Implementation of a simulation free palliative Radiation Therapy pathway: An inter-professional collaborative project.

The Western New South Wales Local Health District (WNSWLHD) has a significant footprint within the state of New South Wales (NSW). Due to the significant size of the WNSWLHD, patients residing in the local health district face many barriers to receiving Radiation Therapy. The inter-professional collaboration behind the successful implementation and evaluation of a simulation free pathway for palliative Radiation Therapy in WNSWLHD will be explored within this narrative. The process known in WNSWLHD as Medical Imaging Simulated Radiation Therapy (MISRT) removes the need for a computed tomography (CT) simulation and allows for palliative Radiation Therapy to be planned on previously acquired diagnostic CT imaging. The implementation of MISRT has required significant inter-professional collaboration. This also extends to inter-centre partnership, intra-district cooperation with Medical Imaging and inter-discipline teamwork amongst Radiation Oncologists, Radiation Oncology Medical Physicists, Radiation Oncology Nursing and Radiation Therapists. The impact and involvement of the inter-disciplinary teamwork will be explored. The methods of implementing MISRT will be outlined covering changes to standard workflow, educational requirements and inclusion criteria. The evaluation of the implementation will also be covered with two evaluation surveys being conducted. Inter-professional communication, education, teamwork and collaboration is highlighted to demonstrate improving access to quality care in a rural and regional healthcare setting whilst reducing known barriers to accessing Radiation Oncology.

Reintroducing face-to-face support alongside remote support to form a hybrid stop smoking service in England: a formative mixed methods evaluation.

BACKGROUND: During the COVID-19 pandemic, United Kingdom (UK) stop smoking services had to shift to remote delivery models due to social distancing regulations, later reintroducing face-to-face provision. The "Living Well Smokefree" service in North Yorkshire County Council adopted a hybrid model offering face-to-face, remote, or a mix of both. This evaluation aimed to assess the hybrid approach's strengths and weaknesses and explore potential improvements. METHODS: Conducted from September 2022 to February 2023, the evaluation consisted of three components. First, qualitative interviews involved 11 staff and 16 service users, analysed thematically. Second, quantitative data from the QuitManager system that monitored the numbers and proportions of individuals selecting and successfully completing a 4-week quit via each service option. Third, face-to-face service expenses data was used to estimate the value for money of additional face-to-face provision. The qualitative findings were used to give context to the quantitative data via an "expansion" approach and complementary analysis. RESULTS: Overall, a hybrid model was seen to provide convenience and flexible options for support. In the evaluation, 733 individuals accessed the service, with 91.3% selecting remote support, 6.1% face-to-face, and 2.6% mixed provision. Remote support was valued by service users and staff for promoting openness, privacy, and reducing stigma, and was noted as removing access barriers and improving service availability. However, the absence of carbon monoxide monitoring in remote support raised accountability concerns. The trade-off in "quantity vs. quality" of quits was debated, as remote support reached more users but produced fewer carbon monoxide-validated quits. Primarily offering remote support could lead to substantial workloads, as staff often extend their roles to include social/mental health support, which was sometimes emotionally challenging. Offering service users a choice of support options was considered more important than the "cost-per-quit". Improved dissemination of information to support service users in understanding their options for support was suggested. CONCLUSIONS: The hybrid approach allows smoking cessation services to evaluate which groups benefit from remote, face-to-face, or mixed options and allocate resources accordingly. Providing choice, flexible provision, non-judgmental support, and clear information about available options could improve engagement and match support to individual needs, enhancing outcomes.

A qualitative study exploring the effect of communicating with partially intelligible speech.

Few studies have investigated how individuals with partially intelligible speech choose to communicate, including how, when, and why they might use a speech-generating device (SGD). This study aimed to add to the literature by exploring how this group of individuals use different communication strategies. Qualitative interviews were carried out with 10 participants with partially intelligible speech with the aim of investigating participants' perceptions of modes of communication and communication strategies. Transcripts were analyzed using Framework Analysis to investigate the role of SGDs alongside other communication strategies. Factors that influence why, when, and how a person chooses to communicate were identified and these were interpreted as an explanatory model of communication with partially intelligible speech. Participants described how they made the decision whether to attempt to communicate at all and then which communication method to use. Decision-making was influenced by the importance of the message, how much time is available, past experience, and the communication partner. Each communication attempt adds to an individuals' experience of communicating and influences subsequent decisions. This study suggests that individuals with partially intelligible speech are at risk of reduced communication environments and networks and that current SGDs may not be designed in a way that recognizes their particular needs.

Involving young people in sexual health research and service improvement: conceptual analysis of patient and public involvement (PPI) in three projects.

BACKGROUND: Although increasingly recognised as valuable within sexual and reproductive health (SRH) research and service improvement, examples of patient and public involvement (PPI) are underdocumented, including specific issues relating to young people's involvement. This article aims to contribute to greater transparency about the practical, methodological and ethical considerations of SRH-related PPI with young people, and to offer recommendations for their meaningful involvement. METHODS: Guided by a conceptual tool for evaluating youth participation (the '7P' framework), we analysed learning from PPI within three projects (two academic studies and one service improvement project) that worked with young people to shape sexual health research and practice in Scotland. ANALYSIS: Cross-project analysis of seven interconnected domains (purpose, positioning, perspectives, power relations, protection, place and process) generated productive dialogue about the nuances of meaningfully involving young people in shaping SRH research and services. Key learning includes the importance of: young people's early involvement in agenda-setting for SRH improvement; developing trusting partnerships that can support involvement of diverse groups of young people; creating multiple ways for young people to contribute, including those that do not rely on direct conversation; and formative evaluation of young people's experiences of involvement. CONCLUSIONS: Mainstreaming young people's meaningful involvement in shaping SRH research and services requires systems-level change. Resources are required to support SRH researchers and practitioners to share learning and build sustainable multi-sector partnerships, which in turn can increase opportunities for young people from diverse groups to engage with SRH-related PPI activities.

Policies and interventions to reduce harmful gambling: an international Delphi consensus and implementation rating study.

There is increasing public health concern about harmful gambling, but no consensus on effective policies and interventions to reduce risk and prevent harm has been reached. Focusing on policies and interventions (ie, measures), the aim of this study was to determine if expert consensus could be reached on measures perceived to be effective that could be implemented successfully. Our work involved a pre-registered, three-round, independent Delphi panel consensus study and an implementation rating exercise. A starting set of 103 universal and targeted measures, which were sourced from several key resources and inputs from public health stakeholders, were grouped into seven domains: price and taxation; availability; accessibility; marketing, advertising, promotion, and sponsorship; environment and technology; information and education; and treatment and support. Across three rounds, an independent panel of 35 experts individually completed online questionnaires to rank each measure for known or potential effectiveness. A consensus was reached if at least 70% of the panel judged a measure to be either not effective, moderately effective, or highly effective. Then, each measure that reached a consensus for effectiveness was evaluated on four implementation dimensions: practicability, affordability, side-effects, and equity. A summative threshold criterion was used to select a final optimal set of measures for England. The panel reached consensus on 83 (81%) of 103 measures. Two measures were judged as ineffective by the panel. The remaining 81 effective measures were drawn from all domains (14 of 15 measures in the the marketing, advertising, promotion, and sponsorship domain were judged as effective, whereas five of ten measures in the information and education domain were judged as effective). During the evaluation exercise, the 81 measures were assessed for likelihood of implementation success. This assessment considered the practicality, affordability, ability to generate unanticipated side-effects, and ability to decrease differences between advantaged and disadvantaged groups in society of each measure. We identified 40 universal and targeted measures to tackle harmful gambling (three measures from the price and taxation domain; ten from the availability domain; five from the accessibility domain; six from the marketing, advertising, promotion, and sponsorship domain; eight from the environment and technology domain; three from the information and education domain; and five from the treatment and support domain). Implementation of these measures in England could substantially strengthen regulatory controls while providing new resources. The findings of our work offer a blueprint for a public health approach to preventing harms related to gambling.

Tutorial: guidelines for annotating single-cell transcriptomic maps using automated and manual methods.

Single-cell transcriptomics can profile thousands of cells in a single experiment and identify novel cell types, states and dynamics in a wide variety of tissues and organisms. Standard experimental protocols and analysis workflows have been developed to create single-cell transcriptomic maps from tissues. This tutorial focuses on how to interpret these data to identify cell types, states and other biologically relevant patterns with the objective of creating an annotated map of cells. We recommend a three-step workflow including automatic cell annotation (wherever possible), manual cell annotation and verification. Frequently encountered challenges are discussed, as well as strategies to address them. Guiding principles and specific recommendations for software tools and resources that can be used for each step are covered, and an R notebook is included to help run the recommended workflow. Basic familiarity with computer software is assumed, and basic knowledge of programming (e.g., in the R language) is recommended.

Evaluating a novel cervical orthosis, the Sheffield Support Snood, in patients with amyotrophic lateral sclerosis/motor neuron disease with neck weakness.

Current practice and guidelines recommend the use of neck orthoses for people with amyotrophic lateral sclerosis (ALS) to compensate for neck weakness and to provide surrogate neck control. However, available options are frequently described by patients as restrictive and unsuitable and there was a need for a new device that addressed the needs of people with ALS. This project utilized a co-design process to develop a new neck orthosis that was more flexible yet supportive. Following development of a prototype device, a mixed methods cohort study was undertaken with patients and carers, in order to evaluate the new orthosis. Twenty-six patients were recruited to the study, with 20 of these completing all phases of data collection. Participants described the impact of neck weakness on their life and limitations of existing supports. Evaluation of the new orthosis identified key beneficial features: notably, increased support while providing a greater range of movement, flexibility of use, and improved appearance and comfort. In conclusion, the results of this evaluation highlight the value of this alternative option for people with ALS, and potentially other patient groups who require a neck orthosis.

Head-Up; An interdisciplinary, participatory and co-design process informing the development of a novel head and neck support for people living with progressive neck muscle weakness.

This paper presents the Head-Up project, that aims to provide innovative head support to help improve posture, relieve pain and aid communication for people living with progressive neck muscle weakness. The initial focus is motor neurone disease. The case study illustrates collaborative, interdisciplinary research and new product development underpinned by participatory design. The study was initiated by a 2-day stakeholder workshop followed by early proof-of-concept modelling and patient need evidence building. The work subsequently led to a successful NIHR i4i application funding a 24-month iterative design process, patenting, CE marking and clinical evaluation. The evaluation has informed amendments to the proposed design refered to here as the Sheffield Support Snood (SSS). The outcome positively demonstrates use and performance improvements over current neck orthoses and the process of multidisciplinary and user engagement has created a sense of ownership by MND participants, who have since acted as advocates for the product.

Sumanirole versus placebo or ropinirole for the adjunctive treatment of patients with advanced Parkinson's disease.

The aims of this study were to assess the safety, tolerability, and efficacy of sumanirole, a highly selective D(2) dopamine receptor agonist, versus placebo in subjects with advanced Parkinson's disease (PD), and to demonstrate noninferiority of sumanirole to ropinirole. In this flexible-dose, randomized, double-blind, double-dummy, parallel-group study, 948 subjects were treated with sumanirole 1 to 48 mg/day, ropinirole 0.75 to 24 mg/day, or placebo. Treatment consisted of 13 weeks of dose escalation, 26 weeks of maintenance, and 1 week of tapering. Approximately 70% of subjects treated with either sumanirole or ropinirole completed the study. Statistical significance (P < 0.0001) was achieved when both sumanirole and ropinirole groups were compared with placebo, with mean differences of -7.7 and -8.8 on combined sum of the Unified Parkinson's Disease Rating Scale (UPDRS) part II (average on and off) and part III total scores at the end of maintenance. Noninferiority of sumanirole to ropinirole was also demonstrated, with a sumanirole minus ropinirole difference of 1.17 (90% CI: -0.56 to 2.89). Both dopamine agonists, sumanirole and ropinirole, were statistically superior compared with placebo as adjunctive therapy for patients with advanced Parkinson's disease, based on UPDRS II + III total score. Noninferiority of sumanirole to ropinirole was established, with comparable tolerability profiles.

Differential effects of low and high dose folic acid on endothelial dysfunction in a murine model of mild hyperhomocysteinaemia.

The exact mechanism(s) by which hyperhomocysteinaemia promotes vascular disease remains unclear. Moreover, recent evidence suggests that the beneficial effect of folic acid on endothelial function is independent of homocysteine-lowering. In the present study the effect of a low (400 microg/70 kg/day) and high (5 mg/70 kg/day) dose folic acid supplement on endothelium-dependent relaxation in the isolated perfused mesenteric bed of heterozygous cystathionine beta-synthase deficient mice was investigated. Elevated total plasma homocysteine and impaired relaxation responses to methacholine were observed in heterozygous mice. In the presence of N(G)-nitro-L-arginine methyl ester relaxation responses in wild-type tissues were reduced, but in heterozygous tissues were abolished. Clotrimazole and 18alpha-glycyrrhetinic acid, both inhibitors of non-nitric oxide/non-prostanoid-induced endothelium-dependent relaxation, reduced responses to methacholine in wild-type but not heterozygous tissues. The combination of N(G)-nitro-L-arginine methyl ester and either clotrimazole or 18alpha-glycyrrhetinic acid completely inhibited relaxation responses in wild-type tissues. Both low and high dose folic acid increased plasma folate, reduced total plasma homocysteine and reversed endothelial dysfunction in heterozygous mice. A greater increase in plasma folate in the high dose group was accompanied by a more significant effect on endothelial function. In the presence of N(G)-nitro-L-arginine methyl ester, a significant residual relaxation response was evident in tissues from low and high dose folic acid treated heterozygous mice. These data suggest that the impaired mesenteric relaxation in heterozygous mice is largely due to loss of the non-nitric oxide/non-prostanoid component. While low dose folic acid may restore this response in a homocysteine-dependent manner, the higher dose has an additional effect on nitric oxide-mediated relaxation that would appear to be independent of homocysteine lowering.

Folic acid reverses endothelial dysfunction induced by inhibition of tetrahydrobiopterin biosynthesis.

While folic acid has been shown to reverse endothelial dysfunction, the exact underlying mechanism remains elusive. Here, folic acid reversed both the endothelial dysfunction and increased production of superoxide following depletion of rabbit aortic ring tetrahydrobiopterin (BH4) levels with 2,4-diamino-6-hydroxy-pyrimidine (DAHP) and N-acetyl-5-hydroxy-tryptamine (NAS). Incubation with l-nitroarginine methyl ester also attenuated the production of superoxide. DAHP and NAS reduced BH4 concentrations in both aorta and cultured porcine aortic endothelial cells. Folic acid had no effect on BH4 concentrations in either preparation. The superoxide anion scavenger Tiron but not folic acid reversed the endothelial dysfunction produced in aortic rings by inhibition of copper-zinc superoxide dismutase with diethyldithiocarbamic acid. Neither folic acid nor its metabolite 5-methyltetrahydrofolate prevented the in vitro oxidation of BH4. This study demonstrates that folic acid reverses the endothelial dysfunction induced by BH4 depletion independently of either the regeneration or stabilization of BH4 or an antioxidant effect.

Folate, homocysteine, endothelial function and cardiovascular disease.

Evidence reported from numerous clinical studies over the past decade has revealed an association between increased plasma total homocysteine (tHcy) concentrations and cardiovascular disease (CVD). In addition, epidemiological studies have identified an inverse association between blood folate concentrations, folate intake and cardiovascular endpoints, that are independent of homocysteine. Folic acid supplementation can lower plasma tHcy concentrations safely and inexpensively. Furthermore, folic acid can reverse endothelial dysfunction observed in patients with CVD. This reversal in endothelial dysfunction with folic acid has been shown to be independent of plasma tHcy lowering, suggesting that folate has pleiotropic effects on the vasculature other than homocysteine lowering. In vitro evidence demonstrates that 5-methyltetrahydrofolate (5MeTHF) the main circulating metabolite of folate, can increase nitric oxide production and can directly scavenge superoxide radicals. The potential beneficial role of folic acid supplements on vascular disease are currently being tested in randomized placebo controlled studies.