Exploring flexible polynomial regression as a method to align routine clinical outcomes with daily data capture through remote technologies

Data Availability: The data that support the findings of this study are available from Great Ormond Street Hospital, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Great Ormond Street Hospital.Copyright © The Author(s) 2023. Background: Clinical outcomes are normally captured less frequently than data from remote technologies, leaving a disparity in volumes of data from these different sources. To align these data, flexible polynomial regression was investigated to estimate personalised trends for a continuous outcome over time. Methods: Using electronic health records, flexible polynomial regression models inclusive of a 1st up to a 4th order were calculated to predict forced expiratory volume in 1 s (FEV1) over time in children with cystic fibrosis. The model with the lowest AIC for each individual was selected as the best fit. The optimal parameters for using flexible polynomials were investigated by comparing the measured FEV1 values to the values given by the individualised polynomial. Results: There were 8,549 FEV1 measurements from 267 individuals. For individuals with > 15 measurements (n = 178), the polynomial predictions worked well; however, with < 15 measurements (n = 89), the polynomial models were conditional on the number of measurements and time between measurements. The method was validated using BMI in the same population of children. Conclusion: Flexible polynomials can be used to extrapolate clinical outcome measures at frequent time intervals to align with daily data captured through remote technologies.UCL, GOSH and Toronto SickKids studentship. GD is supported by a Future Leaders Fellowship from UK Research & Innovation (UKRI), Grant reference: MR/T041285. All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre

Investigating the In Vivo Antimicrobial Activity of a Self-Assembling Peptide Hydrogel Using a Galleria mellonella Infection Model

Technological advances in protein biochemistry now enable researchers to modify the structure of peptides to enable them to possess self-assembling properties, forming hydrogels at low concentrations. Peptides can be altered further to provide multifunctional characteristics, for example, to demonstrate antimicrobial properties. The aim of this article is to investigate the in vivo toxicity and antimicrobial properties of a low molecular weight (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFKK-OH) peptide hydrogel using an innovative waxworm (Galleria mellonella) model, as an alternative to mammalian/vertebrate testing. NapFFKK-OH hydrogels did not demonstrate any observable in vivo toxicity or death in G. mellonella larvae over 5 days at concentrations studied (≤2% w/v). A dose-dependent log10 reduction in viable (CFU/mL) Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria implicated in nosocomial infections was observed over 72 h. NapFFKK-OH was especially effective against in vivo infection models of S. aureus with a significant 4.4 log10 CFU/mL reduction in viable bacteria at 2% w/v after 72 h. Our results show G. mellonella to be a useful model for preliminary determination of in vivo toxicity and antimicrobial efficacy profiles of novel nanomaterials, including peptide-based hydrogels. This contributes to the 3R principles of animal testing, reduction, refinement, and replacement. The results also show NapFFKK-OH to be a promising alternative to standardly employed antimicrobials with the potential to be utilized as a novel therapeutic in the treatment and prevention of hospital infections

Rising obesity-related hospital admissions among children and young people in England: national time trends study

Objective: To describe the trends in hospital admissions associated with obesity as a primary diagnosis and comorbidity, and bariatric surgery procedures among children and young people in England. Design: National time trends study of hospital admissions data between 2000 and 2009. Participants: Children and young people aged 5 to 19 years who were admitted to hospital with any diagnosis of obesity. Main outcome measures: Age- and sex-specific admission rates per million children. Results: Between 2000 and 2009, age- and sex-specific hospital admission rates in 5–19 year olds for total obesity-related diagnoses increased more than four-fold from 93.0 (95% CI 86.0 to 100.0) per million children to 414.0 (95% CI 410.7 to 417.5) per million children, largely due to rising admissions where obesity was mentioned as a co-morbidity. The median age of admission to hospital over the study period was 14.0 years; 5,566 (26.7%) admissions were for obesity and 15,319 (73.3%) mentioned obesity as a comorbidity. Admissions were more common in girls than boys (56.2% v 43.8%). The most common reasons for admission where obesity was a comorbid condition were sleep apnoea, asthma, and complications of pregnancy. The number of bariatric surgery procedures has risen from 1 per year in 2000 to 31 in 2009, with the majority were performed in obese girls (75.6%) aged 13–19 years. Conclusions: Hospital admission rates for obesity and related comorbid conditions have increased more than four-fold over the past decade amongst children and young people. Although some of the increase is likely to be due to improved case ascertainment, conditions associated with obesity in children and young people are imposing greater challenges for health care providers in English hospitals. Most inpatient care is directed at dealing with associated conditions rather than primary assessment and management of obesity itself

Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence.

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30–60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa

Sharing and reuse in OER: experiences gained from open reusable learning objects in health

Normal 0 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} Abstract: &nbsp;The open educational resource (OER) movement has the potential to have a truly transformative effect on higher education, but in order to do so it must move into the mainstream and facilitate widespread participation in the sharing or creating of resources and in their reuse. To help in this process, experience can be gained from projects and initiatives which have acted as forerunners to this movement.&nbsp; Here we present the experiences gained and lessons learnt from one such project based around the open sharing of reusable learning objects in health sciences education. In particular we share our experiences of reuse, its patterns, measurement, drivers, barriers, and tools designed to balance the pedagogical tensions between use and reuse. Like many in the OER movement we promote an emphasis on the role of community-building. We also argue that in order to produce materials that are worth sharing, value must firstly be placed on developing materials suitable for primary use, including robust evaluation and an alignment to real-world learning needs. Lastly, unlike the prevailing trends in OER we urge a consideration of quality assurance and outline the role that it can play in promoting sharing and reuse

Using Rheo-Small-Angle Neutron Scattering to Understand How Functionalised Dipeptides Form Gels

We explore the use of rheo-small-angle neutron scattering as a method to collect structural information from neutron scattering simultaneously with rheology to understand how low-molecular-weight hydrogels form and behave under shear. We examine three different gelling hydrogel systems to assess what structures are formed and how these influence the rheology. Furthermore, we probe what is happening to the network during syneresis and why the gels do not recover after an applied strain. All this information is vital when considering gels for applications such as 3D-printing and injection

Comparing how patients value and respond to information on risk given in three different forms during dental check-ups: the PREFER randomised controlled trial

Background: This study aims to compare patient preference for, and subsequent change in, oral health behaviour for three forms of risk information given at dental check-ups (verbal advice compared to verbal advice accompanied by a traffic light (TL) risk card; or compared to verbal advice with a quantitative light fluorescence (QLF) photograph of the patient's mouth). Methods: A multi-centre, parallel-group, patient-randomised clinical trial was undertaken between August 2015 and September 2016. Computer-generated random numbers using block stratification allocated patients to three arms. The setting was four English NHS dental practices. Participants were 412 dentate adults at medium/high risk of poor oral health. Patients rated preference and willingness to pay (WTP) for the three types of information. The primary outcome was WTP. After receiving their check-up, patients received the type of information according to their group allocation. Follow-up was by telephone/e-mail at 6 and 12 months. Mean and median WTP for the three arms were compared using Wilcoxon signed-rank tests. Tobit regression models were used to investigate factors affecting WTP and preference for information type. Secondary outcomes included self-rated oral health and change in oral health behaviours (tooth-brushing, sugar consumption and smoking) and were investigated using multivariate generalised linear mixed models. Results: A total of 412 patients were randomised (138 to verbal, 134 to TL and 140 to QLF); 391 revisited their WTP scores after the check-up (23 withdrew). Follow-up data were obtained for 185 (46%) participants at 6 months and 153 (38%) participants at 12 months. Verbal advice was the first preference for 51% (209 participants), QLF for 35% (145 participants) and TL for 14% (58 participants). TL information was valued lower than either verbal or QLF information (p Conclusions: Although a new NHS dental contract based on TL risk stratification is being tested, patients prefer the usual verbal advice. There was also a practice effect which will needs to be considered for successful implementation of this government policy

Re-engineering the post-myocardial infarction medicines optimisation pathway: A retrospective analysis of a joint consultant pharmacist and cardiologist clinic model

Background: Inadequate medicines optimisation and adherence are significant problems among patients taking secondary prevention medications following myocardial infarction (MI). A novel joint consultant cardiology pharmacist and cardiologist medicines optimisation clinic was initiated for patients recently discharged following MI. Methods: Patients completed a locally developed tool, the 'My Experience of Taking Medicines' questionnaire, designed to allow sharing of barriers to adherence with medications. They then attended a clinic with the consultant pharmacist or cardiologist (or both). Secondary prevention medicines needs and barriers to adherence were identified and discussed, and an action plan developed. The data provided are from a retrospective review of 270 post-MI patients attending the service between October 2015 and December 2016. Results: Mean age was 67.3 years and 67.8% were male. The mean time from discharge to first outpatient clinic attendance was reduced by 56.1% (49.4 days vs 88 days before the service began). More than 95% of patient without planned non-pharmacological intervention postdischarge did not need a cardiologist's input. Levels of medicines optimisation were improved substantially after attendance: patients receiving a recommended angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose increased from 16.3% to 73.9% (p<0.001); patients receiving a recommended beta-blocker dose increased from 6.2% to 46.1% (p<0.001). Patient concerns about their medications were significantly decreased (all p<0.001). Rates of non-Adherence fell by 42.6%-70.8% at 3-6 months post-clinic. Readmission rates also declined after the service opened. Conclusions: A medicines optimisation and patient adherence strategy based on a joint consultant cardiology pharmacist and cardiologist clinic can improve both adherence and outcomes post-MI