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In recent years, the life expectancy of Multiple Myeloma (MM) patients has substantially improved, but this cancer remains incurable with increasing incidence in the developed world. Most MM patients will eventually relapse due to residual drug-resistant cancerous cells that survive treatment, commonly referred to as minimal residual disease (MRD). Methods to improve MRD detection in MM patients are generating considerable interest as a means of monitoring patients' response to treatment. In clinical laboratories, these methods currently require bone marrow aspirates which are invasive and frequently miss detection of localised disease due to the spatial heterogeneity of disease infiltration. By simplifying serial sampling and allowing for the detection of extramedullary disease, a blood-based method could significantly impact treatment duration and intensity and minimise chemotherapy-induced toxicity. This review will describe the current blood-based techniques available to detect MRD in MM and compare their potential to evaluate patient prognosis and drive therapeutic decisions.

Background Physical inactivity is highly prevalent after stroke, increasing the risk of poor health outcomes including recurrent stroke. Tailoring of exercise programs to individual preferences can improve adherence, but no tools exist for this purpose in stroke. Methods We identified potential questionnaire items for establishing exercise preferences via: (i) our preliminary Exercise Preference Questionnaire in stroke, (ii) similar tools used in other conditions, and (iii) expert panel consultations. The resulting 35-item questionnaire (SEPI-35) was administered to stroke survivors, along with measures of disability, depression, anxiety, fatigue and self-reported physical activity. Exploratory factor analysis was used to identify a factor structure in exercise preferences, providing a framework for item reduction. Associations between exercise preferences and personal characteristics were analysed using multivariable regression. Results A group of 134 community-dwelling stroke survivors (mean age 64.0, SD 13.3) participated. Analysis of the SEPI-35 identified 7 exercise preference factors (Supervision-support, Confidence-challenge, Health-wellbeing, Exercise context, Home-alone, Similar others, Music-TV). Item reduction processes yielded a 13-item version (SEPI-13); in analysis of this version, the original factor structure was maintained. Lower scores on Confidence-challenge were significantly associated with disability (p = 0.002), depression (p = 0.001) and fatigue (p = 0.001). Self-reported barriers to exercise were particularly prevalent in those experiencing fatigue and anxiety. Conclusions The SEPI-13 is a brief instrument that allows assessment of exercise preferences and barriers in the stroke population. This new tool can be employed by health professionals to inform the development of individually tailored exercise interventions.

The often-invisible access barriers to public transport encountered by people with communication disabilities, who have sensory, language or cognitive impairments have gained little attention. This study investigated the experiences of people with communication disabilities on a rail network in Victoria, Australia to identify the barriers they encountered.Twenty-one passengers with communication disabilities participated in either an individual interview or a focus group. They talked about their experiences of train travel, factors that made travelling difficult and suggestions for making travelling easier. A six-phase approach to thematic analysis was conducted to identify themes.The difficulties identified in travelling fell into three themes: (a) variable accessibility of information, (b) negative impact of a large and complex service system, and (c) an uncertain culture of help seeking and giving. Only two passengers had ever complained but all identified ways to improve the service. They suggested, better staff training, more use of communication tools, mechanisms to enable passengers to seek help, and attention to making information easier to understand.For transport to be accessible to people with communication disabilities many different types of adjustment are required. Using multiple modes of communication with attention to understandability and consistent responses from public contact staff skilled to interact in multiple ways, may be the most flexible and effective means of responding to difficulties posed by the complex and unpredictable nature of train services. Implications for Rehabilitation People with communication disabilities are a diverse group which includes people with physical, sensory, speech, language, and cognitive impairments. Public transport services need to provide a range of communication adjustments to enable people with communication disabilities to travel successfully. Transport services must retain and refine accessible alternatives to online information and booking systems for people with cognitive impairments to avoid widening the digital divide. Frequent and unavoidable changes to train services mean that skilled public contact staff, access to information and a culture of help seeking and giving are particularly important in facilitating access for people with communication disabilities.

Aim of study: Recurrent in-hospital cardiac arrest (IHCA) is associated with morbidity and mortality in adults. We aimed to describe the risk factors and outcomes for paediatric recurrent IHCA. Methods: Retrospective cohort study of patients ≤18 years old with single or recurrent IHCA. Recurrent IHCA was defined as ≥2 IHCA within the same hospitalization. Categorical variables expressed as percentages and compared via Chi square test. Continuous variables expressed as medians with interquartile ranges and compared via rank sum test. Outcomes assessed in a propensity match cohort. Results: From July 1, 2015 to January 26, 2021, 139/894 (15.5%) patients experienced recurrent IHCA. Compared to patients with a single IHCA, recurrent IHCA patients were more likely to be trauma and less likely to be surgical cardiac patients. Median duration of cardiopulmonary resuscitation (CPR) was shorter in the recurrent IHCA (5 vs. 11 min; p < 0.001) with no difference in IHCA location or immediate cause of CPR. Patients with recurrent IHCA had worse survival to intensive care unit (ICU) discharge (31% vs. 52%; p < 0.001), and worse survival to hospital discharge (30% vs. 48%; p < 0.001) in unadjusted analyses and after propensity matching, patients with recurrent IHCA still had worse survival to ICU (34% vs. 67%; p < 0.001) and hospital (31% vs. 64%; p < 0.001) discharge. Conclusion: When examining those with a single vs. a recurrent IHCA, event and patient factors including more pre-existing conditions and shorter duration of CPR were associated with risk for recurrent IHCA. Recurrent IHCA is associated with worse survival outcomes following propensity matching.

BACKGROUND: Research consistently shows that Australian employment services are failing those they are intended to serve. Based on findings in other human service areas, a valid and reliable instrument to measure unemployed workers’ experiences may provide an opportunity for improvement in this sector. OBJECTIVE: To establish a basis for developing a suitable rating scale. METHODS: An exploratory factor analysis combined with qualitative cross check for face validity of an existing large survey of Australian unemployed workers. RESULTS: Six factors appear to be important elements of service delivery: (F1) useful and competent, (F2) client-centred, (F3) receptive to feedback, (F4) trustworthy, (F5) fair, and (F6) friendly. CONCLUSIONS: While each of these factors have been either described explicitly or referred to implicitly in previous studies, this study is the first to attempt to combine these factors and is a precursor to establishing a valid and reliable rating scale for use by unemployed workers in evaluating their employment service providers. At a time when Australia is exploring new approaches to employment services, such a scale using a robust set of factors may allow for the improvement of employment services and thus be held accountable to a significant stakeholder group whom they aim to serve –unemployed workers.

BackgroundPatients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear.ObjectiveTo determine the immunogenicity of mRNA-based SARS-CoV-2 vaccines in patients with CID.DesignProspective observational cohort study.SettingTwo U.S. CID referral centers.ParticipantsVolunteer sample of adults with confirmed CID eligible for early COVID-19 vaccination, including hospital employees of any age and patients older than 65 years. Immunocompetent participants were recruited separately from hospital employees. All participants received 2 doses of mRNA vaccine against SARS-CoV-2 between 10 December 2020 and 20 March 2021. Participants were assessed within 2 weeks before vaccination and 20 days after final vaccination.MeasurementsAnti-SARS-CoV-2 spike (S) IgG+ binding in all participants, and neutralizing antibody titers and circulating S-specific plasmablasts in a subset to assess humoral response after vaccination.ResultsMost of the 133 participants with CID (88.7%) and all 53 immunocompetent participants developed antibodies in response to mRNA-based SARS-CoV-2 vaccination, although some with CID developed numerically lower titers of anti-S IgG. Anti-S IgG antibody titers after vaccination were lower in participants with CID receiving glucocorticoids (n=17) than in those not receiving them; the geometric mean of anti-S IgG antibodies was 357 (95% CI, 96 to 1324) for participants receiving prednisone versus 2190 (CI, 1598 to 3002) for those not receiving it. Anti-S IgG antibody titers were also lower in those receiving B-cell depletion therapy (BCDT) (n=10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites (n=48), tumor necrosis factor inhibitors (n=39), and Janus kinase inhibitors (n=11); however, 95% CIs were wide and overlapped. Neutralization titers seemed generally consistent with anti-S IgG results. Results were not adjusted for differences in baseline clinical factors, including other immunosuppressant therapies.LimitationsSmall sample that lacked demographic diversity, and residual confounding.ConclusionCompared with nonusers, patients with CID treated with glucocorticoids and BCDT seem to have lower SARS-CoV-2 vaccine-induced antibody responses. These preliminary findings require confirmation in a larger study.Primary funding sourceThe Leona M. and Harry B. Helmsley Charitable Trust, Marcus Program in Precision Medicine Innovation, National Center for Advancing Translational Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Tumor infiltrating lymphocytes (TILs) and regression are thought to be distinct markers of the immune response to melanoma.This study sought to analyze the relationship of TIL grade and presence of regression to each other and to other prognostic histopathologic and clinical values in melanoma.A retrospective analysis was conducted using patients diagnosed with melanoma between 2013 and 2019 whose complete histopathologic reports were available.Regression was seen in 48.9%, 30.1% and 37.9% of patients with brisk, non-brisk, and absent TILs respectively (P=0.019). Melanoma tumors with brisk TILs were found to have a lower Breslow thickness than those with non-brisk or absent (P= 0.001). Tumors with regression were also found to have lower Breslow thickness (P0.001). Neither TIL grade nor regression were protective of nodal metastasis or associated with improved survival.Brisk TILs have a positive association with thinner tumors and the presence of tumor regression relative to non-brisk or absent TILs. This may suggest a more robust immune response in tumors with brisk TILs. Further exploration of the interplay between TIL grade, lymphocyte cell subtype and lymphocyte density may help explain this finding.

RationalePulmonary rehabilitation is an effective treatment for people with chronic respiratory disease but is delivered to MethodsA multicentre randomised controlled trial with assessor blinding, powered for equivalence was undertaken. Individuals with a chronic respiratory disease referred to pulmonary rehabilitation at four participating sites (one rural) were eligible and randomised using concealed allocation to pulmonary rehabilitation or telerehabilitation. Both programmes were two times per week for 8 weeks. The primary outcome was change in Chronic Respiratory Disease Questionnaire Dyspnoea (CRQ-D) domain at end-rehabilitation, with a prespecified equivalence margin of 2.5 points. Follow-up was at 12 months. Secondary outcomes included exercise capacity, health-related quality of life, symptoms, self-efficacy and psychological well-being.Results142 participants were randomised to pulmonary rehabilitation or telerehabilitation with 96% and 97% included in the intention-to-treat analysis, respectively. There were no significant differences between groups for any outcome at either time point. Both groups achieved meaningful improvement in dyspnoea and exercise capacity at end-rehabilitation. However, we were unable to confirm equivalence of telerehabilitation for the primary outcome ΔCRQ-D at end-rehabilitation (mean difference (MD) (95% CI) −1 point (−3 to 1)), and inferiority of telerehabilitation could not be excluded at either time point (12-month follow-up: MD −1 point (95% CI −4 to 1)). At end-rehabilitation, telerehabilitation demonstrated equivalence for 6-minute walk distance (MD −6 m, 95% CI −26 to 15) with possibly superiority of telerehabilitation at 12 months (MD 14 m, 95% CI −10 to 38).Conclusiontelerehabilitation may not be equivalent to centre-based pulmonary rehabilitation for all outcomes, but is safe and achieves clinically meaningful benefits. When centre-based pulmonary rehabilitation is not available, telerehabilitation may provide an alternative programme model.Trial registration numberACtelerehabilitationN12616000360415.

Stylistics is a branch of linguistics concerned with the systematic analysis of style in language, particularly literary style. Poetry has been a staple of stylistics. Creative performance of poems and stylistic analysis, however, have rarely been bedfellows. I showcase a stylistics pedagogy for creatively interpreting poetry in higher education where students make digitally multimodal storied interpretations of poems. The pedagogy reflects contemporary internet mashup culture, recognising that students inhabit a “postdigital” world where commonplace software and resources offer opportunities for DIY juxtaposition of audio and video for different purposes – artistic, comedic, etc. An advantage of such Postdigital Stylistics is that it integrates performance-based readers, marginalised in exegetical reading practices associated with print. I illustrate the pedagogy with a student video of Charles Bukowski’s poem “the bluebird”, accessible analysis of its foregrounded style, and explanation of how this analysis – crucially – motivates shot design.

Objective: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.

Various lifestyle and environmental factors are known to influence sleep. Increasingly, evidence points to a role for the microbiota in regulating brain and behaviour. This article explores how the microbiota-gut-brain axis affects sleep directly and indirectly. We summarize the possible molecular mechanisms underlying sleep-microbiome interactions and discuss how various factors interact with the gut microbiota to influence sleep. Furthermore, we present the current evidence of alterations of the microbiota-gut-brain axis in various sleep disorders and pathologies where comorbid sleep disturbances are common. Since manipulating the gut microbiota could potentially improve sleep, we outline ways in which this can be achieved.

We aimed to benchmark the quality of care and describe characteristics of patients newly attending the HIV clinic at differing time points over the past 10 years, against the Infectious Disease Society of America HIV/AIDS performance measures. We performed a retrospective analysis of records for patients newly attending the HIV clinic in 2011, 2016 and 2018. There was an increase in male attendees in 2018 and 2016 compared to 2011 (88%, 88% vs. 59% p < .001), viral suppression rates were 97%, 83% and 99% ( p < .001), respectively. We observed an increase in patients of South American origin over time. Acquisition risk changed, with increased proportion of MSM (24% in 2011 vs 78% in 2018, p < .001), lower rates of heterosexual (20% in 2018 vs 48% in 2011, p < .001) and IDU transmission (1.5% in 2018 vs 24% in 2011, p < .001). There were lower rates of Chlamydia trachomatis and Neisseria gonorrhoeae testing in 2018 (72%, p < .001), compared to 2016 (84%) and 2011 (83%). Hepatitis B virus vaccination and pneumococcal vaccine rates are declining ( p < .001). We demonstrate the changes in both ethnicity and risk of acquisition over time, high rates of antiretroviral therapy prescription and viral suppression, and highlight the importance of health prevention with sexual health screening and vaccination in this population.

Although COVID-19-associated hospitalizations and deaths have occurred more frequently in adults,† COVID-19 can also lead to severe outcomes in children and adolescents (1,2). Schools are opening for in-person learning, and many prekindergarten children are returning to early care and education programs during a time when the number of COVID-19 cases caused by the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, is increasing.§ Therefore, it is important to monitor indicators of severe COVID-19 among children and adolescents. This analysis uses Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET)¶ data to describe COVID-19-associated hospitalizations among U.S. children and adolescents aged 0-17 years. During March 1, 2020-August 14, 2021, the cumulative incidence of COVID-19-associated hospitalizations was 49.7 per 100,000 children and adolescents. The weekly COVID-19-associated hospitalization rate per 100,000 children and adolescents during the week ending August 14, 2021 (1.4) was nearly five times the rate during the week ending June 26, 2021 (0.3); among children aged 0-4 years, the weekly hospitalization rate during the week ending August 14, 2021, was nearly 10 times that during the week ending June 26, 2021.** During June 20-July 31, 2021, the hospitalization rate among unvaccinated adolescents (aged 12-17 years) was 10.1 times higher than that among fully vaccinated adolescents. Among all hospitalized children and adolescents with COVID-19, the proportions with indicators of severe disease (such as intensive care unit [ICU] admission) after the Delta variant became predominant (June 20-July 31, 2021) were similar to those earlier in the pandemic (March 1, 2020-June 19, 2021). Implementation of preventive measures to reduce transmission and severe outcomes in children is critical, including vaccination of eligible persons, universal mask wearing in schools, recommended mask wearing by persons aged ≥2 years in other indoor public spaces and child care centers,†† and quarantining as recommended after exposure to persons with COVID-19.§§.

Increasingly, people turn to online sources for health information, creating human-non-human relationalities. Health websites are considered accessible in scope and convenience but can have limited capacity to accommodate complexities. There are concerns about who gets to 'assemble' with these resources, and who is excluded. Guided by Ahmed's socio-political theories of emotions, we questioned our feelings as we intra-acted with a consumer information website about back pain (MyBackPain). This encouraged us to approach resource evaluation in a way that alters conventional rational/cognitive judgement processes. Our inquiry was 'supra-disciplinary' involving public health, sociology, allied health and consumer collaborators. Specifically, we considered relationality - the feelings circulating between bodies/objects and implicated in MyBackPain's affective practices; impressions - the marks, images or beliefs MyBackPain makes on bodies/objects; and directionality - how these intra-actions pushed in some directions and away from others. Although Ahmed would likely not consider herself 'post-humanist', we argue that her socio-political theories of how objects and emotions entangle are of great interest to furthering critical post-human understandings of health. Rather than threatening decision-making, we suggest that feelings (and their affects) are central to it. The article demonstrates the productive potential of critical post-human inquiry in identifying/countering 'othering' possibilities, and catalysing a 'nomadic shift' towards new human-non-human formations.

Historically, adrenal glands diseases causing hypertension, such as Primary Aldosteronism (PA), have been treated through pharmacotherapy or surgical resection. Given the shortcomings of the available treatment options, the interest in alternative and less invasive treatment modalities such as microwave ablation (MWA), has increased. In order to develop and optimize this novel electromagnetic-based therapy, an accurate knowledge of the dielectric properties of human adrenal glands, as well as preclinical animal models, is crucial. In particular, ovine models represent a feasible animal model to test the safety and performances of MWA. In this study, the dielectric properties of ovine adrenal glands and of normal and diseased human adrenal glands are characterized ex vivo in the microwave frequency range. The dielectric properties of the two functional tissues (cortex and medulla) composing ovine adrenal glands are measured using the open-ended coaxial probe technique and represented with a two pole Cole-Cole model in the frequency range from 0.5 GHz to 8 GHz. This paper presents the first dielectric data of normal and diseased human adrenal tissues, including a functioning adenoma responsible for PA and it compares the human data with data from the animal model. peer-reviewed

Little is known regarding community participation in individuals with chronic obstructive pulmonary disease (COPD). The aim of this study was to explore community participation in individuals with COPD and to determine whether there is an association between community participation and activity-related outcome variables commonly collected during pulmonary rehabilitation assessment. We also sought to investigate which of these variables might influence community participation in people with COPD. Ninety-nine individuals with COPD were enrolled (67 ± 9 years, FEV1: 55 ± 22% predicted). We assessed community participation (Community Participation Indicator (CPI) and European Social Survey (ESS) for formal and informal community participation), daily physical activity levels (activity monitor), exercise capacity (6-minute walk test), breathlessness (Modified Medical Research Council, MMRC scale), self-efficacy (Pulmonary Rehabilitation Adapted Index of Self-Efficacy) and anxiety and depression (Hospital Anxiety and Depression Scale). Higher levels of community participation on the CPI were associated with older age and greater levels of physical activity (total, light and moderate-to-vigorous) (all rs = 0.30, p

Obesity has been reported to be associated with short sleep duration. It follows that patients with a BMI >35kg/m2 could be expected to have the poorest sleep. This poor sleep could be explained by the presence of obstructive sleep apnoea (OSA), although treatment with positive airway pressure (PAP) may modify this. The purpose of this study is to determine if patients attending for bariatric surgery have poor sleep independent of OSA status. Sleep duration and quality, using the Pittsburgh Sleep Quality Index (PSQI), was analysed in 203 patients undergoing bariatric surgery between June 2016 and May 2019 in a single centre. Anthropometric data on all patients were recorded as well as presence of OSA and PAP usage. The bariatric population reported an average (standard deviation) sleep duration of 6.5 (1.6) h, and 67.9% of patients had a documented poor sleep quality (PSQI>5). The presence of OSA did not significantly influence either sleep duration (p=0.23) or sleep quality (p=0.5). On logistic regression, there was no significant relationship between sleep duration or sleep quality and the following variables: age, sex, and AHI. There was however a significant association between BMI and sleep quality (p= 0.007). PSQI was inversely associated with BMI. This equated to 1 kg/m2 weight gain being associated with 0.097 decrease in PSQI score. The presence of OSA does not influence either sleep duration or sleep quality in the bariatric surgical population. This suggests that clinically severe obesity itself may cause poor sleep.

The purpose of this study was to explore the way Australian national sport organisations (NSOs) create, develop and implement their policies relevant to trans athletes. Representatives of nine NSOs were interviewed utilising in-depth semi-structured interviews. Four key themes emerged from the organisation spokespersons’ accounts: a) finding the right policy, b) underfunded and under resourced, c) challenges of educating employees and the public, and lastly, d) communication between NSOs and the trans athletic community. Findings revealed that only two NSOs reported had specific policies directed at trans athlete’s sport participation. Several NSOs indicated that they had plans to develop separate policies for the different levels of competition to assist trans athletes to participate in their sport as their identified gender. This is the first study to explore the perspective and views of NSOs on the participation of trans athletes in sport.

Rationale & Objective Adaptive design methods are intended to improve the efficiency of clinical trials and are relevant to evaluating interventions in dialysis populations. We sought to determine the use of adaptive designs in dialysis clinical trials and quantify trends in their use over time. Study Design We completed a novel full-text systematic review that used a machine learning classifier (RobotSearch) for filtering randomized controlled trials and adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Setting & Study Populations We searched MEDLINE (PubMed) and ClinicalTrials.gov using sensitive dialysis search terms. Selection Criteria for Studies: We included all randomized clinical trials with patients receiving dialysis or clinical trials with dialysis as a primary or secondary outcome. There was no restriction of disease type or intervention type. Data Extraction & Analytical Approach We performed a detailed data extraction of trial characteristics and a completed a narrative synthesis of the data. Results 57 studies, available as 68 articles and 7 ClinicalTrials.gov summaries, were included after full-text review (initial search, 209,033 PubMed abstracts and 6,002 ClinicalTrials.gov summaries). 31 studies were conducted in a dialysis population and 26 studies included dialysis as a primary or secondary outcome. Although the absolute number of adaptive design methods is increasing over time, the relative use of adaptive design methods in dialysis trials is decreasing over time (6.12% in 2009 to 0.43% in 2019, with a mean of 1.82%). Group sequential designs were the most common type of adaptive design method used. Adaptive design methods affected the conduct of 50.9% of trials, most commonly resulting in stopping early for futility (41.2%) and early stopping for safety (23.5%). Acute kidney injury was studied in 32 trials (56.1%), kidney failure requiring dialysis was studied in 24 trials (42.1%), and chronic kidney disease was studied in 1 trial (1.75%). 27 studies (47.4%) were supported by public funding. 44 studies (77.2%) did not report their adaptive design method in the title or abstract and would not be detected by a standard systematic review. Limitations We limited our search to 2 databases (PubMed and ClinicalTrials.gov ) due to the scale of studies sourced (209,033 and 6,002 results, respectively). Conclusions Adaptive design methods are used in dialysis trials but there has been a decline in their relative use over time.

Background The COVID‐19 pandemic has been accompanied by the largest mobilization of therapeutic convalescent plasma (CCP) in over a century. Initial identification of high titer units was based on dose–response data using the Ortho VITROS IgG assay. The proliferation of severe acute respiratory syndrome coronavirus 2 serological assays and non‐uniform application has led to uncertainty about their interrelationships. The purpose of this study was to establish correlations and analogous cutoffs between multiple serological assays. Methods We compared the Ortho, Abbott, Roche, an anti‐spike (S) ELISA, and a virus neutralization assay. Relationships relative to FDA‐approved cutoffs under the CCP emergency use authorization were identified in convalescent plasma from a cohort of 79 donors from April 2020. Results Relative to the neutralization assay, the spearman r value of the Ortho Clinical, Abbott, Roche, anti‐S ELISA assays was 0.65, 0.59, 0.45, and 0.76, respectively. The best correlative index for establishing high‐titer units was 3.87 signal‐to‐cutoff (S/C) for the Abbott, 13.82 cutoff index for the Roche, 1:1412 for the anti‐S ELISA, 1:219 by the neutralization assay, and 15.9 S/C by the Ortho Clinical assay. The overall agreement using derived cutoffs compared to a neutralizing titer of 1:250 was 78.5% for Abbott, 74.7% for Roche, 83.5% for the anti‐S ELISA, and 78.5% for Ortho Clinical. DISCUSSION Assays based on antibodies against the nucleoprotein were positively associated with neutralizing titers and the Ortho assay, although their ability to distinguish FDA high‐titer specimens was imperfect. The resulting relationships help reconcile results from the large body of serological data generated during the COVID‐19 pandemic.

This study explores the presentation, management and outcomes of traumatic venous sinus thrombosis (VST) and identifies risk factors associated with poor outcomes. This study is a retrospective review of all patients with VST secondary to trauma who presented to a major trauma centre, between April 2015 and January 2020. VST was confirmed by CT venogram and a consultant neuroradiologist. Forty-six patients were identified (38 male), mean age of 43 (range 12–78) and median follow-up 10.2 months (range 0.7–39.1). Fifty-two percent presented as a severe traumatic brain injury, and all had an associated skull fractures overlying the sinus. Ninety-six percent had cerebral contusions, 96% had an intracranial haematoma, 91% had traumatic subarachnoid haemorrhage (tSAH) and 22% had acute cerebral infarction. Thirty-seven percent of the VSTs were occlusive. Fifty-eight percent had sustained, unprovoked intracranial pressure (ICP) spikes (> 20 mmHg). Fifty percent underwent surgical intervention—20% external ventricular drain and 46% craniotomy/craniectomy. Nine percent were treated with anticoagulation and 4% with antiplatelets, at a median of 13.5 days and 9.5 days post-injury, with no additional complications. Age > 60 was associated with poor outcome (GOS of 3–5) (p = 0.0098). On follow-up CT, 52% of the VSTs remained unchanged, 29% re-canalised, 14% improved and 5% worsened, independent of treatment. This study demonstrated a higher incidence of VST in severe TBI and strong associations with skull fractures, cerebral contusions, tSAH, raised ICP and surgical intervention. Management was inconsistent, with no difference in outcome with or without anticoagulation. Larger, prospective cohort studies are needed to better understand this condition and establish evidence-based guidelines.

Background The SARS-CoV-2 pandemic has had profound implications on healthcare institutions. Aims This study aims to assess and compare referral patterns during COVID-19 to corresponding dates for the preceding 3 years (2017–2019), in order to preemptively coordinate the logistics of the surgical unit for similar future experiences. Methods Retrospective review for our institution, a national tertiary referral centre for spine pathology. Two distinct time-points were chosen to represent the varied levels of social restriction during the current pandemic: (i) study period 1 (SP1) from 11 November 2020 to 08 June 2020 represents a national lockdown, and (ii) study period 2 (SP2) from 09 June 2020 to 09 September 2020 indicates an easing of restrictions. Both periods were compared to corresponding dates (CP1: 11 March–08 June and CP2 09 June–09 September) for the preceding 3 years (2017–2019). Data collected included age, gender, and mechanism of injury (MOI) for descriptive analyses. MOIs were categorised into disc disease, cyclist, road-traffic-accident (RTA), falls 2 m, malignancy, sporting injuries, and miscellaneous. Results All MOI categories witnessed a reduction in referral numbers during SP1: disc disease (−29%), cyclist (−5%), RTAs (−66%), falls 2 m (−17%), malignancy (−33%), sporting injuries (−100%), and miscellaneous (−58%). Four of 8 categories (RTAs, falls 2 m) showed a further reduction (−34%, −27%) during SP2. One category (sporting injuries) portrayed a complete return to normal values during SP2 while a notable increase in cyclist-related referrals was witnessed (+ 63%) when compared with corresponding dates of previous years. Conclusion Spinal injury continues to occur across almost all categories, albeit at considerably reduced numbers. RTAs and falls remained the most common MOI. Awareness needs to be drawn to the reduction of malignancy-related referrals to dissuade people with such symptoms from avoiding presentation to hospital over periods of social restrictions.

Background When considering adherence to antiretroviral therapy (ART) for HIV, many different cut-points are used. The primary goals of this study were to identify a level of self-reported medication adherence that best distinguished HIV viral suppression from non-suppression, and to compare the ability of a single-item and a 3-item adherence questionnaire to predict HIV viral suppression. Methods This cross-sectional analysis included 380 persons with HIV (PWH) from the Florida Cohort study who completed a self-reported ART adherence measure within 30-days of having an HIV viral load test. We used Receiver Operating Characteristic (ROC) curve analyses and ROCContrast to compare the ability of a single-item and a 3-item self-reported adherence measure to predict HIV viral suppression (defined as ≤ 200 copies/mL). We used the Youden index and chi square statistics to assess specific cut-points, and repeated the analysis with a different definition of HIV viral suppression (≤ 1000 copies/mL). Results The mean percent adherence was 92.4% using the single-item score and 90.4% using the 3-item score; 81.6% had viral suppression. The areas under the curve for the single-item and 3-item adherence measures were generally poor overall and not significantly different from each other (0.589 and 0.580, p = 0.67). The Youden index identified cut-points of 93% and 89% as maximizing the sensitivity and specificity for the single-item and 3-item measures, respectively, whereas a cut-point of 80% on the single-item measure was best able to discriminate those with viral suppression (58% vs. 84%, p < 0.001). Results were similar with viral suppression defined as ≤ 1000 copies/mL. Conclusions In this sample of PWH, a single question on medication adherence was as good as a 3-item questionnaire in predicting HIV viral suppression, although neither had good discriminatory ability. A cut-point close to 90% adherence maximized sensitivity and specificity, although viral suppression was very similar for nearly all measures above 80%.

The "contingent valuation" method is used to quantify the value of services not available in traditional markets, by assessing the monetary value an individual ascribes to the benefit provided by an intervention. The aim of this study was to determine preferences for home or center-based pulmonary rehabilitation for participants with chronic obstructive pulmonary disease (COPD) using the "willingness to pay" (WTP) approach, the most widely used technique to elicit strengths of individual preferences. This is a secondary analysis of a randomized controlled equivalence trial comparing center-based and home-based pulmonary rehabilitation. At their final session, participants were asked to nominate the maximum that they would be willing to pay to undertake home-based pulmonary rehabilitation in preference to a center-based program. Regression analyses were used to investigate relationships between participant features and WTP values. Data were available for 141/163 eligible study participants (mean age 69 [SD 10] years

Stop-signal reaction time (SSRT), the time needed to cancel an already-initiated motor response, quantifies individual differences in inhibitory control. Electrophysiological correlates of SSRT have primarily focused on late event-related potential (ERP) components over midline scalp regions from successfully inhibited stop trials. SSRT is robustly associated with the P300, there is mixed evidence for N200 involvement, and there is little information on the role of early ERP components. Here, machine learning was first used to interrogate ERPs during both successful and failed stop trials from 64 scalp electrodes at 4 ms resolution (n = 148). The most predictive model included data from both successful and failed stop trials, with a cross-validated Pearson's r of 0.32 between measured and predicted SSRT, significantly higher than null models. From successful stop trials, spatio-temporal features overlapping the N200 in right frontal areas and the P300 in frontocentral areas predicted SSRT, as did early ERP activity (200 ms). As a demonstration of the reproducibility of these findings, the application of this model to a separate dataset of 97 participants was also significant (r = 0.29). These results show that ERPs during failed stops are relevant to SSRT, and that both early and late ERP activity contribute to individual differences in SSRT. Notably, the right lateralized N200, which predicted SSRT here, is not often observed in neurotypical adults. Both the ascending slope and peak of the P300 component predicted SSRT. These results were replicable, both within the training sample and when applied to ERPs from a separate dataset.

Background We have co-designed a tailored blended physiotherapy intervention for people with progressive multiple sclerosis (PwPMS) who often struggle to access support for physical activity. Underpinned by self-management principles, the Lifestyle, Exercise and Activity Package for people with Multiple Sclerosis (LEAP-MS) intervention incorporates face-to-face or online physiotherapy coaching sessions with an accompanying online physical activity platform. The LEAP-MS platform is a multi-user system enabling user and physiotherapist to co-create activity plans. The LEAP-MS platform consists of an information and activity suite, interactive components enabling selection of exercises into an activity programme, goal setting and activity logging. The platform also facilitates online remote support from a physiotherapist through an embedded online messaging function. We aim to evaluate the LEAP-MS platform in a feasibility trial. Methods LEAP-MS will be evaluated within a single-arm feasibility study with embedded process evaluation. After registration and initial eligible screening, 21 participants will be required to complete baseline self-completion measures. This will be followed by an initial home-based or online coaching session with a physiotherapist (who has received tailored self-management and digital resource training) and access to the online intervention for an initial 3-month period. During this period, participants are given the option to request up to five further home-based or online physiotherapy coaching sessions. Follow-up questionnaires and semi-structured interviews will be administered 3 months after baseline with participants and intervention physiotherapists. The LEAP-MS platform will be available to participants for a further 3 months. Usage of the LEAP-MS platform will be tracked during the full 6-month period and final follow-up will be conducted 6 months after baseline. Discussion Feasibility outcomes (recruitment, retention, intervention uptake and safety) will be reported. The process evaluation will be undertaken to identify possible mechanisms for any observed effects. The data will inform full-scale evaluations of this co-produced, blended physiotherapy intervention. Trial registration ClinicalTrials.gov, NCT03951181. Registered 15 May 2019

The GORE® CARDIOFORM ASD occluder (ASDO) is approved for closure of ASDs up to 35 mm diameter. With an adaptable central waist, each device size is suitable over a range of defect diameters. Understanding deployed dimensions across various defect sizes will assist operators. Therefore, this study investigates the deployed dimensions of the ASDO as a function of defect size. A 2-mm-thick ASD model with circular defects ranging from 5 to 35 mm was 3D printed. Diameter, width, and left–right disc diameter were measured by fluoroscopy after ASDO devices were deployed in applicable defects. Linear regression evaluated relationships between device size, defect size, and deployed dimensions. Six ASDOs of each size (27, 32, 37, 44, and 48 mm) were deployed in all applicable defects. There was significant ASDO size–defect size interaction in determining deployed ASDO diameter. Diameter was positively associated with defect size for 48-mm (B = 0.13, p

Background Integrase strand transfer inhibitors (INSTIs) are first-line regimens for HIV treatment. We aimed to examine their impact on cognitive performance and depressive symptoms in women with HIV (WWH). Setting Women's Interagency HIV Study, a multisite, prospective, cohort study. Methods WWH who started or switched to INSTI-based antiretroviral therapy (ART) and completed neuropsychological testing and the Center for Epidemiological Studies-Depression (CES-D) scale before and after INSTI start/switch were included in the analyses. Primary outcomes were demographically corrected cognitive domain T-scores. Linear mixed-effects models adjusted for relevant covariates were used to examine effects of start/switch of any INSTI and individual INSTI drugs on cognition and CES-D scores. Results Six hundred thirty-nine WWH, median age 49 (interquartile range 12) years, 66% Black non-Hispanic, had neuropsychological and CES-D scale data before and after INSTI start/switch. Although 14% started INSTI-based ART, the remainder switched to INSTI-based ART from another regimen. Overall, any INSTI use was associated with poorer learning post-INSTI. Specifically, use of dolutegravir and elvitegravir, but not raltegravir, was associated with poorer learning. In analyses restricted to INSTI switch, any INSTI use, and dolutegravir use, was associated with poorer learning. Among those switching from a PI-based regimen, INSTIs overall and dolutegravir remained associated with poorer learning; switching from a nonnucleoside reverse transcriptase inhibitor to dolutegravir was also associated with poorer learning. INSTI start/switch was not related to depressive symptom changes. Conclusions INSTI use was associated with poorer learning among WWH. These changes were mainly observed in elvitegravir and dolutegravir users, indicating that the impact of INSTI on cognition in WWH may not be a class effect.

Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265, Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272, Funder: Marker Diagnostics, Funder: Rugby Football Union, Funder: Midland Neuroscience Teaching and Research Fund, Objective: To investigate the role of salivary small non-coding RNAs (sncRNAs) in the diagnosis of sport-related concussion. Methods: Saliva was obtained from male professional players in the top two tiers of England’s elite rugby union competition across two seasons (2017–2019). Samples were collected preseason from 1028 players, and during standardised head injury assessments (HIAs) at three time points (in-game, post-game, and 36–48 hours post-game) from 156 of these. Samples were also collected from controls (102 uninjured players and 66 players sustaining a musculoskeletal injury). Diagnostic sncRNAs were identified with next generation sequencing and validated using quantitative PCR in 702 samples. A predictive logistic regression model was built on 2017–2018 data (training dataset) and prospectively validated the following season (test dataset). Results: The HIA process confirmed concussion in 106 players (HIA+) and excluded this in 50 (HIA−). 32 sncRNAs were significantly differentially expressed across these two groups, with let-7f-5p showing the highest area under the curve (AUC) at 36–48 hours. Additionally, a combined panel of 14 sncRNAs (let-7a-5p, miR-143-3p, miR-103a-3p, miR-34b-3p, RNU6-7, RNU6-45, Snora57, snoU13.120, tRNA18Arg-CCT, U6-168, U6-428, U6-1249, Uco22cjg1,YRNA_255) could differentiate concussed subjects from all other groups, including players who were HIA− and controls, immediately after the game (AUC 0.91, 95% CI 0.81 to 1) and 36–48 hours later (AUC 0.94, 95% CI 0.86 to 1). When prospectively tested, the panel confirmed high predictive accuracy (AUC 0.96, 95% CI 0.92 to 1 post-game and AUC 0.93, 95% CI 0.86 to 1 at 36–48 hours). Conclusions: SCRUM, a large prospective observational study of non-invasive concussion biomarkers, has identified unique signatures of concussion in saliva of male athletes diagnosed with concussion.

Background Perioperative optimisation can improve outcomes for older people having surgery. Integration with primary care could improve quality and reduce variability in access to preoperative optimisation. Aim Our aim was to explore attitudes, beliefs and behaviours of general practitioners (GPs) regarding the perioperative pathway, and evaluate enablers and barriers to GP-led preoperative optimisation. Methods Stakeholder interviews (n=38) informed survey development. A purposive sampling frame was used to target delivery of online and paper surveys. Results were analysed using descriptive statistics. Results We had 231 responses (response rate 32.7%). Enablers included belief among GPs that optimisation improves postoperative outcomes (86%) and that they have a role discussing modifiable risk factors with patients (85%). Barriers included low frequency exposure to older surgical patients, minimal training in perioperative medicine and rare interaction with perioperative services. Conclusion This survey illustrates the importance of interprofessional education, cross-sector training opportunities and collaboration to deliver integrated preoperative optimisation for older people undergoing surgery.

BACKGROUND: Estrogen receptor (ER) status provides invaluable prognostic and therapeutic information in breast cancer (BC). When clinical decision making is driven by ER status, the value of assessing progesterone receptor (PgR) status is less certain. AIM: To describe the clinicopathologic features of ER positive (ER+) /PgR negative (PgR-) BC and to determine the effect of PgR negativity on oncologic outcomes in ER+ disease.METHODS: Consecutive female patients with ER+ BC managed in a single institution between 2005-2015 were included. Clinicopathological features of PgR- BC were determined. Factors associated with PgR- disease were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier curves and Cox regression analysis.RESULTS: 2660 patients were included with a median age of 59.6±13.3 years (21-99). Median follow-up was 97.2 months (3.0-181.2). 2208 cases were PgR+ (83.0%) and 452 were PgR- (17.0%). Being postmenopausal (OR:1.656, 95% Confidence interval (CI):1.249-2.195, P Citation Format: Matthew G Davey, Éanna J Ryan, Padraig J Folan, Niamh O'Halloran, Michael R Boland, Michael Kevin Barry, Karl J Sweeney, Carmel M Malone, Ray J McLaughlin, Michael J Kerin, Aoife J Lowery. The impact of progesterone receptor negativity on oncologic outcomes in estrogen receptor positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-45.

Background: Gastrostomy tubes (G-tubes) are invaluable clinical tools that play a role in palliation and nutrition in patients with cancer. This study aimed to better understand the risks and benefits associated with the placement and maintenance of G-tubes. Methods: Patients who underwent placement of a G-tube for cancer from January 2013 through December 2017 at a tertiary care center were considered for inclusion. Clinical data were retrospectively collected from medical records. Results: A total of 242 patients with cancer, whose average age at diagnosis was 61 years (range, 21–94 years), underwent G-tube placement for nutrition (76.4%), decompression (22.7%), or both (0.8%). Successful insertion was achieved in 96.8%, but 8 patients required >1 attempted method of insertion. In the decompression group, minor postplacement complications were less common (23.6% vs 53.5%; PPP=.01). Conclusions: Half of the patients who received decompressive G-tubes presented with stage IV disease and died within 1 month of placement. Those with >1 consult were more likely to be discharged to hospice. Patients with G-tubes for nutrition saw no change in functionality, complication rate, or survival, regardless of adjunct chemotherapy status. These findings illustrate the need for a tool to allow a better multidisciplinary approach and interventional decision-making for patients with cancer.

AIMS: To describe trends in pediatric in-hospital cardiac arrest drug administration and to assess temporal associations of the Pediatric Advanced Life Support (PALS) guideline changes with drug usage.METHODS: Pediatric patients RESULTS: A total of 6107 patients were analyzed. The adjusted odds of receiving lidocaine (0.33; 95% CI, 0.18, 0.61; p CONCLUSIONS: Changes to the PALS guidelines for lidocaine and bicarbonate were not temporally associated with acute changes in the use of these medications; however, better alignment with these updates was observed over time. A minor update to the language surrounding atropine in the PALS text was associated with a modest acute change in the observed use of atropine. Future studies exploring other factors that influence prescribers in pediatric IHCA are needed.

Background: Physical activity levels are low in people with chronic obstructive pulmonary disease, and there is limited knowledge about how pulmonary rehabilitation transforms movement behaviors. This study analyzed data from a pulmonary rehabilitation trial and identified determinants of movement behaviors.Methods: Objectively assessed time in daily movement behaviors (sleep, sedentary, light-intensity physical activity, and moderate- to vigorous-intensity physical activity) from a randomized controlled trial (n = 73 participants) comparing home- and center-based pulmonary rehabilitation was analyzed using conventional and compositional analytical approaches. Regression analysis was used to assess relationships between movement behaviors, participant features, and response to the interventions.Results: Compositional analysis revealed no significant differences in movement profiles between the home- and center-based groups. At end rehabilitation, conventional analyses identified positive relationships between exercise capacity (6-min walk distance), light-intensity physical activity, and moderate- to vigorous-intensity physical activity time. Compositional analyses identified positive relationships between a 6-minute walk distance and moderate- to vigorous-intensity physical activity time, accompanied by negative relationships with sleep and sedentary time (relative to other time components) and novel relationships between body mass index and light-intensity physical activity/sedentary time.Conclusion: Compositional analyses following pulmonary rehabilitation identified unique associations between movement behaviors that were not evident in conventional analyses.

Background: There is increasing policy interest in the consideration of frailty measures (rather than chronological age alone) to inform more equitable allocation of health and social care resources. In this study the Clinical Frailty Scale (CFS) classification tree was applied to data from The Irish Longitudinal Study on Ageing (TILDA) and correlated with health and social care utilisation. CFS transitions over time were also explored. Methods: Applying the CFS classification tree algorithm, secondary analyses of TILDA data were performed to examine distributions of health and social care by CFS categories using descriptive statistics weighted to the population of Ireland aged ≥65 years at Wave 5 (n=3,441; mean age 74.5 (SD ±7.0) years, 54.7% female). CFS transitions over 8 years and (Waves 1-5) were investigated using multi-state Markov models and alluvial charts. Results: The prevalence of CFS categories at Wave 5 were: 6% ‘very fit’, 36% ‘fit’, 31% ‘managing well’, 16% ‘vulnerable’, 6% ‘mildly frail’, 4% ‘moderately frail’ and 1% ‘severely frail’. No participants were ‘very severely frail’ or ‘terminally ill’. Increasing CFS categories were associated with increasing hospital and community health services use and increasing hours of formal and informal social care provision. The transitions analyses suggested CFS transitions are dynamic, with 2-year probability of transitioning from ‘fit’ (CFS1-3) to ‘vulnerable’ (CFS4), and ‘fit’ to ‘frail’ (CFS5+) at 34% and 6%, respectively. ‘Vulnerable’ and ‘frail’ had a 22% and 17% probability of reversal to ‘fit’ and ‘vulnerable’, respectively. Conclusions: Our results suggest that the CFS classification tree stratified the TILDA population aged ≥65 years into subgroups with increasing health and social care needs. The CFS could be used to aid the allocation of health and social care resources in older people in Ireland. We recommend that CFS status in individuals is reviewed at least every 2 years.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability. Its diagnosis, classification and management are complex. There is a paucity of data on the standard of COPD management in Irish general practice. We studied whether COPD diagnosis and management was in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. We investigated if patients who were smokers had received smoking cessation advice. We examined whether influenza and pneumococcal vaccination had been given. Ten general practices affiliated with the Irish Mid-West Specialist Training Programme in General Practice (GP) were searched, to determine which patients had a diagnosis of COPD. A data-collection audit tool was developed using GOLD 2019 guidelines. Results were tabulated in SPSS. Descriptive statistics were used. Of 482 patients studied, 91.7% were eligible for free GP care. In 49.4%, the diagnosis of COPD had been made appropriately. In 56.2%, there was no evidence that the stage of COPD had been formally assessed. Of the patients studied, 33.2% were deemed to be receiving appropriate therapy. Smoking status was documented in 99.6% of cases studied and 59.9% were ex-smokers, while 25.9% were current smokers. Appropriate smoking cessation advice had been offered to 71% of eligible patients. Influenza vaccine had been given to 66.2% in the previous 12 months. A total of 53.9% had ever received pneumococcal vaccination. This study provides a comprehensive snapshot of care in Irish general practice for patients with COPD prior to introduction of the Chronic Disease Management programme (CDM).

The aging process is characterized by the presence of high interindividual variation between individuals of the same chronical age prompting a search for biomarkers that capture this heterogeneity. Epigenetic clocks measure changes in DNA methylation levels at specific CpG sites that are highly correlated with calendar age. The discrepancy resulting from the regression of DNA methylation age on calendar age is hypothesized to represent a measure of biological aging with a positive/negative residual signifying age acceleration (AA)/deceleration, respectively. The present study examines the associations of 4 epigenetic clocks—Horvath, Hannum, PhenoAge, GrimAge—with a wide range of clinical phenotypes (walking speed, grip strength, Fried frailty, polypharmacy, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), Sustained Attention Reaction Time, 2-choice reaction time), and with all-cause mortality at up to 10-year follow-up, in a sample of 490 participants in the Irish Longitudinal Study on Ageing (TILDA). HorvathAA and HannumAA were not predictive of health; PhenoAgeAA was associated with 4/9 outcomes (walking speed, frailty MOCA, MMSE) in minimally adjusted models, but not when adjusted for other social and lifestyle factors. GrimAgeAA by contrast was associated with 8/9 outcomes (all except grip strength) in minimally adjusted models, and remained a significant predictor of walking speed, .polypharmacy, frailty, and mortality in fully adjusted models. Results indicate that the GrimAge clock represents a step-improvement in the predictive utility of the epigenetic clocks for identifying age-related decline in an array of clinical phenotypes promising to advance precision medicine.

Background The effectiveness of manipulation versus mobilization for the management of spinal conditions, including cervicogenic headache, is conflicting. However, a pragmatic approach comparing manipulation to mobilization has not been examined in a patient population with cervicogenic headache. Objectives To evaluate the effectiveness of manipulation compared to mobilization applied in a pragmatic fashion for patients with cervicogenic headache. Methods Forty-five (26 females) patients with cervicogenic headache (mean age 47.8 ± SD 16.9 years) were randomly assigned to receive either pragmatically selected manipulation or mobilization. Outcomes were measured at baseline, the second visit, discharge, and 1-month follow-up and included the Neck Disability Index (NDI), Numeric Pain Rating Scale (NPRS), the Headache Impact Test (HIT-6), the Global Rating of Change (GRC), the Patient Acceptable Symptoms Scale (PASS). The primary aim (effects of treatment on disability and pain were examined with a mixed-model analysis of variance (ANOVA), with treatment group (manipulation versus mobilization) as the between subjects variable and time (baseline, 48 hours, discharge and follow-up) as the within subjects variable. Results The interaction for the mixed model ANOVA was not statistically significant for NDI (p = 0.91), NPRS (p = 0.81), or HIT (p = 0.89). There was no significant difference between groups for the GRC or PASS. Discussion and conclusion The results suggest that manipulation has similar effects on disability, pain, GRC, and cervical range of motion as mobilization when applied in a pragmatic fashion for patients with cervicogenic headaches. Clinicaltrials.gov NCT03919630.

Background While the concerns regarding the long-term cognitive effects of repeated sports related head injury have become a major source of debate, it is not uncommon for these patients to require neurosurgical interventions in the acute setting. The aim of this study was to provide a unique insight into the acute nature and neurosurgical management of sports and exercise related traumatic brain injury. Methods We retrospectively analysed electronic records of all referrals made between July 2016 and December 2018 to the National Neurosurgical Centre at Beaumont Hospital to identify instances of sport and exercise related traumatic brain injuries (TBI). A sub-group analysis was carried out on patients transferred to the tertiary centre requiring neurosurgical/neuro-critical care. Results Over the 30-month period, 194 patients (mean age: 36) were referred with sports and exercise related TBI, of which 56 were transferred to our unit (26 adults, 30 paediatrics). The most frequently encountered sporting activities were cycling, gaelic football, horse riding and rugby. Injuries included cerebral contusions, subdural haematomas, extradural haematomas and skull fractures. Neurosurgical intervention via intracranial pressure monitoring (ICP), decompressive craniectomy and elevation of depressed skull fracture was required in 28 out of 194 patients (14.4%). 85.7% (n = 48) of patients had a discharge Glasgow Coma Scale (GCS) of 15. 4 patients had a tracheostomy in place at discharge and there were 4 mortalities. Conclusions Sports and exercise activities, ranging from contact team sports to individual activities, are a common cause of traumatic brain injury and maybe associated with a significant morbidity and mortality.

This paper presents the findings from a case study which explores how students engage with learning materials mediated through 360-degree panoramic videos. The case study extends findings from a pr...

Objectives The eICU Collaborative Research Database is a publicly available repository of granular data from more than 200,000 ICU admissions. The quantity and variety of its entries hold promise for observational critical care research. We sought to understand better the data available within this resource to guide its future use. Design We conducted a descriptive analysis of the eICU Collaborative Research Database, including patient, practitioner, and hospital characteristics. We investigated the completeness of demographic and hospital data, as well as those values required to calculate an Acute Physiology and Chronic Health Evaluation score. We also assessed the rates of ventilation, intubation, and dialysis, and looked for potential errors in the vital sign data. Setting American ICUs that participated in the Philips Healthcare eICU program between 2014 and 2015. Patients A total of 139,367 individuals who were admitted to one of the 335 participating ICUs between 2014 and 2015. Interventions None. Measurements and main results Most encounters were from small- and medium-sized hospitals, and managed by nonintensivists. The median ICU length of stay was 1.57 days (interquartile range, 0.82-2.97 d). The median Acute Physiology and Chronic Health Evaluation IV-predicted ICU mortality was 2.2%, with an observed mortality of 5.4%. Rates of ventilation (20-33%), intubation (15-24%), and dialysis (3-5%) varied according to the query method used. Most vital sign readings fell into realistic ranges, with manually curated data less likely to contain implausible results than automatically entered data. Conclusions Data in the eICU Collaborative Research Database are for the most part complete and plausible. Some ambiguity exists in determining which encounters are associated with various interventions, most notably mechanical ventilation. Caution is warranted in extrapolating findings from the eICU Collaborative Research Database to larger ICUs with higher acuity.

Predictive models are common in orthopedic research; however, most models are not validated in an external population. The Nonunion Risk Determination (NURD) score was developed using a single-center cohort of 382 patients to reliably predict tibia shaft nonunions at the time of initial intramedullary nail fixation. The purpose of this study was to externally validate the NURD score using data from the SPRINT Trial.The SPRINT trial was a multicenter study comparing reamed versus unreamed intramedullary nails in tibial shaft fracture patients. We assessed the prognostic performance of the NURD score in the SPRINT trial data with comparisons of the c-statistics, calibration plots, and a comparison of predicted probabilities at cut-points defined in the study to derive the NURD score. In addition, we compared the odds ratios of the NURD score components between the derivation (NURD) and external validation (SPRINT) data.The NURD score demonstrated significantly worse discrimination in the SPRINT data than was observed in the original data (c-statistic: 0.61 vs. 0.85, p0.01). The NURD score was well-calibrated in the derivation and SPRINT data. The SPRINT data had less heterogeneity, as determined by the standard deviation of the linear predictors (NURD: 1.4 vs.0.4). Once we adjusted for case-mix differences, the NURD score had similarly strong discrimination in the SPRINT data (c-statistic: 0.81 vs. 0.85, p = 0.17).Based on our external validation, the NURD score lacks generalizability as it underperforms with respect to discrimination in the SPRINT trial data. However, after adjusting for case-mix differences, the performance of the NURD score is comparable between the two datasets, suggesting robust reproducibility.

Objective Our goal was to identify aspects of residency applications predictive of subsequent performance during pediatric internship. Methods We conducted a retrospective cohort study of graduates of US medical schools who began pediatric internship in a large pediatric residency program in the summers of 2013 to 2017. The primary outcome was the weighted average of subjects’ Accreditation Council for Graduate Medical Education pediatric Milestone scores at the end of pediatric internship. To determine factors independently associated with performance, we conducted multivariate linear mixed-effects models controlling for match year and Milestone grading committee as random effects and the following application factors as fixed effects: letter of recommendation strength, clerkship grades, medical school reputation, master's or PhD degrees, gender, US Medical Licensing Examination Step 1 score, Alpha Omega Alpha membership, private medical school, and interview score. Results Our study population included 195 interns. In multivariate analyses, the aspects of applications significantly associated with composite Milestone scores at the end of internship were letter of recommendation strength (estimate 0.09, 95% confidence intervals [CI]: 0.04, 0.15), numbers of clerkship honors (est. 0.05, 95% CI: 0.01–0.09), medical school ranking (est. 0.04, 95% CI: 0.08–0.01), having a master's degree (est. 0.19, 95% CI: 0.03–0.36), and not having a PhD (est. 0.14, 95% CI: 0.02–0.26). Overall, the final model explained 18% of the variance in milestone scoring. Conclusions Letter of recommendation strength, clerkship grades, medical school ranking, and having obtained a Master's degree were significantly associated with higher clinical performance during pediatric internship.