Dystonia is a hyperkinetic movement disorder characterised by sustained or intermittent muscle contractions resulting in abnormal movements and postures (Albanese, A. et al. Phenomenology and classification of dystonia: A consensus update. Movement Disorders vol. 28 863–873 (2013) and up to 70% of individuals with dystonia report sleep difficulties (Bailey, G. A. et al. Sleep disturbance in movement disorders: Insights, treatments and challenges. J. Neurol. Neurosurg. Psychiatry 92, 723–736 (2021)).
Introduction
Gold standard sleep assessments require overnight admission to a sleep clinic with polysomnography – which can be expensive and time-consuming. Wearable devices, paired with a mobile application, provide the opportunity for a minimally intrusive monitoring system with minimal input from the patients.
Methodology
We recruited 50 individuals diagnosed with dystonia and 47 age- and sex-matched unaffected controls. Our primary objective was to identify sleep disturbances by comparing accelerometer-determined sleep variables between the cohorts.
Individuals wore a consumer-grade wrist device (Garmin vívosmart® 4) continuously over seven days on their non-dominant wrist, while completing patient-reported outcomes (PROs) using Aparito’s clinical trial platform.
Aparito utilised the Garmin health SDK to access the raw accelerometer data which is not otherwise available via Garmin Connect.
In this whitepaper we:
Show the feasibility of using wearable devices in estimating sleep measures and architecture
Emphasise the need for clinicians to screen for sleep disturbances as part of routine clinical assessments
Identify that monitoring of sleep may be important for the prevention and management of non-motor symptoms
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Sleep disturbances are an important component of the phenotypic profile of adult-onset idiopathic focal cervical dystonia (AOIFCD), reported in up to 70% of patients. Given the chronic nature of dystonia, greater understanding of potential sleep disturbances would require minimally intrusive monitoring and minimal input from the patients themselves.
The aims and objectives of this study were to
To analyse sleep stages in detail amongst individuals diagnosed with AOIFCD using wrist-worn accelerometers and subjective PROs
Evaluate concordance between subjective PROs and objective accelerometer measures
Grace A Bailey1, Megan Wadon1, Sandra Komarzynski2, Konrad Szewczyk-Krolikowski3, Peter Moore4, Clare Matthews2, Elin Haf Davies2, Kathryn J Peall1
1Neuroscience and Mental Health Research Institute, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK 2Aparito Limited, Wrexham, UK 3North Bristol NHS Trust, UK 4The Walton Centre NHS Foundation Trust, UK
In February 2022 we announced the launch of the Digital Tools for Rare Disease project (DT4RD), a product of the Rare Disease Research call placed by the European Joint Programme on Rare Diseases in partnership with Fondation Maladies Rares, sponsored by Chiesi and CSL Behring.
The project’s aim is to develop non-invasive tools for measuring mobility in rare disease patients with state-of-the-art wearable sensors integrated with Aparito’s Atom5TM clinical trial platform to capture physiological and psychosocial parameters.
Having reached a major milestone with the first successful technical integration, we caught up with the team to find out how the collaboration between Aparito and Yumen Bionics has progressed!
“With DT4RD we set out to create a pioneering toolbox to research and collect data from patients with neuromuscular disease,” says Sjaak Kok, a Development Engineer at Yumen Bionics, a specialist in developing assistive exoskeletons and motion sensors for Duchenne Muscular Dystrophy patients, “and we see DT4RD as a pilot programme for how a device like ours should be built to connect to a healthcare platform.”
Yumen Bionics’ non-motorized upper-body exoskeleton provides close-to-body support that cancels out gravity in every possible natural position of both arms, the data from which is captured alongside patient questionnaires, video capture, and data from other wearable devices to provide rich insight into the daily life of patients living with muscular dystrophy.
Maintaining a patient-centric approach has been a guiding principle and as Caroline LeBarbier, Project Manager at Aparito, points out, “We want the patient to be as autonomous as possible and able to apply and remove the device themselves, and that’s something also that was discussed extensively. We keep in mind the patient burden, not only like the weight of the device but also how long they’re going to wear it and how comfortable it is.”
Aparito and Yumen Bionics have successfully navigated a number of early challenges: the first being how to devise a data structure that was minimal to account for the small memory available in the microchips on the Yumen device!
The first big challenge
Collaborating remotely via bi-weekly meetings, the teams formulated a method to transmit large data packets into the Aparito platform, gradually increasing the amount of data captured.
“We had to agree on a data structure that could be transmitted and received from the Yumen device to the Atom5TM platform”, said Christian Weaves, a Full Stack Developer at Aparito. “We started off with just sending one encrypted data packet and cross-referencing what had arrived with what was sent and then we ramped it up gradually to fifteen minutes’ worth of data.”
This milestone sets a great standard for others wanting to replicate the challenge of capturing more physical data in a digital platform. We’re now able to connect our device’s data to the DT4RD toolbox alongside other wearable data and the platform’s video capture.
Alifandri Sangadji, Sensor Electronics and Embedded Systems Development Engineer at Yumen Bionics
With data capture and transmission in place, the next stage of development is the user interface for clinicians and patients and the Aparito Data Science team can access the data for interpretation and analysis – great progress so far!
Acknowledgements
None of this would be possible without the support of Paris Institut de Myologie (Institute of Myology), The John Walton Muscular Dystrophy Research Centre at Newcastle University, Metabolic Support UK, and our biotechnology and pharmaceutical industry partners, CSL Behring and Chiesi Pharmaceuticals.
As the project progresses we’ll provide updates about this pioneering work!
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Aparito were fortunate to have the brilliant Rhian Thomas-Turner join us on secondment in the capacity of Head of Academic Partnerships.
As keen proponents of cross-sector working and the collective effort to drive more collaboration between industry and academia, we asked Rhian for her thoughts on her time at Aparito and the benefits of seeing things from both sides of the table.
‘I have known Elin Haf Davies since we met at a paediatric medicines conference in 2018. I discovered that through Aparito, she was working to improve clinical trials for patients through the use of technology.
I also attended Aparito’s fifth birthday celebration in 2019 and was excited by the potential that Atom5TM had in making research better for all patients, but particularly for child participants, although at this point I still had a limited understanding of how that technology worked and how it could practically be integrated into clinical trials.
I have now worked in child health research for nearly 11 years; six of those years working in clinical trial delivery after establishing Wales’ first and only clinical research facility for children and young people at the Noah’s Ark Children’s Hospital for Wales. Children need access to good quality clinical trials to support better health outcomes and to provide a greater understanding of how well medicines work for them.
However, children don’t always want to be at a hospital site, they want to be with their friends, doing activities that they find fun, they don’t want to be, as one mum described it, “othered”, made to feel different to their peers.
This is why I believe that technology can make such a big difference to paediatric clinical trials and to the lives of children who are participating in them and why I felt it important to fully understand the tools that could support this change.
A secondment at Aparito offered this opportunity.
The past six months have given me a real opportunity to understand the different tools that can be used to support patients in their own homes, in particular, I’ve had the chance to work on the vTUG, a virtual timed up-and-go test that can be used to assess gait and balance in patients with neurological conditions.
Together with studies using video assessments, I’ve engaged with a number of academic studies that use ePROs, and electronic Patient Reported Outcomes, capturing how the patient feels using a much more accurate electronic record rather than pen and paper.
In addition, I’ve seen how wearables can be integrated into studies, continuously recording data to give a real-time picture of the patient’s health, and creating digital biomarkers that can and will revolutionise drug development.
However, I didn’t just learn about Atom5™; I learnt to drive a tractor and to herd sheep but seriously, I also came to understand why cross-sector working is so vital to improving patient outcomes and that those of us who work in large institutions need to learn how to better work with our SME colleagues.
Firstly, cross-sector working provides opportunities to find solutions to problems that no one sector can solve alone, such as the development of new drugs for the paediatric population. ‘Moonshot’ is the word of the moment, but it is a recognition that solutions to problems can and are likely to come from all various sources. Secondly, working with SMEs. SMEs can bring agility to projects that an institution the size of the NHS is not able to. Having experienced, albeit a short period of time working for an SME, I feel that we need to recognise that they cannot work for free, they are not a ‘big industry’ with deep pockets, and we need to properly cost them into our projects and we cannot just expect them to provide ‘in-kind’ contributions.
We, in the NHS, can also be easier to work with! Routes in are often too difficult and that can be a detriment to our patients and our services. We need to recognise the opportunities of working with industry, not just see the risks, so we can provide a sustainable future for the NHS.
I want to say thank you to the whole Aparito team for making me feel welcome. This secondment has taken me out of my comfort zone but has given me a lot back!”
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Last week our CEO Dr Elin Haf Davies was in San Diego to participate in the Illumina Genomics Forum, a four-day event with an impressive lineup of speakers including Former President Barack Obama, Bill Gates (Gates Foundation), Anne Wojcicki (23&me – consumer genetics) and tennis star Chris Evert, all with a personal ambition to realise the value of the genome.
Elin Haf moderated a panel on the need to end the odyssey of diagnosis, a particularly important issue for the rare disease community who can often encounter numerous incorrect diagnoses and as long as a 7-year delay in diagnosis, delaying access to genetic counselling, opportunity to take part in clinical trials, and access to treatment.
With global representation from the UK, US, Brazil and Israel on the panel the complexities of cultural, religious and infrastructure differences were discussed. But two common fundamental aspects of the global widespread adoption of whole genome sequencing agreed upon by all are trust and communication, tied to the importance of a truly informed consent process.
While the science and technology might be already here, society as a whole needs an opportunity to keep afoot of the rapidly changing approach to medical care and the impact on them as individuals, families and communities, set against a backdrop of increased distrust towards government, big tech and science.
Newborn screening that enables access to life-saving treatment before a baby becomes critically ill is an obvious advantage. But what other risk factors, carrier status and variants do excited new parents need to know within two weeks of birth?
Can too much data be a bad thing?
Does data really empower individuals to lead to better health?
Data is knowledge and knowledge is power is the old adage but is it true for all individual people in relation to their own health?
Many similar challenges apply to the widespread adoption of digital health. Cost, the vast amount of data, secure and accessible infrastructure, equity and education.
As we endeavour to make digitised clinical trials, electronic Clinical Outcome Assessments and hybrid or decentralised clinical trials a viable patient-centric option for the rare disease community most of the barriers are those linked to beliefs, perception and fear of change or the unknown.
The world is changing. Genomics and digital health are here to stay. Pandora is out of the box! It’s down to us to ensure that communication and trust are integrated into the development of both by building strong relationships with individual people, patient communities, regulators and industry.
To finish with an old African proverb, which is apt to note as we risk creating more inequalities in health,
“If you want to go fast, go alone. If you want to go far, go together.”
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We showed the usability of the DMD Home app as a method to video record motor tasks, deliver instructions to participants, and to collect patient-reported outcomes (e.g., DMD-QoL).
We also demonstrated that computer vision analysis with OpenPose allowed us to characterise movement in an objective manner and using parameters other than conventional clinical assessments. While the sample size was small and participants were self-assigned to the different cohorts, hence not having a representative sample of all DMD stages, we could still extract highly relevant information particularly from upper body tasks from participants who were in the ambulant and non-ambulant stages of the disease.
Abstract
Digital health technologies are transforming the way health outcomes are captured and measured. Digital biomarkers may provide more objective measurements than traditional approaches as they encompass continuous and longitudinal data collection and use of automated analysis for data interpretation. In addition, the use of digital health technology allows for home-based disease assessments, which in addition to reducing patient burden from on-site hospital visits, provides a more holistic picture of how the patient feels and functions in the real world.
Tools that can robustly capture drug efficacy based on disease-specific outcomes that are meaningful to patients, are going to be key to the successful development of new treatments. This is particularly important for people living with rare and chronic complex conditions, where therapeutic options are limited and need to be developed using a patient-focused approach to achieve the biggest impact. Working in partnership with patient Organisation Duchenne UK, we co-developed a video-based approach, delivered through a new mobile health platform (DMD Home), to assess motor function in patients with Duchenne muscular dystrophy (DMD), a genetic, rare, muscular disease characterized by the progressive loss of muscle function and strength.
Motor function tasks were selected to reflect the “transfer stage” of the disease, when patients are no longer able to walk independently but can stand and weight-bear to transfer. This stage is important for patients and families as it represents a significant milestone in the progression of DMD but it is not routinely captured and/or scored by standard DMD clinical and physiotherapy assessments.
A total of 62 videos were submitted by eight out of eleven participants who onboarded the app and were analysed with pose estimation software (OpenPose) that led to the extraction of objective, quantitative measures, including time, pattern of movement trajectory, and smoothness and symmetry of movement. Computer vision analysis of video tasks to identify voluntary or compensatory movements within the transfer stage merits further investigation.
Longitudinal studies to validate DMD home as a new methodology to predict progression to the non-ambulant stage will be pursued.
Aparito is delighted to contribute to a landmark Long COVID paper with the Centre for Patient Reported Outcome Research (CPROR) team at the University of Birmingham as part of the Therapies for Long COVID (TLC) study.
The Aparito Atom5™ platform collected data from patients allowing them to self-report symptoms, quality of life and work capabilities.
“Symptoms and risk factors for long COVID in non-hospitalized adults” provides a comprehensive assessment of symptoms and risk factors for Long COVID.
Published in Nature Medicine, the study found that people with Long COVID experience a wider set of symptoms than is officially recognised by the WHO.
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID.
We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection.
Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02–8.39), hair loss (3.99, 3.63–4.39), sneezing (2.77, 1.40–5.50), ejaculation difficulty (2.63, 1.61–4.28) and reduced libido (2.36, 1.61–3.47).
Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.
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Harnessing the power of patients: Developing and validating the Neuronopathic Gaucher Disease Patient Reported Outcomes (nGD-PRO) and Observer Reported Outcomes (nGD-ObsRO) to measure HRQoL in patients with Gaucher Disease Type 2 and Type 3 documents over three and a half years of research to develop and assess the content validity ofnGD-specific patient-reported outcomes (PRO) and observer-reported outcomes (ObsRO) measure in partnership with patients, caregivers, and other stakeholders as part of the GARDIAN project.
GARDIAN is a patient-owned registry developed by the IGA together with Cerner Enviza and Aparito to improve Gaucher disease understanding, management and support for patients with Gaucher Disease Type 2 and Type 3. It also provides a research platform to provide evidence-based data for advancing disease management, designing safer treatments and improving patient outcomes.
This poster documents how the Neuronopathic Gaucher Disease Patient Reported Outcomes (nGD-PRO) and Observer Reported Outcomes (nGD-ObsRO) were developed and validated to measure HRQoL in patients with Gaucher Disease Type 2 and Type 3!
On Amyotrophic lateral sclerosis (ALS) awareness day, we are extremely proud and happy to announce our partnership with ALS Liga Belgium and welcome them into Aparito’s Patient Group Accelerator Programme!
About the Accelerator
Aparito launched the Accelerator in 2020 to provide an initiative where a company and patient community, with the support of patient advocacy groups, can collaborate as peers.
The Accelerator is designed to understand and ideally fulfil the patients’ needs, by working closely with patient organisations and finding new endpoints that would be relevant to their specific conditions.
By developing technological solutions, novel endpoints and digital biomarkers (Digital vs traditional) designed for and with the patients (Patient involvement), the objective is to collect sufficient exploratory data as a starting point for future validation and use in clinical trials.
About ALS
ALS, also known as Motor Neurone Disease (MND) affects nerve cells in the brain and spinal cord that control voluntary movements of muscles, progressively causing muscle weakness, paralysis and eventually death, within 2-5 years of diagnosis. The cause of ALS is still unknown, and the course of the disease and life expectancy varies from patient to patient. ALS results in loss of strength in hands or limbs and then spreads to other parts of the body. As the disease progresses, patients lose the ability to swallow, speak and breathe.
While there is no cure for ALS yet, a few approved treatments help slow the progression and manage ALS symptoms and there are new experimental drugs in the ALS treatment pipeline. Due to its rapid progression, ALS may benefit from specific digital biomarkers that would allow more frequent remote monitoring and mitigate the high attrition rates of ALS patients involved in clinical trials.
The first stage of the Accelerator programme will be dedicated to exploring and understanding the unmet needs of ALS patients regarding digital outcomes measures through a co-creation approach in partnership with the ALS Liga Belgium.
Using Aparito’s Atom5TM we will co-develop a prototype to test the usability and potential clinical utility of such a platform to capture and analyse digital biomarkers that are relevant to ALS patients.
We are very excited to launch this new partnership with ALS Liga Belgium as part of the Accelerator Programme. This is an excellent opportunity to co-develop patient-driven solutions to support the ALS patient community
In our second year of the Patient Group Accelerator we are thrilled to see the programme grow from strength to strength. The Accelerator is a critical part of Aparito’s DNA and vision for a patient centric solution to conveying what’s important to them. Partnering with ALS Belgium is an exciting reflection of this and a strong addition to the partnership that we have with DuchenneUK and PCD Support UK
Aparito is a global health tech company that brings clinical trials to patients and unlocks real-world data through mobile apps, video assessments & wearable devices. Aparito provides a patient-centric platform that integrates clinical & regulatory expertise to capture patient data and develop digital endpoints for hybrid and decentralised clinical trials.
Earlier this year Aparito received the EURORDIS Company Award for Health Technology at the 2022 EURORDIS Black Pearl Awards, a great recognition from the rare disease community to acknowledge that Aparito makes a difference in the rare disease space.
Learn more about Aparito’s Patient Group Accelerator Programme here.
SARAhome is a digital assessment of ataxia at home. Ataxias are a heterogeneous group of rare movement disorders and the core clinical features of these disorders are progressive gait disturbance, impaired coordination and speech disturbance.
Aparito documented the story behind the development of SARAhome by Dr Marcus Grobe-Einsler MD and the team at Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. and below is an extract from the paper that led to this breakthrough!
Background
Clinical scales such as the Scale for the Assessment and Rating of Ataxia (SARA) cannot be used to study ataxia at home or to assess daily fluctuations.
The objective of the current study was to develop a video-based instrument, SARAhome, for measuring ataxia severity easily and independently at home.
Methods
Based on feasibility of self-application, we selected 5 SARA items (gait, stance, speech, nose-finger test, fast alternating hand movements) for SARAhome (range, 0–28). We compared SARAhome items with total SARA scores in 526 patients with spinocerebellar ataxia types 1, 2, 3, and 6 from the EUROSCA natural history study.
To prospectively validate the SARAhome, we directly compared the self-applied SARAhome and the conventional SARA in 50 ataxia patients.
To demonstrate feasibility of independent home recordings in a pilot study, 12 ataxia patients were instructed to obtain a video each morning and evening over a period of 14 days.
