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Background: The complement component C5 inhibitor, ravulizumab, is approved in Canada for the treatment of adults with AQP4-Ab+ NMOSD. Updated efficacy and safety results from the ongoing CHAMPION-NMOSD (NCT04201262) trial are reported. Methods: Participants received IV-administered, weight-based dosing of ravulizumab, with loading on day 1 and maintenance doses on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Outcome measures included safety, time to first adjudicated on-trial relapse (OTR), risk reduction, and disability scores. Results: 56/41 patients entered/completed the LTE as of June 14, 2024. Median follow-up was 170.3 weeks (186.6 patient-years). No patients experienced an OTR. 94.8% (55/58 patients) had stable or improved Hauser Ambulation Index scores. 89.7% (52/58 patients) had no clinically important worsening in Expanded Disability Status Scale scores. Treatment-emergent adverse events (98.4%) were predominantly mild and unrelated to ravulizumab. Serious adverse events occurred in 25.9% of patients. Two cases of meningococcal infection occurred during the PTP, and none in the LTE. One unrelated death (cardiovascular) occurred during the LTE. Conclusions: Ravulizumab demonstrated long-term clinical benefit in AQP4-Ab+ NMOSD relapse prevention while maintaining or improving disability measures, with no new safety concerns.
Background: Attitudes toward aging influence many health outcomes, yet their relationship with cognition and Alzheimer’s disease (AD) remains unknown. To better understand their impact on cognition and AD risk, we examined whether positive attitudes predict better cognition and diminished risk on AD biomarkers. Methods: A subsample of older adults with a family history of AD (n=54; women=39) from the McGill PREVENT-AD cohort participated in this study. Participants completed the Attitudes to Ageing Questionnaire (AAQ-24), providing three scores: psychosocial loss, psychological growth and physical change. Participants underwent cognitive testing (Rey Auditory Verbal Learning Test, RAVLT; Delis-Kaplan Executive Function System-Color Word Interference Test, D-KEFS-CWIT), and AD blood-based biomarker assessments (p-tau217, Aβ42/40). Regression models tested associations, adjusting for covariates (age, sex, education, depression, APOE4), and were Bonferroni corrected. Results: Positive attitudes were associated with better recall and recognition (RAVLT) and improved word reading, colour naming, switching, and inhibition (D-KEFS-CWIT) (p<0.00077), while negative attitudes showed the opposite pattern. Negative attitudes were correlated with lower Aβ42/40 ratios, while positive attitudes were linked to lower p-tau217 (p<0.0167). Conclusions: These findings demonstrate that positive attitudes predict better cognition and a lower risk profile for AD biomarkers, suggesting that life outlook may be an early disease feature or a risk factor.
Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.
Via molecular and morphological analyses, we describe adult specimens of a new species of Versteria (Cestoda: Taeniidae) infecting mink and river otter (Carnivora: Mustelidae) in Western Canada, as well as larval forms from muskrat and mink. These sequences closely matched those reported from adult specimens from Colorado and Oregon, as well as larval infections in humans and a captive orangutan. We describe here a new species from British Columbia and Alberta (Canada), Versteria rafei n. sp., based upon morphological diagnostic characteristics and genetic distance and phylogeny. Versteria rafei n. sp. differs from the three other described species of the genus in the smaller scolex and cirrus sac. It also differs from V. mustelae (Eurasia) and V. cuja (South America) by having an armed cirrus, which is covered in hair-like bristles, and in the shape of its hooks, with a long thorn-like blade, and short or long handle (vs. a short sharply curved blade and no difference in handle size in previously described species). The poorly known V. brachyacantha (Central Africa) also has an armed cirrus and similarly shaped hooks. However, it differs from the new species in the number and size of hooks. Phylogenetic analysis of the cox1 and nad1 mitochondrial regions showed that our specimens clustered with isolates from undescribed adults and larval infections in North America, and separate from V. cuja, confirming them to be a distinct species from the American Clade.
Interventions in environmental conservation are intended to make things better, not worse. Yet unintended and unanticipated consequences plague environmental conservation; key is how uncertainty plays out. Insights from the intellectual humility literature offer constructive strategies for coming to terms with uncertainty. Strategies such as self-distancing and self-assessment of causal complexity can be incorporated into conservation decision-making processes. Including reflection on what we know and do not know in the decision-making process potentially reduces unintended and unanticipated consequences of environmental conservation and management decisions. An important caution is not to have intellectual humility legitimate failing to act in the face of uncertainty.
Defence Science and Technology Group (DSTG) is currently preparing for the launch of the Buccaneer Main Mission (BMM) satellite, the successor to the Buccaneer Risk Mitigation Mission (BRMM). BMM hosts a high-frequency (HF) antenna and receiver to contribute to the calibration of the Jindalee Operational Radar Network (JORN). Verification of the successful deployment and stability of the large HF antenna is critical to the success of the mission. A bespoke deployable optics payload has been developed by DSTG to fulfil the dual purpose of direct verification of the deployed state of the HF antenna and capturing images of the Earth through a rotatable, dual-surfaced mirror and a variable-focus liquid lens. The payload advances research at DSTG in several fields of space engineering, including deployable mechanisms, precision actuation devices, radiation-tolerant electronics, advanced metal polishing and optical metrology. This paper discusses the payload design, material selection, trade-offs considered for the deployable optics payload and preliminary test results.
Mental health problems are elevated in autistic individuals but there is limited evidence on the developmental course of problems across childhood. We compare the level and growth of anxious-depressed, behavioral and attention problems in an autistic and typically developing (TD) cohort.
Methods
Latent growth curve models were applied to repeated parent-report Child Behavior Checklist data from age 2–10 years in an inception cohort of autistic children (Pathways, N = 397; 84% boys) and a general population TD cohort (Wirral Child Health and Development Study; WCHADS; N = 884, 49% boys). Percentile plots were generated to quantify the differences between autistic and TD children.
Results
Autistic children showed elevated levels of mental health problems, but this was substantially reduced by accounting for IQ and sex differences between the autistic and TD samples. There was small differences in growth patterns; anxious-depressed problems were particularly elevated at preschool and attention problems at late childhood. Higher family income predicted lower base-level on all three dimensions, but steeper increase of anxious-depressed problems. Higher IQ predicted lower level of attention problems and faster decline over childhood. Female sex predicted higher level of anxious-depressed and faster decline in behavioral problems. Social-affect autism symptom severity predicted elevated level of attention problems. Autistic girls' problems were particularly elevated relative to their same-sex non-autistic peers.
Conclusions
Autistic children, and especially girls, show elevated mental health problems compared to TD children and there are some differences in predictors. Assessment of mental health should be integrated into clinical practice for autistic children.
The term “blue justice” was coined in 2018 during the 3rd World Small-Scale Fisheries Congress. Since then, academic engagement with the concept has grown rapidly. This article reviews 5 years of blue justice scholarship and synthesizes some of the key perspectives, developments, and gaps. We then connect this literature to wider relevant debates by reviewing two key areas of research – first on blue injustices and second on grassroots resistance to these injustices. Much of the early scholarship on blue justice focused on injustices experienced by small-scale fishers in the context of the blue economy. In contrast, more recent writing and the empirical cases reviewed here suggest that intersecting forms of oppression render certain coastal individuals and groups vulnerable to blue injustices. These developments signal an expansion of the blue justice literature to a broader set of affected groups and underlying causes of injustice. Our review also suggests that while grassroots resistance efforts led by coastal communities have successfully stopped unfair exposure to environmental harms, preserved their livelihoods and ways of life, defended their culture and customary rights, renegotiated power distributions, and proposed alternative futures, these efforts have been underemphasized in the blue justice scholarship, and from marine and coastal literature more broadly. We conclude with some suggestions for understanding and supporting blue justice now and into the future.
This study compares various morphometric features of two strains of broilers, selected and ‘relaxed’ (ie random-bred), raised under two feeding regimes, ad-libitum-fed and restricted-fed. We consider the possible consequences of the different body shapes on the musculoskeletal system. The ad-libitum-fed selected birds reached heavier bodyweights at younger ages, had wider girths, and developed large amounts of breast muscle which probably displaced their centre of gravity cranially. At cull weight, they had shorter legs than birds in the other groups and greater thigh-muscle masses; therefore, greater forces would have to be exerted by shorter lever arms in order to move the body. The tarsometatarsi were broader, providing increased resistance to greater loads, but the bones had a lower calcium and phosphorus content, which would theoretically make them weaker. Many of these morphological changes are likely to have detrimental effects on the musculoskeletal system and therefore compromise the walking ability and welfare of the birds.
This study tests the hypothesis that growth rate and bodyweight affect walking ability in broilers by comparing objective measurements of the spatial and temporal gait parameters of several groups of birds. Two strains of birds were used (relaxed and selected), raised on two feeding regimes (ad-libitum and restricted), and culled at the same final bodyweight (commercial cull weight of 2.4 kg). The ad-libitum-fed selected birds walked more slowly, with lower cadences, and took shorter steps. The steps were wider, and the toes were pointed outwards, resulting in a wider walking base. They kept their feet in contact with the ground for longer periods, having longer percentage stance times, shorter percentage swing times and increased double-contact times compared to the relaxed birds. These changes serve to increase stability during walking and are a likely consequence of the morphological changes in the selected broiler — in particular, the rapid growth of breast muscle moving the centre of gravity forward, and the relatively short legs compared to their bodyweight (see Corr et al, pp 145-157, this issue). This altered gait would be very inefficient and would rapidly tire the birds, and could help to explain the low level of activity seen in the modern broiler.
We compared the effectiveness of 4 sampling methods to recover Staphylococcus aureus, Klebsiella pneumoniae and Clostridioides difficile from contaminated environmental surfaces: cotton swabs, RODAC culture plates, sponge sticks with manual agitation, and sponge sticks with a stomacher. Organism type was the most important factor in bacterial recovery.
As COVID-19 was declared a health emergency in March 2020, there was immense demand for information about the novel pathogen. This paper examines the clinician-reported impact of Project ECHO COVID-19 Clinical Rounds on clinician learning. Primary sources of study data were Continuing Medical Education (CME) Surveys for each session from the dates of March 24, 2020 to July 30, 2020 and impact surveys conducted in November 2020, which sought to understand participants’ overall assessment of sessions. Quantitative analyses included descriptive statistics and Mann-Whitney testing. Qualitative data were analyzed through inductive thematic analysis. Clinicians rated their knowledge after each session as significantly higher than before that session. 75.8% of clinicians reported they would ‘definitely’ or ‘probably’ use content gleaned from each attended session and clinicians reported specific clinical and operational changes made as a direct result of sessions. 94.6% of respondents reported that COVID-19 Clinical Rounds helped them provide better care to patients. 89% of respondents indicated they ‘strongly agree’ that they would join ECHO calls again.COVID-19 Clinical Rounds offers a promising model for the establishment of dynamic peer-to-peer tele-mentoring communities for low or no-notice response where scientifically tested or clinically verified practice evidence is limited.
After implementing a coronavirus disease 2019 (COVID-19) infection prevention bundle, the incidence rate ratio (IRR) of non–severe acute respiratory coronavirus virus 2 (non–SARS-CoV-2) hospital-acquired respiratory viral infection (HA-RVI) was significantly lower than the IRR from the pre–COVID-19 period (IRR, 0.322; 95% CI, 0.266–0.393; P < .01). However, HA-RVIs incidence rates mirrored community RVI trends, suggesting that hospital interventions alone did not significantly affect HA-RVI incidence.
Initial assessments of coronavirus disease 2019 (COVID-19) preparedness revealed resource shortages and variations in infection prevention policies across US hospitals. Our follow-up survey revealed improvement in resource availability, increase in testing capacity, and uniformity in infection prevention policies. Most importantly, the survey highlighted an increase in staffing shortages and use of travel nursing.
Current first-line treatments for paediatric depression demonstrate mild-to-moderate effectiveness. This has spurred a growing body of literature on lifestyle recommendations pertaining to nutrition, sleep and exercise for treating paediatric depression.
Aims
Paediatric depression clinical practice guidelines (CPGs) were reviewed for quality and to catalogue recommendations on nutrition, sleep and exercise made by higher-quality CPGs.
Method
Searches were conducted in Medline, EMBASE, PsycINFO, Web of Science and CINAHL, and grey literature CPGs databases for relevant CPGs. Eligible CPGs with a minimum or high-quality level, as determined by the Appraisal of Guidelines for Research and Evaluation, Second Edition instrument, were included if they were (a) paediatric; (b) CPGs, practice parameter or consensus or expert committee recommendations; (c) for depression; (d) the latest version and (e) lifestyle recommendations for nutrition, sleep or exercise. Key information extracted included author(s), language, year of publication, country, the institutional body issuing the CPG, target disorder, age group, lifestyle recommendation and the methods used to determine CPG lifestyle recommendations.
Results
Ten paediatric CPGs for depression with a minimum or high-quality level contained recommendations on nutrition, sleep or exercise. Lifestyle recommendations were predominately qualitative, with quantitative details only outlined in two CPGs for exercise. Most recommendations were brief general statements, with 50% lacking supporting evidence from the literature.
Conclusions
Interest in lifestyle interventions for treatment in child and youth depression is growing. However, current CPG lifestyle recommendations for nutrition, sleep or exercise are based on expert opinion rather than clinical trials.
To estimate population-based rates and to describe clinical characteristics of hospital-acquired (HA) influenza.
Design:
Cross-sectional study.
Setting:
US Influenza Hospitalization Surveillance Network (FluSurv-NET) during 2011–2012 through 2018–2019 seasons.
Methods:
Patients were identified through provider-initiated or facility-based testing. HA influenza was defined as a positive influenza test date and respiratory symptom onset >3 days after admission. Patients with positive test date >3 days after admission but missing respiratory symptom onset date were classified as possible HA influenza.
Results:
Among 94,158 influenza-associated hospitalizations, 353 (0.4%) had HA influenza. The overall adjusted rate of HA influenza was 0.4 per 100,000 persons. Among HA influenza cases, 50.7% were 65 years of age or older, and 52.0% of children and 95.7% of adults had underlying conditions; 44.9% overall had received influenza vaccine prior to hospitalization. Overall, 34.5% of HA cases received ICU care during hospitalization, 19.8% required mechanical ventilation, and 6.7% died. After including possible HA cases, prevalence among all influenza-associated hospitalizations increased to 1.3% and the adjusted rate increased to 1.5 per 100,000 persons.
Conclusions:
Over 8 seasons, rates of HA influenza were low but were likely underestimated because testing was not systematic. A high proportion of patients with HA influenza were unvaccinated and had severe outcomes. Annual influenza vaccination and implementation of robust hospital infection control measures may help to prevent HA influenza and its impacts on patient outcomes and the healthcare system.
To describe a pilot project infection prevention and control (IPC) assessment conducted in skilled nursing facilities (SNFs) in New York State (NYS) during a pivotal 2-week period when the region became the nation’s epicenter for coronavirus disease 2019 (COVID-19).
Design:
A telephone and video assessment of IPC measures in SNFs at high risk or experiencing COVID-19 activity.
Participants:
SNFs in 14 New York counties, including New York City.
Intervention:
A 3-component remote IPC assessment: (1) screening tool; (2) telephone IPC checklist; and (3) COVID-19 video IPC assessment (ie, “COVIDeo”).
Results:
In total, 92 SNFs completed the IPC screening tool and checklist: 52 (57%) were conducted as part COVID-19 investigations, and 40 (43%) were proactive prevention-based assessments. Among the 40 proactive assessments, 14 (35%) identified suspected or confirmed COVID-19 cases. COVIDeo was performed in 26 (28%) of 92 assessments and provided observations that other tools would have missed: personal protective equipment (PPE) that was not easily accessible, redundant, or improperly donned, doffed, or stored and specific challenges implementing IPC in specialty populations. The IPC assessments took ∼1 hour each and reached an estimated 4 times as many SNFs as on-site visits in a similar time frame.
Conclusions:
Remote IPC assessments by telephone and video were timely and feasible methods of assessing the extent to which IPC interventions had been implemented in a vulnerable setting and to disseminate real-time recommendations. Remote assessments are now being implemented across New York State and in various healthcare facility types. Similar methods have been adapted nationally by the Centers for Disease Control and Prevention.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.