Surgically facilitated orthodontics with clear aligners for severe malocclusion and gingival recessions.

Background: Gingival recession defects (GRDs) pose functional and esthetic concerns and may be associated with unfavorable tooth positions. Surgically facilitated orthodontic treatment (SFOT) with clear aligners can be a valuable option for adults with severe malocclusion and GRDs.

Methods: A 28-year-old male presented with severe dental crowding, Class III dental malocclusion, localized tooth crossbites, and tapered maxillary arch.

Novel non-opioid analgesics in pain management.

Effective pain management has long been hindered by the limitations and risks associated with opioid analgesics, necessitating the exploration of novel, non-opioid alternatives. A comprehensive literature search was conducted using PubMed and Google Scholar during October and November 2024 to identify studies on emerging non-opioid pain management therapeutics. This review evaluates three promising classes of mechanism-specific therapeutics: nerve growth factor (NGF) monoclonal antibodies, transient receptor potential vanilloid 1 (TRPV1) antagonists, and selective sodium channel blockers.

Assessing the effectiveness of an online cycling training for adults to master complex traffic situations.

Background: Acknowledging the significance of both subjective and objective safety in promoting cycling, there is a need for effective measures aimed at improving cycling skills among a broader population. Hence, the aim of the current study is to evaluate and investigate the impact of online cycling training targeted at adults.

Methods: An online cycling training consisting of three modules was developed to train safe behaviour in seven prototypical safety-relevant situations.

Assessing the feasibility of the GOTT (Gabapentinoid and Opioid Tapering Toolkit) in a primary care setting in North-East England.

Objective: To assess the feasibility and possible impacts of implementation of systematic non-pharmacological interventions to reduce the level of prescribing of opioid and gabapentinoid analgesics for chronic non-cancer pain (CNCP), particularly high-dose prescriptions, through a proof-of-concept study in a deprived area (second lowest decile) primary care practice in North-East England.

Participant: Twenty-five primary care staff (clinical and non-clinical) of which 18 clinicians received the intervention.

Intervention Used In This Study Practice Known As Gott Gabapentinoid And Opioid Toolkit: All clinicians received an educational skills programme to support patient pain self-management, tailored on the clinicians' self-assessment of their learning needs, embedding both clinician skill learning and patient self-care resources for rapid access within consultations into a GP clinical management computer system.

Do primary care quality improvement frameworks consider equity?

Background: Quality improvement (QI) is used by healthcare organisations internationally to improve care. Unless QI explicitly addresses equity, projects that aim to improve care may exacerbate health and care inequalities for disadvantaged groups. There are several QI frameworks used in primary care, but we do not know the extent to which they consider equity.

A systematic review of 'equity-focused' game-based learning in the teaching of health staff.

Background: An unequal distribution of the social determinants of health drives health inequalities. Existing training fails to communicate the impossible circumstances that disadvantaged groups face. Game-based learning is increasingly used as an innovative method with the potential to enhance health staff's ability to address health inequalities, but its effectiveness is unknown.

Evaluating niraparib versus active symptom control in patients with previously treated mesothelioma (NERO): a study protocol for a multicentre, randomised, two-arm, open-label phase II trial in UK secondary care centres.

Background: Malignant mesothelioma is a rapidly lethal cancer that has been increasing at an epidemic rate over the last three decades. Targeted therapies for mesothelioma have been lacking. A previous study called MiST1 (NCT03654833), evaluated the efficacy of Poly (ADP-ribose) polymerase (PARP) inhibition in mesothelioma.

Association of selective serotonin reuptake inhibitor use with marginal bone level changes around osseointegrated dental implants: A retrospective study.

Background: Selective serotonin reuptake inhibitors (SSRIs) are used for the management of anxiety and depression. Existing evidence shows their negative impact on implant osseointegration, survival rates, and peri-implant health. Currently, there are limited data on their effect on peri-implant marginal bone levels.

Adapt and Adjust: Doing UK-Based Ethnographic Fieldwork During the Covid-19 Pandemic.

The Covid-19 pandemic has required many anthropologists to do fieldwork differently: research that would otherwise have been done face-to-face has been shifted online, sometimes very quickly. When doing research with people with chronic illnesses, it is important to acknowledge both the histories of online ethnography and the way that disability studies has engaged with the internet over time. This article uses the example of my PhD fieldwork, based in Northeast England, to explore how living in an increasingly digital world may impact how medical anthropologists could, and perhaps should, do ethnography.

An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2.

Repurposing approved drugs may rapidly establish effective interventions during a public health crisis. This has yielded immunomodulatory treatments for severe coronavirus disease 2019 (COVID-19), but repurposed antivirals have not been successful to date because of redundancy of the target in vivo or suboptimal exposures at studied doses. Nitazoxanide is a US Food and Drug Administration (FDA) approved antiparasitic medicine, that physiologically-based pharmacokinetic (PBPK) modeling has indicated may provide antiviral concentrations across the dosing interval, when repurposed at higher than approved doses.

Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial.

Background: No phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients.

Methods: This was a multicentre, placebo-controlled, double-blind, parallel group, randomised, phase 3 trial done in 24 hospitals in the UK.

Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label, dose-escalating, randomized controlled study.

Objectives: AGILE is a Phase Ib/IIa platform for rapidly evaluating COVID-19 treatments. In this trial (NCT04746183) we evaluated the safety and optimal dose of molnupiravir in participants with early symptomatic infection.

Methods: We undertook a dose-escalating, open-label, randomized-controlled (standard-of-care) Bayesian adaptive Phase I trial at the Royal Liverpool and Broadgreen Clinical Research Facility.

AGILE: a seamless phase I/IIa platform for the rapid evaluation of candidates for COVID-19 treatment: an update to the structured summary of a study protocol for a randomised platform trial letter.

Background: There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g.

Fractional flow reserve derived from computed tomography coronary angiography in the assessment and management of stable chest pain: the FORECAST randomized trial.

Aims: Fractional flow reserve (FFRCT) using computed tomography coronary angiography (CTCA) determines both the presence of coronary artery disease and vessel-specific ischaemia. We tested whether an evaluation strategy based on FFRCT would improve economic and clinical outcomes compared with standard care.

Methods And Results: Overall, 1400 patients with stable chest pain in 11 centres were randomized to initial testing with CTCA with selective FFRCT (experimental group) or standard clinical care pathways (standard group).

Neurally adjusted ventilatory assist versus pressure support ventilation: a randomized controlled feasibility trial performed in patients at risk of prolonged mechanical ventilation.

Background: The clinical effectiveness of neurally adjusted ventilatory assist (NAVA) has yet to be demonstrated, and preliminary studies are required. The study aim was to assess the feasibility of a randomized controlled trial (RCT) of NAVA versus pressure support ventilation (PSV) in critically ill adults at risk of prolonged mechanical ventilation (MV).

Methods: An open-label, parallel, feasibility RCT (n = 78) in four ICUs of one university-affiliated hospital.

Neonatal mannequin comparison of the Upright self-inflating bag and snap-fit mask versus standard resuscitators and masks: leak, applied load and tidal volumes.

Objective: Neonatal mask ventilation is a difficult skill to acquire and maintain. Mask leak is common and can lead to ineffective ventilation. The aim of this study was to determine whether newly available neonatal self-inflating bags and masks could reduce mask leak without additional load being applied to the face.

Guilty by dissociation-development of gas chromatography-mass spectrometry (GC-MS) and other rapid screening methods for the analysis of 13 diphenidine-derived new psychoactive substances (NPSs).

The prevalence of new psychoactive substances (NPSs) in forensic casework has increased prominently in recent years. This has given rise to significant legal and analytical challenges in the identification of these substances. The requirement for validated, robust and rapid testing methodologies for these compounds is obvious.

The accuracy of delivery of target pressures using self-inflating bag manometers in a benchtop study.

Aim: We tested whether operators using manometers attached to self-inflating bags could accurately deliver set targeted peak inspiratory pressures (PIPs) compared to the Neopuff(™) T-piece resuscitator (TPR).

Methods: Participants provided positive pressure ventilation to a leak-free neonatal test lung at a rate of 60 inflations/min and a flow of 8 L/min. Participants used three manometers attached to self-inflating bags and a Neopuff(™) TPR to target PIPs of 20, 30 and 40 cmH2 O on each device.

An integrative biological approach to the analysis of tissue culture data: application to the antitumour agent RHPS4.

We describe a mathematical model of cell growth and death and explain how it can be used to integrate data from classic tissue culture experiments on antitumour agents and thus aid the identification of their mechanism of action. Experimental data relating to time- and dose-dependent changes in growth rate, cell cycle distribution, plus apoptotic and senescent fractions, are reinterpreted in terms of modulations to kinetic parameters that describe the rates at which cells transit between phenotypic compartments. The mathematical model is analytical, in the sense that the kinetic parameters are calculated from the experimental data directly, without any fitting process.

Management of pain due to sickle cell disease.

Assessment of pain in sickle cell disease is briefly described and a case of a 32-year-old Nigerian woman who had sickle cell pain is presented. The management and outcomes of her care in the UK are described and commentaries are presented on this case of sickle cell pain by specialists from Spain and The Netherlands.