1

Industry 4.0 and Health: Internet of Things, Big Data,

and Cloud Computing for Healthcare 4.0
Giuseppe Aceto, Valerio Persico, and Antonio Pescapé
Department of Electrical Engineering and Information Technology, University of Napoli Federico II (Italy)
E-Mail: {giuseppe.aceto, valerio.persico, pescape}@unina.it

Abstract—Industry 4.0 and its main enabling information and control), and heavily relies on three groups of technologies
and communication technologies are completely changing both (pillars): the Internet of Things (IoT) paradigm (characterized
services and production worlds. This is especially true for the by the pervasive presence of a variety of uniquely addressable
health domain, where the Internet of Things, Cloud and Fog Com-
puting, and Big Data technologies are revolutionizing eHealth cooperating objects such as mobile phones, sensors, and
and its whole ecosystem, moving it towards Healthcare 4.0. By actuators); Cloud and Fog Computing (providing virtually
selectively analyzing the literature, we systematically survey how unlimited computing, storage, and communication resources as
the adoption of the above-mentioned Industry 4.0 technologies utilities, i.e. on-demand and pay-per-use); Big Data Analytics
(and their integration) applied to the health domain is changing (to extract value from challenging amounts of data).
the way to provide traditional services and products. In this
paper, we provide (i) a description of the main technologies and The evidence of the rapid and pressing technological
paradigms in relation to Healthcare 4.0 and discuss (ii) their main evolution—joint with the worldwide rising governmental
application scenarios; we then provide an analysis of (iii) carried efforts—leads to the conclusion that the healthcare sector is
benefits and (iv) novel cross-disciplinary challenges; finally, we already facing the impact of I4.0, effectively moving eHealth
extract (v) the lessons learned. towards Healthcare 4.0 (henceforth also “HC4.0”). Although
the term Smart Health is often adopted with different accep-
tation to generally refer to the adoption ICT-based healthcare
I. I NTRODUCTION
solutions, it is worth noting that the paradigm we define here
The growth of world population and the rising expecta- as Healthcare 4.0 has its own peculiarities. Indeed, in the
tions for effective treatments and overall better quality of scientific literature several definitions for Smart Health can
life are putting increasing pressure on healthcare. Therefore, be found ranging from “the medical and public health practice
healthcare keeps being one of the most important social and supported by smart mobile devices (i.e. smart-phones)” [7] , or
economic challenges worldwide, asking for new and more “the intelligent health management and medical service using
advanced solutions from science and technology [1, 2]. In information technology” [8], to “the use of technologies such
response to such needs, since the early 1990s, the Information as smart mobiles, smart cards, robots, sensors, and tele-health
and Communication Technologies (ICTs) have positively im- systems via Internet on pay-per-use basis for best medical
pacted the access, the efficiency, the quality of virtually any practices” [9]. Healthcare 4.0 is instead deeply characterized
process related to the healthcare [3]. Hence, the expression by the adoption of three main paradigms: the Internet of
eHealth, intended as the application of ICTs to healthcare, has Things, Big Data, and Cloud Computing that together are
become of common use. Indeed, eHealth has attracted great revolutionizing eHealth and its whole ecosystem, like Industry
public and private interest and fostered unprecedented levels 4.0 is doing for the manufacturing sector [10]. The intrinsic
of investment in terms of both research effort and funding [4]. multi-disciplinary nature of Healthcare 4.0 makes it harder and
As the founding technologies evolve, also eHealth is fol- harder for the operators and stakeholders in this field to keep
lowing along, therefore the specific characterization of the the pace with technological progress. While several introduc-
term has undergone progressive changes and specifications [5], tions and surveys exist regarding either the technologies at the
the most recent ones regarding the paradigm known as In- basis of Industry 4.0, or single ICT applications to healthcare
dustry 4.0 (hereafter also “I4.0”). In its broader meaning, (eHealth) [11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21], we
the concept of I4.0 can be seen as a governmental explicit found a lack of an up-to-date work focusing on the aspects
commitment to foster a set of technologies and the cultural most relevant to Healthcare 4.0. Therefore, with this paper
and legal framework necessary to harness their full potential. we aim at introducing the technological aspects at the basis
The term itself is tracked back to November 2011, in an article of the ongoing industrial revolution as applied or applicable
by the German government defining its high-tech strategy, to healthcare, to shed light on their use and deepen their
named “Industrie 4.0”, for 2020 [6]. Besides the technologies understanding. This way, we provide for specialists in some
involved, there are in fact also development plans including of the involved fields also an overview of the others, fostering
aspects of enterprise management and work organization, reg- the cross-disciplinary interactions at the basis of HC4.0.
ulatory frameworks, and dissemination and training. From the We adopted a systematic approach in exploring the literature,
strictly technical point of view, this so-called fourth industrial following the methodology described in [22]. For the aims
revolution is based mainly on the concept of Cyber-Physical and scope of our paper, the identified keywords have been: “e-
Systems or CPS (integration of computing, communication, health”, “healthcare”, “cloud computing”, “Fog Computing”,
 2

“Iot”, “Internet of Things”, “Big Data”. As research engine Internet of Things

Cloud/Fog Computing
Big Data
eHealth
Industry 4.0

Google Scholar has been selected, to avoid bias on publishers 100000

Cumulative Hits on Google Scholar

according to best practice. From the +800 results we selected
an initial set of 80 papers for the snowballing methodology, 10000

using the following criteria: paper written in English, full text

1000
available either publicly or by subscription by University of
Napoli Federico II, then based on relevance of title and highest 100
number of citations. By applying the backward and forward
snowballing process, considering the abstract for relevance 10
and for papers candidate to inclusion also the full paper, we
obtained a set of 160 papers. These have been organized in 1
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
sections pertaining to the technological Pillars. Both generic Year

and specific suggestions by the anonymous reviewers for Figure 1: Popularity in the scientific literature of HC4.0 pillars
expanding the resulting set have been also evaluated and (number of publications per year). Data source: Google Scholar (exact
included, leading to a final total of 171 papers. match in title).
Our contribution is fivefold: (i) we introduce the I4.0 pillars for their importance: IoT, Cloud Computing, and Big Data, by
highlighting their properties more relevant to healthcare, char- detailing the use of these technologies in the field of healthcare.
acterizing the HC4.0; (ii) we review the state-of-art application Their growth in terms of academic interest and production is
scenarios of HC4.0; we discuss (iii) the main benefits and shown in Fig. 1. We acknowledge that other aspects, both tech-
(iv) the main challenges deriving from the advent of HC4.0; nological and not, can be considered in relation with HC4.0,
(v) we draw lessons learned. but compared with the pillars above, they are either secondary
This paper is structured as follows. We briefly describe each or are supported by technologies at a lower degree of maturity.
pillar to the depth necessary to appreciate its contribution to Among these, the 5G ecosystem [27]—whose specifications
HC4.0 in Section II. Then we review all the main application and technical solutions are still being defined and are under
scenarios enabled by HC4.0 in Section III. We highlight and extensive discussion—undoubtedly plays a major role. Indeed,
discuss the main benefits and challenges of the ICT pillars for the advantages of these emerging technologies (e.g., near-zero
HC4.0 in Section IV, also considering the point of view of latency, advanced quality-of-service capabilities, and data rates
patients and healthcare professionals. In Section V we extract on the order of Gbps), are expected to bring multiple benefits
the lessons learned through our study. Finally Section VI draws to fuel the broad expansion of health solutions [28].
the conclusions. A. Internet of Things in HC4.0
A general vision of the IoT is presented by ITU as the move
from anytime, anyplace connectivity for anyone, forward to
II. ICT PILLARS FOR H EALTHCARE 4.0
connectivity for anything, initially with focus on digital identi-
Today’s world is being transformed by the availability of fication and machine-to-machine (M2M) communications [11].
anywhere-and-anytime connectivity. The unprecedented ubiq- The objects conforming to the IoT have a wide range of
uitous presence of wireless and mobile technologies also in understandings and connotations, including RFID [29] and
developing countries, the availability of low-cost, miniaturized Wireless Sensor Networks (WSNs) [30] and all share some set
wireless sensors, as well as the cost-efficient services provided of strict requirements in terms e.g. of size, power consumption,
by new hardware infrastructures (e.g., huge-scale datacen- processing capabilities. Of specific interest for healthcare,
ters leveraging virtualization technologies) have enabled new Wireless Body Area Networks (WBANs) are composed by
healthcare services, or new levels of quality and cost-efficiency wireless devices (sensors and actuators) attached on or im-
in established ones. Examples go from the rising availability planted in the human body [15, 31].
and quality of medical software applications—also as mobile Due to such complex and heterogeneous scenario, IoT-
apps—driven by the integration of mobile devices into clinical related topics are often addressed referencing different logical
practice [23], to backing people suffering from obesity or layers [32], i.e.—from bottom to top: (i) perception layer
chronic diseases as well as aging population [15] by means (made up of sensors and actuators); (ii) transmission layer
of large-scale analysis of massive digitized data [5, 21]. A (conveying sensed information to the upper layers); (iii) com-
sign of the radical change in medicine enabled by these new putation layer (in charge of processing data and taking deci-
technologies can be found in the concept of P4 Medicine [24], sions); (iv) application layer (using of the IoT infrastructure
i.e. predictive, preventive, personalized and participatory. This for high-level goals such as healthcare, home automation,
approach—based on a comprehensive understanding of each transport, manufacturing, etc.). Most of the academic and
patient’s own biology instead of clustering patients into treat- industrial research on IoT has focused on the transmission
ment groups—is being applied to significantly reduce global layer and its communication protocols. Although designing
health budgets, e.g. by reducing hospitalization and by mini- and implementing a low-power, highly reliable, and Internet-
mizing the unnecessary or inappropriate use of drugs and pro- enabled communication stack is a commonly agreed require-
cedures [25, 26]. These innovations all come from the broad ment, IoT definition still appears somehow fuzzy for some
set of ICTs, and among them in this section we will focus aspects. We refer to [33] and [34] for a detailed discussion on
on three fundamental enablers, that we dub pillars of HC4.0 standards as well as related challenges and opportunities.
 3

The most recent vision of IoT, when applied to industry IoT Paradigm Year Ref.
(e.g., manufacturing processes), greatly overlaps with I4.0. Internet of Medical Things (IoMT) 2017 [45]
This can be in fact considered as a step beyond IoT, either Internet of Health Things (IoHT) 2016 [41]
adding reference architectures with logistic and manufacturing Internet of Nano Things (IoNT) 2015 [2]
details [35], or conversely adding IoT technologies to already Wearable Internet of Things (WIoT) 2014 [44]
automated processes, with a number of new opportunities (and Internet of m-health Things (m-IoT) 2011 [46]
challenges) as a consequence [36]. Healthcare proved to be Table I: Internet of Things paradigms in Healthcare.
among the most attractive areas for IoT application [14, 37].
The success of this paradigm is reshaping modern healthcare,
with promising technological, economic, and social prospects:
IoT is arguably the main enabler for distributed healthcare
applications [38], thus giving a significant contribute to the
overall decrease of healthcare costs while increasing the health
outcomes, although behavioral changes of the stakeholders in
the system are needed [38, 39]. Progress in wireless technolo- Figure 2: Main drivers to the adoption of Cloud Computing in
gies with related performance improvements heavily supports Healthcare (percentage of motivations reported in surveyed papers).
real-time monitoring of physiological parameters, thus easing
the uninterrupted care of chronic diseases, allowing early it does not require a careful dimensioning and forecast of
diagnoses, and the management of medical emergencies [14]. needed resources, allowing pay-per-use billing on a short-
In this context, medical, diagnostic, and imaging sensor de- term basis, without upfront commitment by the user. More-
vices are central for fruitfully leveraging IoT in the health over, cloud customers take advantage of apparently infinite
domain [14, 40]. However, a huge number of applications resources on demand, and are able to either leverage or
also take advantage of general-purpose smart devices (PDAs, deliver everything as-a-service: the most common services
tablets, and smartphones) [14, 41, 42]. are characterized as Infrastructure, Platform, or Software as-
For instance, IoT enables scenarios where smart devices a-Service (IaaS, PaaS, and SaaS, respectively) [47], with
interact with other smart objects in order to gain new knowl- further variations such as Function-as-a-Service (also dubbed
edge and awareness about both users and the environment for “Serverless Computing” [48]). Notably, Cloud is necessary to
supporting decision [43]. Inspired by the prime IoT paradigm, satisfy a number of needs deriving from IoT [37], to the extent
a number of variations have been derived in the health field, that, according to some visions, it is intended as one of the
each with its peculiarities (see Tab. I). The Wearable Internet IoT upper layers [49, 32]. The occurring migration to cloud
of Things (WIoT) [44] intends to implement telehealth to services is fueled by a trend emerging in the last decade:
achieve an ecosystem for automated interventions. Leveraging i.e., the extension of functionalities embedded in field devices
body-worn sensors, WIoT enables monitoring data useful in that has endowed them with more intelligence and flexibility,
enhancing individuals’ everyday quality of life (e.g., focus- thus allowing to move some functions to the Cloud [50],
ing on factors such as behaviors, wellness, habits, etc.) and with the related scalability and responsiveness (and eventually,
connects patients to medical infrastructures. The Internet of economic) gains.
Health Things (IoHT) is based on the combination of mobile However, several shortcomings of the Cloud Computing
apps, wearables, and other connected devices and leverages paradigm have become apparent over the years, mostly related
context-aware always-on professional-grade sensor medical with the communication between the end device and the
devices [41]. The Internet of Medical Things (IoMT) [45] datacenter hosting the cloud services: latency, bandwidth, cost,
refers to applications consisting of implantable and wearable and availability of the connection all contribute to limit a
devices connected to a personal a smartphone or a smartwatch number of uses for Cloud Computing. The proliferation of
that is connected to the Internet and acting as personal pervasive mobile devices further worsened this phenomenon,
hub. The Internet of Nano Things (IoNT) [2] refers to the highly challenging the Cloud paradigm. Indeed, in several
application of IoT in nanomedicine, to implement more per- contexts the Cloud cannot meet all the requirements of many
sonalized monitoring, diagnostics, and treatment to implement applications—specifically, for healthcare—surfacing the need
proactive monitoring, preventive health, chronic care disease for a different architecture [51]. Different concepts, terms, and
management, and follow-up care. The Internet of mobile- expressions have been coined for the solutions proposed as
health Things (m-IoT) [46] envisions a connectivity model detailed in the following. Fog computing [52] proposes to
between low-power personal-area networks and evolving 4G transfer some cloud computing services to the edge network,
networks, emphasizing the existing specific features intrinsic close to user devices and possibly partially relying also on
to the global mobility of participating entities. users’ device resources, thus distributing the load between end
B. Cloud and Fog Computing in HC4.0 devices and traditional cloud datacenters and bringing, among
“Cloud Computing” (or simply “Cloud”) is a paradigm that others, local-term security, low-latency rates and faster respon-
enables “Utility Computing”, i.e. the leasing of computing siveness, while helping to improve performance scalability to
resources (computational power, storage, and the related net- the whole system.
working resources) in real time, with minimal interaction In fact, fog computing enhances on-time service delivery
with the provider. This way, Cloud simplifies operation, as and significantly mitigates a number of issues related with
 4

cloud such as cost overheads, delay, and jitter while informa- systems with contextual information, allowing for more user-
tion is transferred to the cloud [53]. friendly and personalized services and adaptive quality of ser-
It also supports user mobility, resource and interface het- vice management [56]. Summing up, Cloud, Fog and Mobile
erogeneity, and distributed data analytics to address the re- Edge Computing constitute a big part of HC4.0, with positive
quirements of distributed applications requiring low latency. impacts on both healthcare research and services improvement
Moreover, it simplifies the management and programming of (enhancing quality, making them affordable for a bigger set of
computing, storage, and networking services between data- people than currently possible, and enhancing the outcomes
centers and end devices [54]. Therefore, Fog computing is for patients).
a powerful tool to support the decentralized and intelligent C. Big Data in HC4.0
processing of unprecedented data volumes generated by IoT The expression Big Data has a much discussed scope and
sensors deployed to integrate physical and cyber environments, definition. Over time, its focus has moved from datasets
thus helping the IoT reach its vast potential. characteristics in relation to the current technologies (datasets
When clients are mobile nodes and the computing capa- which could not be captured, managed, and processed by
bilities are moved to the radio access network, this concept general computers within an acceptable scope, according to
specializes as mobile edge computing (proposed ETSI stan- Apache Hadoop definition) to the technologies designed to
dard [55]). Mobile Cloud has been proposed as umbrella economically extract value from very large volumes of a
term [56], including the following scenarios: (i) applications wide variety of data, by enabling the high-velocity capture,
are run on (resources-rich) remote servers, with the mobile discovery, or analysis [67]. A commonly agreed and concise
devices being the (thin) clients; (ii) mobile devices are used characterization based on five Vs captures the largest and
as resource providers for the Cloud, in a mobile peer-to-peer most cited common set of properties associated with Big Data:
network; (iii) mobile devices offload their workload to a (local) (i) Volume (data scale increases); (ii) Velocity (collection and
edge cloud. In this context the idea of cloudlet was developed analysis are subject to time bounds); (iii) Variety (data is
by the Carnegie Mellon University [57], referring to a middle composed of various types, i.e. structured data, unstructured,
tier (between the mobile device and the traditional Cloud): and semi-structured); (iv) Veracity (data has varying degrees
the cloudlet is a self-managed “datacenter in a box”, a mini- of trustworthiness, according to provenance, management,
cloud with resources sufficient to host workloads for a handful and processing); (v) Value (the whole architecture is aimed
of (mobile) users concurrently. Cloud Computing is indirectly at—economical—value extraction). This 5-V characterization
implied in the other pillars of HC4.0, namely Big Data and IoT, highlights the strong context-dependent nature of Big Data,
but also for Visual/Virtual Computing and other healthcare that is so defined necessarily with reference to specific ap-
applications. plications (Value) and technical constraints (Volume, Velocity,
The characteristic benefits of Cloud Computing in contain- Variety, Veracity). These peculiar requirements—challenging
ing integration costs and optimizing resources are specifically the available technologies by definition of Big Data—have
significant in the healthcare scenario. Cloud Computing meets spun significant innovation over data management techniques
the IT needs of the healthcare sector to simplify health and tools in the last two decades, also leveraging Cloud
processes [18, 16, 5, 58], facilitate the adoption of healthcare Computing as an enabler for the new distributed paradigms.
best practices, and inspire and foster more innovations [9]. The For an overall technological analysis of the evolution of Big
adoption of Cloud technologies in the context of healthcare Data we refer to [68]. Big Data and related concepts are
has been dubbed Healthcare as a Service (HaaS) [59, 47]. directly implied in I4.0 in general and massively in HC4.0
Compared with the common drivers to the adoption of Cloud applications in several ways. Being aware of the great variety
technologies in more general applications and in the IoT of available data sources is of the utmost importance for
paradigm [37], HaaS applications share the same benefits realizing the actual effectiveness of Big Data applied to HC4.0.
from scalable, on-demand, and virtually infinite computation, The most traditional source of Big Data, that historically led
storage, and networking resources; in addition to these, other the big-data applications and pushed for the necessary tools,
aspects have been found to be important, such as: ease of is Online Social Network data. Initially aimed at targeted
data sharing, ease of data collection and integration, and advertising and market analysis, in the context of I4.0 this data
in some cases enhanced performance, availability, reliability is more directly used to tune the value chain, in an automated
and security [60, 61, 62, 63] (see Fig. 2). Moreover the fashion. From a point of view, whole I4.0 can be seen as
technologies related to mobile and personal devices benefit an effort to foster such timely feedback from in-the-wild
from Cloud and Fog Computing for managing the growth data collection back into the design-production-delivery cycle.
in digital data and anywhere-and-anytime request for medical For what strictly concerns the health sector, social media are
services [16, 64, 37]. Specific contributions to the healthcare reshaping the nature of health-related interactions, changing
sector regard the overall improvement of the quality of service: the way healthcare practitioners review medical records and
when many smart devices and objects are the more and more share medical information. As access to web resources—in
part of everyday’s life of patients and physicians, availability particular to social networking sites and feeds, social-media
and communication latency can be serious issues, affecting sources, and on-line discussion forums—provides more and
predictability, delaying decision processes, and potentially more valuable information, social media and related technolo-
compromising the delivery of healthcare services [65, 66]. gies are dramatically changing medicine practice [69].
Mobile cloud mitigates or solves these issues and also provides Another already present source of Big Data that is in-
 5

creasing its importance in I4.0 is enterprise data. Enterprises

already produce and manage high volumes of data: besides
internal accounting, employee data, internal communications, Monitoring
Physiological and
there are also data custody requirements from regulations. This Pathological
also applies to healthcare institutions where this kind of data Signals Self-management
(e.g., administrative, billing, and scheduling information) even Rehabilitation Wellness
Monitoring and
if not only and strictly related to the health domain, enrich the Prevention
list of potential sources, allowing to implement studies that
encompass not exclusively biological and medical aspects. In
I4.0 this is only expected to ramp up, due to focus on extensive Medication-intake
Assisted HEALTHCARE 4.0 Monitoring
exploitation of the stream of data, enriched with more data Living and Smart
sources and with metadata on the process itself. This will Pharmaceuticals

add to external data (i.e. from outside the enterprise), coming

from sold products, customers, and from suppliers/partners,
Telemedicine,
calling for more and more application and evolution of Big Telepathology, Personalized
Data technologies. and Disease Healthcare
Monitoring Cloud-based
Further increase of data has come from the advancing Health
of technologies. Indeed, stream processing systems monitor Information
Systems
people’s health status in real time, generating large amounts
of structured and unstructured streamed data thanks to the
fast and significant market penetration of personal devices
and the progress in wireless sensors and mobile communi- Figure 3: Main HC4.0 Application Scenarios.
cation technologies [70]. In addition to this, medical tests,
images, and descriptions from clinicians, result in clinical
information about patients, that is collected through records from long-term elderly care and home surveillance to acute
that may assume several forms and denominations. The most healthcare rehabilitation systems. As these setups produce
popular ones are [71, 72]: Electronic Health Records (EHR); larger and larger volumes of a wide variety of data by enabling
Electronic Medical Records (EMR); Personal Health Records high-velocity capture, discovery, and analysis, new-generation
(PHR). While EHR are intended to report episodes of care big-data technologies and architectures are required to extract
across multiple care delivery organizations, EMRs are real- value from them [75]. This is further pushing for a shift to
time patient health records with access to evidence-based de- cloud architectures, needed for securely and reliably handling
cision support tools, possibly used to aid clinicians in decision- both processing and storage requirements to analyze these
making. PHR are layperson-comprehensible, lifelong tools large amounts of data [75].
for managing relevant health information, promoting health Thanks to IoT, Cloud and Fog, as well as Big Data,
maintenance and assisting with chronic disease management researchers and practitioners are allowed to design novel
and—differently from EHR and EMR—are typically managed solutions, that are able to efficiently and effectively renew con-
by patients. solidated healthcare practices or even provide novel ground-
Moreover, the scientific literature still represents an essential breaking results to address and mitigate long-lasting healthcare
source of biomedical knowledge [73] (although structured issues. In this section we discuss the main health-related
resources are increasingly available). It requires dedicated text- application scenarios enabled by these three ICT pillars and
mining web tools for indexing and cataloging, thus helping their convergence as stemming out from the scientific literature
users quickly and efficiently search and retrieve relevant (with no aim to be exhaustive, see Fig. 3).
publications. A. Monitoring physiological and pathological signals.
Finally, large amounts of biological data in various forms The literature shows how the IoT paradigm—supported by
(e.g., genomics, microbiomics, proteomics, metabolomics, the progress achieved in mobile communication technologies
epigenomics, transcriptomics. etc.) are today generated and as well as in wearables and sensing devices often organized
collected at an unprecedented speed and scale [26], since in WSNs and WBANs, together with the availability of on-
the cost of acquiring and analyzing data is decreasing with demand cloud and fog resources and Big-Data technologies—
technology update. This data can be organized in four different is able to provide a valuable framework to support pervasive
levels [74] (molecular-level data, tissue-level data, patient- monitoring applications. The resulting framework supports
level data, and population data). the collection of health records, potentially providing the
generation of statistical information related to health condi-
III. HC4.0 A PPLICATION S CENARIOS tion [76, 12, 2, 77, 43], and the delivery of new types of
Market trends as well as scientific literature witness the cloud services [78, 79], able to replace or complement existing
role of healthcare in being a driver for the main pillars hospital information systems [80]. This kind of automated
supporting the I4.0 vision. Indeed, considering each pillar, IoT approaches guarantee to dramatically lower the risk of in-
is leveraged for remote monitoring in all its facets, thus en- troducing errors if compared to methods requiring manual
abling healthcare implementation in various settings, ranging intervention [81]. Systems for patients’ remote monitoring
 6

consist of three main components [82]: (i) the sensing and data- disabilities. Monitoring medication intake addresses related
collection hardware to gather physiological and movement issues. In addition, these systems are a valuable tool for
data; (ii) the communication hardware and software to relay clinicians in disease management as they provide a quantitative
data to a remote center; (iii) the data analysis techniques to way of assessing treatment efficacy [82]. Early prototypes
extract clinically-relevant information from physiological and designed for the elderly leveraged combined use of sensor
movement data. According to the type of sensors adopted, ap- networks and RFID [93]. According to the extreme relevance
plications can be either in-body or on-body [70]. The adoption of timing of drug delivery in drug treatments for achieving the
of advanced medical and environmental sensors [31, 15]— optimal effectiveness and minimizing adverse effects, several
such as accelerometers and gyroscopes (often integrated in mobile apps are today available that have features such as
mobile devices), temperature and humidity sensors, as well reminder scheduling, prescription reminder and medication
as ECG, glucose, blood-pressure, and gas, sensors—enables intake tracking [94]. Advanced solutions (e.g., consisting of
continuously monitor patients’ physiological and physical wearable or ingestible sensors, as well as integrated IoT
conditions. IoT devices can transmit these data to remote connectivity and intelligence) are also being presented [95]. In
datacenters where data integration can be performed to lever- this context, smart pharmaceuticals are defined as electronic
age seemingly infinite storage, scalable processing capabil- packages, delivery systems, or pills that provide intelligent
ity as well as high service availability provided by Cloud added value [96] (e.g., through a wireless connection to an
Computing [43, 83, 84, 85, 86, 87]. This approach further internet-enabled device or direct internet communication that
requires a reliable network connection for remote storage, allows communication to a remote system that can compile,
processing, and retrieval of medical records in the Cloud and store, and analyze the data). Future smart pharmaceuticals are
imposes many challenges related to network connectivity and expected to collect a range of micro- and macro-level metadata
traffic [65]. Indeed, among the applicative scenarios driving able to offer new insights into disease, aid service design, and
5G communication infrastructure evolution, health monitor- facilitate personalized healthcare.
ing is the one listed under ultra-reliable communications D. Personalized healthcare.
requirement [27]. Other attempts aiming at mitigating these Personalized healthcare is intended to be user-centric i.e. it
challenges for improving health-monitoring systems exploit aims at taking patient-specific decisions (rather than stratifying
Fog Computing at smart gateways, providing services such patients into typical treatment groups) [14, 44, 97, 2]. Gather-
as embedded data mining, distributed storage, and notification ing data from multiple sources (e.g., from both patients and
service at the edge of network to mitigate challenges imposed the environment) is crucial, as related data analysis facilitates
by the adoption of remote cloud services [51, 66]. Fog com- health and social care decision making and delivery. Typical
puting also plays a major role in augmented-reality latency- sources can be wearable (or even implantable micro- and nano-
sensitive applications (e.g., pervasive brain monitoring appli- technologies) with sensors or therapy delivery devices, such
cations leveraging EEG-based brain-computer interfaces [88] as fall detectors, implantable insulin pumps, defibrillator vests,
or cognitive assistance systems [89]). Fog-based architectures etc. These properties (namely, user-centrality and integration
are also expected to provide the tools for supporting medical of data from multiple heterogeneous sources, including wear-
devices to be implanted in human bodies to enhance and able devices, to offer highly personalized services) are typical
restore human functions such as-pacemakers to stimulate the of the I4.0 vision. They strongly characterize HC4.0 and are
heart muscle, deep brain stimulation system [53]. further emphasized when considered under the P4 Medicine
B. Self-management, wellness monitoring, and prevention. paradigm [24, 25, 98, 99, 100], that heavily relies on the ge-
HC4.0 significantly supports solutions for self-management. netic information of each individual. Indeed, comprehensively
Indeed, big-data technologies allow to implement a shift from understanding the biology of each individual (personalized
cure to prevention [19], which is also one of the peculiarities omics) allows to impact on predisposition, screening, diag-
introduced by P4 medicine [24]. Researchers have investigated nosis, prognosis, pharmacogenomics, and surveillance [26].
how to design intelligent services beyond simple functions Accordingly, big-data analytics is crucial for implementing
such as indicating measured data and storing data temporarily, personalized healthcare, both at individual and population
but being able to provide effective feedbacks to individuals. level [100, 97, 101].
For instance, these solutions can implement algorithms to help E. Cloud-based Health Information Systems.
prevent diseases by identifying modifiable risk factors and In a number of cases, cloud-based architectures have been
designing interventions for health behavior change [90]. Man- largely adopted to strengthen and simplify the design, the
agement of chronic diseases is another of the most important development, and the deployment of information systems, for
examples of these self-management for health. For instance, collecting, processing, and sharing clinical records [102, 103,
considering the management and prevention of diabetes and 104, 105, 106, 107, 108, 109, 110], hospital administrative
obesity, these systems are able to provide suggestions for information [111], or medical images [112, 113, 5, 114].
educating to and empowering good nutritional habits [91, 92] These architectures, help enhance the data collection process
and plan fitness programs [38, 14]). (e.g., the involved entities are often provided with mobile
C. Medication intake monitoring and smart pharmaceuti- user interfaces to cloud services for gathering and managing
cals. healthcare information [114]). Furthermore, information shar-
Medication noncompliance is common in elderly and chron- ing across different medical structures [112, 105] or between
ically ill subjects and is exacerbated in case of cognitive hospitals and patients [105, 103] is also benefited, as in
 7

several cases these systems also aim at integrating data in conferencing robotic solutions (e.g., equipped with display
several different formats [106, 63, 111] Although concerns and webcam and remotely controlled over the Internet) have
about system performance are taken in consideration only in been proposed [122] to better connect older people with other
few cases [106]. the design of these systems focused often persons (e.g. distant relatives, or physicians) without moving
on security and privacy aspects, that are both considered as or traveling, and without requiring to learn new technologies.
critical. As the overall health condition of elderly and people with
F. Telepathology, telemedicine, and disease monitoring. disabilities can be estimated from their heart beat rate, blood
First noticeable attempts for practical telepathology, i.e. the pressure, and accelerometer data, wearable sensors and thus
remote acquisition, transmission, and inspection of pathology WBAN technologies are of utmost importance for assisted-
specimens, date back to the 1980s, when the integration living facilities. Specially in home environments, WBANs
of robotic microscopy, video imaging, databases, and then- can be integrated with ambient sensors to create an ambient-
seminal availability of broadband telecommunications was assisted living, AAL [95], where the parameters of the living
envisioned as the infrastructure for supporting telepathology environment can be sensed and controlled, and body data can
services [115]. This promise has proven true, as of today be delivered to a central station. In order to make sense of the
many contributions are available, showing how ICTs support huge amount of monitoring data, and to efficiently scale with
a plethora of different applications related to telemedicine, the number of patients being ambient-assisted, artificial intelli-
telepathology, and disease monitoring [116, 31]. Available gence methodologies can be adopted for ambient-intelligence
studies can be divided in two classes: i) generic frameworks, systems in the healthcare domain, providing automated learn-
applicable to the vast majority of use cases [117]; ii) works ing, reasoning, and planning capabilities [123]. These technolo-
focused on specific diseases, such as cancer detection, car- gies would allow to automatically alert a healthcare center for
diovascular diseases [118], diabetes [119], Parkinson [120], observation and emergency assistance, in case deviations from
and Alzheimer [121]. These monitoring systems can be in the normal activities and parameters are detected [123], or for
turn adopted both to feed large-scale studies, and to inform less urgent cases would allow to propose medical or life-style
treatments tailored according to the results of the specific engagements [124]. As with other applications, Cloud and Fog
individual (as in the P4 Medicine approach). technologies can provide the on-demand infrastructure (with
In the future, also surgery is expected to become more trans- desired communication and processing capabilities) necessary
parent. Indeed, video cameras are often integrated in operating- to collect patients’ data in real time and process it, supporting
room lights for open surgery. Accordingly, the surgical proce- pervasive healthcare and AAL [125, 62, 126].
dure becomes potentially visible to an unlimited number of H. Rehabilitation.
spectators. These tools enable teleconsultation which allows In line with assisted living, home-based rehabilitation is
to avoid the physical presence of the consultant. If an active expected to bring significant cost savings for the healthcare
camera holder is used during a surgery, telepresence may take systems and better quality of life for the patients. Likewise,
place, in case the remote consultant can move the camera. WBAN technologies are the main tool allowing detection
Telesurgery represents the final evolution of this application and tracking of human movement associated with rehabilita-
scenario, with the surgeon and his/her cockpit being physically tion practice. Different from generic assisted living solutions,
separated from the operating room [96]. home-based rehabilitation is characterized by a number of
Since best-effort Internet connections are not enough to specific constraints and requirements, and associated solu-
support several classes of applications (e.g., when the goal tions [127, 116], involving multi-sensor data fusion, real-time
is recreating the effect of a microscope locally handled), the feedback for patients, and virtual-reality integration. A key
availability of constrained virtual paths to Fog services at the feature provided by WBANs in home-based rehabilitation
edge can help fill this gap. For instance, it can enable remote is related to biofeedback: the measurement of physiological
federated sites to collaborate on non-trivial diagnoses e.g., activity and other parameters, fed back to the users themselves.
providing tools for offloading complex image processing and This practice effectively enables the patient to control and
data mining tasks without suffering higher delays of a Cloud modify their physiological activities, with the final goal of
access. improving their health and performance [116, 128, 129, 130].
G. Assisted living.
A side-effect of better nutrition and overall better healthcare IV. D ISCUSSION
is the increasing aging of world population, that therefore is The new technological paradigms converging in the Industry
likely to become the more and more an issue in the future. As 4.0 are generating a profound change in mindset and approach
a way to deal with the growth of costs associated with elderly to traditional applications. This phenomenon is in development
and individuals with chronic conditions [39], aging in place also for the sector of healthcare, that already started a progres-
has been proposed, i.e. to avoid unnecessary hospitalization sive transition towards e-health, expected to further expand
by allowing patients to remain in the home environment, and accelerate in the HC4.0 scenario. The mindset change will
in so-called enhanced living environments (ELEs). Several imply the understanding of new possibilities and opportunities
ICT technologies are involved in this kind of solution, as as well as new challenges and risks: in this section we discuss
described in the following. Remote monitoring of patients both aspects (summarized in Tab. II), to foster a conscious and
is required for safety and for facilitating the implementation effective integration of new methods, technologies and tools
of clinical interventions [82], while telepresence and video- in the healthcare processes.
 8

Table II: Main benefits and challenges from the adoption of I4.0 pillars in healthcare.
Benefits Challenges
• enhanced electromedical devices (closed-loop design,
• energy constraints [133]
predictive maintenance, new service lines) [131]
IoT • security [134, 135, 136, 81, 137, 138].
• interoperability, evolvability thanks to open
• scalability [81, 139, 133, 31, 135]
communication standards [132]
• infrastructure for high-level functions • performance monitoring
Cloud/Fog (data analysis, information systems) [102, 103, 104, 106, 107, 110, 5, 111] • opacity of the infrastructure [109]
Computing • paradigmatic model for offering of services • data privacy [18, 52, 109]
to patients or to healthcare operators themselves [47] • infrastructure availability [18, 16]
• new insights and actionable information
from new data sources [140] • extreme heterogeneity [142]
Big Data
• natural transformation of descriptive research • opacity of analytics [143, 144]
into predictive and prescriptive one [141]

A. Benefits The overall picture emerging from the state-of-art is that

Several positive aspects of the IoT apply to healthcare almost Cloud Computing is a fundamental enabler for HC4.0 first of
fully when considering electromedical devices or pharmaceu- all as an extremely powerful and cost-effective infrastructure
tics industry. With reference to these, IIoT carries a number for high-level functions (data analysis, high-end information
of benefits [131, 145, 146], the most relevant summarized systems), but also as a paradigmatic model. The first aspect
in the following. Closed-loop design—Feedback on product is the charaterizing function of Cloud technologies, whose
usability and effectiveness from physicians, health operators, main properties have been introduced in Section II. Regarding
and patients themselves can be constantly put back into the the second aspect, Cloud Computing inspires (and provides
design phase: analyzing real-world usage data, designers better the means to) Healthcare-as-a-Service mindset, both for the
understand how products are being used and can design offering of healthcare services to patients, and for the usage
improved versions. Predictive maintenance—thanks to the of analysis, diagnostic, communication services for healthcare
ability to continuously gather data, IoT enables fault prediction operators. In offering services to patients, healthcare operators
and thus maintenance before failures occur, allowing for can consider providing remote front-office, remote consulting,
timely servicing or substitution or avoiding machine down- etc. knowing that such services have high impact on time,
time altogether. The impact of such possibility on economy transportation, and comfort for patients and can cover much
and management of life-critical services can be hardly over- broader population at a fraction of the cost compared with in-
stated. New service lines—manufacturers can offer better or person activities, thus will result in better quality of life for
more convenient remote monitoring and maintenance services, patients (and some categories of operators) and competitive ad-
through devices that can be continuously improved or fixed. vantage for operators in the private sector. Similarly, healthcare
operators can benefit from best-of-breed, physical-location-
Electro-medical devices communication systems have re-
independent, fully outsourced, and cost-effective services that
quirements centered around robustness and reliability, and also
are offered through Internet—backed by Cloud technologies—
often tightly bounded latency and jitter. In addition to these,
e.g. as Software-as-a-Service. Fog computing in turn can
the robustness to mutual radio interference is required to allow
provide the technical means to enjoy the same benefits above
the coexistence of multiple wireless networks, with different
mentioned while using mobile terminals, that are ubiquitous
radio technologies, in small volumes (the close surroundings
and personal, thus already familiar to large part of population.
of a human body). The ongoing development and wide
Regarding the pharmaceutical industry, Cloud technologies
adoption of open standards for protocols designed with
are the essential enablers for achieving (logical) decentraliza-
these constraints (IEEE 802.15.6 and IEEE 802.15.4) [132])
tion of manufacturing execution and planning systems [148],
means that a variety of non-mutually exclusive solutions
and for allowing seamless introduction of human intellectual
will be available, also improving interoperability between
work where and when needed (e.g., crowdsourcing difficult
devices and components from different vendors (with conse-
tasks [149]). For all these reasons the future of HC4.0 will be
quent reduction of costs, and improved evolvability of the
even more tightly bound to the research on Cloud Computing
whole system). Along these lines, in the last decades, in
and its evolution.
the IT world the ubiquity and interoperability of the TCP/IP
communication stack has already provided real-world testing Big Data techniques are fulfilling the promise of extract-
and wide adoption of wireless local area networks (Wi-Fi) ing value (actionable information) from amounts of data
and their interconnection to the Internet, recently expanding previously unthinkable or unmanageable. The operators in
from the original Small-Office-Home-Office scenario also in healthcare sector can now explore their processes looking for
the much more demanding industrial scenarios [147]. The new possibilities of continuous and massive data collection,
technologies are thus ripe to allow the HC4.0 to extensively knowing that Big Data techniques have the potential to extract
benefit from them, merging (Wireless) Body Area Networks, new meaning and useful information from it. Adopting a big-
Personal Area Networks, (Wireless) Local Area Networks, data approach, the medical researcher can naturally transform
Internet technologies, but also the Internet itself, as a global descriptive research questions (what happened?) into predic-
communication infrastructure. tive ones (what could happen?), with the aim to reach the
 9

prescriptive ones (what to do, to get one specific achievable ities with appealing prices by masking the real infrastructure,
outcome?) [141]. By discovering new data sources, or applying sparing the cloud customer to manage the details of operations
the derived data-driven results, the stakeholder in healthcare related to the cloud resources, and offering economies-of-
sector can effectively use big-data analytics to reduce concerns scale grade prices [152]. While these are exactly the desired
and uncertainty, and ultimately causing the improvement of the properties of Cloud Computing, the opacity of infrastructure
healthcare system [140] in one of its many aspects. Indeed, can become a limit when performance is required. Indeed,
big-data analytics can contribute to evidence-based medicine, computing performance [153], efficiency of communication
genomic analysis, as well as to patient-profile analyses, or protocols [125], network performance (e.g., because of poor
pre-adjudication fraud analysis. More in general, big data bandwidth and unpredictable latencies when transferring high
technologies will provide insights to reduce inefficiency, be volumes of traffic) [83, 18, 84, 154, 110, 155], still represent
it in clinical operations, public health, or research and devel- barriers. Moreover, although cloud technologies are known to
opment [150, 151]. be scalable, works in the literature report scalability of the
B. Challenges implemented solutions to be a common concern [85, 156, 157].
In general terms, IoT is in its infancy in the healthcare We refer to [158] for an analysis of issues and techniques in
field [14]. Considering that IoT consists of interconnected Cloud status and performance monitoring. Recently, accord-
smart objects, most of the issues regard the design of either ing to the increasing adoption of systems implemented through
smart-objects and communication technologies. Energy is a public clouds, research has also focused on the performance
major technical challenge. In fact, research is needed on of public-cloud networks [159, 160]. According to the above
energy harvesting, energy conservation, energy and usage, to considerations, when dealing with data intensive applications,
design and develop zero-entropy systems systems harvesting co-design approaches involving different stakeholders (partic-
energy from the environment and not wasting any under ularly those in network/performance engineering roles) have
operation [133]. Scalability is another important challenge to be taken into account to manage and troubleshoot service
to be addressed, that is exacerbated by the specific domain. performance [161].
Indeed, interconnected objects will outnumber by several Introducing the Fog paradigm brings additional open issues
orders of magnitude those composing classical Internet (IoT to be properly addressed to make the Fog a reality in the
is expected to be composed of up to trillions devices) and healthcare context. The Fog exacerbates scalability issues as
healthcare services are generally characterized by high de- it potentially deals with billions of small devices to be con-
mand. Therefore, because of the potentially drastic escalation figured (e.g., due to the possible integration with BANs). and
of the connected devices, architecture scalability is among requires scalable and decentralized management mechanisms
main concerns [81, 139]. For instance, performance and that need to be properly tested at this unprecedented scale [52],
manageability would benefit from organization in hierarchical Computing nodes and applications running on top of the Fog
subdomains [133]. Specific design issues are dictated by also need to be properly configured. In addition to this, safety,
the deployment and adoption of BANs [31, 135]. Moreover, reliability, availability, flexibility, maintainability, and power
further research is required to develop and design appropriate efficiency are commonly considered issues [162].
IoT security solutions, e.g., primitives resilient to run-time More in general, since Cloud and Fog solutions allow
attacks as well as scalable security protocols. As for today, IoT applications to process users data in third-party’s hardware
systems are not sufficiently enhanced to fulfill the desired func- and software, their adoption introduces strong concerns about
tional requirements and bear security and privacy risks [134], data privacy [52]. These issues often derive from the concern
specially when also addressing scalability requirements [135]. of loosing control over data [18] due to the limited confidence
Existing security solutions are inappropriate since they do in the provider in charge to store very sensitive information in
not scale to large networks of heterogeneous devices and its infrastructure [109]. Some proposals to solve these issues
cyberphysical systems with constrained resources and real- are being proposed recently, e.g. [163] introduces an Identity
time requirements. Moreover, as sensors that monitor health Management architecture enabling patient-controlled partial
signals continuously generates enormous data (often feeding disclosure of EHR to selected recipients. These solutions
critical applications), secure and effective architectures are have yet to see validation, standardization, or wide adoption,
needed for organizations to process the big data in integrated and come to additional complexity costs, still to be assessed.
industry 4.0 [152]. The scientific literature witnesses how Therefore this remains an open and hot research field.
protecting IoT requires a holistic cybersecurity framework However, provided solutions increasingly leverage external
covering all abstraction layers of heterogeneous systems and services as replacement of in-house solutions, as the former
across platform boundaries [134]. Additional security impli- are often equipped with advanced security settings (e.g., they
cations are generated by connected healthcare devices (e.g., adopt proper encryption algorithms, such those used by the fi-
wearables) that can be at risk to hacking and hence may nancial sector [164]). Moreover, these services offer increased
need a secure uniqueness management and authentication availability, helping to provide uninterrupted delivery with
to be implemented [136, 81, 137]. Therefore, due to the minimum downtimes [16]. In the case of critical applications,
resource limited devices usually adopted, it is an essential availability remains a concern, specially if access technologies
requirement to design lightweight algorithms in the secure data (prone to service outages) are involved. High reliability is
management system [138]. One of the main issues with Cloud indeed one of the goal of 5G communications technologies,
is more essential to its nature: it provides its as-a-service facil- but at the time of writing only experimental deployments have
 10

been performed, so their pace of adoption (and the geographic practices at the different hospitals, and between doctors and
and population extent of their coverage) are still to be known. nurses, while major differences in experience and attitude
It is worth noting that a temporally or spatially uneven de- were found between psychiatric and somatic care. Health
ployment of 5G technologies would arguably create or worsen professionals working in psychiatry questioned the suitability
unprecedented levels of digital divide, instead of relieving of the service for the sickest and most vulnerable patients,
it. To further improve availability for critical services, multi- suggesting that adaptations, or training might be necessary for
cloud solutions have been also proposed [165]. Depending on EHR access by patients in psychiatry field. EHR represents
the kind of cloud service that is leveraged (SaaS, PaaS, or a necessary component of an evolution from e-health to
IaaS), the promises of the Cloud paradigm can be achieved by Healthcare 4.0, especially in the scenario of self-management,
means of intelligent dynamic allocation of physical and virtual therefore we can project to Healthcare 4.0 both the expected
resources. This process is computationally high demanding positive outcomes, further emphasized, and also the caveats
and will require cloud resources itself, moreover its complexity and skepticism raised by healthcare professionals in specific
is expected to dramatically grow in the context of I4.0: this fields (namely, psychiatry).
is currently an open issue, requiring its own part of future
research [166]. Regarding the expectations on patients experience, both
Because of its characteristics, the huge amount of healthcare- the analyzed scenarios B and C (Self-management, wellness
related data satisfies the requirements (in terms of volume, monitoring, and prevention; Medication intake monitoring
velocity, and variety) to be considered as Big Data [150]. and smart pharmaceuticals) are involved in the study [169],
Among its peculiarities, a significant challenge for HC4.0 where a smartphone app was used to gather evidence-based
(highlighted and addressed within the Big Data paradigm) is information on effectiveness of Adjuvant Endocrine Therapy
heterogeneity of sources, formats, attributes of data (an (prescribed for reducing reoccurrence risk of breast cancer),
extreme example of big-data Variety): Jirkovsky et al. [142] together with an electronic side-effects diary, a peer support
focused on semantic heterogeneity and propose a framework forum, and a repeat prescription reminder. The objective was to
to foster interoperability. Moreover, due to constant real-time counter the low adherence to the therapy over the prescription
monitoring—that is of the utmost importance in many medi- years, that results in a two to three-fold increased risk of
cal situations—velocity of mounting data has increased with mortality. The qualitative survey explored the acceptability, the
respect to traditional static healthcare data. Indeed, its volume perceived usefulness of the services provided through the app,
is growing exponentially, requiring proper solutions to store and its usability. The findings showed that the patients almost
larger and larger amounts of information. All these aspects unanimously appreciated the app and valued the services
make healthcare data both interesting and challenging. Finally, provided through it, supporting the hope that higher adherence
considering that big-data analytics and outcomes have to be to the therapy and therefore lowered risks will be attained in
error-free and credible, big-data techniques, due to novel usage the future years. Single cases did not value the app more than
of machine-learning algorithms on unparalleled and unknown- the information provided by health professionals in person.
before amounts of data, present an opacity issue, that is most Moreover the disadvantage has been highlighted regarding
significant when dealing with health, life-related decision, and lack of access for those with low incomes, rural communities,
high-impact and social relevant matters, such is the case with older people, who would experience higher difficulties for
HC4.0 [143, 144]. The issue of lack of transparency in Big these e-health platforms. Similar results, both positive and with
Data has been raised so far mainly regarding the fields of AI warnings and caveats, emerge from the literature [170].
and Robotics, discussing its relationship with regulation and
innovation [167] without reaching a solution. On the one hand, these aspects can be extrapolated to
C. Patients and Professionals the Healthcare 4.0: a continuous, simpler, and bidirectional
To take into account also non-ICT actors directly involved exchange of information among patients and a more handy and
by Healthcare 4.0, we here discuss also the viewpoint of accurate monitoring of both health conditions and medicine
healthcare professionals and patients, referring to surveys that intake well represent the objective of Healthcare 4.0 new
investigate on the acceptance of technologies at the basis of technologies. Likely, these new services will further deepen
Healthcare 4.0, to extrapolate sensible expectations regarding the difference of experience and service between medium-high
their evolution. income, young, well-educated patients and low-income, or
In an online survey in collaboration with the Northern otherwise disadvantaged ones: special care should be taken in
Norway Regional Health Authority and the Norwegian Direc- preferring technologies that have the broadest accessibility. On
torate of eHealth, the authors of [168] investigated hospital the other hand, Healthcare 4.0 is already pursuing the goal of
health professionals’ experiences for the case of patients extending the population served with high-quality healthcare,
accessing their own EHRs, also looking for differences in specifically in scenarios D, F, G (Personalized healthcare;
experiences and attitudes according to hospitals, doctors and Telepathology, telemedicine, and disease monitoring; Assisted
nurses, and between psychiatry and somatic care. The results living) whose traditional versions are heavily limited by eco-
revealed positive experiences, including patients highlighting nomics, and thus available to a restricted affluent or privileged
mistakes and omissions in their own EHR, and also being population. Further challenges regard the acceptance and usage
better informed about all the aspects of their healthcare. Minor of technology by users for their own healthcare: we refer to
differences in experiences and attitudes were found based on [171] for a meta-analysis of studies on this specific aspect.
 11

V. L ESSONS L EARNED vigilance and regulation, that potentially can hamper fast
innovation. All these issues must be accounted for, and at least
The evolution of ICTs is deeply transforming all human a basic knowledge of the technological pillars that are affected
activities, heavily impacting also the healthcare sector. From by them, with their characteristics, inter-relations, potential,
our analysis we have derived the following main lessons. and limitations, is necessary to a conscious, controlled, and
First, both the technological possibilities and above all the full progress of HC4.0.
innovating mindset brought forth by HC4.0 are reshaping
the vision of the future of healthcare, into the ubiquitous VI. C ONCLUSION
and continuous availability of personalized medical services.
This work is intended as a reference aimed at helping
Among the technical innovations behind this vision, specially
researchers and practitioners in ICTs in applying their ex-
wearable devices, the IoT, and its health-related specializations
pertise to address the needs of the healthcare sector, and
(e.g., Internet of Medical/Health Things) are the most evident
those in the field of healthcare information systems and
pillars sustaining HC4.0, being easily recognized as the newly
automation to effectively and profitably face the new concepts
improved, more powerful, and less constrained versions of
and approaches coming from the IT field and constituting the
medical sensors and equipment. Wireless Body Area Net-
envisioned HC4.0 evolution.
works, integrating also nanoscale sensors and devices, are at
We have introduced and discussed in depth in Section II
the forefront of such technologies. The impact on wellbeing
the main groups of technologies from the so-called Fourth
and on the overall quality of life—for both healthy people
Industrial Revolution, namely the Internet of Things, Cloud
and diseased patients—is easier to envision, as good habits
and Fog Computing, and Big Data Analytics, focusing on their
and timely treatments are promoted while hospitalization and
application in the Healthcare sector. From such analysis of
healthcare costs are reduced. Another clearly recognizable
literature we have surfaced how this specific sector, already
innovation fueling HC4.0 regards the Big Data analysis tools
moving towards an ICT-backed e-health, will experience fur-
and platforms—including Artificial Intelligence techniques—
ther radical transformation in the new context of HC4.0, in
that in turn extract the knowledge hidden in massive amounts
which ICTs not only offer improvements for traditional
of data fast flowing from the ubiquitous wearable sensors:
processes and systems like Cloud-based Health Information
based on future populations studies of unprecedented size and
Systems, Advanced Monitoring of physiological and patholog-
richness, previously undetectable patterns and correlations will
ical signals, medication intake, and activities, but inspire and
be revealed and exploited, further advancing prevention and
make possible new unforeseen approaches, processes, and
cure possibilities.
applications such as Enhanced Living Environments, Home-
Other technologies, such as Cloud/Fog computing—and the based Rehabilitation, Personalized Healthcare (Section III).
rising 5G telecommunication infrastructure integrating it with We have discussed a number of strictly technical benefits
IoT—are less immediately recognized as pillars for HC4.0 as (closed-loop design, predictive maintenance, advanced service
they work “behind the scenes”. However, they are (or will be) lines, development of open standards) at the basis of the afore-
essential to the novel applications for providing the basis for mentioned technologies, together with the related technical
the ubiquity of the medical services and the required perfor- challenges (opacity of the infrastructure, need for monitoring,
mance at an affordable cost. These less evident technologies heterogeneity of formats and standards), detailed in Section IV.
contribute also to the shared drawbacks, limitations, and issues Finally, Section V draws the main lessons learned that cross
of future health-related applications: (i) security of devices, the pillars and involve non-strictly-technical aspects.
communications and processes; (ii) privacy and ethical issues
related with extensive monitoring, selectiveness, and massive
R EFERENCES
automation of health-related processes; (iii) unprecedented
[1] I. Chiuchisan, H.-N. Costin, and O. Geman. Adopting the internet of things
complexity of systems backing the new applications, limiting technologies in health care systems. In Electrical and Power Engineering (EPE),
or altogether impairing their full understanding (and thus, 2014 International Conference and Exposition on. IEEE, 2014.
[2] E. Omanović-Mikličanin, M. Maksimović, and V. Vujović. The future of
control); (iv) the fast pace of technical innovation, hard to healthcare: Nanomedicine and internet of nano things. Folia Medica Facultatis
catch-up with regulation and civic vigilance; and (v) the Medicinae Universitatis Saraeviensis, 50(1), 2015.
[3] G. Aceto, V. Persico, and A. Pescapé. The role of information and communication
intrinsic multidisciplinary nature of HC4.0, including many technologies in healthcare: taxonomies, perspectives, and challenges. Journal of
technical fields and deeply involving non-technical areas as Network and Computer Applications, 107, 2018.
[4] P. Germanakos, C. Mourlas, and G. Samaras. A mobile agent approach for
well. ubiquitous and personalized ehealth information systems. In Proceedings of the
Workshop on’Personalization for e-Health’of the 10th International Conference
Some of the issues are well-known and cross multiple on User Modeling (UM’05). Edinburgh, 2005.
research fields: security and privacy are the most prominent [5] C. Pino and R. Di Salvo. A survey of cloud computing architecture and
applications in health. In International Conference on Computer Science and
and well studied. Nonetheless, the integration of different Electronics Engineering, 2013.
technologies and above all their application to novel scenarios [6] K. Zhou, T. Liu, and L. Zhou. Industry 4.0: Towards future industrial opportunities
and challenges. In Fuzzy Systems and Knowledge Discovery (FSKD), 2015 12th
call for an ever-renewal of the study of the issues and research International Conference on. IEEE, 2015.
of new solutions. This is further worsened by the implicit trade- [7] J. Lee. Smart health: Concepts and status of ubiquitous health with smartphone.
In ICTC 2011. IEEE, 2011.
off and the inter-relation between some solutions and other [8] J. Park and M. Kim. A study on the potential needs and market promotion of
issues: this is the case of the enhancement of security, often smart health in korea. In 2013 International Conference on ICT Convergence
(ICTC). IEEE, 2013.
causing also an increase of complexity, in turn challenging [9] M. Bamiah, S. Brohi, S. Chuprat, et al. A study on significance of adopting
transparency and understanding of the system, that impairs cloud computing paradigm in healthcare sector. In 2012 International Conference
 12

on Cloud Computing Technologies, Applications and Management (ICCCTAM). An iot-based mobile gateway for intelligent personal assistants on mobile health
IEEE, 2012. environments. Journal of Network and Computer Applications, 71, 2016.
[10] G. Aceto, V. Persico, and A. Pescapé. A survey on information and communication [44] S. Hiremath, G. Yang, and K. Mankodiya. Wearable internet of things: Concept,
technologies for industry 4.0: state of the art, taxonomies, perspectives, and architectural components and promises for person-centered healthcare. In Wireless
challenges. IEEE Communications Surveys & Tutorials, 2019. Mobile Communication and Healthcare (Mobihealth), 2014 EAI 4th International
[11] L. Atzori, A. Iera, and G. Morabito. The internet of things: A survey. Computer Conference on. IEEE, 2014.
Networks, 54(15), 2010. [45] N. K. Jha. Internet-of-medical-things. In Proceedings of the on Great Lakes
[12] P. A. Laplante and N. L. Laplante. A structured approach for describing healthcare Symposium on VLSI 2017, GLSVLSI ’17, New York, NY, USA, 2017. ACM.
applications for the internet of things. In Internet of Things (WF-IoT), 2015 IEEE [46] R. S. H. Istepanian, S. Hu, N. Y. Philip, and A. Sungoor. The potential of
2nd World Forum on. IEEE, 2015. internet of m-health things “m-iot” for non-invasive glucose level sensing. In
[13] P. A. Laplante and N. Laplante. The internet of things in healthcare: Potential 2011 Annual International Conference of the IEEE Engineering in Medicine and
applications and challenges. IT Professional, 18(3), 2016. Biology Society, Aug 2011.
[14] S. M. R. Islam, D. Kwak, M. H. Kabir, M. Hossain, and K. S. Kwak. The internet [47] P. D. Kaur and I. Chana. Cloud based intelligent system for delivering health care
of things for health care: A comprehensive survey. IEEE Access, 3, 2015. as a service. Computer methods and programs in biomedicine, 113(1), 2014.
[15] H. Cao, V. Leung, C. Chow, and H. Chan. Enabling technologies for wireless [48] S. Hendrickson, S. Sturdevant, T. Harter, V. Venkataramani, A. C. Arpaci-Dusseau,
body area networks: A survey and outlook. IEEE Communications Magazine, 47 and R. H. Arpaci-Dusseau. Serverless computation with openlambda. Elastic, 60,
(12), Dec 2009. 2016.
[16] S. P. Ahuja, S. Mani, and J. Zambrano. A survey of the state of cloud computing [49] L. Atzori, A. Iera, and G. Morabito. Understanding the internet of things:
in healthcare. Network and Communication Technologies, 1(2), 2012. definition, potentials, and societal role of a fast evolving paradigm. Ad Hoc
[17] H. Alemdar and C. Ersoy. Wireless sensor networks for healthcare: A survey. Networks, 56, 2017.
Computer Networks, 54(15), 2010. [50] J. Schlechtendahl, M. Keinert, F. Kretschmer, A. Lechler, and A. Verl. Making
[18] T. Ermakova, J. Huenges, K. Erek, and R. Zarnekow. Cloud computing in existing production systems industry 4.0-ready. Production Engineering, 9(1),
healthcare–a literature review on current state of research. 2013. 2015.
[19] D. Ramesh, P. Suraj, and L. Saini. Big data analytics in healthcare: A survey [51] T. N. Gia, M. Jiang, A.-M. Rahmani, T. Westerlund, P. Liljeberg, and H. Tenhunen.
approach. In Microelectronics, Computing and Communications (MicroCom), Fog computing in healthcare internet of things: A case study on ecg feature
2016 International Conference on. IEEE, 2016. extraction. In Computer and Information Technology; Ubiquitous Computing
[20] J. Archenaa and E. M. Anita. A survey of big data analytics in healthcare and and Communications; Dependable, Autonomic and Secure Computing; Pervasive
government. Procedia Computer Science, 50, 2015. Intelligence and Computing (CIT/IUCC/DASC/PICOM), 2015 IEEE International
[21] Q. Zou, X.-B. Li, W.-R. Jiang, Z.-Y. Lin, G.-L. Li, and K. Chen. Survey of Conference on. IEEE, 2015.
mapreduce frame operation in bioinformatics. Briefings in Bioinformatics, 15(4), [52] L. M. Vaquero and L. Rodero-Merino. Finding your way in the fog: Towards a
2013. comprehensive definition of fog computing. SIGCOMM Comput. Commun. Rev.,
[22] C. Wohlin. Guidelines for snowballing in systematic literature studies and a 44(5), October 2014.
replication in software engineering. In Proceedings of the 18th international [53] A. Kumari, S. Tanwar, S. Tyagi, and N. Kumar”. Fog computing for healthcare 4.0
conference on evaluation and assessment in software engineering. Citeseer, 2014. environment: Opportunities and challenges. Computers & Electrical Engineering,
[23] C. L. Ventola. Mobile devices and apps for health care professionals: uses and 72, 2018.
benefits. PT, 39(5), 2014. [54] A. V. Dastjerdi and R. Buyya. Fog computing: Helping the internet of things
[24] P. Sobradillo, F. Pozo, and lvar Agust. P4 medicine: the future around the corner. realize its potential. Computer, 49(8), 2016.
Archivos de Bronconeumologa ((English Edition)), 47(1), 2011. [55] M. ETSI. Mobile-edge computing. Introductory Technical White Paper, 2014.
[25] E. C. Nice. From proteomics to personalized medicine: the road ahead. Expert [56] N. Fernando, S. W. Loke, and W. Rahayu. Mobile cloud computing: A
Review of Proteomics, 13(4), 2016. PMID: 26905403. survey. Future Generation Computer Systems, 29(1), 2013. Including Special
[26] R. Chen and M. Snyder. Promise of personalized omics to precision medicine. section: AIRCC-NetCoM 2009 and Special section: Clouds and Service-Oriented
Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 5(1), 2013. Architectures.
[27] A. Annunziato. 5g vision: Ngmn - 5g initiative. In 2015 IEEE 81st Vehicular [57] M. Satyanarayanan, P. Bahl, R. Caceres, and N. Davies. The case for vm-based
Technology Conference (VTC Spring), May 2015. cloudlets in mobile computing. IEEE pervasive Computing, 8(4), 2009.
[28] W. D. de Mattos and P. R. L. Gondim. M-health solutions using 5g networks and [58] B. Calabrese and M. Cannataro. Cloud computing in healthcare and biomedicine.
m2m communications. IT Professional, 18(3), May 2016. Scalable Computing: Practice and Experience, 16(1), 2015.
[29] E. Ilie-Zudor, Z. Kemny, F. van Blommestein, L. Monostori, and A. van der [59] N. John and S. Shenoy. Health cloud - healthcare as a service(haas). In
Meulen. A survey of applications and requirements of unique identification 2014 International Conference on Advances in Computing, Communications and
systems and rfid techniques. Computers in Industry, 62(3), 2011. Informatics (ICACCI), Sept 2014.
[30] P. Rawat, K. D. Singh, H. Chaouchi, and J. M. Bonnin. Wireless sensor [60] M. Chen. Ndnc-ban: supporting rich media healthcare services via named data
networks: a survey on recent developments and potential synergies. The Journal networking in cloud-assisted wireless body area networks. Information Sciences,
of supercomputing, 68(1), 2014. 284, 2014.
[31] M. Chen, S. Gonzalez, A. Vasilakos, H. Cao, and V. C. Leung. Body area networks: [61] R. Cimler, J. Matyska, and V. Sobeslav. Cloud based solution for mobile healthcare
A survey. Mobile networks and applications, 16(2), 2011. application. In Proceedings of the 18th International Database Engineering &
[32] A. J. Trappey, C. V. Trappey, U. H. Govindarajan, A. C. Chuang, and J. J. Sun. Applications Symposium. ACM, 2014.
A review of essential standards and patent landscapes for the internet of things: [62] M. Deng, M. Petkovic, M. Nalin, and I. Baroni. A home healthcare system in the
A key enabler for industry 4.0. Advanced Engineering Informatics, 33, 2017. cloud–addressing security and privacy challenges. In Cloud Computing (CLOUD),
[33] M. R. Palattella, N. Accettura, X. Vilajosana, T. Watteyne, L. A. Grieco, G. Boggia, 2011 IEEE International Conference on. IEEE, 2011.
and M. Dohler. Standardized protocol stack for the internet of (important) things. [63] E. Ekonomou, L. Fan, W. Buchanan, and C. Thuemmler. An integrated cloud-
IEEE communications surveys & tutorials, 15(3), 2013. based healthcare infrastructure. In Cloud Computing Technology and Science
[34] Z. Sheng, S. Yang, Y. Yu, A. Vasilakos, J. Mccann, and K. Leung. A survey (CloudCom), 2011 IEEE Third International Conference on. IEEE, 2011.
on the ietf protocol suite for the internet of things: Standards, challenges, and [64] M.-H. Kuo. Opportunities and challenges of cloud computing to improve health
opportunities. IEEE Wireless Communications, 20(6), 2013. care services. Journal of medical Internet research, 13(3), 2011.
[35] M. Weyrich and C. Ebert. Reference architectures for the internet of things. IEEE [65] F. Andriopoulou, T. Dagiuklas, and T. Orphanoudakis. Integrating iot and fog
Software, 33(1), 2016. computing for healthcare service delivery. In Components and Services for IoT
[36] F. Shrouf, J. Ordieres, and G. Miragliotta. Smart factories in industry 4.0: A Platforms. Springer, 2017.
review of the concept and of energy management approached in production based [66] Y. Shi, G. Ding, H. Wang, H. E. Roman, and S. Lu. The fog computing
on the internet of things paradigm. In Industrial Engineering and Engineering service for healthcare. In Future Information and Communication Technologies
Management (IEEM), 2014 IEEE International Conference on. IEEE, 2014. for Ubiquitous HealthCare (Ubi-HealthTech), 2015 2nd International Symposium
[37] A. Botta, W. de Donato, V. Persico, and A. Pescapè. Integration of cloud on. IEEE, 2015.
computing and internet of things: A survey. Future Generation Comp. Syst., 56, [67] J. Gantz and D. Reinsel. Extracting value from chaos. Technical Report 2011,
2016. 2011.
[38] J. Couturier, D. Sola, G. S. Borioli, and C. Raiciu. How can the internet of things [68] H. Hu, Y. Wen, T.-S. Chua, and X. Li. Toward scalable systems for big data
help to overcome current healthcare challenges. Communications & Strategies, analytics: A technology tutorial. IEEE Access, 2, 2014.
(87), 2012. [69] N. Waxer, D. Ninan, A. Ma, and N. Dominguez. How cloud computing and social
[39] V. Osmani, S. Balasubramaniam, and D. Botvich. Human activity recognition media are changing the face of health care. Physician Exec, 39(2), 2013.
in pervasive health-care: Supporting efficient remote collaboration. Journal of [70] S. Ullah, H. Higgins, B. Braem, B. Latre, C. Blondia, I. Moerman, S. Saleem,
Network and Computer Applications, 31(4), 2008. Z. Rahman, and K. S. Kwak. A comprehensive survey of wireless body area
[40] C. Doukas and I. Maglogiannis. Bringing iot and cloud computing towards networks. Journal of Medical Systems, 36(3), 2012.
pervasive healthcare. In Innovative Mobile and Internet Services in Ubiquitous [71] D. Garets and M. Davis. Electronic medical records vs. electronic health records:
Computing (IMIS), 2012 Sixth International Conference on. IEEE, 2012. yes, there is a difference. Policy white paper. Chicago, HIMSS Analytics, 2006.
[41] N. Terry. Will the internet of things disrupt healthcare? 2016. [72] K. Smolij and K. Dun. Patient health information management: searching for the
[42] R. Marques, J. Gregório, D. S. M. Mira, and L. Lapão. The promise of the internet right model. Perspectives in Health Information Management, 3(10), 2006.
of things in healthcare: How hard is it to keep? Studies in health technology and [73] F. Martin-Sanchez and K. Verspoor. Big data in medicine is driving big changes.
informatics, 228, 2016. Yearb Med Inform, 9(1), Aug 2014. 25123716[pmid].
[43] J. Santos, J. J. Rodrigues, B. M. Silva, J. Casal, K. Saleem, and V. Denisov. [74] M. Herland, T. M. Khoshgoftaar, and R. Wald. A review of data mining using
 13

big data in health informatics. Journal Of Big Data, 1(1), Jun 2014. [104] N. Sultan. Making use of cloud computing for healthcare provision: Opportunities
[75] F. F. Costa. Big data in biomedicine. Drug discovery today, 19(4), 2014. and challenges. International Journal of Information Management, 34(2), 2014.
[76] C. Habib, A. Makhoul, R. Darazi, and C. Salim. Self-adaptive data collection and [105] Z.-R. Li, E.-C. Chang, K.-H. Huang, and F. Lai. A secure electronic medical
fusion for health monitoring based on body sensor networks. IEEE Transactions record sharing mechanism in the cloud computing platform. In Consumer
on Industrial Informatics, 12(6), 2016. Electronics (ISCE), 2011 IEEE 15th International Symposium on. IEEE, 2011.
[77] Y. Yuehong, Y. Zeng, X. Chen, and Y. Fan. The internet of things in healthcare: [106] C.-T. Yang, L.-T. Chen, W.-L. Chou, and K.-C. Wang. Implementation of a
An overview. Journal of Industrial Information Integration, 1, 2016. medical image file accessing system on cloud computing. In Computational
[78] E. Jovanov and A. Milenkovic. Body area networks for ubiquitous healthcare Science and Engineering (CSE), 2010 IEEE 13th International Conference on.
applications: opportunities and challenges. Journal of medical systems, 35(5), IEEE, 2010.
2011. [107] A. Bahga and V. K. Madisetti. A cloud-based approach for interoperable electronic
[79] M. Barua, X. Liang, R. Lu, and X. Shen. Espac: Enabling security and patient- health records (ehrs). IEEE Journal of Biomedical and Health Informatics, 17(5),
centric access control for ehealth in cloud computing. International Journal of 2013.
Security and Networks, 6(2-3), 2011. [108] Y.-Y. Chen, J.-C. Lu, and J.-K. Jan. A secure ehr system based on hybrid clouds.
[80] P. Kulkarni and Y. Ozturk. mphasis: Mobile patient healthcare and sensor Journal of Medical Systems, 36(5), 2012.
information system. Journal of Network and Computer Applications, 34(1), 2011. [109] G. Fernández, I. de la Torre-Dez, and J. J. P. C. Rodrigues. Analysis of the cloud
[81] K. Darshan and K. Anandakumar. A comprehensive review on usage of internet of computing paradigm on mobile health records systems. In Innovative Mobile
things (iot) in healthcare system. In Emerging Research in Electronics, Computer and Internet Services in Ubiquitous Computing (IMIS), 2012 Sixth International
Science and Technology (ICERECT), 2015 International Conference on. IEEE, Conference on, July 2012.
2015. [110] G. Fernández-Cardeñosa, I. de la Torre-Dı́ez, M. López-Coronado, and J. J.
[82] S. Patel, H. Park, P. Bonato, L. Chan, and M. Rodgers. A review of wearable sen- Rodrigues. Analysis of cloud-based solutions on ehrs systems in different
sors and systems with application in rehabilitation. Journal of neuroengineering scenarios. Journal of medical systems, 36(6), 2012.
and rehabilitation, 9(1), 2012. [111] M. Rodriguez-Martinez, H. Valdivia, J. Rivera, J. Seguel, and M. Greer. Medbook:
[83] A. Ochian, G. Suciu, O. Fratu, C. Voicu, and V. Suciu. An overview of cloud mid- A cloud-based healthcare billing and record management system. In Cloud
dleware services for interconnection of healthcare platforms. In Communications Computing (CLOUD), 2012 IEEE 5th International Conference on. IEEE, 2012.
(COMM), 2014 10th international conference on. IEEE, 2014. [112] C. He, X. Jin, Z. Zhao, and T. Xiang. A cloud computing solution for hospital
[84] D. Thilakanathan, S. Chen, S. Nepal, R. Calvo, and L. Alem. A platform for secure information system. In Intelligent Computing and Intelligent Systems (ICIS), 2010
monitoring and sharing of generic health data in the cloud. Future Generation IEEE International Conference on, volume 2. IEEE, 2010.
Computer Systems, 35, 2014. [113] G. Kanagaraj and A. Sumathi. Proposal of an open-source cloud computing
[85] X. Xu and M. Zhong. Wireless body sensor networks with cloud computing system for exchanging medical images of a hospital information system. In
capability for pervasive healthcare: Research directions and possible solutions. 3rd International Conference on Trendz in Information Sciences & Computing
In Frontier and Future Development of Information Technology in Medicine and (TISC2011). IEEE, 2011.
Education. Springer, 2014. [114] C. Doukas, T. Pliakas, and I. Maglogiannis. Mobile healthcare information man-
[86] M. S. Hossain and G. Muhammad. Cloud-assisted speech and face recognition agement utilizing cloud computing and android os. In 2010 Annual International
framework for health monitoring. Mobile Networks and Applications, 20(3), 2015. Conference of the IEEE Engineering in Medicine and Biology. IEEE, 2010.
[87] A. Bourouis, M. Feham, and A. Bouchachia. A new architecture of a ubiquitous [115] R. S. Weinstein, A. Bhattacharyya, A. R. Graham, and J. R. Davis. Telepathology:
health monitoring system: a prototype of cloud mobile health monitoring system. A ten-year progress report. Human Pathology, 28(1), 1997.
arXiv preprint arXiv:1205.6910, 2012. [116] R. Negra, I. Jemili, and A. Belghith. Wireless body area networks: Applications
[88] J. K. Zao, T.-T. Gan, C.-K. You, C.-E. Chung, Y.-T. Wang, S. J. Rodrı́guez Méndez, and technologies. Procedia Computer Science, 83, 2016.
T. Mullen, C. Yu, C. Kothe, C.-T. Hsiao, et al. Pervasive brain monitoring and [117] C. Chakraborty, B. Gupta, and S. K. Ghosh. A review on telemedicine-based
data sharing based on multi-tier distributed computing and linked data technology. wban framework for patient monitoring. Telemedicine and e-Health, 19(8), 2013.
Frontiers in human neuroscience, 8, 2014. [118] Z. Jin, J. Oresko, S. Huang, and A. C. Cheng. Hearttogo: A personalized medicine
[89] K. Ha, Z. Chen, W. Hu, W. Richter, P. Pillai, and M. Satyanarayanan. Towards technology for cardiovascular disease prevention and detection. In 2009 IEEE/NIH
wearable cognitive assistance. In Proceedings of the 12th annual international Life Science Systems and Applications Workshop, April 2009.
conference on Mobile systems, applications, and services. ACM, 2014. [119] J. Wang, Z. Zhang, X. Yang, L. Zuo, and J.-U. Kim. A novel three-tier diabetes
[90] M. Margaret, T. Miron-Shatz, A. Lau, and C. Paton. Big data in science and patients monitoring architecture in hospital environment. In Proceedings, The 2nd
healthcare: A review of recent literature and perspectives. 2014. International Conference on Computer and Applications CCA, 2013.
[91] S. Vicini, S. Bellini, A. Rosi, and A. Sanna. An internet of things enabled [120] N. Kernen, M. Srestniemi, J. Partala, M. Hmlinen, J. Reponen, T. Seppnen,
interactive totem for children in a living lab setting. In 2012 18th International J. Iinatti, and T. Jms. Ieee802.15.6 -based multi-accelerometer wban system for
ICE Conference on Engineering, Technology and Innovation, June 2012. monitoring parkinson’s disease. In 2013 35th Annual International Conference of
[92] M. Vazquez-Briseno, C. Navarro-Cota, J. I. Nieto-Hipolito, E. Jimenez-Garcia, the IEEE Engineering in Medicine and Biology Society (EMBC), July 2013.
and J. D. Sanchez-Lopez. A proposal for using the internet of things concept [121] P. Khan, M. A. Hussain, and K. S. Kwak. Medical applications of wireless body
to increase children’s health awareness. In CONIELECOMP 2012, 22nd Interna- area networks. Int. J. Digital Content Technol. Appli, 2009.
tional Conference on Electrical Communications and Computers, Feb 2012. [122] T. S. Dahl and M. N. K. Boulos. Robots in health and social care: A
[93] M. Moh, L. Ho, Z. Walker, and T.-S. Moh. A prototype on rfid and sensor complementary technology to home care and telehealthcare? Robotics, 3(1), 2014.
networks for elder health care. RFID handbook: applications, technology, security, [123] G. Acampora, D. J. Cook, P. Rashidi, and A. V. Vasilakos. A survey on ambient
and privacy, 17, 2008. intelligence in healthcare. Proceedings of the IEEE, 101(12), 2013.
[94] B. M. Silva, J. J. Rodrigues, I. de la Torre Dez, M. Lpez-Coronado, and [124] H. Xia, I. Asif, and X. Zhao. Cloud-ecg for real time ecg monitoring and analysis.
K. Saleem. Mobile-health: A review of current state in 2015. Journal of Computer methods and programs in biomedicine, 110(3), 2013.
Biomedical Informatics, 56, 2015. [125] M. Chen, Y. Ma, S. Ullah, W. Cai, and E. Song. Rochas: robotics and cloud-
[95] G. Yang, L. Xie, M. Mäntysalo, X. Zhou, Z. Pang, L. Da Xu, S. Kao-Walter, assisted healthcare system for empty nester. In Proceedings of the 8th international
Q. Chen, and L.-R. Zheng. A health-iot platform based on the integration of conference on body area networks. ICST (Institute for Computer Sciences, Social-
intelligent packaging, unobtrusive bio-sensor, and intelligent medicine box. IEEE Informatics and Telecommunications Engineering), 2013.
transactions on industrial informatics, 10(4), 2014. [126] D. Gachet, M. de Buenaga, F. Aparicio, and V. Padrón. Integrating internet of
[96] C. Thuemmler and C. Bai. Health 4.0: How Virtualization and Big Data Are things and cloud computing for health services provisioning: The virtual cloud
Revolutionizing Healthcare. Springer Publishing Company, Incorporated, 1st carer project. In Innovative Mobile and Internet Services in Ubiquitous Computing
edition, 2018. (IMIS), 2012 Sixth International Conference on. IEEE, 2012.
[97] M. Viceconti, P. Hunter, and R. Hose. Big data, big knowledge: big data for [127] H. Zhou and H. Hu. Human motion tracking for rehabilitationa survey. Biomedical
personalized healthcare. IEEE journal of biomedical and health informatics, 19 Signal Processing and Control, 3(1), 2008.
(4), 2015. [128] O. Pereira, J. M. L. P. Caldeira, and J. J. P. C. Rodrigues. Body sensor network
[98] L. Hood and M. Flores. A personal view on systems medicine and the emergence mobile solutions for biofeedback monitoring. Mobile Networks and Applications,
of proactive {P4} medicine: predictive, preventive, personalized and participatory. 16(6), 2011.
New Biotechnology, 29(6), 2012. [129] J. M. L. P. Caldeira, J. A. F. Moutinho, B. Vaidya, P. Lorenz, and J. J. P. C.
[99] A. Holzinger, C. Röcker, and M. Ziefle. From Smart Health to Smart Hospitals. Rodrigues. Intra-body temperature monitoring using a biofeedback solution.
Springer International Publishing, Cham, 2015. In 2010 Second International Conference on eHealth, Telemedicine, and Social
[100] N. T. Issa, S. W. Byers, and S. Dakshanamurthy. Big data: the next frontier for Medicine, Feb 2010.
innovation in therapeutics and healthcare. Expert review of clinical pharmacology, [130] J. J. Rodrigues, O. R. Pereira, and P. A. Neves. Biofeedback data visualization
7(3), 2014. for body sensor networks. Journal of Network and Computer Applications, 34(1),
[101] N. V. Chawla and D. A. Davis. Bringing big data to personalized healthcare: a 2011.
patient-centered framework. Journal of general internal medicine, 28(3), 2013. [131] M. McKnight. Iot, industry 4.0, industrial iot why connected devices are the
[102] D. Chen, Y. Chen, B. N. Brownlow, P. P. Kanjamala, C. A. G. Arredondo, B. L. future of design. KnE Engineering, 2(2), 2017.
Radspinner, and M. A. Raveling. Real-time or near real-time persisting daily [132] S. Movassaghi, M. Abolhasan, J. Lipman, D. Smith, and A. Jamalipour. Wireless
healthcare data into hdfs and elasticsearch index inside a big data platform. IEEE body area networks: A survey. IEEE Communications Surveys & Tutorials, 16
Transactions on Industrial Informatics, 13(2), 2017. (3), 2014.
[103] M. Li, S. Yu, Y. Zheng, K. Ren, and W. Lou. Scalable and secure sharing of [133] R. van Kranenburg and A. Bassi. Iot challenges. Communications in Mobile
personal health records in cloud computing using attribute-based encryption. IEEE Computing, 1(1), Nov 2012.
transactions on parallel and distributed systems, 24(1), 2013. [134] A.-R. Sadeghi, C. Wachsmann, and M. Waidner. Security and privacy challenges
 14

in industrial internet of things. In Design Automation Conference (DAC), 2015 management. IEEE journal of biomedical and health informatics, 21(6), 2017.
52nd ACM/EDAC/IEEE. IEEE, 2015. [164] E. E. Schadt. The changing privacy landscape in the era of big data. Molecular
[135] H. Huang, T. Gong, N. Ye, R. Wang, and Y. Dou. Private and secured medical Systems Biology, 8(1), 2012.
data transmission and analysis for wireless sensing healthcare system. IEEE [165] H. Wu, Q. Wang, and K. Wolter. Mobile healthcare systems with multi-
Transactions on Industrial Informatics, 13(3), 2017. cloud offloading. In 2013 IEEE 14th International Conference on Mobile Data
[136] F. A. Alaba, M. Othman, I. A. T. Hashem, and F. Alotaibi. Internet of things Management, volume 2. IEEE, 2013.
security: A survey. Journal of Network and Computer Applications, 88, 2017. [166] Z.-H. Zhan, X.-F. Liu, Y.-J. Gong, J. Zhang, H. S.-H. Chung, and Y. Li. Cloud
[137] S. Liu, S. Hu, J. Weng, S. Zhu, and Z. Chen. A novel asymmetric three-party computing resource scheduling and a survey of its evolutionary approaches. ACM
based authentication scheme in wearable devices environment. Journal of Network Computing Surveys (CSUR), 47(4), 2015.
and Computer Applications, 60, 2016. [167] S. Wachter, B. Mittelstadt, and L. Floridi. Transparent, explainable, and account-
[138] Y. Yang, X. Zheng, and C. Tang. Lightweight distributed secure data manage- able ai for robotics. Science Robotics, 2(6), May 2017.
ment system for health internet of things. Journal of Network and Computer [168] M. A. Johansen, P. E. Kummervold, T. Sørensen, and P. Zanaboni. Health
Applications, 89, 2017. Emerging Services for Internet of Things (IoT). professionals’ experience with patients accessing their electronic health records:
[139] A. Kulkarni and S. Sathe. Healthcare applications of the internet of things: A Results from an online survey. 2019.
review. International Journal of Computer Science and Information Technologies, [169] J. Brett, M. Boulton, and E. Watson. Development of an e-health app to support
5(5), 2014. women prescribed adjuvant endocrine therapy after treatment for breast cancer.
[140] K. Jee and G.-H. Kim. Potentiality of big data in the medical sector: focus on Patient preference and adherence, 12, 2018.
how to reshape the healthcare system. Healthcare informatics research, 19(2), [170] T. Corbett, K. Singh, L. Payne, K. Bradbury, C. Foster, E. Watson, A. Richardson,
2013. P. Little, and L. Yardley. Understanding acceptability of and engagement with
[141] H. Chang and M. Choi. Big data and healthcare: building an augmented world. web-based interventions aiming to improve quality of life in cancer survivors: A
Healthcare Informatics Research, 22(3), 2016. synthesis of current research. Psycho-oncology, 27(1), 2018.
[142] V. Jirkovsky, M. Obitko, and V. Marik. Understanding data heterogeneity in the [171] D. Tao, T. Wang, T. Wang, T. Zhang, X. Zhang, and X. Qu. A systematic review
context of cyber-physical systems integration. IEEE Transactions on Industrial and meta-analysis of user acceptance of consumer-oriented health information
Informatics, PP(99), 2016. technologies. Computers in Human Behavior, 2019.
[143] S. Barocas and D. Boyd. Engaging the ethics of data science in practice.
Communications of the ACM, 60(11), 2017.
[144] C. O’Neil. Weapons of math destruction: How big data increases inequality and
threatens democracy. Broadway Books, 2017.
[145] R. Higberg and G. Larsson. Realization of industry 4.0 through rfid. Master
of Science in Engineering Technology, Industrial Design Engineering. Lulea
University of Technology, Department of Business Administration, Technology and
Social Sciences, 2016.
[146] H. Lasi, P. Fettke, H.-G. Kemper, T. Feld, and M. Hoffmann. Industry 4.0.
Business & Information Systems Engineering, 6(4), 2014.
[147] X. Li, D. Li, J. Wan, A. V. Vasilakos, C.-F. Lai, and S. Wang. A review of
industrial wireless networks in the context of industry 4.0. Wireless Networks,
2015.
[148] F. Almada-Lobo. The industry 4.0 revolution and the future of manufacturing
execution systems (mes). Journal of Innovation Management, 3(4), 2016.
[149] B. Kehoe, S. Patil, P. Abbeel, and K. Goldberg. A survey of research on
cloud robotics and automation. IEEE Transactions on Automation Science and
Engineering, 12(2), 2015.
[150] W. Raghupathi and V. Raghupathi. Big data analytics in healthcare: promise and
potential. Health Information Science and Systems, 2(1), 2014.
[151] R. Nambiar, R. Bhardwaj, A. Sethi, and R. Vargheese. A look at challenges
and opportunities of big data analytics in healthcare. In Big Data, 2013 IEEE
International Conference on. IEEE, 2013.
[152] G. Manogaran, C. Thota, D. Lopez, and R. Sundarasekar. Big Data Security
Intelligence for Healthcare Industry 4.0. Springer International Publishing, Cham,
2017.
[153] Y. Tong, J. Sun, S. S. Chow, and P. Li. Cloud-assisted mobile-access of health data
with privacy and auditability. IEEE Journal of biomedical and health Informatics,
18(2), 2014.
[154] C. Thuemmler, J. Mueller, S. Covaci, T. Magedanz, S. De Panfilis, T. Jell, and
A. Gavras. Applying the software-to-data paradigm in next generation e-health
hybrid clouds. In Information Technology: New Generations (ITNG), 2013 Tenth
International Conference on. IEEE, 2013.
[155] A. ODriscoll, J. Daugelaite, and R. D. Sleator. big data, hadoop and cloud
computing in genomics. Journal of biomedical informatics, 46(5), 2013.
[156] B. Fabian, T. Ermakova, and P. Junghanns. Collaborative and secure sharing of
healthcare data in multi-clouds. Information Systems, 48, 2015.
[157] J. Biswas, J. Maniyeri, K. Gopalakrishnan, L. Shue, J. E. Phua, H. N. Palit, Y. S.
Foo, L. S. Lau, and X. Li. Processing of wearable sensor data on the cloud-
a step towards scaling of continuous monitoring of health and well-being. In
2010 Annual International Conference of the IEEE Engineering in Medicine and
Biology. IEEE, 2010.
[158] G. Aceto, A. Botta, W. de Donato, and A. Pescapè. Cloud monitoring: Definitions,
issues and future directions. In 1st IEEE International Conference on Cloud
Networking, CLOUDNET 2012, Paris, France, November 28-30, 2012, 2012.
[159] V. Persico, A. Montieri, and A. Pescapè. On the network performance of
amazon s3 cloud-storage service. In Cloud Networking (Cloudnet), 2016 5th
IEEE International Conference on. IEEE, 2016.
[160] V. Persico, A. Botta, P. Marchetta, A. Montieri, and A. Pescapè. On the
performance of the wide-area networks interconnecting public-cloud datacenters
around the globe. Computer Networks, 112, 2017.
[161] R. B. Antequera, P. Calyam, D. Chemodanov, W. de Donato, A. Mishra,
A. Pescapé, and M. Skubic. Socio-technical approach to engineer gigabit
app performance for physicaltherapy-as-a-service. In IEEE 19th International
Conference on e-Health Networking, Applications and Services (IEEE Healthcom
2017).
[162] X. M. Zhang and N. Zhang. An open, secure and flexible platform based on
internet of things and cloud computing for ambient aiding living and telemedicine.
In 2011 International Conference on Computer and Management (CAMAN), May
2011.
[163] R. Sánchez-Guerrero, F. A. Mendoza, D. Dı́az-Sánchez, P. A. Cabarcos, and A. M.
López. Collaborative ehealth meets security: Privacy-enhancing patient profile