Subtalar instability (STI) is a disabling complication after an acute lateral ankle sprain and remains a challenging problem. The pathophysiology is difficult to understand. Especially the relative contribution of the intrinsic subtalar ligaments in the stability of the subtalar joint is still controversial. Diagnosis is difficult because of the overlapping clinical signs with talocrural instability and the absence of a reliable diagnostic reference test. This often results in misdiagnosis and inappropriate treatment. Recent research offers new insights in the pathophysiology of subtalar instability and the importance of the intrinsic subtalar ligaments. Recent publications clarify the local anatomical and biomechanical characteristics of the subtalar ligaments. The cervical ligament and interosseous talocalcaneal ligament seem to play an important function in the normal kinematics and stability of the subtalar joint. In addition to the calcaneofibular ligament (CFL), these ligaments seem to have an important role in the pathomechanics of subtalar instability (STI). These new insights have an impact on the approach to STI in clinical practice. Diagnosis of STI can be performed be performed by a step-by-step approach to raise the suspicion to STI. This approach consists of clinical signs, abnormalities of the subtalar ligaments on MRI and intraoperative evaluation. Surgical treatment should address all the aspects of the instability and focus on a restoration of the normal anatomical and biomechanical properties. Besides a low threshold to reconstruct the CFL, a reconstruction of the subtalar ligaments should be considered in complex cases of instability. The purpose of this review is to provide a comprehensive update of the current literature focused on the contribution of the different ligaments in the stability of the subtalar joint. This review aims to introduce the more recent findings in the earlier hypotheses on normal kinesiology, pathophysiology and relation with talocrural instability. The consequences of this improved understanding of pathophysiology on patient identification, treatment and future research are described. Lateral ankle sprains are the most prevalent musculoskeletal injuries in the physically active population and form an important health problem given the associated high socio-economic cost . MoreoveIn contrast to talocrural instability, the literature about subtalar instability (STI) is far more limited and until recently its pathophysiology remained less well known. The contribution of the subtalar ligament in the stability of the subtalar joint is a main research question. The limited understanding often results in misdiagnosis and inappropriate treatment . STI canSTI is a challenging problem for different reasons. First, the literature about the anatomy of the subtalar ligaments is equivocal . In liteFinally, the reliability of the different diagnostic tools is unclear . Stress The difficulties in diagnosis and treatment result in persisting complaints of instability despite a surgical treatment . TherefoThe purpose of this review is to provide a comprehensive update of the current literature related to the pathophysiology of STI. The hypothesis of this review is that the intrinsic subtalar ligaments play an important role in the stability of the subtalar joint. Recent literature clarifies the local anatomical and biomechanical characteristics of the subtalar ligaments. This allows to improve the understanding of kinesiology and pathophysiology . This imA review of the literature was performed to identify peer-reviewed articles about 1) the pathophysiology, diagnosis and treatment of STI and 2) anatomical and biomechanical properties of the intrinsic subtalar ligaments. A comprehensive search in the following databases was performed: PubMed, Web of Science and, Embase. This review aimed to introduce the more recent findings in the earlier hypotheses on normal kinesiology, pathophysiology and relation with talocrural instability. The consequences of this improved understanding of the pathophysiology on patient identification, treatment and future research are described.The basic mechanical stability of the subtalar joint is determined by a complex interaction between articulating bones and different ligaments.The subtalar joint consists of two articulating components: the posterior and the anterior component. The posterior subtalar joint has an ovoid shape and is formed by the relatively concave posterior facet of the talus and the convex posterior facet of the calcaneus . The antA complex of ligamentous structures connects the talus to the calcaneus. We distinguish the extrinsic and intrinsic subtalar ligaments which contribute to joint stability.The most important extrinsic ligaments are the CFL, which limits inversion, and deltoid ligament, which limits eversion. Some studies indicate that the anterior talofibular ligament (ATFL) has an indirect function in the stability of the subtalar joint .The talus and calcaneus are directly connected by the intrinsic subtalar ligaments. A recent publication clarified the confusing terminology that has been used in the past . Jotoku We distiThe ATFL commonly consists of two bands: the superior and inferior fascicle, which are characterized by distinct anatomical and biomechanical properties . Both faThe CFL is bridging both the talocrural and subtalar joint. In a recent study, Pereira et al. described four distinct morphological-oriented shapes of the CFL: 1) a single bundle (44.7%), 2) Y-shape double bundle, 3) V-shape double bundle, and 4) a separated bundle . Type 4 Studies assessing the material properties of both the CFL and ATFL demonstrated a higher failure load of the CFL compared to that of the ATFL, supporting its important role in stabilizing the subtalar joint . The CFLThe cervical ligament is located in the sinus tarsi and has similar dimensions as the ATFL and CFL . In neutThe CL has a low failure load and a low stiffness, similar to the ATFL . The CL The ITCL is a vertical ligament located in the tarsal canal. Both attachment sites or footprints of the ligament have a linear shape that run parallel with the tarsal canal . The ITCThe ACaL is a vertical rectangle band and corresponds to a thickened part of the anterior joint capsule of the posterior facet . The ACaThe kinematics of the subtalar joint correspond to the major functions of foot: support and propulsion. The foot acts as a flexible structure to adapt to uneven surfaces but also as rigid structure to allow force transmission. The subtalar joint plays a key role in both functions and the transition between both functions. The unique triplanar motion of the subtalar joint is a direct result of the interaction between the bony shape of the articular surfaces of the PTC and TCN joints and the ligaments . As the In a simplified concept, motion at the subtalar joint can be seen as uniaxial motion resulting in eversion and inversion. The motion is triplanar: eversion is intrinsically linked to dorsiflexion and abduction, whereas inversion is linked to plantar flexion and adduction of the foot. From eversion to inversion the calcaneus rotates with respect to the talus from dorsolateral to medioplantar. In eversion, maximum contact caused by joint surface congruency at the posterior subtalar joint generates a high degree of inherent stability . In invein vivo kinematics demonstrated that the footprints of the ITCL are very close to the axis of rotation (The uniaxial motion can be described by a single oblique axis of motion that runs obliquely from posteroplantolateral to anterodorsomedial . It penerotation . The shorotation .Although this basic uniaxial motion concept is well accepted and useful in clinical practice, it should be seen as a simplification. A more complex concept depicts a combination of sliding, rolling and spinning at the joints with the ITCL and CL as most important guiding ligaments . Both liRecent findings about the CL clarify its function in this multiaxial motion concept. As the CL is located distantly from the centre of movement, it allows a swinging motion of the calcaneus around the talar neck . The CL As the ACaL appears to have different anatomical characteristics, it should no longer be confused with the ITCL. The ACaL plays a rather supporting role in this multiaxial motion. The laterally located ACaL fibres are longer and have more excursion than the medially located ITCL fibres . This exSeveral hypotheses about the injury mechanisms related to STI have been described but are not yet confirmed . An inveMeyer et al. proposed two different mechanisms that involve the subtalar ligaments . The firThe pathological process starts with a first ankle injury resulting in one or more damaged ligaments. As there is a narrow interdependence between the talocrural and subtalar joints, lesions may occur at both levels and will have an impact on each other. After the injury, healing processes and coping mechanisms will affect the further outcome . HoweverAn ATFL lesion is the most commonly injured ligament during an ankle sprain. An isolated ATFL lesions occurs in 35%–65% of the lateral ankle sprains . KemmochA complete lesion of the ATFL is not uncommon. This involves the interruption of both fascicles of the ATFL. A rupture of the ATFL allows the talus to move forward to the fibula resulting in an instability of the talocrural joint. In clinical examination this corresponds to a positive anterior drawer test.Although the ATFL does not bridge the subtalar joint, several biomechanical studies also demonstrate a relation between an isolated sectioning of the ATFL and abnormally increased mobility of the subtalar joint . Cass etThese findings can be explained by a complex interaction of the ATFL and CFL. Indirectly, the intact ATFL holds the CFL under tension. An intact ATFL limits the anterior translation of the talus to the fibula and thereby retains the fibula its normal position. In a more direct way, the arciform fibers may transmit tension from the intact ATFL to the CFL . This trIt remains unknown what the long term impact is of such isolated ligament lesion on the other ligaments. The altered kinematics may cause further ligament damage and result in a multiligament involvement.An isolated injury of the CFL seems to be very rare in clinical practice . The limDespite the low occurrence of isolated CFL lesions, many biomechanical studies demonstrated that an isolated sectioning the CFL has an important impact on the stability of the subtalar joint . These sA combined ATFL and CFL injury is the second most commonly reported injury pattern to the lateral ankle ligament complex. A recent MRI study with 180 patients reports ATFL lesions in 96.3% of all 108 included patients with CFL lesions . The occLesions of the intrinsic subtalar ligaments are difficult to identify and are probably underreported. These lesions are most commonly associated with lesions of ATFL and CFL . They arAlso in a chronic situation, lesions of the intrinsic subtalar ligaments are not uncommon. Tourné et al. found lesions of the CL and/or ITCL in 30% of patients in 150 patients selected for a surgical stabilisation procedure . Lee et Currently, the relevance of partial lesions is still unknown. Karlsson et al. described their results in 176 patients with chronic symptoms of instability . In all The occurrence of partial lesions is also a diagnostic challenge as they may be difficult to recognize with imaging techniques such as ultrasound and MRI. Also during intraoperative assessment, the visual presence of the ligament may misguide the interpretation of the remaining stabilising capacities. Therefore, partial lesions are more likely to pass unnoticed. The impact of these lesions on joint stability needs further investigation.Diagnosis of STI is still challenging but several clinical and radiographic signs seem to be correlated with a subtalar origin of the complaints. The earlier discussed new insights allow to improve interpretation of injury patterns during imaging and also during surgery. Recently published research used these different aspects to present an algorithm to diagnose and treat STI in clinical practice . Michel A step-bThe first step, during history taking, is considering this diagnosis in case of persistent symptoms of instability. Recent research demonstrated a correlation between persistent symptoms and abnormalities at the subtalar joint . SubjectThe following step corresponds to physical examination. Painful areas may indicate the most plausible origin of the complaints. Tenderness in the sinus tarsi is a typical symptom that may indicate involvement of the intrinsic subtalar ligaments. Lateral ankle swelling and stiffness may be present. An increase in inversion on of the subtalar joint and an increase in forward translation of the calcaneus beneath the talus may be found . There aIn a next step, imaging techniques can be used to challenge this tentative diagnosis. A recent systematic review assessed the different diagnostic tools and found insufficient evidence to use Brodén stress radiographs . AnterioIn a next step, intraoperative evaluation may be helpful to identify subtalar pathology. If surgery seems necessary, one can use this opportunity to add a intraoperative assessment to the earlier findings. The direct view during surgery allows a direct visual assessment of the ligaments and may detect an abnormal opening of the joints during certain movements. Some earlier studies suggested an endoscopic approach to assess the characteristics of the ACaL . AbnormaIn literature there is already agreement for non-surgical treatment, which is similar to patients with talocrural instability . If the In earlier literature, the non-anatomical tenodesis techniques were popular. By attaching the proximal part of the peroneus brevis tendon to one or more bones around the ankle joint, the mobility of the different joints becomes limited. As these tenodesis techniques bridge both the talocrural and subtalar joint, they limit the mobility of both the talocrural and subtalar joint. Moreover, they also span and limit the midfoot joints. By limiting the range of motion they are successful in treating related symptoms of instability including subtalar and midfoot instability. However, the non-anatomical approach results in disturbed joint biomechanics, restricted range of motion, inferior functional results and increased risk of degenerative changes of time . TherefoAfter the popularity of tenodesis, ligament repair techniques became more popular, with the Broström procedure as most known example . A ligamThese repair techniques are straightforward and easy, offering good-to-excellent postoperative results on the short and medium term. The techniques also present some drawbacks though. First, there are some concerns on return of instability in the longer term . Second,More recently, the anatomical ligament reconstruction techniques were described . These tBecause the CFL is recognized as an important stabilizer of both the talocrural and subtalar joint , many auIn more complex cases of STI, reconstruction of both the ATFL and CFL may not be sufficient to restore the subtalar stability. Therefore, several authors have proposed a reconstruction of the subtalar ligaments . Some puOther publications described the reconstruction of the cervical ligament . Based oThe most recent literature supports the multi-ligament hypothesis to explain the pathophysiology of STI. Further research should focus on the exact injury mechanisms and the exact injury patterns. Such studies should investigate which ligaments are most commonly injured. This should also include the presence of partial lesions as this incidence remains unknown.in vivo condition of an ankle sprain and to assess the different ligaments before and after injury. The injury patterns induced in the lab can be correlated with imaging aspects. The knowledge about the most common injury patterns would help optimize selective sectioning studies that assess the characteristics of chronic instability.In basic research, it would be valuable to develop lab conditions to mimic the In clinical research, improved imaging techniques may offer a more extensive assessment of acute injuries in clinical practice. Larger observational studies are needed to identify the most common injury patterns and to look for a correlation the primary lesion and long-term symptoms. Studies with repeated MRI may be interesting to look for correlations between chronic and acute conditions. Intraoperative assessment should be compared with imaging and patient related outcome measures.Subtalar instability is a challenging complication after an acute lateral ankle sprain. More recent literature focused on this topic resulted in an improved understanding of the pathophysiology of subtalar instability.Besides the CFL, the intrinsic subtalar ligaments seem to play an important function in the subtalar joint. The CL has a low failure load, similar to the ATFL . This loInjuries of the subtalar ligaments are probably underreported because of their small size and the occurrence of partial ruptures. The different injury patterns are an opportunity for further research.Diagnosis should be based on a step-by-step approach to raise the suspicion to STI. This approach consists of clinical signs, abnormalities on MRI and intraoperative evaluation. Surgical treatment should address all the anatomical aspects of the instability and focus on a restoration of the normal anatomical situation and its biomechanical properties. A low threshold to reconstruct the CFL is recommended. In complex cases, a reconstruction of the cervical ligament should be considered.


Enhanced recovery after surgery (ERAS) interventions aim to improve patient outcomes. Vascular surgery patients have unique requirements and it is unclear which ERAS interventions are supported by an evidence base.We conducted a scoping review to identify ERAS randomized controlled trials (RCTs) published in the biomedical or nursing literature. We assessed interventions for applicability to vascular surgery and differentiated interventions given at preadmission, preoperative, intraoperative, and postoperative surgery stages. We documented the research in an evidence map.We identified 76 relevant RCTs. Interventions were mostly administered in preoperative  or intraoperative surgery stages . The majority of studies reported mortality outcomes , but hospital  and intensive care unit  length of stay outcomes were less consistently described.The ERAS evidence base is growing but contains gaps. Research on preadmission interventions and more consistent reporting of key outcomes is needed.The online version contains supplementary material available at 10.1186/s13643-023-02324-z. Enhanced recovery after surgery (ERAS) consists of interventions designed to support patients recovering from surgery throughout the continuum of care . ImproveTo better understand this literature, we conducted a scoping review and created an evidence map of randomized controlled trials (RCTs) for ERAS interventions, mapped by surgical stage, that evaluate key patient-centered outcomes . The evidence map  approachAs part of a larger project on ERAS, we searched PubMed and the Cumulative Index to Nursing and Allied Health Literature for published literature, and searched ClinicalTrials.gov for clinical trial records from inception to March 2023 (search strategies shown in Supplementary Material The search identified 4,483 citations, and we included 79 RCTs of ERAS interventions for vascular surgery (evidence table: Table Figure We identified a substantial body of evidence of ERAS interventions for vascular surgery. Our analysis utilized an evidence map to categorize the available research on RCTs reporting mortality and length of stay outcomes for these interventions by surgical stage, a strategy not previously employed by other reviews. The map shows that existing research has primarily addressed pre- or intraoperative, rather than preadmission, surgical stages. In addition, while more than half of studies reported on mortality, information on hospital or ICU length of stay remains sparse.A recent review  of 19 RCAdditional primary research on ERAS interventions is also needed. The existing evidence base lacks studies of preadmission ERAS interventions, and mortality and length of stay outcomes were not consistently reported. Future primary research should aim to study preadmission interventions and consistently measure and report mortality and length of stay outcomes.ERAS research is rapidly growing and an evidence base for vascular surgery is also emerging. Our evidence map clearly outlines research gaps, including a lack of research on ERAS interventions at all surgery stages and the sparseness of information on key outcomes. ERAS interventions hold promise to improve patient recovery after vascular surgery and further applications should be explored.Additional file 1: Supplementary Material 1. Search strategies. Supplementary Material 2. Eligibility criteria and data abstraction methods.


In IoT environments, voluminous amounts of data are produced every single second. Due to multiple factors, these data are prone to various imperfections, they could be uncertain, conflicting, or even incorrect leading to wrong decisions. Multisensor data fusion has proved to be powerful for managing data coming from heterogeneous sources and moving towards effective decision-making. Dempster–Shafer (D–S) theory is a robust and flexible mathematical tool for modeling and merging uncertain, imprecise, and incomplete data, and is widely used in multisensor data fusion applications such as decision-making, fault diagnosis, pattern recognition, etc. However, the combination of contradictory data has always been challenging in D–S theory, unreasonable results may arise when dealing with highly conflicting sources. In this paper, an improved evidence combination approach is proposed to represent and manage both conflict and uncertainty in IoT environments in order to improve decision-making accuracy. It mainly relies on an improved evidence distance based on Hellinger distance and Deng entropy. To demonstrate the effectiveness of the proposed method, a benchmark example for target recognition and two real application cases in fault diagnosis and IoT decision-making have been provided. Fusion results were compared with several similar methods, and simulation analyses have shown the superiority of the proposed method in terms of conflict management, convergence speed, fusion results reliability, and decision accuracy. In fact, our approach achieved remarkable accuracy rates of 99.32% in target recognition example, 96.14% in fault diagnosis problem, and 99.54% in IoT decision-making application. The IoT environment consists of tiny sensor-enabled connected devices or things able of sensing, communicating, computing, and reasoning. Data generated in IoT environments are voluminous, with diverse representations, different qualities, and different reliability levels. Additionally, due to multiple factors such as environmental noise, sensor defects, or calibration errors, these data are prone to various imperfections. Then, they could be noisy, uncertain, conflicting, or even erroneous, which may lead to wrong decisions if those features are not taken into account properly.Multisensor data fusion has been proven to be a very powerful technique to manage data coming from heterogeneous sources and to move towards effective decision-making. It aims to combine data gathered from various sensors in the best possible manner to get more precise, accurate, and consistent information. Multisensor data fusion technique can be performed at various levels, depending on the representation of data to be merged and according to the stage at which the combining operation takes place. One can distinguish low, intermediate, and high-level fusion . SeveralD–S theory has been extensively applied in various multisensor data fusion applications such as decision-making ,6,7, fauFor the first category, scholars believe that the unreasonable results come from the direct normalization of the conflicting evidence, so they have proposed new combination rules ,18,19,20In this paper, an improved evidence combination method for multisensor data fusion in IoT environments is proposed to overcome the Dempster–Shafer theory flaw and fuse highly conflicting evidence without generating counter-intuitive results. It is based on a newly defined evidence distance and belief entropy. The method aims to evaluate the importance of each source in the fusion process by assigning evidence weights. The main idea is to weight the reliable sources most heavily and assign lower weights to the less reliable ones. This strategy intends to reduce the conflicting impact of less reliable sources on the final combination result, thereby enhancing decision-making accuracy.-We first propose an improved evidence distance based on Hellinger distance, which can effectively quantify the conflict degree between the pieces of evidence.-The improved evidence distance considers the dependencies between the bodies of evidence through a Jaccard matrix, it satisfies true metric properties , and it allows a better conflict measurement.-We develop a novel multisensor data fusion strategy based on the improved evidence distance and Deng entropy for conflict and uncertainty measurements, respectively. Reward and penalty functions are designed to assign the weights accordingly. We reward the reliable pieces of evidence by weighting them more heavily, making their role more important in the final fusion result and, conversely, for the less reliable ones.-Finally, we apply the proposed approach to a benchmark example for target recognition, a fault diagnosis problem, and an IoT decision-making application to demonstrate its effectiveness compared to other similar existing methods. The results have shown the superiority and efficiency of the proposed method in terms of conflict management, convergence speed, fusion results reliability, and decision accuracy.The main contributions of this study are summarized as follows:The remainder of this work is organized as follows: In this section, some relevant preliminaries are introduced. First, we provide in Dempster–Shafer theory (D–S), also known as evidence theory or the theory of belief functions, is an effective mathematical method for reasoning under uncertainty; it was first initiated by A.P. Dempster in 1967  as a genDefinition 1.Frame of discernment:Denoted by Ω, it is a finite, nonempty set of mutually exclusive and exhaustive hypotheses, . It is expressed as follows:The power set of Ω, denoted by , is a set of all the possible combinations of all the elements in Ω. For all A ⊆ Ω, it is defined as follows:Definition 2.Basic Probability Assignment, BPA (or Mass function)BPA represents how strongly the evidence supports a hypothesis by assigning a probability to the different subsets. In a discernment frame, the mass function of a subset symbolized by m is defined as follows:satisfying the following conditions:A ⊆ Ω, if m(A) > 0, A is called a focal element of evidence.Definition 3.Uncertainty representationBased on the definition of BPAs, belief function (Bel) and plausibility function (Pl), which represent, respectively, the lower and upper bounds of the uncertainty interval, are defined as follows:where the belief function represents the total belief in hypothesis A to be true, while the plausibility function refers to the possible belief in the Hypothesis A.Definition 4.Evidence combination ruleIn evidence theory, the two BPAs and under the same frame of discernment, separately obtained from two independent sources, can be combined using Dempster’s combination rule, which provides a method to compute the orthogonal sum denoted by as follows:where K is the conflict coefficient used to measure the conflict degree between two bodies of evidence. The case K = 0 means that the sources are consistent and in perfect agreement, while K = 1 implies that the sources are in total conflict.Dempster’s combination rule satisfies both commutativity and associativity properties as follows:thus, it can be extended to the combination of N bodies of evidence.It should be noted that Dempster’s combination rule is efficient only when the pieces of evidence are not in conflict, unreasonable results will be generated when the sources are contradictory, as highlighted in Zadeh’s counter-example [-example .M), brain tumor (BT), or concussion (C). The frame of discernment is then defined as follows: Ω = {M, BT, C}. The two doctors express their opinions, and the results are interpreted as mass functions as follows:Suppose a diagnosis of a patient from two doctors with three possible diseases, i.e., meningitis dHm1Hellinger distance satisfies the following properties:Non-negativity: Symmetry: Triangle inequality: Positive definiteness: Hellinger distance is an effective tool to quantify conflict degrees between pieces of evidence, The smaller the distance is, the more similar and less conflicting the bodies of evidence.The concept of entropy was first introduced in physics to characterize the disorder and chaos degree of a molecular state in thermodynamics . In infoDeng entropy definitely degenerates to Shannon entropy when the mass function is only allocated to singletons (single elements), as follows:As mentioned in the Introduction, one of the major problems with Dempster’s combination rule is the fact that it leads to counter-intuitive results when fusing highly conflicting evidence. To solve such a problem, two major methodologies are popular. One is to modify the combined rule, and the other is to preprocess the bodies of evidence.For the first methodology, scholars believe that the unreasonable results come from the direct normalization of the conflicting evidence, so they have proposed new combination rules. According to Yager , conflicThe second category believes that the problem of counter-intuitive results in conflict situations is caused by unreliable evidence rather than Dempster’s combination rule itself. A methodology aiming at pre-processing mass functions without changing the combination rule is then proposed. The main idea is to revise and reconstruct the evidence model in order to reduce the conflicting evidence impact on the final fusion result. To this end, diverse methods such as weighted averaging of mass functions are used. Weights are assigned to the original BPAs to determine their roles in the fusion process. On this basis, several weighted combination approaches have been proposed in the literature with various weight measurements ,89,90,91In this paper, we newly define an enhanced evidence distance based on Hellinger distance for D–S evidence theory by building on the concept of the belief functions transformation presented in . The proIt is worth noting that when all the elements are singletons, the mass function conforms to the classical probability distribution. In this case, the Jaccard matrix degenerates to the identity matrix, and, consequently, the improved evidence distance simplifies to the traditional Hellinger distance.We define the improved evidence distance as follows:The improved Hellinger distance satisfies the properties of non-negativity, symmetry, triangle inequality, and positive definiteness.Proof. In the following, the properties of non-negativity, symmetry, triangle inequality, and positive definiteness of the improved distance are verified.The improved evidence distance Formula (13) can be written as follows:Proof. Non-negativity m on Ω satisfies Since The non-negativity property of the proposed evidence distance is proven. □Proof. Symmetry It’s obvious thatProof. Triangle inequality: We use Minkowski inequality :∑i=1nai+We receive the following:Proof. Positive definiteness Finally, the positive definiteness property of the proposed evidence distance is proven. □It can be seen from the above proofs that the improved evidence distance satisfies all the requirements, so it can be applied as a true metric under the Dempster–Shafer framework.To address the issue of the classical Dempster’s combination rule, we propose a new evidence combination method based on the revision of the evidence source model.The proposed method utilizes (i) the newly defined improved evidence distance based on Hellinger distance to measure the conflict degree between the bodies of evidence and (ii) Deng entropy to quantify the uncertainty degree of each piece of evidence. These measurements are used to generate weighting factors that are applied to adjust the original pieces of evidence prior to the application of Dempster’s combination rule to get the final fusion results.We evaluate the trustworthiness of the evidence based on a reliability condition set as the average credibility and design reward and penalty functions accordingly. We reward the reliable pieces of evidence by weighting them more heavily making their role more important in the final fusion result. On the other hand, we penalize unreliable pieces of evidence by using Deng entropy to diminish their impact on the final fusion result. The steps for our improved combination method are described as follows:Step 1: According to Equation (13), the improved evidence distance between the two bodies of evidence D is expressed below:The N × N distance matrix Step 2: Similarity degree between every two pieces of evidence is obtained using the formula proposed in  as folloThe N × N similarity matrix can now be written as follows:Step 3: The support degree of each evidence can be evaluated using the previously calculated similarity degrees as follows: Step 4: The degree of credibility reflects the level of trustworthiness associated with the evidence. The greater the credibility is, the more reliable the evidence; it is given by the following:Step 5: According to Equation (11), Deng entropy for each evidence is calculated to quantify the uncertainty degree.Step 6: In this step, we establish a condition for determining reliability by setting a threshold that classifies pieces of evidence as either reliable or unreliable. The threshold rate is defined as follows:When the credibility of a piece of evidence exceeds the threshold Step 7: Subsequently, we establish the initial weights by evaluating the fulfillment of the reliability condition. The objective is to increase the weights that surpass the threshold while decreasing the weights that fall below it, as outlined below:, a reward function is defined as follows:If , a penalty function is defined as follows:If Step 8: The final weights can be determined based on both credibility degree and the initial weight, resulting in the following definition:Thus, the weighted BPAs can be obtained by the following:Step 9: Finally, for N body of evidence The flowchart of the proposed approach is given in In this section, we present a benchmark example for target recognition and two application cases for fault diagnosis and IoT decision-making to demonstrate the feasibility and effectiveness of our proposed method. Additionally, we have selected several similar methods from the existing literature to conduct a comparative analysis with the newly proposed approach.Similar to our prior research , we appl1), sound sensor (S2), infrared sensor (S3), radar (S4), and ESM sensor (S5), three objects, A, B, and C, are detected. Let us suppose that the frame of discernment Ω = {A, B, C} is complete and A is the current target.In a multisensor-based automatic target recognition system, based on five different kinds of sensors, CCD sensor , all the methods achieve reasonable results and correctly identify the target A. Regarding the other fusion methods, including our proposed method, they also initially identify the wrong target B when only considering the two sensors SIn summary, the proposed method exhibits superior performance compared to other methods, with the belief degrees of the right target A approaching 1 as the number of combined sensors increases. When five pieces of evidence are combined, it achieves the highest accuracy of 99.32% for identifying the right target, surpassing all other methods. It is worth noting that even a slight increase in accuracy is meaningful and represents a significant improvement in performance.These results prove the effectiveness and superiority of our proposed method, it can handle the conflict between the pieces of evidence effectively, with the best convergence speed and decision accuracy. It is designed to evaluate the credibility of each piece of evidence, determine the importance of each sensor in the final fusion result, and assign the weights accordingly, which allows to overcome the influence of conflicting pieces of evidence, and therefore achieve better decision accuracy and fusion results reliability.To validate and demonstrate the effectiveness of the proposed method, a fault diagnosis application previously presented by Lin et al.  is used.The fusion results of the proposed method are compared to those of the Dempster–Shafer method, our previous work , and oth1 = “Imbalance”, F2 = “Shaft crack”, F3 = “Misalignment”, and F4 = “Bearing loose”. Therefore, the frame of discernment is Ω = {F1, F2, F3, F4}. To monitor the system status and determine the fault type, five different sensors were used.In rotating machinery, the faults can be categorized into four types: FFault features were extracted from the data provided by the various sensors to calculate the BPAs of the five sensors. 1, S2, and S4 indicate that the fault type is F3, whereas S3 and S5 indicate conflicting fault types, namely, F2 and F4, respectively.Data provided by SFusion results obtained by varying the number of pieces of evidence for the different methods are shown in -3 after each combination of five pieces of evidence.-3 for the various compared methods using different numbers of sensors. Our proposed method exhibits superior performance compared to all other methods, as demonstrated in the figure.-3 for D–S, Lin [3. However, the inclusion of S4 in the fusion process causes the belief degree of F3 to increase again, reaching 0.7755 for D–S, 0.7906 for Lin, 0.8026 for Wang, and 0.8029 for IDCR, only to decrease once more when S5 is incorporated in the fusion process for all methods.Combining three sensors results in a slight decrease in the belief degree of FD–S, Lin , Wang [5D–S, Lin , and IDCD–S, Lin  methods,-3 continues to increase despite the inclusion of the conflicting sources S3 and S5.However, both the method proposed in our previous work  and the -3 with a value of 0.9614, which is greater than the maximum value achieved by any other method, including our previous work, which did not exceed 0.90.Upon combining five sensors, our proposed method achieves the highest belief degree for FAn IoT decision-making application from the work of Boulkaboul et al.  is consiIn the considered scenario, IoT-enabled wireless sensors are used to monitor office occupancy and ambient light to control electrical lighting and optimize energy, and data fusion method is applied to make a decision about the light switch ON/OFF.1, S2, S3, and a light sensor S4 have been placed in optimal positions on the ceiling of the office and four hypotheses  are defined as follows: H1: the office is occupied, and the lighting value exceeds 580 lx; H2: the office is empty, and the lighting value exceeds 580 lx; H3: the office is occupied, and the lighting value does not exceed 580 lx; and H4: the office is empty, and the lighting value does not exceed 580 lx. A basic scenario is considered when hypothesis H1 is verified, and the system has generated evidence when hypothesis H1 occurs.Three (03) PIR (Passive Infrared) sensors S1, H2, H3, H4}.In , the impWe use the proposed method to combine the pieces of evidence and we compare the results obtained with Dempster–Shafer method (D–S) and six of similar existing methods including the following: Wang , Xiao 9, Jiang e-1 due to the absence of substantial conflicts among the pieces of evidence.As evident from -1. However, upon employing various combination methods, including the proposed approach, it is evident that the results converge to yield high belief degrees.Prior to the combination of the pieces of evidence, none of the sensors in -1 than the other methods. This is evidenced by the maximum belief degree of 0.9958, as illustrated in Figure 7It is worth noting that our proposed combination method delivers significantly better results, providing stronger support for the right hypothesis H-The primary reason for this enhancement is that our proposed method accounts for the relevance and disparities among the pieces of evidence, which is enabled by the improved evidence distance. By identifying even minor conflicts among the pieces of evidence and assigning appropriate weights accordingly, the influence of untrustworthy pieces of evidence is reduced, and that of reliable evidence is increased. This leads to a significant improvement in convergence and decision accuracy.In this paper, an improved evidence combination method for multisensor data fusion in IoT environments has been proposed that aims to address the conflict issues encountered in the Dempster–Shafer theory. The approach relies on the revision of the evidence source model; it is devised to greatly reduce the conflicting impact of unreliable pieces of evidence while strengthening the influence of reliable ones on the final fusion results. To this end, an improved evidence distance based on the Hellinger distance was introduced to measure the degree of conflict among the pieces of evidence, while Deng entropy was employed to quantify the degree of uncertainty of each piece of evidence. The original mass functions are then adjusted using comprehensive weights derived from these metrics, and the classical Dempster’s combination rule is then applied to obtain the final fusion results.To demonstrate the effectiveness of the proposed method, a benchmark example for target recognition and two real application cases in Fault diagnosis and IoT decision-making have been provided. Several comparable methods have been selected from the literature to conduct a comparative analysis with the newly proposed approach, and simulation analyses have shown the efficiency and superiority of the proposed method in terms of conflict management, convergence speed, fusion results reliability, and decision accuracy. In fact, the proposed approach effectively achieved the highest accuracy rate of 99.32% in correctly identifying the target compared to other considered methods in the benchmark example. It also demonstrated a better performance in converging to the right fault type, with a remarkable accuracy rate of 96.14% in the fault diagnosis problem. Furthermore, in the IoT decision-making application, it correctly recognized the right hypothesis and outperformed other related methods, achieving the highest accuracy rate of 99.58%For future research directions, we intend to apply the proposed method on larger data to demonstrate its broader applicability; we also plan to further improve the proposed method by considering more relevant factors in weighting factors’ construction such as data timeliness. The proposed method is only applicable in the closed-world situation, so adjusting the approach in order to obtain reasonable and accurate results in an open-world assumption is also a promising axis.


The control group received intraperitoneal administration of normal saline. The second group was injected with metaproterenol (MET) 3 days a week for 4 weeks. The third, fourth, and fifth groups were given cranberry extract in doses of 75, 100, and 150, respectively, along with heart‐damaging drugs. Blood samples were collected and sent to the laboratory on the fourth weekend and 1 week after completing the injections in the fourth week (the sixth weekend) for analyzing serum factors such as cardiac creatine kinase MB, cardiac troponin I (cTnI), and aspartate aminotransferase (AST). The serum activity of the cardiac evaluation parameters in the fourth week demonstrated a highly significant correlation among the groups with respect to AST and cTnI (p < .001). Additionally, a significant relationship was observed between AST and cTnI within the target groups (p < .05). Ultimately, the findings indicated that the consumption of cranberry extract, due to its impact on heart function, could effectively modify serum indicators associated with heart damage. The utilized extract also exhibited efficacy, albeit with variable effects. Therefore, it is recommended to use cranberry extract synergistically with other chemical and herbal medications to achieve more sustained effects.Cranberry offers numerous cardiovascular benefits. According to several studies, this fruit promotes the oxidation of low‐density lipoprotein, enhances high‐density lipoprotein, reduces platelet coagulation, and improves vascular activity. Albino male rats were divided into five groups ( Administration of cranberry extract effectively modifies serum indices associated with heart damage in rats. Cranberry extract effectively improves heart damage by reducing the release of these serum factors. According to the Global Burden of Disease, cardiovascular patients have almost doubled from 1990 to 2019, and their mortality rate has increased from 12 million in 1990 to 18 million in 2019 , and AST in rats with experimental heart damage with MET.22.1Cranberry (Vaccinium macrocarpon) extract: This formulation was created by utilizing dried cranberry fruits and an alcoholic solvent. Metaproterenol sulfate  is purchased from the drugstore.2.2Albino male rats weighing 120–150 g and 6 weeks old were obtained from the Faculty of Veterinary Medicine of the Islamic Azad University of Tabriz. The tested animals were kept at a standard temperature under humidity conditions in the research center of the Islamic Azad University of Tabriz. A suitable diet was provided to the mice.2.3n = 5 per group). In the control group, normal saline was administered intraperitoneally. The second group was injected with metaproterenol (MET) 3 days a week for 4 weeks. The third, fourth, and fifth groups received 75, 100, and 150 doses of cranberry extract and heart‐damaging drugs. Then the blood samples were taken and sent to the laboratory on the fourth weekend and a week after finishing the injections in the fourth week (the sixth weekend) to check the serum factors, including cardiac CK‐MB, cardiac troponin I (cTnI), and aspartate aminotransferase (AST) , the process was repeated for the other half of the rats. Cranberry extract was not used from week 4 to week 6 to evaluate the stability of the cranberry's effect in rats.2.5Following the serum separation, the levels of cTnI, CK‐MB, and AST were evaluated using special commercial kits  and an autoanalyzer device .2.6The quantitative measurement of troponin is underpinned by the immune‐quantitative luminescence sandwich method. A monoclonal antibody covers the solid phase (magnetic particles), and a polyclonal antibody is used for the tracer. During the incubation of the troponin in the calibrator, the sample or control is attached to the solid phase of the monoclonal antibody. Subsequently, the conjugated antibody reacts with the troponin attached to the solid phase. This test must be performed in the LIAISON® analyzer. The analysis operation includes the following steps: 100 μL of a serum sample, calibrator or control, 200 μL of tracer conjugate, 20 μL of coated magnetic particles, 10‐min incubation and subsequent washing cycle, measurement within 3 s.2.7CK‐MB is a dimer enzyme consisting of two subunits, M (muscle) and B (brain), which combine to form the CK‐MM, CK‐MB, and CK‐BB isozymes. In this method, by using a specific antibody, the activity of the M subunit is inhibited, and CK‐MB corresponding to the activity of the remaining B subunit is measured by the CK‐NAC method. Since CK‐MB consists of two identical subunits, its activity is obtained by multiplying the obtained value by 2. The CK‐MB measurement is basically similar to the cTnI measurement test.2.8This reaction is underpinned by the optimized method proposed by ECCLS, which is the same as the IFCC method with no pyridoxal being used.2.9p < .05 was set as the significance level.The collected data were analyzed with SPSS software version 24. The ANOVA test was used to compare the mean scores of the groups. In this study, 3Tables According to the findings, there was no significant relationship between the time of consumption of the cranberry alcoholic extract (4 or 6 weeks) and the serum variations of the measured parameters Table .4The present study evaluated the beneficial effect of cranberry extract on the cardiotoxicity caused by metaproterenol in laboratory mice.Similar to some of their reported antitumor activities, the antioxidant properties of phenolics in cranberry fruit play a major role in the observed ability to reduce cardiovascular and age‐related diseases. Cranberry's role in preventing oxidative processes included a decrease in the oxidation of lipoproteins. Cranberry ranks high among fruits in antioxidant quality and quantity for their inherent flavonoid content, including proanthocyanidins, anthocyanins, flavonols, and phenolic acids . Kalın et al.'s study helps to understand the antioxidant properties of blueberry extract and the presence of specific polyphenolic compounds. Our study provides insights into the effect of cranberry extract on cardiac function and its potential as a modifier of serum indices associated with cardiac injury. While both studies support the idea that cranberry extract offers health benefits, particularly in relation to cardiovascular health and antioxidant effects. Studies show that cranberry extract can be used synergistically with other drugs or antioxidants to increase effectiveness and create lasting effects. More research and exploration into the potential health benefits of cranberry extract are warranted , lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and cholesterol ; data curation ; formal analysis ; investigation ; methodology ; project administration ; resources ; validation . Ali Hassanpour: Conceptualization ; data curation ; formal analysis ; funding acquisition ; investigation ; methodology ; project administration ; resources ; software ; supervision ; validation ; visualization ; writing – original draft ; writing – review and editing . Bahram Amouoghli Tabrizi: Conceptualization ; data curation ; formal analysis ; investigation ; methodology . Sina Moghaddam: Conceptualization ; data curation ; formal analysis ; investigation ; methodology ; project administration ; resources ; software ; supervision ; validation ; visualization ; writing – original draft ; writing – review and editing .Not applicable.The authors report no conflict of interest.The protocol of this study was developed according to the ethical principles approved by the international committees for the protection of the rights of laboratory animals (Code: IR.IAU.TABRIZ.REC.1400.120).


Sustaining evidence-based interventions in resource-limited settings is a perennial challenge. Despite growing research on the significance of sustainability, few frameworks describe why and how to plan for sustainability in settings limited with resources. Drawing on a synthesis of the literature on sustainability, including the Dynamic Sustainability Framework, we review lessons learned from research to date, to point out a path forward for sustaining evidence-based interventions in resource-limited settings.why people learning, adapting, and nurturing the core values of an intervention can enhance its sustainability over time. PLAN is a dynamic framework that simplifies the process of planning for sustainability of evidence-based interventions throughout the lifecyle of an intervention, taking into consideration the people that matter as well as the learning, adaptation, and nurturing involved with understanding and studying the interactions between interventions/innovations, practice settings, intervention fit, and the broader ecological contexts in which implementation occurs. We use case-study data from our ongoing pragmatic HIV implementation trial, the 4 Youth by Youth project, to detail the value and implications of why people learning, adapting, and nurturing HIV interventions implemented in resource-limited settings matter.We describe PLAN or PLAN at the bare minimum may ensure that the goals of continuing and maintaining desirable features of any evidence-based interventions can be realized.PLAN is designed to further the dialogue on ways research and practice teams can critically work to ensure the sustainability of their evidence-based interventions from the onset, particularly in settings and with populations limited with resources. It also illustrates how attention to sustainability from the beginning may foster actions necessary for sustained program → sustained benefits → sustained capacity → sustained value, but in the absence of early and active planning, none of this will occur. Ultimately, we hope to accelerate the sustainability of evidence-based HIV interventions, and making a  What can be done from the onset or across the lifecycle of an intervention to sustain effective interventions and why does this matter? Many researchers have attempted to answer this fundamental question in implementation science –3. We deMuch of the literature on sustainability focuses on operational definitions, barriers, and facilitators –3, 6–15.Similarly, and among researchers funded to conduct implementation research, only about two-thirds of the studies made references to sustainability, and none included any sustainability planning . As a rereach, implementation, effectiveness, or even adoption of any evidence-based intervention will not necessarily lead to maintenance without specific planning and action [This shift away from static to the dynamic conceptualization of sustainability is consistent with the Dynamic Sustainability Framework, which draws attention to the significance of planning. The goal is for “continuous learning and evaluation, problem-solving, improvement, and ongoing adaptation of evidence-based interventions to enhance fit with contexts and populations over time” . Framewod action –21. Yet,d action . Howeverd action . Prior rd action . We are why people learning, adapting, and nurturing the core values of an intervention can enhance its sustainability over time. The core values help to ensure that aspects of implementation trials are sustainable whether with [4 Youth by Youth Project (4YBY), an ongoing implementation trial using innovative and pragmatic tools to expand youth-friendly HIV self-testing in Nigeria. We conclude the paper with a discussion on how public health agencies, funders, researchers, and intended beneficiaries can be thoughtfully engaged in planning the sustainability of HIV implementations. Engaging the key people to learn, adapt, and nurture their core values of any intervention is likely to ensure the continued use of intervention components and activities for the continued achievement of desirable outcomes overtime.The aim of this paper is to describe a sustainability strategy that focuses on PLAN, or her with  continuaher with  continuaher with  adequateher with . PLAN isWe define PLAN here as how core values of evidence-based interventions with the key people can foster learning, adaptation, and nurturing of resources for continuous feedback and dialogue so that the intervention remains over time. PLAN originated from a prior systematic review we conducted where we argued for the need to understand not only what is to be sustained but the how-to-do-it literature on sustainability . It alsoPLAN begins with identifying an evidence-based intervention’s core values. In the book “Built to Last,” Collins and Porras  defined Next, PLAN includes people. At the heart of any sustainability, the effort focuses on how people understand sustainability in practice . SustainLearning here refers to collaborative and iterative problem-solving to consistently adhere to core values. Sustainability planning facilitates learning, particularly a constant vigilance of the core values identified. In its broadest sense, learning, especially in collaboratives or communities, is like the anthills of a savannah . Even ifBy adaptation, we refer to the thoughtful and deliberate alteration to the design or delivery of an intervention with the goal of improving its fit or effectiveness in a given context , 47. SusFinally, sustainability planning provides an opportunity for continuous feedback to nurture conditions and contexts, particularly those currently existing and likely to support the sustainability of effective evidence-based interventions. By nurturing and guided by the PEN-3 cultural model –54, we rThe ongoing 4YBY project is a pragmatic trial seeking to address the HIV prevention gap among Nigerian youth . TappingFirst, a core group of stakeholders, including a youth advisory board , helped to identify our core value as working with young people to help create interventions that are “youth-driven, youth-inspired.” Our core value was also informed by our use of youth participatory action research, which considers youth not only as beneficiaries or partners but as potential leaders and co-creators of knowledge , 59. OurFollowing the identification of the project’s core values, the next step was to identify and gather the key people to foster continued use of intervention components among young people. With the goal to sustain our youth-driven and youth-inspired HIV self-testing delivery strategies, we identified key stakeholders and potential program champions likely to be crucial using a stakeholder mapping analysis at the start of the project. Some of the key stakeholders included the Nigeria Federal Ministry of Health, local government area leaders, the Nigerian AIDS Control Agency, the Lagos State AIDS Control Agency, Community Alliances , and 4YBY youth ambassadors , and Co-creation Hub for the development of the HIV self-testing mobile phone verification application. The identification and involvement of these stakeholders helped to foster ownership and fit of the youth-led HIV self-testing interventions to the local context. In addition to national and local agencies, we identified and engaged with several international organizations that work in Nigeria  as key stakeholders of the research. Finally, and leveraging existing research resources in Nigeria, our local implementers are the Nigerian Institute of Medical Research, the apex research establishment in the country. NIMR is responsible for leading and coordinating all implementation, thus enhancing the opportunities for continuation of intervention components over time.In addition to identifying the key people, learning is at the core of 4YBY implementation in Nigeria. Learning is both a collaborative and iterative process, and for 4YBY, it occurred both at the individual participant level and the organization/setting level. At the individual participant level, we utilized learning communities as an implementation strategy whereby young people worked together to collectively solve problems on ways to expand HIV self-testing to their peers, learn best practices, apply quality improvement methods in the process of implementation, and exchange experiences with implementation . Our leaWith adaptation and alignment with the National HIV Strategy for Adolescents and Young People , 4YBY woWith nurturing, 4YBY uses existing resources and supporting structures to spur continuous feedback via ongoing dialogue around its sustainability. Documents like the Nigerian National HIV/AIDS Strategic Framework and the National HIV Strategy for Adolescents and Young People guided the research activities, and engagement of key stakeholders. For example, following dialogue and engagement with key stakeholders such as NACA and LSACA, the goals and outcomes of 4YBY were aligned squarely with the existing policy documents such as the Nigerian National HIV/AIDS Strategic Framework . Indeed Bringing attention to sustainability as a core component embedded within an intervention overall cycle requires planning. We have demonstrated with case-study evidence from the 4YBY project that sustainability planning can be made simple with a dynamic plan that draws attention to assembling the key people while learning, adapting, and nurturing the core values of evidence-based intervention components or activities from the onset of implementation and overtime. Previous research indicates that the most crucial way to ensure sustainability is to be clear on the intervention’s values then establish goals and objectives needed to accomplish said values . With vaNevertheless, much work remains to be done to understand how PLAN contributes and advances the research agenda sustainability over longer periods of time. It will also require additional streams of data, particularly from implementation trials that specifically target sustainability as a process, incorporating concepts of learning, adaptation, and continuous improvement or nurturing of existing resources within particular contexts. If these implementation studies carefully think long and deep about the core values of evidence-based interventions, and rigorously plan from the onset to even wean off their projects to the key people, learning from them, adapting where necessary, and nurturing existing resources overtime, then the vision of the continued use of these components for the continued achievement of desirable health outcomes within a population of interest. We are closer than ever before to facilitating the how-to-do-it literature on the sustainability process of evidence-based interventions, but it will require a theory-informed and dynamic PLAN, at the bare minimum. Thus, we call for future application across different populations and contexts, and mixed-methods research to evaluate and further refine the PLAN approach for sustainability planning throughout the life cycle of an EBI.


The number of U.S. drug overdose deaths increased continuously from 1999 to mid-2017,6 Behavioral therapies have been shown to increase retention in some studies, but they are highly resource intensive. Digital health technologies (DHTs) offer the potential to expand the availability of behavioral therapies and to reduce cost. We examine the evidence for 3 such promising DHTs in this review: reSET-O, Connections, and DynamiCare.Medication-assisted treatment (MAT) is the most effective treatment for OUD, but more than half of patients starting MAT drop out of treatment within 3 to 6 months.7DHTs for OUD offer the potential to enhance access to evidence-based MAT for patients whose schedules or locations present challenges to inperson appointments or for whom in-person appointments raise concerns about the stigma attached to this condition. The 3 DHTs evaluated in our review are all apps but differ in important ways. The first, reSET-O, is a 12-week prescription digital therapeutic that combines contingency management (CM) with OUD-specific cognitive behavioral therapy (CBT). The CM component of reSET-O gives small rewards  for desired behaviors , and the size of the potential reward increases, on average, with consecutive desired behaviors.The second intervention, Connections, is an app that combines a form of digital CBT (CBT4CBT) with a program that enhances patient communication with addiction experts, peer support groups, and counselors (A CHESS). The third DHT, the DynamiCare app, includes CBT with CM, substance use screening results, Bluetooth-enabled breathalyzer for alcohol testing, drug saliva testing, and appointment monitoring and reminders.https://icer.org/wp-content/uploads/2020/08/ICER_DHTs_for_OUD_Final_Evidence_Report_121120-1.pdf.The Institute for Clinical and Economic Review (ICER) conducted a systematic literature review and cost-effectiveness analysis to evaluate the health and economic outcomes of DHTs for OUD. Complete details of ICER’s systematic literature search and protocol, as well as the methodology and model structure for the economic evaluation are available on ICER’s website. In this review, we present the summary of our findings and highlights of the policy discussion with key stakeholders held at a public meeting of the Midwest Comparative Effectiveness Public Advisory Council on November 20, 2020. The detailed report is available on the ICER website at 10 We found that none of the studies of these apps has any data on the outcomes that matter to patients, and earlier studies of the components of these DHTs do not show improvements in long-term retention.The most important clinical benefit reported in the trials is retention in MAT. Long-term retention (6 months to 2 years or longer) is associated with abstinence and with the outcomes that really matter to patients: employment, reduced financial stress, decreased hospitalizations and emergency room visits, and improved relationships.Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-4) criteria for opioid dependence and the FDA qualification criteria for buprenorphine treatment.11 There was no significant difference in the primary outcome: number of days of continuous abstinence at 12 weeks. Any other significant findings should therefore be considered hypothesis generating. The study did find a reduced likelihood of dropping out of treatment at 12 weeks  as compared with those who only received contingency management (CM) in addition to MAT. However, a study of the same intervention with 1-year follow-up found no difference in drop-out rates (38.8% vs. 38.8%). Very recently, two uncontrolled studies of reSET-O were published suggesting potential benefits, but due to the possible selection bias and lack of a control group, we did not consider them to add to confidence in the relative effectiveness of the intervention.13In the evidence base available before our draft report, we found no randomized trials, cohort studies, or case series that evaluated any of the DHTs reviewed in this report. The 510(k) clearance of reSET-O by the U.S. Food and Drug Administration (FDA) was based on its similarity to reSET, a web-based precursor to reSET-O. The trial evaluating reSET involved participants who met the There were no clinical trials of the Connections app. The trial of the CBT4CBT portion of the app was a fair quality pilot trial that was judged promising but was not definitive, given that the app in this trial did not include the A CHESS intervention that is part of this app, so the degree to which the results are applicable to Connections is highly uncertain.For the Dynami Care app, there was 1 clinical trial, but it was not solely in the population of interest for this review, and no subgroup results were available in the nonpeer-reviewed report of the trial. Thus, we were unable to assess the potential effect of this app in patients with OUD on MAT.The primary source of limitations in the clinical evidence for these DHTs is the complete lack of peer-reviewed data on the effect of their use for patients with OUD treated with MAT. In addition, the trial designs that demonstrated some efficacy for the behavioral components implemented in the DHTs did not measure outcomes with long enough followup. The minimum follow-up to demonstrate a meaningful effect on adherence would be 6 months, and 12 to 24 months would be more convincing. Finally, no data were reported on key health outcomes that matter to patients, such as ER visits, hospitalizations, return to work, and improved relationships with family and friends.Given the dearth of data on Connections and DynamiCare, we only modeled the cost-effectiveness of reSET-O. Where data allowed, the model compared reSET-O as an adjunct to outpatient buprenorphine with outpatient buprenorphine alone. The base-case analysis took a health care system perspective and a 5-year time horizon. We deviated from the ICER Reference Case lifetime time horizon because there was no identified or plausible effect on costs or outcomes beyond the 5-year time horizon.https://icer.org/wp-content/uploads/2020/08/ICER_Digital-Therapeutics-for-OUD_Model Analysis-Plan_08032020.pdf and includes a modified societal perspective, given the high societal costs and consequences of OUD.Despite no evidence on the effects of reSET-O after 12 weeks, our model extrapolated the potential downstream benefits of having a higher percentage of individuals retained on MAT at 12 weeks. At the end of reSET-O completion (12 weeks), the reSET-O and comparator arm in the model discontinued MAT at the same rate of discontinuation observed in the comparator arm of the trial. We used $1,219 per download as the cost for reSET-O, which was the price provided to us by the manufacturer that was calculated net of rebates, discounts, allowances, and warranty payments. The outcomes of interest included the incremental cost per additional year in MAT and the cost per quality-adjusted life-year (QALY) gained, life-years gained, and equal value of life-years gained (evLYG). Full details on ICER’s cost-effectiveness analysis and model are available on ICER’s website at As noted earlier, there is considerable uncertainty about the long-term effectiveness of reSET-O, and nearly all of the major effects on MAT and other outcomes require retention beyond the 12-week duration of the trial evidence. The model’s assumptions therefore can be viewed as an optimistic scenario. The base-case findings should therefore be interpreted with caution.The Midwest Comparative Effectiveness Public Advisory Council (CEPAC) is one of the independent appraisal committees convened by ICER to engage in the public deliberation of the evidence on clinical and cost-effectiveness of health care interventions. The Midwest CEPAC is composed of medical evidence experts, including practicing clinicians, methodologists, and leaders in patient engagement and advocacy. Their deliberation includes input from clinical experts and patient representatives specific to the condition under review, as well as formal comment from manufacturers and the public. A policy roundtable concludes each meeting, during which representatives from insurers and manufacturers join clinical experts and patient representatives to discuss how best to apply the findings of the evidence to clinical practice, insurance coverage, and pricing negotiations.The ICER report on DHTs for OUD was the subject of a Midwest CEPAC meeting on November 20, 2020. Following the discussion, the panel members deliberated on key questions raised by ICER’s report. The results of their votes on the clinical evidence were as follows: (a) the panel voted 10-3 that the clinical evidence was not adequate to demonstrate greater net health benefit for reSET-O compared with best supportive care; (b) the panel voted 13-0 that the evidence was not adequate to demonstrate greater net health benefit for either the Connections app or the Dynamicare app compared with best supportive care.The CEPAC panel also voted on “other potential benefits” and “contextual considerations” as part of a process intended to signal to policymakers whether there are important considerations when making judgments about long-term value for money not adequately captured in analyses of clinical effectiveness and/or cost-effectiveness. The results of these votes are shown in As described in ICER’s Value Assessment Framework, questions on long-term value for money are subject to a value vote when incremental cost-effectiveness ratios for the interventions of interest are between $50,000 and $175,000 per QALY in the primary base-case analysis. Eight members of the CEPAC voted that reSET-O at the current discounted price represented low value for money, and 5 members voted that it represented intermediate value. No one voted that it represented high long-term value for money.https://icer.org/wp-content/uploads/2020/08/ICER_DHTs_for_OUD_Final_Evidence_Report_121120-1.pdf. Several key policy recommendations for DHTs follow:The policy roundtable discussion explored how best to translate the evidence and additional considerations into clinical practice and into pricing and insurance coverage policies. The full set of policy recommendations can be found in the Final Evidence Report on the ICER website: MAT saves lives and money inside the health system and outside of it. DHTs may be important aids in improving care for many individuals, but it is vital that adequate evidence be generated to evaluate the relative effectiveness of different options so that each person can receive effective treatment tailored to maximize their health. Poor evidence that leads to ineffective use of DHTs represents a health risk to individuals, a financial risk to the health system, and a moral risk for us all that society will fail in its responsibility to use its resources to the greatest effect in combatting an ongoing national epidemic.Manufacturers should provide robust evidence of the clinical effectiveness and broader effect of new DHTs. For DHTs such as those featured in this report that have a function of guiding or enhancing treatment outcomes, a minimum evidence requirement is high-quality observational or quasi-experimental studies with an appropriate comparator and relevant patient outcomes. However, many DHTs should undergo formal evaluation through randomized controlled trials to minimize the risk of bias in trial results.Given the limited evidence supporting the efficacy of DHTs for OUD, alternative payment models, such as guaranteed outcomes, a subscription model, or initial pilot projects may be appropriate if coverage is provided.Manufacturers and researchers should design trials of DHTs to be able to identify potential subgroups of patients who benefit most from a DHT to better target the intervention.