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Background The Long-ter M O U tcomes after the Multisystem Inflammatory S yndrome I n C hildren (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood. Methods This multicenter observational cohort study will enroll at least 600 patients Conclusion The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.

Objectives The inclusion of musculoskeletal conditions within multimorbidity research is inconsistent, and working-age populations are largely ignored. We aimed to: (1) estimate multimorbidity prevalence among working-age individuals with a range of musculoskeletal conditions; and (2) better understand the implications of decisions about the number and range of conditions constituting multimorbidity on the strength of associations between multimorbidity and burden (e.g., health status and health care utilization). Study Design and Setting Using data from the Australian National Health Survey 2007–08, the associations between burden measures and three ways of operationalizing multimorbidity (survey, policy, and research based) within the working-age (18–64 years) musculoskeletal population were estimated using multiple logistic regression (age and gender adjusted). Results Depending on definition, from 20.2% to 75.4% of working-age individuals with musculoskeletal conditions have multimorbidity. Irrespective of definition, multimorbidity was associated with increased likelihood of subjective health burden, pain or musculoskeletal medicines use, nonmusculoskeletal specialist and pharmacist (advice only) consultations, and reduced likelihood of not consulting health professionals. A group with intermediate health outcomes was considered multimorbid by some, but not all definitions. With the restrictive policy and research multimorbidity definitions, this intermediate group is included within the reference population (i.e., are considered nonmultimorbid). This worsens the reference group's apparent health status thereby leveling the comparative burden between those with and without multimorbidity. Consequently, dichotomous cut points lead to similar associations with burden measures despite the increasingly restrictive multimorbidity definitions used. Conclusions All multimorbidity definitions were associated with burden among the working-age musculoskeletal population. However, dichotomous cut points obscure the gradient of increased burden associated with restrictive definitions.

Background Health systems globally promote appropriate prescribing by healthcare providers and safe and effective medicine use by consumers. Rx for Change, a publicly available database, provides access to systematic reviews regarding best practices for prescribing and using medicines. Despite the value of the database for improving prescribing and medicine use, its use remains suboptimal. This study aimed to develop a training program for five medicine-focused organisations in Canada and Australia to facilitate the use and understanding of the Rx for Change database. Methods Four steps were undertaken: 1) key informant interviews were completed across all organisations to understand the knowledge user perspective; 2) a directed content analysis was completed of the interview transcripts and proposed training was developed; 3) a second round of feedback on the proposed training by knowledge users was gathered; and 4) feedback was integrated to develop the final training. Results Sixteen key informant interviews with knowledge users were conducted. Themes for training content included the scope of, navigation and strategies for using Rx for Change (generic content) and practical examples on incorporating evidence within their workplace context (tailored content). The final training consisted of an informational video, a 60-minute face-to-face workshop and two post-training reminders. Conclusions A method of engaging knowledge users in the development of a training program to improve the use of an on-line database of systematic reviews was established and used to design training. Next steps include the delivery and evaluation of the training.

BACKGROUND In an era of pay for performance metrics, we sought to increase understanding of factors driving high resource utilization (HRU) in emergent (EGS) versus same-day elective (SDGS) general surgery patients. METHODS General surgery procedures from the 2016 ACS-NSQIP public use file were grouped according to the first four digits of the primary procedure CPT code. Groups having at least 100 of both elective and emergent cases were included (22 groups; 83,872 cases). HRU patients were defined as those in-hospital >7D, returned to the OR, readmitted, and/or had morbidity likely requiring an intensive care unit (ICU)stay. Independent NSQIP predictors of HRU were identified through forward regression; P for entry 0.10. RESULTS Of all patients, 33% were HRU. The three highest HRU procedures (total colectomy, enterolysis, and ileostomy) comprised a higher proportion of EGS than SDGS cases (10.3 versus 2.6%, P < 0.001). The duration of operation was 40 Min lower in EGS after adjustment. Thirty-nine of the remaining 40 HRU predictors were higher in EGS including preoperative SIRS/Sepsis (50 versus 2%), ASA classification IV-V (31 versus 5%), albumin

Background Higher education is responsible for providing education that meets international benchmarks relevant to the needs of the international community. Due to the increase of digital tools in higher education, the possibility of sharing learning resources across nations has expanded. In the current project, a Norwegian university invited universities in Spain and the United Kingdom to adapt and translate e-learning resources originally developed for Norwegian nursing students for use within their respective Bachelor in Nursing programmes. Aim The aim of the current study was to gain insights into the usability and value for learning of e-compendiums shared and implemented across three European universities. Methods The study adopted a descriptive cross-sectional design and included nursing students from the University of Nottingham, Valencia Catholic University, and the University of Stavanger. Data were collected in Autumn 2017 through a questionnaire adapted from the validated “Centre for Excellence in Teaching and Learning Reusable Learning Object evaluation questionnaire” The questionnaire consisted of 19 items that included two aspects: e-compendiums’ value for learning and e-compendiums’ usability. The different study sites were compared using a binary logistic regression analysis. Subgroups of students were compared based on their gender and age. Results A total of 480 nursing students participated in the study. The e -compendiums were overall positively rated, especially for reinforcing and retaining knowledge. Compared to the students from the University of Stavanger, students from Valencia Catholic University rated the e-compendiums more positively in most aspects of learning. Students from University of Nottingham found the e-compendiums to be more important for learning engagement compared to students at the Norwegian study site, and no differences were found in any other aspects of learning. Younger students rated the interactivity and visual components as more important compared to older students. Conclusions Students from the University of Nottingham and Valencia Catholic University seem to accept the e-compendiums despite the fact that they were originally developed for use in another country. We argue that, when sharing e-learning resources across countries, an adaptation and translation process that includes a multicultural and multidisciplinary perspective should be carried out.

Osteoarthritis (OA) is one of the most prevalent conditions in the world, particularly in the developed world with a significant increase in cases and their predicted impact as we move through the twenty-first century and this will be exacerbated by the covid pandemic. The degeneration of cartilage and bone as part of this condition is becoming better understood but there are still significant challenges in painting a complete picture to recognise all aspects of the condition and what treatment(s) are most appropriate in individual causes. OA encompasses many different types and this causes some of the challenges in fully understanding the condition. There have been examples through history where much has been learnt about common disease(s) from the study of rare or extreme phenotypes, particularly where Mendelian disorders are involved. The often early onset of symptoms combined with the rapid and aggressive pathogenesis of these diseases and their predictable outcomes give an often-under-explored resource. It is these “rarer forms of disease” that William Harvey referred to that offer novel insights into more common conditions through their more extreme presentations. In the case of OA, GWAS analyses demonstrate the multiple genes that are implicated in OA in the general population. In some of these rarer forms, single defective genes are responsible. The extreme phenotypes seen in conditions such as Camptodactyly Arthropathy-Coxa Vara-pericarditis Syndrome, Chondrodysplasias and Alkaptonuria all present potential opportunities for greater understanding of disease pathogenesis, novel therapeutic interventions and diagnostic imaging. This review examines some of the rarer presenting forms of OA and linked conditions, some of the novel discoveries made whilst studying them, and findings on imaging and treatment strategies.

Background The risk of bloodstream infections may be increased in hospitalized patients receiving ready-made parenteral nutrition (PN) multichamber bags (MCBs) compared with customized PN; however, as highlighted in recent international guidelines, there are no comparable data relating to home PN (HPN). Methods Data from a prospectively maintained database were analyzed to compare incidence rates of catheter-related bloodstream infections (CRBSIs) between patients receiving customized HPN compared with MCB HPN at a national UK referral center between May 2018 and August 2020. Results Sixty patients with chronic intestinal failure were commenced on MCBs and 45 received customized HPN for a total of 5914 and 7641 catheter days, respectively. No difference in CRBSI incidence was found (0.51/1000 catheter days for MCBs, 0.39/1000 catheter days for customized HPN; incidence rate ratio, 1.29; 95% CI, 0.26-6.37). Eighteen patients were switched from customized HPN to MCB HPN. The study period covered 7401 catheter days receiving customized HPN and 4834 days on MCBs. No significant change was noted in the CRBSI rates following this switch (0.27/1000 catheter days receiving customized HPN vs 0.21/1000 catheter days on MCBs; incidence rate ratio, 1.31; 95% CI, 0.12-14.3). Conclusion The use of MCBs for HPN patients is not associated with an increased risk of CRBSI. This study will inform international guidelines and provide reassurance for the continued, safe use of MCB HPN.

BACKGROUND & AIMS: Home parenteral nutrition (HPN) is a life-saving therapy for patients with chronic intestinal failure but can be associated with a degree of psychological distress. The factors associated with the need for antidepressants (AD) in this cohort have not yet been described.METHODS: The study involved prospective data collection from patients attending HPN clinic at a national intestinal failure referral centre. Patients requiring HPN as a result of active malignancy were excluded. Patients were divided in two groups according to AD usage; demographic, anthropometric, socioeconomic characteristics and IVS regimens were compared between groups.RESULTS: A total of 184 patients were recruited between July 2018 and April 2019, with an overall prevalence of AD use of 41.7%. Daily mean IVS volume was significantly higher among patients taking AD ('AD' group; 2125.48±991.8 ml/day, 'no-AD' group; 1828.54±847.0 ml/day, P = 0.039) with the proportion of patients needing high volume IVS (≥3000ml/day) being three-times higher in the AD group (20.0% vs. 6.1%, P = 0.006). The average energy IVS infusion per day was similar between the two groups. Hypnotic use (25.7% vs. 5.1%, P

PurposeThis paper focusses on the leaders' ability to recognise and empathise with emotions. This is important because leadership and particularly transformational leadership are principally focussed on an individual's social interactions and their ability to identify emotions and to react empathetically to the emotions of others (Psychogios and Dimitriadis, 2020). Many leadership theorists suggest the ability to have and display empathy is an important part of leadership (Bass, 1990; Walumbwa et al., 2008).Design/methodology/approachTo examine the extent to which those who work in jobs with a significant element of leadership education can recognise and empathise with emotions, 99 part-time postgraduate executive Master of Business Administration (MBA) students took part in an emotional recognition test. First, all participants were shown a sequence of pictures portraying different human facial expressions and the electrical activity in the brain as a result of the visual stimuli were recorded using an electroencephalogram (EEG). The second stage of the research was for the participants to see the same seven randomised images, but this time, they had to report what emotion they believed they had visualised and the intensity of it on a self-reporting scale.FindingsThis study demonstrated that the ability to recognise emotions is more accurate using EEG techniques compared to participants using self-reporting surveys. The findings from this study provide academic departments with evidence that more work needs to be done with students to develop their emotional recognition skills. Particularly for those students who are or will go onto occupy leadership roles.Originality/valueThe use of neuroscientific approaches has long been used in clinical settings. However, few studies have applied these approaches to develop the authors’ understanding of their use in social sciences. Therefore, this paper provides an original and unique insight into the use of these techniques in higher education.

Objective: Endovascular chemical angioplasty has been in practice in patients with symptomatic cerebral vasospasm secondary to aneurysmal subarachnoid haemorrhage in many neurosurgical centres. However, the evidence base is derived from clinical case series and expert consensus. The aim of this retrospective cohort study is to evaluate the immediate and functional outcomes of endovascular intervention in aneurysmal subarachnoid haemorrhage cerebral vasospasm treated with a combination of vasodilators. Methods: A cohort of 25 patients was identified. Each patient underwent surgical clipping, and endovascular treatment for vasospasm. A combination of Verapamil and Nimodipine was intra-arterially administered. Statistical analysis was performed to determine the rate of response. The angiographic response and functional outcome on discharge (modified Rankin score - MRS) were used as markers of outcome. Results: The study cohort consisted of 25 patients with a mean age of 50.3 (SD 11.2). A total of 135 therapeutic DSA’s were performed. There was an associated between MRS outcomes and number of vasodilation’s each patient received. For each additional vasodilation episode, the odds of a poor outcome increased by 1.190. An angiographic response was demonstrated in 88% of patients, a clinical response in 27%. A good functional outcome was achieved in 17/25, 71% at discharge. Conclusion: The combination therapy of Intra-arterial nimodipine and verapamil in patients with aneurysmal subarachnoid haemorrhage vasospasm appears to have a synergistic, if not comparable, outcome to from solitary vasodilatory treatment results and potentially promote future studies with prospective designs to measure the outcomes.

Background COPD exacerbations occur more frequently with disease progression and are associated with worse prognosis and higher healthcare expenditure. Purpose To utilize a networked system, optimized with statistical process control (SPC), for remote patient monitoring (RPM) and to identify potential predictors of COPD exacerbations. Methods Seventeen subjects, mean (SD) age of 69.7 (7.2) years, with moderate to severe COPD received RPM. Over 2618 patient-days (7.17 patient-years) of monitoring, we obtained daily symptom scores, treatment adherence, self-reported activity levels, daily spirometry (SVC, FEV1, FVC, PEF), inspiratory capacity (IC), and oxygenation (SpO2). These data were used to identify predictors of exacerbations defined using Anthonisen and other criteria. Results After implementation of SPC, concordance analysis showed substantial agreement between FVC (decrease below the 7-day rolling average minus 1.645 SD) and self-reported healthcare utilization events (κ=0.747, P 1.645 SD below the 7-day rolling average) and self-reported healthcare utilization events (κ=0.475, P

Previous reports of paraneoplastic encephalitis occurring in primary fallopian tube carcinoma have been exclusively classified as paraneoplastic cerebellar degeneration, with MR imaging either unremarkable or demonstrating cerebellar atrophy. We report a case of paraneoplastic encephalitis in a 64-year-old female with primary fallopian tube carcinoma, reminiscent of N-methyl d-aspartate receptor encephalitis, with MR imaging demonstrating bilateral subcortical and deep white matter T2-FLAIR hyperintensities sparing cerebellar and brainstem structures. To our knowledge, this represents the first reported case of noncerebellar paraneoplastic encephalitis related to primary fallopian tube carcinoma.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a form of extracorporeal life support that provides total gas exchange (CO2 and O2) within the central venous circulation. The bicaval dual lumen cannula (DLC) is an option for patients requiring respiratory support with VV-ECMO. The catheter is inserted via the internal jugular vein into the superior and inferior vena cava, drains blood into the ECMO circuit for gas exchange, and then returns arterialized blood to the right heart for circulation. The DLC facilitates physical therapy, ambulation, and early extubation. This chapter will review the uses, advantages, and unique complications of the DLC.

The lobular distribution of 9 different anticoagulant rodenticide (AR) residues in the liver of a sentinel predator/scavenger i.e. the red fox (Vulpes vulpes) was determined following multi-residue analysis using Ultra (High) Performance Liquid Chromatography tandem Mass Spectrometry (UHPLC-MS/MS). The aim of the study was to address concerns that if distribution of AR residues in the liver was significantly heterogeneous, analysis of random sub-samples or finite remnants of liver could result in false negatives or lead to incorrect toxicological diagnoses. Intact livers excised from animals shot as part of routine legal pest control activities in Scotland during 2018 and 2019 were sub-sectioned and the lobular concentration of AR residues was investigated. Analysis of individual lobes from 10 different fox livers revealed that AR residues initially detected in a randomly selected small portion of liver tissue were present throughout the liver. Also, in cases where AR residues were not found in the initial randomly selected portion, they were not found in the subsequent more detailed examination. The limit of quantitation was 3 μg kg‐1 and AR residue concentrations ranged from 3 to 885 μg kg−1. Statistical analysis of variance (ANOVA) was performed on the eight and six out of ten livers that tested positive for bromadiolone and brodifacoum, respectively. No statistical evidence was found of differences in mean residue levels of bromadiolone throughout the liver i.e. within and between liver lobes. However, brodifacoum showed a statistically significant difference (p < .001) in mean residue concentration between the lobes but there was no statistical evidence of mean differences within the lobes.

Purpose Herein, we evaluate the use of MRI as a tool for assessing iron oxide nanoparticle (IONP) distribution within IONP perfused organs and vascularized composite allografts (VCAs) (i.e., hindlimbs) prepared for cryopreservation. Methods Magnetic resonance imaging was performed on room-temperature organs and VCAs perfused with IONPs and were assessed at 9.4 T. Quantitative T1 mapping and T 2 ∗ -weighted images were acquired using sweep imaging with Fourier transformation and gradient-echo sequences, respectively. Verification of IONP localization was performed through histological assessment and microcomputer tomography. Results Quantitative imaging was achieved for organs and VCAs perfused with up to 642 mMFe (36 mgFe /mL), which is above previous demonstrations of upper limit detection in agarose (35.7mMFe [2 mgFe /mL]). The stability of IONPs in the perfusate had an effect on the quality of distribution and imaging within organs or VCA. Finally, MRI provided more accurate IONP localization than Prussian blue histological staining in this system, wherein IONPs remain primarily in the vasculature. Conclusion Using MRI, we were able to assess the distribution of IONPs throughout organs and VCAs varying in complexity. Additional studies are necessary to better understand this system and validate the calibration between T1 measurements and IONP concentration.

PURPOSE Large, generalizable real-world data can enhance traditional clinical trial results. The current study evaluates reliability, clinical relevance, and large-scale feasibility for a previously documented method with which to characterize cancer progression outcomes in advanced non–small-cell lung cancer from electronic health record (EHR) data. METHODS Patients who were diagnosed with advanced non–small-cell lung cancer between January 1, 2011, and February 28, 2018, with two or more EHR-documented visits and one or more systemic therapy line initiated were identified in Flatiron Health’s longitudinal EHR-derived database. After institutional review board approval, we retrospectively characterized real-world progression (rwP) dates, with a random duplicate sample to ascertain interabstractor agreement. We calculated real-world progression-free survival, real-world time to progression, real-world time to next treatment, and overall survival (OS) using the Kaplan-Meier method (index date was the date of first-line therapy initiation), and correlations between OS and other end points were assessed at the patient level (Spearman’s ρ). RESULTS Of 30,276 eligible patients,16,606 (55%) had one or more rwP event. Of these patients, 11,366 (68%) had subsequent death, treatment discontinuation, or new treatment initiation. Correlation of real-world progression-free survival with OS was moderate to high (Spearman’s ρ, 0.76; 95% CI, 0.75 to 0.77; evaluable patients, n = 20,020), and for real-world time to progression correlation with OS was lower (Spearman’s ρ, 0.69; 95% CI, 0.68 to 0.70; evaluable patients, n = 11,902). Interabstractor agreement on rwP occurrence was 0.94 (duplicate sample, n = 1,065) and on rwP date 0.85 (95% CI, 0.81 to 0.89; evaluable patients n = 358 [patients with two independent event captures within 30 days]). Median rwP abstraction time from individual EHRs was 18.0 minutes (interquartile range, 9.7 to 34.4 minutes). CONCLUSION We demonstrated that rwP-based end points correlate with OS, and that rwP curation from a large, contemporary EHR data set can be reliable, clinically relevant, and feasible on a large scale.

All face-to-face studies were affected by the COVID-19 pandemic, as they could not be run in person due to rules and guidance linked to social distancing which were in force during the outbreak. Finding and testing an available COVID-secure approach for both participants and researchers was important as was the need to continue conducting such studies during this critical time. At present, the extant literature indicates a clear gap in research that elucidates how to carry out a Q methodology study online, step by step. This paper describes an option for online Q methodology using an approach that simulates all of the steps performed in a face-to-face setting using an open-source software known as Easy-HtmlQ. Using a case study in telemedicine adoption as illustration, this paper also considers the perspective of both research participants and Q methodology researchers via semi-structured interviews. Using Easy-HtmlQ V1.1 in online Q methodology studies appears to be an affordable, practical and user-friendly solution. Some of the benefits associated with running Q methodology studies online were the decreased costs, enabling the recruitment of wider number of participants, providing a COVID-19-secure environment and offering convenience to both participants and researchers during the research process. The findings of this study may contribute to increasing the number of online Q methodology studies in the future, as it has succeeded in offering a feasible approach for Q methodology researchers.

Contains fulltext : 244566.pdf (Publisher’s version ) (Closed access) BACKGROUND AND AIMS: The case-mix of patients with intestinal failure due to short bowel syndrome (SBS-IF) can differ among centres and may also be affected by the timeframe of data collection. Therefore, the ESPEN international multicenter cross-sectional survey was analyzed to compare the characteristics of SBS-IF cohorts collected within the same timeframe in different countries. METHODS: The study included 1880 adult SBS-IF patients collected in 2015 by 65 centres from 22 countries. The demographic, nutritional, SBS type (end jejunostomy, SBS-J; jejuno-colic anastomosis, SBS-JC; jejunoileal anastomosis with an intact colon and ileocecal valve, SBS-JIC), underlying disease and intravenous supplementation (IVS) characteristics were analyzed. IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorized as 3 L/day. RESULTS: In the entire group: 60.7% were females and SBS-J comprised 60% of cases, while mesenteric ischaemia (MI) and Crohn' disease (CD) were the main underlying diseases. IVS dependency was longer than 3 years in around 50% of cases; IVS was infused ≥5 days/week in 75% and FE in 10% of cases. Within the SBS-IF cohort: CD was twice and thrice more frequent in SBS-J than SBS-JC and SBS-JIC, respectively, while MI was more frequent in SBS-JC and SBS-JIC. Within countries: SBS-J represented 75% or more of patients in UK and Denmark and 50-60% in the other countries, except Poland where SBS-JC prevailed. CD was the main underlying disease in UK, USA, Denmark and The Netherlands, while MI prevailed in France, Italy and Poland. CONCLUSIONS: SBS-IF type is primarily determined by the underlying disease, with significant variation between countries. These novel data will be useful for planning and managing both clinical activity and research studies on SBS.

BACKGROUND Measurement of body composition is a valuable clinical tool for nutrition assessments, but there are no data on the merits of assessment modalities in type 2 intestinal failure (IF). The aim of this study was to evaluate the prevalence of low muscle mass and quality in type 2 IF, comparing bioelectric impedance analysis (BIA) and computed tomography (CT) at the third lumbar vertebra level. METHODS Patients admitted with acute severe (type 2) IF to a national UK IF center who had BIA measurement and CT scan as part of routine care within 40 days of anthropometric measurement were included in this cross-sectional study. Data were also collected on patient demographics and clinical characteristics. RESULTS Forty-four patients meeting inclusion criteria were included. Low muscle mass was detected in 37 out of 44 (84.1%) patients by CT scan and in 30 of out 44 (68.2%) by BIA. Low muscle quality was detected in 22 out of 44 (50%) patients by CT scan and in 40 out of 44 (90.1%) by BIA. Comparison of CT and BIA measurements showed a moderate correlation of muscle, Spearman ρ 0.65 (95% CI, 0.42-0.81; P < 0.001), and a strong correlation of body fat mass measurements, Spearman ρ 0.79 (95% CI, 0.62-0.89; P < 0.001). CONCLUSION This is the first study to demonstrate that low muscle mass is common in patients with type 2 IF, regardless of body composition assessment modality. A larger cohort study is required to validate the impact of low muscle mass and quality on clinical outcomes and the role of targeted interventions to improve the care of patients with type 2 IF.

Mucopolysaccharidosis (MPS) type I is a rare lysosomal storage disorder caused by an accumulation of glycosaminoglycans (GAGs) resulting in multisystem disease. Neurological morbidity includes hydrocephalus, spinal cord compression, and cognitive decline. While many neurological symptoms have been described, stroke is not a widely-recognized manifestation of MPS I. Accordingly, patients with MPS I are not routinely evaluated for stroke, and there are no guidelines for managing stroke in patients with this disease. We report the case of a child diagnosed with MPS I who presented with overt stroke and repeated neurological symptoms with imaging findings for severe ventriculomegaly, infarction, and bilateral terminal carotid artery stenosis. Direct intracranial pressure evaluation proved negative for hydrocephalus. The patient was subsequently treated with cerebral revascularization and at a 3-year follow-up, the patient reported no further neurological events or new ischemia on cerebral imaging. Cerebral arteriopathy in patients with MPS I may be associated with GAG accumulation within the cerebrovascular system and may predispose patients to recurrent strokes. However, further studies are required to elucidate the etiology of cerebrovascular arteriopathy in the setting of MPS I. Although the natural history of steno-occlusive arteriopathy in patients with MPS I remains unclear, our findings suggest that cerebral revascularization is a safe treatment option that may mitigate the risk of future strokes and should be strongly considered within the overall management guidelines for patients with MPS I.

Background Exacerbations of chronic obstructive pulmonary disease (COPD) occur with increasing frequency as the disease progresses and account for poor health status, worse prognosis, and higher healthcare expenditure. Methods We developed a networked system for remote physiological monitoring (RPM) at home and optimized it with statistical process control (SPC) with the goal of earlier detection of COPD exacerbations. We enrolled 17 patients with moderate to severe COPD with a mean (SD) age of 71.1 (7.2) years. We obtained daily symptom scores, treatment adherence and activity levels using a programmable device, and measured daily slow and forced spirometry (FEV1, FVC, PEF), inspiratory capacity (IC) and oxygenation (SpO2). To identify exacerbations, we developed rolling prediction intervals for FVC, FEV1, IC and SpO2 using SPC. Results The time taken to perform daily monitoring was reduced from 12.7 (5.4) minutes to 6.5 (2.6) minutes through software refinements during the study. Adherence to forced and slow spirometry was 62.6% and 62.4%, respectively. The within-subject coefficients of variation for FEV1, PEF and IC were 12.2%, 16.2%, and 13.1%, respectively. Event rates per patient-year for exacerbations were: self-reported 0.42, 2/3 Anthonisen Criteria (AC) 0.42, modified AC 2.23, systemic corticosteroid use 0.56, and antibiotic use 0.56. Conclusion We successfully implemented a networked system for RPM of symptoms, treatment adherence, and physiology at home in patients with COPD. We demonstrated that SPC improves the feasibility of RPM in COPD patients which may increase the likelihood of detecting COPD exacerbations.

RationaleOur intestinal failure unit provides care for patients from a wide geographical area. Patients dependent on home parenteral nutrition (HPN) are routinely reviewed in the clinic at 3–6 monthly intervals. Between March 2008 and 2015, we noted a significant rise in the number of patients under our care, with an associated 51% increase in clinic appointments offered. We evaluated whether telemedicine would provide a strategy to reduce patients’ need to travel while maintaining safe clinical standards.MethodsImplementation began in December 2015 via patient consultation and small tests of change. Clinical data were obtained from a prospectively maintained database. Remote video consultation discussions were carried out via internet video call service (Skype). An anonymous satisfaction questionnaire was offered to patients for completion following consultation. The number of miles saved by obviating the need to attend hospital was calculated for each patient.ResultsDuring the study period, patients receiving HPN rose by 18% to 288. Twenty-five patients used telemedicine for HPN follow-up, three of these for follow-up with the psychologist. By avoiding hospital attendance, this saved a mean travel distance of 56.7 miles with a total of 18 346.6 cumulative miles saved. Sixty-three per cent of patients rated their satisfaction with the system at ≥90%, with a mean satisfaction of 85%. Eight per cent of the telemedicine cohort was admitted with an HPN complication, compared with an admission rate of 24% for the whole HPN cohort. One emergency admission was avoided.ConclusionTelemedicine can obviate the need for clinic attendance in HPN-dependent patients, so reducing the need of individuals with chronic illness to travel while maintaining standards for follow-up.

Oncology drug development increasingly relies on single‐arm clinical trials. External controls (ECs) derived from electronic health record (EHR) databases may provide additional context. Patients from a US‐based oncology EHR database were aligned with patients from randomized controlled trials (RCTs) and trial‐specific eligibility criteria were applied to the EHR dataset. Overall survival (OS) in the EC‐derived control arm was compared with OS in the RCT experimental arm. The primary outcome was OS, defined as time from randomization or treatment initiation (EHR) to death. Cox regression models were used to obtain effect estimates using EHR data. EC‐derived hazard ratio estimates aligned closely with those from the corresponding RCT with one exception. Comparing log HRs among all RCT and EC results gave a Pearson correlation coefficient of 0.86. Properly selected control arms from contemporaneous EHR data could be used to put single‐arm trials of OS in advanced non‐small cell lung cancer into context.

Summary Introduction The management of intestinal failure (IF) requires safe and sustained delivery of parenteral nutrition (PN). The long-term maintenance of central venous catheter (CVC) access is therefore vital, with meticulous catheter care and salvage of infected CVCs being of prime importance. CVC-related infection and loss of intravenous access are important causes of morbidity and mortality in IF. Avoidance, prompt recognition and appropriate management of CVC-related infections are crucial components of IF care. However, there are few, if any, data on the occurrence of CVC-related infections in patients with acute, type 2, IF managed on a dedicated IF unit and no data on the salvage outcomes of infected CVCs in this group of patients. Methods This is a retrospective observational study conducted between January 2011 and July 2017. All patients with acute, type 2 IF newly admitted to a national U.K. IF unit (IFU) during these dates were included. All patients admitted to the unit with a CVC in place underwent immediate ‘screening’ paired central and peripheral blood cultures on arrival before the CVC was used for any infusate. A prospectively maintained database was used to record all confirmed catheter-related blood stream infections (BSI)/colonisations, demographic and clinical data. Diagnosis of catheter-related BSI/colonisation was based on quantitative and qualitative analysis of paired central and peripheral blood cultures. A standardized 10–14-day catheter salvage treatment protocol involving antibiotic and urokinase CVC locks and systemic antibiotic administration was used to salvage any infected or colonised CVCs, as appropriate. The CVC was not used for PN until successful salvage had been confirmed by negative blood cultures drawn 48 h after antibiotic completion. The development of a subsequent catheter-related BSI was recorded for all patients, both during the remaining in-patient stay on the IFU and after discharge home on PN. Results Of the 509 patients with type 2 IF admitted to the IFU during the study period, 341 (54% female; mean age 54.6 (range 16–86 years)) had an indwelling CVC that had been placed in the referring hospital. Surgical complications and mesenteric ischaemia were the most common underlying disease aetiologies. Sixty-five of 341 (19.1%) patients had an infected/colonised CVC on the initial screening set of blood cultures. A successful CVC salvage rate of 91% was achieved in this cohort after antibiotic therapy. The subsequent in-patient catheter-related BSI rate for those admitted with a CVC (n = 341) on the IFU was 0.042 per 1000 catheter days, over a total of 23,548 in-patient catheter days. Two hundred and seventy nine of 341 patients were discharged on home PN (HPN); with a subsequent catheter-related BSI rate on HPN of 0.22 per 1000 catheter days (mean duration of HPN = 778 catheter days (range:)) over a follow-up period of 216,944 out-patient catheter days. There was no increased risk of HPN-related catheter-related BSI (p = 0.09) or mortality (p = 0.4) in those admitted with an infected CVC. Conclusion This is the first study to report catheter-related BSI/colonisation rates and salvage outcomes in patients with type 2 IF newly admitted to a dedicated IF Unit. We report that nearly one-fifth of all patients were referred with evidence of a catheter related BSI/colonisation; despite this, successful catheter salvage is possible and, with stringent CVC care, an extremely low subsequent catheter related BSI rates can be achieved and maintained during in-patient stay on a dedicated IF Unit and after discharge on HPN. These data provide novel evidence to support ESPEN recommendations that patients with type 2 IF are managed on a dedicated IF Unit.

Background The use of real-world data to generate evidence requires careful assessment and validation of critical variables before drawing clinical conclusions. Prospective clinical trial data suggest that anatomic origin of colon cancer impacts prognosis and treatment effectiveness. As an initial step in validating this observation in routine clinical settings, we explored the feasibility and accuracy of obtaining information on tumor sidedness from electronic health records (EHR) billing codes. Methods Nine thousand four hundred three patients with metastatic colorectal cancer (mCRC) were selected from the Flatiron Health database, which is derived from de-identified EHR data. This study included a random sample of 200 mCRC patients. Tumor site data derived from International Classification of Diseases (ICD) codes were compared with data abstracted from unstructured documents in the EHR (e.g. surgical and pathology notes). Concordance was determined via observed agreement and Cohen’s kappa coefficient (κ). Accuracy of ICD codes for each tumor site (left, right, transverse) was determined by calculating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and corresponding 95% confidence intervals, using abstracted data as the gold standard. Results Study patients had similar characteristics and side of colon distribution compared with the full mCRC dataset. The observed agreement between the ICD codes and abstracted data for tumor site for all sampled patients was 0.58 (κ = 0.41). When restricting to the 62% of patients with a side-specific ICD code, the observed agreement was 0.84 (κ = 0.79). The specificity (92–98%) of structured data for tumor location was high, with lower sensitivity (49–63%), PPV (64–92%) and NPV (72–97%). Demographic and clinical characteristics were similar between patients with specific and non-specific side of colon ICD codes. Conclusions ICD codes are a highly reliable indicator of tumor location when the specific location code is entered in the EHR. However, non-specific side of colon ICD codes are present for a sizable minority of patients, and structured data alone may not be adequate to support testing of some research hypotheses. Careful assessment of key variables is required before determining the need for clinical abstraction to supplement structured data in generating real-world evidence from EHRs. Electronic supplementary material The online version of this article (10.1186/s12874-019-0824-7) contains supplementary material, which is available to authorized users.

Introduction:Chagasic Megaesophagus (CME) is the manifestation of the disease characterized by luminal enlargement and muscular hypertrophy. Physiotherapy is an area that can be beneficial to CME patients in both pre and postoperative stages due to evidence of its success rate in preventing pulmonary complications. Objective:analyze the use of physiotherapeutic treatment in treating patients that underwent surgical treatment for CME. Methods: Study developed at University Federal of Goiás- Hospital das Clínicas, in Goiânia – Goiás. Of the 1096 surgical procedures, 38 of them were to treat CME. Results: was an average age of 59,4±13 years, 77% male and 23% female, physiotherapeutic care was part of the postoperative routine in 68% of the cases with no record of its occurrence in the preoperative stages.Conclusion: Physiotherapy was used only in the postoperative stage. Despite the importance of Physiotherapy in the treatment of CME, the studies pertaining to its use in this context are scarce. As a result, more research is necessary to emphasize that its use from the moment of hospitalization could increase the possibilities of surgical recovery.

Purpose The aim of this study was to assess the impact of missing death data on survival analyses conducted in an oncology EHR‐derived database. Methods The study was conducted using the Flatiron Health oncology database and the National Death Index (NDI) as a gold standard. Three analytic frameworks were evaluated in advanced non‐small cell lung cancer (aNSCLC) patients: median overall survival [mOS]), relative risk estimates conducted within the EHR‐derived database, and “external control arm” analyses comparing an experimental group augmented with mortality data from the gold standard to a control group from the EHR‐derived database only. The hazard ratios (HRs) obtained within the EHR‐derived database (91% sensitivity) and the external control arm analyses, were compared with results when both groups were augmented with mortality data from the gold standard. The above analyses were repeated using simulated lower mortality sensitivities to understand the impact of more extreme levels of missing deaths. Results Bias in mOS ranged from modest (0.6–0.9 mos.) in the EHR‐derived cohort with (91% sensitivity) to substantial when lower sensitivities were generated through simulation (3.3–9.7 mos.). Overall, small differences were observed in the HRs for the EHR‐derived cohort across comparative analyses when compared with HRs obtained using the gold standard data source. When only one treatment arm was subject to estimation bias, the bias was slightly more pronounced, but increased substantially when lower sensitivities were simulated. Conclusions The impact on survival analysis is minimal with high mortality sensitivity with only modest impact associated within external control arm applications.

Summary Background & aims Prevention of catheter related blood stream infections (CRBSI) and salvage of infected central venous catheters (CVC) are vital to maintaining long term venous access in patients needing home parenteral nutrition (HPN). It remains unclear as to whether patients are best trained for catheter care at home or in hospital or whether CRBSIs are lower if the patient self-cares for the CVC. Furthermore, there is minimal data on the longer term outcome following salvage of infected catheter and limited consensus on agreed protocols for catheter salvage. Method We conducted a retrospective 5-year evaluation of CRBSI occurrence and CVC salvage outcomes in adult patients requiring HPN managed at a national UK Intestinal Failure Unit from 2012 to 2016. Prior to 2012, patients were primarily trained to administer PN in hospital; thereafter, patients underwent training at home. Results A total of 134 CRBSI were recorded in 92 patients (62 patients with a single CRBSI and 30 patients with more than 1 CRBSI) in a cohort of 559 HPN patients, with a total of 1163 HPN years. The overall CRBSI rate was 0.31 per 1000 catheter days. CNS were the most common isolates (41/134 (30.5%)), followed by polymicrobial infections (14/134 (10.4%)), Klebsiella spp. (16/134 (11.9%)) and methicillin – sensitive Staphylococcus aureus (MSSA) 5/134 ((3.7%)). Salvage was not attempted in 34 cases due to methicillin – resistant (MRSA) infection (1/34), fungal infection (13/34) or clinical instability due to sepsis (20/34). Of the 100 cases where salvage was attempted, 67% were successful. 82.8% of CNS salvage attempts were successful; there was no difference in salvage rates between CNS CRBSIs salvaged with a 10-day (22/26) or 14-day protocol (7/9) (p = 0.4). CRBSI rate, in those cared for by trained home care nurses was the lowest at 0.270 (self care: 0.342 and non-medical carer (e.g. family member): 0.320) (p = 0.03). Conclusion We previously reported a sustained very low CRBSI rate in a large cohort of HPN patients in a national unit; we now further report that this is not influenced by training patients at home rather than in hospital but is influenced by the individual managing the catheter at home. CNS remains the primary cause of CRBSIs and can be successfully salvaged with a reduced duration of antibiotic therapy compared to our previous experience.

Approximately half of melanoma tumors lack a “druggable” target and are unresponsive to current targeted therapeutics. One proposed approach for treating these therapeutically-orphaned tumors is by targeting transcriptional dependencies (“oncogene starvation”), whereby survival factors are depleted through inhibition of transcriptional regulators. A drug screen identified a cyclin-dependent kinase 9(CDK9) inhibitor (SNS-032) to have therapeutic selectivity against BRAF(wt)/NRAS(wt) melanomas compared to BRAF(mut)/NRAS(mut) melanomas. We then used two strategies to inhibit CDK9 in vitro- a CDK9 degrader (TS-032) and a selective CDK9 kinase inhibitor (NVP-2). At 500 nM, both TS-032 and NVP-2 demonstrated greater suppression of BRAF(wt)/NRAS(wt)/NF1(wt) cutaneous and uveal melanomas (BNFwt) than mutant melanomas (BNFmut). RNAseq analysis of 8 melanoma lines with NVP-2 treatment demonstrated that the context of this vulnerability appears to converge on a cell cycle network which includes many transcriptional regulators such as the E2F family members. Human TCGA melanoma tumor data further supported a potential oncogenic role for E2F1/E2F2 in BRAF(wt)/NRAS(wt)/NF1(wt) tumors and a direct link to CDK9. Our results suggest that transcriptional blockade through selective targeting of CDK9 is an effective method of suppressing therapeutically-orphaned BRAF/NRAS/NF1 wild-type melanomas.

Summary Engaging patients—defined broadly as individuals with lived experience of a given condition, family members, caregivers, and the organisations that represent them—as partners in research is a priority for policymakers, funders, and the public. Nonetheless, formal efforts to engage patients are absent from most studies, and models to support meaningful patient engagement in clinical anaesthesia research have not been previously described. Here, we review our experience in developing and implementing a multifaceted patient engagement strategy within the Regional Versus General Anesthesia for Promoting Independence After Hip Fracture (REGAIN) surgery trial, an ongoing randomised trial comparing spinal vs general anaesthesia for hip fracture surgery in 1600 older adults across 45 hospitals in the USA and Canada. This strategy engaged patients and their representatives at both the level of overall trial oversight and at the level of individual recruiting sites. Activities spanned a continuum ranging from events designed to elicit patients' input on key decisions to longitudinal collaborations that empowered patients to actively participate in decision-making related to trial design and management. Engagement activities were highly acceptable to participants and led to concrete changes in the design and conduct of the REGAIN trial. The REGAIN experience offers a model for future efforts to engage patients as partners in clinical anaesthesia research, and highlights potential opportunities for investigators to increase the relevance of anaesthesia studies by incorporating patient voices and perspectives into the research process.

Background Stereotactic radiosurgery (SRS) or fractionated SRS (fSRS) are effective options for the treatment of brain metastases. When treating multiple metastases with a linear accelerator-based approach, a single isocenter allows for efficient treatment delivery. In this study, we present our findings comparing dosimetric parameters of Brainlab (Munich, Germany) Elements™ Multiple Brain Mets SRS (MME) software (version 1.5 versus version 2.0) for a variety of scenarios and patients. The impact of multileaf collimator design and function on plan quality within the software was also evaluated. Materials and methods Twenty previously treated patients with a total of 58 lesions (from one to seven lesions each) were replanned with an updated version of the multiple brain Mets software solution. For each plan, the mean conformity index (CI), mean gradient index (GI), the volume of normal brain receiving 12 Gy (V12), and mean brain dose were evaluated. Additionally, all v2.0 plans were further evaluated with jaw tracking for by Elekta (Stockholm, Sweden) and HD120™ multileaf collimator by Varian Medical Systems (Palo Alto, USA). Results The new software version demonstrated improvements for CI, GI and V12 (p

Penile squamous cell carcinoma (SCC) is a rare and aggressive urological malignancy. Advanced penile SCC requires multimodal management, including surgery and systemic therapy. Given its rarity, there have been few substantial advances in our understanding of the molecular and genomic drivers of penile SCC, especially for patients with relapsed or advanced disease. In this review, we discuss the molecular and genomic landscape of penile SCC, clinical trials in progress and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a platform for investigation and validation of new molecular pathways for testing of therapeutics.

Cholera toxin (CT) is an AB5 protein toxin that activates the stimulatory alpha subunit of the heterotrimeric G protein (Gsα) through ADP-ribosylation. Activation of Gsα produces a cytopathic effect by stimulating adenylate cyclase and the production of cAMP. To reach its cytosolic Gsα target, CT binds to the plasma membrane of a host cell and travels by vesicle carriers to the endoplasmic reticulum (ER). The catalytic CTA1 subunit then exploits the quality control mechanism of ER-associated degradation to move from the ER to the cytosol. ER-associated degradation is functionally linked to another quality control system, the unfolded protein response (UPR). However, the role of the UPR in cholera intoxication is unclear. We report here that CT triggers the UPR after 4 h of toxin exposure. A functional toxin was required to induce the UPR, but, surprisingly, activation of the adenylate cyclase signaling pathway was not sufficient to trigger the process. Toxin-induced activation of the UPR coincided with increased toxin accumulation in the cytosol. Chemical activation of the heterotrimeric G protein or the UPR also enhanced the onset of CTA1 delivery to the cytosol, thus producing a toxin-sensitive phenotype. These results indicate there is a cAMP-independent response to CT that activates the UPR and thereby enhances the efficiency of intoxication.

Objective: This paper describes the development of a novel mobile health (mHealth) educational intervention, called m2Hear, designed for first-time hearing aid users based on previously developed e...