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Abstract Aims Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID‐19. Our hypothesis is that in patients with AHF and elevated C‐reactive protein (CRP) levels without symptoms or signs of infection, a 7‐day course of steroid therapy will lead to reduced inflammation and short‐term improvement in quality of life and a reduced risk of worsening HF (WHF) events. Methods and results The study, which is currently ongoing, will include 100 patients with AHF ages 18–85, regardless of ejection fraction, screened within 12 h of presentation. Patients will be included who have NT‐proBNP > 1500 pg/mL and CRP > 20 mg/L at screening. Exclusion criteria include haemodynamic instability and symptoms and signs of infection. After signed consent, eligible patients will be randomized according to a central randomization scheme stratified by centre 1:1 to either treatment once daily for 7 days with 40 mg prednisone orally or to standard care. Patients will be assessed at study day 2, day 4 or at discharge if earlier, and at days 7 and 31 at the hospital; and at day 91 through a telephone follow‐up. The primary endpoint is the change in CRP level from baseline to day 7, estimated from a mixed model for repeated measures (MMRM) including all measured timepoints, in patients without a major protocol violation. Secondary endpoints include the time to the first event of WHF adverse event, readmission for HF, or death through day 91; and changes to day 7 in EQ‐5D visual analogue scale score and utility index. Additional clinical and laboratory measures will be assessed. Conclusions The results of the study will add to the knowledge of the role of inflammation in AHF and potentially inform the design of larger studies with possibly longer duration of anti‐inflammatory therapies in AHF.

Abstract Due to variable and complex work environments, nonlinearities, uncertainty and disturbances are inevitable in multi‐agent systems. Approximation‐free control can address these issues without involving approximators, such as fuzzy logic systems and neural networks. However, some issues like the singularity problem caused by the signals exceeding the preset boundary in changing work conditions still remain. This paper proposes an adaptive and reliable approximation‐free control, which comprises a novel singularity compensator and a modified transforming function. The proposed control scheme performs better in terms of convergence rate and overshoot, avoids issues relating to singularity, and has added flexibility in terms of parameter choice. The proposed control law adapts to changes in operating conditions and nonlinearities—the efficacy of which is demonstrated using simulations.

Background: Although the FDA approved acetaminophen toxicity dosing regimen for intravenous n-acetylcysteine (NAC) is a three-bag regimen, alternate regimens have been published which are generally simpler, and decrease errors and adverse effects. It is not clear how pervasive alternative regimens are used in hospitals in the US and reasons for a change from the FDA regimen. Objective: Characterize practice patterns for treating acetaminophen toxicity. Methods: An pilot-tested, electronic survey containing demographic and practice pattern questions for acetaminophen toxicity management was sent to residency program directors. The survey was open for 4 weeks with several reminder e-mails sent to non-responders. Descriptive statistics were used to summarize the data. Results: There were 119 responses (9.2% response rate). Responses were representative of all geographic areas in the US and were most commonly from community hospitals (67.2%) and those with 300 or more beds (72.2%). Nearly two-thirds used the FDA approved NAC regimen, whereas others used an alternate regimen. Reasons for making the change were for simplicity, to decrease errors or adverse events, or based on local poison center recommendations. More than one-third of respondents reported not using a maximum dosing weight. Conclusions: N-acetylcysteine is usually administered intravenously using the FDA approved regimen for acetaminophen toxicity. The weight for dosing was commonly capped at 100 kg, but some institutions did not use a maximum. Alternative intravenous regimens have been implemented at some institutions with the impetus for change being safety and simplicity.

Abstract We report on single-molecule nanopore sensing combined with position-encoded DNA molecular probes, with chemistry tuned to simultaneously identify various antigen proteins and multiple RNA gene fragments of SARS-CoV-2 with high sensitivity and selectivity. We show that this sensing strategy can directly detect spike (S) and nucleocapsid (N) proteins in unprocessed human saliva. Moreover, our approach enables the identification of RNA fragments from patient samples using nasal/throat swabs, enabling the identification of critical mutations such as D614G, G446S, or Y144del among viral variants. In particular, it can detect and discriminate between SARS-CoV-2 lineages of wild-type B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.539 (Omicron) within a single measurement without the need for nucleic acid sequencing. The sensing strategy of the molecular probes is easily adaptable to other viral targets and diseases and can be expanded depending on the application required.

Abstract Introduction Linking individual competencies to entrustable professional tasks provides a holistic view of Sonography graduate work readiness. The Australian Sonographers Accreditation Registry (ASAR) publishes a set of entrustable professional activities (EPAs) as part of its Standards for Accreditation of Sonography Courses. EPAs are distinct ultrasound examinations grouped within six critical practice units. This study reports on industry perspectives of current EPAs and their classification for graduates completing general sonography courses in Australia. The article also examines the value of EPAs and links their function to the assessment of graduate competency. Methods An online survey tool elicited stakeholder feedback on graduate EPAs across six critical practice units and the potential for including a new Paediatric unit. From an original sample size of 655, 309 responded to questions about general sonography courses. Results A majority (55.3%) recommended no changes to the existing EPA list, and 44.7% recommended amending the list. From respondents that recommended changes (138/309), all current EPAs received >80% agreement to be retained; in addition, nine new examinations received >70% agreement for inclusion at the graduate level. Whilst 42.7% (132/309) supported the current ASAR model requiring competency in five out of six critical practice units, 45.6% (141/309) recommended increasing it to all six. There was limited support, 11.7% (36/309), to reduce this number. Responding to the potential to add a new Paediatric specific critical practice unit, 61.8% (181/293) recommended its inclusion. Conclusions The findings demonstrate that the current list of EPAs aligns with industry expectations. In contrast, there are divergent views on the modelling and grouping of critical practice units. The article's critical analysis of the results and implications provides stakeholders with a practical approach to clinical teaching and EPA assessment, and helps to inform any review of accreditation standards.

Abstract Aims Acute heart failure (AHF) has an impact on human health worldwide. Despite guidelines for treatment and management of AHF, mortality rates remain high. The main objective of this study was to compare standard in‐hospital treatment and management of AHF against current clinical guidelines and variations across regions. Methods Between February 2018 and May 2021, investigators were approached to participate in the STRONG‐HF study. The lead investigator at 158 sites in 20 countries completed a site feasibility questionnaire. Sites were grouped by country into five different regions: Africa and the Middle East, Eastern Europe, Russia, South America, and Western Europe. Results According to the questionnaires, there are large differences in how patients present due to AHF and where in the hospital they are treated. There were significant differences in reported percentage of AHF patients receiving angiotensin converting enzymes inhibitors across the regions (P

Abstract Background In this phase 2 randomised placebo-controlled clinical trial in patients with COVID-19, we hypothesised that blocking mineralocorticoid receptors using a combination of dexamethasone to suppress cortisol secretion and spironolactone is safe and may reduce illness severity. Methods Hospitalised patients with confirmed COVID-19 were randomly allocated to low dose oral spironolactone (50 mg day 1, then 25 mg once daily for 21 days) or standard of care in a 2:1 ratio. Both groups received dexamethasone 6 mg daily for 10 days. Group allocation was blinded to the patient and research team. Primary outcomes were time to recovery, defined as the number of days until patients achieved WHO Ordinal Scale (OS) category ≤ 3, and the effect of spironolactone on aldosterone, D-dimer, angiotensin II and Von Willebrand Factor (VWF). Results One hundred twenty patients with PCR confirmed COVID were recruited in Delhi from 01 February to 30 April 2021. 74 were randomly assigned to spironolactone and dexamethasone (SpiroDex), and 46 to dexamethasone alone (Dex). There was no significant difference in the time to recovery between SpiroDex and Dex groups (SpiroDex median 4.5 days, Dex median 5.5 days, p = 0.055). SpiroDex patients had significantly lower D-dimer levels on days 4 and 7 (day 7 mean D-dimer: SpiroDex 1.15 µg/mL, Dex 3.15 µg/mL, p = 0.0004) and aldosterone at day 7 (SpiroDex 6.8 ng/dL, Dex 14.52 ng/dL, p = 0.0075). There was no difference in VWF or angiotensin II levels between groups. For secondary outcomes, SpiroDex patients had a significantly greater number of oxygen free days and reached oxygen freedom sooner than the Dex group. Cough scores were no different during the acute illness, however the SpiroDex group had lower scores at day 28. There was no difference in corticosteroid levels between groups. There was no increase in adverse events in patients receiving SpiroDex. Conclusion Low dose oral spironolactone in addition to dexamethasone was safe and reduced D-dimer and aldosterone. Time to recovery was not significantly reduced. Phase 3 randomised controlled trials with spironolactone and dexamethasone should be considered. Trial registration The trial was registered on the Clinical Trials Registry of India TRI: CTRI/2021/03/031721, reference: REF/2021/03/041472. Registered on 04/03/2021.

Abstract As the UK, together with numerous countries in the world, moves towards a new phase of the COVID-19 pandemic, there is a need to be able to predict trends in sufficient time to limit the pressure faced by the National Health Service (NHS) and maintain low hospitalisation levels. In this study, we explore the use of an epidemiological compartmental model to devise a periodic adaptive suppression/intervention policy to alleviate the pressure on the NHS. The proposed model facilitates the understanding of the progression of the specific stages of COVID-19 in communities in the UK including: the susceptible population, the infected population, the hospitalised population, the recovered population, the deceased population, and the vaccinated population. We identify the parameters of the model by relying on past data within the period from 1 October 2020 to 1 June 2021. We use the total number of hospitalised patients and the fraction of those infected who are being admitted to hospital to develop adaptive policies: these modulate the recommended level of social restriction measures and realisable vaccination target adjustments. The analysis over the period 1 October 2020 to 1 June 2021 demonstrates our periodic adaptive policies have the potential to reduce the hospitalisation by 58% on average per month. In a further prospective analysis over the period August 2021 to May 2022, we analyse several future scenarios, characterised by the relaxation of restrictions, the vaccination ineffectiveness and the gradual decay of the vaccination-induced immunity within the population. In addition, we simulate the surge of plausible variants characterised by an higher transmission rate. In such scenarios, we show that our periodic intervention is effective and able to maintain the hospitalisation rate to a manageable level.

Introduction: This study investigated the relationship between anatomical compression introduced via ultrasound probe pressure and maximum perineum dose in prostate radiotherapy patients using the Clarity transperineal ultrasound (TPUS) system. Methods: 115 patient ultrasound and computed tomography scans were retrospectively analysed. The probe to prostate apex distance (PPA), probe to inferior corpus spongiosum distance (PICS) and maximum perineum dose were calculated. Compression was represented by the PICS and the calculated corpus to prostate ratio (CPR). Demographics included treatment technique, image quality, body mass index (BMI) and age. Multiple linear regression analysis assessed the relationship between compression measures and perineum dose. Results: The maximum dose to perineum ranged from 1.81 to 45.56 Gy, with a median of 5.87 Gy (Interquartile range (IQR) 3.17). The PICS distance and CPR recorded was 1.67 cm (IQR 0.63) and 0.51 (range 0.29–0.85) respectively. Regression analysis demonstrated both PICS and CPR were significant predictors of maximum dose to the perineum (p

Abstract Aims The current study explores whether degree of inflammation, reflected by C‐reactive protein (CRP) level, modifies the effect of intravenous (IV) corticosteroid administered in the emergency department (ED) on clinical outcomes in patients with acute heart failure (AHF). Methods and results We selected patients diagnosed with AHF in the ED, with confirmed N‐terminal pro‐B‐type natriuretic peptide > 300 pg/mL and CRP > 5 mg/L in the ED from the Epidemiology of Acute Heart Failure in the Emergency Departments (EAHFE) registry. In these 1109 patients, 121 were treated by corticosteroid. The corticosteroid therapy hazard ratio (HR) for 30 day all‐cause mortality was 1.26 [95% confidence interval (CI) 0.75–2.09, P = 0.38]. Although not statistically significant, HRs tended to decrease with increasing CRP level, with point estimates favouring corticosteroid at CRP levels above 20. In patients with CRP > 40 mg/L, with adjusted HRs of 0.56 (95% CI 0.20–1.55, P = 0.27) for 30 day all‐cause mortality, 0.92 (95% CI 0.52–1.62, P = 0.78) for 30 day post‐discharge ED revisit, hospitalization, or death, and adjusted odds ratio of 0.61 (95% CI 0.17–2.14, P = 0.44) for in‐hospital all‐cause mortality. Conclusions The present analysis suggests that corticosteroids might have the potential to improve outcomes in AHF patients with inflammatory activation. Larger, prospective studies of anti‐inflammatory therapy should be considered to assess potential benefit in patients with the highest degree of inflammation.

Abstract In this paper, a quasi‐linear parameter varying sliding mode control allocation law is proposed for the fault tolerant control of an octorotor. In the event of rotor faults/failures, an allocation law redistributes the control effort among the remaining healthy rotors. The sliding mode control law is designed to guarantee asymptotic tracking of a reference model which is tuned on‐line, through an interpolated feedback gain, to ensure that the control signals remain within their saturation limits. A method for designing the parameterised feedback gain is proposed which is shown to maximise a defined stability criteria whilst preventing undesirable performance characteristics in the reference model. The proposed scheme is tested on a non‐linear octorotor model in the presence of severe rotor failures and uncertainty/disturbances.

Abstract Background Loss of resistance (LOR) for epidural catheter placement has been utilized for almost a century. LOR is a subjective endpoint associated with a high failure rate. Nerve stimulation (NS) has been described as an objective method for confirming placement of an epidural catheter. We hypothesized that the addition of NS to LOR would improve the success of epidural catheter placement. Methods One-hundred patients were randomized to thoracic epidural analgesia (TEA) utilizing LOR-alone or loss of resistance plus nerve stimulation (LOR + NS). The primary endpoint was rate of success, defined as loss of sensation following test dose. Secondary endpoints included performance time. An intention-to-treat analysis was planned, but a per-protocol analysis was performed to investigate the success rate when stimulation was achieved. Results In the intention-to-treat analysis there was no difference in success rates (90% vs 82% [LOR + NS vs LOR-alone]; P = 0.39). The procedural time increased in the LOR + NS group (33.9 ± 12.8 vs 24.0 ± 8.0 min; P

BackgroundDigital health technologies (DHTs), such as electronic health records and prescribing systems, are transforming health care delivery around the world. The quality of information in DHTs is key to the quality and safety of care. We developed a novel clinical information quality (CLIQ) framework to assess the quality of clinical information in DHTs. ObjectiveThis study explored clinicians’ perspectives on the relevance, definition, and assessment of information quality dimensions in the CLIQ framework. MethodsWe used a systematic and iterative eDelphi approach to engage clinicians who had information governance roles or personal interest in information governance; the clinicians were recruited through purposive and snowball sampling techniques. Data were collected using semistructured online questionnaires until consensus was reached on the information quality dimensions in the CLIQ framework. Responses on the relevance of the dimensions were summarized to inform decisions on retention of the dimensions according to prespecified rules. Thematic analysis of the free-text responses was used to revise definitions and the assessment of dimensions. ResultsThirty-five clinicians from 10 countries participated in the study, which was concluded after the second round. Consensus was reached on all dimensions and categories in the CLIQ framework: informativeness (accuracy, completeness, interpretability, plausibility, provenance, and relevance), availability (accessibility, portability, security, and timeliness), and usability (conformance, consistency, and maintainability). A new dimension, searchability, was introduced in the availability category to account for the ease of finding needed information in the DHTs. Certain dimensions were renamed, and some definitions were rephrased to improve clarity. ConclusionsThe CLIQ framework reached a high expert consensus and clarity of language relating to the information quality dimensions. The framework can be used by health care managers and institutions as a pragmatic tool for identifying and forestalling information quality problems that could compromise patient safety and quality of care. International Registered Report Identifier (IRRID)RR2-10.1136/bmjopen-2021-057430

Abstract Background and Aim Liver histology changes are the current gold standard for evaluating non‐alcoholic steatohepatitis (NASH), but are limited by their invasiveness and variability for sampling and interpretation. We evaluated noninvasive biomarkers as an indication of histologic changes in NASH. Methods Associations between 12‐month biomarker and NASH Clinical Research Network histologic score changes in 339 patients with NASH in the EMMINENCE trial was examined with multivariable models and partial canonical correlation. A meta‐analysis of 17 NASH trials including 3717 patients examined associations between these same changes and histologic response within treatment groups, and treatment effects on biomarkers and on liver histology. Biopsy measures assessed were changes in ballooning, steatosis, inflammation, and fibrosis, NASH improvement without worsening of fibrosis, and fibrosis improvement without worsening of NASH. All analytic methods suggest that a combination of aspartate aminotransferase (AST), cytokeratin‐18 (CK‐18 [M30 or M65]), and hemoglobin A1C (HbA1c) changes best predicts overall liver biopsy changes in response to interventions. Results The weighted average of standardized mean changes (0.403 × AST, 0.314 × CK‐18, 0.283 × HbA1c) facilitated comparisons of within‐group responses and treatment effects among studies included in the meta‐analysis. This composite in EMMINENCE discriminated between patients with and without NASH resolution without worsening fibrosis with area under the receiver‐operator characteristic curve of 0.7880, and for fibrosis improvement without NASH worsening of 0.7553. Conclusion A composite score based on changes in AST, HbA1c, and CK‐18 could serve as a surrogate for liver histologic improvement and an effective objective, noninvasive tool for comparative assessment of treatment effects of novel interventions.

Abstract In paediatric patients, ultrasonography is one of the preferred medical imaging modalities due to the lack of ionising radiation. Abdominal ultrasonography can be a useful tool in diagnosing cases of fungal infections but may introduce some risks for further infection in vulnerable patients or cause anxiety and discomfort. The aim of this narrative review is to analyse the utility of abdominal ultrasonography in diagnosing fungal infections in children in terms of its positive hit rates and utility in typical use. Text words and indexed terms related to ‘fungal infection and ultrasonography’ and ‘children’ were searched on MEDLINE, EMBASE, Cochrane Library and Scopus. Paediatric oncology patients, neonates and generally immunocompromised children were found to be at‐risk groups with increasing susceptibility to risk factors for contracting fungal infections. Abdominal ultrasonography was found to aid in the diagnosis of fungal infection in many cases, but not all patients with the identified risk factors were diagnosed with fungal infections and not all patients diagnosed with fungal infections had identified risk factors. Ultrasonography was found to be overutilised and the current decision process in requesting abdominal ultrasonography in diagnosing fungal infection should be revised. Further study into an effective criterion in requesting abdominal ultrasonography is suggested to reduce the overutilisation of ultrasonography, thus reducing risk of infection and discomfort while also saving time and money.

Abstract Aims The relationship between N‐terminal pro‐brain natriuretic peptide (NT‐pro‐BNP) and galectin‐3 and outcomes has not been studied in African patients with acute heart failure (AHF). The current analysis sought to describe the association between plasma levels of NT‐pro‐BNP and galectin‐3 and cardiovascular (CV) death or heart failure (HF) hospitalization, as well as their associations with symptoms and echocardiography markers of left and right ventricular remodelling among AHF patientsv in sub‐Saharan Africa. Methods and results In a subset of 80 patients with complete data in a study assessing the effects of hydralazine and nitrates in patients with AHF (BAHEF trial; NCT01822808), NT‐pro‐BNP and galectin‐3 analyses were performed, and the association with various characteristics and outcome measures assessed. The mean age of the patients for whom the aforementioned biomarkers were measured was 52.6 years, with 52.5% women. Galectin‐3 at baseline predicted changes (Week 24 to baseline) in left ventricular ejection fraction, left ventricular end‐systolic diameter, left ventricular end‐diastolic diameter, and tricuspid annular plane systolic excursion. Biomarkers and their changes were not associated with changes in 6 min walk test at 24 weeks. Baseline galectin‐3 and change in NT‐pro‐BNP were associated with improvements in dyspnoea at 24 weeks. Nine patients had an HF readmission or died of CV causes through 24 weeks (11.6%). Both biomarkers at baseline predicted combined CV death or HF hospitalization through Week 24 (P‐values = 0.0328 and 0.0001, respectively). Conclusions In a cohort of patients with AHF from sub‐Saharan Africa, NT‐pro‐BNP and galectin‐3 at baseline and their changes were associated with some changes in dyspnoea, echocardiographic remodelling, and CV death or HF hospitalization through Week 24. These tests have potential of being used for risk stratification of AHF patients in sub‐Saharan Africa where resources are scarce.

Abstract Aims Limited data are available on clinical characteristics and prognosis of heart failure (HF) in black African populations especially with respect to current classifications and HF management guidelines. Methods and results In this post hoc analysis, African patients admitted with acute HF and enrolled in the THESUS‐HF registry in one of 12 hospitals in 9 countries were classified as having preserved left ventricular ejection fraction (LVEF) (HFpEF), mid‐range LVEF (HFmrEF), and reduced LVEF (HFrEF) based on echocardiography performed close to the time of admission. Sociodemographic and clinical characteristics, management, and 60 and 180 day outcomes were compared between the groups. Of 888 patients with LVEF available, there were 472 (53.2%) with HFrEF, 174 (19.6%) with HFmrEF, and 243 (27.3%) with HFpEF. History of atrial fibrillation was higher in patients with HFmrEF (28.5%) than in patients with HFrEF (14.5%). Patients with HFrEF had a larger mean LV systolic diameter (54.1 ± 9.67 mm) than patients with HFmrEF (42.9 ± 8.47 mm), who had a larger mean LV diameter than patients with HFpEF (32.6 ± 8.64 mm); a similar pattern with LV diastolic diameter was observed. The mean posterior diastolic wall thickness (10.2 ± 2.94 mm) was lower in patients with HFrEF than in those with HFmrEF (11.1 ± 2.59 mm) and HFpEF (11.2 ± 2.90 mm). Patients with HFpEF were less likely to use angiotensin‐converting enzyme inhibitor/angiotensin receptor blockers, and aldosterone inhibitors, and more likely to use beta‐blockers than those with HFrEF at either admission or discharge/Day 7. Death or readmission rates through Day 60 and 180 day death rates did not differ significantly among the groups; unadjusted hazard ratios relative to patients with HFrEF were 1.32 [95% confidence interval (CI) 0.84–2.08] and 1.24 (95% CI 0.82–1.89) for 60 day death or readmission and 0.92 (95% CI 0.59–1.43) and 0.78 (95% CI 0.51–1.20) for 180 day death in patients with HFmrEF and HFpEF, respectively. Conclusions Classification by LVEF according to European Society of Cardiology guidelines revealed some differences in clinical presentation but similar mortality and rehospitalization rates across all EF groups in Africans admitted for HF.

Abstract This paper presents a novel form of control allocation, designed within a sliding mode framework, for the fault tolerant control of over‐actuated systems. The control allocation is designed in such a way as to allow a subset of the actuators to remain inactive under nominal fault‐free conditions. In the event that the active set of actuators becomes unable to provide the desired performance, an adaption process takes place which allows the inactive actuators to compensate. A computationally light gradient descent algorithm is proposed to govern the adaption which guarantees that, if possible, actuator saturation is avoided and system performance is maintained, even in the event of severe actuator faults/failures. Rigorous conditions are derived, in terms of the faults/failures, uncertainties in fault reconstruction information and the adaptive process, which ensure sliding occurs in a finite time and that the resulting motion is stable. To demonstrate the effectiveness of the control scheme, a high‐fidelity blended wing body aircraft model is also proposed in this paper; this particular configuration of aircraft is nominally unstable, with poor control authority and a large amount of redundancy, making it a suitable candidate for testing reconfigurable fault tolerant control laws in the presence of input constraints.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain and inflammation. NSAID complications include acute kidney injury (AKI), causing burden to patients and health services through increased morbidity, mortality, and hospital admissions. Aim: To measure the extent of NSAID prescribing in an adult population, the degree to which patients with potential higher risk of AKI were exposed to NSAIDs, and to quantify their risk of AKI. Design & setting: Retrospective 2-year closed-cohort study. Method: A retrospective cohort of adults was identified from a pseudonymised electronic primary care database in Hampshire, UK. The cohort had clinical information, prescribing data, and complete GP- and hospital-ordered biochemistry data. NSAID exposure (minimum one prescription in a 2-month period) was categorised as never, intermittent, and continuous, and first AKI using the national AKI e-alert algorithm. Descriptive statistics and logistic regression were used to explore NSAID prescribing patterns and AKI risk. Results: The baseline population was 702 265. NSAID prescription fell from 19 364 (2.8%) to 16 251 (2.4%) over 2 years. NSAID prescribing was positively associated with older age, female sex, greater socioeconomic deprivation, and certain comorbidities (diabetes, hypertension, osteoarthritis, and rheumatoid arthritis) and negatively with cardiovascular disease (CVD) and heart failure. Among those prescribed NSAIDs, AKI was associated with older age, greater deprivation, chronic kidney disease (CKD), CVD, heart failure, diabetes, and hypertension. Conclusion: Despite generally good prescribing practice, NSAID prescribing was identified in some people at higher risk of AKI (for example, patients with CKD and older) for whom medication review and NSAID deprescribing should be considered.

Sonography is a highly specialized diagnostic imaging profession facing significant workforce challenges due to increased service delivery demands and a shortage of clinical training opportunities. Developing sustainable solutions is crucial for workforce growth. Using examples from the Australian workforce and education context, this paper explores the current sonography training pathways available and the benefits and challenges of each, highlighting the importance of work-integrated learning (WIL) in facilitating the development of professional identity, clinical competence and the quality of sonographer education. Conclusions are drawn that WIL is integral to the future of the sonography profession to improve patient outcomes and address workforce shortages. However, effective implementation requires careful planning and consideration of many factors, including regulatory requirements, industry partnerships, student and supervisor/tutor support, and issues related to equitable access and participation in WIL. Key recommendations are provided to encourage ethical student learning, university-industry collaboration, effective resource allocation, and WIL-specific research.

This paper suggests that ATP release induced by the SARS-CoV-2 virus plays a key role in the genesis of the major symptoms and complications of COVID-19. Infection of specific cells which contain the Angiotensin-Converting Enzyme 2 (ACE2) receptor results in a loss of protection of the Mineralocorticoid Receptor (MR). Local activation by cortisol stimulates the release of ATP initially into the basolateral compartment and then by lysosomal exocytosis from the cell surface. This then acts on adjacent cells. In the nose ATP acts as a nociceptive stimulus which results in anosmia. It is suggested that a similar paracrine mechanism is responsible for the loss of taste. In the lung ATP release from type 2 alveolar cells produces the non-productive cough by acting on purinergic receptors on adjacent neuroepithelial cells and activating, via the vagus, the cough reflex. Infection of endothelial cells results in the exocytosis of WeibelPalade bodies. These contain the Von Willebrand Factor responsible for micro-clotting and angiopoietin-2 which increases vascular permeability and plays a key role in the Acute Respiratory Distress Syndrome. To test this hypothesis this paper reports proof of concept studies in which MR blockade using spironolactone and low dose dexamethasone (SpiDex) was given to PCR-confirmed COVID-19 patients. In 80 patients with moderate to severe respiratory failure 40 were given SpiDex and 40 conventional treatment with high dose dexamethasone (HiDex). There was 1 death in the HiDex group and none in the SpiDex. As judged by clinical, biochemical and radiological parameters there were clear statistically significant benefits of SpiDex in comparison to HiDex. A further 20 outpatients with COVID-19 were given SpiDex. There was no control group and the aim was to demonstrate safety. No adverse effects were noted and no patient became hyperkalaemic. 90% were asymptomatic at 10 days. The very positive results suggest that blockade of the MR can produce major benefit in COVID19 patients. Further larger controlled studies of inpatients and outpatients are required not only for SARS-CoV-2 infection per se but also to determine if this treatment affects the incidence of Long COVID.

Current methods to measure extracellular pH are often limited in resolution and response times. Here the authors present a label-free nanoprobe, consisting of a zwitterionic nanomembrane at the tip of a nanopipette, which enables high spatiotemporal resolution pH measurements and topography-pH 3D mapping in live cancer cells.

Introduction The perinatal–postnatal family environment is associated with childhood outcomes including impacts on physical and mental health and educational attainment. Family longitudinal cohort studies collect in-depth data that can capture the influence of an era on family lifestyle, mental health, chronic disease, education and financial stability to enable identification of gaps in society and provide the evidence for changes in government in policy and practice.Methods and analysis The Queensland Family Cohort (QFC) is a prospective, observational, longitudinal study that will recruit 12 500 pregnant families across the state of Queensland (QLD), Australia and intends to follow-up families and children for three decades. To identify the immediate and future health requirements of the QLD population; pregnant participants and their partners will be enrolled by 24 weeks of gestation and followed up at 24, 28 and 36 weeks of gestation, during delivery, on-ward, 6 weeks postpartum and then every 12 months where questionnaires, biological samples and physical measures will be collected from parents and children. To examine the impact of environmental exposures on families, data related to environmental pollution, household pollution and employment exposures will be linked to pregnancy and health outcomes. Where feasible, data linkage of state and federal government databases will be used to follow the participants long term. Biological samples will be stored long term for future discoveries of biomarkers of health and disease.Ethics and dissemination Ethical approval has been obtained from the Mater Research Ethics (HREC/16/MHS/113). Findings will be reported to (1) QFC participating families; (2) funding bodies, institutes and hospitals supporting the QFC; (3) federal, state and local governments to inform policy; (4) presented at local, national and international conferences and (5) disseminated by peer-review publications.

Access to healthcare services for underrepresented minority populations can be improved by having a diverse profession that reflects the diversity of the patient population being served. The criteria used for pharmacy school admissions may inhibit or strengthen the opportunities that URM students have to be accepted into the University of Arizona R. Ken Coit College of Pharmacy (COP) program. It is currently unclear how personal characteristics are associated with pharmacy school admissions at the COP. This study evaluates whether Hispanic ethnicity was associated with pharmacy school admission status, and secondarily, determines other characteristics associated with admissions. This retrospective database study used admissions data from 2005 to 2018. Completed applications were included in the analysis. The outcome variable was admitted versus not admitted to the pharmacy program. A multivariable logistic regression model was used to identify variables associated with admission status using an a priori alpha level of 0.05. A total of 2096 applicants were included in the analysis (mean age 25.1 ± 5.2 years, 59.9% female, 13.0% Hispanic). Hispanic ethnicity was not associated with admission status. Characteristics significantly associated with admission to pharmacy school were age, gender, high school attended, previous application to the college, and Pharmacy College Admission Test (PCAT) biology and chemistry scores. Although bias was not seen in the admissions process, this study highlights the need for intervention to ensure future cohorts better reflect the diversity of the region.

Video content is increasingly being consumed on the move using mobile devices such as smart phones and tablets. In order to deal with the challenges of heterogeneity of network access technologies and fluctuating resources, which are inherent features of mobile communication, HTTP adaptive streaming (HAS) is becoming the default technology for online video streaming. However, little research has been carried out to better understand the impact of handover schemes of the various mobility management protocols on the video quality of HAS. In this study, the authors present a comprehensive experimental measurement of the impact of handover on three representative HAS players. First, they implement three existing mobility management protocols, MIPv6, LISP‐MN and PMIPv6, on a network testbed. Using the fluid flow mobility model, the impact of frequent handover on the average video quality, the bandwidth utilisation and stability of the players was investigated. Their results show a degradation of all the observed parameters in all the reviewed players.

Hydrologic modeling can be used to aid in decision-making at the local scale. Developed countries usually have their own hydrologic models; however, developing countries often have limited hydrologic modeling capabilities due to factors such as the maintenance, computational costs, and technical capacity needed to run models. A global streamflow prediction system (GSPS) would help decrease vulnerabilities in developing countries and fill gaps in areas where no local models exist by providing extensive results that can be filtered for specific locations. However, large-scale forecasting systems come with their own challenges. These New hydroinformatic challenges can prevent these models from reaching their full potential of becoming useful in the decision making process. This article discusses these challenges along with the background leading to the development of a large-scale streamflow prediction system. In addition, we present a large-scale streamflow prediction system developed using the GloFAS-RAPID model. The developed model covers Africa, North America, South America, and South Asia. The results from this model are made available using a Hydrologic Modeling as a Service approach (HMaaS) as an answer to some of the discussed challenges. In contrast to the traditional modeling approach, which makes results available only to those with the resources necessary to run hydrologic models, the HMaaS approach makes results available using web services that can be accessed by anyone with an internet connection. Web applications and services for providing improved data accessibility, and addressing the discussed hydroinformamtic challenges are also presented. The HydroViewer app, a custom application to display model results and facilitate data consumption and integration at the local level is presented. We also conducted validation tests to ensure that model results are acceptable. Some of the countries where the presented services and applications have been tested include Argentina, Bangladesh, Colombia, Peru, Nepal, and the Dominican Republic. Overall, a HMaaS approach to operationalize a GSPS and provide meaningful and easily accessible results at the local level is provided with the potential to allow decision makers to focus on solving some of the most pressing water-related issues we face as a society.

The availability of 2-Dimensional Shear Wave Elastography (2D-SWE) technology on modern medical ultrasound systems is becoming increasingly common. The technology is now being used to investigate a range of soft tissues and related pathological conditions. This work investigated the reliability of a single commercial 2D-SWE system using a tissue-mimicking elastography phantom to understand the major causes of intra-system variability. Sources of shear wave velocity (SWV) measurement variability relates to imaging depth, target stiffness, sampling technique and the operator. Higher SWV measurement variability was evident with increasing depth and stiffness of the phantom targets. The influence of the operator was minimal, and variations in sampling technique had little impact on the SWV.

Background: Synovitis (inflamed joint synovial lining) in rheumatoid arthritis (RA) can be assessed by clinical examination (CE) or ultrasound (US). Objective: To investigate the added value of US, compared with CE alone, in RA synovitis in terms of clinical effectiveness and cost-effectiveness. Data sources: Electronic databases including MEDLINE, EMBASE and the Cochrane databases were searched from inception to October 2015. Review methods: A systematic review sought RA studies that compared additional US with CE. Heterogeneity of the studies with regard to interventions, comparators and outcomes precluded meta-analyses. Systematic searches for studies of cost-effectiveness and US and treatment-tapering studies (not necessarily including US) were undertaken. Mathematical model: A model was constructed that estimated, for patients in whom drug tapering was considered, the reduction in costs of disease-modifying anti-rheumatic drugs (DMARDs) and serious infections at which the addition of US had a cost per quality-adjusted life-year (QALY) gained of £20,000 and £30,000. Furthermore, the reduction in the costs of DMARDs at which US becomes cost neutral was also estimated. For patients in whom dose escalation was being considered, the reduction in number of patients escalating treatment and in serious infections at which the addition of US had a cost per QALY gained of £20,000 and £30,000 was estimated. The reduction in number of patients escalating treatment for US to become cost neutral was also estimated. Results: Fifty-eight studies were included. Two randomised controlled trials compared adding US to a Disease Activity Score (DAS)-based treat-to-target strategy for early RA patients. The addition of power Doppler ultrasound (PDUS) to a Disease Activity Score 28 joints-based treat-to-target strategy in the Targeting Synovitis in Early Rheumatoid Arthritis (TaSER) trial resulted in no significant between-group difference for change in Disease Activity Score 44 joints (DAS44). This study found that significantly more patients in the PDUS group attained DAS44 remission (p = 0.03). The Aiming for Remission in Rheumatoid Arthritis (ARCTIC) trial found that the addition of PDUS and grey-scale ultrasound (GSUS) to a DAS-based strategy did not produce a significant between-group difference in the primary end point: composite DAS of

This study explores the use of a butyrylcholinesterase (BChE)-based, reversible reaction biosensor using screen-printed electrodes (SPEs) having a smaller working surface area than the single-use electrodes previously studied. Previous research demonstrated the prospective application of a single-use biosensor fabricated with an acetylcholinesterase (AChE) enzyme encapsulated in peptide nanotubes (PNTs) and enhanced with horseradish peroxidase (HRP) to detect organophosphorus compounds (OPCs) in aqueous and gas phases. In the current study, potential improvements to the biosensor are investigated. BChE-based biosensors were fabricated using PNTs, HRP, and Nafion in combination to increase the reactive surface area, enhance sensitivity, and maintain enzyme stability. Cyclic voltammetry (CV) was used along with the new modified sensor to measure malathion concentration in the gas phase. The results show that a BChE-based biosensor could reliably measure gas phase malathion concentrations between 6−25 ppbv by CV with the extent of inhibition linearly proportional to the malathion concentration (R2 = 0.941). This research demonstrated that fabricated BChE-based biosensors could be stored without cold storage requirement for up to six weeks with minimal performance degradation. Moreover, the sensor electrodes were each reused several times, and were still useable at the conclusion of the research. This research demonstrates the potential of fabricating a reusable, inexpensive biosensor that is capable of OPC detection with high sensitivity and a low detection limit without a long-term cold storage requirement.

Category: Lesser Toes Introduction/Purpose: Instability at the MTPJ of the lessor toes is challenging to treat, particularly when both transverse and sagittal plane deformity coexist. Previous studies have utilized a subligamentous transfer of the EDB for crossover toes. The purpose of this pilot study was to evaluate a transosseous transfer of the EBD to correct multiplanar instability of the lessor toe. Routine exposure of the MTP was performed through a dorsal approach and a Z lengthening of the EDL was performed. The median number of concomitant produres performed was 4 and included hallux valgus repair, neuroma excision, metatarsal osteotomy, hammertoe correction and capsulotomies of other toes as needed. 27 tendon transfers were performed in 25 patients (2nd MTPJ: 20, 3 rd MTPJ: 5, 4th MTPJ: 2) Methods: A capsular release was performed on the concave side (contracted) and the convex side (lax) of the proximal phalanx and metatarsal head were exposed. A tenotomy of the EDB was performed at the musculotendinous junction and its insertion remained intact. The EDB was then transferred through a 2.5 mm drill hole in the base of the proximal phalanx. The drill hole began on the concave side and exited on the convex side with a similar hole from the convex side of the metatarsal neck to the concave side. To correct sagittal deformity the drill hole was oriented from dorsal to plantar. A low profile 1.5 mm polyethylene suture tape augmented the EDB transfer in both the proximal phalanx and metatarsal neck. A 3.0 mm interference screw is placed distally and the tape and EDB were appropriately tensioned and proximal fixation was achieved with another interference screw. Results: Results Median age in years (25-75th interquartile range) Females (N,%) 24, 96% 64(58-85) BMI (25-75th interquartile range) Previous surgery (N,%) Smoking history (N,%) Inflammatory arthritis (N,%) 27.8(21-32) 8, 32% 7, 28% 5, 25% Median number of concomitant procedures (25-75th IQR) Preop AP MTPJangle in degrees (25-75th IQR) Postop AP MTPJ angle in degrees (25-75th IQR) % Transverse Plane Improvement Preoperative to Postoperative 4(3-6) 19(11.5-24.0) 13(4.5-20.5) 31.5% (p < 0.0001) Preop Lateral MTPJ angle in degrees (25-75th IQR) Postop Lateral MTPJ angle in degrees (25-75th IQR) 41(26-58) 29(22.5-36) % Sagittal Plane Improvement Preoperative to Postoperative 29.2%(p < 0.0001) Conclusion: At a median follow up 19 weeks (12-32 weeks), EDB transfer augmented by polyethylene tape resulted in significant improvement in the transverse (31.5%) and sagittal planes (29.2%) without using temporary K wire fixation across the MTPJ. Twenty of 25 patients (80%) were completely satisfied, 4 patients (16%) were partially satisfied and 1 patient (4%) was dissatisfied. One mild infection occurred which was treated with oral antibiotics. No fractures occurred. This study is limited by relatively short follow up and the need to confirm these findings by independent surgeons. A biomechanical study is underway to assess pull out strength of the construct

In this paper, the problem of estimating the shear force affecting the tip of the cantilever in a Transverse Dynamic Force Microscope (TDFM) using a real-time implementable sliding mode observer is addressed. The behaviour of a vertically oriented oscillated cantilever, in close proximity to a specimen surface, facilitates the imaging of the specimen at nano-metre scale. Distance changes between the cantilever tip and the specimen can be inferred from the oscillation amplitudes, but also from the shear force acting at the tip. Thus, the problem of accurately estimating the shear force is of significance when specimen images and mechanical properties need to be obtained at submolecular precision. A low order dynamic model of the cantilever is derived using the method of lines, for the purpose of estimating the shear force. Based on this model, an estimator using sliding mode techniques is presented to reconstruct the unknown shear force, from only tip position measurements and knowledge of the excitation signal applied to the top of the cantilever. Comparisons to methods assuming a quasi-static harmonic balance are made.