Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments.

BACKGROUND: The COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE (Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses) is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within approximately 24-48 h of their test result. METHODS: A multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (approximately within 24-48 h of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology. RESULTS: Prior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1013 recruits to PRINCIPLE at the start of October 2020 to 2802 recruits by 20 December 2020. Whilst procedural caveats were identified by the public consultation, out of 2639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached. CONCLUSIONS: This paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions. TRIAL REGISTRATION: PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22 . 26/03/2020 ISRCTN registry: ISRCTN86534580 . 20/03/2020 REC number: 20/SC/058 IRAS number: 281958.

Effective in vitro inactivation of SARS-CoV-2 by commercially available mouthwashes.

Infectious SARS-CoV-2 can be recovered from the oral cavities and saliva of COVID-19 patients with potential implications for disease transmission. Reducing viral load in patient saliva using antiviral mouthwashes may therefore have a role as a control measure in limiting virus spread, particularly in dental settings. Here, the efficacy of SARS-CoV-2 inactivation by seven commercially available mouthwashes with a range of active ingredients were evaluated in vitro. We demonstrate ≥4.1 to ≥5.5 log10 reduction in SARS-CoV-2 titre following a 1 min treatment with commercially available mouthwashes containing 0.01-0.02 % stabilised hypochlorous acid or 0.58 % povidone iodine, and non-specialist mouthwashes with both alcohol-based and alcohol-free formulations designed for home use. In contrast, products containing 1.5 % hydrogen peroxide or 0.2 % chlorhexidine gluconate were ineffective against SARS-CoV-2 in these tests. This study contributes to the growing body of evidence surrounding virucidal efficacy of mouthwashes/oral rinses against SARS-CoV-2, and has important applications in reducing risk associated with aerosol generating procedures in dentistry and potentially for infection control more widely.

Modelling net energy of commercial cat diets.

Net energy accounts for the proportion of energy expenditure attributed to the digestion, metabolism, and absorption of ingested food. Currently, there are no models available to predict net energy density of food for domestic cats. Therefore, the objectives of this study were to measure the heat increment of feeding in cats, and to model the net energy of commercial diets. Metabolizable energy and calorimetry data from two previous studies was reanalyzed to create net energy models in the present study. Energy expenditure was calculated using measurements of CO2 production and O2 consumption. Net energy was determined as the metabolizable energy of the diets minus the heat increment of feeding. The heat increment of feeding was determined as the area under the energy expenditure curve above the resting fed metabolic rate. Eight net energy models were developed using metabolizable energy, 1 of 4 dietary parameters (crude protein, fat, fiber, and starch), and heat increment of feeding values from 0-2 h or 0-21 h. Two hours postprandial, and over the full calorimetry period, the heat increment of feeding amounted for 1.74, and 20.9% of the metabolizable energy, respectively. Of the models tested, the models using crude protein in combination with metabolizable energy as dietary parameters best fit the observed data, thus providing a more accurate estimate of dietary energy availability for cats.

Removable partial dentures: The clinical need for innovation.

STATEMENT OF PROBLEM: The number of partially dentate adults is increasing, and many patients will require replacement of missing teeth. Although current treatment options also include fixed partial dentures and implants, removable partial dentures (RPDs) can have advantages and are widely used in clinical practice. However, a significant need exists to advance materials and fabrication technologies because of the unwanted health consequences associated with current RPDs. PURPOSE: The purpose of this review was to assess the current state of and future need for prosthetics such as RPDs for patients with partial edentulism, highlight areas of weakness, and outline possible solutions to issues that affect patient satisfaction and the use of RPDs. MATERIAL AND METHODS: The data on treatment for partial edentulism were reviewed and summarized with a focus on currently available and future RPD designs, materials, means of production, and impact on oral health. Data on patient satisfaction and compliance with RPD treatment were also reviewed to assess patient-centered care. RESULTS: Design, materials, ease of repair, patient education, and follow-up for RPD treatment all had a significant impact on treatment success. Almost 40% of patients no longer use their RPD within 5 years because of factors such as sociodemographics, pain, and esthetics. Research on RPD-based treatment for partial edentulism for both disease-oriented and patient-centered outcomes is lacking. CONCLUSIONS: Future trials should evaluate new RPD materials and design technologies and include both long-term follow-up and health-related and patient-reported outcomes. Advances in materials and digital design/production along with patient education promise to further the application of RPDs and improve the quality of life for patients requiring RPDs.

Contemporary management of generalized erosive tooth surface loss.

UNLABELLED: Management of generalized erosive tooth surface loss can be challenging. Careful pre-operative assessment of the patient and treatment planning is essential. The aim of any treatment provided is to prevent further tooth surface loss, restore aesthetics and function, and provide a stable occlusal relationship. Whilst attempting to fulfil these goals, it is important to protect the remaining tooth structure by using restorations which are conservative and do not cause further damage to teeth which are already compromised. This paper aims to describe a conservative approach to restoring patients with generalized tooth surface loss. CLINICAL RELEVANCE: To highlight conservative treatment options available for the management of generalized erosive tooth surface loss and show how they contrast with other destructive irreversible conventional techniques.

Dentinogenesis imperfecta: full-mouth rehabilitation using implants and sinus grafts--a case report.

UNLABELLED: This case report outlines one possible treatment modality to manage the developmental abnormality dentinogenesis imperfecta (DI). In this case, the patient's dentition is restored using a combination of full-coverage crowns for the remaining teeth and implant-supported crowns to replace missing teeth in a re-organized occlusal scheme. The case also demonstrates the effective use of the sinus graft procedure with simultaneous placement of dental implants. This paper also aims to make the reader aware of the current thinking behind treatment delivered to this group of patients, focusing on full-mouth rehabilitation using a combination of implant-supported and conventional metal ceramic crowns. CLINICAL RELEVANCE: For the general dental practitioner this case outlines the prevalence and cause of DI. It demonstrates how early diagnosis and appropriate referral has an impact on future treatment.

Aesthetic preview: a novel approach.

UNLABELLED: Planning the final aesthetic result of restorative treatment is a key skill needed by the clinician to ensure predictable success. This paper aims to review current techniques that may be used by clinicians for an aesthetic preview, whilst also highlighting a simple technique that may be readily utilized in practice. CLINICAL RELEVANCE: It is considered good practice to give patients an aesthetic preview of the end result prior to commencing active treatment. This article demonstrates the different techniques available and those that are easily utilized in general practice. The aesthetic preview is of benefit to both the clinician and technician in defining treatment goals and improving communication.

The effect of hearing augmentation on cognitive assessment scales at admission to hospital.

OBJECTIVES: : The aim was to assess how the use of a commercially available hearing augmentation device affected performance on cognitive assessment scales on admission to hospital. DESIGN: : This was a randomized controlled trial. SETTING: : The study was conducted on all of the acute assessment wards in a department of medicine for the elderly. PARTICIPANTS: : All patients admitted to the department from December 1, 2007, until February 28, 2008, were considered for admission to the study. Patients with delirium were excluded. INTERVENTION: : A commercially available device provided hearing augmentation in the intervention group on the second day. MEASUREMENTS: : All participants had cognitive assessments using the Mini-Mental State Examination (MMSE) and the Abbreviated Mental Test (AMT) on two consecutive days. RESULTS: : A total of 192 patients (60.4% women, mean [±SD] age 82.4 [±7.0] years) were recruited and randomized into control (N = 58) or intervention groups (N = 134). Paired and unpaired t-tests were used to compare mean improvements in scores within and between groups, respectively. The mean improvement in MMSE scores was 2.00 (p <0.001) in the intervention group and 0.49 in the control group (p = 0.46), and the mean improvement in AMT scores was 0.48 (p <0.001) for the intervention group and 0.24 (p = 0.04) for the control group. In comparing mean improvements between groups, unpaired t-test results were significant for MMSE (p <0.001) but not for AMT (p = 0.23). These results were confirmed on repeated-measures ANOVA (group by time interaction). CONCLUSIONS: : Hearing augmentation significantly improves performance on MMSE scores. The use of hearing augmentation devices in routine screening for cognitive impairment merits further study.

Neuroimaging studies of delirium: a systematic review.

OBJECTIVE: Neuroimaging offers clear potential in developing a better understanding of the pathophysiology of delirium. We performed a systematic review of structural and functional neuroimaging findings in delirium. The aims were to categorize and summarize the existing literature, and to determine whether this literature provides conclusive information on structural or functional brain predictors, correlates, or consequences of delirium. METHODS: Studies were identified by comprehensive textword and MeSH-based electronic searches of MEDLINE, EMBASE, and Evidence-Based Medicine reviews, combining multiple terms for neuroimaging, brain structure, and delirium. RESULTS: Twelve studies met the inclusion criteria. There were a total of 194 patients with delirium and 570 controls. Patient age, population, comorbidities, and identified precipitating factors were heterogeneous. Of the 10 structural studies, 3 studies used computed tomography (CT), 3 studies used magnetic resonance imaging (MRI), and 4 studies used a mixture of CT and MRI. One functional study used xenon CT, and the other used single photon emission computed tomography. There was a wide range of measurement techniques and timing of scans. Some studies found associations between delirium and cortical atrophy, and between ventricular enlargement and white matter lesion burden, but many studies did not control for potential confounders. Only two small studies of cerebral blood flow were identified, with both suggesting that there may be reduced regional cerebral blood flow, but the data were limited and somewhat inconsistent. CONCLUSIONS: The small sample sizes and other limitations of the studies identified in this review preclude drawing any clear conclusions regarding neuroimaging findings in delirium, but these studies suggest multiple avenues for future research.

Quality of life and its correlates in octogenarians. Use of the SEIQoL-DW in Wave 5 of the Aberdeen Birth Cohort 1921 Study (ABC1921).

BACKGROUND: The direct-weighted Schedule for the Evaluation of Individual Quality of Life, Direct Weighting (SEIQoL-DW) is an individualised measure of QoL that has been little used in very elderly people. METHODS: We administered SEIQoL-DW during Wave 5 of the Aberdeen Birth Cohort 1921 Study (ABC1921) and sought statistical correlations with other variables in the data set. ABC1921 participants had been IQ-tested in 1932 at age 11. Since 1997, data about cognition, mental/physical function, personality, health, and socioeconomic status have been gathered in five waves of investigations. RESULTS: Ninety-six out of 98 individuals, mean age 82.2, completed the SEIQoL-DW. Health, family, relationships, finances and social pastimes were the commonest cues nominated, but age/gender differences existed. The mean SEIQoL-DW score (74.0) was significantly lower than in an approximately 60% sample from Wave 3, the fall being greater in men. Variables statistically associated with Wave 5 SEIQoL-DW usually reflected current rather than past status [including Short-Form 36 Health Survey (SF-36) components and depression], although there were weaker correlations with years of education, housing in childhood, conscientiousness, and IQ in 1998. CONCLUSIONS: SEIQoL-DW proved feasible and acceptable in community-dwelling octogenarians. Recent (i.e. statelike) rather than early or long-standing (i.e. traitlike) influences appeared to have the greater effect on QoL.

Surface analysis under ambient conditions using plasma-assisted desorption/ionization mass spectrometry.

A novel plasma-assisted desorption/ionization (PADI) method that can be coupled with atmospheric pressure sampling mass spectrometry to yield mass spectral information under ambient conditions of pressure and humidity from a range of surfaces without the requirement for sample preparation or additives is reported. PADI is carried out by generating a nonthermal plasma which interacts directly with the surface of the analyte. Desorption and ionization then occur at the surface, and ions are sampled by the mass spectrometer. The PADI technique is demonstrated and compared with desorption electrospray ionization (DESI) for the detection of active ingredients in a range of over-the-counter and prescription pharmaceutical formulations, including nonsterodial anti-inflammatory drugs (mefenamic acid, Ibugel, and ibuprofen), analgesics (paracetamol, Anadin Extra), and Beecham's "all in one" cold and flu remedy. PADI has also been successfully applied to the analysis of nicotine in tobacco and thiosulfates in garlic. PADI experiments have been performed using a prototype source interfaced with a Waters Platform LCZ single-quadrupole mass spectrometer with limited modifications and a Hiden Analytical HPR-60 molecular beam mass spectrometer (MBMS). The ability of PADI to rapidly detect active ingredients in pharmaceuticals without the need for prior sample preparation, solvents, or exposed high voltages demonstrates the potential of the technique for high-throughput screening in a pharmaceutical or forensic environment.