Validation of actigraphy sleep metrics in children aged 8 to 16 years: considerations for device type, placement and algorithms.

BACKGROUND: Actigraphy is often used to measure sleep in pediatric populations, despite little confirmatory evidence of the accuracy of existing sleep/wake algorithms. The aim of this study was to determine the performance of 11 sleep algorithms in relation to overnight polysomnography in children and adolescents. METHODS: One hundred thirty-seven participants aged 8-16 years wore two Actigraph wGT3X-BT (wrist, waist) and three Axivity AX3 (wrist, back, thigh) accelerometers over 24-h. Gold standard measures of sleep were obtained using polysomnography (PSG; Embletta MPRPG, ST + Proxy and TX Proxy) in the home environment, overnight. Epoch by epoch comparisons of the Sadeh (two algorithms), Cole-Kripke (three algorithms), Tudor-Locke (four algorithms), Count-Scaled (CS), and HDCZA algorithms were undertaken. Mean differences from PSG values were calculated for various sleep outcomes. RESULTS: Overall, sensitivities were high (mean ± SD: 91.8%, ± 5.6%) and specificities moderate (63.8% ± 13.8%), with the HDCZA algorithm performing the best overall in terms of specificity (87.5% ± 1.3%) and accuracy (86.4% ± 0.9%). Sleep outcome measures were more accurately measured by devices worn at the wrist than the hip, thigh or lower back, with the exception of sleep efficiency where the reverse was true. The CS algorithm provided consistently accurate measures of sleep onset: the mean (95%CI) difference at the wrist with Axivity was 2 min (-6; -14,) and the offset was 10 min (5, -19). Several algorithms provided accurate measures of sleep quantity at the wrist, showing differences with PSG of just 1-18 min a night for sleep period time and 5-22 min for total sleep time. Accuracy was generally higher for sleep efficiency than for frequency of night wakings or wake after sleep onset. The CS algorithm was more accurate at assessing sleep period time, with narrower 95% limits of agreement compared to the HDCZA (CS:-165 to 172 min; HDCZA: -212 to 250 min). CONCLUSION: Although the performance of existing count-based sleep algorithms varies markedly, wrist-worn devices provide more accurate measures of most sleep measures compared to other sites. Overall, the HDZCA algorithm showed the greatest accuracy, although the most appropriate algorithm depends on the sleep measure of focus.

Knowledge sharing in virtual communities of practice of family caregivers of people with Alzheimer's.

INTRODUCTION: Knowledge sharing can only happen in the context of a trusting and supportive environment, such as evolves in communities of practice and their virtual equivalent, virtual communities of practice. The main objective of this study was to understand knowledge sharing between participants in a virtual community of practice of caregivers of people with Alzheimer's. METHODS: The authors designed their own mobile application, and two virtual communities of practice were created independently and differentiated by how they were moderated: one by an expert caregiver and the other by three health professionals. 38 caregivers and four moderators were involved in the study, which ran between July 2017 and April 2018. A total of 1925 messages were exchanged within the two communities and used as data in the study. Message data was analysed using LINKS (Leveraging Internet Networks for knowledge sharing). RESULTS: Participants were more motivated to acquire knowledge related to caring for the person with Alzheimer's rather than caring for themselves. The purpose of the messages was to inform others about the sender and not to seek answers. It seems that the interaction was more to socialise and to feel heard, than to gain information. Face to face meetings appear to have accelerated community development. On nearly every parameter, behaviour was significantly different in the two communities, reflecting the importance of the character of the moderator. Caring for oneself was a much stronger theme in the community that included health professionals. Experiential knowledge sharing was particularly strong in the group led by a caregiver. DISCUSSION: Caregivers adapted the virtual community of practice to their own needs and mainly shared social knowledge. This focus on social support, which seems to be more valued by the caregivers than information about the disease, was not an expected pattern. Virtual communities of practice where peers count on each other, function more as a support group, whereas those moderated by health professionals function more as a place to go to acquire information. The level of interactivity points to such communities being important for knowledge sharing not mere knowledge transfer.

Cancer risk-factor and symptom awareness among adults with intellectual disabilities, paid and unpaid carers, and healthcare practitioners: a scoping review.

BACKGROUND: The physical health of people with intellectual disabilities (ID) has been identified as an area of ongoing concern and priority. Research has increasingly focused on cancer, with studies indicating that people with ID are at an increased risk of cancer and of mortality, compared with the general population. This review aims to systematically identify and synthesise the published academic literature exploring cancer risk-factor and symptom awareness among people with IDs, carers and healthcare professionals. METHODS: In line with Arksey and O'Malley's (2005) framework for scoping reviews, five incremental stages were followed: (1) identifying research question, (2) identifying relevant studies, (3) study selection, (4) extracting and charting of data, and (5) collating, summarising and reporting results. Findings were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews (PRISMA-Scr). RESULTS: The search strategy identified 352 records, 16 records met all eligibility criteria and were included for review. The studies address a range of areas including knowledge and awareness of cancer risk-factors and symptoms and interventions to promote awareness of cancer. CONCLUSIONS: Cancer risk-factor and symptom awareness is low among adults with ID, paid and unpaid carers and healthcare practitioners (HCPs). Theoretically underpinned, co-designed tools and interventions to improve awareness are lacking. There is uncertainty surrounding how to best support people with ID in raising cancer awareness, even within the professional healthcare environment. There is a predominance of research on breast cancer awareness. Future studies focusing on other cancers are needed to build a complete picture of awareness among adults with IDs, paid and unpaid carers, and HCPs.

An Ambulatory Pathway for the Investigation of Patients with Suspected Pulmonary Embolism.

Aims The aim of this project was to provide an ambulatory pathway for diagnosis and management of patients with suspected Pulmonary Embolism (PE) with "low-risk" features. Methods A structured algorithm for the management of suspected PE was designed and implemented in April 2021. This involved the development of local guidelines to identify those "low-risk" patients with suspected PE, through the use of modified sPESI and Hestia criteria. This pathway was audited monthly to establish effect on admission and hospital length of stay. Results 51 CT PAs were performed by the Emergency Department in April 2021. Total number of CT confirmed PEs in April was 7(11%). 12 "low-risk" patients with suspected PE were identified and placed on the "Ambulatory Suspected Pulmonary Embolism Pathway". One (8.3%) patient on this pathway had a confirmed PE. Patients placed on this pathway spent significantly less time in the Emergency Department and in hospital with greater satisfaction by physicians using this pathway. Conclusion This pathway has succeeded in significantly decreasing length of stay both in the ED and in hospital for patients with suspected and confirmed PE.

Novel homozygous variant in BMP1 associated with a rare osteogenesis imperfecta phenotype.

Osteogenesis imperfecta (OI) is characterized by bone fragility and increased fracture susceptibility. BMP1 variants have been reported in the rare OI type XIII, specifically referred to herein as BMP1-associated autosomal recessive (AR) OI. We report the clinical presentation and diagnostic evaluation of a patient found to have a novel homozygous variant in BMP1. We also provide an overview of reported BMP1 variants to date, with discussion focusing on the use of bisphosphonate therapy in these patients. A 7-year-old male with speech and motor delay sustained five bilateral tibial fractures with minimal trauma since age 2.5 years. At age 6, he developed severe back pain after a fall. Diffuse spinal osteopenia and multiple vertebral compression fractures (VCF) at T9, L1, L3, and L5 were identified. Total hip BMD was generous (adjusted Z-score* = 1.76), and femoral neck BMD was high (adjusted Z-score* = 2.67). VCFs precluded assessment of lumbar spine BMD. Genetic analysis identified a homozygous missense variant in exon 4 of BMP1 (c.C505T; p.Arg169Cys). Unlike most forms of OI, patients with BMP1-associated AR OI may have normal or paradoxically increased BMD, making BMD and fracture risk correlation difficult. While bisphosphonates (BP) may help reduce recurrent fractures and provide symptomatic relief, the broad phenotypic spectrum and underlying bone pathology, often in the setting of increased BMD, complicate management. HR-pQCT assessment of bone microarchitecture and quality may aid in the decision of BP therapy and subsequent monitoring. Evidence is limited with respect to the effectiveness of BP in this rare form of OI. *Z-score was adjusted for height Z-score.

Comparison of polysaccharide glycoconjugates as candidate vaccines to combat Clostridiodes (Clostridium) difficile.

Two known Clostridiodes (Clostridium) difficile surface antigens, a lipoteichoic acid (LTA) and a polysaccharide (PS-II) were isolated and purified in order to prepare glycoconjugate vaccines to the carrier protein human serum albumin utilising a reductive amination strategy. Mice and rabbits were immunized with a prime and two boost strategy and the resulting sera were examined for their ability to recognise the purified homologous antigens and subsequently killed whole cells of C. difficile strains and other Clostridia species. Immunisation derived antisera from rabbits and mice, recognised all strains of C. difficile vegetative cells examined, with generally similar titers from animals that received the LTA or the PS-II conjugates. Sera raised to the LTA conjugates were able to recognise other Clostridia species C. butyricum, C. bifermentans and C. subterminale whereas sera raised to the PS-II conjugates were not. These LTA and PS-II sera recognised live cells in an immunofluorescence assay and were also able to recognise the spore form of the bacterium. This study has confirmed that the LTA and PS-II polysaccharides are both highly conserved surface polymers of C. difficile that are easily accessible to the immune system and as such may have potential as vaccine antigens or as targets for therapeutics to combat C. difficile infection.

Correlates of PrEP Uptake Among Young Sexual Minority Men and Transgender Women in New York City: The Need to Reframe "Risk" Messaging and Normalize Preventative Health.

Pre-exposure prophylaxis (PrEP) is an effective form of HIV prevention, but young sexual minority men face myriad barriers to PrEP uptake. Participants (n = 202) completed a survey on healthcare experiences and beliefs about HIV and PrEP. While 98% of the sample knew about PrEP, only 23.2% reported currently taking PrEP. Participants were more likely to be taking PrEP if they received PrEP information from a healthcare provider and endorsed STI-related risk compensation. Conversely, PrEP uptake was less likely among those with concerns about medication use and adherence. While there were no racial/ethnic differences in PrEP uptake, there were differences in correlates of PrEP use for White participants and participants of color. To facilitate PrEP uptake, clinicians should provide PrEP education and screen all patients for PrEP candidacy. Additionally, public health messaging must reframe HIV "risk", highlight benefits of STI testing, and emphasize the importance of preventive healthcare for SMM.

Measurement of the Antineutrino Spectrum from

This Letter reports the first measurement of the ^{235}U ν[over ¯]_{e} energy spectrum by PROSPECT, the Precision Reactor Oscillation and Spectrum experiment, operating 7.9 m from the 85 MW_{th} highly enriched uranium (HEU) High Flux Isotope Reactor. With a surface-based, segmented detector, PROSPECT has observed 31678±304(stat) ν[over ¯]_{e}-induced inverse beta decays, the largest sample from HEU fission to date, 99% of which are attributed to ^{235}U. Despite broad agreement, comparison of the Huber ^{235}U model to the measured spectrum produces a χ^{2}/ndf=51.4/31, driven primarily by deviations in two localized energy regions. The measured ^{235}U spectrum shape is consistent with a deviation relative to prediction equal in size to that observed at low-enriched uranium power reactors in the ν[over ¯]_{e} energy region of 5-7 MeV.

First Search for Short-Baseline Neutrino Oscillations at HFIR with PROSPECT.

This Letter reports the first scientific results from the observation of antineutrinos emitted by fission products of ^{235}U at the High Flux Isotope Reactor. PROSPECT, the Precision Reactor Oscillation and Spectrum Experiment, consists of a segmented 4 ton ^{6}Li-doped liquid scintillator detector covering a baseline range of 7-9 m from the reactor and operating under less than 1 m water equivalent overburden. Data collected during 33 live days of reactor operation at a nominal power of 85 MW yield a detection of 25 461±283 (stat) inverse beta decays. Observation of reactor antineutrinos can be achieved in PROSPECT at 5σ statistical significance within 2 h of on-surface reactor-on data taking. A reactor model independent analysis of the inverse beta decay prompt energy spectrum as a function of baseline constrains significant portions of the previously allowed sterile neutrino oscillation parameter space at 95% confidence level and disfavors the best fit of the reactor antineutrino anomaly at 2.2σ confidence level.

Plasma cell depletion with bortezomib in the treatment of refractory N-methyl-d-aspartate (NMDA) receptor antibody encephalitis. Rational developments in neuroimmunological treatment.

BACKGROUND AND PURPOSE: The aim was to assess the therapeutic potential of bortezomib in the treatment of refractory N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis and its potential in other immune-mediated, B-cell-driven neurological diseases. METHODS: Two cases of severe NMDAR antibody encephalitis, resistant to first and second line therapy with steroids, intravenous immunoglobulins, plasma exchange, cyclophosphamide and rituximab, were treated with four and five cycles of 1.3 mg/m2 bortezomib at 350 and 330 days following initial presentation. RESULTS: Both patients showed significant clinical improvement with reductions of NMDAR antibody titres following bortezomib treatment. This is the first case in the literature where the NMDAR antibody level was undetectable following treatment with bortezomib. CONCLUSION: Bortezomib's unique ability to target long-lived autoreactive plasma cells appears to be a useful adjunct to standard second line immunosuppressive therapy in treatment-refractory NMDAR antibody encephalitis. The drug's pharmacodynamics, cell targeting and mechanism of action are reviewed, and it is postulated that bortezomib may be useful in a host of B-cell-driven neuroimmunological diseases.

Shocking the system: AEDs in military resuscitation.

Automated external defibrillator (AED) devices have been in routine clinical use since the early 1990s to deliver life-saving shocks to appropriate patients in non-clinical environments. As expectations of survival from out-of-hospital cardiac arrest increase, and evidence incontrovertibly points to reduced timelines as the most crucial factor in achieving return of spontaneous circulation, questions regarding the availability and location of AEDs in the UK military need to be readdressed. This article explores the background of AEDs and reviews their history, life-saving potential and defines current and best practice. It goes on to review the evidence surrounding training and looks to identify knowledge gaps that might be addressed effectively by future research. Finally, it makes recommendations regarding training, availability of AEDs on military bases and locations most likely to deliver good outcomes for military personnel in the future.

Military application of mechanical CPR devices: a pressing requirement?

Maintaining high-quality chest compressions during cardiopulmonary resuscitation following cardiac arrest presents a challenge. The currently available mechanical CPR (mCPR) devices are described in this review, coupled with an analysis of the evidence pertaining to their efficacy. Overall, mCPR appears to be at least equivalent to high-quality manual CPR in large trials. There is potential utility for mCPR devices in the military context to ensure uninterrupted quality CPR following a medical cardiac arrest. Particular utility may be in a prohibitive operational environment, where manpower is limited or where timelines to definitive care are stretched resulting in a requirement for prolonged resuscitation. mCPR can also act as a bridge to advanced endovascular resuscitation techniques should they become more mainstream therapy.

Phantom menace: novel psychoactive substances and the UK Armed Forces.

Novel psychoactive substances (NPS) encompass a large group of synthesised compounds specifically designed to mimic traditional recreational drugs. Current UK Armed Forces compulsory drug testing does not screen for these substances, making them tempting to the small proportion of UK Armed Forces personnel who indulge in recreational drug use. The acute and chronic sequelae of NPS misuse are widely variable and associated with high morbidity. In this paper, we discuss NPS pharmacology and clinical presentation. We describe toxidromes and management of patients who have misused NPS.Finally, we reflect on the legal, ethical and military consequences of NPS misuse for both the service person misusing NPS and the Military Physician providing their care.

Deployed military general internal physician's toolkit: the recent past and near future.

INTRODUCTION: The role of the military physician in Deployed Hospital Care involves the diagnosis and management of a wide variety of disease states. Broad clinical skills need to be complemented by judicious use of a limited array of investigations. No study has specifically quantified what investigations physicians use on operations. METHODS: A retrospective cross-sectional study was performed to ascertain what investigations were undertaken on all patients managed by the General Internal Medicine teams over a 14 month period during a recent enduring operation in Afghanistan. A record was also made of investigations that were unavailable but considered desirable by the treating physician in order to inform clinical or occupational decisions. RESULTS: 676 patients were admitted during the study period. Blood tests were performed in 96% of patients, plain radiographs in 50%, CT in 12% and ultrasound in 12%. An ECG was performed in over half (57%) and a peak flow in 11%. The most desirable, but unavailable, investigations were cardiac monitoring and echocardiography (24% and 12% of patients, respectively). DISCUSSION: The data produced by this study both identified and quantified the investigations used by physicians during a mature operational deployment. This can be used in addition to accurate medical intelligence to inform and rationalise the diagnostic requirements for future operations as well as the provision of training. Technological advancements, particularly in weight and portability, are likely to enable more complex investigational modalities to be performed further forward on military deployments.

Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections.

Inflammasomes are multi-protein complexes integrating pathogen-triggered signaling leading to the generation of pro-inflammatory cytokines including interleukin-18 (IL-18). Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are associated with elevated IL-18, suggesting inflammasome activation. However, there is marked person-to-person variation in the inflammasome response to HCV and HIV. We hypothesized that host genetics may explain this variation. To test this, we analyzed the associations of plasma IL-18 levels and polymorphisms in 10 genes in the inflammasome cascade. About 1538 participants with active HIV and/or HCV infection in three ancestry groups are included. Samples were genotyped using the Illumina Omni 1-quad and Omni 2.5 arrays. Linear regression analyses were performed to test the association of variants with log IL-18 including HCV and HIV infection status, and HIV RNA in each ancestry group and then meta-analyzed. Eleven highly correlated single-nucleotide polymorphisms (r2=0.98-1) in the IL-18-BCO2 region were significantly associated with log IL-18; each T allele of rs80011693 confers a decrease of 0.06 log pg ml-1 of IL-18 after adjusting for covariates (rs80011693; rs111311302 ß=-0.06, P-value=2.7 × 10-4). In conclusion, genetic variation in IL-18 is associated with IL-18 production in response to HIV and HCV infection, and may explain variability in the inflammatory outcomes of chronic viral infections.

Analysis of resistance-associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents.

Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naïve patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up.

Phylogenetic analysis of full-length, early infection, hepatitis C virus genomes among people with intravenous drug use: the InC3 Study.

Cross-continental phylogenetic analysis is important to understand subtle molecular differences of currently circulating hepatitis C virus (HCV) subtypes. Existence of such differences can be crucial in pursuing a universal hepatitis C vaccine. We characterized molecular epidemiology of early HCV infections identified across nine cohorts [North America (n=4), Australia (n=4) and Europe (n=1)] in the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC3 ). One hundred and ninety-two full-length HCV genomes were amplified from plasma of incident infections and subjected to next generation sequencing to establish the largest cross-continental, full-length acute HCV genomic data set available to date. Genomes from the most common subtypes (1a: n=94, 2b: n=15 and 3a: n=68) were used in phylogenetic analysis. Using full genome trees, 78 sequences (44%) were found to lie within 29 phylogenetic clusters/pairs defined on the basis of molecular similarity of consensus sequences. Of these, 26 each had exclusively Australian or North American sequences indicating a strong geographical bias for molecular similarity. On further analysis of behavioural and demographic associations, binary logistic regression analysis showed that older age and non-Caucasian ethnicity were significantly associated with clustering. HCV probably evolves in micro-epidemics within geographically isolated communities.

Systematic Review and Meta-analysis of the Effect of Internal Iliac Artery Exclusion for Patients Undergoing EVAR.

OBJECTIVE: Endovascular abdominal aortic aneurysm repair (EVAR) sometimes requires internal iliac artery (IIA) coverage to achieve a landing zone in the external iliac artery. The aim of this study was to determine complication rates following IIA exclusion. MATERIALS AND METHODS: A systematic review of key journals was undertaken from January 1980 to April 2016. Studies detailing occlusion (using coils or plugs) or coverage of the IIA with outcome data were included. Weighted means were calculated for continuous variables. Meta-analysis was performed when comparative data were available. Quality was assessed using the GRADE system. RESULTS: Sixty-one non-randomised studies (2671 patients; 2748 IIAs) were analysed. Fifteen per cent of EVARs require IIA sacrifice. Buttock claudication (BC) occurred in 27.9% of patients, although 48.0% resolved after 21.8 months. BC rates were 32.6% with coils, 23.8% with plugs, and 12.9% with coverage alone, and less with unilateral (vs. bilateral) IIA treatment (OR 0.57, 95% CI 0.36-0.91). More proximal coil placement resulted in lower rates of BC (OR 0.12, 95% CI 0.03-0.48). Erectile dysfunction occurred in 10.2% of males, with higher rates after coiling. Type II endoleaks were more frequent after covering alone; however re-interventions were rare. Significant ischaemic events (bowel/gluteal/spinal ischaemia) were very rare. Plugs were quicker to place and required less radiation (p < .001) than coils. GRADE scoring was very low for all outcomes. CONCLUSION: Overall the quality of reported data on IIA sacrifice is poor. Buttock claudication and erectile dysfunction occurred frequently after IIA sacrifice. Where both options are technically possible, plugs could be considered preferential to coils, and placed as proximally in the IIA as possible.

Formulating and improving care while mitigating risk in a military Ebola virus disease treatment unit.

This paper describes the development of the UK military's Ebola Virus Disease Treatment Unit (EVD TU) that was deployed to Sierra Leone as part of the UK response to the West African Ebola virus disease (EVD) epidemic in 2014 and 2015. It highlights specific challenges faced within this unique Field Hospital environment. The military EVD TU was initially established to provide confidence to international healthcare workers coming to Sierra Leone to assist in the international response to the EVD epidemic and formed a key part of the action plan by the UK's Department for International Development. It was designed and staffed to provide a high level of care to those admitted with suspected or confirmed EVD and was prepared to admit the first patient within 6 weeks of the original activation order by the Ministry of Defence. This article outlines the main hazards perceived at the outset of the operation and the methods used to mitigate the risk to the healthcare workers at the EVD TU. The article examines the mechanisms that enabled the hospital to respond positively to challenges that emerged during the deployment, while simultaneously reducing the risk to the healthcare workers involved in care delivery.