Pilot observational cohort study to determine whether waveform and flow traces from mechanical insufflation-exsufflation (MI-E) can be used to identify laryngeal responses to MI-E and thus optimise treatment algorithms in neuromuscular patients in a tertiary centre: a protocol description.

INTRODUCTION: Patients with neuromuscular disease often have a weak and ineffective cough due to respiratory muscle weakness. One treatment option is mechanical insufflation-exsufflation (MI-E), also known as cough assist, which is known to increase cough strength. However, some patients have a laryngeal response to MI-E, which can make the treatment ineffective. Currently, the only method for assessing this is via nasal endoscopy while using MI-E. Some MI-E devices have onboard secure data (SD) cards, which allow the visualisation of waveforms. We hypothesise that the waveforms can be used to identify laryngeal responses to the MI-E. METHODS AND ANALYSIS: Participants will complete baseline assessments of spirometry, peak cough flow and sniff nasal inspiratory pressure. A nasal endoscope will be used to visualise the larynx during simultaneous MI-E via a mask with a drilled hole. MI-E will be delivered by an experienced physiotherapist. Four cycles of MI-E at a range of prescriptions will be delivered. MI-E waveforms will be downloaded into Care Orchestrator Essence software (Philips, Murraysville). Data will be collected prospectively and reviewed in a descriptive context, providing trends and potential rationales describing the waveforms in comparison to the nasal endoscope videos. ETHICS AND DISSEMINATION: This protocol has been reviewed by the East of England-Cambridge Central Research Ethics Committee, who have granted a favourable ethical opinion. The study opened to recruitment in January 2022 and aims to publish trial results in June 2024. TRIAL REGISTRATION NUMBER: NCT05189600.

Trial of N-Acetyl-l-Leucine in Niemann-Pick Disease Type C.

BACKGROUND: Niemann-Pick disease type C is a rare lysosomal storage disorder. We evaluated the safety and efficacy of N-acetyl-l-leucine (NALL), an agent that potentially ameliorates lysosomal and metabolic dysfunction, for the treatment of Niemann-Pick disease type C. METHODS: In this double-blind, placebo-controlled, crossover trial, we randomly assigned patients 4 years of age or older with genetically confirmed Niemann-Pick disease type C in a 1:1 ratio to receive NALL for 12 weeks, followed by placebo for 12 weeks, or to receive placebo for 12 weeks, followed by NALL for 12 weeks. NALL or matching placebo was administered orally two to three times per day, with patients 4 to 12 years of age receiving weight-based doses (2 to 4 g per day) and those 13 years of age or older receiving a dose of 4 g per day. The primary end point was the total score on the Scale for the Assessment and Rating of Ataxia (SARA; range, 0 to 40, with lower scores indicating better neurologic status). Secondary end points included scores on the Clinical Global Impression of Improvement, the Spinocerebellar Ataxia Functional Index, and the Modified Disability Rating Scale. Crossover data from the two 12-week periods in each group were included in the comparisons of NALL with placebo. RESULTS: A total of 60 patients 5 to 67 years of age were enrolled. The mean baseline SARA total scores used in the primary analysis were 15.88 before receipt of the first dose of NALL (60 patients) and 15.68 before receipt of the first dose of placebo (59 patients; 1 patient never received placebo). The mean (±SD) change from baseline in the SARA total score was -1.97±2.43 points after 12 weeks of receiving NALL and -0.60±2.39 points after 12 weeks of receiving placebo (least-squares mean difference, -1.28 points; 95% confidence interval, -1.91 to -0.65; P<0.001). The results for the secondary end points were generally supportive of the findings in the primary analysis, but these were not adjusted for multiple comparisons. The incidence of adverse events was similar with NALL and placebo, and no treatment-related serious adverse events occurred. CONCLUSIONS: Among patients with Niemann-Pick disease type C, treatment with NALL for 12 weeks led to better neurologic status than placebo. A longer period is needed to determine the long-term effects of this agent in patients with Niemann-Pick disease type C. (Funded by IntraBio; ClinicalTrials.gov number, NCT05163288; EudraCT number, 2021-005356-10.).

Rehabilitation using virtual gaming for Hospital and hOMe-Based training for the Upper limb post Stroke (RHOMBUS II): protocol of a feasibility randomised controlled trial.

INTRODUCTION: Upper limb (UL) rehabilitation is most effective early after stroke, with higher doses leading to improved outcomes. For the stroke survivor, the repetition may be monotonous. For clinicians, providing a clinically meaningful level of input can be challenging. As such, time spent engaged in UL activity among subacute stroke survivors remains inadequate. Opportunities for the stroke survivor to engage with UL rehabilitation in a safe, accessible and engaging way are essential to improving UL outcomes following stroke. The NeuroBall is a non-immersive virtual reality (VR) digital system designed for stroke rehabilitation, specifically for the arm and hand. The aim of the Rehabilitation using virtual gaming for Hospital and hOMe-Based training for the Upper limb post Stroke study is to determine the safety, feasibility and acceptability of the NeuroBall as a rehabilitation intervention for the UL in subacute stroke. METHODS AND ANALYSIS: A feasibility randomised controlled trial (RCT) will compare the NeuroBall plus usual care with usual care only, in supporting UL rehabilitation over 7 weeks. Twenty-four participants in the subacute poststroke phase will be recruited while on the inpatient or early supported discharge (ESD) stroke pathway. Sixteen participants will be randomised to the intervention group and eight to the control group. Outcomes assessed at baseline and 7 weeks include gross level of disability, arm function, spasticity, pain, fatigue and quality of life (QoL). Safety will be assessed by recording adverse events and using pain, spasticity and fatigue scores. A parallel process evaluation will assess feasibility and acceptability of the intervention. Feasibility will also be determined by assessing fidelity to the intervention. Postintervention, semistructured interviews will be used to explore acceptability with 12 participants from the intervention group, four from the usual care group and with up to nine staff involved in delivering the intervention. ETHICS AND DISSEMINATION: This trial has ethical approval from Brunel University London's Research Ethics Committee 25257-NHS-Oct/2020-28121-2 and the Wales Research Ethics Committee 5 Bangor (Health and Care Research Wales) REC ref: 20/WA/0347. The study is sponsored by Brunel University London. CONTACT: Dr Derek Healy, Chair, University Research Ethics committee (Derek.healy@brunel.ac.uk). Trial results will be submitted for publication in peer-reviewed journals, presented at national and international conferences and distributed to people with stroke. TRIAL REGISTRATION NUMBER: ISRCTN11440079; Pre-results.

Experiences and views of patients, carers and healthcare professionals on using modems in domiciliary non-invasive ventilation (NIV): a qualitative study.

BACKGROUND: Advances in technology means that domiciliary non-invasive ventilation (NIV) devices can be remotely monitored via modems in patients' homes. Possible benefits and challenges of modem technology have yet to be established. This study explored the perspectives and experiences of patients, their carers and healthcare professionals (HCPs) on the addition of modem technology in managing home NIV. METHODS: A qualitative study using a combination of focus groups for HCPs and interviews for carers/patients was undertaken. 12 HCPs and 22 patients/carers participated. These focus groups and interviews were audio-recorded, transcribed verbatim and analysed thematically. RESULTS: Five main themes were identified. 'Surveillance: a paradox of findings': HCPs were concerned about unduly scrutinising patients' lives, potentially impacting on HCP patient relationships. Conversely, patients welcomed modem monitoring and did not express concerns regarding invasion of privacy. 'Sanctions': HCPs reported the modem increased access to care and allowed appropriate assessment of ongoing treatment. 'Complacency and ethics': HCPs expressed concerns patients may become complacent in seeking help due to expectations of modem monitoring, as well as being concerned regarding the ethics of modems. There was a suggestion patients and carers' expectations of monitoring were different to that of clinical practice, resulting in complacency in some cases. 'Increased time for patient focused care': HCPs in the focus groups described a number of ways in which using modems was more efficient. 'Confidence: can be improved with technology': patients and carers were positive about the impact of the modems on their health and well-being, particularly their confidence. CONCLUSION: HCPs expressed concerns about surveillance were not corroborated by patients, suggesting acceptability of remote monitoring. Data suggests a need for increased clarity to patients/carers regarding clinical practice relating to responsiveness to modem data. The issue of complacency requires further consideration. Modem technology was acceptable and considered a useful addition by HCPs, patients and carers. TRIAL REGISTRATION NUMBER: NCT03905382.