Pre-hospital prediction of adverse outcomes in patients with suspected COVID-19: Development, application and comparison of machine learning and deep learning methods.

BACKGROUND: COVID-19 infected millions of people and increased mortality worldwide. Patients with suspected COVID-19 utilised emergency medical services (EMS) and attended emergency departments, resulting in increased pressures and waiting times. Rapid and accurate decision-making is required to identify patients at high-risk of clinical deterioration following COVID-19 infection, whilst also avoiding unnecessary hospital admissions. Our study aimed to develop artificial intelligence models to predict adverse outcomes in suspected COVID-19 patients attended by EMS clinicians. METHOD: Linked ambulance service data were obtained for 7,549 adult patients with suspected COVID-19 infection attended by EMS clinicians in the Yorkshire and Humber region (England) from 18-03-2020 to 29-06-2020. We used support vector machines (SVM), extreme gradient boosting, artificial neural network (ANN) models, ensemble learning methods and logistic regression to predict the primary outcome (death or need for organ support within 30 days). Models were compared with two baselines: the decision made by EMS clinicians to convey patients to hospital, and the PRIEST clinical severity score. RESULTS: Of the 7,549 patients attended by EMS clinicians, 1,330 (17.6%) experienced the primary outcome. Machine Learning methods showed slight improvements in sensitivity over baseline results. Further improvements were obtained using stacking ensemble methods, the best geometric mean (GM) results were obtained using SVM and ANN as base learners when maximising sensitivity and specificity. CONCLUSIONS: These methods could potentially reduce the numbers of patients conveyed to hospital without a concomitant increase in adverse outcomes. Further work is required to test the models externally and develop an automated system for use in clinical settings.

A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue.

PURPOSE: The purpose of the present systematic review was to develop a practice guideline to inform health care providers about screening, assessment, and effective management of cancer-related fatigue (crf) in adults. METHODS: The internationally endorsed adapte methodology was used to develop a practice guideline for pan-Canadian use. A systematic search of the literature identified a broad range of evidence: clinical practice guidelines, systematic reviews, and other guidance documents on the screening, assessment, and management of crf. The search included medline, embase, cinahl, the Cochrane Library, and other guideline and data sources to December 2009. RESULTS: Two clinical practice guidelines were identified for adaptation. Seven guidance documents and four systematic reviews also provided supplementary evidence to inform guideline recommendations. Health professionals across Canada provided expert feedback on the adapted recommendations in the practice guideline and algorithm through a participatory external review process. CONCLUSIONS: Practice guidelines can facilitate the adoption of evidence-based assessment and interventions for adult cancer patients experiencing fatigue. Development of an algorithm to guide decision-making in practice may also foster the uptake of a guideline into routine care.

Prophylactic feeding tubes for patients with locally advanced head-and-neck cancer undergoing combined chemotherapy and radiotherapy-systematic review and recommendations for clinical practice.

GOALS: This work aimed to determine the benefits and risks of prophylactic feeding tubes for adult patients with squamous cell carcinoma of the head and neck who receive combined chemotherapy and radiotherapy with curative intent and to make recommendations on the use of prophylactic feeding tubes and the provision of adequate nutrition to this patient population. METHODS: A national multidisciplinary panel conducted a systematic review of the evidence and formulated recommendations to guide clinical decision-making. The draft evidence summary and recommendations were distributed to clinicians across Canada for their input. MAIN RESULTS: No randomized controlled trials have directly addressed this question. Evidence from studies in the target population was limited to seven descriptive studies: two with control groups (one prospective, one retrospective) and five without control groups. Results from ten controlled studies in patients treated with radiotherapy alone were also reviewed. CONCLUSIONS: The available evidence was insufficient to draw definitive conclusions about the effectiveness of prophylactic feeding tubes in the target patient population or to support an evidence-based practice guideline. After review of the evidence, of guidelines from other groups, and of current clinical practice in Canada, the multidisciplinary panel made consensus-based recommendations regarding comprehensive interdisciplinary clinical care before, during, and after cancer treatment. The recommendations are based on the expert opinion of the panel members and on their understanding of best clinical practice.

Ureaplasma urealyticum is significantly associated with non-gonococcal urethritis in heterosexual Sydney men.

We investigated the prevalence of various genital organisms in 268 men with (cases) and 237 men without (controls) urethral symptoms/signs (urethral discharge, dysuria and/or urethral irritation) from two sexual health clinics in Sydney between April 2006 and November 2007. The presence of urethral symptoms/signs was defined as non-gonococcal urethritis (NGU) for this study. Specific aims were to investigate the role of Ureaplasma urealyticum in NGU and the prevalence of Mycoplasma genitalium in our population. Multiplex polymerase chain reaction-based reverse line blot (mPCR/RLB) assay was performed to detect 14 recognized or putative genital pathogens, including Chlamydia trachomatis, M. genitalium, U. urealyticum and U. parvum. U. urealyticum was associated with NGU in men without another urethral pathogen (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.1-3.8; P = 0.04); this association remained after controlling for potential confounding by age and history of unprotected vaginal sex in the last four weeks (OR 2.0, 95% CI: 1.1-3.9; P = 0.03). C. trachomatis (OR 7.5, P < 0.001) and M. genitalium (OR 5.5, P = 0.027) were significantly associated with NGU. The prevalence of M. genitalium was low (4.5% cases, 0.8% controls). U. urealyticum is independently associated with NGU in men without other recognized urethral pathogens. Further research should investigate the role of U. urealyticum subtypes among heterosexual men with NGU.

Audit of a sexual health website email link for general practitioners.

The aim of this review was to evaluate an 'Email a Clinician' link on a medically reviewed sexual health website, which was established to allow general practitioners (GPs) to communicate remotely with sexual health clinic specialists. The website was developed in consultation with GPs and extensively promoted throughout the relevant professional primary health-care networks. Despite this, the email link appeared to fail in its objective of facilitating GP access to specialist sexual health physician opinion within five working days. An audit examining use of the email link was conducted for a one-year period, during which time 324 emails were received. Results showed that the bulk of the emails (93.2%) were spam, and only 6.8% were genuine enquiries. Of the 22 genuine emails, 21 (95%) originated from the general public and there were no enquiries from the GPs, who were the target audience of the website, resulting in removal of the email link from the site. Direct survey of local GPs to evaluate reasons for non-utilization of the link was not possible. However, discomfort with the technology, time added to existing workload, lack of direct perceived benefit and lack of immediate response have been cited as contributing factors that may limit widespread adoption of other telemedicine services. As a new generation of recently graduated GPs enters the Australian workforce, who might be expected to be skilled and comfortable with electronic medical communication, the option of a direct email link to a sexual health clinic, with a faster turnaround time, may be worth re-visiting in the future.

TTX blocks baclofen-induced phase shifts of the mammalian circadian pacemaker in vitro.

The mammalian circadian pacemaker, located in the suprachiasmatic nucleus (SCN), expresses 24-h rhythms when isolated in vitro. The GABA(A) agonist, muscimol, induces phase advances during the mid-subjective day, while the GABA(B) agonist, baclofen, induces both daytime phase advances and nighttime phase delays. Here, we present evidence that tetrodotoxin (TTX) completely blocks baclofen-induced phase shifts in vitro, but does not block in vitro phase advances induced by muscimol. These results suggest that GABA(A), but not GABA(B), receptors are located on SCN pacemaker cells.

Neuropeptide Y blocks GABAB-induced phase-shifts of the suprachiasmatic circadian clock in vitro.

The mammalian circadian clock in the suprachiasmatic nucleus (SCN) generates 24-h rhythms of neuronal activity in vitro. We have previously shown that the GABAB agonist baclofen resets the SCN pacemaker in vitro in a phase-dependent manner: advances are induced at zeitgeber time (ZT) 6 and delays are induced at ZT 22. We have also previously shown that neuropeptide Y (NPY) phase-shifts the SCN clock when applied at ZT 10 but not at other times. Here, we show that NPY blocks the baclofen-induced phase-shifts at ZT 6 and ZT 22. The inhibition by NPY appears dose-dependent, and a higher concentration of NPY is required for complete inhibition of the baclofen-induced phase-advances than the phase-delays. Conversely, NPY-induced phase-shifts at ZT 10 are unaffected by co-application of baclofen. These results are consistent with previous findings showing that NPY blocks in vitro phase-shifts induced by a variety of neuromodulators during both the daytime and nighttime.

Determining the current roles of physical and occupational therapists in burn care.

The team approach has enjoyed great success in the care of patients with burns, and it has been shown to decrease morbidity and mortality in these cases. Although the concept of the team approach is well-defined, the delineation of roles within this approach remains unclear. This study was designed to better explain the roles of physical therapists (PTs) and occupational therapists (OTs) in burn care. With the use of a questionnaire, PT and OT responsibilities were reviewed. The results showed that OTs perform the majority of activities of daily living training, PTs perform the majority of functional mobility training, both professions are involved in scar management, and neither profession has significant responsibility for care of the burn wound itself. Role delineation occurs to help avoid role confusion and the duplication of services. The title burn therapist offers an example of unclear role definition when a physical therapy assistant uses that title to identify himself or herself. Communication is critical to define these roles within individual burn centers.

GABAB receptor stimulation phase-shifts the mammalian circadian clock in vitro.

The mammalian circadian clock in the suprachiasmatic nucleus (SCN) generates 24-h rhythms in vitro. Here we show that the GABAB agonist baclofen resets the SCN pacemaker in vitro in a phase-dependent manner: advances were induced at zeitgeber time (ZT) 6, and delays were induced at ZT 22. Both effects were blocked the GABAB antagonist, 2-hydroxysaclofen, while the GABAA antagonist, bicuculline was ineffective. Thus, the SCN pacemaker is sensitive to resetting by GABAB stimulation.

The burn camp experience: variables that influence the enhancement of self-esteem.

Since 1982, there have been summer camps for children and adolescent burn survivors. Although the primary focus of camp is to have "fun," the principal goal is psychosocial readjustment through peer interactions and the resulting enhancement of self-esteem (SE). This study was initiated to test the hypothesis that the burn camp experience enhances the SE of campers. Forty-three campers at the Connecticut Burns Care Foundation Summer Camp were invited to participate in this study with the Rosenberg Self-Esteem Scale. The age range was 8 to 18 years (mean 12 years). The extent of previous burn injury ranged from 10% to 98% total body surface area (mean 40%). The interval between hospital discharge and camp experience was 4 to 144 months (mean 54 months). Thirty-seven percent of the children demonstrated an increase in SE to varying degrees, whereas 30% showed no change, and 3% exhibited a decrease in SE. This study failed to support the working hypothesis.

Solubilization of covalently bound extensin from capsicum cell walls.

Acidified sodium chlorite cleaves isodityrosine and solubilizes covalently bound hydroxyproline-rich material from cell walls. This has been taken as evidence that isodityrosine acts as a cross-link holding the hydroxyproline-rich glycoprotein extensin in the cell wall. However, acidified chlorite was found to cleave peptide bonds in salt-soluble extensin and in bovine serum albumin (BSA). This invalidates the use of conventional acidified chlorite treatment to provide evidence for isodityrosine cross-links. The ratio of BSA:chlorite was important in determining peptidyl cleavage. At a ratio of 0.75:1.00 (mole amino acid residues/mole chlorite), or higher, peptidyl cleavage was not detected. Furthermore, in samples where a low concentration of radioactive extensin was present, BSA substantially protected the peptide bonds of the extensin against peptidyl cleavage during treatment with acidified chlorite, while not preventing the cleavage of isodityrosine. Therefore, acidified sodium chlorite plus BSA was a more specific reagent for the cleavage of isodityrosine than was acidified chlorite alone. This modified treatment solubilized in intact form the ;covalently bound' extensin from cell walls of Capsicum frutescens (chili pepper) suspension cultures, providing new evidence compatible with the view that extensin molecules are held in the cell wall by isodityrosine cross-links.

Oligosaccharins from xyloglucan and cellulose: modulators of the action of auxin and H+ on plant growth.

UNLABELLED: The dose/response curve for auxin's action as a plant growth promoter is extremely wide. How does the cell vary its response to such a wide range of signal intensity? We suggest that cell wall-bound cellulase, and the products of its action on the wall polysaccharides xyloglucan and cellulose, provide a complex regulatory system, acting at three or possibly four different levels. Our recent observations will be presented in terms of the following speculations. (1) SPECULATION: Low levels of auxin activate cellulase (by inducing H(+)-secretion?), which cuts inter-microfibrillar xyloglucan chains, loosening the cell wall and tending to promote growth. OBSERVATION: auxins induce xyloglucan turnover and decrease the mean Mr of wall xyloglucan. Re-incorporation of xyloglucan fragments suggests that transglycosylation predominates over hydrolysis. (2) SPECULATION: Moderate levels of auxin activate cellulase further; the enzyme generates small amounts (nM) of oligosaccharides, some of which are growth-inhibitory. This process tends to moderate growth. OBSERVATION: Xyloglucan nonasaccharide (XG9-see Fig. 2) at 1-10 nM antagonises auxin-induced growth. The effect is seen with fucose-containing oligosaccharides (XG9, XG5, fucosyl-lactose), but not with XG7 or XG8. XG9 (1 nM) and XG10 (0.1 nM) and cellohexaose (10 nM) also block H(+)-induced growth. (3) SPECULATION: Higher levels of auxin induce cellulase synthesis leading to the generation of higher concentrations of oligosaccharides that can mimic auxin. This process thus tends to restore growth. OBSERVATION: all xyloglucan-oligosaccharides tested (HPLC-pure XG7, XG8, XG9, XG9n - Fig. 2) promote growth at 1 microM, the order of effectiveness being XG9n greater than XG8 greater than XG7 conquent to XG9. The same oligosaccharides (at 1-100 microM) promote the mid-chain hydrolysis of xyloglucan by plant cellulase, while slightly inhibiting total hydrolysis. The order of effectiveness is XG9n congruent to XG8 greater than XG7 congruent to XG9. The promotion of mid-chain hydrolysis (and/or transglycosylation) might be expected to be particularly effective at loosening the cell wall: most of the wall's xyloglucan molecules might suffer a single cleavage rather than a few of them undergoing complete degradation. (4) SPECULATION: Very high levels of auxin induce excessive levels of cellulase, and therefore of oligosaccharides. This inhibits growth. OBSERVATION: XG7, XG9 and XG9n lose their auxin-like activity at 10 microM.