Nil per os in the management of oropharyngeal dysphagia-exploring the unintended consequences.

Nil per os (NPO), also referred to as Nil by Mouth (NBM), is a health-related intervention of withholding food and fluids. When implemented in the context of a person with dysphagia, NPO aims to mitigate risks of aspiration. However, evidence demonstrating that NPO is beneficial as an intervention for people with dysphagia is lacking. This paper explores the theoretical and empirical evidence relating to the potential benefits and adverse effects of NPO and asserts that NPO is not a benign intervention. This paper argues for applying an ethics framework when making decisions relating to the use of NPO as an intervention for dysphagia, in particular addressing informed consent and a person's right to self-determination.

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. Participants (adult outpatients with PCR-confirmed SARS-CoV-2 infection within 5 days of symptom onset) were randomized 2:1 in groups of 6 participants to 300, 600 and 800 mg doses of molnupiravir orally, twice daily for 5 days or control. A dose was judged unsafe if the probability of 30% or greater dose-limiting toxicity (the primary outcome) over controls was 25% or greater. Secondary outcomes included safety, clinical progression, pharmacokinetics and virological responses. RESULTS: Of 103 participants screened, 18 participants were enrolled between 17 July and 30 October 2020. Molnupiravir was well tolerated at 300, 600 and 800 mg doses with no serious or severe adverse events. Overall, 4 of 4 (100%), 4 of 4 (100%) and 1 of 4 (25%) of the participants receiving 300, 600 and 800 mg molnupiravir, respectively, and 5 of 6 (83%) controls, had at least one adverse event, all of which were mild (≤grade 2). The probability of ≥30% excess toxicity over controls at 800 mg was estimated at 0.9%. CONCLUSIONS: Molnupiravir was safe and well tolerated; a dose of 800 mg twice daily for 5 days was recommended for Phase II evaluation.

Oral health is Essential to the Well-Being of Older People.

Although the highest attainable standard of health is a fundamental human right, oral health is often not considered an important component of overall health. Older people experience poorer quality of life due to discomfort and uncleanliness of their mouth and there continue to be barriers within health systems that contribute to this poor oral health. This paper advocates for oral health to be considered part of the basic human right to good health care and discusses how stakeholders can collaborate and work together to begin to meet the needs of this population, proposing solutions and recommendations to bring about change.

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. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pressing need to investigate novel candidates within early phase trial platforms, from which promising candidates can feed into established later phase platforms. AGILE grew from a UK-wide collaboration to undertake early stage clinical evaluation of candidates for SARS-CoV-2 infection to accelerate national and global healthcare interventions. METHODS/DESIGN: AGILE is a seamless phase I/IIa platform study to establish the optimum dose, determine the activity and safety of each candidate and recommend whether it should be evaluated further. Each candidate is evaluated in its own trial, either as an open label single arm healthy volunteer study or in patients, randomising between candidate and control usually in a 2:1 allocation in favour of the candidate. Each dose is assessed sequentially for safety usually in cohorts of 6 patients. Once a phase II dose has been identified, efficacy is assessed by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol can be adapted for each candidate based on prior knowledge of the candidate (i.e. population, primary endpoint and sample size can be amended). This information is detailed in each candidate specific trial protocol of the master protocol. DISCUSSION: Few approved treatments for COVID-19 are available such as dexamethasone, remdesivir and tocilizumab in hospitalised patients. The AGILE platform aims to rapidly identify new efficacious and safe treatments to help end the current global COVID-19 pandemic. We currently have three candidate specific trials within this platform study that are open to recruitment. TRIAL REGISTRATION: EudraCT Number: 2020-001860-27 14 March 2020 ClinicalTrials.gov Identifier: NCT04746183  19 February 2021 ISRCTN reference: 27106947.

Improving the oral health of older people in hospital.

OBJECTIVE: To determine whether an oral health therapist daily oral hygiene intervention, compared with the same routine performed by nurses with some dental support, can improve the oral health of older inpatients. METHODS: A prospective study was conducted at two tertiary referral hospitals with three phases: (i) pre-intervention (PI) usual oral care; (ii) oral health therapist intervention (OHTI); and (iii) nurse-led intervention (NI). Oral health was assessed with the Oral Health Assessment Tool. RESULTS: Three hundred and fifty nine patients participated across three phases (PI (n = 206); OHTI (n = 77); NI (n = 76)). In the intervention groups, there was a significant decrease in 'unhealthy' oral cleanliness at day 7, OHTI; 86 to 53% (P < 0.001), NI; 80 to 50% (P < 0.001) compared to PI; 78 to 72% (P > 0.14). Movement from 'unhealthy' oral cleanliness at day 1 to 'healthy' at day 7 was significantly higher in the OHTI (35%) and NI (37%) compared to PI (17%) (P < 0.001). CONCLUSION: With support, nurses can improve the oral health of older patients similarly to an oral health therapist.

The oral health status of older patients in acute care on admission and Day 7 in two Australian hospitals.

Objective: to determine the oral health status of older patients in acute care wards at admission and after 7 days. Methods: a prospective descriptive study was conducted in two acute tertiary referral hospitals in New South Wales, Australia. Oral health was assessed on admission (within 24 h) and Day 7 using the Oral Health Assessment Tool. Results: a total of 575 patients were admitted under the Geriatric teams at the two hospitals. Four hundred and thirty-five (76%) patients had oral cleanliness (debris) scores in the 'not healthy' range with food particles, tartar or plaque evident in at least one area in most areas of the mouth, teeth or dentures. At Day 7 206 were reassessed. One hundred and forty-nine patients (73%) were in the 'not healthy' range and of these 127 (62%) had the same score as on admission. Conclusion: poor oral health is common in older people admitted to hospital acute care wards and does not improve over a 7-day period. Given the link between oral health and general health the next steps are to determine how oral health can be improved in this setting and see whether this leads to better patient outcomes.