Acquired brain injury (ABI) is a major global public health problem and source of disability. A major contributor to disability after severe ABI is limited access to multidisciplinary rehabilitation, despite evidence of sustained functional gains, improved quality of life, increased return-to-work, and reduced need for long-term care. A societal model of value in rehabilitation matches patient and family expectations of outcomes and system expectations of value for money. A policy analysis of seven studies (2009–2019) exploring outcomes and cost-savings from access to multi-disciplinary rehabilitation identified average lifetime savings of $1.50M per person, with costs recouped within 18 months.Recommendations: Increase access to multi-disciplinary rehabilitation following severe ABI; strengthen prevention focus; increase access to case management; support return-to-work; and systematically collect outcome and cost data. Acquired brain injury (ABI) from traumatic brain injury (TBI), stroke, infectious disease, metabolic disorders, and brain tumors is a major global public health problem . A severThe lifetime economic cost of TBIs that occurred in the United States in 2010, including direct medical costs and indirect costs in lost wages, lost productivity, and non-medical expenditures, was estimated to be ~$76.5 billion (in 2010 dollars) . Ninety In the U.S. some 20 million Americans are living with disabilities from TBI (from a blow or jolt to the head) and stroke , 12. LacOne way to conceptualize value in access to multi-disciplinary rehabilitation after sABI, is to consider three different value models for the provision of healthcare: the market, lifetime, and societal models. The market model informs access to rehabilitation in the market-based health-care system in the U.S. The lifetime model informs healthcare in countries with global healthcare budgets and a universal system of coverage, such as the U.K. . The socFor the market model value is determined by health payers . When paFor the lifetime model of rehabilitation services, common in countries with integrated, single-payer health systems , 23, cliThe societal model considers total societal costs and benefits inside and outside the medical care system. It places a high value on prevention and providing a range of effective services to support independence for individuals. Value in access to multi-disciplinary rehabilitation is determined through shared decision-making by patients, families, and clinicians , 21. TheIn this policy brief, we examine evidence from seven studies in three countries of savings in lifetime care costs from access to multi-disciplinary inpatient rehabilitation supporting physical, cognitive, and social skills after sABI. We provide a model of the continuum of care for sABI and note where policy investments can generate long-term savings. We provide actionable recommendations for policy options at the state and federal level intended to increase access to rehabilitation services after sABI. The analysis uses insights from the lifetime and societal models of healthcare to inform efficiency gains in the market model.Our policy analysis of seven studies published between 2009 and 2019 explores outcomes and cost-savings from access to rehabilitation services within 12 months of an ABI requiring hospitalization. Study inclusion criteria were (a) published between 2009 and 2019; (b) a TBI or mixed ABI sample of patients with high dependency on admission, which indicated sABI; (c) admitted within 12 months post-injury; and (d) provided access to multi-disciplinary, inpatient rehabilitation services for up to 6 hours per day, 5 or 6 days per week. Study sample size ranged from 33 to 3,289 (median 133). Patient age averaged 42 years (39–49 years). Length of stay in multi-disciplinary inpatient rehabilitation averaged 151 days (89–227 days).Our calculations of lifetime savings involved several steps. First, we calculated minimum and maximum life expectancy for each sample using a standardized approach for people with TBI . Second,Across the seven studies lifetime savings from access to multidisciplinary rehabilitation services within 12 months of a severe brain injury averaged $1.58M (SD$.36M) per person using an exchange rate method and $1.50M using a PPP approach (SD$.35M). The cost of services was recouped within 17.2 months 12–27.6 months) on average. Lifetime savings were realized due to patients' increased independence and decreased reliance on services and supports for activities of daily living following discharge , 27–30..6 monthsThe studies calculated rehabilitation savings by comparing the cost of rehabilitation  and a reduction in post-discharge supervision costs  based on reduced dependency or need for supervision , 27–30. In a U.S. study  three inPatient gains in independence were maintained over time. In Great Britain, three intervention studies compared dependency measures at intake, discharge, and 6-months , 27, 28.A 2019 study in Great Britain  used theA weakness in the studies included in The continuum of care for severe brain injury includes prevention, hospital-based services, post-hospital services, and community-based programs. Traditionally the emphasis has been on acute medical care with less attention on post-acute rehabilitation or community-based care, where most survivor time—and public costs—are spent. Our depiction of the continuum of care for severe brain injury see  illustraIn the U.S., the Medical Care phase after a brain injury is largely covered by an individual or a families' health insurance, or by worker compensation if the injury occurred when working. Delays or interruptions in access to rehabilitation services can mean lower gains in function, quality of life, independence, and vocation . Within While not explored in this paper, prevention policy to reduce the number of brain injuries would maximize population health and minimize total social costs , 40. EnhThe second recommendation is to improve access to rehabilitation after sABI to generate value within the lifetime and societal models of value in healthcare see . The greThe third recommendation is universal case management from the time of injury to recovery or end-of-life. It is not enough to have services covered if people do not know what is available and how to access the appropriate care. TBI is, by definition, traumatic causing sudden and massive changes in the lives of individuals and families. Independent case managers provided by state-sanctioned entities not tied to providers or insurers would be provided to all patients regardless of income . Case maThe fourth recommendation is to support back to work efforts. Vocational rehabilitation has been shown to help move people toward greater independence and improved quality of life and save money. Indiana's program “Resource Facilitation,” led to significant cost savings to that state through improved long-term function, reduced annual lost wages, and increased annual earnings , 47, ideThe final recommendation is to systematically collect service utilization, outcomes, and cost data to better document the costs and savings of rehabilitation services and social supports. The evidence we presented shows unequivocal society and even medical care rates of return from access to rehabilitation after sABI. Having longitudinal data can help to identify where and how savings are achieved and could be maximized, and can help to make an even stronger political case for the upfront investment in multi-disciplinary rehabilitation services after sABI. One approach to data is to create a national brain injury or trauma registry , which cAcquired brain injury is a major global public health problem and source of disability. Greater access to multi-disciplinary rehabilitation after a severe ABI will improve lives and save money. Savings are achieved through sustained functional gains, improved quality of life, increased return-to-work, and reduced need for long-term care. The societal and lifetime models of healthcare perceive long-term function of sABI patients as providing value. A societal model centers patient and family needs and promotes public health approaches to prevention and care. Insights from this model can be used to adjust the market model to achieve greater efficiencies and this is reflected in our recommendations. An analysis of seven studies (2009–2019) exploring outcomes and cost-savings from access to rehabilitation after a brain injury requiring hospitalization identified average lifetime savings of $1.50M per person, with rehabilitation costs recouped within 18 months. Our recommendations are to promote prevention, require public and private insurers to provide the range of post-acute rehabilitation services, facilitate access through case management, support back-to-work efforts, and systematically collect and analyze data to better pinpoint where additional health and costs savings can be realized.The models presented here are informed by work on ethical frameworks to promote health systems change related to access to care for persons with brain injury  and on tThe continuum of care shows the types of care being provided (or not being provided) after a severe acquired brain injury and their typical sequence over an individual's lifetime. Individuals hospitalized for a severe acquired brain injury are not denied acute care, and while saving someone's life can be a heroic act, we argue it is access to multi-disciplinary rehabilitation that can help the individual have better function and quality of life in both the short- and long-term.LSL and MD developed the conceptual framework for the paper. LSL took the lead on the analysis and computations in the piece. MD took the lead on applying the theory to the analysis and drafting the policy recommendations and conclusions. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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Moreover, difference in FMA and MBI scores between the two at the 17th weekend was not significant. The total cost of the clinical pathway group, particularly at the ninth weekend, was higher than that of the conventional rehabilitation group, but the cost-benefit ratio was better and the incidence of complications was lower than that of the other group.According to the statistical analysis, the incidence of stroke disease has gradually increased, particularly in recent years, which poses a huge threat to the safety of human life. Due to the advancement in science and technology specifically big data and sensors, a new research dome known as data mining technology has been introduced, which has the potential value from the perspective of large amount of data analysis. Information has become a new trend of science and technology, and data mining has been used in various application areas to analyze and predict strokes at home and abroad. In this study, big data technology is utilized to collect potential information and explores clinical pathways of level-3 rehabilitation in certain regions of China. Moreover, application effects of data mining in the rehabilitation of patients with the first ischemic stroke have been evaluated and reported. For this purpose, fifty (50) first-time ischemic stroke patients have been screened through big data and were nonartificially assigned to level-3 clinical pathway and conventional rehabilitation groups, respectively, specifically through software. The first group of patients enters the clinical path of the corresponding level according to the way of three-level referral. These patients were analyzed based on the collected results of completing the unified rehabilitation treatment plan of the three-level rehabilitation medical institution in the patient record form. The second group was selected according to the routine rehabilitation model and method of the medical institution where the patients visited were divided into four stages: before treatment, three weeks after treatment, nine weeks after treatment, and seventeen weeks after treatment. For this purpose, a simplified Fugl-Meyer analysis (FMA), recording of various functions of limb movement, and modified Barthel index (MBI) scale were used to analyze and evaluate the ability of daily activities and compare their effects. The final results showed that FMA and MBI scores of the two groups were improved in the three stages after treatment. The FMA and MBI scores of the clinical pathway group on 3rd and 9th weekends were significantly different from those of the conventional rehabilitation group (which is  Every year, approximately 17 million people throughout the world suffer from stroke where 5 million of those patients die and 5 million people have permanent dysfunction or disability, which places a serious burden on the society in general and affected families in particular . The burThe three-level stroke rehabilitation clinical path of community rehabilitation is connected with the clinical path of the acute phase of stroke.To shorten the average hospital stay of patients, limit the growth of medical expenses, standardize diagnosis and treatment methods, and strengthen the exchange and cooperation of rehabilitation team personnel.Improve the satisfaction of patients and their families and promote the rational use of medical resources. To realize this, we have focused on three levels of stroke rehabilitation in the rehabilitation medicine department of tertiary hospitals, secondary specialist rehabilitation hospitals, and community rehabilitation.Finally, significant effects of the clinical pathway on the limb motor function and activities of daily living in patients with stroke in related hospitals in southern Jiangsu and the effect of its application are evaluated.In this article, we have aimed at “hierarchical and staged rehabilitation medical service institutions,” namely, the rehabilitation medicine department of tertiary hospitals, rehabilitation hospitals, and rehabilitation hospitals. Some of the major contributions of this article are shown in Stroke has the characteristics of high morbidity, high mortality, and high disability rate. It is the leading cause of Chinese adult disability. China is a country with a high incidence of stroke. According to the statistics of the Ministry of Health, approximately 2 million new strokes are triggered in China every year. Among these patients, about three-quarters of have varying degrees of dysfunction or disability , 9. The In 1980s, the New England Medical Center in the United States took the lead in proposing the concept of clinical pathways to standardize the disease treatment process, improve the utilization of health resources, and curb the growth rate of medical expenses. Subsequently, the British National Health Service (NHS) proposed “clinical management”  concept to develop clinical pathways and create a clinical pathway user group, called “integrated care pathway” (ICP). In September 1996, Singapore Changi General Hospital tried out the clinical pathway project and sent specialists to different hospitals in the United States to conduct training on clinical pathway theory, practice, and management. This is the first attempt in Asia to try the clinical pathway. This is a work group composed of doctors, nurses, managers, and related medical personnel for transplantation. Clinical pathway management projects were planned, implemented, and evaluated locally. Afterwards, developed countries such as Germany and Japan successively carried out a lot of research and exploration on the formulation and management of clinical pathways. After more than 20 years of practice and development, foreign countries have formed a relatively complete clinical pathway implementation and management system. As far as the clinical pathway of stroke is concerned, foreign studies are relatively diverse and relatively mature. The clinical pathways are studied from various perspectives such as the course of the disease, the place of medical treatment, basic principles, program design, and service integration. Discuss , where tThe research on clinical pathways in China, its research methods, research angles, and evaluation indicators are similar to those of foreign countries, and most of these are based on advanced foreign experience. Foreign research objects are mainly based on multiple medical institutions to explore the role of clinical pathways. Most domestic research studies on the clinical pathways of stroke from the perspective of nursing mainly study the effect analysis of clinical nursing pathways in a certain hospital. This is also different from the domestic and foreign medical systems, severity of the disease, and differences in treatment. Moreover, it is more feasible to explore the application of clinical pathways of stroke from the perspective of nursing. Most domestic reports on the effects of clinical pathways of stroke are mainly positive reports, and there are few negative reports. If more, it can effectively promote the patient's limbs, rehabilitation, reduction of hospitalization days, reduction of hospitalization costs, and improvement of patient satisfaction, etc. It may be currently in a critical period of medical system reform, and it is necessary to report positively promoting the application of clinical pathways. Although a clinical pathway treatment system for stroke has also been established in China. However, most of them are mainly based on the clinical pathways in the acute phase of stroke and the clinical pathways in the recovery phase of stroke, aiming at the treatment design in stroke units and rehabilitation wards, and lack of relevant clinical pathways in community hospitals, and lack of continuous hierarchical levels, and clinical path of stroke rehabilitation at different stages.The personal response and recovery of nerve injury after stroke are complex and changeable. This requires not only the cooperation of emergency physicians, neurologists, and nurses but also the cooperation of personnel from multiple disciplines, such as rehabilitation physicians and physical therapists, teachers (PT), occupational therapists (OT), speech and language therapists (SALT), and nursing workers, by providing their knowledge and professional skills to benefit stroke patients. A review of the literature, as well as the analysis of quantitative and qualitative research data related to improving the recovery after stroke, demonstrated that different levels of medical staff have different intervention times for the clinical path of stroke, different treatment modes, and different contributions to improving rehabilitation after stroke. It is mainly reflected in three stages, namely the first stage, the acute stage of rehabilitation; the second stage, the inpatient rehabilitation; and the third stage, the rehabilitation after discharge.The first phase, acute rehabilitation. In the National Stroke Strategy for England, Wales, and Northern Ireland, 6 out of 22 quality standards clearly emphasize the early intervention of rehabilitation professionals, providing professional skills and knowledge to improve the quality of treatment and improve patient outcomes. There is clear evidence that shows that a multidisciplinary team with the cooperation of rehabilitation therapists is significantly more effective for stroke hospitalization. This study evaluates all previous randomized trials and has rehabilitation treatment. A comparison of the comprehensive stroke unit cooperated by the teacher with the treatment effect in the traditional medical ward  proves that the former reduces the mortality rate and the patients receiving comprehensive rehabilitation treatment are more independent; this advantage is in stroke that persists within one year of living at home after being discharged from the hospital. Therefore, regardless of age, gender, disability, and the severity or type of stroke, multidisciplinary treatment involving rehabilitation professionals in stroke treatment is to provide high-quality brain stroke treatment.The second phase, inpatient rehabilitation. Stroke inpatient rehabilitation usually refers to professional stroke rehabilitation institutions, including rehabilitation doctors, rehabilitation nurses, physical therapists, occupational therapists, speech and language therapists, and assistants. In most National Health Service agencies, dietitians, clinical psychologists, and social workers are not unit-based and work more on the periphery. Patients are usually evaluated early within 24 hours and are based on national clinical guidelines, and the Sentinel National Stroke Plan standard provides appropriate referrals to ensure that these professionals assist in recovery when specific needs are identified.In most countries, inpatient stroke rehabilitation is supported by evidence-based national clinical guidelines and relies on rehabilitation teams to plan, provide, and evaluate treatment. Langhorne  believesThe third phase is rehabilitation after discharge (community rehabilitation). It must be realized that the treatment of stroke cannot be indefinite by specialist doctors. Although stroke patients and their caregivers have clear long-term medical support demand, there is currently little information on how to better support treatment. The expert consensus is that once the rehabilitation goal is reached, the treatment plan may be taken over by a nonprofessional, community-based medical institution. This reflects a point of view that stroke treatment varies according to the needs of patients, and in stroke community rehabilitation, what medical staff need most is knowledge and understanding of community rehabilitation treatment, not stroke specialist knowledge. Currently proposed by the UK, all stroke patients should be followed up regularly within 6 months after the illness. Although the background and implementation of this plan are not specified, and the current implementation is not complete, stroke patients need some form of longer-term follow-up. The treatment has been recognized. Self-management is increasingly seen as the most appropriate way for patients who need long-term support, and it has now become part of helping people adapt to life after stroke. This adjustment takes time and, therefore, requires to develop a staged clinical path of stroke through the education and support of stroke patients and their families. In later stage of inpatient rehabilitation treatment, patients will be less dependent on professional rehabilitation personnel. They will be more able to understand and manage themselves, so that stroke patients can become self-conscious.Meet the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke, and it was confirmed as the first onset by CT or MRI.Age 45–75 years.Course of disease 7–15 days.Clear consciousness, GCS ≥13 points.Cognitive function.Around fifty (50) cases of ischemic stroke patients, specifically those who were hospitalized in the Department of Rehabilitation Medicine of a University Hospital in China from January 2013 to January 2015, were screened through the big data and divided into clinical pathway (25 cases). Furthermore, routine groups were divided according to the random number table method rehabilitation groups (25 cases). The possible selection criteria are based on the following:MMSE (illiterate) ≥18 points; MMSE (primary school) ≥ 21 points; MMSE  ≥23 points; MMSE (university) ≥24 points; (6) severity of neurological impairment: National Institutes of Health Stroke Scale (NIHSS) ≤16 points; (7) moderate to severe motor dysfunction: simplified Fugl-Meyer motor function <85 points; (8) if the patient at the same time accompanied by other diseases, no special treatment is required during the hospitalization and does not affect the implementation of the clinical pathway process of the first diagnosis; (9) all patients have signed the informed consent.A history of cerebral infarction of two or more times.Severe clinical complications or complications: severe liver and kidney disease, decompensated heart insufficiency, heart or respiratory arrest or myocardial infarction within 3 months, severe pneumonia or chronic obstructive pulmonary disease, deep vein thrombosis, etc.Other diseases or medical history that affect motor function, such as a history of fractures of limb dysfunction on the side of hemiplegia, amputation, and history of lower limb osteoarthritis that affects walking, malignant tumors, pregnancy, etc.Suffering from severe mental illness or accompanied by mental symptoms.Severe aphasia, which affects communication and cannot cooperate with examinations and rehabilitation training.p > 0.05 is considered statistically significant as depicted in Those who have not signed an informed consent based on big data records. There is no difference in gender, age, course of disease, and hemiplegia between the two groups. Exclusion criteria:Department of Rehabilitation Medicine in a tertiary general hospital: the standard hospital stay is 20-21 days (3 weeks). After acute clinical treatment , select the corresponding one based on the patient's rehabilitation evaluation results. Class-level rehabilitation program. Specific items include exercise therapy training; occupational therapy, corresponding speech and swallowing therapy for patients with speech and swallowing disorders, physical factor therapy, and traditional Chinese medicine rehabilitation therapy. Specific time requirements: exercise therapy training and homework. The daily training time totals 1.5 hours, of which the exercise therapy training intensity is 60 minutes a day, and other additional training time can be appropriately increased depending on the patient's tolerance; the daily training time of swallowing function is 70 minutes in total, of which the manual training intensity is 30 minutes a day, neuromuscular electrical stimulation is 2 times a day, 20 minutes each time, and other additional training time depends on the patient's tolerance and can be increased appropriately; speech function training time: training intensity 30 minutes a day, other additional training time depends on the patient's tolerance level that can be increased appropriately; nursing education and psychological counseling: according to the content of nursing records, 1 time/day; depending on the needs of the patient, increase appropriately during admission and discharge.Second-level specialist rehabilitation hospitals: standard hospitalization days are 40–42 days ((6 weeks). According to the patient's rehabilitation assessment results, select the corresponding second-level rehabilitation program. The specific items are the same as those of the rehabilitation medicine department of a third-level general hospital. Specific time requirements: exercise therapy training and occupational therapy, a total of 3 training hours per day; the exercise therapy training intensity is 90 minutes a day, and other additional training time can be appropriately increased depending on the patient's tolerance; the training schedule of swallowing function and speech function is the same as that of the rehabilitation department of tertiary general hospitals; nursing education and psychological counseling: according to the contents of the nursing records, 1 time/day, depending on the needs of the patient during admission and discharge.Community rehabilitation organization (family rehabilitation guidance for 8 weeks). Patient rehabilitation records were collected based on big data, which follow the family training program record form. It is required to formulate a corresponding weekly training program, and it is required to complete the content of the family training program once a day, and the training time is not less than 60 minutes a day. During the implementation process, the opinions of patients and their families are solicited, with a view to continuous modification and supplementation.According to the patient files recorded by the big data, select the patients in the clinical path group and then perform comprehensive index evaluation according to the unified rehabilitation treatment plan of the three-level rehabilitation medical institution in the record, that is, the rehabilitation medicine department of the tertiary general hospital , second-level specialist rehabilitation hospitals , and community rehabilitation institutions (family rehabilitation guidance for 8 weeks). According to big data, it takes 17 weeks for the clinical pathway group to complete a set of three-level referrals. The clinical pathway group rehabilitation training requirements are given as follows:The treatment content records of the conventional rehabilitation group were collected by big data while ensuring that the basic conditions at the time of enrollment are consistent with the clinical pathway group. Moreover, the experimental process is completed according to the conventional rehabilitation mode and method in the current three-level rehabilitation institutions and standard hospitalization days and rehabilitation treatment. There are no restrictions on the content and treatment time and intensity, but the treatment content and time need to be truthfully recorded in the rehabilitation treatment record sheet, recorded once a week for a total of 17 weeks of follow-up.Experimental results are completed by the same evaluator, who has been trained in the training process. Evaluators will not participate in the enrolled patients' rehabilitation treatment and other test processes except for the evaluation. They will be conducted at the beginning of the treatment, on the 3rd weekend after the treatment, the 9th weekend, and the 17th weekend. Evaluation. The simplified Fugl-Meyer motor function scale is used to evaluate motor function of the limbs, which is divided into total scores, i.e., upper limb and lower limb scores, respectively. For muscle reflex, flexor and extensor coordinated movement, activities accompanied by coordinated movement, activities that depart from coordinated movement, and reflexes. The hyperactivity, joint stability, coordination ability, and speed are scored. Each item is worth 0∼2 points, and the total score is calculated; The hyperactivity, joint stability, coordination ability, and speed are scored. Each item is worth 0∼2 points, and the total score is calculated; the modified Barthel index scale is used to assess the patient's activities of daily living, according to toileting, eating, urinating and defecation control, bed and chair transfer, level walking, and other 10 content items, each item is given 0–15 points, and the total score is calculated. On the 9th weekend after treatment, compare the total hospitalization and rehabilitation costs of the two groups as well as the required costs and MBI and increase the ratio of points.According to the patient records collected by big data, at the 9th week after treatment, the two groups of complications were compared, including pulmonary infection, urinary tract infection, lower extremity venous thrombosis, shoulder-hand syndrome, and pressure ulcers. Lung infection by auscultation and chest lung lobe imaging changes on film examination are the criteria. Urinary tract infections are determined by urinary tract irritation and positive mid-level urine culture as the criteria. Lower limb venous thrombosis is the presence of lower limb swelling and pain. B-ultrasound changes in vascular imaging are the criteria. Shoulder-hand syndrome is based on pain, swelling, and restricted movement in the shoulder and hand on the hemiplegic side, and X-rays and related examinations have excluded other causes. The criterion for pressure skin ulcers is the appearance of skin ulcer at the compressed site.x ± s). The paired-sample t-test was used for comparison within groups, and the independent sample t-test was used for comparison between groups. The homogeneity of variance was performed before the t-test. If variance is uniform, then use the t and rank sum tests for statistical analysis. p < 0.05 considers the difference to be statistically significant.Statistical software was used to analyze the data, which were expressed as the mean ± standard deviation . Compared with the pretreatment within the group, FMA and MBI scores of two groups increased gradually on the 3rd weekend, 9th weekend, and 17th weekend after treatment, and difference was statistically significant (p < 0.05). At the 3rd weekend after treatment, MBI score was significantly higher than that of the conventional rehabilitation group (p < 0.05). At the 17th weekend after treatment, there was no significant difference in FMA and MBI scores between the clinical pathway group and the conventional rehabilitation group (p > 0.05) as shown in 2According to the treatment of two groups recorded by big data, particularly before treatment, difference in FMA and MBI scores between the clinical pathway group and conventional rehabilitation group was not statistically significant (p < 0.05). See p < 0.05).During the treatment of two groups of patients, total hospitalization expenses and rehabilitation expenses of the clinical pathway group from the start of enrollment to the 9th weekend after treatment were significantly higher than those of the conventional rehabilitation group, and the comparison was statistically significant (p < 0.05), which is shown in During the treatment of two groups of patients, the clinical pathway group had 3 cases of pulmonary infection, 2 cases of urinary tract infection, 0 cases of lower limb venous thrombosis, 1 case of shoulder-hand syndrome, and 0 cases of pressure sores in the clinical pathway group from the beginning of the group to the 9th weekend after treatment. In the conventional rehabilitation group, there were 5 cases of pulmonary infection, 3 cases of urinary system infection, 1 case of lower limb venous thrombosis, 3 cases of shoulder-hand syndrome, and 1 case of pressure ulcers. All patients improved after symptomatic treatment, and there were no deaths in both groups. The overall complication rate of patients was 24.0% and 52.0%, and the difference between the two was statistically significant (The results show that with the extension of treatment time, the FMA and MBI scores of the two groups increased significantly compared with the previous time point, suggesting that whether it is the clinical pathway group or the conventional rehabilitation group, tertiary rehabilitation treatment can effectively improve the motor function of the limbs and activities of daily living of stroke patients. The FMA and MBI scores of the clinical pathway group were significantly higher than those of the conventional rehabilitation group on the third weekend and the ninth weekend after treatment. It can more effectively improve the motor function and ability of daily living of stroke patients and improve the quality of rehabilitation. However, after the patient enters the community or home to receive rehabilitation treatment at the 17th weekend after treatment, there is no significant difference between the FMA and MBI scores of the two groups. Explain that when it comes to the third-level rehabilitation stage, that is, the community or family rehabilitation stage, because it is only pure rehabilitation education or guidance, the patient does not go to a special rehabilitation institution, does not have professional rehabilitation personnel on-site guidance and supervision, and cannot be completed as required. Their athletic ability and the ability of activities of daily living have not been further improved, which may also indicate that the curative effect of the tertiary rehabilitation clinical pathway lasts for less than 17 weeks.In recent years, as China's economic development has continued to accelerate, comprehensive national strength continues to increase and the country's investment in medical resources has gradually increased. China's tertiary rehabilitation network has continued to strengthen, and tertiary first-class hospitals have established rehabilitation medicine departments and second-level specialist rehabilitation hospitals. Community rehabilitation centers and other institutions have gradually increased. From the perspective of the rational deployment of medical resources, stroke patients have a very large demand for community rehabilitation, but it is currently difficult to meet. Patients perceive a doctor between different levels of rehabilitation institutions, and there is no unified referral and rehabilitation treatment system standard that can be used for reference. In order to make the three-level rehabilitation system for stroke patients as effective and cost-effective as possible, it is imperative to establish a unified referral process and rehabilitation plan.In this study, we have designed a big data technology-based information collection system specifically for stroke patients based on the original three-level rehabilitation, which are treated in a hospital in a certain region of China. It compares changes in FMA and MBI scores of the clinical pathway group and conventional rehabilitation group, as well as the related costs. In order to meet the precision rehabilitation, the requirement is to provide individualized rehabilitation treatment for dysfunction. The ultimate goal is to actively improve the patient's various functions and activities of daily living, and help the patient return to a normal society and family life as soon as possible. On the basis of conventional rehabilitation treatment for patients with ischemic stroke, the implementation of the three-level rehabilitation clinical path can promote the patient's limb motor function and better recovery of the ability of daily living in the early stage, and improve the patient's quality of life. It is worthy of further research and promotion. In the later stage or in community or family rehabilitation training, it is necessary to encourage and guide patients to persist in training according to the requirements of the path and at the same time to do a good job in the training of relevant rehabilitation knowledge for family members, to play its role in supervision and assistance, and to enhance patient confidence, so that patients can take care of themselves and return to life. A normal social life lays the foundation. It is very important for patients who return to their families or communities after inpatient rehabilitation treatment to enter a standardized community rehabilitation system to receive rehabilitation treatment.


There was no product obtained in presence of catalysts, such as Et3N, C2H5ONa, C4H9OK, (CH3)3COK and pyridine. But in present of DABCO, this reaction has proceeded and monitored the concentration of catalyst and various temperature effects on reaction progress. In addition, the computational approaches for speculative investigation of solvents effect has employed for predicating and comparatively verified with the proposed reaction mechanism in presence of DABCO catalyst through the Density Functional Theory (DFT). The most acceptable tools for the thermodynamic had been illustrated to get the reaction kinetics by formation energy, entropy, enthalpy for reactant, product and transition state. Finally, the Gibbs free energy for reactions from the reactants and product has calculated to predict the occurring spontaneously possibility with and without solvents, and it is said that the reaction is spontaneously occurred through the water, DMSO, THF solvent although it is opposed fact without solvent even other solvents. It might be concluded that the optimization conditions of reaction are the THF solvent in presence of 20% DABCO catalyst at room temperature with high (about 90%) throughout 6–8 h where the 4- position of nitro group in arylaldehyde is the most preferable in case of time and yield.The 4-diazabicyclo[2. 2. 2] octane, DABCO, had widely established with gigantic and celestial applications on catalysis for carbon-carbon bond formation reactions. Thus, it has been employed to synthesize the alkyl 2-(hydroxyl (nitrophenyl) methyl)acrylate by the reaction of arylaldehydes and alkylacrylates under a mild condition with good yields. First of all, reaction was examined effect of various solvents, such as water, MeOH, Dioxane, DMSO, t-Butanol, DMF, Toluene, and THF and THF was the best solvent in term of yield. Next, the room temperature (R.T) was the optimized condition than 60 °C and 80 °C. The overall reaction progress was monitored in presence of DABCO, Et DABCO, Arylaldehyde, Alkylacrylates, Computational chemistry, Carbon-carbon bond and DFT. Found: C, 55.85; H, 4.82; N, 6.10.Anal. Calcd for CEthyl 2-[hydroxyl (4-nitrophenyl) methyl] acrylate 7Light yellowish liquid, Yield: 90%, 1.129 gmax (KBr) 3500.92 (O–H), 2986–3134 (C–H), 1710 (C–O), 1610 (-O-), 1350 (NO2), 700–1000, cm−1.IR: ν3): λmax 336.00, 273.00, 218.80, 214.40, 204.60 nm.UV  δ (ppm) 8.16 , 7.54 , 6.37 , 5.85 , 5.60 , 4.134 ), 3.48 , 1.23 .13C NMR  δ (ppm) 165.93 (CO), 148.77 (Ar–C), 147.35 (Ar–C), 141.20 (1-ethylene-CO), 127.34 (Ar-CH), 126.96 (1-ethylene), 123.54 (Ar-CH), 72.61 (C-methine), 61.29 (-OCH2), 13.98 (CH3).2), 13.98 (CH3).DEPT: 127.34 (Ar-CH), 126.96 (1-ethylene), 123.50 (Ar-CH), 72.34 (C-methine), 61.29 (-OCHMethyl 2-[hydroxy (3-nitrophenyl) methyl] acrylate 8Colourless liquid; Yield: 83%, 1.143 gmax (KBr) 3476.81(O–H), 2987.84 (C–H), 1709.95 (C–O), 1531.53 (–CO–), 1352.14 (NO2), 700-1000 cm−1.IR: ν3): λmax 676.50, 263.50, 224.50 nm.UV  δ (ppm) 8.26 , 8.14 , 7.74 , 7.52 , 6.42 , 5.93 , 5.65 , 3.75 .13C NMR  δ (ppm) 166.39 (CO), 148.37 (Ar–C), 143.67 (Ar–C), 141.04 (1-ethylene), 132.68 (Ar-CH), 129.36 (Ar-CH), 127.26 (Ar-CH), 122.77 (Ar-CH), 121.57 (1-ethylene), 72.56 (C-methine), 52.19 (CH3).11H11NO5: C, 55.70; H, 4.67; N, 5.90. Found: C, 55.87; H, 4.78; N, 6.08.Anal. Calcd for CEthyl 2-[hydroxy (3-nitrophenyl)methyl] acrylate 9Colourless liquid; Yield: 70%, 0.878 gmax (KBr) 3489.34 (O–H), 2956.01 (C–H), 1712.85 (C–O), 1536.53 (–CO–), 1350 (NO2), 700-1000 cm−1.IR: ν3): λmax 652.50, 264.00, 230.00 nm.UV  δ (ppm) 8.27 , 8.14 , 7.75 , 7.51 , 6.42 , 5.91 , 5.64 , 4.17 , 3.76 , 1.26 .13C NMR  δ (ppm) 165.95 (CO), 148.33 (Ar–C), 143.67 (Ar–C), 141.28 (1-ethylene), 132.67 (Ar-CH), 129.36 (Ar-CH), 126.95 (Ar-CH), 122.72 (Ar-CH), 121.57 (1-ethylene), 72.56 (C-methine), 61.30 (O–CH2), 14.02 (CH3).12H13NO5: C, 57.37; H, 5.22; N, 5.58. Found: C, 57.52; H, 5.45; N, 5.71.Anal. Calcd for CMethyl2-[hydroxy(2-nitrophenyl)methyl] acrylate 10Light yellowish liquid; Yield: 80%, 1.102 gmax (KBr) 3446.91(O–H), 2956.01 (C–H), 1718.63 (C–O), 1532.50 (–CO–), 1352.14 (NO2), 600-1000 cm−1.IR: ν3): λmax 257.40, 214.20 nm.UV  δ (ppm) 7.95 , 7.76 , 7.64 , 7.46 , 6.38 , 6.22 , 5.74 , 3.75 .13C NMR , δ (ppm) 166.43 (CO), 148.36 (Ar–C), 140.78 (Ar–C), 136.11 (1-ethylene), 133.45 (Ar-CH), 128.91 (Ar-CH), 128.71 (Ar-CH), 126.47 (Ar–H), 124.58 (1-ethylene), 67.70 (C-methine), 52.17 (CH3).11H11NO5: C, 55.70; H, 4.67; N, 5.90. Found: C, 55.62; H, 4.73; N, 5.78.Anal. Calcd for CEthyl 2-[hydroxyl (2-nitrophenyl) methyl] acrylate 11Light yellowish liquid; Yield: 84%, 1.054 gmax (KBr) 3518.28 (O–H), 2986.87 (C–H), 1719.60 (C–O), 1532.50 (–CO–), 1332.50 (NO2), 600-1000 cm−1.IR: ν3): λmax 355.60, 335.60, 256.00, 211.80 nm.UV  δ (ppm) 7.97 , 7.75 , 7.64 , 7.46 , 6.39 , 6.20 , 5.75 , 4.15 , 2.86 , 1.21 .13C NMR , δ (ppm) 165.97 (CO), 148.41 (Ar–C), 140.90 (Ar–C), 136.22 (1-ethylene), 133.49 (Ar-CH), 128.93 (Ar-CH), 128.70 (Ar-CH), 126.29 (Ar–H), 124.57 (1-ethylene), 67.75 (C-methine), 61.20 (OCH2), 13.99 (CH3).12H13NO5: C, 57.37; H, 5.22; N, 5.58. Found: C, 57.54; H, 5.38; N, 5.75.Anal. Calcd for CIt is reported here that the coupling between alkylacrylates with arylaldehydes were accomplished in presence of DABCO in good yield% .2.43 code of material studio 8.0. To perform this work, the B3LYP functional and DND basis set was used. In this case, the reactants and products were used to form the transition state. Next, the reactants, products and transition complexes were simulated using the B3LYP functional and DND basis set and recorded to the heat of formation, entropy, enthalpy and Gibbs free energy. Secondly, the evaluate the solvent effect, the reactant and product were also simulated using the same method and condition, and Water, MeOH, Dioxane, DMSO, t-Butanol, DMF, Toluene, and THF solvent were executed from the DFT methods to calculate the Gibbs free energy and heat of formation. On the other hand, to calculate the quantum properties, structural stability, the B3LYP functional and DND basis set from the DMol3 code of material studio 8.0. The HOMO, LUMO and Electrostatic potential 3D map were optimized and analyzed for illustrate the chemical descriptors. At last for calculating the stereocnetre of optimized molecules, the Gaussian 16 software packet was used for determination the stereoisomer for the synthesized molecules  acrylate and its derivates (06–11), it might be revealed that 4-position of nitro group in aryl acrylate is highly reactive for reactant due to low static hindered force occurring the proton transferring. Then, the synthesized acrylate derivates (06–11) were characterized by 1H NMR, 13C NMR FTIR and UV data. Finally, with the computational evidence, it could be said that this reaction follows the 2nd order reaction mechanism with THF solvent in presence of DABCO catalyst at room temperature for formation of carbon-carbon single bond between aryl acrylates and aldehydes. The control of stereochemistry of BH adducts and it might develop chemical transformation of –OH group at chiral centre and addition reaction at double bond. By the computational calculation, it was found that the synthesized acrylate derivates (06–11) are the S-stereoisomer at C7 carbon atom. At last, the HOMO and LUMO and energy gaps make the further study for the biological significances as bioactive molecules.The synthesis of alkyl 2-[hydroxyl (nitrophenyl) methyl] acrylate in one step under mild conditions has been discussed in details of catalytic nature at optimized temperature and suitable solvents. To kick off, THF solvent is obtained the best solvent among 1, 4-dioxane, tetrahydrofuran (THF), dimethylsulfoxide (DMSO), dimethylformide (DMF), dichloromethane (DCM), toluene, acetonitrile, Laila Arifun Nahar: Conceived and designed the experiments; Performed the experiments.Ajoy Kumer: Performed the experiments; Analyzed and interpreted the data; Wrote the paper.Md Wahab Khan: Contributed reagents, materials, analysis tools or data.10.13039/501100009500Bangladesh University of Engineering & Technology (BUET), Dhaka-1000, Bangladesh.This work was supported by Data included in article/supplementary material/referenced in article.The authors declare no conflict of interest.No additional information is available for this paper.


COVID-19 is the disease caused by SARS-CoV-2, one of a large family of coronaviruses. Severe forms of the disease can lead to respiratory failure with multiple organ failure necessitating rehabilitation in both acute and long-term care. With the increasing prevalence of COVID-19 and rehabilitation needs, the African Rehabilitation Network (AFRENET) produced a guidance document to assist in reducing variation in clinical practice among rehabilitation professionals in the Africa Region. This report outlines the process of the guideline development. COVID-19 is the disease caused by SARS-CoV-2, one of a large family of coronaviruses .In Africa, COVID-19 is reported through the WHO AFRO , and the WHO EMRO . The first cases of COVID-19 were confirmed on 14 February 2020 in Egypt, and soon after in Algeria, Nigeria, and Senegal .Although African health systems are growing, there are still many places where health services are inadequate. The COVID-19 pandemic has increased the strain on already fragile health systems with insufficient rehabilitation services across the region also challenged. Many existing rehabilitation services across Africa often suffer from lack of infrastructure and human resources with increased workload for rehabilitation professionals. There are few clinical practice guidelines in rehabilitation that were adapted or contextualized to the region to improve practice. To the best of our knowledge there were no existing guidelines developed, adapted, or contextualized for rehabilitation professionals during this period of COVID-19.As the pandemic grew, rehabilitation professionals took notice of the increasing rehabilitation needs in the region. The African Rehabilitation Network (AFRENET) was formed by a diverse group of rehabilitation professionals in Africa. We thought of innovative ways to mobilize resources and deliver effective services despite the extra burden imposed by COVID-19. With these initiatives and efforts, we created a community of practice involving rehabilitation professionals practicing in Africa, using WhatsApp and Zoom to bring practitioners together from many countries to discuss the important role of rehabilitation in the region during the crisis.One action taken by AFRENET was to develop a set of guidelines for rehabilitation practitioners to improve on the effectiveness of service delivery, decrease costs, prevent avoidable mistakes, and reduce variation in clinical practice in the region. This process was inspired by, and adapted with permission from, a group at McMaster University in Canada who had already published rehabilitation guidelines during the COVID-19 pandemic , and anoReviewing the literature: given the fact that COVID-19 is a new disease of pandemic proportions and data is still evolving, very little was published in the academic literature specifically about COVID-19 and rehabilitation. At that time, we found no academic literature specific to COVID-19 and rehabilitation emanating from the Africa Region. As such we gathered literature that was being shared from professional networks, gray literature, and from academic databases on related topics across the globe. We also identified and adopted guidelines from other settings within the region. All the available data was collected into a Zotero library and made accessible to all members of the rehabilitation professional group.Online discussions: following the group initiative, a draft list of guidelines was developed based on existing literature. A Google document was generated with the drafted guidance document to allow for contributions. There was significant discussion which recognized the diversity, the strengths, and the challenges across the continent. Discussion centered on what was feasible and acceptable within the African context based on existing infrastructure and human resources. Contributors talked about the existence of a very low ratio of health professionals to patients and need to improve practice and quality of care during this period. This lack of health personnel is even more evident among rehabilitation workers such as community-based rehabilitation workers (CBRWs), occupational therapists (OTs), physiotherapists (PTs), speech and language therapists (SLTs) in the continent. Other frontline workers who had firsthand experience or who had participated in developing any form of guidance document related to rehabilitation at the institutional or national level also shared their experiences for discussion on what was most relevant and practical in the region.The authors recognized that the situations in various settings, cities, regions, and countries can be very different based on infrastructure and availability of rehabilitation professionals. We discussed the need for guidelines to be applicable in a variety of settings. For example, there are significant differences between the management of COVID-19 in the better resourced healthcare settings, and the many other African settings where rehabilitation is not fully supported. Social and cultural conditions were also considered where rehabilitation professionals represented and shared their experiences. It was agreed that the document would not replace institutional policies and practices but rather supplement existing efforts and resources put in place to improve client/patient and healthcare professionals´ safety and practice during this period.Consultation with experts: the complete draft guideline for rehabilitation professionals in Africa was then forwarded to experts in guideline development and specialist clinicians in rehabilitation including the team at McMaster University, Ontario, Canada and the Community-based rehabilitation Africa Network, who provided detailed constructive feedback. This feedback was then discussed among the writing group members and integrated into the document.Rehabilitation of patients with COVID-19 in African Settings: Guidance for Community Based Rehabilitation Workers, Physiotherapists, Occupational Therapists, Speech and Language Therapists, and Assistants. The guidelines are available online. Updates of this document will also be posted on these sites when made. The final guidance document is divided into two main sections. The first section is composed of seven interconnected key considerations applicable to all rehabilitation providers. Each of these key considerations is further supported with specific recommendations. The key considerations are: i) assessment of risk and actions to be taken to reduce risk and spread of COVID-19 in rehabilitation settings; ii) working as a team; iii) avoidance of person to person contact as much as possible; iv) anticipation of an increased demand of workforce; v) type of personal protective equipment (PPE) needed for patient contact; vi) inclusion of people with other impairments and disabilities apart from those due to COVID-19; vii) streamlining of documentation procedures.The result was a set of guidelines called The second section is composed of best practice statements for specific rehabilitation providers notably, statements for community-based rehabilitation workers for homes and communities where the present COVID-19 patients are established and where the presence of COVID-19 is unknown. We also provided specific statements for different phases of the rehabilitation process in hospital settings, as well as therapeutic procedures for physiotherapists, occupational therapists, and speech and language therapists.The guidance document was designed to be practical and to meet the need of a diverse group of rehabilitation professionals  in the African context. While clinical practice guidelines have evolved from being opinion-based to evidence-informed with an increasing sophisticated methodology in development , expertsChallenges: from the conception to realization of the guidelines, there were challenges principally due to insufficient availability of rehabilitation professionals with skills on guideline development and COVID-19 disease. This perceived lack of skilled professionals was further compounded by the absence of a well-established international or national guideline development group or manual in the region such as the Scottish Intercollegiate Guideline Network (SIGN) [k (SIGN) . Other fWe report a successful adaptation and contextualization of a clinical practice guideline for rehabilitation professionals working in African settings with patients with or without COVID-19, through the efforts of a small team of dedicated volunteers with variable understanding of developing clinical practice statements and recommendations. We encourage similar efforts and collaboration in rehabilitation within the region.


Significant aortic regurgitation (AR) is a common complication after continuous-flow left ventricular assist device (LVAD) implantation. Using machine-learning algorithms, this study was designed to examine valuable predictors obtained from LVAD sound and to provide models for identifying AR. During a 2-year follow-up period of 13 patients with Jarvik2000 LVAD, sound signals were serially obtained from the chest wall above the LVAD using an electronic stethoscope for 1 min at 40,000 Hz, and echocardiography was simultaneously performed to confirm the presence of AR. Among the 245 echocardiographic and acoustic data collected, we found 26 episodes of significant AR, which we categorized as “present”; the other 219 episodes were characterized as “none”. Wavelet (time–frequency) analysis was applied to the LVAD sound and 19 feature vectors of instantaneous spectral components were extracted. Important variables for predicting AR were searched using an iterative forward selection method. Seventy-five percent of 245 episodes were randomly assigned as training data and the remaining as test data. Supervised machine learning for predicting concomitant AR involved an ensemble classifier and tenfold stratified cross-validation. Of the 19 features, the most useful variables for predicting concomitant AR were the amplitude of the first harmonic, LVAD rotational speed during intermittent low speed (ILS), and the variation in the amplitude during normal rotation and ILS. The predictive accuracy and area under the curve were 91% and 0.73, respectively. Machine learning, trained on the time–frequency acoustic spectra, provides a novel modality for detecting concomitant AR during follow-up after LVAD. Left ventricular assist devices (LVADs) have become an important treatment of choice for patients with end-stage heart failure, not only as a bridge to heart transplantation, but also as a destination therapy . With thThe purpose of the present study was to determine whether acoustic signal analyses and machine-learning modeling could be used to detect serious AR occurring after LVAD implantation.We prospectively followed 13 patients who received the Jarvik2000 continuous-flow implantable LVAD as a bridge to heart transplantation between 2015 and 2017. LVAD was implanted in a standard manner with cardiopulmonary bypass. The pump housing was implanted at the apex of the left ventricle, and the outflow graft was anastomosed to the ascending aorta. The driveline cable passed the subfascial route and exited the right abdominal wall. All patients provided informed consent for participation in this study, and hospital institutional review board approval (No. 15335) was obtained.Sound signals were obtained on the chest wall just above the LVAD implantation site, with a Bresco commercially available electronic stethoscope . Acoustic data were collected monthly at each outpatient visit, or more frequently for inpatients depending on the patients’ clinical status. The Jarvik2000 features intermittent low-speed (ILS) function, which reduces the rotational speed to 7000 revolutions per minute (rpm) for 8 s every 64 s, to allow opening of the aortic valve for the purpose of reducing the risk of thrombus formation by washing-out effect of the native heartbeat . TherefoThe grade of AR was confirmed by the transthoracic echocardiography performed at a time closest to the time of the LVAD sound recording. The grade of AR was assessed by the width of the regurgitant jet on the color-Doppler image, divided by the dimension of the aortic annulus, and was categorized as none, trivial, mild, moderate, or severe. In this study, moderate or severe grades of AR were judged as “significant” AR.The sound signal processing and visualization were performed using custom software developed in MATLAB . Generally, sound is composed of multiple sound waves of different frequencies (Hertz: fluctuations or unit/time) and amplitudes (sound strength). Spectrographic analysis was performed for each sound signal by plotting acoustic data as a function of time, frequency, and amplitude based on the discrete wavelet transform using a Gabor basis wavelet. Because the amplitude of the recorded sound is susceptible to environmental conditions such as the physical distance between the LVAD and electronic stethoscope, the magnitude of the amplitude fraction was normalized to the percentage of the largest amplitude that was observed within the selected time period .The acoustic spectrum from LVAD generally has recognizable peaks produced by the turning of the impeller  and its harmonics. The Jarvik2000, operating normally, rotates at between 8000 and 12,000 rpm, so the basic frequency peak of the impeller appears between 133 and 200 Hz. The second harmonic frequency peak, which is double the basic frequency, appears between 266 and 400 Hz. According to these recognizable peaks, the frequency spectrum in this study was divided into frequency regions to facilitate further calculations . The frequency and amplitude fractions of the basic, second, and third harmonic peaks were further processed using a fast Fourier transform. The fluctuations of the frequency and amplitude fractions from each peak were calculated in the order of Hz and a.u., respectively.While analyzing the frequency fluctuations of the basic sound, a strong peak is usually observed between 1 and 1.5 Hz, which corresponds to the heart rate of the patient. The analysis of amplitude fluctuation also reveals a strong peak below 0.5 Hz, which corresponds to the respiratory rate of the patient.During the period of ILS operation, the acoustic spectrum from LVAD has the same structural characteristics as the normal operation, which is composed of a recognizable basic peak and its harmonics. The rotational speed at ILS is set at 7,000 rpm, so the basic frequency peak appears around 167 Hz. Fluctuations in the frequency and amplitude fractions of the basic peak during ILS were also analyzed and quantified.Overall, 19 numerical feature vectors were extracted from each sound signal to prepare for the machine-learning process , naïve Bayes (NB), kernel NB, random forest, support vector machine (SVM), kernel SVM, and decision tree. We did not use a neural network as a machine-learning algorithm in the current study because of the small sample size. All these algorithms were applied to the best feature combination determined by feature engineering while performing model optimization through hyper-parameter tuning and leave-one-out cross-validation, with the exception of the random forest algorithm. The optimal machine-learning algorithm was determined by comparing its performance. The performance of a built-up machine-learning model was evaluated by misclassification error, area under the curve (AUC), true positive rate, and true negative rate.The baseline characteristics of the patients in this study are shown in Table During the follow-up period, a total of 245 LVAD sound signals were obtained. Of those, 26 10.6%) sound signals were obtained from 2 (15%) patients with significant AR (Fig. 0.6% sounThe results and data quality of the extracted features from each sound signal are summarized in Table Utilizing the dataset of important features selected, the ensemble classifier best predicted AR with an AUC of 0.73 (Table The major findings of this study can be summarized as follows: in patients with a Jarvik2000 LVAD, the machine-learning algorithm, trained on acoustic spectra obtained from LVAD sound signals, effectively predicted significant AR. During processing of the recorded sound signals, 19 features were extracted from each sound signal using wavelet time–frequency analysis. Of these 19 features, 4 features were selected as important predictors for AR. With this dataset, the ML algorithm was trained and predicted AR with an accuracy of 91%. The observed efficacy suggests that machine learning trained on acoustic spectra has an important role in detecting clinically important conditions in patients with LVAD.AR is one of the major complications after CF-LVAD implantation, and it is said that mild-to-moderate AR occurs in approximately 25% of cases within one year after surgery , 12. ExaIn utilizing a machine-learning algorithm for predicting the outcome, preparing datasets that are relevant and not redundant is important to achieve satisfactory predictive accuracy. In this study, wavelet time–frequency analysis extracted 19 features characterizing the recognizable peaks of basic rotational sound and its harmonics, and the noises existing between the peaks for each sound signal. This feature extraction might contribute to improving the predictive accuracy of the machine-learning process. To date, acoustic signal analysis has been used to detect pump thrombi but fails to provide accurate diagnostic tools , 16–19. Feature selection is also an important step in achieving improved predictive accuracy in the machine-learning process. Choosing a set of features that has the best predictive value and eliminating the redundancy between extracted features is useful not only for enhancing the predictive accuracy of machine learning but also for reducing the number of calculations the algorithm has to process. Previous machine-learning articles have utilized several different algorithms at the feature selection step –22. TherFeature selection is also beneficial for clinicians because the selected important features enable us to interpret the relationships between the features and the outcome. In this study, three features were selected as being highly predictive of concomitant AR: the amplitude of the first harmonic, LVAD rotational speed during ILS, and the variation of the amplitude both during normal rotation and ILS. The first harmonic is the most basic sound produced by the LVAD rotation, reflecting the rotational speed of the device. In cases without significant AR, these first harmonics appear prominently, while in cases with AR, acoustic components appear in addition to the first harmonics; therefore, it is presumed that the intensity of the first harmonics are relatively weakened. In AR cases, the LVAD rotational speed tended to decrease more during ILS than in non-AR cases. In AR cases, the LVAD preload increases with AR, and it is presumed that this works in the direction of lowering the LVAD rotational speed to a greater extent than in non-AR cases. Furthermore, in AR cases, the intensity of the LVAD sound fluctuated to a greater degree. The fluctuation range of the intensity of the LVAD sound seems to represent the change in the amount of work performed by the LVAD, and this may depend on the change in the preload of the LVAD. In AR cases, as a result of insufficient unloading of the left ventricle due to AR, it is presumed that the increase and/or decrease in preload of the LVAD, caused by the native cardiac output, appears more easily than in non-AR cases, which affects the degree of fluctuation of the device’s rotational speed. Further research is needed with more large number of clinical datasets or bench testing with artificial mock circulation to clarify the clinical implications of these important predictive features for the detection of AR.Among the three important features selected to predict concomitant AR included acoustic data during ILS. As ILS is a function specifically equipped with Jarvik2000, our results cannot be simply applied to other LVAD systems. However, methodologies described in this study including feature extraction from acoustic signals, selecting the best predictive dataset, and choosing best classifier algorithm to predict clinical outcome, can be theoretically applied to other LVAD systems with clinical outcomes other than AR.Machine learning trained on the time–frequency acoustic spectra provides a novel modality for detecting concomitant AR during follow-up after CF-LVAD implantation. This could allow automated identification of pathological conditions related to the device, resulting in earlier diagnosis and subsequent intervention.


Augmented Reality (AR) represents an evolution of navigation-assisted surgery, providing surgeons with a virtual aid contextually merged with the real surgical field. We recently reported a case series of AR-assisted fibular flap harvesting for mandibular reconstruction. However, the registration accuracy between the real and the virtual content needs to be systematically evaluated before widely promoting this tool in clinical practice. In this paper, after description of the AR based protocol implemented for both tablet and HoloLens 2 smart glasses, we evaluated in a first test session the achievable registration accuracy with the two display solutions, and in a second test session the success rate in executing the AR-guided skin paddle incision task on a 3D printed leg phantom.via tablet and via HoloLens 2 headset. The registration accuracy for both solutions was verified on a 3D printed leg phantom obtained from the virtual models, by repeatedly applying the tracking function and computing pose deviations between the AR-projected virtual skin paddle profile and the real one transferred to the phantom via a CAD/CAM cutting guide. The success rate in completing the AR-guided task of skin paddle harvesting was evaluated using CAD/CAM templates positioned on the phantom model surface.From a real computed tomography dataset, 3D virtual models of a human leg, including fibula, arteries and skin with planned paddle profile for harvesting, were obtained. All virtual models were imported into Unity software to develop a marker-less AR application suitable to be used both On average, the marker-less AR protocol showed comparable registration errors (ranging within 1-5 mm) for tablet-based and HoloLens-based solution. Registration accuracy seems to be quite sensitive to ambient light conditions. We found a good success rate in completing the AR-guided task within an error margin of 4 mm . All subjects reported greater usability and ergonomics for HoloLens 2 solution.Results revealed that the proposed marker-less AR based protocol may guarantee a registration error within 1-5 mm for assisting skin paddle harvesting in the clinical setting. Optimal lightening conditions and further improvement of marker-less tracking technologies have the potential to increase the efficiency and precision of this AR-assisted reconstructive surgery. Augmented reality (AR) in medicine is a technology that expands on image-guided surgery, allowing intraoperative guidance and navigation. This technique integrates imaging information with the real-world surgical field to give the surgeon a sort of “x-ray vision”.In recent years, AR technology has been proposed and applied in neurosurgery , 2, urolA variety of technologies including traditional projectors, mobile devices such as tablets and smartphones, and head mounted displays (HMDs) have been proposed and used to perceive the augmented surgical field , 10. SpeIn craniomaxillofacial surgery, the AR technology can be considered an evolution of the navigation-assisted surgery, and it represents a promising tool in aiding complex surgical procedures, such as mandible reconstruction with fibula flap, with potential to avoid or limit the use of cutting guide technology. The osteomyocutaneous microvascular fibular flap harvesting represents the reconstructive gold standard for complex mandibular defects resulting from tumor resections, trauma or malformations . For theOnly few recent experiences reported the use of accurate virtual planning and CAD/CAM technology for skin paddle harvesting and localization of the cutaneous perforator vessels of the fibula vascular anatomy for supplying the free flap , 22. In It would be possible to plan and reproduce the soft tissue resection and reconstruction and not only the bony part of the 3D-aided surgery. In order to achieve this goal, once the planning is carried out either on the resection and on the fibular skin area planned for soft tissue reconstruction, the reconstructed 3D virtual plan may be transferred to AR technology. This will give the surgeon the opportunity to reproduce the planned reconstruction, based on the three-dimensional position and reciprocal position to the bony segments and flap insetting, in restoring the defect.As great advantage, the AR technology, when deployed on a wearable head mounted display, allows the direct view of the planned resection and reconstruction on the surgical field without the need for the surgeon to alternate viewing between the surgical field and external monitors such as in the case of standard navigation systems, with potential clinical benefits of reducing operative time and improving surgical outcomes. We have recently reported preliminary case series where the feasibility of a proof-of-concept AR based protocol implemented on a tablet for assisting procedures of free fibula bone harvest  and of gIn this paper, we describe the AR based protocol we developed for assisting skin paddle harvesting in osteomyocutaneous fibular flap reconstructive procedure, usable both with a handheld device, such as a tablet, and with a HMD, such as Microsoft HoloLens 2 smart glasses. The study was also designed to evaluate the registration errors associated with the two display solutions, and the achievable success rate when simulating the AR-guided task of skin paddle harvesting on a 3D printed human leg phantom.The study was designed in order to first implement the AR based protocol on both the tablet and the HoloLens 2 smart glasses. Then, a first testing session to quantify the achievable registration accuracy with the two display solutions, and a second testing session to evaluate the success rate in executing the AR-guided skin paddle incision task on a 3D printed leg phantom were performed.In the following sections the development and implementation phase, as well as the experimental phase of the study were reported.This phase consists of three steps: A) Image segmentation and virtual content preparation; B) Design and manufacturing of the human leg phantom; C) Development of the AR application Figure 1The process started from acquisition of real computed tomography angiography (CTA) datasets of a patient lower leg, which represents the donor-site for osteomyocutaneous fibular flap harvesting procedure. CTA scans were acquired after administering nonionic contrast media intravenously (Xenetix 350 Guerbet) and with a slice thickness of 0.6 mm .Anatomical areas of interest of the subject’s leg were segmented using D2P™ software : bones (tibia and fibula), arterial vessels  and leg skin .Three-dimensional meshes were then generated from all the segmented masks, and saved in STL format.via a stereolithography (SLA) 3D printer .From the virtual models obtained in the previous step, a tangible phantom made of photosensitive resin was produced To make the virtual leg model compatible with the build volume of Form 3 printer (14.5 × 14.5 × 17.5 cm), CAD processing was carried out using MeshMixer software  in order to create a modular phantom composed of several parts. In detail, for the skin layer and the bones/vessels block, three cross sections were designed, each divided into two symmetrical portions defined by a longitudinal cutting plane, and a set of joints among the various separate parts was created. Each component was printed individually, using a grey resin for the skin (4 mm thick shell) and a clear resin for bone and vessel structures. Then, arteries were colored red to differentiate them from bones, and all pieces were assembled Figure 2The obtained virtual models of the lower leg, i.e. bone anatomy, arteries and the planned skin paddle profile with the corresponding selected perforator vessel, were imported into Unity 3D software  extended with a specific software development kit for creating augmented reality apps .The tracking algorithm and registration between the virtual content and the real scene were implemented using the “Model Target” function of Vuforia Engine, which allows the marker-less tracking of a physical object in the real world by recognition of the shape of the 3D object itself observed from a certain perspective. Model Target function enables to recognize and track objects in the real world based on their shape. To make a Model Target for a particular object the 3D model data for the object, such as a 3D CAD model or a 3D scan of the object, is necessary. A Model Target requires that the user holds the AR display device at a particular angle relative to the object, and at a particular distance to initialize the tracking. To aid with this process, the application typically draws an image (“guide view”) showing an approximation of the object shape from this distance and viewing angle, so that the user just needs to move the AR display until the object matches this guide view. After that, tracking can begin Figure 3In this study, the CAD model of the leg skin was used as Model Target for virtual-to-real scene registration. The created AR application was built both as an Android app for mobile devices then deployed on a Samsung Galaxy TAB S5E Figure 4In both cases, the AR application generates “holographic” overlays, by rendering the bony and vascular anatomy of the simulated patient leg, and also the planned skin paddle profile for harvesting to be used as guiding information during the experimental task performed on leg phantom.Interactable user interface toggles (check boxes) were added to turn off and on the rendering of each virtual anatomical structure   Core i7-10750H, CPU@ 2.60GHz, 16GB RAM, NVIDIA GeForce RTX 2070) was used for the virtual content preparation and for development of the AR application that was then deployed and run directly in the tablet or HoloLens 2 smart glasses.Experimental tests on phantom were carried out in the following two phases.We evaluated the registration error of the two AR display types (tablet-based and HoloLens-based). For each solution, we tested two lighting conditions: 1) environment illuminated by natural daylight (OFF_lamp); 2) artificial lamp light that points directly on the phantom (ON_lamp).In order to evaluate the registration error, the “real” skin paddle profile and the virtual one projected in AR were compared. The “real” skin paddle profile was obtained from the planned skin paddle: from patient CT angiography the 3D model of the chosen perforator vessel was also reconstructed, then the skin paddle outline was drawn in order to centre this perforator, as we have already described in a previous work . Then, wThe real profile was obtained by tracing a line on an adhesive tape applied over the leg phantom while following the groove of the CAD/CAM template . Each subject performed the task using both the tablet-based and the HoloLens-based AR application.The virtual skin paddle profile was designed and displayed as a dashed line to facilitate the optimal visibility of both the virtual and the real trajectory drawn gradually with the pencil during the execution of the AR-guided task, thus avoiding that the line traced by the user become occluded, to some extent, by holograms Figure 7For tests using tablet, the mobile device was anchored to an articulated arm fixed to the table on which the leg phantom was placed. By means of the articulated arm the tablet can be oriented and locked in the most appropriate position to allow the correct visualization of the holographic overlay, and the user to freely carry out the task.For tests using HoloLens 2, a preliminary user experience with the mixed reality headset was provided, also including the calibration procedure which is required to ensure the best hologram viewing experience for each subject.Each subject was instructed that the primary goal of the test was to accurately trace a line following the virtual skin paddle profile displayed in AR  with a groove of different widths  in order to evaluate three levels of achievable accuracy: ± 2.0 mm, ± 1.0 mm, and ± 0.5 mm Figure 8All results about the registration errors (Test Session 1) and the percentage of success rate in performing the AR-guided task (Test Session 2) were reported as mean values and standard deviation (SD).For Test Session 1, T-test for unpaired data was used to compare the mean registration errors, both in X and Y direction, for the tablet-based and HoloLens-based groups, as well as to evaluate for each AR display type the difference of mean values between the “OFF_lamp” and “ON_Lamp” lightening condition.For Test Session 2, the difference of the mean percentage success rate obtained with the two AR display types was evaluated using T-test for paired samples.SPSS software  was used to perform the statistical analysis, and a p value of <0.05 was considered statistically significant.On average, we found a similar registration errors for tablet-based and HoloLens-based solutions, ranging between 1-5 mm Figure 9For tablet-based application, the “ON-Lamp” lightening condition provided a statistically significant reduction of the registration error in the vertical direction if compared with “OFF-lamp” condition , while the registration error in horizontal direction did not significantly change. The “ON-Lamp” lightening condition seems to reduce also the registration error for Hololens-based application, particularly in vertical direction, although this reduction did not result statistically significant .Results from Test Session 2 are summarized in For accuracy level ±1 mm and ±0.5 mm, lower success rates resulted for both tablet and HoloLens solutions , Table 1.From Test Session 1 we realized that the implemented marker-less registration is quite sensitive to environment lightening conditions, and that holograms can appear to project accurately over the leg phantom only from a certain perspective , whereas from other perspectives the hologram revealed very inaccurate placement.In performing Test Session 2, we observed some inherent drawbacks of the marker-less registration based on the recognition of the 3D object profile using Vuforia Engine Model Target function. Especially in tablet-based application we observed that the hologram tends to shift away a little bit from the optimal registration position as soon as the subject approaches the hand to the phantom to start drawing the AR-guided trajectory. This behavior may be due to the fact that the subject places his hand between the camera and the tracked real object, thus interfering with the correct recognition of the skin layer profile of the leg phantom used as Model Target.In terms of user experience, all subjects reported greater usability and ergonomics of the HoloLens solution, although the brightness of the virtual content was lower than the one displayed on the tablet.AR is a promising technology for craniofacial surgeons to obtain a “see-through” effect in the operating room. However, some problems with AR, such as depth perception  and regivia a tablet and a HoloLens 2 headset, that we developed for assisting skin paddle harvesting in osteomyocutaneous fibular flap procedure for mandibular reconstruction. The perspective of clinical application of the proposed AR protocol for head and neck reconstruction is the 3D planning of the soft tissue resection and reconstruction, having the opportunity to reduce the donor site morbidity, improving eventually the three-dimensional reconstructive outcome.The present study aims to increase the information regarding the achievable registration accuracy with a marker-less AR application usable From a technical point of view, the primary challenge that needs to be addressed for AR to become a viable tool for surgery is the accuracy of registration between the displayed virtual content and the real scene. The registration error, mainly caused by registration method and camera performance, results in a “misalignment” effect in the subjective perception for virtual and reality image. The registration error is divided into static registration error and dynamic registration error. The static registration error deals with the error caused by the system when the user’s viewpoint is still at rest with the real object, whereas the dynamic registration error refers to the error that occurs when the real object has relative motion in the user’s view or environment . In our Most of the current AR approaches are limited to invasive marker fixation to provide virtual-to-patient registration. In craniomaxillofacial surgery, AR solutions based on a marker-less tracking, like the one we propose, may offer the advantage to overcome the inherent drawbacks of standard navigation systems, such as the use of reference marks to be positioned on the patient, and the need for a quite long registration procedure. Therefore, a marker-less tracking approach offers a less intrusive solution and limits the need for manufacturing dedicated CAD/CAM trackers anchored for example to occlusal splints, which may obstruct the operative field.On the other hand, marker-less solutions, as we observed in our experiments, may suffer from poor robustness, being sensitive to ambient light conditions, to changes in viewpoint, to contrast image and to the integrity of the 3D object profile used as Model Target. Indeed, in our previous experience in real clinical setting  we obserIn the present study we found mean registration errors ranging within 1-5 mm, for both tablet-based and HoloLens-based solution, considering two dimensions, i.e. horizontal (X) and vertical (Y) directions. Our findings were quite in line with other studies on HoloLens accuracy for surgical applications that reported visualization errors up around 2 millimeters –32 and mWe observed largest deviations in the vertical (Y) direction. This may be due to the “Model Target” registration function which is based on recognition of the shape of a 3D object (i.e. the leg) observed from a certain perspective. In horizontal direction (X) there is an excellent fitting between the real and virtual content since the proximal and distal edge of the leg are correctly recognized and matched; however, the virtual-to-real matching with the Model Target function can occur also with a persisting rotational component along the leg long axis; this leads to a more relevant misalignment of the projected skin paddle profile in the vertical direction (Y).2 at least, so a sub-millimetric accuracy in virtual-to-real registration is not required and even an error of 5-10 millimeters can be acceptable, since it does not affect the clinical outcome. Therefore, our findings are satisfying in terms of accuracy since the resulting average registration errors are absolutely compatible with the objectives and clinical applications of the proposed AR protocol.Typically, the skin paddle used for reconstruction is a soft tissue area of average 6x4cmFor marker-less tracking we chose the external profile of the leg skin as Model Target to be used in Vuforia Engine package; this means that all the virtual structures of interest to be projected in AR  are included in the chosen Model Target. This could be a favorable aspect to minimize the registration error, since the farther the augmented virtual object is from the object used for tracking, the greater the registration error.For the AR-guided task we found a good success rate (around 100%) in completing the task within an error margin of 4 mm for both AR display solutions. These results have to take into account that for each test we started from a condition of optimal registration error (around 2 mm), which was visually checked before the subject started tracing the trajectory under the AR guidance, in order to maximize the achievable success rate.Regarding AR display types, HMDs are emerging as efficient and promising media to support complex manual surgical tasks typically performed under direct vision , 34, sinThis does not exclude that they can be useful and usable, as in the case of the present study, to assist surgical procedures where there are no stringent accuracy requirements (i.e. submillimetric accuracy). Indeed, the expectation for AR system accuracy should be commensurated with the surgical tasks for which the tool is intended. In our study, all the performed AR-guided tracings on phantom encompassed appropriate skin regions to include the planned perforator vessel for fibular flap harvesting, also in those cases where low percentage of success rate resulted from accuracy verification through CAD/CAM templates.When surgeons need to accomplish extremely delicate procedures such as precise drilling or cutting in narrow operative areas, AR systems specifically designed for high-precision surgical tasks, i.e. capable of guaranteeing a submillimetric accuracy level, should be preferred , 35, 36.From our experience, comparing the tablet-based and the HoloLens-based solution the following pros and cons emerged. The major advantage of a tablet solution is the good brightness of the virtual rendered anatomy. On the other hand, the advantage of a “surgeon-centered’ point of view is lost, and it is necessary to fix the mobile device in a suitable position that allows the AR view for the surgeon and at the same time the possibility to perform manually the AR-guided surgical task.Regarding HoloLens 2 we received feedbacks from users of a quite comfortable and ergonomics headset, that offers the advantages of optical see-through technology and hands-free operation. However, the provided contrast image is quite low.The preoperative planning time for the proposed AR protocol is about 3 hours: 2 hours for CT image segmentation and virtual content preparation, if good quality imagining is provided, and 1 hour for AR application development and its deployment on HoloLens smart glasses. This time would not represent a limitation for clinical use. Indeed, the proposed AR protocol for skin paddle incision can be used as an alternative to CAD/CAM approach based on skin paddle outline guides that require a comparable or even longer preoperative planning time . Moreover, the AR technology, implemented in a mark-less way, has the great potential of being a “streamlined”, non-obstructive technology, which can be easily transferred and applied in the surgical setting.Our study has some limitations. In Test Session 1 we quantified only the static registration error, while dynamic misalignment that occurs when the leg phantom has relative motion in the user’s view or environment was not evaluated.Moreover, in Test Session 2, each subject performed the task consecutively using the two different AR display types, so in the second execution of the same task he/she could have benefited from a little training effect. We tried to limit this bias, inverting the order of execution of the test with tablet and HoloLens between one subject and another.As future development, we plan to enriched the AR based protocol with additional features that allow the simultaneous tracking of multiple 3D objects, e.g. a target anatomical region and a movable bone segment to be repositioned or displayed relative to the target. This may open the way to exploring new surgical or outpatient applications of augmented reality in the craniomaxillofacial field.Future perspective will address to transfer the proposed AR protocol in the real clinical field to assist the skin paddle harvesting in osteomyocutaneous fibular flap reconstructive surgery. Surely, the head mounted display such as the HoloLens 2 solution is the most promising and viable option for use in the operating room setting. So, our future efforts will be focused on promoting a clinical study on the use of the AR protocol with HoloLens 2 headset.In this study we present the development of a marker-less AR based protocol proposed to assist skin paddle harvesting in osteomyocutaneous fibular flap procedure for mandibular reconstruction. The developed AR guidance system was evaluated on a 3D printed leg phantom, thus allowing a systematic comparison of the achievable static registration accuracy and of the success rate in performing the AR-guided skin paddle harvesting task, when using two different AR display solutions, i.e. a tablet and HoloLens 2 headset. Results revealed that the AR based protocol provides a registration error within the range 1-5 mm for assisting skin paddle harvesting in the clinical setting, in both solutions. Greater usability and ergonomics resulted for HoloLens 2. Optimal lightening conditions and further improvement of marker-less tracking technologies have the potential to increase the efficiency and precision of this AR-assisted reconstructive surgery.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethical Committee of IRCCS Hospital - University of Bologna, Policlinico S. Orsola-Malpighi . The patients/participants provided their written informed consent to participate in this study.LC: study concept and design, manuscript preparation, and dataanalysis. FB: software development, and data collection and analysis. GB, SB, and AT: study design and data interpretation. CM: study supervision. EM: study concept and study supervision. LC, GB, AT, CM, SB, and EM: contributed to the manuscript review. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.