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\begin{document}

\title{From bed-side to web-side, Advanced-Telemedicine platform for Spinal
Muscular Atrophy}



\author[1]{David korn}%
\author[1]{Beatrice Berti}%
\author[1]{Andrea  Cambieri}%
\author[1]{giovanni scambia}%
\author[1]{paolo sergi}%
\author[1]{emilio meneschincheri}%
\author[1]{daniela leone}%
\author[1]{maria carmela pera}%
\author[1]{concetta palermo}%
\author[2]{Danilo Buonsenso}%
\author[3]{Roberta Onesimo}%
\author[4]{Cristina De Rose}%
\author[3]{Marika Pane}%
\author[3]{Eugenio Mercuri }%
\affil[1]{Policlinico Universitario Agostino Gemelli Dipartimento Scienze della Salute della Donna e del Bambino}%
\affil[2]{Ospedale Pediatrico Bambino Gesu}%
\affil[3]{Policlinico Universitario Agostino Gemelli}%
\affil[4]{Universita Cattolica del Sacro Cuore Sede di Roma}%


\vspace{-1em}



  
  \date{May 18, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
We aimed to assess feasibility, accuracy, satisfaction of an
advanced-telemedicine (A-TM) platform designed for remote physical
evaluation, especially focused on lung auscultation, in spinal muscular
atrophy (SMA) patients. Children affected by type 1 and 2 SMA, typically
present generalized weakness, scoliosis, chest deformities the leading
cause of progressive respiratory insufficiency and recurrent
hospitalization. Covid-19 stimulated efforts to adopt innovative digital
health solutions especially when caring for people living with
disabilities. Because of chest asymmetry and scoliosis, SMA patients are
not always the ideal candidates for telemedicine tools that have proved
to be useful in the general population. 23 children affected by SMA (15
type 1 and 8 type 2) with different degree of scoliosis and chest
asymmetry. Prospective study: We localized optimal thoracic auscultatory
landmarks with traditional stethoscope and lung ultrasound for each
child. Carers were trained to record complete lung auscultation
independently and share data with our physicians via A-TM platform.
After the first remote exam, carers videorecorded their experience
(satisfaction). Our physicians blindly rated the audio files shared via
A-TM which were compared to traditional auscultation findings for each
child. to assess. Overall feasibility and accuracy of carers-performed
remote physical evaluation. Our study showed that remotely performed
lung auscultation was possible in all type 1 and 2 SMA children but
adaptations to find optimal landmarks were needed in cases with
asymmetrical or rotated chest and trunk. A-TM tools may simplify access
to care, reduce logistic/economic burden for families, improve
communication, safety and disease management while limiting infection
exposure.%
\end{abstract}%



\sloppy


\textbf{From \emph{bed-side}to \emph{web-side}, Advanced-Telemedicine
platform for Spinal Muscular Atrophy}

David Korn MD\textsuperscript{1,*}, Beatrice Berti
MD\textsuperscript{2,*}, Daniela Leone PhD\textsuperscript{2}, Concetta
Palermo PhD \textsuperscript{2}, Danilo Buonsenso
MD\textsuperscript{1,3}, Roberta Onesimo PhD\textsuperscript{1},
Cristina De Rose MD\textsuperscript{1}, Maria Carmela Pera
PhD\textsuperscript{2,3}, Andrea Cambieri MD \textsuperscript{4}, Emilio
Meneschincheri\textsuperscript{5}, Paolo Sergi\textsuperscript{5},
Giovanni Scambia MD\textsuperscript{2,6,3}, Marika Pane
PhD\textsuperscript{2,3} and Eugenio Mercuri PhD\textsuperscript{2,3}.

1 Pediatric Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS,
Rome, Italy.

2 Pediatric Neurology Unit and Centro Clinico Nemo, Fondazione
Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

3 Catholic University of Rome, Italy.

4 Healthcare Management - Fondazione Policlinico Universitario Agostino
Gemelli -IRCCS, Rome, Italy.

5 ICT management Fondazione Policlinico Universitario Agostino Gemelli
-IRCCS, Rome, Italy.

6 Ginecology Oncology Unit, Fondazione Policlinico Universitario
Agostino Gemelli -IRCCS, Rome, Italy.

* Both first authors, contributing equally to this paper.

\textbf{Corresponding Authors}

Eugenio Mercuri,

Pediatric Neurology Unit

Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Gemelli
00168, Roma, Italy

Tel.: +39 06 30155340; fax: +39 06 30154363.

E-mail address:

\emph{eugeniomaria.mercuri@unicatt.it}

\textbf{Keywords:} Spinal Muscular Atrophy, Advance-Telemedicine
platforms, Covid-19, Chest and spine deformities

\textbf{Running title:} Advanced-Telemedicine platform for Spinal
Muscular Atrophy

\textbf{Conflicts of Interest and Source of Funding:} All authors
declare that they have not conflict of interest.

\emph{Abstract}

\textbf{Objective:} To assess feasibility, accuracy, satisfaction of an
advanced-telemedicine (A-TM) platform designed for remote physical
evaluation, especially focused on lung auscultation, in spinal muscular
atrophy (SMA) patients. Children affected by type 1 and 2 SMA, typically
present generalized weakness, scoliosis, chest deformities the leading
cause of progressive respiratory insufficiency and recurrent
hospitalization. Covid-19 stimulated an effort to adopt innovative
digital health solutions especially when caring for people living with
disabilities. Because of chest asymmetry and scoliosis, SMA patients are
not always the ideal candidates for telemedicine tools that have proved
to be useful in the general population.

\textbf{Design:} Prospective study.

\textbf{Patients:} 23 children affected by SMA (15 type 1 and 8 type 2)
with different degree of scoliosis and chest asymmetry\textbf{.}

\textbf{Methodology:} We localized optimal thoracic auscultatory
landmarks with traditional stethoscope and lung ultrasound for each
child. Carers were trained to record complete lung auscultation
independently and share data with our physicians via A-TM platform.
After the first remote exam, carers videorecorded their experience
(\emph{satisfaction} ). Our physicians blindly rated the audio files
shared via A-TM which were compared to traditional auscultation findings
for each child. to assess. Overall \emph{feasibility} and\emph{accuracy}
of carers-performed remote physical evaluation.

\textbf{Results:} Our study showed that remotely performed lung
auscultation was possible in all type 1 and 2 SMA children but
adaptations to find optimal landmarks were needed in cases with
asymmetrical or rotated chest and trunk.

\textbf{Conclusion} : A-TM tools may simplify access to care, reduce
logistic/economic burden for families, improve communication, safety and
disease management while limiting infection exposure.

\emph{(249 w)}

\emph{Introduction}

Spinal Muscular Atrophy is a rare neuromuscular disorder caused by
autosomic recessive mutations in the Survival Motor Neuron 1 (SMN1)
gene. According to age of onset and clinical severity, SMA is associated
with different pediatric forms, among them type 1 and 2 are the most
severe ones {[}1{]}. The weakness classically also involves the
respiratory muscles with a typical diaphragmatic breathing pattern, most
obvious in type 1 infants with subsequent need for mechanical
ventilation support, recurrent hospitalization and, before treatment
became available, premature exitus {[}2, 3{]}.

The advent of new therapies increasing SMN protein either by gene
replacement or incrementing SMN2 mRNA splicing, has produced a dramatic
change in progression of the disease, improvement in survival, motor and
respiratory function, more obvious in type 1 infants, who, until the
advent of therapy, rarely survived beyond the 2nd year and never
achieved independent sitting {[}4, 5, 6{]}.

With increased survival it has become even more important to follow
these patients over time. According to the SMA International
Standard-of-Care (SoC), the assessments should be repeated every 3 to 6
months, involving a multidisciplinary team of specialists at tertiary
centers for neuromuscular diseases, for routine
\emph{in-person}assessment and \emph{bed-side} physical evaluations
{[}2, 3{]}.

Unfortunately, as a result of Covid-19 pandemic, the physical access to
care, as well as our chance to guarantee the SoC, became more difficult
since many tertiary centers had to limit routine in-person evaluation,
focus resources and reduce the risk of infection. In order to address
some of the difficulties faced by families to attend routine
assessments, we first developed a ``\emph{contactless} '' patient
video-monitoring platform {[}7{]} to assure a safe, privacy compliant
and reliable access to specialists while providing, through
questionnaires and tutorials, some essential care, including
rehabilitation, that could not be otherwise guaranteed during the
pandemic. While the platform proved to be extremely useful to replace
some of the routine follow up assessments, SMA families were still very
concerned about the difficulties experienced in getting physical
examinations during acute events. Several parents reported that in the
last few months ``red flags'' of respiratory infections, happened to go
unnoticed or underestimated by themselves or local practitioners, who
had little experience with neuromuscular diseases. In some cases that
led to preventable complications which could have been avoided. In
others, the absence of reliable assessment, parents rushed their
children to emergency rooms even if this was often not necessary. And
they were worried it may happen again.

We therefore decided to move beyond the video-monitoring solution to
explore the feasibility of an innovative
home-based\emph{advanced-telemedicine platform} to perform challenging
remote physical evaluation in type 1 and 2 SMA patients. Although there
are many commercially available tools that could have been theoretically
used to perform remote physical evaluation, there were however some
concerns related to their applicability to type1 and 2 SMA patients. The
concerns were related to the chest and trunk appearance of the SMA
patients as most children present with kyphoscoliosis and thoracic
asymmetry, ribs crowding, thoracic organ displacement (Fig. 1), that are
often associated with pulmonary functional impairment and impaired
airway clearance {[}8, 9, 10{]}. This has become particularly true in
type 1 infants who now generally survive beyond the first year but
despite the functional improvements, still have variable degree of trunk
hypotonia and weakness causing kyphoscoliosis that has become one of the
key features of the emerging post treatment new phenotypes.

Because of these concerns, we aimed to explore the feasibility of one of
the advanced telemedicine platforms and explore its possible application
into a clinical SMA setting.

More specifically, we wished to explore feasibility, accuracy, and
experience with home-based virtual physical evaluation, especially
focused on challenging lung auscultation, versus traditional bed-side
exam in type 1 and 2 SMA children with different degrees of scoliosis
and chest asymmetry. Our expectation is to find an innovative solution
to guarantee safety and access to care, reduce infection exposure,
logistic and economic burden for families and improve disease
management, during Covid-19 and beyond.

\textbf{Material and Method}

\emph{1.1 Study Population}

We enrolled 23 consecutive children, aged 0-18 years, with type1 or 2
SMA, regularly followed at our Unit. The study is part of a larger
natural history study on SMA approved by the Ethics Committee of our
Institution, and a fully informed consent from the parents of each
participant was obtained before the study.

For all the participating families, information on type of SMA, degree
of neuroscoliosis/chest deformities, type of treatment, number of
previous lung infections/ICU admissions, type of ventilation
(non-invasive vs mechanical vs spontaneous breathing) were collected in
a dedicated form.

\emph{1.2 Digital Health Solution}

All families who agreed to participate in the study were offered the
possibility to use a new device providing home-based virtual physical
evaluations. Tytocare\selectlanguage{ngerman}® is an all-in-one innovative digital health
solution, FDA/CE approved, Class IIa medical device, designed to perform
on-demand remote physical evaluations. The device mounts 3 different
sensors that allow users to capture and share with their remote
physician: ears-nose-throat (ENT) videos, skin images; heart, lung,
bowel auscultations through a digital stethoscope; heart rate and body
temperature via infrared touchless sensor. The device displays useful
interactive pictures to guide parents through the lung evaluation but
only shows traditional auscultation landmarks, four on the back and four
on the front.

\emph{1.3 Lung Ultrasound point of care}

Lung Ultrasound (LUS) was performed to assess optimal lung auscultation
landmarks in children with different degrees of scoliosis and chest
asymmetry and to detect areas of atelectasis, air trapping, pleural
effusion, lung consolidations and other anomalies.

The ultrasound machine ESAOTE MyLab \selectlanguage{english} 40, complies with the Medical
Device Directive (MDD) 93 \textbackslash{} 42 \textbackslash{} EEC and
subsequent amendments. In accordance with this directive, Esaote has
classified it as Class IIa devices. The preset used was small parts.
Linear probe (12 - 6 MHz) was used in preschool children. In older
children, we used a curved probe (8 - 5 MHz). The focus was always
positioned at the level of the pleural line. Images and clips were
stored and archived. The ultrasound scans were performed by
pediatricians and pediatric residents with certifications and / or with
an experience of at least 3 years of practice with LUS.

The scans were made by investigating the anterior, lateral and posterior
regions of the bilaterally thorax and placing the probe transversely and
longitudinally along the lines considered traditional ultrasound
findings: the parasternal line, the axillary line and the paravertebral
line so as to fully explore the chest wall according to a methodical
scheme previously described {[}11{]}. To investigate the anterior and
lateral lung fields, patients were positioned, according to age, in a
seated or supine position. The posterior lung fields have been explored
in lateral decubitus and in sitting position.

\emph{1.4 Study method}

We designed a two-steps, pilot study to compare home-based virtual care
vs. in-person physical evaluation. Two different units: a ``bed-side''
and a ``remote'' evaluation team were recruited.

The study was divided in three phases:

1. \emph{Identification of the auscultatory landmarks in SMA patients
and concordance with the standard landmarks}

Children were first assessed during one of the routine consultations by
a pediatric neurologist with expertise in SMA, one pediatrician expert
in digital health and one pediatric ultrasonographer who were in charge
of locating optimal lung auscultation landmarks for each child with
different methodologies. Each of them examined the children separately
and located what she/he believed to be optimal chest auscultation
landmarks after evaluating with either traditional stethoscope or lung
ultrasound point of care (Fig. 2). According to her/his expertise, each
of the examiners filled the medical reports for each patient, drawing an
individual map of auscultation landmarks and specifying any additional
respiratory (vesicular murmur, crackle, rhonchus, wheeze, pleural rub or
stridor) or sonographic findings.

The landmarks identified by the multidisciplinary team were compared to
the standard auscultation landmarks, four on the back and four on the
front, provided by the device for patients with typical configuration of
chest and trunk in the absence of spinal deformities.

\emph{Fig. 2} \emph{Identification of optimal chest auscultation
landmarks}

2. \emph{Training sessions and application of the new device by carers}

The medical part of the ``remote'' team gave a 30 minutes in-person
practical training. The carers were shown how to place the device
following the map of optimal landmarks identified for each child and to
perform lung auscultation while an ICT expert offered technical support
for the whole team. After training, as soon as they felt confident, they
autonomously placed the Tytocare digital stethoscope at the
corresponding landmarks, perform the entire respiratory evaluation back
and front on their own, made sure each lung recording was as clear as
possible without background noise (the device provide such features) and
forward the files. In case of poor quality recording sessions the device
displays on its screen several alert messages inviting the examiner to
repeat the step until acceptable quality is obtained before moving
forward. At the end of the session parents alone or with their children,
recorded one or more free short videos to describe their experiences,
ease-of -use, difficulties, expectations and so on.

3. \emph{Assessment of accuracy and sensitivity of the device in our
cohort of SMA children.}

Data obtained by the carers were reviewed by an independent pediatric
team who blindly accessed the encrypted patient's charts. The blinded
team examined the lung sounds from each recorded station (landmarks)
using high quality headset in a quiet room and filled a report assigning
an overall quality value, from 1 (very poor) to 5 (very good), identify
and report possible interfering/background noise (mechanical
ventilation, heart sounds, voices, rustle, TV/music) for each of the
auscultation landmark

The blinded team also compared the recordings of respiratory findings
obtained using the device by the carers with the reports of the bedside
team who used conventional auscultation techniques.

\emph{1.5 Statistical analysis}

Inter-correlation coefficient was used to establish inter-observer
reliability as part of the development of the study.

\textbf{Results}

We enrolled 23 SMA children. Their age range between 6 months and 18
years. Eight of the 23 (35\%) were affected by type 2 SMA and the other
15 (65\%) by type 1. In agreement with the Dubowitz decimal
classification {[}12{]}, 2 (13\%) of the 15 type 1 SMA patients were
classified as 1.1, 8 (53\%) as 1.5 and 5 (33\%) as 1.9.

Three of the 23 (13\%) had no scoliosis (Cobb angle \textless{}20deg),
12/23 (52\%) were classified as mild or moderate (Cobb angle between 20deg
and 50deg), while 8/23 (35\%) showed severe scoliosis ( Cobb angle
\textgreater{} 50deg) complicated by different degree of kyphosis or
rotoscoliosis (Tab. 1).

Five of the 23 (22\%) were on spontaneous breathing, 12/23 (52\%) used
non-invasive ventilation less than 16 hours/daily, none of them used
non-invasive ventilation more than 16 hours/daily and 6/23 (26\%) were
mechanically ventilated through tracheostomy (Tab. 1).

\emph{1. Identification of the auscultatory landmarks in SMA patients
and concordance with the standard landmarks}

The identification of landmarks using a traditional stethoscope showed
high concordance between examiners (100\%), ICC= 1. The landmarks
identified through clinical auscultation using a traditional stethoscope
and lung ultrasound assessment also had high concordance (100\%) in all
patients, irrespective of their scoliosis or chest deformities. Lung
vertical artifacts, sub-pleuric consolidation and small atelectasis were
quite common US findings, as confirmed by literature but did not
interfere with lung auscultation. This allowed to draw a lung
auscultation map for each patient with 8 different sites, 4 on the back
and 4 on the front, with children-friendly an-allergic colored stickers,
placed directly on the children's body (Fig. 2, Fig. 3). Parents were
encouraged to take as many pictures as they wanted for future
independent evaluations.

The landmarks identified through auscultation and LUS were identical to
the standard landmarks provided by the device in 7 of the 23 (30\%), in
another 8 (35\%) were located in proximity to the standard ones (within
2 to 5 cm circular area) while in the remaining 8 (35\%) resulted in
completely different areas.

The concordance between personalized auscultatory and standard landmarks
was higher in the non-sitters, i-e the children with the most severe
phenotypes who can be only assessed in the supine position and can be
postured to at least partially correct scoliosis, when present (table
1). The concordance was much lower in children with Cobb\textgreater{}
50deg and chest deformities irrespective of the SMA type.

\emph{2. Training sessions and application of the new device by carers.}

Once the auscultation landmarks were identified, the use of the device
by the carers was very easy and fast. All carers reported that they
found very useful that device showed notification of under-optimal
recording and gave advice to improve exam quality reducing environment
noise like talking or TV sounds or reduce pressure that may create
annoying friction sounds between the digital stethoscope and the skin,
likewise on a traditional stethoscope.

\emph{3. Assessment of accuracy and sensitivity of the device in our
cohort of SMA children.}

The audio files recorded by carers with the Tytocare digital stethoscope
resulted clear when listened to remotely. The overall quality value
assigned by the remote team was ``very good'' (5/5 points). The
vesicular murmur was detectable and rated as ``very clear'' in 20 (87\%)
children out of 23 (\%) and 3/23 (13\%) was ``slightly disturbed'' due
to background noise (same as digital stethoscope friction, TV, voices).
The remote team did not rate as ``highly disturbed'' none of the
recordings.

All our patients had normal respiratory findings and these were
concordant between the \emph{``bed-side'' multidisciplinary
team}conventional auscultation and the remote assessment in all cases.

\textbf{Discussion}

For children affected by type 1 and 2 SMA, advanced telemedicine
platforms seem to be a feasible and accurate solution that represents an
unanticipated positive experience to overcome old and new limitations in
time of Covid.

Our study showed that lung auscultation in type 1 and 2 SMA children can
be remotely performed even by layman parents. The feasibility of the
tool in patients with SMA revealed that the tool can always be used to
obtain reliable auscultation but adaptations to find optimal landmarks
are often needed in cases with asymmetrical or rotated chest and trunk.

In our experience, remote auscultation resulted almost straightforward
in children with symmetric chest or mild-moderate scoliosis. In
contrast, in patients with severe scoliosis optimal landmarks for
digital lung auscultation could still be identified but required a
preliminary assessment by experienced physicians, with traditional
stethoscopes that allowed a tailor-made mapping of the landmarks for
future reference to be used at home by the carers. In this study we also
used lung ultrasound but it did not provide additional information on
the landmarks compared to the traditional stethoscope auscultation. Once
the landmarks were identified, after adequate 30 minutes in-person
training, all carers were able to perform the lung examination following
the step-by-step procedure as displayed by the device. The carers of
children with severe scoliosis (Cobb angle\textgreater{}50deg),
roto-scoliosis, kyphosis or chest deformities, reported that extra care
was required to firmly hold in place the digital device.

Our results would therefore suggest, that following some preliminary
work for landmarks identification, the device can be easily used by
carers. As several factors, such as growth, increasing scoliosis or
chest deformities due to the progression of the disease may interfere
with the position of the landmarks, we expect that the landmarks should
be reassessed at each hospital visit

In our study, recording good quality sounds did not represent a
challenge for most carers as confirmed by the remote assessment of their
recordings by the expert medical team. Obtaining good results was
probably facilitated by the device displaying several alert messages
when poor quality sounds were recorded, inviting the examiner to record
again until acceptable quality was obtained. There were very few
disturbed recordings that had minor issues rated by examiner as due to
interfering noises such as friction (unsteady holding in place the
device) or human voices heard in the background.

Interestingly, in the 5 patients who were ventilated, the sound of
mechanical ventilation did not interfere with auscultation and was
correctly recognized in 100\% of cases, probably due to its
characteristic noise and unchanged rhythm. Surprisingly, it did not even
trigger an alert message from the device which would have prevented
remote recording in these children.

When asked to comment on their experience in video, all carers reported
an overall enthusiastic experience, with ``surprising'' ``unexpected''
and ``easy'' being the 3 more frequently used adjectives. When asked
about the potential future implementation ``hope'' was the most common
comment followed by ``I wish I'll not make mistakes'' apparently
revealing the mixed feelings between excitement and anxiety. Some carers
revealed some auscultation-related-stress which waned over time, with
exercise, and with remote assistance by our trained physicians and by
the ICT group. In all cases a carer's personal motivation contributed to
the fast learning and to the high number of successful lung evaluations,
regardless of previous technical skills, age, gender or scientific
background.

As expected, having their carers performing the assessment was very well
accepted and perceived as a low-stress procedure for children. The
application of colorful stickers was perceived as a fun game, according
to their carers opinion. We believe that such ``hands-on'' training
could be scheduled as part of the routine clinical evaluation in
neuromuscular centers.

One of the limitations of this study, that was meant to assess the
suitability of the new devices, was that while we were able to establish
the feasibility of the tool to obtain reliable recordings and to
establish the adaptations needed and the level of training, we could not
assess the sensitivity of the device to detect pathological findings,
probably due to Covid-related restrictions and parental extra
precautions, all the patients enrolled in this study were all in good
health and were evaluated in the absence of lung infections. Further
studies are therefore needed to evaluate the sensitivity of the device
and the concordance of responses in comparison with traditional
auscultation in neuromuscular patients affected by respiratory
infections. In conclusion the results of our study, that is part of a
larger Advance Telemedicine project , suggest, for the first time, that
remote devices may be used to address the un-meet need reported by
patients with chronic disabilities (such SMA) and their carers regarding
the possibility to assess patients in the presence of a possible acute
event. Although the use of the new device has been driven by the needs
at the time of pandemic, their use could be postulated also in the
future as they may facilitate some aspects of care, reduce the number of
visits to the hospital and ease direct costs (i.e. transport, overnight
stays) and indirect costs (work and school permits or organizational
expenses) for families.

\textbf{(3103 w)}

\textbf{Author's contributions:}

DK, BB, MP, EM: Conceptualization, Formal Analysis, Investigation,
Methodology, Writing Original Draft Preparation. DL, CP, RO, MCP: Data
Curation, Formal Analysis, Investigation. DB, CdR: Data Curation, Formal
Analysis, Methodology. AC, EM, PS, GS: Methodology.

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{[}12{]} Dubowitz V. Chaos in classification of the spinal muscular
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\includegraphics[width=0.70\columnwidth]{figures/Fig-1-SMA-TYTOCARE-x-ray/Fig-1-SMA-TYTOCARE-x-ray}

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\begin{figure}[H]
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\includegraphics[width=0.70\columnwidth]{figures/Fig-2-SMA-TYTOCARE-landmarks/Fig-2-SMA-TYTOCARE-landmarks}

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\includegraphics[width=0.70\columnwidth]{figures/Fig-3-carers-recording/Fig-3-carers-recording}

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\textbf{Hosted file}

\verb`SMA TYTO tabella 1.docx`  available at \url{https://authorea.com/users/437149/articles/538989-from-bed-side-to-web-side-advanced-telemedicine-platform-for-spinal-muscular-atrophy}

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