Combining robotics and functional electrical stimulation for assist-as-needed support of leg movements in stroke patients: A feasibility study.

PURPOSE: Rehabilitation technology can be used to provide intensive training in the early phases after stroke. The current study aims to assess the feasibility of combining robotics and functional electrical stimulation (FES), with an assist-as-needed approach to support actively-initiated leg movements in (sub-)acute stroke patients. METHOD: Nine subacute stroke patients performed repetitions of ankle dorsiflexion and/or knee extension movements, with and without assistance. The assist-as-needed algorithm determined the amount and type of support needed per repetition. The number of repetitions and range of motion with and without assistance were compared with descriptive statistics. Fatigue scores were obtained using the visual analogue scale (score 0-10). RESULTS: Support was required in 44 % of the repetitions for ankle dorsiflexion and in 5 % of the repetitions of knee extension, The median fatigue score was 2.0 (IQR: 0.2) and 4.0 (IQR: 1.5) for knee and ankle, respectively, indicating mild to moderate perceived fatigue. CONCLUSION: This study demonstrated the feasibility of assist-as-needed assistance through combined robotic and FES support of leg movements in stroke patients. It proved particularly useful for ankle dorsiflexion. Future research should focus on implementing this approach in a clinical setting, to assess clinical applicability and potential effects on leg function.

A robot-based hybrid lower limb system for Assist-As-Needed rehabilitation of stroke patients: Technical evaluation and clinical feasibility.

BACKGROUND: Although early rehabilitation is important following a stroke, severely affected patients have limited options for intensive rehabilitation as they are often bedridden. To create a system for early rehabilitation of lower extremities in these patients, we combined the robotic manipulator ROBERT® with electromyography (EMG)-triggered functional electrical stimulation (FES) and developed a novel user-driven Assist-As-Needed (AAN) control. The method is based on a state machine able to detect user movement capability, assessed by the presence of an EMG-trigger and the movement velocity, and provide different levels of assistance as required by the patient (no support, FES only, and simultaneous FES and mechanical assistance). METHODS: To technically validate the system, we tested 10 able-bodied participants who were instructed to perform specific behaviors to test the system states while conducting knee extension and ankle dorsal flexion exercises. The system was also tested on two stroke patients to establish its clinical feasibility. RESULTS: The technical validation showed that the state machine correctly detected the participants' behavior and activated the target AAN state in more than 96% of the exercise repetitions. The clinical feasibility test showed that the system successfully recognized the patients' movement capacity and activated assistive states according to their needs providing the minimal level of support required to exercise successfully. CONCLUSIONS: The system was technically validated and preliminarily proved clinically feasible. The present study shows that the novel system can be used to deliver exercises with a high number of repetitions while engaging the participants' residual capabilities through the AAN strategy.

As-Needed Pilocarpine for Radiation-Induced Xerostomia in Head and Neck Cancers.

OBJECTIVES: This study aimed to evaluate the efficacy of as-needed pilocarpine for the management of radiation-induced xerostomia. Additionally, the study sought to assess the side effects associated with an as-needed regimen. METHODS: A randomized, double-blinded, placebo-controlled crossover study was conducted on patients who had undergone radiation therapy for head and neck cancers and developed xerostomia. Participants took pilocarpine or placebo as needed for symptom relief at 2 weeks per treatment, which included a one-week washout period. The primary outcome measure was the severity of dry mouth symptoms, quantified using the Xerostomia Inventory (XI). The primary outcome was the change in the XI score. RESULTS: Among the 20 participants who completed the crossover study, there was a significant reduction in XI scores during the treatment phase with pilocarpine compared to the scores during the placebo phase. The mean difference in XI scores was -18.05 (95% CI: -17.17, -6.13, p < 0.001), with a-49.77 ± 3.22% change (p < 0.001). Only one participant withdrew due to pilocarpine side effects. CONCLUSION: As-needed pilocarpine administration is effective in relieving symptoms of radiation-induced xerostomia, with fewer side effects and reduced treatment costs compared to fixed-dose regimens. This study guides the potential shift toward flexible dosing strategies in clinical practice, promoting enhanced patient-centered, tailored care and adherence. LEVEL OF EVIDENCE: Level 2. According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines Laryngoscope, 2024.

Patient's Healthy-Limb Motion Characteristic-Based Assist-As-Needed Control Strategy for Upper-Limb Rehabilitation Robots.

The implementation of a progressive rehabilitation training model to promote patients' motivation efforts can greatly restore damaged central nervous system function in patients. Patients' active engagement can be effectively stimulated by assist-as-needed (AAN) robot rehabilitation training. However, its application in robotic therapy has been hindered by a simple determination method of robot-assisted torque which focuses on the evaluation of only the affected limb's movement ability. Moreover, the expected effect of assistance depends on the designer and deviates from the patient's expectations, and its applicability to different patients is deficient. In this study, we propose a control method with personalized treatment features based on the idea of estimating and mapping the stiffness of the patient's healthy limb. This control method comprises an interactive control module in the task-oriented space based on the quantitative evaluation of motion needs and an inner-loop position control module for the pneumatic swing cylinder in the joint space. An upper-limb endpoint stiffness estimation model was constructed, and a parameter identification algorithm was designed. The upper limb endpoint stiffness which characterizes the patient's ability to complete training movements was obtained by collecting surface electromyographic (sEMG) signals and human-robot interaction forces during patient movement. Then, the motor needs of the affected limb when completing the same movement were quantified based on the performance of the healthy limb. A stiffness-mapping algorithm was designed to dynamically adjust the rehabilitation training trajectory and auxiliary force of the robot based on the actual movement ability of the affected limb, achieving AAN control. Experimental studies were conducted on a self-developed pneumatic upper limb rehabilitation robot, and the results showed that the proposed AAN control method could effectively estimate the patient's movement needs and achieve progressive rehabilitation training. This rehabilitation training robot that simulates the movement characteristics of the patient's healthy limb drives the affected limb, making the intensity of the rehabilitation training task more in line with the patient's pre-morbid limb-use habits and also beneficial for the consistency of bilateral limb movements.

A multicenter, open-label long-term safety study of rimegepant for the acute treatment of migraine.

BACKGROUND: The present study evaluated the long-term safety and tolerability of rimegepant, an orally administered small molecule calcitonin gene-related peptide receptor antagonist, in people with migraine. METHODS: This multicenter, long-term, open-label safety study included adults (≥18 years) with ≥1 year history of migraine who were sequentially enrolled into three groups: participants in the first two groups had either 2-8 or 9-14 moderate to severe migraine attacks per month by history and treated as needed (pro re nata [PRN]) with one rimegepant 75 mg oral tablet up to once per calendar day for 52 weeks (PRN 2-8 and PRN 9-14); a third group, included to collect safety data during higher-frequency dosing, had 4-14 moderate to severe migraine attacks per month by history and who took one rimegepant tablet every other day as scheduled dosing plus PRN dosing of one rimegepant tablet for migraine attacks of any severity on nonscheduled dosing days for 12 weeks (every other day (EOD) + PRN). RESULTS: Overall, 1800 participants self-administered rimegepant (PRN 2-8: n = 1033; PRN 9-14: n = 481; EOD + PRN: n = 286). The most common on-treatment adverse events (AEs) were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%) and sinusitis (5.1%). Most AEs were mild or moderate and considered unrelated to rimegepant. Serious AEs considered possibly (n = 1) or unlikely (n = 9) related to rimegepant were reported in ten (0.6%) participants. No signal of drug-induced liver injury because of rimegepant was identified. CONCLUSIONS: Rimegepant 75 mg up to once per day as EOD + PRN for 12 weeks or PRN for up to 52 weeks was safe and well tolerated. No signal of hepatotoxicity, potential drug abuse, or medication-overuse headache was identified.Trial registration: Clinicaltrials.gov: NCT03266588.

[Research on mode adjustment control strategy of upper limb rehabilitation robot based on fuzzy recognition of interaction force].

In the process of robot-assisted training for upper limb rehabilitation, a passive training strategy is usually used for stroke patients with flaccid paralysis. In order to stimulate the patient's active rehabilitation willingness, the rehabilitation therapist will use the robot-assisted training strategy for patients who gradually have the ability to generate active force. This study proposed a motor function assessment technology for human upper-limb based on fuzzy recognition on interaction force and human-robot interaction control strategy based on assistance-as-needed. A passive training mode based on the calculated torque controller and an assisted training mode combined with the potential energy field were designed, and then the interactive force information collected by the three-dimensional force sensor during the training process was imported into the fuzzy inference system, the degree of active participation σ was proposed, and the corresponding assisted strategy algorithms were designed to realize the adaptive adjustment of the two modes. The significant correlation between the degree of active participation σ and the surface electromyography signals (sEMG) was found through the experiments, and the method had a shorter response time compared to a control strategy that only adjusted the mode through the magnitude of interaction force, making the robot safer during the training process.

The Use of Albuterol/Budesonide as Reliever Therapy to Reduce Asthma Exacerbations.

Prevention of asthma exacerbations and reduction of systemic corticosteroid burden remain unmet needs in asthma. US asthma guidelines recommend concomitant short-acting ß2-agonist (SABA) and inhaled corticosteroid (ICS) as an alternative reliever at step 2. The Food and Drug Administration approved a pressurized metered-dose inhaler containing albuterol and budesonide for as-needed treatment or prevention of bronchoconstriction and for reducing exacerbation risk in patients with asthma aged ≥18 years. This combination is approved for use as a reliever with or without maintenance therapy, but it is not indicated for maintenance therapy (or for single maintenance and reliever therapy). Intervening with as-needed SABA-ICS during the window of opportunity to reduce inflammation during loss of asthma control can reduce exacerbation risk, by exerting both genomic and nongenomic anti-inflammatory effects. We propose that the use of albuterol-budesonide rather than albuterol as a reliever to manage episodic symptoms driven by acute bronchoconstriction and airway inflammation can improve outcomes. This combination approach, shown to decrease asthma exacerbations and oral corticosteroid burden in patients with moderate-to-severe asthma, represents a paradigm shift for asthma treatment in the United States. Further safety and efficacy studies should provide evidence that this type of reliever should be standard of care.

Effects of an assist-as-needed equipped Tenodesis-Induced-Grip Exoskeleton Robot (TIGER) on upper limb function in patients with chronic stroke.

BACKGROUND: The original version of the Tenodesis-Induced-Grip Exoskeleton Robot (TIGER) significantly improved the motor and functional performance of the affected upper extremity of chronic stroke patients. The assist-as-needed (AAN) technique in robot-involved therapy is widely favored for promoting patient active involvement, thereby fostering motor recovery. However, the TIGER lacked an AAN control strategy, which limited its use in different clinical applications. The present study aimed to develop and analyze the training effects of an AAN control mode to be integrated into the TIGER, to analyze the impact of baseline patient characteristics and training paradigms on outcomes for individuals with chronic stroke and to compare training effects on the upper limb function between using the AAN-equipped TIGER and using the original prototype. METHODS: This was a single-arm prospective interventional study which was conducted at a university hospital. In addition to 20 min of regular task-specific motor training, each participant completed a 20-min robotic training program consisting of 10 min in the AAN control mode and 10 min in the functional mode. The training sessions took place twice a week for 9 weeks. The primary outcome was the change score of the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), and the secondary outcomes were the change score of the Box and Blocks Test (BBT), the amount of use (AOU) and quality of movement (QOM) scales of the Motor Activity Log (MAL), the Semmes-Weinstein Monofilament (SWM) test, and the Modified Ashworth Scale (MAS) for fingers and wrist joints. The Generalized Estimating Equations (GEE) and stepwise regression model were used as the statistical analysis methods. RESULTS: Sixteen chronic stroke patients completed all steps of the study. The time from stroke onset to entry into the trial was 21.7 ± 18.9 months. After completing the training with the AAN-equipped TIGER, they exhibited significant improvements in movement reflected in their total score (pre/post values were 34.6 ± 11.5/38.5 ± 13.4) and all their sub-scores (pre/post values were 21.5 ± 6.0/23.3 ± 6.5, 9.5 ± 6.2/11.3 ± 7.2, and 3.6 ± 1.0/3.9 ± 1.0 for the shoulder, elbow, and forearm sub-category, the wrist and hand sub-category, and the coordination sub-category, respectively) on the FMA-UE (GEE, p < 0.05), as well as their scores on the BBT (pre/post values were 5.9 ± 6.5/9.5 ± 10.1; GEE, p = 0.004) and the AOU (pre/post values were 0.35 ± 0.50/0.48 ± 0.65; GEE, p = 0.02). However, the original TIGER exhibited greater improvements in their performance on the FMA-UE than the participants training with the AAN-equipped TIGER (GEE, p = 0.008). The baseline score for the wrist and hand sub-category of the FMA-UE was clearly the best predictor of TIGER-mediated improvements in hand function during the post-treatment assessment (adjusted R2 = 0.282, p = 0.001). CONCLUSIONS: This study developed an AAN-equipped TIGER system and demonstrated its potential effects on improving both the function and activity level of the affected upper extremity of patients with stroke. Nevertheless, its training effects were not found to be advantageous to the original prototype. The baseline score for the FMA-UE sub-category of wrist and hand was the best predictor of improvements in hand function after TIGER rehabilitation. Clinical trial registration ClinicalTrials.gov, identifier NCT03713476; date of registration: October19, 2018. https://clinicaltrials.gov/ct2/show/NCT03713476.

A rehabilitation robot control framework with adaptation of training tasks and robotic assistance.

Robot-assisted rehabilitation has exhibited great potential to enhance the motor function of physically and neurologically impaired patients. State-of-the-art control strategies usually allow the rehabilitation robot to track the training task trajectory along with the impaired limb, and the robotic motion can be regulated through physical human-robot interaction for comfortable support and appropriate assistance level. However, it is hardly possible, especially for patients with severe motor disabilities, to continuously exert force to guide the robot to complete the prescribed training task. Conversely, reduced task difficulty cannot facilitate stimulating patients' potential movement capabilities. Moreover, challenging more difficult tasks with minimal robotic assistance is usually ignored when subjects show improved performance. In this paper, a control framework is proposed to simultaneously adjust both the training task and robotic assistance according to the subjects' performance, which can be estimated from the users' electromyography signals. Concretely, a trajectory deformation algorithm is developed to generate smooth and compliant task motion while responding to pHRI. An assist-as-needed (ANN) controller along with a feedback gain modification algorithm is designed to promote patients' active participation according to individual performance variance on completing the training task. The proposed control framework is validated using a lower extremity rehabilitation robot through experiments. The experimental results demonstrate that the control scheme can optimize the robotic assistance to complete the subject-adaptation training task with high efficiency.

Assessing walking ability using a robotic gait trainer: opportunities and limitations of assist-as-needed control in spinal cord injury.

BACKGROUND: Walking impairments are a common consequence of neurological disorders and are assessed with clinical scores that suffer from several limitations. Robot-assisted locomotor training is becoming an established clinical practice. Besides training, these devices could be used for assessing walking ability in a controlled environment. Here, we propose an adaptive assist-as-needed (AAN) control for a treadmill-based robotic exoskeleton, the Lokomat, that reduces the support of the device (body weight support and impedance of the robotic joints) based on the ability of the patient to follow a gait pattern displayed on screen. We hypothesize that the converged values of robotic support provide valid and reliable information about individuals' walking ability. METHODS: Fifteen participants with spinal cord injury and twelve controls used the AAN software in the Lokomat twice within a week and were assessed using clinical scores (10MWT, TUG). We used a regression method to identify the robotic measure that could provide the most relevant information about walking ability and determined the test-retest reliability. We also checked whether this result could be extrapolated to non-ambulatory and to unimpaired subjects. RESULTS: The AAN controller could be used in patients with different injury severity levels. A linear model based on one variable (robotic knee stiffness at terminal swing) could explain 74% of the variance in the 10MWT and 61% in the TUG in ambulatory patients and showed good relative reliability but poor absolute reliability. Adding the variable 'maximum hip flexor torque' to the model increased the explained variance above 85%. This did not extend to non-ambulatory nor to able-bodied individuals, where variables related to stance phase and to push-off phase seem more relevant. CONCLUSIONS: The novel AAN software for the Lokomat can be used to quantify the support required by a patient while performing robotic gait training. The adaptive software might enable more challenging training conditions tuned to the ability of the individuals. While the current implementation is not ready for assessment in clinical practice, we could demonstrate that this approach is safe, and it could be integrated as assist-as-needed training, rather than as assessment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02425332.

Evaluating as-needed inhaled corticosteroid strategies in asthma: expanding the benefits to mild asthma.

INTRODUCTION: Adherence to regular anti-inflammatory treatment is commonly low, and short-acting ß2 agonist (SABA) overuse is common in patients with asthma, leading to an increased risk of asthma-related adverse events. AREAS COVERED: Given the pivotal role of inflammation in asthma, multiple as-needed inhaled corticosteroid (ICS)-containing therapies have been developed, leading to a reduction in asthma exacerbations and improvement in symptom control. Currently, as-needed ICS/formoterol is one of the most commonly available formulations; however, other combinations such as ICS/SABA have been shown to be superior to as-needed SABA alone. Therefore, we performed a comprehensive review of the available scientific literature to enhance the advantages and disadvantages of each combination in clinical practice. EXPERT OPINION: The future direction we foresee in asthma management consists in abandoning as-needed short-acting bronchodilators in favor of as-needed ICS-containing therapies. Each patient is unique and differs from others; consequently, a single option will not fit everyone. Patients' and physicians' awareness of this perspective can be reached through the development of multiple therapeutic options suitable for each condition that can be found in 'real life'.

Anti-Vascular Endothelial Growth Factor Therapy Regimens for Polypoidal Choroidal Vasculopathy: A Systematic Review.

INTRODUCTION: There are no guidelines on the optimal anti-vascular endothelial growth factor (anti-VEGF) monotherapy regimen for patients with polypoidal choroidal vasculopathy (PCV). In this study, we aimed to assess the comparative safety and efficacy of different treatment regimens of anti-VEGF monotherapy for PCV. METHODS: We conducted a systematic literature search on Ovid MEDLINE, Embase, and Cochrane Library from January 2000 to May 2023 for comparative articles reporting on different treatment regimens of anti-VEGF agents in PCV. Our primary outcomes were the final best-corrected visual acuity (BCVA) and the change in BCVA from baseline. Secondary outcomes were the final retinal thickness (RT), the change in RT from baseline, the rate of polyp closure, and the incidence of adverse events. RESULTS: A total of 10,440 studies were screened, and seven studies reporting on 636 eyes with PCV at baseline were included in this systematic review. One RCT of 53 eyes found a similar final BCVA, change in BCVA from baseline, final RT, and complete polyp closure rate between a treat-and-extend (T&E) regimen and a bimonthly fixed-dosing regimen of aflibercept. This trial also found superiority of T&E for change in RT from baseline. One observational study of 33 eyes found a similar BCVA at last study observation between a pro re nata (PRN) regimen and bimonthly fixed-dosing regimen of aflibercept. One observational study of 42 eyes found a similar change in BCVA from baseline and complete polyp closure rate between a PRN regimen and bimonthly fixed-dosing regimen of aflibercept. One RCT of 249 eyes found a similar change in BCVA and RT from baseline, as well as polyp closure, between a T&E regimen and fixed 12-week dosing regimen of conbercept. One observational study of 30 eyes found a superiority of T&E aflibercept for change in BCVA and risk of polyp recurrence, compared to a PRN regimen. CONCLUSION: Overall, there is a paucity of evidence comparing various treatment regimens of anti-VEGF therapy in patients with PCV. This limited evidence suggests that current treatment regimens are similarly efficacious, though T&E aflibercept achieved superior outcomes when compared to bimonthly dosing or PRN in some individual studies. Further trials are needed to confirm or refute these findings.

Comparison of one-year outcomes between as-needed brolucizumab and aflibercept for polypoidal choroidal vasculopathy.

PURPOSE: To compare the one-year visual and anatomic outcomes of an as-needed regimen of brolucizumab and aflibercept for polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: A retrospective comparative study. METHODS: A retrospective medical chart review was performed for consecutive 56 eyes from 56 patients with PCV initially treated with thee monthly intravitreal aflibercept (n = 33, 2.0 mg/0.05 ml) or brolucizumab (n = 23, 6.0 mg/0.05 ml) followed by as-needed administration, followed up for at least 12 months. All patients were followed up monthly, and fluorescein and indocyanine green angiography (ICGA) were performed at baseline, 3-month, and 12-month visits. RESULTS: At the 12-month visit, best-corrected visual acuity significantly improved from 0.30 ± 0.31 to 0.21 ± 0.29 (p = 0.042) in the brolucizumab-treated group and from 0.24 ± 0.25 to 0.14 ± 0.25 (p = 7.7×10-3) in the aflibercept-treated group, suggesting comparable visual improvement in both groups. Central retinal thickness and subfoveal choroidal thickness decreased by 38.4% and 14.2%, respectively, in the brolucizumab-treated group and by 34.8% and 13.9%, respectively, in the aflibercept-treated group at the 12-month visit. The mean number of additional injections was significantly higher in the aflibercept-treated group (2.9 ± 2.7) than in the brolucizumab-treated group (1.3 ± 1.2, p = 0.045). The complete resolution of polypoidal lesions on ICGA was higher in the brolucizumab-treated group than in the aflibercept-treated group (3-month visit: 56.5% vs 30.3%, 12-month visit: 56.5% vs 30.3%). CONCLUSIONS: In treatment-naïve eyes with PCV, the as-needed administration regimen of brolucizumab was comparable to aflibercept in terms of visual and anatomical outcomes, with fewer additional injections during the 12-month follow-up.

SABAs as Reliever Medications in Asthma Management: Evidence-Based Science.

The role of as-needed inhaled short-acting ß2-agonists (SABAs) in the management of asthma has become a subject of debate due to differing opinions in the professional community relating to the use of SABAs. In this article, we summarize the current position of SABAs when used as reliever medications and examine the challenges to appropriate use including a critique of the data that have led to the condemnation of SABA used as a reliever. We consider the evidence for the appropriate use of SABA as a reliever together with practical solutions to ensure such use, including identifying patients at risk of misusing their SABA relievers and managing issues of inhaler technique and treatment adherence. We conclude that inhaled corticosteroid (ICS)-based maintenance treatment with SABA used as-needed as a reliever is an effective and safe treatment for patients with asthma, with no scientific evidence of a causal link between SABA use as a reliever and mortality or serious adverse events (including exacerbations). Increased SABA use warns of a deterioration in asthma control, and patients at risk of misusing their ICS and SABA medication should be rapidly identified to ensure they are receiving adequate ICS-based controller therapy. Appropriate use of ICS-based controller therapy and as-needed SABA should be encouraged and promoted with educational activities.

Feasibility of an Intelligent Algorithm Based on an Assist-as-Needed Controller for a Robot-Aided Gait Trainer (Lokomat) in Neurological Disorders: A Longitudinal Pilot Study.

Most robotic gait assisted devices are designed to provide constant assistance during the training without taking into account each patient's functional ability. The Lokomat offers an assist-as-needed control via the integrated exercise "Adaptive Gait Support" (AGS), which adapts the robotic support based on the patient's abilities. The aims of this study were to examine the feasibility and characteristics of the AGS during long-term application. Ten patients suffering from neurological diseases underwent an 8-week Lokomat training with the AGS. They additionally performed conventional walking tests and a robotic force measurement. The difference between robotic support during adaptive and conventional training and the relationship between the robotic assessment and the conventional walking and force tests were examined. The results show that AGS is feasible during long-term application in a heterogeneous population. The support during AGS training in most of the gait phases was significantly lower than during conventional Lokomat training. A relationship between the robotic support level determined by the AGS and conventional walking tests was revealed. Moreover, combining the isometric force data and AGS data could divide patients into clusters, based on their ability to generate high forces and their level of motor control. AGS shows a high potential in assessing patients' walking ability, as well as in providing challenging training, e.g., by automatically adjusting the robotic support throughout the whole gait cycle and enabling training at lower robotic support.

Efficacy and safety of anti-vascular endothelial growth agents for the treatment of polypoidal choroidal vasculopathy: A systematic review and meta-analysis.

There remains limited agreement regarding the efficacy and safety of different antivascular endothelial growth factor (anti-VEGF) agents for the management of polypoidal choroidal vasculopathy (PCV). Our meta-analysis compares different anti-VEGF agents for PCV treatment. Ovid MEDLINE, EMBASE, and Cochrane Library were systematically searched from January 2000 to July 2022. We included articles comparing the efficacy and safety of different anti-VEGF agents, specifically bevacizumab (BEV), ranibizumab (RAN), aflibercept AFL), and brolucizumab (BRO), for patients with PCV. 10,440 studies were identified, 122 underwent full-text review, and seven were included. One study was a randomized trial, and six were observational studies. Ranibizumab and aflibercept were associated with a similar best-corrected visual acuity (BCVA) at the last visit in three observational studies (P = 0.10), similar retinal thickness at the last visit in two observational studies (P = 0.85). One observational study comparing BEV versus RAN found comparable outcomes for final BCVA, retinal thickness, and polyp regression. One randomized trial on BRO versus AFL found comparable outcomes for improvement in BCVA, while anatomical outcomes favored BRO. The available evidence suggests that final BCVA is comparable across different anti-VEGF agents, however, further investigation is warranted due to paucity of evidence.

Simulation study on assist-as-needed control of a rehabilitation robotic walker.

BACKGROUND: Along with China entering an aging society, the percentage of people that over 60 will reach 34.9% in 2050, resulted in a significant increase in stroke patients. OBJECTIVE: This paper proposes a rehabilitation robotic walker for walking assistance during the daily life, and a control method for the motor relearning during the gait training. The walker consists of an omni-directional mobile platform (OMP) which ensures the walker can move on the ground, a body weight support system (BWS) which is capable of providing the desired unloading force, and a pelvic assist mechanism (PAM) to provide the user with four degrees of freedom and avoid the rigid impact. The study goal is to gain a better understanding of the assist-as-needed control strategy during the gait training. METHODS: For the man-machine interaction control, the assist-as-needed control strategy is adopted to guide the users' motions and improve the interaction experience. To build the force field in the three-dimensional space, the dynamics of the system is derived to increase the accuracy of force control. RESULTS: The simulation results show that the force field around the motion trajectory was generated in the three-dimensional space. In order to understand the force field, we designed the simulation on sagittal plane and the controller can generate the appropriate force field. The preliminary experiment results were consistent with the simulation results. CONCLUSION: Based on the mathematical simulation and the preliminary test, the results demonstrate that the proposed system can provide the guide force around the target trajectory, the accuracy of force control still remains to be improved.

Fuzzy Adaptive Passive Control Strategy Design for Upper-Limb End-Effector Rehabilitation Robot.

Robot-assisted rehabilitation therapy has been proven to effectively improve upper-limb motor function in stroke patients. However, most current rehabilitation robotic controllers will provide too much assistance force and focus only on the patient's position tracking performance while ignoring the patient's interactive force situation, resulting in the inability to accurately assess the patient's true motor intention and difficulty stimulating the patient's initiative, thus negatively affecting the patient's rehabilitation outcome. Therefore, this paper proposes a fuzzy adaptive passive (FAP) control strategy based on subjects' task performance and impulse. To ensure the safety of subjects, a passive controller based on the potential field is designed to guide and assist patients in their movements, and the stability of the controller is demonstrated in a passive formalism. Then, using the subject's task performance and impulse as evaluation indicators, fuzzy logic rules were designed and used as an evaluation algorithm to quantitively assess the subject's motor ability and to adaptively modify the stiffness coefficient of the potential field and thus change the magnitude of the assistance force to stimulate the subject's initiative. Through experiments, this control strategy has been shown to not only improve the subject's initiative during the training process and ensure their safety during training but also enhance the subject's motor learning ability.

Effects of stance control via hidden Markov model-based gait phase detection on healthy users of an active hip-knee exoskeleton.

Introduction: In the past years, robotic lower-limb exoskeletons have become a powerful tool to help clinicians improve the rehabilitation process of patients who have suffered from neurological disorders, such as stroke, by applying intensive and repetitive training. However, active subject participation is considered to be an important feature to promote neuroplasticity during gait training. To this end, the present study presents the performance assessment of the AGoRA exoskeleton, a stance-controlled wearable device designed to assist overground walking by unilaterally actuating the knee and hip joints. Methods: The exoskeleton's control approach relies on an admittance controller, that varies the system impedance according to the gait phase detected through an adaptive method based on a hidden Markov model. This strategy seeks to comply with the assistance-as-needed rationale, i.e., an assistive device should only intervene when the patient is in need by applying Human-Robot interaction (HRI). As a proof of concept of such a control strategy, a pilot study comparing three experimental conditions (i.e., unassisted, transparent mode, and stance control mode) was carried out to evaluate the exoskeleton's short-term effects on the overground gait pattern of healthy subjects. Gait spatiotemporal parameters and lower-limb kinematics were captured using a 3D-motion analysis system Vicon during the walking trials. Results and Discussion: By having found only significant differences between the actuated conditions and the unassisted condition in terms of gait velocity (ρ = 0.048) and knee flexion (ρ ≤ 0.001), the performance of the AGoRA exoskeleton seems to be comparable to those identified in previous studies found in the literature. This outcome also suggests that future efforts should focus on the improvement of the fastening system in pursuit of kinematic compatibility and enhanced compliance.

Taking Placebos as Needed to Reduce Appetite: A Randomized Controlled Trial with Ecological Momentary Assessment.

Placebos can reduce appetite. However, when placebos are prescribed over a longer period of time, compliance and response rates are not always satisfactory. A new administration approach 'as needed' was tested to improve adherence to placebo treatment and its effectiveness. Participants could decide on the time of placebo intake (when their appetite had increased substantially). A randomized controlled trial was conducted over seven days. The participants were allocated to one of two groups: a placebo group (PG; n = 41) or a control group with no placebo treatment (CG; n = 34). During the intervention, participants used a mobile phone application to rate their daily appetite, mood, and the occurrence of binge-eating episodes in their normal environment. The placebo effect was short-lived; the placebo reduced self-reported appetite only on days 1 and 2 of the trial. The placebo neither influenced mood nor binge-eating frequency. This study found an app-assisted approach with continuous monitoring to be helpful for identifying the temporal course of the placebo response. Future placebo trials should implement this method.