Experiences of dental behaviour support techniques: A qualitative systematic review.

BACKGROUND: Little is known about patients' or carers' reported experiences of dental care provided using dental behaviour support (DBS) techniques. Qualitative literature can provide unique insight into these experiences. AIM: To explore and synthesize qualitative literature related to patient experience of dental behaviour support. METHODS: A PROSPERO-registered systematic review of qualitative articles was undertaken. Studies were identified through MEDLINE, Embase and PsycINFO. Abstracts were screened by two reviewers and data were extracted to summarize the qualitative findings included within them. A thematic summary approach was used to synthesize the qualitative data identified. RESULTS: Twenty-three studies were included. Studies primarily explored experiences of dental care of children by speaking to their parents (n = 16), particularly regarding paediatric dental general anaesthesia (DGA) (n = 8). Studies of adults' experiences of DBS (n = 7) covered a range of techniques. Nine studies explored broader dental care experiences and did not study specific DBS approaches. A thematic synthesis identified five themes applicable across the studies identified: Trust and the therapeutic alliance supporting effective care delivery; considered information sharing often alleviated anticipatory anxiety; control and autonomy-reduced anxieties; variations in the perceived treatment successes and failures of DBS techniques; and DBS techniques produced longer positive and negative impacts on patients beyond direct care provision. CONCLUSION: Qualitative research has been under-utilized in research on DBS techniques. Care experiences of most DBS techniques outside of paediatric DGA are poorly understood. Building trust with patients and enabling autonomy appear to support positive patient-reported experiences of care.

Insights from a single centre implementation of a digitally-enabled atrial fibrillation virtual ward.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and poses a significant public health burden. Virtual wards are a novel approach utilising digital solutions to provide hospital-level care remotely; their rollout has become a key priority for the UK National Health Service to expand acute care capacity. We devised and implemented a digitally-enabled AF virtual ward to monitor patients being established onto medical therapy following an AF diagnosis or an AF-related hospitalisation. Patients were onboarded either as outpatients to avoid admission or on discharge after an acute AF hospitalisation. Remote monitoring was undertaken using a clinically validated photoplethysmography-based smartphone app. Over a 1-2 week period, patients performed twice daily measurements of heart rate and rhythm and provided corresponding symptoms. A traffic light system guided frequency of telephone assessments by specialist practitioners. Red flag symptoms or abnormal heart rate parameters prompted an urgent care escalation. We report our experience of the first 73 patients onboarded to the AF virtual ward from October 2022 to June 2023 (mean age 65 years, median 68 years, IQR range 27-101 years; 33 females). Thirty-nine (53%) patients had red flag features requiring care escalation, of whom 9 (23%) were advised to attend ED (emergency department) for urgent assessment, 10 (26%) attended for expedited review and 14 (36%) required medication changes. By 3 months post-monitoring, only 3 patients (4%) had re-attended ED with an arrhythmia-related presentation. Virtual ward patients had an average 3-day shorter inpatient stay (mean duration 4 days) compared with AF patients hospitalised prior to virtual ward implementation (mean duration 7 days). Overall, 22 arrhythmia-related readmissions were prevented via the virtual ward model. In this study, we present a novel implementation of a digitally-enabled virtual ward for the acute management of patients with newly diagnosed or poorly controlled AF. Our pilot data indicate that this model is feasible and is potentially cost-effective. Further longitudinal study is needed to definitively evaluate long-term clinical utility and safety.

Discovery and Characterization of a Bicyclic Peptide (Bicycle) Binder to Thymic Stromal Lymphopoietin.

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived pro-inflammatory cytokine involved in the development of asthma and other atopic diseases. We used Bicycle Therapeutics' proprietary phage display platform to identify bicyclic peptides (Bicycles) with high affinity for TSLP, a target that is difficult to drug with conventional small molecules due to the extended protein-protein interactions it forms with both receptors. The hit series was shown to bind to TSLP in a hotspot, that is also used by IL-7Rα. Guided by the first X-ray crystal structure of a small peptide binding to TSLP and the identification of key metabolites, we were able to improve the proteolytic stability of this series in lung S9 fractions without sacrificing binding affinity. This resulted in the potent Bicycle 46 with nanomolar affinity to TSLP (KD = 13 nM), low plasma clearance of 6.4 mL/min/kg, and an effective half-life of 46 min after intravenous dosing to rats.

Elucidating the effects of microbubble pinch-off dynamics on mammalian cell viability.

In the biotechnology industry, ensuring the health and viability of mammalian cells, especially Chinese Hamster Ovary (CHO) cells, plays a significant role in the successful production of therapeutic agents. These cells are typically cultivated in aerated bioreactors, where they encounter fluid stressors from rapidly deforming bubbles. These stressors can disrupt essential biological processes and potentially lead to cell death. However, the impact of these transient, elevated stressors on cell viability remains elusive. In this study, we first employ /cgqamicrofluidics to expose CHO cells near to bubbles undergoing pinch-off, subsequently collecting and assaying the cells to quantify the reduction in viability. Observing a significant impact, we set out to understand this phenomenon. We leverage computational fluid dynamics and numerical particle tracking to map the stressor field history surrounding a rapidly deforming bubble. Separately, we expose CHO cells to a known stressor level in a flow constriction device, collecting and assaying the cells to quantify the reduction in viability. By integrating the numerical data and results from the flow constriction device experiments, we develop a predictive model for cell viability reduction. We validate this model by comparing its predictions to the earlier microfluidic results, observing good agreement. Our findings provide critical insights into the relationship between bubble-induced fluid stressors and mammalian cell viability, with implications for bioreactor design and cell culture protocol optimization in the biotechnology sector.

A scoping review of interventions and outcome measures in trials of dental behavior support.

BACKGROUND: Dental behavior support (DBS) describes all techniques used by dental professionals to ensure that dental care is safe, effective, and acceptable. There is a need to standardize outcome measures across DBS techniques to reduce heterogeneity, limit selective reporting, promote consistency, and optimize outcomes across DBS research. A comprehensive review of existing measures is a prerequisite to understanding potential outcomes related to the area of interest. AIM: This review had three aims: first, to identify the outcome measures (OMs) reported in trials of dental behavior support; second, to categorize the component DBS techniques reported within interventions according to emerging agreed terminology; and, third, to map outcome measures to intervention type. METHODS: A scoping review of trials evaluating DBS techniques was undertaken from 2012 to 2022. The review was prospectively registered. Studies were identified through Medline, Embase, and PsycINFO. Study abstracts were screened by two reviewers. Data were extracted by single selector. Outcome measures were sorted according to measurement domains (physiological, behavioral, psychological, and treatment). Responses were assimilated and summed to produce a refined list of distinguishable outcome measures. Intervention types were categorized according to accepted descriptors. Frequencies were presented; associations between outcome domain and DBS type were also reported (Chi-square test of independence). RESULTS: A total of 344 trials were included in the review from an initial 14,793 titles / title and abstracts screened. Most involved children (n = 215), most were from India (n = 104), involving basic dental care (n = 117). The median number of outcome measures per trial was four (range = 1-12); 1,317 individual outcomes were reported, categorized as: psychological (n = 501, 38.0%); physiological (n = 491, 37.3%), behavioral (n = 123, 9.3%) or, treatment-related (n = 202, 15.3%). DBS interventions were split between 239 (45.7%) pharmacological and 283 (54.1%) non-pharmacological; 96.6% of interventions mapped to accepted descriptors. A significant relationship was noted between the type of intervention and the outcome domain reported. CONCLUSION: The findings demonstrate massive variation in outcome measures of DBS interventions that likely lead to unnecessary heterogeneity, selective reporting, and questionable relevance in the literature. A large range of DBS interventions were mapped according to BeSiDe list. There is a need for consensus on a core outcome set across the spectrum of DBS techniques.

Universal non-monotonic drainage in large bare viscous bubbles.

Bubbles will rest at the surface of a liquid bath until their spherical cap drains sufficiently to spontaneously rupture. For large film caps, the memory of initial conditions is believed to be erased due to a visco-gravitational flow, whose velocity increases from the top of the bubble to its base. Consequently, the film thickness has been calculated to be relatively uniform as it thins, regardless of whether the drainage is regulated by shear or elongation. Here, we demonstrate that for large bare bubbles, the film thickness is highly nonuniform throughout drainage, spanning orders of magnitude from top to base. We link the film thickness profile to a universal non-monotonic drainage flow that depends on the bubble thinning rate. These results highlight an unexpected coupling between drainage velocity and bubble thickness profiles and provide critical insight needed to understand the retraction and breakup dynamics of these bubbles upon rupture.

Enrichment of Scavenged Particles in Jet Drops Determined by Bubble Size and Particle Position.

When small bubbles rupture in a contaminated water source, the resulting liquid jet breaks up into droplets that can aerosolize solid particulates such as bacteria, viruses, and microplastics. Particles collected on the bubble surface have the potential to become highly concentrated in the jet drops, dramatically increasing their impact. It has been assumed that only particles small enough to fit within a thin microlayer surrounding the bubble can be transported into its influential top jet drop. Yet here, we demonstrate that not only can larger particles be transported into this jet drop, but also that these particles can exceed previous enrichment measurements. Through experiments and simulations, we identify the prerupture location of the liquid that develops into the top jet drop and model how interfacial rearrangement combines with the bubble size, particle size, and the angular distribution of particles on the bubble surface to set the particle enrichment.

Analyzing proteolytic stability and metabolic hotspots of therapeutic peptides in two rodent pulmonary fluids.

Peptides and peptide drug conjugates are emerging modalities to treat pulmonary diseases. Peptides are susceptible to proteolytic cleavage. Expression levels of specific proteases in the lung can be significantly increased in disease state and may lead to exaggerated peptide proteolysis. To support optimization of peptides for inhaled administration, we have recently reported a streamlined high-throughput LC-HRMS protocol to determine enzymatic protease stability of peptides. This method has now been complemented with profiling of peptide metabolic stability in two respiratory fluids, a lung supernatant (lung S9) and a bronchioalveolar lavage fluid (BALF) taken from rats. We have tested a set of 28 peptides with high structural diversity, analyzed the whole data set for formed metabolites, and identified the differences of cleavage pattern in the two test fluids. Comparison of our experimental results and literature-derived cleavage site estimates based on e.g. MEROPS show significant differences for a number of peptides. This indicates the need for an experimental workflow using both protease panels and testing of metabolic stability in lung fluid (BALF) to guide peptide optimization and selection of peptides for inhaled in vivo PK/PD studies in our drug discovery projects.

Nurse staffing and inpatient mortality in the English National Health Service: a retrospective longitudinal study.

OBJECTIVE: To examine the impact of nursing team size and composition on inpatient hospital mortality. DESIGN: A retrospective longitudinal study using linked nursing staff rostering and patient data. Multilevel conditional logistic regression models with adjustment for patient characteristics, day and time-invariant ward differences estimated the association between inpatient mortality and staffing at the ward-day level. Two staffing measures were constructed: the fraction of target hours worked (fill-rate) and the absolute difference from target hours. SETTING: Three hospitals within a single National Health Service Trust in England. PARTICIPANTS: 19 287 ward-day observations with information on 4498 nurses and 66 923 hospital admissions in 53 inpatient hospital wards for acutely ill adult patients for calendar year 2017. MAIN OUTCOME MEASURE: In-hospital deaths. RESULTS: A statistically significant association between the fill-rate for registered nurses (RNs) and inpatient mortality (OR 0.9883, 95% CI 0.9773 to 0.9996, p=0.0416) was found only for RNs hospital employees. There was no association for healthcare support workers (HCSWs) or agency workers. On average, an extra 12-hour shift by an RN was associated with a reduction in the odds of a patient death of 9.6% (OR 0.9044, 95% CI 0.8219 to 0.9966, p=0.0416). An additional senior RN (in NHS pay band 7 or 8) had 2.2 times the impact of an additional band 5 RN (fill-rate for bands 7 and 8: OR 0.9760, 95% CI 0.9551 to 0.9973, p=0.0275; band 5: OR 0.9893, 95% CI 0.9771 to 1.0017, p=0.0907). CONCLUSIONS: RN staffing and seniority levels were associated with patient mortality. The lack of association for HCSWs and agency nurses indicates they are not effective substitutes for RNs who regularly work on the ward.

A general recognition theory model for identifying an ideal stimulus.

A probabilistic, multidimensional model is described that accounts for sensory and hedonic ratings that are collected from the same experiment. The model combines a general recognition theory model of the sensory ratings with Coombs' unfolding model of the hedonic ratings. The model uses sensory ratings to build a probabilistic, multidimensional representation of the sensory experiences elicited by exposure to each stimulus, and it also builds a similar representation of the hypothetical ideal stimulus in this same space. It accounts for hedonic ratings by measuring differences between the presented stimulus and the imagined ideal on each rated sensory dimension. Therefore, it provides precise estimates of the sensory qualities of the ideal on all rated sensory dimensions. The model is tested successfully against data from a new experiment.

Using data analytics to enhance quality improvement projects.

With the introduction of electronic health record systems in healthcare organisations, there is a significant opportunity within nursing, and as part of the multidisciplinary team, to access a wealth of data and use this to drive improvements in patient care and outcomes. Quality improvement has often involved the collection of data via manual audit, a time-consuming process with data fed back from small sample sizes over a short time period. In contrast, a data analytics approach enables data collection from larger sample sizes to be automated and for data to be presented in a way that is easy for staff to access and interpret. This article discusses the benefits and challenges of a data analytics approach as well as the resources required, the importance of stakeholder involvement, the setting and review of key performance indicators and how to optimise data presentation to achieve the greatest effect.

Automated high-throughput in vitro assays to identify metabolic hotspots and protease stability of structurally diverse, pharmacologically active peptides for inhalation.

The inhalation of peptides comes with the advantage of directly targeting the lung as tissue of interest. However, peptides are often rapidly metabolized in lung tissue through proteolytic cleavage. We have developed an assay workflow to obtain half-life and metabolite ID data for peptides incubated with four proteases abundant in lungs of asthma and COPD patients. The assay system has been validated using 28 structurally diverse linear and cyclic peptides with a molecular weight between 708 and 5808 Da. Experimental conditions for incubation, sample preparation, chromatography, data acquisition and analysis are compatible with the required throughput in early stage peptide projects. Together with co-crystal structures and Ala scans, we are using the described assay workflow to guide the first chemical modifications of peptide hits in early respiratory drug discovery projects.

Microscale heterogeneous pore occupancy with variable background resistance.

Fluid flow through porous media often involves the spontaneous displacement of one immiscible fluid by another. On the level of adjacent channels, a pore doublet model can estimate the relative flow rates in the two channels and the final fluid occupancy of the pair. Pore doublet models nominally capture the dominant roles of capillarity and viscosity, by describing the flow using hydraulic circuit theory. However, this approach neglects the more complex fluid flow in the region where the immiscible fluids meet, and therefore the applicability of this model for low aspect-ratio pores commonly seen in natural media is questionable. We show that for large channel aspect ratios, the numerical results replicate the traditional pore doublet models; however, as the aspect ratio approaches unity, the accuracy of these models break down. We quantify the effect of complex flow on the final fluid occupancy, which we link to the excess energy dissipation rate from the flow near the immiscible interface. Our results indicate that a minimal 1D pore doublet model may be sufficient to model global dynamics, including the fraction of residual oil that remains trapped in a reservoir, where the pore diameter and length are comparable.

Audit of flumazenil use in special care and oral surgery sedation services.

Background The National Patient Safety Agency (2008) has advised against routine reliance on flumazenil for reversal of sedation and encourages regular audit to help identify issues with excessive dosing of midazolam. This multi-centre audit of flumazenil use across both community-based special care and dental hospital oral surgery specialist services was conducted to compare practice against that reported from other UK sedation services.Methods A six-year retrospective audit was conducted using controlled drug records and patient case notes.Results Both services used flumazenil at very infrequent levels and far below the agreed standard. The dose of flumazenil and justification for its use was recorded in all records. There was variability in the nature of the justifications between the two services, which likely relates to the differing patient groups seen by the specialties. The majority of cases related to supporting the patient's escort for their journey home; however, this was not always pre-planned.Conclusions There was a low level of flumazenil use over an extended period of time, supporting the concept of a culture of safe sedation provision in both services. The audit highlighted variation in record-keeping and need for improved communication with patients about escort requirements.

Using aeration to probe the flow characteristics associated with long-term marine macrofouling growth and suppression.

It is well-established that hydrodynamics affect the settlement of biofouling organisms. Laboratory studies have demonstrated a connection between larval attachment rates and the prevalence of time windows that satisfy certain instantaneous flow conditions. However, it is unclear whether a link exists between short-term hydrodynamics and long-term macrofouling survival and growth, or if it is applicable at an ecosystem-wide level. This study used single bubble stream aeration in field and laboratory experiments to find critical flow characteristics that correlate to long-term, multi-species fouling prevention. The research was accomplished by combining PIV-derived flow statistics with fouling severity measured over seven weeks in the field. Flows with a decreasing proportion of time windows defined by a flow speed < 15.1 mm s-1 for longer than 0.03 s correlated to decreased biofouling growth and survival. These results provide a potential framework for studying and comparing flow fields that successfully inhibit biofouling growth.

Evaluation of a new rapid assessment and treatment (RAT) tablet app for Emergency Department (ED) nurses: Is earlier identification of investigations and treatments feasible?

Although doctor-led RAT has advantages, serial processing (triage - investigation - treatment) still predominates in UK EDs. We have designed a RAT decision-support app to assist ED nurses to select investigations and treatments at initial patient assessment and aid acuity scoring. METHODS: Test nurses accompanied triage ('control') nurses in an observational study of 529 adult patients. Investigations, treatments and procedures, selected using the app, were compared with those selected later by ED clinicians. Acuities set by both nurses were re-evaluated blind by a consultant panel. RESULTS: Data capture and decision making using RAT-support took a median of 1.43 min (IQR 1.13-2.07). Odds ratios are reported for matching of test versus control investigation and treatment orders. The ability to predict, within minutes, control investigations which were ordered at median of 50 min (IQR 21-99) is encouraging. Median times to order treatments (analgesia 88 min, IV antibiotics 112 min) were also reduced. Acuity scores versus the consultant panel gave weighted kappa of 0.54 (CI 0.48-0.61) for study nurses and for controls 0.45 (CI 0.36-0.53). CONCLUSIONS: We conclude that nurse-led RAT for use in initial assessment is feasible given decision support. We also identified improvements required for the app.

Aerosol agitation: Quantifying the hydrodynamic stressors on particulates encapsulated in small droplets.

Lower respiratory tract infections originate from multiple aerosol sources, varying from droplets erupting from bursting bubbles in a toilet or those produced by human speech. A key component of the aerosol-based infection pathway-from source to potential host-is the survival of the pathogen during aerosolization. Due to their finite-time instability, pinch-off processes occurring during aerosolization have the potential to rapidly accelerate the fluid into focused regions of these droplets, stress objects therein, and if powerful enough, disrupt biological life. However, the extent that a pathogen will be exposed to damaging hydrodynamic stressors during the aerosolization process is unknown. Here we compute the probability that particulates will be exposed to a hydrodynamic stressor during the generation of droplets that range in size from one to 100 microns. For example, particulates in water droplets less than 5 µm have a 50% chance of being subjected to an energy dissipation rate in excess of 1011 W/m3, hydrodynamic stresses in excess of 104 Pa, and strain rates in excess of 107 s-1, values known to damage certain biological cells. Using a combination of numerical simulations and self-similar dynamics, we show how the exposure within a droplet can be generally predicted from its size, surface tension, and density, even across different aerosolization mechanisms. Collectively, these results introduce aerosol agitation as a potential factor in pathogen transmission and implicate the pinch-off singularity flow as setting the distribution of hydrodynamic stressors experienced within the droplet.

A new wrinkle on liquid sheets: Turning the mechanism of viscous bubble collapse upside down.

Viscous bubbles are prevalent in both natural and industrial settings. Their rupture and collapse may be accompanied by features typically associated with elastic sheets, including the development of radial wrinkles. Previous investigators concluded that the film weight is responsible for both the film collapse and wrinkling instability. Conversely, we show here experimentally that gravity plays a negligible role: The same collapse and wrinkling arise independently of the bubble's orientation. We found that surface tension drives the collapse and initiates a dynamic buckling instability. Because the film weight is irrelevant, our results suggest that wrinkling may likewise accompany the breakup of relatively small-scale, curved viscous and viscoelastic films, including those in the respiratory tract responsible for aerosol production from exhalation events.