-brain atrophy compared with placebo, and was well tolerated and safe. These results support the advancement of this treatment to phase 3 testing. The Moulton Foundation [charity number 1109891], Berkeley Foundation [268369], the Multiple Sclerosis Trials Collaboration [1113598], the Rosetrees Trust [298582] and a personal contribution from A Pidgley, UK National Institute of Health Research (NIHR) University College London Hospitals/UCL Biomedical Research Centres funding scheme.

SARS-CoV-2 lineage B.1.1.7, a variant that was first detected in the UK in September 2020 1 , has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than pre-existing variants, but have not identified whether it leads to any change in disease severity 2 . Here we analyse a dataset that links 2,245,263 positive SARS-CoV-2 community tests and 17,452 deaths associated with COVID-19 in England from 1 November 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because mutations in this lineage prevent PCR amplification of the spike ( S ) gene target (known as S gene target failure (SGTF) 1 ). On the basis of 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% confidence interval, 39–72%) higher than in cases without SGTF after adjustment for age, sex, ethnicity, deprivation, residence in a care home, the local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old man increasing from 0.6% to 0.9% (95% confidence interval, 0.8–1.0%) within 28 days of a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate that the hazard of death associated with B.1.1.7 is 61% (42–82%) higher than with pre-existing variants. Our analysis suggests that B.1.1.7 is not only more transmissible than pre-existing SARS-CoV-2 variants, but may also cause more severe illness. Analysis of community-tested cases of SARS-CoV-2 indicates that the B.1.1.7 variant is not only more transmissible than pre-existing variants, but may also cause more severe illness, and is associated with a higher risk of death.

In the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures. We did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov, number NCT00647348. Baseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6–7·8; p<0·0001) and non-verbal memory (decline of 6·8 points, 4·8–8·7; p<0·0001). At 24 months, the FAB score was 1·2 points higher in the simvastatin-treated group than in the placebo group (95% CI 0·2–2·3). The simvastatin group also had a 2·5 points better mean physical component score of the SF-36 (95% CI 0·3–4·8; p=0·028). A treatment effect was not noted for any other outcomes. To our knowledge, this SPMS cohort is the largest studied to date with comprehensive longitudinal cognitive, neuropsychiatric, and HRQoL assessments. We found evidence of a positive effect of simvastatin on frontal lobe function and a physical quality-of-life measure. Although we found no effect of simvastatin on the other outcome measures, these potential effects warrant confirmation and underline the importance of fully assessing cognition and quality of life in progressive multiple sclerosis treatment trials. The Moulton Foundation, the Berkeley Foundation, the Multiple Sclerosis Trials Collaboration, the Rosetrees Trust, a personal contribution from A W Pidgley CBE, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre and University College London.

The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.

In Cambodian villages, 3-month mass drug administration with high coverage using dihydroartemisinin-piperaquine was safe and was followed by the absence of clinical Plasmodium falciparum cases for at least 1 year, despite the presence of multidrug-resistant parasites. Abstract Background The increase in multidrug-resistant Plasmodium falciparum in Southeast Asia suggests a need for acceleration of malaria elimination. We evaluated the effectiveness and safety of mass drug administration (MDA) to interrupt malaria transmission. Methods Four malaria-endemic villages in western Cambodia were randomized to 3 rounds of MDA (a 3-day course of dihydroartemisinin with piperaquine-phosphate), administered either early in or at the end of the study period. Comprehensive malaria treatment records were collected during 2014-2017. Subclinical parasite prevalence was estimated by ultrasensitive quantitative polymerase chain reaction quarterly over 12 months. Results MDA coverage with at least 1 complete round was 88% (1999/2268), ≥2 rounds 73% (1645/2268), and all 3 rounds 58% (1310/2268). Plasmodium falciparum incidence in intervention and control villages was similar over the 12 months prior to the study: 39 per 1000 person-years (PY) vs 45 per 1000 PY (P = .50). The primary outcome, P. falciparum incidence in the 12 months after MDA, was lower in intervention villages (1.5/1000 PY vs 37.1/1000 PY; incidence rate ratio, 24.5 [95% confidence interval], 3.4-177; P = .002). Following MDA in 2016, there were no clinical falciparum malaria cases over 12 months (0/2044 PY) in all 4 villages. Plasmodium vivax prevalence decreased markedly in intervention villages following MDA but returned to approximately half the baseline prevalence by 12 months. No severe adverse events were attributed to treatment. Conclusions Mass drug administrations achieved high coverage, were safe, and associated with the absence of clinical P. falciparum cases for at least 1 year. Clinical Trials Registration NCT01872702.

BackgroundAn increasing number of studies have shown an association between migraine and cardiovascular disease, in particular cardio- and cerebro-vascular events.MethodsThree electronic databases (PubMed, Embase and Scopus) were searched from inception to May 22, 2021 for prospective cohort studies evaluating the risk of myocardial infarction, stroke and cardiovascular mortality in migraine patients. A random effects meta-analysis model was used to summarize the included studies.ResultsA total of 18 prospective cohort studies were included consisting of 370,050 migraine patients and 1,387,539 controls. Migraine was associated with myocardial infarction (hazard ratio, 1.36; 95% CI, 1.23–1.51; p =  < 0.001), unspecified stroke (hazard ratio, 1.30; 95% CI, 1.07–1.60; p = 0.01), ischemic stroke (hazard ratio, 1.35; 95% CI, 1.03–1.78; p = 0.03) and hemorrhagic stroke (hazard ratio, 1.43; 95% CI, 1.07–1.92; p = 0.02). Subgroup analysis of migraine with aura found a further increase in risk of myocardial infarction and both ischemic and hemorrhagic stroke, as well as improved substantial statistical heterogeneity. Migraine with aura was also associated with an increased risk of cardiovascular mortality (hazard ratio, 1.27; 95% CI, 1.14–1.42; p =  < 0.001).ConclusionMigraine, especially migraine with aura, is associated with myocardial infarction and stroke. Migraine with aura increases the risk of overall cardiovascular mortality.

Although ocular manifestations are reported in patients with COVID-19, consensus on ocular tropism of SARS-CoV-2 is lacking. Here, we infect K18-hACE2 transgenic mice with SARS-CoV-2 using various routes. We observe ocular manifestation and retinal inflammation with production of pro-inflammatory cytokines in the eyes of intranasally (IN)-infected mice. Intratracheal (IT) infection results in dissemination of the virus from the lungs to the brain and eyes via trigeminal and optic nerves. Ocular and neuronal invasions are confirmed using intracerebral (IC) infection. Notably, the eye-dropped (ED) virus does not cause lung infection and becomes undetectable with time. Ocular and neurotropic distribution of the virus in vivo is evident in fluorescence imaging with an infectious clone of SARS-CoV-2-mCherry. The ocular tropic and neuroinvasive characteristics of SARS-CoV-2 are confirmed in wild-type Syrian hamsters. Our data can improve the understanding regarding viral transmission and clinical characteristics of SARS-CoV-2 and help in improving COVID-19 control procedures. SARS-CoV-2 pathogenesis is very complex and not fully understood yet. Here, Jeong et al. show that intranasally infected K18-hACE2 transgenic mice develop ocular infection and retinal inflammation, while intratracheal infection results in the dissemination of SARS-CoV-2 from mouse lungs to their brain and eyes via unidirectional route and confirm the tissue tropism in Syrian hamster model.