Allergic rhinitis is a common upper airway disease caused by hypersensitivity to various aeroallergens. It causes increased inflammation throughout the body and may be complicated by other otolaryngological pathologies such as chronic hyperplastic eosinophilic sinusitis, nasal polyposis, and serous otitis media. Allergic rhinitis is an IgE-mediated disease and immunotherapy can be a possible approach for patients to limit the use of antihistamines and corticosteroids. There is evidence that allergen immunotherapy can prevent the development of new sensitizations and reduce the risk of later development of asthma in patients with allergic rhinitis. However, some patients do not benefit from this approach and the efficacy of immunotherapy in reducing the severity and relapse of symptoms is still a matter of debate. This review highlights new aspects of allergic rhinitis with a particular focus on the impact of sexual dimorphism on the disease manifestation and efficacy to the allergen specific immunotherapy. The symptoms of AR may be variegated and arise after inhalation and primary sensitization to few or numerous allergens such as pollen of various plants, house dust mite, hair, and organic material from certain animals , 2.AR is estimated to affect around the 20% of the occidental world population causing a detrimental effect on productivity and lifestyle quality, including the development of emotional challenges and a decline in sleep, social interaction, daily activities, and work and academic performance , 4. In fIn this review we update on relevant topics on AR, in particular on gender-related differences in the prevalence and manifestation of AR and the molecular mechanism behind them. Moreover, we review the current knowledge regarding the use of allergen specific immunotherapy (AIT) for the control of AR especially when AR is associated with asthma or chronic rhinosinusitis.2.AR can be phenotypically classified following several criteria such as severity , time and type of exposure , as well as duration of symptoms (intermittent or persistent) . MoreoveAR is often associated to other comorbidities of the airways. Indeed, AR and asthma are strongly correlated also because they show a similar immune response for what concerns inflammatory cells and mediators even if they differ in the extent of the immune response itself. As a proof, a metanalysis of European and non-European studies confirmed that history of AR is greatly linked to asthma even if with different association in different studies . Rhiniti+T lymphocytes, intervene in the response (+ T cells into specific T helper 2 (Th2) cells. Then, these cells produce IL-4 and IL-13 which in turn allow B cell isotype-switching to IgE production. IgEs are then recognized by specific cell-surface receptors (FcεRI) on mast cells, for further release of proinflammatory mediators  mainly through degranulation. In the late phase, so 4–6 h from allergen encounter, different cell types  as well as numerous molecular mediators (such as elastase and basic proteins) are involved  receptor antagonists, such as montelukast and zafirlukast , bind toThrough their agonistic activity at 1 and 2-adrenergic receptors on nasal mucosal endothelial cells, nasal decongestants alleviate nasal congestion symptoms by reducing mucosal edema. Commonly used nasal sprays are oxymetazoline, phenylephrine, and pseudoephedrine. However, if excessively used nasal decongestant might result in rhinitis medicamentosa  , which iIntranasal corticosteroids are useful for treating both mild and moderate-severe AR in both children and adults and represent a non-specific symptomatic treatment as they inhibit immune cells. For severe or uncontrollable symptoms, systemic corticosteroids (by mouth or by injection) should only be used as a last choice.Mast cell stabilizers, such as sodium cromoglicate, interfere with exocytosis of mast cell granules and can limit the release of inflammatory mediators from activated mast cells . ConsequAn adjunct to symptomatic drug treatment, nasal irrigation with topical nasal sprays containing isotonic sodium chloride solution is used.5.Since some patients with AR do not benefit from standard medical care, allergen specific immunotherapy (AIT) could be employed as a disease modifying therapeutic approach.AIT was first reported by Noon  and FreeAIT involves the repeated administration of high-dose allergens towards two main ways: subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) for at least 3 years to confer clinical benefits . IntralyAlternaria alternata, Alt a 1, caused reductions in the allergic symptoms scores in AR patients , and recombinant fusion proteins  . RecombiNotably, the identification of the specific allergen is mandatory. Molecular diagnosis of allergy is constantly evolving and has been implemented as a complementary diagnostic tool for AIT . To bett6.AIT is based on the long term and repeated administration of specific doses of allergens to modify the immune response and induce protective immunity. The administration of AIT achieves a successful outcome when the allergic patient develops tolerance to the allergen. Specifically, AIT is reputed to be working not only when the patient lives his or her life without discomfort caused by the symptomatology, but also when from an immunological point of view a tolerance profile is achieved in the context of both innate and adaptive immunity. Indeed, AIT uses general mechanisms of immune tolerance to allergens to normalize allergen-specific T and B cells, IgE and IgG production, as well as modification of mast cells and basophil activation thresholds. The efficacy of AIT depends on one side on the induction of allergen-neutralizing IgG antibodies that block allergens at the mucosal sites, preventing FcεRII-mediated facilitated allergen presentation, and inhibiting mast cell degranulation and allergic inflammation. On the other side it depends on maintenance of regulatory cells  in order to suppress type 2 immune responses and allergic inflammation.Treatment for AR that focuses on immune regulation aims to shift the normal courses of response to an allergen rather than bringing about a transformation to an immunologically ignorant or unresponsive state.6.1.Part of the success of AIT is the unresponsiveness of T cells to the allergen. This occurs in presence of anergic T cells possibly due to high-dose tolerance  and a re+ and Forkhead box P3 (FOXP3+) Treg population in the nasal mucosa of treated patients (In the context of subcutaneous AIT (SCIT) there is evidence of a local increase in the tolerogenic CD25patients . Besidespatients , 74.As mentioned above, a key role in the context of AIT is played by IL-10 which, following therapy, is produced in high amounts by T lymphocytes along with other suppressive cytokines (such as TGF-β and IL-35), driving the generation of a tolerogenic immune phenotype: Treg1 cell proliferation, inhibition of Th2 response and, more in general, reduction of tissue-infiltrating proinflammatory cells .Beyond cytokine production, Tregs control suppressive mechanism thanks to metabolic pathways disruption, surface molecules capable of blocking dendritic cells activation, and release of cytotoxic molecules .6.2.After AIT, B cells tend to assume a more protective role modifying their phenotype in terms of type of antibody and cytokine produced, inducing immune tolerance directly or indirectly in the presence of the allergen.For example, regarding antibody production, an isotype switch is observed: instead of allergen specific IgE, IgG4-blocking antibodies against the same antigen are produced . In addi6.3.It has been shown that following AIT, mast cells and basophils, which play a pivotal role in initiating the allergic response, undergo rapid desensitization resulting in a dropped reaction to the allergen even in presence of high levels of specific IgE. At longer times, a decrease in tissue infiltration and release of proinflammatory mediators as well as reduction of allergy-associated receptors are observed , 82. HowFollowing AIT administration, the produced IgG inhibit IgE-mediated degranulation through FcεRI disaggregation, with a simultaneous increase in low-affinity FcγRII exposure on circulating basophil surface: in particular, IgG3 and, to a lesser extent, IgG2 appear to play this role , 84.Another cell population of innate immunity that plays a crucial role in AIT response is that of innate lymphoid cells (ILCs). Of these cells, those belonging to group 2 (ILC2) are the ones that most seem to be involved in allergic rhinitis context and show differences in their phenotype following immunotherapy administration. More specifically, what is observed is a significant decrease in ILC2 frequency  accompan7.AIT is to date the only established treatment able to modify the IgE-mediated allergic diseases by treating the underlying immunological mechanism . Most ofHowever, many meta-analysis and reviews outlined that major limitation in evaluating the clinical outcome of AIT are the broad diversity in composition of products, the study designs, the heterogeneity of the environmental conditions, the age of the population involved and the use of different primary and secondary study endpoints , 94, 95.In order to assess the real-world and long-term effectiveness of AIT in the treatment of AR in a broad population, the retrospective REAl-world effeCtiveness in allergy immunotherapy (REACT) study investigated a score-matched cohort of studies published from 2007 to 2017. The study included almost 100,000 (subjects matched 1:1 with controls) and indicated the overall efficacy of AIT in improvement of clinical and symptoms in AR patients with AIT prescription compared to patients with no AIT prescription across the 9 years of follow-up . The folHowever, the magnitude of the clinical efficacy of AIT remains difficult to establish, due to the use of different types of allergen extracts, doses, dosing regimens and evaluation period , 99. IndFinally, despite reported sex- and gender- related differences in AR, to our knowledge no data on differences in response to AIT between male and female AR patients have been produced so far. There are some evidences that male subjects were more likely to be non-adherent than female subjects to AIT , 103 and8.8.1.Patients with AR frequently suffer simultaneously of asthma sharing the same trigger factors, including pollens, house dust mite, pets, mold, and similar pathogenetic mechanisms. About 10%–40% of patients with AR have also allergic asthma as well as 60%–80% of asthmatic patients experience AR  and the Indeed, some cohorts showed a benefit of AIT in preventing the onset of asthma in AR patients , 106. RaThe EAACI guideline recommended AIT as an add-on to regular asthma therapy in adults with controlled or partially-controlled house dust mite driven allergic asthma , in whicMoreover, the REACT study  demonstr8.2.AR is considered a comorbidity factor in several otolaryngological disorders and is usually thought to be a key factor in the developing of chronic rhinosinusitis (CRS). Chronic rhinosinusitis (CRS) is defined as an inflammatory condition of the nose and paranasal sinus, characterized by nasal discharge, nasal obstruction, hyposmia or anosmia, and facial pressure that lasts more than 12 weeks .CRS is classically divided into two clinical phenotypes based on the presence of endoscopically visualized polyps in the middle nasal meatus: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Novel classification criteria have been recently introduced to identify other endotypes of CRS based on the anatomic distribution , endotype dominance , and clinical phenotypes . PrimaryWhile paranasal sinuses are of similar size at birth, they become larger in males leading to differences in ostium location and presumably to different susceptibility to develop CRS related. In fact, CRS and CRSsNP are more prevalent in females while CRSwNP is more prevalent in males . CRS symThe pathogenesis of the CRS is not completely understood; however it is likely that allergy-induced inflammation of the sinus mucosa can lead to local obstruction and predispose to infection leading to a chronic state of the disease. It has been recently demonstrated that CRSwNP is characterized by local production of polyclonal IgE idiotypes . These IIn 2004, the group of Nathan and colleagues developed a questionnaire to evaluate the impact of immunotherapy in the treatment of 114 atopic patients with associated sinusitis and published that 99% of patients had benefit from the immunotherapy, with a mean reduction of around 50% of symptoms, suggesting that immunotherapy could be effective in treatment for patients with AR and sinus disease .A systematic review published in 2014  analyzedAs concerning AFRS, a subtype of Th2 chronic rhinosinusitis whose determination criteria include also type 1 hypersensitivity to fungi confirmed by skin test or serum-specific blood test positivity, conclusive evidences of efficacy of immunotherapy are not present to date. Indeed some studies demonstrated significant improvement in the endoscopic disease score and CRS survey symptom score, and decreased systemic corticosteroid use in patients with AFRS after allergic immunotherapy treatment , 116. OtIn a recent review published in 2020, it has been stated that intranasal allergens may not penetrate the paranasal sinuses, but instead exert their effects indirectly by means of downstream, systemic factors that then feedback to the sinuses. The authors concluded that there is only limited evidence linking AR and CRS, but some subtypes of disease such as CRSwNP and AFRS may be most related to AR . This wa9.There are several evidences supporting that AIT alleviates symptoms, reduces medication requirements and improves the quality of life in AR individuals. AIT applied in the early stage of allergic disease seems to have a good preventive effect on progression of AR to asthma, especially in young children and in the development of new sensitizations. Female populations who appear to suffer more from AR symptoms in adulthood, may benefit more than male counterpart from AIT, but more studies must be conducted to confirm this hypothesis.As concerning association of AR and chronic rhinosinusitis, it even remains controversial. Despite being a recommendation for patients, the benefit of immunotherapy in the management of CRS is uncertain and it should only be considered as on option.However, AIT still shows high degree of heterogenicity and effectiveness that depend on multiple factors, including the allergen dose, the presence or the absence and the type of adjuvant, the way of delivery , treatment duration, and individual immunological response.In conclusion, beyond the advances in diagnosis and development of novel vaccine formulations, and beyond various evidences of AIT efficacy in AR, a standardization of the composition of products as well as technological improvements are needed to further increase the efficacy of AIT.


During the last few decades, the field of rehabilitation has experienced substantial development, growth, and acceptance. Rehabilitation addresses the impact of a health condition on a person’s everyday life by optimizing their functioning and reducing their experience of disability. Rehabilitation expands the focus of health beyond preventative and curative care to ensure people with a health condition can remain as independent as possible and participate in education, work and meaningful life roles . A definEnsure healthy lives and promote well-being for all at all ages [We also have now a better understanding of the growing global need, demand, and recognition of rehabilitation around the world. For example, it has been estimated that 2.41 billion people in the world could benefit from rehabilitation services. This means that at least one in every three persons in the world needs rehabilitation at some point during the course of their disease or injury . Now morall ages .Notwithstanding the foregoing arguments, there continues to be a high unmet need for rehabilitation globally, with some low- and middle-income countries reporting unmet needs up to 50% of those who could benefit from rehabilitation. Rehabilitation services are not accessible to many people around the world , 8. HealThe field of health policy and systems research (HPSR) seeks to understand and improve how societies organize themselves in achieving collective health goals, and how different actors interact in the policy and implementation processes to contribute to policy outcomes , 10. By In 2022 the WHO Rehabilitation Program established the World Rehabilitation Alliance (WRA)  to strenIn this context the co-authors of this editorial on behalf of their respective academic journals express their full support for the WRA mission in general and for the specific objectives of the research workstream. In concrete terms we, commit that our journals, as much as possible, will implement one or more of the following actions: (1) invite researchers in the field of HPSR for rehabilitation to submit their manuscripts to our Journals for peer review and possible publication, (2) create a special journal section, series, or designation dedicated to HPSR for rehabilitation, (3) appoint editorial board members with expertise in HPSR for rehabilitation, and (4) disseminate research articles among funding agencies and policymakers. These actions by our academic journals will help the WRA achieve its goal of strengthening rehabilitation services for all.


Dysregulation of molecular mechanisms that regulate nervous system development may be at the origin of brain tumors. We reviewed the role of neuropilin-1 (NRP1), a transmembrane glycoprotein that directs neuronal migration during development, in brain cancer types that afflict children or adults. We also present gene expression analysis showing that higher NRP1 expression is associated with higher grade tumors compared to lower grade tumors or non-tumoral brain tissue. Importantly, higher tumoral NRP1 mRNA content in glioblastoma (GBM) is associated with a worst patient prognosis. This evidence supports the view that NRP1 is a potential prognostic biomarker and therapeutic target in brain tumors. Neuropilins are transmembrane glycoproteins that regulate developmental processes in the nervous system and other tissues. Overexpression of neuropilin-1 (NRP1) occurs in many solid tumor types and, in several instances, may predict patient outcome in terms of overall survival. Experimental inhibition of NRP1 activity can display antitumor effects in different cancer models. Here, we review NRP1 expression and function in adult and pediatric brain cancers, particularly glioblastomas (GBMs) and medulloblastomas, and present analyses of NRP1 transcript levels and their association with patient survival in GBMs. The case of NRP1 highlights the potential of regulators of neurodevelopment as biomarkers and therapeutic targets in brain cancer. Neuropilins were first discovered as proteins influencing nervous system development and later emerged as regulators of the development and function of other tissues, including the cardiovascular and immune systems. A role for neuropilins in cancer biology has also been described through influences in angiogenesis and vascular and lymphatic biology as well as by directly modulating signaling within cancer cells. Increasing evidence indicates that neuropilins, particularly neuropilin-1 (NRP1), can affect the progression of different types of brain tumors, and modification of NRP1 activity has been investigated as an experimental therapeutic approach. In this article, we review the current knowledge on the expression and role of NRP1 in brain cancers and its potential as a target in experimental neurooncology.NRP1 gene, which is located on chromosome 10p11.22. The NRP1 gene spans over 120 kb and contains 17 exons. Alternative transcript splicing gives rise to additional protein isoform variants [Neuropilins are transmembrane glycoproteins structurally organized in three domains that act as non-tyrosine kinase surface proteins. They occur specifically in vertebrates in two homologous isoforms, NRP1 and neuropilin-2 (NRP2), which share 44% sequence homology with each other ,4. The tvariants ,4,5,6.NRP1 functions as a co-receptor capable of binding several different ligands to ultimately influence multiple signaling pathways. NRP1 is devoid of kinase activity by itself but can stimulate the kinase function of its co-receptors. The first receptors identified for NRP1 were semaphorins (SEMAs), particularly those belonging to SEMA class 3 (SEMA 3), which are further classified into seven soluble proteins, SEMA3A–SEMA3G. Each SEMA 3 member shows different affinities for NRP1 . NRP1 biSeveral lines of evidence demonstrate a role for NRP1 in regulating the normal development of the peripheral and central nervous system as well as other tissues. NRP1 plays a crucial role in directing neural crest cells that are precursors of peripheral neurons during development . ChimeriDuring neurodevelopment, precise connections between neurons and their appropriate targets are established. The leading edge of an axon, called the growth cone, drives the axon to its targets. This guidance process is mediated by several attractive and repulsive biochemical cues . ThroughFurther studies show that neuropilins direct distinct neuronal populations to different brain areas. Migrating cortical interneurons expressing neuropilins and their receptors, including SEMA 3A and SEMA 3F, are directed to the cortex, whereas neurons lacking neuropilins go to the striatum. SEMA 3A and SEMA 3F thus mediate a chemorepulsive signal from the striatum, which is enabled by neuropilins in migrating cortical neurons, establishing a migratory route to the cortex . This roIn the adult nervous system, NRP1/SEMA 3 may play a role in the regeneration and plasticity of sensory neurons . NRP1 isAn aspect of NRP1’s function related to its regulation of nervous system development and plasticity is its ability to influence the proliferation and differentiation of stem cells. Embryonic stem cells expressing NRP1 can give rise to precursors of neural cells as well as precursors of endothelial cells . NRP1 exGene expression of NRP1 is often but not always higher in tumor cells compared to corresponding non-tumoral tissue ,42. EarlMeasuring NRP1 expression by immunohistochemistry and in situ hybridization shows ubiquitous expression in colon adenocarcinoma tumors, and reverse transcriptase-polymerase chain reaction analysis (RT-PCR) shows NRP1 mRNA expression in colon adenocarcinoma cell lines. Overexpression of NRP1 leads to increased tumor growth and angiogenesis in human colon cancer cells xenografted into nude mice. Moreover, conditioned medium from NRP1-transfected colon cancer cells enhances endothelial cell migration. Regulation of NRP1 levels in colon cancer cells may involve epidermal growth factor (EGF) and MAPK signaling . InhibitExpression of NRP1 is found in hepatocellular carcinoma (HCC) but not in normal hepatocytes. Blockade of NRP1 function induced by peptide N results in inhibition of vascular remodeling and tumor growth in mice with HCC . Also, iSystemic administration of an antibody that blocks VEGF binding to the b domain of NRP1 (anti-NRP1B) slows tumor growth in NRP1-expressing lung carcinoma . MonocloIn melanoma cells, NRP1 expression promotes invasiveness partially through VEGFR-2. NRP1 expression is also sufficient to promote melanoma cell invasion accompanied by MMP-2 secretion. The ability of NRP1 to promote melanoma invasiveness involves Akt activation through its phosphorylation on T308 . NRP1 alA study using tumor biopsies from children with neuroblastomas (NBs) to assess the mRNA expression of neuropilin with quantitative RT-PCR showed that NRP1 and NRP2 mRNA and protein levels are higher in stages I-IV NB compared to non-tumor controls . KnockdoIn addition to directly regulating cancer cell function and angiogenesis, NRP1 can interact with different components of the tumor microenvironment. For example, NRP1 on stromal myofibroblasts acts on soluble fibronectin to promote fibronectin fibril assembly and matrix stiffness, resulting in the stimulation of tumor growth. An increase in fibronectin fibril assembly depends on α5β1 integrin, glycosylation of serine 612 of the extracellular domain of NRP1, an intact intracellular NRP1 SEA domain, and associations between NRP1, GIPC, and the nonreceptor tyrosine kinase c-Abl . In cervNRP1 can modulate tumor resistance to different modalities of therapy. The NRP1 inhibitor EG00229 sensitizes A549 lung carcinoma cells to the cytotoxic chemotherapeutics paclitaxel and 5-FU . AnotherNRP1 expression may be a marker of poor prognosis in different cancer types . For exaA glioblastoma (GBM) is the most prevalent and lethal type of primary brain tumor, accounting for half of newly diagnosed gliomas. Gliomas are a group of cancer types that together comprise about 80 percent of central nervous system (CNS) tumors in adults. . The proHuman malignant glioma cell lines express NRP1 mRNA and protein, as well as SEMA3A and SEMA3C . NRP1 prPatient-derived GBM cells expressing shRNAs for either VEGF or NRP1 show reduced stemness markers and neurosphere-forming capacity, and knockdown of VEGF and NRP1 inhibits the growth of patient-derived GBM xenografts in both zebrafish and mice and prolongs mouse survival. Moreover, NRP1 enhances GBM cell sensitivity to temozolomide . An immuRT-PCR of 37 glioma specimens, out of which 17 were grade IV GBM tumors, showed that NRP1 mRNA expression is higher in GBM than in non-tumoral tissue and lower-grade gliomas, and glioma patients with NRP1 overexpression (56.8%) showed a poorer prognosis indicated by reduced overall survival . MoreoveAnalysis of glioma tumors from the TCGA French cohort shows increased levels of NRP1 transcripts in GBMs as well as in other types of higher-grade gliomas, such as grade III astrocytomas, oligoastrocytomas, and oligodendromas, compared to non-tumoral-brain-tissue or lower-grade gliomas A. IncreaNRP1 expression is higher in grade III astrocytomas, oligoastrocytomas, and oligodendromas compared to grade I and grade II corresponding glioma tumors A. In astMeningiomas, which account for a little over a third of intracranial cancers, are defined as tumors emerging from the meninges, i.e., the dura mater, arachnoid, and pia mater that envelop the brain and spinal cord. Although most meningioma tumors are benign, they can present grades from grade I to grade III  associated with aggressiveness. The current WHO classification divides meningiomas into fifteen histologic subtypes across three grades of malignancy that reflect the recurrence rate and prognosis ,108.Immunohistochemical analysis of NRP1 expression in a series of 48 cases of meningiomas with different types and histological grades showed NRP1 staining in the vessels within all but two tumors and in the neoplastic cells in eighteen tumors . NRP1 mRA medulloblastoma is the most frequent malignant brain tumor type in children and represents an important cause of cancer-related morbidity and mortality in pediatric patients. Although multimodal therapy consisting of chemotherapy, radiotherapy, and surgery has improved cure rates, about one-third of patients relapse, and survivors show long-term sequalae. Medulloblastomas are classified into four consensus molecular subgroups, namely wing-less-activated (WNT), sonic hedgehog (SHH), Group 3, and Group 4, with patients bearing Group 3 and Group 4 tumors having the worst prognosis. Currently, each subgroup is further classified into twelve subtypes ,114.Inhibiting NRP1 function results in antitumor effects in experimental medulloblastomas by influencing cell survival, invasiveness, and stemness . KnockdoAn immunohistochemical study showed NRP1 overexpression in five medulloblastoma samples in comparison with non-tumoral pediatric cerebellar tissue. In a set of 32 medulloblastoma tumors, 90% of samples representing different molecular subtypes showed marked expression of NRP1 expression . AnotherEpendymomas are central nervous system (CNS) tumors that arise in the supratentorial region, posterior fossa, or spinal cord and can afflict both children and adults. These tumors are classified on the basis of histological and molecular features, including DNA methylation, age of onset, gender predominance, and the response to therapy. The prognosis for pediatric patients is generally poorer in comparison with adults ,122. AnaThe evidence reviewed above consistently indicates that, in many instances, increased expression of NRP1 predicts poorer patient outcomes as indicated by a shorter overall survival. In brain tumors, this is observed in GBMs (,88,91, pCurrent evidence also indicates that inhibiting NRP1 activity through any of the different possible approaches, from small molecule-mediated inhibition to RNA interference knockdown, can display antitumor effects in several cancer types and across a range of experimental models and conditions. The fact that NRP1 is a transmembrane glycoprotein makes it a potentially more “druggable” target compared to, for example, transcription factors or other components of the intracellular machinery. Although most of the work performed on NRP1 inhibition in cancer to date remains at the preclinical stage, clinical research initiatives have emerged. Thus, the findings of a stimulating role of the PlGF/NRP1 pathway in pediatric cancers have led to an open-label Phase I clinical trial aimed to evaluate TB-403, a monoclonal antibody against PlGF, in pediatric patients with relapsed or refractory MBs, neuroblastomas, Ewing sarcoma, or alveolar rhabdomyosarcoma . The ong


To date, at least 2.41 billion people with Non-Communicable Diseases (NCDs) are in need of rehabilitation. Rehabilitation care through innovative technologies is the ideal candidate to reach all people with NCDs in need. To obtain these innovative solutions available in the public health system calls for a rigorous multidimensional evaluation that, with an articulated approach, is carried out through the Health Technology Assessment (HTA) methodology. In this context, the aim of the present paper is to illustrate how the Smart&TouchID (STID) model addresses the need to incorporate patients’ evaluations into a multidimensional technology assessment framework by presenting a feasibility study of model application with regard to the rehabilitation experiences of people living with NCDs. After sketching out the STID model’s vision and operational process, preliminary evidence on the experiences and attitudes of patients and citizens on rehabilitation care will be described and discussed, showing how they operate, enabling the co-design of technological solutions with a multi-stakeholder approach. Implications for public health are discussed including the view on the STID model as a tool to be integrated into public health governance strategies aimed at tuning the agenda-setting of innovation in rehabilitation care through a participatory methodology. To date, at least 2.41 billion people with Non-Communicable Diseases (NCDs) are in need of rehabilitation. Rehabilitation treatments through innovative technologies that can make this service widespread, up to the patient’s home, are showing growing substantial evidence of their effectiveness  methodology. However, the route to integrate patients’ perspectives of evaluation, considered essential from this standpoint, is still much debated . MoreovThe aim of the present paper is, therefore, to illustrate how the Smart&TouchID (STID) model addresses the need to incorporate patients’ evaluations into a multidimensional technology assessment framework by presenting a feasibility study of model application with regard to rehabilitation experiences of people living with NCDs.Although the STID model operates to optimize the co-design and development of innovative solutions for rehabilitation care for NCDs, in the present paper the focus is not on specific technologies as outputs of the STID multidimensional evaluation flow. Rather, the attention is drawn to the processes that the STID model enables in order to integrate the standpoints (action and attitudes) of the various stakeholders to obtain technology optimization. This way, the paper targets the feasibility testing of the STID model as a tool in national/regional governance strategies aimed at tuning the agenda-setting of innovation in rehabilitation care through a participatory methodology.After detailing how technological innovation can address the growing need for rehabilitation of people with NCDs, an overview of the STID model will be illustrated, showing how it models the development of health technologies for people with NCDs into a flow that embeds the evaluation of digital solutions from the very first stages of their development and from the perspectives of different stakeholders including patients. Then, as a feasibility study in running the STID model with regard to the embedding of patients’ and citizens’ evaluations in technological development, preliminary evidence from the collection of patients’ and citizens’ experiences on rehabilitation will be described and discussed.In the last thirty years, the need for rehabilitation for people with Non-Communicable Diseases (NCDs) has increased to involve up to 2.41 billion people. Innovative technologies for remote rehabilitation care can help reach all those in need.According to the estimates of the Global Burden of Diseases, Injuries, and Risk Factors Study , NCDs haDigital healthcare technologies, conceived as new means for addressing the big healthcare challenges of the 21st century  can provTo reach the aim of making tech-enabled rehabilitation a widespread service, ensuring accessibility and quality home-based management of chronic conditions requires rigorous and evidence-based evaluation regarding its safety, efficacy, and sustainability balance. The Health Technology Assessment (HTA) methodology provides a more complete and valid approach for evaluating if and how in a health system, new technologies can promote equitable and quality care with available healthcare resources. However, in the last ten years, HTA agencies have strongly highlighted that the assessment of new technologies should not only include the technical and financial dimensions of new treatments, but also patients’ perspectives on usability, acceptability, and their full impact on everyday care routines. That is, an expansion in breadth and depth of the HTA approach is called for to include in the evaluation process the evidence on the impact of new technologies both on patients’ health and on their well-being and quality of life . SeveralSmart&Touch-ID (STID) is a research project funded by the Lombardy Region as part of the HUB Research and Innovation Call . The main outcome of the project is the STID model, which structures the design and development of technological solutions for the home-based management of chronic disabilities. The STID model embeds patient evaluations of technology from the very first stages of its development and provides a dedicated infrastructure whereby the different stakeholders can take action as actors of the same ecosystem, not as isolated segments that act sequentially to the same aim.The vision behind STID consists of harmonizing the health (ID) and well-being (Touch) needs of patients and citizens with the design and development (SMART) actions of Innovators’ eHealth solutions while working on the economic sustainability of the proposed innovation (Governance). This aspect of the STID model provides an answer to the unsolved gap of the patient perspective management in the technology assessment and advancement, by applying a patient-centered and co-design approach, typical of the multidimensional processes . The circular model is concretized through the definition of an operational flow that enables interaction between the involved stakeholders and empowers them to carry out their activities in line with their roles and timelines. The flow has been termed ‘circular’ because the realization of activities relevant to the needs of each stakeholder has impacts on the realization of the activities of the other stakeholders in an iterative way. An operational flow originates from the launch of a challenge in response to a need. A need models the expression of a demand as perceived by the patient and/or citizen, the domain experts, and the clinicians. A challenge is the process that leads to the identification of technological solutions in response to the detected need that is validated against the ID, Touch, SMART, and Governance aspects.The evidence about needs that the technological solutions address is collected from different sources .In the bottom-up challenge, patients and citizens proactively communicate their experiences and attitudes through targeted and anonymous questionnaires (termed “waves”) administered on the website of the project , and the latter manifest interest in the evolution of the challenge and/or declare their interest in testing the solutions.Innovators who propose ideas are assisted by Experts who help them turn their idea into a prototype through mentorship-dedicated sessions.All proposed prototypes are validated against SMART, Touch, and ID criteria. If one or more criteria are not met, Experts help Innovators bring their prototypes in line with the established criteria through mentorship. Once prototypes meet all the SMART, Touch, and ID criteria required, they are evaluated for Governance aspects. Finally, prototypes supporting the needs are discussed in terms of their sustainability to identify the most promising ones also from the point of view of patients’ acceptability.The operational flow has been implemented using PROCS (Process Oriented Development) software, version 1.1.5 . PROCS eThe way STID operates is framed through multidimensional assessment tools, in line with the mainstream methodology for public health interventions. At the same time, its organizational flow takes into account the needs of multiple stakeholders to develop technological solutions that are relevant and applicable to the domain of rehabilitation care, tapping not only the clinical and economic dimensions but also the ones connected to well-being in the real-life experiences of patients . Therefohttps://smart-touch-id.com/en/#/home, accessed on 20 May 2023). People interested in a challenge can subscribe to the website and contribute to it in different ways according to their role .The designed model takes concrete form through a web portal  without having to authenticate. This link was available in the news published on the Regional Open Innovation platform, in the newsletters of Regional and National Clusters, and on the sites of the project partners. People could fill in the survey by accessing it from a computer and mobile devices, such as smartphones and tablets. The participation was anonymous and voluntary, and respondents could abandon completing the questionnaire without consequences. The questionnaire is still accessible through the STID website. The preliminary data here presented were collected from 22 September to 9 November 2022.The data on rehabilitation experiences of patients and citizens were collected via an anonymous online survey generated with the Qualtrics platform using a snowball sampling method but considering the consistent presence of chronic patients equal to 50% of the sample, in accordance with the national data on NCD prevalence  and information about the presence of chronic disabilities. Moreover, it collected information about the frequency and perceived proficiency in the use of technologies of all the samples and perceived health-related Quality of Life and rehabilitation experiences of people with chronic disabilities. The following paragraph describes the measures in detail.Eligible participants were adults over 18 with sufficient Italian language and computer skills to answer the online questionnaire.The study was conducted following the Declaration of Helsinki and all relevant guidelines and regulations covering respect for the rights and dignity of participants and guaranteeing the anonymity of the data and respecting privacy criteria for respondents.All participants reported the frequency of use and the perceived expertise of different technological devices . Moreover, they reported the frequency of use and the perceived proficiency in different activities with technologies, namely using the Internet, e-mail, or social networks, e-gaming, reading online magazines, listening to music, or monitoring one’s health with digital devices.The perceived Quality of Life of respondents with chronic disabilities was measured through the WHODAS 2.0 scale . The WorFor this survey, the 12-item self-report version was used. For each domain, WHODAS 2.0 provides a profile and a summary measure of the level of disability and functioning in daily life applicable to adult and older populations in different cultural contexts. Furthermore, WHODAS 2.0 includes three additional questions that evaluate the frequency and the total or partial impact that the difficulties have on daily life (in the last 30 days). Scoring is on a five-point Likert scale ranging from “no difficulty” to “very difficult.” The scores of all six domains are added. Finally, the total score is converted into a scale from 0 (no disability) to 100 . High scores, therefore, indicate high levels of disability.Perceived health was assessed through two questions created ad hoc. Participants had to move a cursor and stop between 0  and 10 (the best level), corresponding to how they perceived their health on that day or in the last week.Participants with chronic disabilities answered questions referring to their rehabilitation experiences for their prevalent disability (the one that had the most significant impact on daily life). It was asked if a rehabilitation program had ever been proposed. If so, the regimen , the clinical objective , the possible use of technological devices, and the nature of such devices  were explored in detail.Basic attitudes and beliefs about rehabilitation were explored among all respondents. The intent was to collect what respondents believed to be true  about rehabilitation. Attitudes and beliefs were explored through 21 statements on which respondents could express their agreement on a five-point Likert scale, from 1  to 5 (strongly agree). An example item is “Rehabilitation helps to manage the activities of daily life better.” https://www.jamovi.org, accessed on 10 November 2022). All statistical tests were two-tailed, and a p ≤ 0.05 was considered statistically significant.Data analyses were performed using the IBM SPSS Statistics for Windows, version 26.0  and Jamovi  were reported for continuous variables and percentages for categorical variables. The items of the scales created ad hoc for the present study underwent a preliminary analysis to check the normal distribution by calculating mean, standard deviation (SD), and indices of skewness and kurtosis. West and colleagues  recommenMean scores of two original scales (frequency and perceived proficiency in using technologies) were calculated and analyzed. Therefore, their dimensionality was preliminary tested through Exploratory Factor Analysis (EFA). This is the most common approach to scale development and validation . The KaiCronbach’s α was calculated to examine the internal consistency of the scales. Cronbach’s α higher than 0.60 was considered acceptable .The association of the frequency and perceived proficiency in the use of technology scores with the relevant sociodemographic variables  was investigated. Moreover, the differences in dispositions toward rehabilitation between participants who had rehabilitation experience and participants who had not were explored.The associations between continuous variables  were evaluated by correlations. Following guidelines by Cohen , correlat-tests. Assumption checks were performed before each t-test by evaluating skewness and kurtosis to check the normal distribution of the variables and Levene’s test to check the variances’ homogeneity. Based on the assumption checks results, t-tests were performed using Welch’s Test , Student’s Test , or the non-parametric Mann–Whitney U Test.The associations between continuous variables  and categorical variables  were evaluated by A Kruskal–Wallis non-parametric one-way ANOVA was performed to test for differences in the health-related Quality of Life reported by participants with different clinical conditions.There were 95 participants. The distribution by age group is relatively homogeneous, ranging from 25 to 84 years old, the most represented group being between 65 and 74 years old (24% of the sample). Women are 60% of the sample. Most of the sample (78%) lives with someone else, in most cases (63%) the spouse or partner and children (25%). The sample is quite heterogeneous by educational level. The most represented educational qualification is the high school diploma (26%). Half of the sample is retired (55%). More than half of the participants  declared suffering from at least one chronic disability (nine declared at least one comorbidity). Considering, in the case of comorbidity, only the disability that participants considered prevalent , the disabilities more frequent are neurological  and osteoarticular . Cardiovascular and chronic pulmonary disabilities (about 8% and 10% of the sample) are less represented.Seventy-seven percent of the participants stated that they used a smartphone daily in the last year. The use of mobile phones without touch technology is infrequent: 68% of participants have never used it in the last year. Tablet usage is quite rare: 51% of the sample has never used it in the last year. The frequency of computer use is more distributed. Most of the sample has never used a digital watch that detects health data (76%) or a vocal home assistant (77%); 65% of the sample in the last year used the internet daily; on the other hand, a considerable percentage of the sample (22%) had never performed it. The usage of social networks split participants between those who use them daily (46%) and those who never used them (43%). Most of the sample (66%) did not use e-games. Reading online material and listening to digital music is an evenly distributed activity; 55% of the sample used e-mail daily in the last year; on the other hand, a considerable percentage of the sample (32%) never used it; 54% of the sample in the last year never monitored their health with digital devices.2(78) = 707, p < 0.001] and the KMO  ensured that the correlation matrix could be subjected to factor analysis. The analysis indicated that a single-factor solution was the most appropriate. No item displays a loading lower than 0.32 except one . The Bartlett’s sphericity test . There was a statistically significant difference in the use frequency between workers and retirees . Working people used technologies more frequently  than retirees (mean = 2.25). This result overlapped with the result for age . A total “use frequency of technologies” score was calculated based on the mean of the final twelve items; this new variable showed a normal distribution. The use frequency of technologies correlated significantly and negatively with age  in using a smartphone (64%) and a mobile phone without touch technology (70%). Data about tablet and computer use were more distributed. The perceived proficiency in using smartwatches and vocal home assistants reflects the data on their frequency of use: the majority of the sample does not feel proficient in using these devices . Most of the sample (44%) felt expert in internet use. Regarding the navigation of social networks and reading online material, the sample is divided between those who feel very or quite proficient and those who do not. Most of the sample (42%) declared not feeling proficient in e-gaming; on the contrary, they felt very proficient (44%) in using e-mail. Regarding listening to music on digital devices, 35% of the sample felt very proficient, compared with a similar percentage (28%) of respondents who did not feel proficient. The perceived proficiency in using digital health monitoring devices was quite distributed, with a prevalence of respondents who did not feel proficient (34%).2(78) = 1270, p < 0.001] and the KMO  ensured that the correlation matrix could be subjected to factor analysis. The analysis indicated that a single-factor solution was the most appropriate. No item displays a loading lower than 0.32. In this case, the saturation of the item “use of the mobile phone without touch technology” was significant, albeit lower than the other items’ saturations . The Bartlett’s sphericity test . There was a statistically significant difference in perceived proficiency between workers and retirees . Workers felt more proficient  than retirees (mean = 2.41). As already observed for the frequency of use of technologies, this result overlaps with the result relating to age . Frequency of use and perceived competence correlated significantly and positively . The effect size was large. A total “proficiency in the technologies use” score was calculated based on the mean of the final twelve items; this new variable showed a normal distribution. Perceived proficiency in the use of technologies correlated significantly and negatively with age .Participants with chronic disabilities reported a disability level equal to 27.6 (SD = 23.3), indicating a perceived disability of mild to moderate level. The health perceived on the day they completed the questionnaire  and in the last week  confirmed this result. The responses to the WHODAS 2.0 and the questions about perceived health had a normal distribution. Nevertheless, the number of participants for each clinical condition was unequal and in the case of cardiovascular and pulmonary disability was low. Therefore, a Kruskal–Wallis non-parametric one-way ANOVA was performed to test for differences in the health-related quality of life reported by participants with different clinical conditions. Results suggested that the WHODAS 2.0 scores and the declared perceived health did not differ significantly in the function of the different clinical conditions  had never been advised by a clinician to participate in a rehabilitation program. Instead, 31 respondents in that group (58%) were prescribed it, and only one decided not to follow it.Among the 30 respondents with experience of at least one rehabilitation process, half had completed the whole treatment cycle, while the other half had ongoing experiences.Taking into account all the rehabilitation experiences reported by the participants in the various regimes, rehabilitation occurred less frequently during hospitalization (7 cases out of 30) and more often on an outpatient basis at a clinical center (22 respondents) or at home (10 respondents).Considering that participants could have undergone more than one rehabilitation cycle under different regimens and with different clinical objectives , they were asked to respond by thinking of the last rehabilitation cycle carried out in a specific regimen. Of the total rehabilitation experiences reported by the 30 respondents, the type of rehabilitation performed was mainly motor . Less frequent were the experiences of cognitive rehabilitation (seven cases), speech therapy (three cases), or occupational therapy (one case).Regardless of the type of rehabilitation, it emerges that the use of technologies in the rehabilitation context  was limited and referred to specific rehabilitation contexts. Among those who reported experiences in an outpatient setting, about a third (7 cases out of 22) used technological devices. Much less frequent, in the experience of the group described, was the use of technological devices for rehabilitation at home (2 out of 10). On the other hand, no one reported having undergone a rehabilitation cycle with technological devices in hospitalization.Technologies have been an enabling factor mainly for motor rehabilitation . On the other hand, the computer/tablet was more present in cognitive rehabilitation experiences .n = 95). The first result is that, regardless of age, health conditions, and rehabilitation experience, participants believe that rehabilitation is a “useful”, “important”, and “necessary for health” activity. For these three statements, the variable had a strong negative asymmetry; in other words, most respondents agreed very much (ceiling effect). the position of the respondents was more nuanced on the accessibility of rehabilitation . Second, the valuing of rehabilitation as a necessary constituent of one’s well-being was significantly more present among respondents who had experienced it (mean = 4.57) than among respondents who had not . Third, the belief that rehabilitation improves mood was significantly more prevalent among those who had experienced it (mean = 4.07) than those who had not . Fourth, the perception of the fatigue value of doing rehabilitation was significantly more marked among those who had experienced it (mean = 4.57) than those who had not . Finally, the perception of the importance of rehabilitation was significantly clearer among those who had experienced it (mean = 4.70) than in the other group .Considering the comparison between participants with and without rehabilitation experience, the following additional findings are also noteworthy . First, Though preliminary and based on data collected through random waves of detection, our results are in line with the core message by Cieza and colleagues : only 43Although a growing body of evidence shows that a technological boost is transforming rehabilitation by modeling continuity of care pathways from hospital to home, still the main question for the HTA evaluation approach is: does it work? To answer the question, besides validation of clinical benefits, key domains in this multidimensional approach are the usability and the acceptability of a technological solution. It is known that lack of usability provides a substantial barrier to the adoption of new health technologies . ConsideTo this aim, in the STID perspective, when it comes to patients’ involvement in evaluating the usability and acceptability of technologies that enable rehabilitation treatments, the starting point is not the technological devices that the patient can “use” and can “accept”, but the patient’s experience that such technologies enable. That is, evaluations on the usability and acceptability of a technological solution are an integral part of the design and development process of a technology, in a multi-stakeholder  co-design methodological and organizational framework. The design and development of a technology that includes patients from the very first steps of its development is indeed at the core of the User-Centered Design (UCD) methodological approach . AccordiThe vision behind STID whereby technologies for rehabilitation are not devices that the patient uses but consist in constraints that shape the precise experience that they enable implies that the set-up of a technology for rehabilitation consists in the sense-making process that, though a technology, one can cue and activate. That is, it assumes that technologies do not add up to their context of clinical use, but are an integral part of it ,35,36. DThese results on the patient’s perspective on rehabilitation fit into the STID flow for the introduction of new technologies since they provide further dimensions besides health outcomes (as a basic requirement) to be integrated into their design and development. Specifically, the integration of quality of life and well-being outcomes. This theme may not be acknowledged by Innovators , resulting in the design and development of technological solutions that, after a considerable effort in prototype development, run the risk of being evaluated as only partially suitable to meet patients’ needs. The assumption, on the Innovators’ side, may be that technology can be pushed to optimal development without the involvement of patients and citizens since its early prototypical design. In this organizational setup, with pilot studies with end users evaluating existing and quite defined prototypes, hassles connected with multidisciplinary design and development workgroups are minimized. Nonetheless, segmenting the development trajectory into defined parcels increases the risk of having to reorganize the production line, especially if the technological prototype tested in real-life settings fails to address patients’ needs with negative impacts on adherence to treatment, and efficacy. Differently, the early effort connected with a development pipeline of multistakeholder co-design and evaluations provides a more efficient option. Along this line, a further result is that at least two different networks of knowledge and belief are at stake in the ecosystem of technological innovation for rehabilitation care: one shared by Innovators, and one shared by patients, that may not overlap. The STID model acknowledges that such networks of knowledge may—and often are not—consistent. Therefore it provides an organizational flow that not only allows Innovators and patients to have their respective knowledge accessible in one’s own cognitive repertoire but also makes it applicable to the specific domain of rehabilitation care. That is, the STID flow manages to turn the perceived value of respective beliefs (of Innovators and patients) into operational pathways that become applicable to the task at hand. This way, it provides the operational framework to build a community of practices able to transform the culture of rehabilitation care including the patient’s perspectives since the early process of technological innovation. The main limitation of the present study is related to the uncertainty of the real possibility to implement innovation in rehabilitation care processes, not depending directly on the STID model, but on the decision-making process taking place at a regulatory level. To date, the public health supply of rehabilitation treatments for people with Non-Communicable diseases is not able to cover the population’s needs. This misalignment between supply and demand depends, on the one hand, on the inability to guarantee adequate services to all patients in need and, on the other hand, on the difficulty of fully exploiting the potential of technology to innovate rehabilitation. Low capacity and delayed access are also due to outdated and poorly updated reimbursement systems and tariffs not being in line with the current technological opportunities. This aspect may also discourage Innovators since they could not find adequate pricing in relation to their purpose to explore new approaches and/or solutions.The STID model, combining patients’ and citizens’ perspectives with the Governance dimension, would support the public service to solve this specific problem, not only developing the most promising solutions for the market but also providing clear indications of how they can be reimbursed by the healthcare service. Indeed, in the STID model, the patient-citizen perspectives on innovative technologies for rehabilitation are integrated into an operational flow for the creation of innovative, needs- and territory-connected, personalized, and sustainable rehabilitation systems.In STID, the detection of patient health and well-being experiences on rehabilitation works as an integral dimension in the design and development of technologies, providing both in itinere and endpoint evaluations. Since the STID flow also takes into account the needs of the other relevant stakeholders, it taps several dimensions—i.e., the clinical, the economic, and the well-being ones—able to activate the process of multidimensional assessment essential to validate the technologies in line with public health demands. By optimizing the multi-stakeholder innovation process in rehabilitation, STID also enables the construction and stabilization of shared practices for the purpose of offering innovative and customized solutions for the rehabilitation of chronic disabilities.The main strength of the STID model is that it allows the management of patients’ rehabilitation perspectives and evaluations on health and well-being in rehabilitation while enabling their turning into operational practices into a multi-stakeholder co-design framework. This way, the ecosystem of needs and opportunities of all stakeholders in tech-enhanced rehabilitation care is nurtured by distributed shared networks of knowledge, to tune the respective actions and stabilize a participating culture of multidimensional evaluation for technological innovation and advancement. Although preliminary evidence supports this claim, the outcomes of these development and co-creation frameworks require that in the regulatory domain, active pathways for the definition of rates that include specific technologies, or proactive innovative mechanisms for reimbursement are set up and defined, to let such process and organizational innovations transform the public health assets to concretely meet the growing need of rehabilitation for people with NCDs.


Due to growing pressure on the health care system, a shift in rehabilitation to home settings is essential. However, efficient support for home-based rehabilitation is lacking. The COVID-19 pandemic has further exacerbated these challenges and has affected individuals and health care professionals during rehabilitation. Digital rehabilitation (DR) could support home-based rehabilitation. To develop and implement DR solutions that meet clients’ needs and ease the growing pressure on the health care system, it is necessary to provide an overview of existing, relevant, and future solutions shaping the constantly evolving market of technologies for home-based DR.In this scoping review, we aimed to identify digital technologies for home-based DR, predict new or emerging DR trends, and report on the influences of the COVID-19 pandemic on DR.The scoping review followed the framework of Arksey and O’Malley, with improvements made by Levac et al. A literature search was performed in PubMed, Embase, CINAHL, PsycINFO, and the Cochrane Library. The search spanned January 2015 to January 2022. A bibliometric analysis was performed to provide an overview of the included references, and a co-occurrence analysis identified the technologies for home-based DR. A full-text analysis of all included reviews filtered the trends for home-based DR. A gray literature search supplemented the results of the review analysis and revealed the influences of the COVID-19 pandemic on the development of DR.A total of 2437 records were included in the bibliometric analysis and 95 in the full-text analysis, and 40 records were included as a result of the gray literature search. Sensors, robotic devices, gamification, virtual and augmented reality, and digital and mobile apps are already used in home-based DR; however, artificial intelligence and machine learning, exoskeletons, and digital and mobile apps represent new and emerging trends. Advantages and disadvantages were displayed for all technologies. The COVID-19 pandemic has led to an increased use of digital technologies as remote approaches but has not led to the development of new technologies.Multiple tools are available and implemented for home-based DR; however, some technologies face limitations in the application of home-based rehabilitation. However, artificial intelligence and machine learning could be instrumental in redesigning rehabilitation and addressing future challenges of the health care system, and the rehabilitation sector in particular. The results show the need for feasible and effective approaches to implement DR that meet clients’ needs and adhere to framework conditions, regardless of exceptional situations such as the COVID-19 pandemic. Rehabilitation is an essential part of caring for people with acute or chronic health conditions, impairments, or injuries that limits functioning . It is eTwo of the most challenging aspects of rehabilitation are the high costs of inpatient and long-term rehabilitation programs  and the Incorporating new digital technologies into rehabilitation could help to meet these demands. Digital rehabilitation (DR) can be defined as using digital technologies as a part of the rehabilitation process . DR aimsHowever, for the effective application of DR, it is not only important to identify digital technologies and their potential applications that can be integrated into home-based rehabilitation but also essential to equip health care professionals with the skills needed to provide high-quality rehabilitation, conferring them with the potential to develop the field multi-professionally.The COVID-19 pandemic has exacerbated the challenges faced by individuals in need of rehabilitation .To develop and implement DR solutions that meet client needs and ease the growing pressure on the health care system, it is necessary to provide a broad overview of existing, relevant, and future solutions shaping the constantly evolving market of technologies for home-based DR.The scoping review aimed to identify digital technologies for home-based rehabilitation, predict new and emerging trends in DR, and report the influences of the COVID-19 pandemic on DR.The scoping review was performed based on an adapted framework described by Arksey and O’Malley  by addinAs the first step, the following research questions were identified:Research question 1: What are the types of existing new or emerging digital technologies in home-based rehabilitation?Research question 2: Which trends can be identified for the home-based DR technologies and what are their advantages and disadvantages?Research question 3: How does the COVID-19 pandemic influence the development of DR?To identify references related to the research questions, a scientific database search in PubMed, Embase, CINAHL, PsycINFO, and the Cochrane Library was performed in July 2021.The search strategy was first developed for PubMed and adapted to each database by using keywords; their synonyms; and related terms of “rehabilitation,” “home-based,” and “digital technologies.” These terms were connected with the Boolean operators “AND” and “OR” to obtain a wide spectrum of results from the various databases. The full search strategy for each database is presented in To complement the findings regarding the trends of home-based DR, as well as the impact of the pandemic, gray literature sources were searched for unpublished materials in the native languages by the member institutes of the project “Competences for the new era of user-driven Digital Rehabilitation (DIRENE)” . The gray literature was searched using Google, Google Scholar, Yahoo, OpenGrey, specific websites from each country’s government, thesis repositories, and university library websites that offer a comprehensive list of gray literature databases.Study selection was performed using the web-based software, Covidence  . After aInclusionArticle typeEvery article type that is existing as a full textLanguageEnglishPublishing dateFirst phase: references published since January 1, 2015Second phase: references published since July 21, 2021TechnologyDigital technology directly related to home-based rehabilitationFully developed devices, applications, software, or prototypes and ideasInterventionEvery intervention in which a digital technology was usedExclusionArticle typeArticles that were not available as full texts via common publishers, universities databases or directly requested from the publishing authorsLanguageOther languages than EnglishPublishing dateFirst phase: references published before January 1, 2015Second phase: references published before July 21, 2021TechnologyNondigital technologiesTechnologies used after invasive procedures InterventionIntervention via telephone as a stand-alone interventionIntervention in a laboratory settingA bibliometric analysis was performed as the first overview of the included publications. The software Zotero   was usedTo identify new and emerging technologies for home-based rehabilitation, a co-occurrence analysis was performed. The software VOSviewer   was usedFurthermore, a full-text analysis of all included reviews was conducted to filter the trends for home-based DR technologies and to present its advantages and disadvantages. The analysis aimed to extract relevant information about the technologies in terms of the goal, specification and application, population, and advantages and disadvantages of the technologies.The data of the gray literature search were analyzed to complement the results of the review analysis and to determine the influence of the COVID-19 pandemic on the development of DR. Each participating institution used an extraction sheet to obtain the information with respect to the research questions. All data were then summarized according to the following categories: type, aim, description of the technology, target population, and statements regarding the influence of the COVID-19 pandemic.The aim of the stakeholder consultation was to complement the results regarding the trends of digital technologies and the impact of the pandemic on DR from different perspectives. Therefore, a meeting with key stakeholders and experts was organized by 4 of the 5 collaborating universities of the DIRENE consortium . Participants included clients with experience or specific interest in using digital technologies at home ; rehabilitation professionals ; experts from companies for future trends in health care ; experts in digitalization ; and representatives of public health administrations , social and welfare departments , and national platforms for digitalization in rehabilitation .The meetings consisted of a short introduction to the project and the presentation of the preliminary results of the review. Stakeholders shared their views on the identified trends in digital technologies used in rehabilitation. They discussed the potential synthesis of technologies in home-based rehabilitation and examined factors influencing DR. All the information was summarized in a final standardized report by each participating institution. The results were then analyzed in line with the Framework Approach . On the The process of paper selection for each research question is shown in Bibliometric and co-occurrence analyses were performed to provide an overview of the included references and identify new or emerging technologies in home-based rehabilitation. For these analyses, 2437 records were included.All 2437 included records for the bibliometric and co-occurrence analyses were published between January 2015 and January 2022. Over the past years, the number of publications has steadily increased annually, from 211 (8.66%) in 2015 to 544 (22.32%) in 2021. In addition, most research papers were published in 2021 .In total, 53 keywords with a frequency of ≥10 were selected from 59,718 keywords, and a co-occurrence analysis was performed, as shown in As presented in Further analysis of keywords that occurred ≥10 times provided an overview of the mentioned populations in which the identified technologies were used in home-based rehabilitation, as shown in It can be seen that the cumulative sum of stroke and related synonyms are the most occurring conditions related to home-based rehabilitation among the publications. Chronic obstructive pulmonary disease (COPD) and its synonyms ranked second. The third most common disease mentioned in the included publications is multiple sclerosis (MS).To identify the trends for home-based DR technologies and display their advantages and disadvantages, 95 reviews  were included  in the rIt is essential to note that each publication addressed one or more types of technologies that are often used in combination with another. For example, exergames or serious games that are used with a head-mounted display are grouped in the category “virtual/augmented reality,” and the games in which a client plays in a virtual environment without using technology for an immersive experience are categorized as “gamification.” Likewise, the technology was not named in either category to avoid duplication.To provide a definition for each identified technology, the DIRENE consortium developed definitions based on the current literature using a Delphi process until a consensus was reached  ; cameraInertial measurement units (IMUs) are the combination of inertial sensors, namely, the combination of one or more accelerometers, one or more gyroscopes, and, potentially, one or more magnetometers, to measure the force, angular rate, and orientation of the body . These IGiven the existence of IoT, sensors can collect data and transfer them to other devices to visualize the output and thus provide biofeedback to the client. Biofeedback systems consist of an input sensor, a data-processing system, and an output device that displays the feedback . The outPO2 and heart rate) fall below certain thresholds. Thus, the client has the opportunity for self-monitoring, that is, to receive feedback on the correlation between physical activity and body reactions to adjust such behavior as needed. Health care professionals can also estimate these data using a dashboard where the data are collected. After 6 weeks, the application led to a significant reduction in symptoms associated with COPD compared with the control group. The intervention group’s self-assessment of the impact of the disease also improved significantly.It is useful to apply vital parameter sensors to monitor the health status of clients during rehabilitation. Kwon et al  developeOverall, stakeholders emphasized the importance of sensors in DR.In total, 9 reviews investigated the use and effects of robots in rehabilitation. Furthermore, 9 articles that explained the use of brain-computer interfaces (BCIs) in rehabilitation were included.Robotic gloves  are cateExoskeletons are wearable robotic units controlled by computer boards ,158. A dThe application of noninvasive BCIs has changed over the last decade. This change allows health care professionals to offer this treatment in a home-based setting, although this approach remains under development. In the past, the application of BCI technologies in a home environment was hampered by the fact that the operation of these systems required the supervision of an expert. In a home-based setting, BCI technologies are used for people with severe motor impairments, such as those who have experienced a stroke, traumatic brain injury, spinal cord injury, or locked-in syndrome. These technologies can help such clients to enable or support communication with their environment or performing daily tasks.BCI-based applications can be used to control daily aids such as wheelchairs, prosthetics, video games, and various computer applications ,75. YangZulauf-Czaja et al  developeStakeholders saw high potential in the use of exoskeletons in rehabilitation if the devices are able to make their own adjustments in terms of speed and level of assistance based on data collected from the client. Furthermore, stakeholders indicated rehabilitation robots’ low accessibility to clients, as these are mostly available at research level. The stakeholders also emphasized the possibility of the combined use of robotic devices with gamification to encourage clients’ motivation during the rehabilitation process due to gaming elements or appealing environments.In 19 reviews, games were used either specifically for rehabilitation  or commercial use .Gamification was mostly used as an intervention in neurological rehabilitation to improve physical function, balance, gait ,90, and In a number of reviews ,78-80 inPublications deployed exergames using commercial hardware, such as the PlayStation, Nintendo Wii, Xbox Kinect, and associated elements such as the Wii balance board and games for these consoles ,92,160. Overall, a low strength of evidence has been shown until now regarding exergames and serious games in improving physical functioning. This is due to a lack of long-term randomized controlled trials (RCTs) with homogeneous population and large sample sizes and specific outcome measures ,89,91,92For the recent past and as this review shows, more VR technologies  have been the focus of research in relation to rehabilitation compared with AR technologies .In home-based rehabilitation, VR and AR are used to improve physical functioning , balanceVR technologies were mostly used in combination with games that had not been developed for rehabilitation purposes, with the exception of 6 studies -166. In In 1 study , AR was In addition to VR and AR, stakeholders added “Mixed reality” and “Digital twins” as a further trend in rehabilitation. Mixed reality is the merging of real and virtual worlds to produce new environments and visualizations in which physical and digital objects coexist and interact in real time. It includes VR and AR and thus represents the entire spectrum between the physical and digital worlds . A digitCurrently, there is a lack of strong evidence supporting the use of VR and AR for rehabilitation . StakehoIn this study, we identified 3 subcategories within the 26 reviews regarding digital and mobile apps: apps , web-based programs , and videoconference systems . The large number of published papers in this area illustrates their broad use in rehabilitation.Apps, web-based programs, and videoconference systems can be used for remote and home-based rehabilitation as adjuncts to face-to-face therapy or to replace some parts of it. It is noticeable that the use of these technologies is not limited to certain target groups, rather the client must fulfill some preconditions to use these technologies, such as access to the internet, mobile devices, or computers, as well as possessing necessary skills.Apps and web-based programs are used as assessments, specifically providing questionnaires via apps, or delivering guidance regarding assessments, or measuring movement through special sensors embedded in a smartphone ,170-172.Moreover, these technologies are used to improve cognitive functions ,173 and Apps and web-based programs can help improve self-management and encourage a healthy lifestyle, rehabilitation, and adherence through individual goal setting, displaying rehabilitation progress, showing motivational messages, providing educational modules, and enabling symptom recording and social support ,109,112.Digital and mobile apps can further offer the possibility to connect with other people and become part of a social support community .Stakeholders have criticized the lack of a solution that combines all the requirements of the rehabilitation process in one holistic approach. Even if the applications are available at a low price, the stakeholders emphasized that equal access to the internet and hardware should be ensured to decrease social inequality. They also expressed concerns that some clients may be excluded because they did not have the required competences and skills. Appropriate support is required for these clients. Furthermore, stakeholders have critically noted that digital and mobile apps encourage the replacement of face-to-face interventions, which they believe represents a clear disadvantage in terms of the outcomes of the rehabilitation process. In addition to all the benefits and limitations of digital and mobile apps, stakeholders identified this technology as one of the trends in the future health care sector.In total, 4 reviews explored the functionality of IoT principles.In rehabilitation, the IoT is beneficial for the collection of clients’ data through various technologies. These data can be sent to health care professionals to monitor clients’ health in their normal environment. In this manner, data can be collected to provide a complete picture of clients without blind spots. This information can be used to make medical decisions and treatment plans.IoT approaches include smart homes and ambient-assisted living (AAL). A smart home is a residence equipped with smart technologies aimed at providing tailored services to clients . AAL canPiau et al  raised tStakeholders emphasized the complexity of using the devices and high costs of the technologies, as well as expenses for installation, repair, and maintenance, as further barriers to implementing smart homes .Referring to IoT, another approach that could benefit rehabilitation is living labs. The term “living labs” refers to the use of sensors to objectively record and evaluate people’s behavior and physical functioning without interruption over a long period . PersonaStakeholders emphasized the benefits of linking the digital and physical worlds through IoT to enable a holistic approach to rehabilitation. In contrast, stakeholders have stated that clients often have great fears about the use of these technologies with an IoT approach owing to lack of safety.In total, 4 reviews describing the principles of AI were included. In addition, 13 articles were selected to explore its use in rehabilitation with machine learning processes.AI and machine learning processes can be used as diagnostic and prognostic tools in rehabilitation. Abdollahi et al  used a wSimilarly, several articles have developed a home-based monitoring system based on AI and machine learning for use in executing a rehabilitation plan, even in the absence of a rehabilitation professional. For example, Chae et al  developeChatbots and conversational agents are key technologies for AI and machine learning processes in rehabilitation. They could be based on AI and machine learning processes that simulate and process human conversations. They enable communication via text or audio on websites, mobile apps, or telephone .Vaidyam et al  further In their reviews, Schachner et al  and VaidVirtual human technology is based on AI and machine learning processes and used in rehabilitation. Virtual humans are computer-generated cartoon-like characters that have the ability to initiate and respond to verbal and nonverbal communications. The use of virtual humans in assisted care has mainly been implemented for healthy participants -183, witFrom a systemic perspective, the stakeholders expressed that AI and machine learning processes are the most relevant technologies for the future. AI and machine learning processes define future opportunities in the rehabilitation sector because they enable evidence to be generated based on the data collected. This can lead to resource optimization for the client and the health care system. However, stakeholders have stated that technologies such as chatbots and conversational agents have not yet been sufficiently developed for use in rehabilitation. Most of the work is still in the pilot phase, and the effectiveness of the technology has not yet been verified .The 3-year pandemic  has changed many rehabilitation processes for clients and health care professionals. To present the influence of the COVID-19 pandemic on DR, 40 records were included.To continue rehabilitation during the pandemic, remote digitally driven rehabilitation approaches, such as videoconferencing, apps, and web-based programs, were frequently used in practice. However, the crisis did not lead to the development of new DR technologies but rather to an increased use of technologies that were already on the market.This has led to more experiences with DR among clients, health care professionals, and health care providers. Clients accepted DR remotely as a substitute for face-to-face therapy during the pandemic ,185-188.The pandemic has led to an increased awareness of the need to develop further digital health measures . In many countries, efforts have been made to implement digital solutions in the health care sector or help meet the preconditions for their use. However, the COVID-19 pandemic acted as an additional driver in the implementation of these applications. This was supported by political measures such as the softening of strict guidelines, which made it possible to launch and use digital solutions even without proof of their effectiveness . HoweverIn addition, in some countries (Austria and Germany), videoconference (therapy via videoconferencing) was legally approved, considering individual requirements, such as a specific diagnosis, the confirmation of the service provided, safe technical equipment, and a positive prognosis regarding the success of the application ,196. In However, the rapid implementation has also led to the frequent implementation of incomplete solutions that have met the clients’ short-term needs but are not sustainable in the long term, as pointed out by stakeholders. In addition, evaluations of the measures have been less rigorous or have not been conducted, leading to the risk of perpetuating rapidly implemented solutions after the pandemic .This scoping review revealed various digital technologies intended for use in home-based rehabilitation. Trends were identified, and the advantages and disadvantages of each technology were presented. In addition, the influences of the pandemic on the development of DR were shown.The findings of this review reveal that sensors, robotic devices, gamification, VR and AR, and digital and mobile apps are already widely used in home-based rehabilitation. However, AI and machine learning, exoskeletons, and digital and mobile apps represent emerging trends in rehabilitation. Compared with the other identified technologies, VR, AR, and robotics cannot be used independently for home-based rehabilitation for usability and safety reasons. Thus, there is a need to develop sufficient and feasible DR practices that demonstrate clinically relevant effectiveness. Furthermore, we discovered that the COVID-19 pandemic has led to an increased use of digital technologies in a remote approach, especially apps, web-based programs, and videoconferencing, but not to the development of new technologies. Clients and health care professionals accepted this approach during the pandemic, but they also expressed concerns about it. The pandemic acted as a driver for implementing remote approaches for health care systems. However, sustainable solutions that can be applied even after the pandemic should be implemented.One major finding was that the relevance of AI and machine learning will increase in the field of rehabilitation in the future, especially for diagnostic procedures, decision-making, and the development of client-centered care, even though they are not yet broadly applied in rehabilitation. Furthermore, it was found that AI, machine learning, and digital and mobile apps would be essential to process and optimize resources in the health care sector. This finding is consistent with that in the current literature. For example, Hamet and Trembley  stated tNevertheless, there are challenges that need to be overcome when applying AI and machine learning widely in the health care sector. Jiang et al  report aOne further result was that technologies such as gamification, VR and AR, and digital and mobile apps that are already used in home-based rehabilitation have the potential to improve client adherence and motivation. Similarly, approaches based on IoT can increase client participation in the rehabilitation process because they allow self-monitoring; thus, client self-management can be increased. This represents an important factor for successful therapy of chronic diseases to improve quality of life and reduce the use of health care resources .This study revealed that most technologies could be used in home-based rehabilitation without the presence of health care professionals. The emerging developments in the design and possibility of asynchronous or synchronous monitoring via apps, web-based programs, or videoconferencing make the remote rehabilitation approach possible. In other studies ,56,202, In order to offer client-friendly rehabilitation in the home setting, sufficient space for the equipment must also be ensured. Furthermore, the technical equipment needs to meet requirements such as access to the internet or a digital and mobile device, and the costs of purchasing, repairing, and maintaining the technology need to be low  because In addition to the safety and usability factors, the use of DR should be based on an individual rehabilitation goal, considering the motivation of clients and health care professionals to use technologies and the possibility of receiving support when using such technologies . FurtherAnother major finding is that the effectiveness of many technologies has not yet been confirmed scientifically. Several studies have described projects in which the technology is currently under development or tested in laboratory settings. However, it can also be seen that 221 RCTs referring to DR are already registered via ClinicalTrials.gov for 2021 and 2022 . Because many technologies have only been used under controlled conditions, their application in daily life cannot be assessed.In addition, we found that feasible approaches to the implementation and integration of digital technologies for the rehabilitation process are lacking. Accordingly, it is essential to consider not only the effectiveness of the intervention in terms of dedicated outcomes, the design of the intervention itself, and the characteristics of individuals but also the setting in which the approach will be applied, the process of implementation, and factors influenced by policies and government regulations .Therefore, studies are required that present an effective and valid concept that can enable clients and health care professionals to apply digital technologies for (home-based) rehabilitation. This includes the presentation of plans for the modus of DR (blended therapy or replacing face-to-face therapy), the reimbursement of health care professionals, and cost coverage for the technologies needed by clients and rehabilitation units. Other issues must be addressed for a feasible implementation, such as privacy compliance, data protection, insurance coverage, and the assumption of responsibility and liability if harm occurs during remote or unsupervised rehabilitation.The social distancing regulations enacted during the COVID-19 pandemic caused many clients and health care professionals to use DR, especially videoconferencing, apps, and web-based programs. Clients and professionals described their relatively high level of DR positivity along with improvements over the course of the COVID-19 lockdown. However, the question of whether this therapy model will continue to be accepted without exceptional circumstances remains.Digital Rehabilitation that are associated with various technologies. It is likely that the acceptance rates of different technologies vary, which does not allow for a general statement about their acceptance among clients and health care professionals.The literature shows contrary results regarding the acceptance of digital interventions by clients and health care professionals ,207. HowThrough the COVID-19 pandemic, more training opportunities for health care professionals were offered to allow them to gain competence in the field of DR. To be adequately prepared for working life and systematize the acquisition of competencies, health care professionals should already have acquired the necessary skills in higher education. Because DR technologies have already been implemented in rehabilitation, it is crucial that health care professionals are sensitized to the possibility of integrating digital options, acquire useful competencies, and have the ability to recognize which clients will benefit from this approach and then provide adequate assistance to them.Although the pandemic was, in many ways, a driver of the use of DR, it also led to the rapid introduction of solutions that were not based on an efficient concept and left many questions unanswered with regard to realistic implementation. Therefore, careful planning with a phased, linear implementation approach is crucial for establishing sustainable DR practices that will last beyond the pandemic and have the potential to meet the challenges of rehabilitation in the future .The results of this study paint a very broad picture of existing and emerging technologies in rehabilitation because a large number of records were included in the analyses, which were not limited to a specific target group or rehabilitation outcomes. The results derived from the scientific databases were complemented by a search of the gray literature. Through a meeting with key stakeholders, insights were gained beyond those reported in the literature. In addition to health care professionals, politicians, experts in the field of digitalization in rehabilitation, and clients with experience or a specific interest in DR were included.Bibliometric and co-occurrence analyses were performed with a minimum of 10 occurrences per keyword. This may have influenced the completeness of the representation of technologies if newer technologies occurred fewer than 10 times throughout the data set. However, the stakeholder meeting served to close this gap. Moreover, we did not weigh the strength of the evidence from all papers or appraise the efficacy of the approaches, which would have been beyond the scope of this review. In addition, new technologies may have been developed in the meantime and were not presented here because of the rapid development of the market.In the search for relevant literature, we used the word “rehabilitation” and not other terms commonly used in the context, such as “therapy,” “training,” “intervention,” or “treatment,” because we wanted to stick to the concept of rehabilitation, which implies a multimodal, collaborative, and patient-centered process rather than the stand-alone interventions suggested by those terms . HoweverThese findings reflect the growing interest in the use of digital technologies in rehabilitation. Multiple tools are already available and implemented for home-based rehabilitation; however, there are some limitations to their use, such as low usability, safety concerns, ethical challenges, and a lack of efficacy and legal frameworks. DR implementation should be based on the clients’ goals and motivation. AI and machine learning could be of particular interest in redesigning rehabilitation to address future challenges in the rehabilitation sector.On the one hand, the pandemic acted as a driver for the application and acceptance of existing digital solutions in rehabilitation. On the other hand, digital solutions that only met the requirements of the clients during the pandemic were implemented. The results of this research reflect the need for feasible and effective approaches to implement DR sufficiently to meet clients’ needs and adhere to framework conditions to be sustained apart from exceptional situations.